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Acknowledgements

We wish to thank the following professors, colleagues, guests and friends who have contributed their works to the Vietnamese Pharmaceutical Journal (VPhJ) issue No. 5 on Anemia * Dr. Nguyeãn Höõu Tueä, Director of Pharmaceutical Research and Developement at Genentech, Inc., who is the Guest Editor for this issue. * Dr. Toâ Ñoàng, for a thorough Editorial highlighting the main points of articles submitted. * Dr. Nguyeãn Phuùc Böûu Taäp, Mr. Leâ Vaên Nhaân, Dr. Traàn Bình Nhung for their reviews of many articles. * Dr. Nguyeãn Quyeàn Taøi, Dr. Huyønh Ñoã Phi, Mr. Hoà Duy Thieän, Dr. Toâ Leâ Linh, Dr. Traàn Bình Nhung, Mr. Leâ Vaên Nhaân, Dr. Löông Vinh Quoác Khanh, Dr. Nguyeãn Thò Hoaøng Lan, Dr. Trònh Nguyeãn Ñaøm Giang, Mr. Mai Taâm, Dr. Traàn Vieät Höng, Dr. Buøi Quoác Quang, Dr. Nguyeãn Ñöùc Kieân, Dr. Ñaëng Vaên Chaát, Dr. Ñaëng B.C Alan, Dr. Nguyeãn Taøi Mai, Dr. Nguyeãn Ñöùc Thaùi, Dr. Nguyeãn Vaên Ñích for contributing their articles on Anemia and other topics that have brought great value to this journal * Dr. Nguyeãn Ñöùc Thaùi, Dr. Trònh Nguyeãn Ñaøm Giang for contributing their poems which have been translated in English and French by Dr. Traàn Bình Nhung We hope that readers from all countries will share their comments on this issue, so that we can continue improving VPhJ in both form and content. * Mr. Nguyeãn Tuù for designing the journal.

THE VIETNAMESE PHARMACEUTICAL JOURNAL

HOÄI DÖÔÏC SÓ VIEÄT NAM TAÏI HOA KYØ

VIETNAMESE PHARMACISTS ASSOCIATION IN THE USA ASSOCIATION DES PHARMACIENS VIETNAMIENS AUX ETATS UNIS

TAÄP SAN CHUYEÂN NGHIEÄP DÖÔÏC KHOA

Vietnamese Pharmaceutical Journal Revue PharmaceutiqueVietnamienne

14291 Euclid St, Ste# D105, Garden Grove, CA 92843 Tel: (714) 554-1093; Fax: (714) 554-3308; Email: [email protected]

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VPhA - USA

Editor-In-Chief

GS Toâ Ñoàng

HOÄI ÑOÀNG QUAÛN TRÒ

Chuû Tòch

DS Nguyeãn Thuùc Maãn

Deputy Editor-in-Chief

DS Traàn Bình Nhung

DS Cao Thieän Chaùnh TS Nguyeãn Phuùc Böûu Taäp DS Traàn Ñöùc Hieáu GS Nguyeãn Vaên Döông (California) GS Ñaëng Vuõ Bieàn (France) GS Tröông Maïnh Khaûi (California) GS Nguyeãn Phuù Lòch (France) GS Leâ Quang Ngoïc Traâm (France)

Publishers

Phoù Chuû Tòch Ngoaïi Vuï

DS Traàn Moäng Ñaøo

Advisory Board

Phoù Chuû Tòch Noäi Vuï

DS Traàn Thu Haèng

Editorial Board

Community Pharmacy DS Phaïm Vuõ Bieàn (Canada) DS Phaïm Vaân Anh (California) DS Traàn Baïch Loan (California) Hospital Pharmacy DS Trònh Nguyeãn Ñaøm Giang (Tennessee) DS Terrie Nghieâm (California) DS Traàn Naêng Ñaïi (California) Geriatrics DS Kristie Töø (California) Microbiology TS Vónh Tu (UÙc Chaâu) Nuclear Pharmacy DS Döông Quang Nhaøn (Pennsyl.) Oncology DS Trònh Vaân Anh (Texas) Pharmaceutical Industry TS Nguyeãn Höõu Tueä (California DS Tina Leâ (California) Pharmacoeconomics DS Döông Thanh Phong (Pennsyl.) Patient Education DS Leâ Vaên Nhaân (California) DS Tröông Chí Phöôùc (California) Pharmaceutical Research TS Nguyeãn Ñöùc Thaùi (California) TS Nguyeãn Khueâ Caùc (California) TS Huyønh Phöôùc Döông (California) DS Buøi Leâ Lan Chi (California) Pharmacy Education TS Traàn Leâ Nhaân (Washington, DC) DS Ariane An (California) DS Nguyeãn Leâ Thi (UÙc Chaâu) Public Health TS Nguyeãn Tieán Ñöùc (Maryland) Mr. Nguyeãn Ngoïc Bình (Texas) TS Tröông Maïnh Hoàng Haø (Cali.) Ms. Mina Vaên Phaïm (California) Alternative Pharmacy DS Traàn Vieät Höng (Oregon) DS Mai Taâm (Canada) DS Traàn Nghóa Ñôøi (California) DS Traàn Quang Tuaán Anh (Oregon) Art and Culture DS Buøi Khieát (California) DS Vuõ Huy Ñaïo (California) DS Löu Vaên Vònh (California) Pharmacy Activities DS Hoà Duy Thieän (Kentucky) DS Nguyeãn Thuùc Maãn (California) DS Mai Ñoâng Thaønh (California)

Phoù Chuû Tòch Phaùt Trieån Chuyeân Nghieäp

DS Traàn Bình Nhung

Toång Thö Kyù

DS. Chu Taát Thaéng

Thuû Quyõ

DS Nghieâm Bích Vaân

Quaûn Trò Vieân

DS Buøi Khieát DS Buøi Kim AÙnh DS Mai Ñoâng Thaønh DS Nghieâm Xuaân Baûo Sôn DS Nguyeãn Duy AÙi DS Nguyeãn Ñöùc Naêng DS Traàn Ñöùc Hieáu DS Traàn Thuùy Lan DS Vuõ Vaên Tuøng

Publication Committee

DS Chu Taát Thaéng DS Traàn Thuùy Lan

Toxicology TS Buøi Quoác Quang (California) GS Ñaøo Höõu Anh BS Trònh Cöôøng

KS Ñinh Kim Anh DS Nguyeãn Thuùc Maãn Web page: www.vphausa.org

Web Masters

Contributing Writers

BS Nguyeãn Khaéc Minh BS Traàn Duy Toân TS Phaïm Gia Uy

Vietnamese Pharmaceutical Journal No.5 - 1

Taäp San Chuyeân Nghieäp Döôïc Khoa

Table of content - Muïc Luïc

Acknowledgements 4- Opening Letter

Prof. Toâ Ñoàng

III. DÖÔÏC KHOA NGHIEÂN CÖÙU PHARMACY RESEARCH 56- What does the future hold for Acute and Chronic Anemia? The case for Artificial Blood

Chat van Dang, MD and Alan B.C. Dang, MD.

8- Guest editor's letter

Nguyeãn Höõu Tueä, Ph.D.

I. QUAN ÑIEÅM - VIEWPOINT 10- Thöû phaân tích vaø nhaän ñònh: Taïi sao giôùi treû Döôïc khoa ít tham gia hôn giôùi treû Y khoa vaøo nhöõng sinh hoaït cuûa toå chöùc ngheà nghieäp vaø Coäng ñoàng Vieät Nam.

Hoà Duy Thieän thaâu thaäp 14- Vai troø Döôïc só trong vieäc phoøng choáng HIV Nguyeãn Quyeàn Taøi, MD.

59- Treatment of Severe Anemia Using Blood Substitutes

Kien D. Nguyen, PhD.

64- Pure Red Cell Aplasia Associated with Recombinant DNA Erythropoietin Treatment

Nguyeãn Höõu Tueä, Ph.D. Trònh N. Giang, D.Ph.

67- Thaëng dö saét moâ

74- Environmental exposure and anemia

Quang Quoc Bui, Ph.D.

16-AIDS and the role of the Pharmacist

Mary J. Berg, Pharm.D

IV. TIN Y DÖÔÏC (MEDICAL NEWS) 77- Vaøi tröôøng hôïp hôïp Beänh Thieáu maùu ñoû

Nguyeãn Taøi Mai, M.D.

II. DÖÔÏC KHOA THÖÏC HAØNH PHARMACY PRACTICE 19- Anemia of chronic kidney failure

Linh Le To, PharmD.

78- Trình baày moät Tröôøng Hôïp Beänh

Nguyeãn Taøi Mai, M.D.

23-Anemia in Longterm Care: A Common Occurrence

Binh N. Tran, PharmD

80- Sieâu vi cuùm H5N1

Thaùi Ñöùc Nguyeãn, Ph.D

28-Laøm sao ñoïc ñöôïc keát quaû xeùt nghieäm beänh thieáu maùu

DS Leâ van Nhaân

82- Vioxx Recall Trònh N. Giang, D.Ph

83- Vaøi suy nghó veà thuoác môùi

Leâ Vaên Nhaân, R.Ph.

32-Beänh thieáu maùu do thieáu folate vaø Sinh toá B12 ôû nhoùm di daân Vieät nam vuøng Nam California

Löông Vinh Quoác Khanh, MD and Hoaøng Lan Thò Nguyeãn, MD

V. ÑIEÅM BAÙO (ARTICLES REVIEW) 85- Goùp yù veà baøi Beänh thieáu maùu do thieáu Folate vaø Sinh toá B12

Leâ Vaên Nhaân, R.Ph.

36- Beänh thaän kinh nieân. (Chronic Kidney Disease).

Giang Trinh Nguyen, P.D.

41-Thöû tìm hieåu ñeå so saùnh "Thieáu maùu" vaø "Huyeát hö" trong Taây Y vaø Ñoâng Y

DS Mai Taâm

86- Beänh thieáu maùu ôû Beänh nhaân Vieät nam

BS Nguyeãn vaên Ñích.

VI. DÒCH THUAÄT DANH TÖØ Y DÖÔÏC 87-Terminology used in Anemia

Toâ Ñoàng, D.Ph., Leâ Vaên Nhaân, R.Ph.

50-Thieáu maùu vaø trò lieäu baèng phöông phaùp töï nhieân

Traàn Vieät Höng, PharmD

2 - Taäp San Chuyeân Nghieäp Döôïc Khoa

VII. VAÊN HOÏC NGHEÄ THUAÄT (LITERATURE AND ART) 90- Muoân tuoåi Thanh xuaân

Thaùi Sôn - NDT

96- Vietnamese Pharmacists Associations in the Free World 97- The Fifth International Convention of Vietnamese Physicians, Dentists and Pharmacists.

Traàn Bình Nhung

91- Long-Lasting Youthfulness

Traàn Bình Nhung

Em vaø gioù vaø maây laø moät

Ñaøm Giang

99-A Carier in Industrial Pharmacy. Interview of Dr. Tueä Nguyeãn by Traàn Bình Nhung 101- Two Weeks in Australia: A Life-Time of Memories

Traàn Bình Nhung

You with the Wind and Clouds - Le Vent, Les Nuages et Toi

Traàn Bình Nhung

VIII. SINH HOAÏT DÖÔÏC KHOA (PHARMACY ACTIVITIES) TIN TÖÙC COÄNG ÑOÀNG 92- Activities of the Vietnamese Pharmacists Association in the USA: Report of VPhA-USA 2004 Biennial Meeting and Board of Directors Meeting.

Traàn Bình Nhung

104-Tö vaán Y khoa mieãn phí: Giôùi thieäu Paltalk vaø "Chöông trình Vaán ñaùp SOÁNG KHOÛE"

Giaùo Sö Nguyeãn Quyeàn Taøi

IX. IN MEMORIAM 106- Nguyeãn Ñaït Toân, D.Ph. (France) Nguyeãn Taát Ñaït, R.Ph. one of VphA-USA Founders 107- Nguyeãn Vaên Trang, D.Ph.

95- Activities of the Vietnamese Pharmacy Students Association (VPSA-USC)

Vietnamese Pharmaceutical Journal No.5- 3

Thö Môû Ñaàu

Thaân göûi Quí Baïn Ñoäc Giaû:

Ñeà taøi chính yeáu trong Taäp San Chuyeân Nghieäp Döôïc Khoa soá 5 lieân heä ñeán beänh Thieáu Maùu. Toâi raát laáy laøm haân haïnh giôùi thieäu Tieán Só Nguyeãn Höõu Tueä, Chuû Bieân cuûa Taäp san naøy, ñaõ ñieàu haønh vieäc bieân taäp taát caû caùc baøi vieát lieân heä tôùi chöùng beänh quan troïng naøy. Tieán só Tueä, moät Döôc só toát nghieäp taïi ñaïi hoïc Döôïc khoa Saøi goøn vaøo naêm 1973, hieän laø moät khaûo cöùu gia teân tuoåi trong ngaønh sinh hoïc kyõ thuaät cuûa haõng Genetech, Inc. Toâi cuõng xin toùm löôïc nhöõng Chöông Muïc cuûa Taäp san Chuyeân Nghieäp Döôïc Khoa soá 5 nhö sau: Phaàn I: Quan Ñieåm Döôïc só Hoà Duy Thieän ñaõ thu thaäp, phaân tích vaø nhaän ñònh taïi sao giôùi treû Döôïc Khoa ít tham gia hôn giôùi treû Y khoa vaøo nhöõng toå chöùc sinh hoaït ngheà nghieäp trong coäng ñoàng Vieät Nam? Baùc só Nguyeãn Quyeàn Taøi ñaõ phaùc hoïa vai troø cuûa Döôïc só trong caùc chöông trình phoøng ngöøa beänh lieät khaùng. Ñeà taøi naøy cuõng ñöôïc Baùc só Döôïc khoa Mary J. Berg trình baày taïi Hoäi Nghò Quoác teá laàn thöù 61 taïi Singapor, naêm 2001 cuûa Lieân hoäi Quoác teá Döôïc khoa, vaø ñöôïc Baùc só Huynh Ñoã Phi chuyeån tôùi. Phaàn II: Döôïc Khoa Thöïc haønh Beänh Thieáu Maùu, nhö moät bieán chöùng hieåm ngheøo ñöôïc thaáy trong beänh Thaän suy kinh nieân cuûa khoaûng 13 trieäu daân Myõ, ñaõ ñöôïc trình baày bôûi Baùc só Döôïc khoa Leâ Linh Toâ. Beänh coù theå ñöôïc chöõa trò baèng caùch chích gaân hay döôùi da chaát sinh hoïc Erythropoetin EPO hay caùc döôïc phaåm ñoàng loïai. Thoâng thöôøng, khoâng hieäu löïc vì beänh nhaân thieáu chaát saét coù theå ñöôïc ñieàu trò baèng nhöõng döôïc phaåm uoáng hay chích chöùa saét. Vieäc quaûn trò beänh Thieáu Maùu cho caùc beänh nhaân cuûa caùc chung cö ñieàu döôõng laâu daøi ñöôïc moâ taû bôûi Baùc só Döôïc khoa Traàn Bình Nhung. Beänh Thieáu Maùu do thieáu Folate vaø Sinh toá B12 ôû nhoùm di daân Vieät Nam vuøng Nam California ñöôïc caùc Baùc só Löông-Vinh Quoác Khanh vaø Nguyeãn Thò Hoaøng Lan nghieân cöùu. Baøi vieát veà keát quaû khaûo cöùu ñaëc bieät naøy ñaõ ñöôïc Döôïc só Leâ Vaên Nhaân phieân dòch. Laøm sao ñoïc vaø phaùn ñoaùn keát quaû thöû nghieäm trong beänh Thieáu Maùu ñaõ ñöôïc Döôïc só Leâ Vaên Nhaân toång keát, vaø caùc tröôøng hôïp thöôøng gaëp ôû ngöôøi Vieät Nam ñaõ ñuôïc chuù troïng. Beänh thaän kinh nieân ñaõ ñöôïc moâ taû bôûi Döôïc só Trònh Nguyeãn Ñaøm Giang. Döôïc só Mai Taâm ñaõ so saùnh vaø moâ taû beänh Thieáu Maùu vaø Huyeát Hö giöõa Taây Y vaø Ñoâng Y. Töø nhöõng quan nieäm caù bieät veà beänh lyù, Döôïc só Taâm cuõng neâu ra nhöõng nguyeân taéc chöõa trò trong Ñoâng Y thöïc haønh. Döôïc só Taâm coøn cho bieát nhieàu phöông thuoác coå truyeàn noåi tieáng. Döôïc só Traàn Vieät Höng vaø Baùc só Traàn Quang Tuaán Anh ñaõ toång luaän vieäc Trò Lieäu beänh Thieáu maùu baèng caùc Phöông Phaùp Töï Nhieân döïa vaøo söï dinh döôõng ñaëc bieät, hoå trôï hay boå tuùc, cuøng lieät keâ caùc loaïi döôïc thaûo lieân heä. Phaàn III: Döôïc Khoa Nghieân Cöùu Huyeát nhaân taïo ñöôïc trình baày bôûi baùc só Ñaëng Vaên Chaát vaø Alan B.C. Ñaëng. Ñaây laø moät ñeà taøi toái quan troïng ñöôïc nghieân cöùu trong nhieàu thaäp nieân qua. Caùc taùc giaû ñaõ so saùnh ba loïai döôïc phaåm chuyeân chôû oxigen laø perfluorocarbons vaø hemoglobin töï do hay bao boïc trong moät liposome, cuøng cho bieát töông lai cuûa vieäc khaûo cöùu naøy trong laõnh vöïc Truyeàn Maùu vaø trò beänh Thieáu Maùu.

4 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Tieán só Nguyeãn Ñöùc Kieân cuõng moâ taû tính hoùa döôïc, ñoäc döôïc trong vieäc söû duïng caùc chaát thay theá maùu, cuøng caùc khía caïnh laâm saøng lieân heä, ñeå ñieàu trò chöùng Thieáu Maùu hieåm ngheøo. Caùc ñaëc cheá loaïi EPO tuy ñöôïc duøng trong Hoùa döôïc Trò lieäu vaø cho Beänh Thieáu Maùu vì Thaän suy kinh nieân, cuõng coù theå trong moät soá raát ít tröôøng hôïp, laøm ngöng söï saûn xuaát hoàng huyeát caàu (Pure Red Cell Aplasia). Ñeà taøi naøy ñaõ ñöôïc thaûo luaän roäng raõi giöõa caùc thaønh vieân trong Dieãn Ñaøn Döôïc Khoa, vaø ñöôïc toùm taét bôûi moät baøi vieát cuûa Tieán Só Nguyeãn Höõu Tueä. Thaëng dö saét moâ laø moät bieán loaïn di truyeàn, neáu khoâng ñöôïc trò coù theå laøm haïi cô quan thieát yeáu. Baøi ñöôïc Döôïc só Trònh Nguyeãn Ñaøm Giang trình baày ñaëc bieät nôi ngöôøi Vieät. Caùc yeáu toá ñoäc haïi trong moâi sinh gaây ra Beänh Thieáu Maùu ñöôïc Tieán só Buøi Quoác Quang duyeät xeùt. Söï lieân heä cuøng aûnh höôûng cuûa caùc chaát dieät truøng trong Canh noâng vaø beänh maát sinh saûn hoàng caàu (Aplastic Anemia) trong caùc nöôùc ngheøo hay keùm môû mang ñaõ ñöôïc ñeà caäp ñeán. Phaàn IV: Tin Töùc Döôïc Khoa Vaøi tröôøng hôïp thieáu maùu ñoû vaø moät tröôøng hôïp beänh ñöôïc Baùc só Nguyeãn Taøi Mai trình baày. Baøi Phoûng Vaán Tieán só Nguyeãn Ñöùc Thaùi veà Giaûi Maõ Baûn Ñoà di theå cuûa sieâu vi truøng H5N1 gaây ra beänh dòch cuùm gaø taïi Ñoâng Nam AÙ do Dieãn Ñaøn Y Khoa thöïc hieän ñaõ ñöôïc ñaêng laïi trong Taäp San Chuyeân Nghieäp Döôïc Khoa. Taàm möùc quan troïng cuûa vieäc giaûi maõ naøy cho vieäc chaån ñoaùn hay chích ngöøa cuøng aûnh höôûng treân neàn Sinh hoïc Phaân Töû taïi Vieät Nam ñaõ ñöôïc Tieán só Thaùi löôïng ñònh. AÛnh höôûng cuûa söï thu hoài Vioxx, moät loaïi thuoác ngaên chaën Cox-2 trò thaáp khôùp, ñöôïc moâ taû qua caùc baøi cuûa Döôïc só Trònh Nguyeãn Ñaøm Giang vaø Leâ Vaên Nhaân. Phaàn V: Ñieâm Baùo DS Leâ Vaên Nhaân vaø BS Nguyeãn Vaên Ñích goùp yù veà baøi vieát Beänh Thieáu Maùu do thieáu Folate vaø Sinh toá B12. Phaàn VI: Dòch Thuaät Danh Töø Y Döôïc Moät danh saùch caùc danh töø Y Döôïc ñoái chieáu, Vieät Anh Phaùp ñaõ ñöôïc thieát laäp bôûi DS Leâ Vaên Nhaân ñeå caùc ñoäc giaû tieän duïng. Phaàn VII: Vaên Hoïc Ngheä Thuaät Hai baøi thô do Tieán só Nguyeãn Ñöùc Thaùi vaø Döôïc só Ñaøm Giang ñaõ ñöôïc DS Bình Nhung dòch sang tieáng Anh vaø Phaùp. Phaàn VIII: Sinh Hoaït Döôïc Khoa vaø Tin Töùc Coäng Ñoàng Ñaïi Hoäi Löôõng Nieân HDSVNHK 2004 Sinh Hoaït Sinh Vieân DK-USC: VAPSA-USC Baøi phoûng vaán Tieán só Nguyeãn Höõu Tueä cho bieát vieäc laøm taïi vieän döôïc phaåm, cuøng cung caáp taøi lieäu giuùp caùc Döôïc só hoaëc sinh vieän Döôïc khoa theo ngaønh Döôïc khoa Kyû ngheä. Chöông Trình Vaán Ñaùp Soáng Khoûe ñöôïc BS Nguyeãn Quyeàn Taøi moâ taû. Xin chaân thaønh caûm ôn söï ñoùng goùp baøi vôû cuûa taát caû caùc baïn (hoaëc coäng söï vieân). Toâ Ñoàng, D. Sc, Chuû Bieân Taäp san Döôïc khoa

Vietnamese Pharmaceutical Journal No.5- 5

Editorial

Dear Readers,

The main topic of the Vietnamese Pharmaceutical Journal issue #5 is about Anemia. I am very honored to introduce Dr. Tue H. Nguyen, Guest Editor, who oversees the submission of articles written on this important disease. Dr Nguyen was a graduate of the University of Saigon School of Pharmacy in 1973, and is currently Director of Research and Development at Genentech, Inc., the leading biotechnology company in North California. Follows is a summary of articles in this issue:

PART I: Opinions Mr. Thien D. Ho has collected the discussions, analyzed and assessed why young pharmacists and students in pharmacy are less involved with professional activities in the Vietnamese community than their counterparts in medicine. Dr. Tai Q. Nguyen proposes a possible role for pharmacists in HIV/AIDS prevention programs. This subject had been presented by Dr. Mary J. Berg at the 61th International congress of FIP, Singapor, September , 2001, and had been forwarded by Dr. Huynh Do Phi. PART II: Pharmacy Practice Anemia as a serious complication of Chronic Kidney Disease for nearly 13 million Americans is presented by Dr. Linh To. The condition can be treated with intravenous or subcutaneous injections of erythropoietin (EPO) or its analogs. However, this is not effective because patients who are deficient with iron can be treated with oral supplements or injectable iron complexes. The management of anemia in long-term care residents is described by Dr. Binh N. Tran, with recommendations from the Council for Anemia Clinical Strategies in long-term care. Anemia due to Folate and Vitamin B12 deficiency in Vietnamese immigrants living in Southern California has been researched by Dr. Khanh V.Q.Luong and Dr. Lan H. Nguyen. The report is translated by Mr. Nhan V. Le, who also discusses on the interpretation of laboratory results in anemia, stressing the cases prominent in the Vietnamese people. Mr. Mai Tam compares anemia according to the Western and Eastern schools of Medicine. From the particular opinions on the pathology of the condition, Mr. Tam presents the principles used in Eastern Medicine practice. Well-known traditional formulas are also given. Mr. Hung V. Tran and Dr. Tuan A. Q. Tran review the treatment of anemia using natural methods based on particular diets, to provide supplemental or complementary nutrition. They also list the names of related medicinal herbs. PART III. Pharmacy Research Artificial blood is presented by Dr. Chat Dang and Alan B.C.Dang. This very important topic has been researched in the past decades. Three types of oxygen carriers: perfluorocarbons and hemoglobin free or enclosed in a liposome are discussed, along with the prospect of these researches in the area of blood transfusion and anemia treatment. Dr. Kien D. Nguyen also describes the pharmacochemical and toxicological properties of blood substitutes, and presents the clinical aspects of disease management. Although EPO products are used in chemotherapy and treatment of anemia due to chronic kidney failure, in a few cases, they cause the cessation of erythrocyte production. The syndrome (?) of Pure Red Cell Aplasia (PRCA) has

6 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Toxic factors in the environment that cause anemia are examined by Dr. Quang Q. Bui, emphasizing the correlation of pesticides used in agriculture with the presence of aplastic anemia in the poor or third world countries. PART IV: Medical and Pharmacy News Dr. Thai D. Nguyen has been interviewed on the decoding of the genetic map of ultra virus H5N1 causing the avian virus epidemic in South East Asia. The answers are inserted in the VPhJ #5. The importance of this decoding on the viral diagnostic and research for vaccines, and repercussion on other fields of Molecular Biology is evaluated. The impact of the recall of Vioxx, a COX-2 inhibitor used in arthritis is described by Dr. Giang N. Trinh and Mr. Nhan V. Le. PART V: Articles Review Mr. Nhan Van Le and Dr. Dich Van Nguyen contributed their opinion on the article: "Anemia due to Folate and Vitamine B12 deficiency in Vietnamese Immigrants" PART VI: Terminology A list of English, French and Vietnamese terms used in Anemia was compiled by Dr. Dong To and Mr. Nhan Le. The reader can refer to the list while reading the articles. PART VII: Art and Culture Two poems by Dr. Thai Nguyen and Song Viet have been translated by Binh Nhung. The literary works show another aspect of the authors besides their professional activities. PART VIII: Pharmacy Activities Activities of the Vietnamese Pharmacists Association in the USA, the Vietnamese-American Pharmacy students and other health-related Associations are featured, along with highlights from the Vth International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free World in Sydney, Australia. Instructions to participate in the Healthy Living Program on Pal-talk are also given. With my thanks to all the contributors to this journal issue, (Or I wish to express my thanks to all the contributors to this journal issue.) Sincerely, Dong To, D.Sc. Editor-in-Chief Vietnamese Pharmaceutical Journal

Vietnamese Pharmaceutical Journal No.5- 7

Guest Editor

It was with great honor and pleasure that I embarked on the task of assembling and editing the articles for VPhJ issue No. 5 focusing on anemia. I was honored by the trust that Professor To Dong and of the VPhJ editorial board have in me despite my lack of expertise on the subject. I was continuously enlightened by the excellent articles submitted by the most diverse and talented group of colleagues. I started out with the presumption that anemia is a disease of developing countries due mainly to malnutrition and parasitic infection. I learned that anemia is more insidious even in the US with 2 to 3 million cases a year. Its root cause includes the side effect of chemotherapy, exposure to toxic chemical or chronic renal diseases. Most cases of anemia are treatable if diagnosed, especially with the advent of recombinant DNA erythropoetin. A number of tests are available for the diagnosis of anemia. These tests range from biochemistry to cellular morphology. However, laboratory results are not always definitive and they should be carefully combined with clinical observations for accurate diagnosis. The challenges of developing artificial blood for the management of acute blood loss are numerous but its promises continue to fuel research in this field for the past twenty years. Finally, the convergence of eastern and western medicine thinking on this subject has been my greatest surprise. It appears that one of the main challenges in combating anemia is to bring treatment to the mass population in the developing countries. There, the ingenuity of the scientists is endless. One such example is reflected in a study reported in the project IDEA newsletter, the May 2000 issue of the International Life Science Institute. It described a clinical trial where fish sauce fortified with Iron complex was tested in rural Vietnam to provide daily low dose of Iron supplement. Patient compliance is definitely assured. I hope that the scientific focus of this issue will nicely complement the other sections to fulfill the objectives and mission that the editorial board has set for VPhJ. I sincerely thank our colleagues who contributed to VPhJ No.5. My special recognition goes to Professor To Dong and Dr Binh Nhung Tran who have generously devoted so much of their time and effort to the Journal. Tue H. Nguyen PHD Genentech, Inc. Guest editor

8 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Lettre de l'Editeur

C'est avec beaucoup de plaisir que j'ai embarqueù dans la taâche d'assembler et d'eùditer les articles pour la Revue Pharmaceutique Vietnamienne numeùro 5 au sujet de l'aneùmie. Je suis honoreù de l'attention que Professor To Dong et les eùditeurs m'ont reùserveùe malgreù mes lacunes dans ce domaine. Je suis continuellement surpris en lisant les articles reùdigeùs par les colleøgues dans les domaines les plus divers . Au deùbut, j'ai cru que l'aneùmie est une maladie des pays en voie de deùveloppement, et est dueâ aø la malnutrition et aux infections parasitaires. J'ai appris que cette condition est insidieuse meâme aux Etats-Unis, avec de 2 aø 3 millions de cas chaque anneùe. L'eùtiologie comprend les effets secondaires de la cheùmotheùrapie, l'exposition aux produits chimiques toxiques ou conseùquences des maladies reùnales. La plupart des cas d'aneùmie sont traitables si le diagnostic est fait, surtout avec l'eùrythropoeitine au recombinant DNA. Un certain nombre d'essais sont possibles pour diagnostiquer l'aneùmie, utilisant les techniques en biochimie et cytologie. Neùanmoins, les reùsultats ne sont pas toujours conclusifs, et devraient eâtre confirmeùs par les observations clinicales. L'utilisation du sang artificiel pour traiter les heùmorrhagies massives n'est pas aiseùe, mais les relativement bons reùsultats ont encourageù la recherche dans ce domaine pendant les dernieøres vingt anneùes. En fin de compte, la meùdecine traditionnelle a donneù un apport aø la meùdicine occidentale qui m'a surpris grandement. Parmi les difficulteùs dans la lutte contre l'aneùmie est le traitement dans les pays en voie de deùveloppement, ouø l'ingeniositeù en matieøre de science est surprenante. Un cas est rapporteù dans les nouvelles publieùes par l'International Life science Institute, mois de Mai 2000, au sujet du project IDEA. Il s'agissait d'une eùtude clinique sur le "nuoc mam" saumure Vietnamienne - fortifieùe avec une composition de fer pour voir l'effet sur les paysans au Vietnam. Dans ce cas, la complaisance des sujets est deùfinitivement assureùe. J'espeøre que le theøme de l'aneùmie fait partie du groupe des matieøres preùconiseùes par les Editeurs de la Revue Pharmaceutique Vietnamienne, et renforce les objectifs et la mission de la revue. Je remercie les collaborateurs pour ce numeùro 5, en particulier Dr. Dong To et Dr. Binh Nhung Tran pour tant d'heures et d'efforts au service de la Revue. Tue H. Nguyen, Ph.D., Genentech, Inc. Editeur, VPhJ No. 5

Vietnamese Pharmaceutical Journal No.5- 9

Thöû Phaân Tích vaø Nhaän Ñònh:

Taïi sao giôùi treû Döôïc khoa ít tham gia hôn giôùi treû Y khoa vaøo nhöõng sinh hoaït cuûa toå chöùc ngheà nghieäp vaø Coäng ñoàng Vieät nam

DS Hoà Duy Thieän

Thaâu thaäp vaø ñuùc keát

B

aøi naøy ñöôïc vieát nhaân dòp buoåi Hoïp Maët Thaân Höõu cuûa Dieãn Ñaøn Döôïc Khoa Vieät Nam ñöôïc toå chöùc taïi Little Saigon, California, ngaøy 24 thaùng 12 naêm 2000; vaø ñöôïc trình baøy döôùi daïng frame work from a collection of thoughts ñeå duøng laøm neàn taûng cho nhöõng cuoäc thaûo luaän cuûa Ñeà Taøi: Nhöõng Töông Quan giöõa DÑDK vaø Coäng Ñoàng Döôïc Khoa Vieät Nam. Hieän töôïng giôùi treû Döôïc khoa ít daán thaân vaøo nhöõng sinh hoaït cuûa caùc toå chöùc ngheà nghieäp vaø cuûa coäng ñoàng ngöôøi Vieät, neáu so saùnh vôùi giôùi treû cuûa ngaønh Y khoa, ñaõ trôû thaønh moät caâu hoûi lôùn cho nhöõng baäc ñaøn anh trong ngaønh Döôïc töø nhieàu naêm qua. Raát nhieàu ngöôøi ñaõ baên khoaên, thaéc maéc, vaø töï hoûi taïi sao giôùi treû Y khoa xoâng xaùo vaøo haàu heát caùc sinh hoaït cuûa nhöõng toå chöùc ngheà nghieäp vaø coäng ñoàng Vieät Nam; trong khi giôùi treû Döôïc khoa, ña soá, chuû tröông moät cuoäc soáng raát thaàm laëng? Thaät ra, trong ngaønh Döôïc, khoâng phaûi chæ coù giôùi treû, ñaùng buoàn thay, maø giôùi "soàn soàn" vaø giôùi "lôùn tuoåi", cuõng raát ít tham gia, neáu so saùnh vôùi ngaønh Y khoa! WHY? and HOW TO CHANGE? Dó nhieân, nhöõng caâu hoûi naøy seõ phaûi ñeán..... Thöû nhìn laïi cuoäc ñôøi cuûa moät ngöôøi Y só vaø moät ngöôøi Döôïc só: töø ngaøy coøn laø moät hoïc sinh Trung hoïc, ñeán giai ñoaïn öùng tuyeån vaøo Ñaïi hoïc Y khoa vaø Döôïc khoa, qua giai ñoaïn haønh ngheà, roài ñeán tuoåi tröôûng thaønh, vaø veà höu, ... nhöõng gì khaùc nhau ôû moãi giai ñoaïn, ñeå goùp phaàn ñaøo taïo hai "type" ngöôøi khaùc nhau raát nhieàu treân hai phöông dieän: Leadership vaø Outreach. Trong vaán ñeà hoïc vaán vaø ngheà nghieäp ôû haûi ngoaïi, moãi khi noùi ñeán giôùi treû, ngöôøi ta thöôøng nguï yù noùi nhöõng ngöôøi ñaõ toát nghieäp ñaïi hoïc ôû ngoaïi quoác sau naêm 1975. Haõy baét ñaàu töø giai ñoaïn noäp ñôn öùng tuyeån vaøo

10 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Ñaïi hoïc Y khoa vaø Döôïc khoa. Chöông trình hoïc Y khoa thoâng thöôøng (conventional program) baét ñaàu vôùi 4 naêm ñaïi hoïc (undergraduate) ñeå toát nghieäp vôùi baèng Cöû nhaân (Bachelor). Sau ñoù, öùng tuyeån vaøo Ñaïi hoïc Y khoa (Medical School). Neáu ñöôïc thaâu nhaän, seõ hoïc 4 naêm nöõa ñeå toát nghieäp vôùi maûnh baèng Medical Doctor (MD). Sau cuøng, seõ phaûi thöïc taäp theâm nhieàu naêm ñeå trôû thaønh chuyeân gia trong nhöõng ngaønh Y khoa chuyeân bieät (specialist or sub-specialist). Veà phía Döôïc khoa, thoâng thöôøng, ñoøi hoûi 2 naêm ñaàu ñeå hoaøn taát chöông trình Pre-Pharmacy. Sau ñoù, cuõng phaûi noäp ñôn ñeå öùng tuyeån vaøo Ñaïi hoïc Döôïc khoa. Neáu ñöôïc thaâu nhaän, seõ hoïc theâm 3 naêm ñeå toát nghieäp vôùi baèng Bachelor in Pharmacy, hoaëc 4 naêm ñeå toát nghieäp vôùi baèng Pharmacy Doctorate (Pharm.D.). Veà phía Y khoa, trong 4 naêm ôû undergraduate, maëc duø ña soá sinh vieân theo hoïc ngaønh Döï bò Y khoa (Pre-Medicine) hoaëc nhöõng ngaønh töông öùng (equivalent programs), chaúng haïn nhö Biology, Biochemistry, Chemistry ñeå chuaån bò cho Medical School. Tuy nhieân, cuõng coù moät soá ñoâng sinh vieân, maëc duø ñaõ coù yù ñònh vaøo Y khoa, ñaõ choïn nhöõng ngaønh raát xa laï cho undergraduate, chaúng haïn nhö Kyõ thuaät (Engineering or Technology), Toaùn (Mathematics), hay Nhaân chuûng (Humanity or Social Sciences) ñeå theo hoïc. Ñoái vôùi nhöõng sinh vieân theo hoïc nhöõng ngaønh conventional pre-med, chæ coù khoaûng 40% trong chöông trình ñoøi hoûi phaûi hoïc nhöõng lôùp bò baét buoäc, coøn khoaûng 60% coøn laïi hoï ñöôïc töï do choïn löïa nhöõng lôùp hoïc phuø hôïp vôùi sôû thích, maëc duø raát khaùc xa vôùi chöông trình chuaån bò cho ngaønh Y khoa. Trong khi ñoù, veà phía Döôïc khoa, No choice! Taát caû ñeàu phaûi hoïc moät chöông trình raát gaàn gioáng nhau veà nhöõng moân khoa hoïc vaø toaùn, ñeå chuaån bò vaøo hoïc ngaønh Döôïc sau naøy.

Phaân Tích vaø Nhaän Ñònh - VIEWPOINT

Noäi hai chöông trình Döï bò Y khoa (Pre-medicine) vaø Döï bò Döôïc khoa (Pre-pharmacy) ñaõ khaùc nhau. Töø ñaây, chöông trình hoïc ñaõ taïo ra hai giôùi vôùi hai hình thöùc diversification raát khaùc nhau: Moät beân Y só, coù theå ñeán 15-20% ñaõ khoâng xuaát thaân töø nhöõng ngaønh conventional pre-med (nhö Biology, Biochemistry, Chemistry), maø coù theá laø moät Chemical Engineer, Computer Engineer, Economist, Mathematician, Businessperson, Manager, vaø ngay caû nhöõng chính trò gia, hoaëc nhöõng nhaø ngoân ngöõ hoïc etc... Ñoái vôùi nhöõng ngöôøi ñaõ xuaát thaân töø nhöõng ngaønh conventional pre-med, cuõng ñaõ ñöôïc diversified raát nhieàu, nhôø ñöôïc töï do choïn löïa nhöõng lôùp hoïc khoâng bò baét buoäc phaûi laáy (elective courses). Coøn ngaønh Döôïc, raát thuaàn nhaát nhö nhau. Hai naêm Pre, hoïc raát gioáng nhau. Ba ñeán boán naêm sau khi voâ tröôøng Döôïc, cuõng ñöôïc ñaøo taïo raát gaàn gioáng nhau. Hieän töôïng diversification raát khaùc nhau cuûa hai ngaønh ñaõ goùp phaàn ñöa ñeán söï khaùc nhau trong vaán ñeà hoäi nhaäp vaøo xaõ hoäi cuûa hai giôùi. Chính vì hieän töôïng naøy, nhöõng hoäi ñoaøn Döôïc só raát neân chuù taâm môøi theâm nhöõng ngöôøi tuy xuaát thaân töø ngaønh Döôïc, nhöng nay ñaõ chuyeån qua laøm vieäc trong nhöõng ngaønh khaùc; hoaëc nhöõng ngöôøi tuy khoâng xuaát thaân töø ngaønh Döôïc, nhöng hieän ñang theo hoïc hoaëc laøm vieäc trong nhöõng ngaønh raát lieân heä ñeán Döôïc khoa; ñeå goùp phaàn gia taêng söï phong phuù cho nhöõng sinh hoaït cuûa ñoaøn theå. Tuy nhieân, ñaây vaãn chöa phaûi laø nguyeân nhaân chính. Hay noùi cho ñuùng hôn, ñaây chæ môùi laø haäu quaû baét nguoàn töø hai chöông trình raát khaùc nhau trong nhöõng naêm Pre-Professional programs. Sau khi hoaøn taát chöông trình Pre-Professional (Döï bò Y khoa hay Döï bò Döôïc Khoa), ngöôøi sinh vieân phaûi noäp ñôn öùng tuyeån vaøo Medical School hoaëc Pharmacy School. Moät vaán ñeà khoâng töôûng, nhöng khoâng coù nghóa laø seõ khoâng bao giôø xaûy ra, laø moät cuoäc caûi caùch roäng lôùn chöông trình giaùo duïc Döôïc khoa, ñeå trôû thaønh töông töï nhö Y khoa. Vôùi 4 naêm ñaàu ôû undergraduate, moät ngöôøi sinh vieân döï bò Döôïc khoa, ñöôïc quyeàn hoïc baát cöù ngaønh gì, mieãn laø phaûi laáy moät soá lôùp caàn thieát, ñeå chuaån bò cho ngaønh Döôïc sau naøy. Sau khi ñöôïc choïn vaøo Ñaïi hoïc Döôïc khoa, nhöõng Bachelor naøy seõ phaûi hoïc theâm 4 naêm nöõa ñeå toát nghieäp vôùi maûnh baèng Pharmacy Doctor. Moät chöông trình nhö vaäy seõ ñaøo taïo moät theá heä Döôïc khoa môùi, khoâng nhöõng chæ gioûi theâm veà chuyeân moân, maø coøn phong phuù hoùa toaøn dieän ngaønh Döôïc vôùi nhöõng Döôïc só coù nhieàu background raát khaùc nhau. Söï diversification roäng raõi naøy, seõ giuùp cho ngaønh Döôïc coù theâm raát nhieàu nhöõng ñoàng nghieäp "ña naêng vaø ña daïng" ñeå goùp phaàn vaøo vieäc phaùt trieån ngheà nghieäp (noùi theo danh töø cuûa Tröôøng Döôïc ngaøy xöa ôû Vieät Nam, khi ñöa ra chöông trình caûi toå Giaùo Duïc Döôïc Khoa vaøo khoaûng ñaàu thaäp nieân 70). Trôû laïi vaán ñeà tuyeån löïa öùng sinh, caû hai beân, trong tieán trình tuyeån löïa, ñeàu raát chuù troïng ñeán ñieåm trung bình ñaõ ñaït ñöôïc trong thôøi gian theo hoïc Döï bò (GPA or Grade Point Average), nhöõng moân ñaõ theo hoïc, vaø nhöùt laø soá ñieåm

ñaït ñöôïc trong kyø thi tuyeån vaøo tröôøng chuyeân ngaønh, nhö MCAT (Medical School Admission Test) hay PCAT (Pharmacy School Admission Test). Ñaëc bieät, beân Y khoa, coøn coù moät yeáu toá raát quan troïng gaàn nhö ngang haøng vôùi vaán ñeà hoïc vaán: ñoù laø ngöôøi sinh vieân phaûi chöùng minh ñöôïc raèng töø nhieàu naêm qua hoï ñaõ töøng tham gia vaøo nhöõng hoaït ñoäng xaõ hoäi (ñeå ño löôøng baûn chaát Outreach), vaø ñaõ töøng ñaûm nhaän nhöõng vai troø chính yeáu trong nhöõng toå chöùc hoïc sinh vaø sinh vieân (ñeå löôïng ñònh khaû naêng Leadership). Vì moät ngöôøi Y só khi ñöôïc ñaøo taïo ôû Hoa Kyø; ñeå coù theå trôû thaønh moät ngöôøi Y só thaønh coâng trong khoa hoïc, trong ngheà nghieäp, vaø caû treân ñöôøng ñôøi; hai yeáu toá Outreach vaø Leadership raát caàn thieát, beân caïnh kieán thöùc vaø khaû naêng chuyeân moân. Chính vì yeáu toá naøy, nhöõng sinh vieân khi ñaõ döï ñònh ñi vaøo con ñöôøng Y khoa, ñeàu phaûi chuaån bò cho mình moät quaù trình raát toát veà caû hai khía caïnh noùi treân, ñeå chöùng minh ñöôïc mình coù nhieàu kinh nghieäm veà Leadership vaø coù moät baûn chaát raát maïnh veà Outreach. Söï chuaån bò naøy ñaõ laøm cho ngöôøi hoïc sinh hoaëc sinh vieân phaûi maïnh daïn tham gia vaøo nhöõng hoaït ñoäng xaõ hoäi trong coäng ñoàng nôi hoï sinh soáng, phaûi daán thaân hoaït ñoäng vôùi nhöõng hoäi ñoaøn sinh vieân hoïc sinh trong tröôøng hoaëc trong nhöõng ñoaøn theå beân ngoaøi ñeå hoïc hoûi vaø trau doài hai ñöùc tính noùi treân: Outreach vaø Leadership. Söï sinh hoaït naøy ñaõ trôû thaønh nhö moät thoùi quen. Nhôø ñoù, khi ra tröôøng, laïi coäng theâm vôùi nhu caàu cuûa ngheà nghieäp (seõ ñöôïc baøn tôùi sau), ñaõ laøm cho Y giôùi daán thaân vaøo nhöõng hoaït ñoäng cuûa nhöõng toå chöùc ngheà nghieäp vaø coäng ñoàng maïnh meõ hôn Döôïc giôùi nhieàu. Chaúng nhöõng hôn Döôïc giôùi, phaûi noùi ñuùng hôn, tinh thaàn hoäi nhaäp vaøo xaõ hoäi cuûa Y giôùi maïnh meõ hôn haàu heát caùc ngaønh khaùc; chæ thua moät vaøi ngaønh nhö Luaät khoa, Chính trò, vaø Thöông maïi (Law, Politics, and Business). Trong giai ñoaïn tuyeån löïa, Ñaïi hoïc Döôïc khoa ít chuù troïng hôn veà ñieåm naøy. Maëc duø, neáu coù, thì cuõng laø moät ñieåm son. Nhöng neáu khoâng coù, thì cuõng khoâng phaûi laø moät thieáu soùt traàm troïng, ñeå coù theå bò loaïi deã daøng. Vì duø sao, trong soá nhöõng öùng tuyeån vieân vaøo Ñaïi hoïc Döôïc khoa, thaønh phaàn ñaõ töøng tham döï vaøo nhöõng hoaït ñoäng xaõ hoäi vaø coäng ñoàng cuõng khoâng coù nhieàu. Treân lyù thuyeát vaø giaáy tôø, thì tröôøng chuyeân khoa naøo cuõng ñöa ra haøng chuïc nhöõng ñöùc tính caàn thieát ñoøi hoûi nôi öùng vieân. Tuy nhieân, lyù thuyeát vôùi thöïc haønh khoâng phaûi khi naøo cuõng saùnh ñoâi vôùi nhau. Noùi toùm laïi, tieán trình cuûa söï tuyeån löïa sinh vieân vaøo tröôøng chuyeân ngaønh laø moät maáu choát trong vieäc ñöa tôùi hai söï khaùc bieät cuûa hai giôùi naøy veà tinh thaàn hoäi nhaäp vaøo xaõ hoäi, Leadership and Outreach. Voâ ñeán giai ñoaïn ñi hoïc tröôøng chuyeân ngaønh, Medical School vaø Pharmacy School. Veà phöông dieän chuyeân moân, caû hai ñeàu ñöôïc huaán luyeän gaàn gioáng nhau. Tuy nhieân, treân nhöõng phöông dieän khaùc, coù ñieåm raát thieát yeáu ñaõ goùp phaàn gia taêng tinh thaàn Leadership vaø Outreach cho ngöôøi sinh vieân Y khoa nhieàu hôn. Vì ngöôøi Y só, roài ñaây khi ra ñôøi laøm vieäc, vaãn laø ngöôøi seõ phaûi make the final decision trong vaán ñeà trò lieäu cuûa moät treatment team bao goàm

Vietnamese Pharmaceutical Journal No.5 - 11

QUAN ÑIEÅM - Phaân Tích vaø Nhaän Ñònh

nhieàu chuyeân gia khaùc nhau - vaán ñeà naøy ñoøi hoûi Leadership phaûi raát cao. Ngöôøi Y só seõ laø ngöôøi tröïc tieáp ñoái thoaïi vôùi beänh nhaân vaø tieáp tuïc cuoäc ñoái thoaïi cho ñeán khi naøo beänh nhaân laønh haún hay qua ñôøi - söï kieän naøy, ñoøi hoûi ngöôøi Y só phaûi ñöôïc trau doài ñöùc tính Outreach raát caàn thieát ñeå coù theå giao tieáp vôùi ngöôøi beänh. Chöông trình huaán luyeän trong thôøi gian theo hoïc chuyeân ngaønh, cuõng laø moät yeáu toá goùp phaàn gia taêng tinh thaàn hoäi nhaäp vaøo xaõ hoäi cuûa Y giôùi maïnh hôn so vôùi Döôïc giôùi. Sau khi ra tröôøng, chæ moät thieåu soá Y só ñi laøm coâng chöùc cho chaùnh phuû, hoaëc tö chöùc cho nhöõng cô sôû y teá tö nhaân. Ña soá ñi vaøo laõnh vöïc private business. Coøn Döôïc só, thì ñaïi ña soá laø vaøo laøm vieäc cho nhöõng heä thoáng döôïc phoøng. Nhu caàu cuûa ngheà nghieäp ñaõ thuùc ñaåy hai giôùi coù hai cuoäc soáng raát khaùc nhau xeùt treân phöông dieän hoäi nhaäp vaøo xaõ hoäi. Noùi moät caùch töông ñoái toång quaùt vaø ñôn giaûn: Veà phía Y giôùi, the more you know, or to be known (to other physicians or people), the better. Veà phía Döôïc giôùi, the more you work (how many jobs and how many hours), the better. Vì chöõa trò laø moät ngaønh roäng meânh moâng, coøn raát nhieàu bí aån maø loaøi ngöôøi chöa hieåu bieát heát ñöôïc. Caøng hoïc hoûi nhieàu, caøng tìm ra nhöõng caên bònh môùi. Ñaõ vaäy, theo ñaø tieán hoùa cuûa vaïn vaät, nhöõng bònh môùi ñöôïc phaùt hieän theo thôøi ñaïi vaãn xaûy ra ñeàu ñaën. Kieán thöùc hoïc ñöôïc trong 4 naêm ôû tröôøng Y khoa, coäng theâm vaøi naêm ñi tu nghieäp, vaãn coøn quaù ít ñeå coâng vieäc chöõa trò coù hieäu quaû. Vì vaäy, ngöôøi Y só raát caàn phaûi giao du thaân maät vôùi nhieàu Y só khaùc, ñeå hoïc hoûi theâm, ñeå trau doài kinh nghieäm vaø kieán thöùc, vaø ñeå bieát nhöõng chuyeân gia khaùc (specialist) ñang trò lieäu nhöõng caên beänh ñaëc bieät ngoaøi phaïm vi chuyeân moân cuûa mình. Ñeå trong tröôøng hôïp caàn thieát, phaûi hoaùn chuyeån beänh nhaân laãn cho nhau, haàu coâng vieäc chöõa trò ñaït ñöôïc keát quaû. Ñaõ vaäy, nhu caàu thöông maïi cho ngheà nghieäp, cuõng laø moät lyù do thuùc ñaåy ngöôøi Y só phaûi giöõ söï lieân heä vôùi nhieàu baùc só chuyeân khoa khaùc. Chaúng nhöõng phaûi bieát nhöõng ngöôøi khaùc ñang thuoäc veà nhöõng laõnh vöïc chuyeân moân naøo, maø coøn phaûi laøm sao cho nhieàu ngöôøi khaùc bieát mình ñang chöõa trò trong nhöõng laõnh vöïc chuyeân moân gì. Phaûi laøm sao cho quaàn chuùng bieát ñeán mình vaø laõnh vöïc chuyeân moân maø mình ñang trò lieäu caøng nhieàu caøng toát. Ñaây laø moät trong nhöõng lyù do (toâi xin noùi roõ, ñaây khoâng phaûi laø lyù do duy nhaát), ñaõ thuùc ñaåy ngöôøi Y só daán thaân vaøo nhöõng hoaït ñoäng cuûa xaõ hoäi vaø coäng ñoàng. Naém giöõ nhöõng vai troø then choát, ñeå taïo taêm tieáng trong quaàn chuùng. Chæ tieác raèng, ñaõ coù moät soá vò ñi quaù trôùn, ñeå trôû thaønh nhö nhöng thöông gia hôn laø nhöõng chuyeân gia trong ngaønh trò lieäu. Tuy nhieân, ñoù chæ laø thieåu soá. Ngaønh naøo cuõng coù moät thieåu soá laøm chuyeän khoâng hay. Ñöøng neân vì moät thieåu soá khoâng toát, maø haï thaáp giaù trò cuûa moät ngaønh hay moät ngheà nghieäp. Laøm nhö vaäy laø khoâng coâng baèng. Nhôø ñaõ saün coù moät tinh thaàn phuïc vuï vaø daán thaân töø ngaøy coøn hoïc trung hoïc vaø ñaïi hoïc. Nhôø ñaõ ñöôïc huaán luyeän theâm raát nhieàu veà Leadership vaø Outreach trong thôøi gian theo hoïc Y khoa. Laïi theâm tinh thaàn nhaân ñaïo ñöôïc nhieàu cô hoäi ñeå phaùt huy, nhöùt laø khi phaûi boù tay tröôùc caùi cheát

12 - Taäp San Chuyeân Nghieäp Döôïc Khoa

cuûa ngöôøi beänh. Laïi theâm vì nhu caàu cuûa ngheà nghieäp vaø kinh doanh. Raát nhieàu lyù do ñaõ thuùc ñaåy ngöôøi Y só phaûi tham gia tích cöïc vaøo nhöõng sinh hoaït cuûa ngheà nghieäp, vaø vaøo nhöõng hoaït ñoäng cuûa coäng ñoàng vaø xaõ hoäi. Raát hieám khi thaáy ngöôøi Y só naøo soáng aån daät moät mình. Chæ tröø moät thieåu soá laøm vieäc nhö laø moät coâng chöùc hay tö chöùc. Ngoaøi ra, vì thöôøng xuyeân keà caän vôùi caùi cheát cuûa con ngöôøi, keå caû nhöõng ngöôøi thaân yeâu; nhöùt laø nhöõng khi ñaønh phaûi thuùc thuû tröôùc löôûi haùi cuûa töû thaàn, taâm hoàn ngheä só trong ngöôøi Y só gioáng nhö moät ñaùm coû non ñöôïc töôùi nöôùc ñeàu ñaën. Sau nhieàu naêm thaùng theo hoïc Y khoa, sau vaøi naêm ra tröôøng haønh ngheà, nhieàu Y só ñaõ trôû thaønh ñam meâ vôùi nhöõng thuù vui vaên ngheä, nhö aâm nhaïc, hoäi hoïa, vieát vaên, laøm thô... Ban ñaàu, söï theo ñuoåi vaên ngheä ñöôïc duøng nhö moät thöù tieâu khieån ñeå giaûi trí sau nhöõng giôø laøm vieäc caêng thaúng. Daàn daø, khaû naêng vaên ngheä phaùt trieån, laïi laø moät phöông tieän toát ñeå giuùp ngöôøi Y só coù nhieàu cô hoäi xuaát hieän tröôùc quaàn chuùng vaø ñeå taïo theâm taêm tieáng. Nhaát cöû, ba boán thöù tieän, chöù khoâng phaûi chæ löôõng tieän. Trong khi ngaønh Döôïc, ngöôøi Döôïc só khoâng caàn phaûi quen bieát thaät nhieàu vôùi ñoàng nghieäp, vaãn coù theå tìm ñöôïc good job, vaãn coù theå hoaøn taát coâng vieäc cuûa mình trong döôïc phoøng moät caùch thoaûi maùi, vaãn coù theå töï hoïc theâm baèng nhieàu caùch ñeå tieán boä. Söï trao ñoåi kinh nghieäm vaø kieán thöùc khoâng phaûi laø moät ñieàu toái caàn thieát nhö beân ngaønh Y. Söï bieát theâm nhöõng laõnh vöïc chuyeân moân cuûa caùc ñoàng nghieäp khaùc ñeå trao ñoåi bònh nhaân nhöõng khi caàn thieát, gaàn nhö laø chuyeän khoâng coù. Ñoái vôùi quaàn chuùng, vì ña soá ngöôøi Döôïc só khi ra tröôøng, laøm vieäc nhö laø nhöõng tö chöùc cuûa nhieàu heä thoáng döôïc phoøng khaùc nhau, vì theá vaán ñeà xuaát hieän tröôùc coâng chuùng ñeå taïo tieáng taêm, ñeå hoã trôï cho private business, cuõng khoâng phaûi laø ñieàu caàn thieát. Trong ngaønh Y khoa, moãi khi hoûi thaêm nhau veà coâng vieäc, ngöôøi ta thöôøng hay duøng chöõ Practice, chaúng haïn nhö: Anh aáy ñang PRACTICE medicine ôû nôi naøy nôi khaùc. Trong khi trong ngaønh döôïc, khi noùi chuyeän vôùi nhau veà coâng vieäc, ngöôøi ta hay duøng chöõ Work, chaúng haïn nhö: Chò aáy ñang WORK for Walgreen. Noäi hai chöõ Practice vaø Work ñoù, noù ñaõ bao haøm hai yù nghóa raát khaùc nhau veà cuoäc ñôøi vaø ngheà nghieäp cuûa hai ngaønh naøy roài. Practice, coù theå taïm dòch laø thöïc taäp. Caû moät ñôøi ngöôøi Y só, luùc naøo cuõng vaãn coøn laø thöïc taäp, caàn phaûi hoïc hoûi theâm khoâng bao giôø ngöøng, môùi coù hy voïng chöõa trò höõu hieäu cho beänh nhaân. Coøn vôùi ngaønh Döôïc, sau khi ra tröôøng, laø ñaõ ñuû khaû naêng ñeå laøm vieäc, ñeå work, vaø ñeå laõnh löông. Ñaõ vaäy, nhö treân toâi ñaõ ñeà caäp, ñoái vôùi ngaønh Döôïc: the more you work, the better. Moãi giôø laø $30 ñeán $40. Moãi giôø over-time laø $50 ñeán $60. Laøm caøng nhieàu job, caøng nhieàu giôø, thì pay check caøng lôùn. Caøng sôùm mua nhaø, taäu xe, traû nôï.... Laøm ñaùm cöôùi linh ñình, khoâng thua chi Holywood wedding. Honeymoon in the other side of the world. Laøm gì coøn giôø ñeå tham gia vaøo nhöõng sinh hoaït cuûa caùc toå chöùc ngheà nghieäp. Laøm sao coøn söùc ñeå tham gia vaøo nhöõng sinh hoaït cuûa coäng ñoàng. Nhöùt laø ñoái vôùi nhöõng toå chöùc ngheà nghieäp vaø coäng ñoàng Vieät Nam, ñaâu coù ñem ñeán ñöôïc

Phaân Tích vaø Nhaän Ñònh - VIEWPOINT

nhöõng ích lôïi thieát thöïc cho giôùi naøy ñaâu. Nhöõng toå chöùc naøy, gaàn nhö khoù loøng coù theå thu huùt ñöôïc giôùi Döôïc só treû ñeå tham gia. Tröø phi, nhöõng ngöôøi ñieàu haønh phaûi nhaän thöùc ñöôïc söï thaät khaù ñau loøng, vaø phaûi caûi caùch thaät nhieàu, môùi mong thu huùt vaø giöõ laïi ñöôïc moät soá raát ít trong giôùi treû Döôïc khoa coøn coù loøng vôùi nhöõng toå chöùc cuûa coäng ñoàng Vieät. Noùi ñeán ñaây, coøn moät yeáu toá raát quan troïng ñaõ taïo söï khaùc bieät veà söï hoäi nhaäp vaøo xaõ hoäi cuûa hai giôùi treû Y vs. Döôïc, ñoù laø phaùi tính (gender). Ña soá Y só thuoäc phaùi nam, maëc daàu tyû leä nöõ giôùi trong ngaønh Y ñang gia taêng. Nhöng trong coäng ñoàng Vieät Nam noùi rieâng, vaø AÙ Chaâu noùi chung, ñaïi ña soá Y só cuõng vaãn laø phaùi nam. Söï gia taêng cuûa nöõ giôùi raát chaäm. Coøn veà ngaønh Döôïc, thì ñaïi ña soá laø phaùi nöõ. Nhöõng sinh hoaït cuûa caùc toå chöùc ngheà nghieäp vaø coäng ñoàng Vieät, thöôøng thích hôïp vôùi phaùi nam nhieàu hôn laø vôùi phaùi nöõ. Ngoaøi ra, trong ñôøi soáng gia ñình, ñoái vôùi phaùi nöõ, ngoaøi vieäc ñi laøm beân ngoaøi, cuõng khoâng theá naøo traùnh ñöôïc nhöõng nhieäm vuï beân trong cuûa moät ngöôøi "noäi töôùng", nhö nuoâi con, naáu nöôùng, chaêm soùc nhaø cuûa. Vôùi nhöõng phuï nöõ coøn treû, thì seõ coøn phaûi traûi qua nhöõng giai ñoaïn thai ngheùn sinh ñeû, nuoâi con moïn, daïy doã con hoïc. Phaùi tính cuûa moãi ngheà nghieäp cuõng ñaõ goùp phaàn traû lôøi caâu hoûi cuûa töïa ñeà baøi naøy raát nhieàu. Ngoaøi ra, chöa keå raát nhieàu gia ñình, trong ñoù choàng laø Y só, vôï laø Döôïc só. Trong nhöõng gia ñình naøy, vì nhöõng lyù do nhö ñaõ noùi treân, ngöôøi choàng, ngoaøi vieäc ñi laøm, ñaõ daønh khaù nhieàu thì giôø cho vieäc "vaùc ngaø voi". Ngöôøi vôï, vì theá, ñaõ phaûi daønh nhieàu hôn cho gia ñình, ngoaøi giôø laøm vieäc. Con soá nhöõng gia ñình Y vaø Döôïc raát ñoâng trong laønh vöïc y teá. Hình nhö ñaây laø moät coâng thöùc tuyeät haûo cho ñôøi soáng gia ñình, cho con ñöôøng coâng danh, vaø cho caû nhieàu laõnh vöïc khaùc. Trong nhöõng gia ñình naøy, ngöôøi vôï Döôïc só, nhôø nhöõng hoaït ñoäng cuûa choàng, neân cuõng coù nhieàu cô hoäi xuaát hieän vôùi coäng ñoàng Vieät vaø nhöõng toå chöùc ngheà nghieäp, nhöng thöôøng laø ngheà nghieäp cuûa Y giôùi, cuûa phía beân choàng. Vaø nhöõng ngöôøi vôï Döôïc só naøy, gaàn nhö coøn raát ít thì giôø ñeå tham döï vaøo nhöõng hoaït ñoäng cuûa ngheà nghieäp cuûa giôùi Döôïc khoa hay cuûa coäng ñoàng Vieät. Dó nhieân, chæ tröø moät thieåu soá, raát ñaùng neå phuïc. Thöû nhìn vaøo thaønh phaàn nhöõng ñoaøn chí nguyeän nhaân ñaïo (mission group) ñöôïc gôûi ñi khaép nôi treân theá giôùi ñeå saên soùc söùc khoûe vaø yeåm trôï xaõ hoäi trong nhöõng nöôùc ngheøo, coù bao nhieâu Döôïc só goùp maët. Ñaïi ña soá cuõng vaãn laø Y só, sau ñoù laø nhöõng trôï y vaø nhöõng chuyeân vieân khaùc trong ngaønh y teá. Raát nhieàu Y só ñaõ töï yù boû laøm vieäc moät ñeán hai thaùng trong moät naêm, ñeå tình nguyeän ñi theo nhöõng ñoaøn chí nguyeän ñoù ñeán khaép nôi ñeå laøm vieäc khoâng löông. Gaàn ñaây, qua baùo chí vaø heä thoáng Internet, ñöôïc bieát coù raát nhieàu sinh vieân Y khoa Vieät Nam vaø nhöõng baùc só Vieät Nam raát treû, gia nhaäp nhöõng ñoaøn thieän nguyeän quoác teá ñi veà nhöõng laøng maïc xa xoâi heûo laùnh treân toaøn laõnh thoå Vieät Nam ñeå thöïc hieän nhöõng coâng taùc nhaân ñaïo. Töø nhöõng tænh mieàn thöôïng du Baéc Vieät nhö Cao-Baèng Laïng-Sôn, ñeán taän

cuøng mieàn Nam nhö Caø-Mau Haø-Tieân, ngay caû trong nhöõng boä laïc cuûa caùc saéc toäc thieåu soá vuøng cao nguyeân Trung Phaàn. Chöa keå moät soá baùc só Y khoa lôùn tuoåi, nay ñaõ trôû thaønh nhöõng chuyeân gia loãi laïc, moãi naêm ñeàu trôû veà Vieät Nam daïy hoïc trong caùc tröôøng Y khoa vaø caùc beänh vieän. Ñaây laø moät ñieåm son cuûa Y giôùi Vieät Nam ôû haûi ngoaïi. Coù bao nhieâu Döôïc só, nhöùt laø Döôïc só Vieät Nam, trong nhöõng ñoaøn chí nguyeän quoác teá naøy? Raát hieám, toâi chöa thaáy teân moät ai !!! Chöông trình hoïc ñaõ goùp phaàn ñaøo taïo ra hai type ngöôøi raát khaùc nhau treân phöông dieän nhaân ñaïo. Nhö moät Döôïc só ñaøn anh ñaõ nhaän ñònh raát ñuùng khi noùi raèng: giôùi treû khoâng coù nhöõng baên khoaên veà ñaát nöôùc nhö chuùng ta, vì hoï khoâng caûm thaáy coù boån phaän vôùi coäng ñoàng Vieät Nam hay vôùi queâ höông cuõ, maø chæ muoán laøm moät coâng daân löông thieän cuûa quoác gia nôi ñang soáng. Theá taïi sao giôùi treû Y khoa ñaõ daán thaân phuïc vuï nhö ñaõ keå treân? Roõ raøng phaûi coù moät caùi gì khaùc nhau trong chöông trình huaán luyeän cuûa hai ngheà nghieäp. Maëc duø giôùi treû Döôïc khoa, nhö ñaõ noùi treân, coù nhieàu lyù do ñeå ít khi daán thaân vaøo nhöõng toå chöùc ngheà nghieäp hoaëc caùc coäng ñoàng Vieät. Nhöng vaãn coù moät soá ít raát coù loøng, raát muoán ñoùng goùp, raát muoán daán thaân. Tuy nhieân, khi böôùc chaân ra ngoaøi ñeå tham gia vaøo caùc hoaït ñoäng, giôùi naøy ñaõ ñuïng phaûi moät böùc töôøng thaønh vó ñaïi khoù loøng vöôït qua do thaùi ñoä, caù tính, söï ñoái xöû, khaû naêng laõnh ñaïo, chính kieán, ngoân ngöõ, vaên hoùa etc... you name ít, cuûa giôùi "soàn soàn" vaø giôùi "lôùn tuoåi". Nhöõng ngöôøi naøy ñaõ ra coâng taïo döïng nhöõng toå chöùc ngheà nghieäp hoaëc coäng ñoàng töø nhieàu naêm qua. Phaûi ghi nhaän söï hy sinh cao quyù cuûa baäc ñaøn anh ñaõ ñi tröôùc ñeå thieát laäp. Nhöng theo thôøi gian, nhöõng toå chöùc naøy phaûi thu huùt vaø caàm chaân ñöôïc giôùi treû vaøo nhöõng sinh hoaït thì môùi mong tröôøng toàn vaø phaùt trieån. Nhöng tieác thay, söï caùch bieät veà nhieàu khía caïnh giöõa hai giôùi ñaõ voâ hình chung taïo neân moät böùc töôøng thaønh vó ñaïi ngaên chia maõi maõi. Ñeán ñaây, toâi xin taïm keát thuùc Phaàn 1 cuûa loaït baøi Nhaän Ñònh naøy. Toâi vaãn coøn thaâu thaäp caùc yù kieán ñeå boå tuùc cho Phaàn 2. Xin caùc anh chò cöù gôûi theâm veà cho toâi ôû ñòa chæ [email protected] Trong Phaàn 2, toâi seõ vieát tieáp vieäc laøm sao ñeå giaûm thieåu toái ña söï khaùc bieät ñoù. Sau ñoù, laø ñeà nghò ñeå caûi caùch nhöõng chöông trình sinh hoaït, haàu coù theå thu huùt vaø caàm chaân ñöôïc giôùi treû ôû laïi hoaït ñoäng vôùi caùc ñoaøn theå vaø coäng ñoàng. Cuõng töông töï nhö baøi naøy, nhöõng ñeà nghò ñoù laø do söï coâ ñoäng cuûa nhieàu yù kieán maø toâi ñaõ thaâu thaäp ñöôïc trong nhöõng luùc giao tieáp vôùi caû hai giôùi. Vôùi moät nieàm hy voïng, seõ thaâu heïp khoaûng caùch giöõa hai giôùi, seõ cuøng nhau xoâ ngaõ böùc töôøng thaønh vó ñaïi ñaõ ngaên chia, ñeå cuøng nhau naém tay xaây döïng moät theá heä môùi toát ñeïp hôn cho töông lai cuûa coäng ñoàng Vieät treân xöù ngöôøi. Vaø neáu coù theå ñöôïc... ñeå cuøng nhau thoåi nhöõng luoàng gioù maùt töï do daân chuû veà queâ nhaø cho daân ta ñöôïc höôûng sôùm ngaøy naøo hay ngaøy aáy.

Vietnamese Pharmaceutical Journal No.5 - 13

Vai Troø Döôïc Só Trong Vieäc Phoøng Choáng HIV

Nguyeãn Quyeàn Taøi, MD

H

ai thaäp nieân tröôùc ñaây, caùc döôïc só chæ giöõ vieäc phaân phaùt vaø phaân löôïng caùc thuoác men, vaø khoâng chuù yù nhieàu veà caùc beänh lyù ñeå theo doõi ngöôøi beänh khi hoï duøng thuoác. Keå töø thaäp nieân 80, caùc döôïc só taïi Hoa Kyø ñöôïc giaûng daïy theâm veà beänh lyù vaø aûnh höôûng cuûa caùc thuoác treân beänh tình vaø söùc khoeû noùi chung cuûa ngöôøi beänh, vaø chuù yù nhieàu ñeán ngöôøi beänh. Trong nhöõng beänh vieän lôùn, caùc döôïc só "laâm saøng" (clinical pharmacist) laø moät phaàn töû trong nhoùm chuyeân gia ñieàu trò beänh nhaân, vaø thöôøng xuyeân xem xeùt vaø theo doõi vieäc trò lieäu, vaø coá vaán cho baùc só gia giaûm lieàu thuoác ñeå thích hôïp vôùi beänh traïng cuûa töøng ngöôøi . Trong vieäc phoøng choáng HIV-AIDS , döôïc só cuõng ñoùng moät vai troø quan troïng, trong vieäc phoøng ngöøa cuõng nhö trong vieäc ñieàu trò nhöõng ngöôøi maéc phaûi beänh AIDS. Vì theá, caùc döôïc só caàn bieát roõ moïi khiaù caïnh veà beänh dòch naøy ñeå coù theå chæ daãn cho beänh nhaân cuõng nhö cho ñoàng baøo chöa maéc beänh. Dòch HIV-AIDS hieän nay laø moät ñe doaï traàm troïng cho nhöõng nöôùc ôû vuøng Ñoâng Nam AÙ, vì nhöõng lyù do sau ñaây: 1. Ña soá daân chuùng coøn theo nhieàu phong tuïc taäp quaù xöa, neân khoâng theo nhöõng phöông thöùc veä sinh ñeå phoøng ngöøa beänh. 2. Vì phöông tieän truyeàn thoâng chöa ñeán ñöôïc tôùi moïi taàng lôùp daân chuùng moät caùch ñuùng möùc, ña soá daân chuùng chöa ñöôïc höôùng daãn kyû veà nhöõng vaán ñeà söùc khoeû vaø veä sinh, vaø hoï khoâng hieåu roõ veà hieåm hoïa beänh HIV-AIDS . 3. Vì y teá trong nöôùc coøn thieáu keùm, daân chuùng khoâng coù phöông tieän ñeán caùc cô quan y teá vaø caùc dòch vuï y teá cuûa chaùnh phuû cuõng khoâng theå ñeán vôùi ngöôøi daân thöôøng xuyeân, neân beänh dòch lan laây maø khoâng ñöôïc chaån ñoaùn vaø ñieàu trò kòp thôøi vaø ñuùng möùc. 4. ÔÛ nhöõng vuøng maø ngöôøi ñaøn oâng phaûi tha phöông caàu thöïc, xa nhaø trong thôøi gian daøi, nhöõng beänh lan laây qua ñöôøng tình duïc deã phaùt sinh hôn, trong ñoù nguy hieåm nhaát laø HIV-AIDS .

Vì nhöõng lyù do treân, dòch HIV-AIDS coù cô boäc phaùt maïnh taïi nhöõng quoác gia nhö Vieät Nam. 1. Luùc ban ñaàu, HIV-AIDS thöôøng thaáy ôû nhöõng ngöôøi chích ma tuyù. Naïn ma tuyù ñang baønh tröôùng taïi Vieät Nam vaø dòch HIV-AIDS cuõng theo ñoù maø lan roäng ra. 2. Dòch HIV-AIDS cuõng thöôøng thaáy ôû nhöõng gaùi maõi daâm vaø töø gaùi maõi daâm, lan ñeán khaùch laøng chôi. Nhöõng ngöôøi choàng hay thanh nieân ñi chôi bôøi, maéc phaûi HIV-AIDS maø khoâng bieát, laïi laây sang cho vôï vaø baïn gaùi. Ngöôøi vôï nhieãm beänh seõ lan cho con sô sinh, vaø nhöõng baïn gaùi seõ laây cho nhöõng ngöôøi tình môùi. 3. Nhö theá, dòch HIV-AIDS luùc ñaàu giôùi haïn trong caùc giôùi chích ma tuùy vaø maõi daâm, baây giôø ñaõ ñeán thôøi kyø lan sang nhöõng giôùi khaùc, ñaëc bieät laø giôùi treû, coù nhöõng sinh hoaït tình duïc thöôøng xuyeân. Ñeå ngaên chaän beänh dòch HIV-AIDS, moãi chuùng ta caàn tham gia tröïc tieáp trong vieäc phoøng choáng. Vieäc keâu goïi phoøng ngöøa beänh dòch HIV-AIDS khoâng theå chæ giôùi haïn trong thaønh phaàn nhaân vieân y teá, vaø laø traùch nhieäm cuûa moïi ngöôøi daân. Chuùng ta caàn duøng ñuû moïi caùch ñeå keâu goïi vaø höôùng daãn nhöõng thaønh phaàn daân chuùng coù nguy cô maéc beänh (giôùi chích ma tuyù, giôùi maõi daâm, nhöõng thanh nieân coù sinh hoaït tình duïc thöôøng xuyeân vôùi gaùi maõi daâm hay baïn gaùi, caùc binh só, caùc hoïc sinh, sinh vieân), aùp duïng ñuùng möùc nhöõng phöông phaùp phoøng ngöøa, vaø traùnh nhöõng sinh hoaït coù theå laây beänh cho ngöôøi khaùc. Veà vieäc phoøng ngöøa, nhöõng ñieàu caàn noùi roõ cho moïi ngöôøi bieát nhö sau: 1. Ai cuõng coù theå maéc beänh HIV-AIDS 2. Thaønh phaàn xaõ hoäi naøo, ngheà nghieäp naøo, ngöôøi ôû löùa tuoåi naøo (giaø treû beù lôùn) deã coù theå maéc beänh maø khoâng bieát. 3. Khoâng theå ñoaùn ai laø ngöôøi maéc beänh HIV-AIDS ngoaøi vieäc thöû nghieäm maùu. Vì theá, neáu coù laøm ñieàu gì khieán mình nghi ngôø ñaõ maéc beänh thì phaûi ñi thöû nghieäm maùu

14 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Vai Troø Döôïc Só - VIEWPOINT

ngay laäp töùc (xin noùi laïi: Ngay laäp töùc, khoâng chôø ñeán ngaøy hoâm sau) ñeå ñöôïc cho thuoác ngöøa. 4. Caàn bieát mình coù beänh hay khoâng ñeå khoûi phaûi laây beänh cho ngöôøi khaùc. 5. Khi ñaõ maéc beänh roài thì caàn ñöôïc ñieàu trò suoát ñôøi vaø ñuùng möùc, töùc phaûi uoáng thuoác ñuùng lieàu, vaø ñöôïc nhaân vieân y teá theo doõi thöôøng xuyeân. 6. Ngöôøi maéc beänh, neáu ñöoïc ñieàu trò ñuùng möùc, thì coù theå soáng moät cuoäc soáng khaù "bình thöôøng", vaø tuoåi thoï coù theå khoâng keùm giaûm nhieàu. Vì theá maø ngöôøi beänh caàn ñöôïc chaån ñoaùn vaø ñieàu trò sôùm vaø ñuùng möùc.

Ngöôøi döôïc só coù theå höôùng daãn nhöõng thaønh phaàn keå treân ñeå hoï hieåu roõ veà beänh dòch HIV-AIDS , ñeå hoï khoâng hoang mang, khoâng sôï haûi, vaø hoï coù theå hy voïng soáng moät cuoäc ñôøi khaù bình thöôøng neáu hoï ñöôïc ñieàu trò sôùm . Ngöôøi döôïc só chæ daån caùc ngöôøi nghi ngôø maéc beänh ñeán caùc cô quan y teá ñeå ñöôïc chaån ñoaùn ñieàu trò, vaø coù theå giaûi thích cho nhöõng ngöôøi beänh caùch duøng thuoác, vaø bieát ñöôïc nhöõng phaûn öùng vaø bieán chöùng do thuoác gaây neân. Noùi toùm laïi, nhôø söï hieåu bieát veà beänh lyù vaø thuoác men, cuõng nhö nhöõng phöông tieän y teá taïi ñiaï phöông, ngöôøi döôïc só coù theå ñoùng goùp nhieàu trong vieäc tieáp tay vôùi chaùnh quyeàn vaø caùc cô quan y teá trong vieäc ngaën chaän söï lan truyeàn beänh dòch HIV-AIDS .

Vietnamese Pharmaceutical Journal No.5 - 15

Anemia of Chronic Kidney Disease

Linh Le To, Pharm.D Clinical Nephrology Pharmacist - VA San Diego Healthcare System

Abstract

Anemia, a major application in chronic renal failure, is also a cause for significant morbidity. The introduction of recombinant DNA human erythropoietin (Epogen, Amgen; Procrit, Ortho Biotech), and more recently a second generation erythropoietin product, darbepoietin (Aranesp, Amgen) offers safe and affective treatments for the patients. Clinical results demonstrated improvement in cardiac function, increase in exercise tolerance, and enhancement in quality of life. There are many factors that can cause inadequate response to therapy but the most common one is iron deficiency. Thus, iron level should be tested and iron store maintained by co-administration of iron supplement.

Toùm Löôïc

Beänh thieáu maùu, moät bieán chöùng chính cuûa beänh suy thaän maõn tính, cuõng laø nguyeân nhaân ñaùng keå veà beänh suaát. Erythropoietin saûn xuaát baèng phöông phaùp taùi toå hôïp DNA (Epogen, Amgen; Procrit, Biotech), vaø saûn phaåm theá heä tthöù hai darbepoietin (Aranesp, Amgen) cung öùng moät loái ñieàu trò an toaøn vaø höõu hieäu cho beänh nhaân - keát quaû laâm saøng chöùng minh caûi thieän chöùc naêng tim, taêng söùc chòu ñöïng khi taäp theå duïc, vaø caûi thieän giaù trò cuoäc soáng.

T

here are approximately 13 million Americans with chronic kidney disease (CKD).1 Anemia is one of the major complications of CKD and is a cause of significant morbidity in patients. Anemia is defined as a deficiency in the number of erythrocytes or red blood cells.2,3 Anemia of CKD usually develops when the glomerular filtration rate (GFR) falls below 20 to 30 ml/min. It is characterized as a normocytic, normochromic type of anemia. The primary cause of anemia in CKD patients is insufficient production of erythropoietin (EPO) by the kidneys. EPO stimulates the proliferation and differentiation of erythroid progenitor cells leading to red blood cell (RBC) production. The kidneys produce approximately 90% of EPO with only 10% synthesized by the liver. As kidney function declines, anemia occurs because the diseased kidneys are unable to produce adequate amounts of EPO. Without appropriate therapy, anemia may lead to poor exercise tolerance, fatigue, dizziness, dyspnea on exertion, cardiac enlargement, ventricular hypertrophy, angina, congestive heart failure, decreased cognition, and impaired immune response. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKFK/DOQI) developed clinical practice guidelines in the areas of hemodialysis adequacy,

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DÖÔÏC KHOA THÖÏC HAØNH - Anemia of Chronic Kidney Disease

peritoneal dialysis adequacy, anemia management, and vascular access care. These guidelines are based on clinical studies and expert opinion and intended to increase efficiency of patient care and improve patient outcomes. According to NKF-K/DOQI Clinical Practice Guidelines on the treatment of anemia of CKD, the target hemoglobin range is 11gm/dl to 12 gm/dl (hematocrit range is 33% to 36%).4 The recommendation for target transferrin saturation (TSAT) range is 20% to 50% and target ferritin range is 100 ng/ml to 800 ng/ml. Prior to the introduction of recombinant human erythropoietin (rHuEPO) in 1989, the mainstay of therapy for anemia in CKD patients was androgens and blood transfusions.2,3 These therapies produced suboptimal results and were associated with many undesirable risks and complications. Currently epoetin alfa is the standard therapy for anemia in CKD patients with numerous data showing improvement in quality of life,5 increased exercise tolerance,6 and improvement in cardiac function.7-8 Epoetin alfa (Epogen by Amgen Inc. and Procrit by Ortho Biotech) is a recombinant 165 amino acid glycoprotein with identical amino acid sequence as natural EPO and has a molecular weight of 30,400 daltons.9,10 Epoetin alfa stimulates RBC production similar to natural EPO. Epoetin alfa can be administered intravenously (IV) or subcutaneously (SQ). The half-life of IV epoetin alfa is 6 hours and 22 hours with SQ administration.9,10 Several studies have shown that SQ administration can achieve the same desired hemoglobin with a lower total weekly dose of epoetin alfa compared to IV administration and is the preferred route of administration.11 Epoetin alfa should be initiated at a dose of 80 to 120 units/kg/wk SQ administered in two or three divided doses per week. If given IV, the dose should be initiated at 120 to 180 units/kg/wk IV given in three divided doses. The epoetin alfa dose should be increased by 50% if hematocrit (HCT) rise is less than 2% over a 2 to 4 week period. Epoetin alfa dose should be decreased by 25% if HCT rise exceeds 8% points (or Hgb rise exceeds 3gm/dl) within one month. The epoetin alfa dose should be held if the HCT rise is greater than 8% points in a month. The HCT or Hgb level should be monitored weekly when epoetin alfa therapy is initiated or after each dosage adjustment. Once a stable dose has been established, the HCT or Hgb level should be monitored at least every 2 weeks. Although epoetin alfa is welltolerated, adverse reactions including hypertension, headaches, hyperkalemia, seizures, thrombotic events, and skin reactions may occur. Recently a new erythropoietic agent has been approved by the Food and Drug Administration (FDA) for the treatment of anemia of chronic kidney disease. Darbepoetin alfa (Aranesp by Amgen Inc.) is structurally different from epoetin alfa in that there is a five amino acid change in the primary EPO sequence allowing for the addition of two Nlinked carbohydrate side chains.12 Darbepoetin alfa stimulates RBC production similar to endogenous EPO and epoet20 - Taäp San Chuyeân Nghieäp Döôïc Khoa

in alfa. Several studies have demonstrated that darbepoetin alfa is as effective as epoetin in the treatment of anemia in CKD patients.13,14 Darbepoetin alfa can be administered as an IV or SQ injection once weekly. It has a long half-life of 25.3 hours and 48.8 hours for IV and SQ administration, respectively. Darbepoetin alfa is initiated at a dose of 0.45 mcg/kg/wk IV or SQ once weekly. Dosage adjustments should not be made more often than once a month. If Hgb rise is greater than 1gm/dl in a 2-week period, darbepoetin alfa dose should be decreased by 25%. The dose should be increased by 25% if the Hgb rise is less than 1gm/dl over a 4-week period. Patients previously receiving epoetin alfa three times weekly can be converted to darbepoetin alfa once weekly. Darbepoetin alfa can be administered once every two weeks for patients previously receiving epoetin once weekly. However there is data demonstrating that darbepoetin alfa initiated at every other week dosing can maintain a stable Hgb in rHuEPO-naïve CKD patients.15 There is also on-going studies evaluating once every three weeks to once every four weeks administration of darbepoetin alfa.16 Similar to epoetin alfa, adverse reactions for darbepoetin alfa include hypertension, hypotension, headaches, seizures, myalgia, fever, chest pain, infections, and thrombotic events. Numerous factors may cause inadequate erythropoietic response to epoetin alfa or darbepoetin including infections, inflammations, chronic blood loss, osteitis fibrosa, aluminum toxicity, malignancy, iron deficiency, folate deficiency, and vitamin B12 deficiency.2-4 Among these, iron deficiency is the most common cause of poor response to epoetin alfa therapy. An adequate supply of iron is required for hemoglobin synthesis and the production of RBCs, thus, iron status should be evaluated prior to initiating epoetin alfa or darbepoetin therapy. Iron deficiency may be characterized as functional or absolute. Functional iron deficiency is defined as inadequate iron supply sufficient to support increased erythropoiesis. Iron deficiency is considered absolute when iron stores are depleted. This occurs when the ferritin level is less than 100 ng/ml and transferrin saturation (TSAT) less than 20% in CKD patients. Iron deficiency in CKD patients may occur for several reasons including chronic blood loss, decreased iron intake, and decreased iron absorption; therefore it is imperative that adequate iron stores are maintained to achieve optimal results with epoetin alfa or darbepoetin alfa therapy. Iron replacement can be achieved by administering oral or IV iron preparations. Oral iron products are inexpensive and can decrease the use of IV iron. There are various oral iron preparations available including ferrous sulfate, ferrous fumarate, ferrous gluconate, and iron polysaccharide. The recommended oral iron dose for CKD patients is 200mg of elemental iron per day in 2 to 3 divided doses. Inadequate intestinal absorption (approximately 10-20% absorption) and poor patient compliance significantly reduces the effectiveness of oral iron and studies have shown that oral iron alone cannot maintain adequate iron stores for patients on epoetin alfa. For absolute iron deficiency, IV iron is recommended for rapid repletion of iron stores.

Anemia of Chronic Kidney Disease - PHARMACY PRACTICE

There are currently three parenteral iron preparations available for use in the United States. There is extensive data on the use of iron dextran for iron replacement in CKD patients. NKF-K/DOQI recommends an iron dextran dose of 100mg IV administered with each dialysis for 10 doses for iron repletion in hemodialysis patients.4,17 For CKD patients, iron dextran can be administered as a one-time total IV infusion dose of 500mg to 1000mg. A test dose of 25mg of IV iron dextran should be given prior to initiation of IV iron dextran therapy. Iron dextran has a higher incidence of adverse reactions compared to sodium ferric gluconate and iron sucrose. Severe reactions to IV iron dextran manifests as dyspnea, hypotension, chest pain, angioedema, or urticaria. In addition, dose-related reactions such as arthralgias and myalgias may occur. Although IV iron dextran has a higher incidence of adverse reactions, anaphylatic reactions are rare (less than 1%). Sodium ferric gluconate (Ferrlecit by Schein Pharmaceutical) is another IV iron preparation FDA approved for use in the United States. Sodium ferric gluconate can be administered as IV infusion or IV bolus at a maximum rate of 12.5mg/min.18 For iron repletion, sodium ferric gluconate dose of 125mg IV with each hemodialysis treatment for 8 consecutive doses. For maintenance of iron stores, sodium ferric gluconate dose of 62.5mg to 125mg IV administered once weekly to once monthly. Although severe adverse reactions are rare, reactions such as hypotension, flushing, abdominal cramps, and diarrhea may occur. In addition to having less adverse reactions when compared to iron dex-

tran, there have not been any deaths reported due to the use of sodium ferric gluconate. Therefore, a test dose is not required for sodium ferric gluconate. The newest IV iron preparation FDA approved for use is iron sucrose (Venofer by American Regents Laboratories, Inc.). This is a polynuclear iron hydroxide sucrose complex with a molecular weight of 43,300 daltons.19 For iron replacement, iron sucrose dose of 100mg IV with each hemodialysis session for 10 consecutive doses. Iron sucrose dose of 100mg IV once weekly to once monthly is adequate for maintenance of iron stores. Iron sucrose can be administered as an IV infusion or IV bolus at a maximum rate of 20mg/min. Similar to sodium ferric gluconate, there have not been any reported cases of life-threatening reactions with iron sucrose. Due to the low incidence of severe adverse reactions, a test dose is not required for iron sucrose administration. Although the occurrence of anaphylactic reactions are extremely rare, serious adverse reactions such as urticaria, pruritis, flushing, hypotension, and angioedema have been reported. Anemia is a significant cause of morbidity and mortality in CKD patients, if left untreated. However, with the availability of effective pharmacological agents such as epoetin alfa and darbepoetin alfa, early screening and initiation of therapy would improve the quality of life and reduce morbidity in these patients. Early initiation of treatment of anemia not only improves patient outcomes but may also reduce the costs of healthcare in the future.

References:

1. Nissenson AR, Collins AJ, Hurley J, Petersen H, Pereira BJG, Steinberg EP. Opportunities for improving the care of patients with chronic renal insufficiency: Current practice patterns. J Am Soc Nephrol 2001;12:1713-1720. 2. Eschbach JW, Haley NR, and Adamson JW. The anemia of chronic renal failure: Pathophysiology and effects of recombinant erythropoietin. Contrib Nephrol. 1990; 78:24-37. 3. Eschbach JW and Adamson JW. Anemia of end-stage renal disease (ESRD). Kidney Int. 1985; 28:1-5. Editorial. 4. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease, 2000. Am J Kidney Dis. 37:S182-S238,2001 (suppl 1). 5. Barany P, Pettersson E, and Konarski-Svensson JK. Long-term effects on quality of life in haemodialysis patients of correction of anaemia with erythropoietin. Nephrol Dial Transplant. 1993; 8:426-432. 6. Robertson HT, Haley NR, Guthrie M et al. Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients. Am J Kidney Dis. 1990;15:325-332. 7. Radermacher J, Koch KM. Treatment of renal anemia by erythropoietin substitution-the effects on the cardiovascular system. Clin Nephrol. 1995;44(1 Suppl):S56-S60. 8. Pascual J, Teruel JL, Moya JL et al. Regression of left ventricular hypertrophy after partial correction of anemia with erythropoietin in patients on hemodialysis: A prospective study. Clin Nephrol. 1991;35:280-287. 9. Epogen , epoetin alfa, Package Insert. Amgen Inc., Thousand Oaks, CA. 10. Procrit , epoetin alfa, Package Insert. Ortho Biotech Inc., Raritan, NJ. 11. Ashai NI, Paganini EP, Wilson JM. Intravenous versus subcutaneous dosing of epoetin: a review of the literature. Am J Kidney Dis 1993;22(suppl 1):23-31. 12. Aranesp , darbepoetin alfa, Package Insert. Amgen Inc., Thousand Oaks, CA.

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DÖÔÏC KHOA THÖÏC HAØNH - Anemia of Chronic Kidney Disease

13. Locatelli F, Olivares J, Walker R, et al. Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency. Kidney Int. 2001;60:741-747. 14. Nissenson AR, Swan SK, Lindberg JS, et al. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002;40:110-118. 15. Suranyi M. Novel erythropoiesis stimulating protein (darbepoetin alfa) administered once every other week corrects anemia in patients with CKD. Nephrology 2002;7 (suppl 1):A96. 16. Walker R. AranespTM (darbepoetin alfa) administered at a reduced frequencies of once every 3 weeks (q3w) and once every 4 weeks (q4w) maintains hemoglobin levels in patients with chronic kidney disease (CKD) receiving dialysis. Presented at NKF Clinical Nephrology Meeting. Chicago, IL; 2002 April 19. 17. Bailie GR, Johnson CA, Mason NA. Parenteral iron use in the management of anemia in end-stage renal disease patients. Am J Kidney Dis. 2000;1:1-12. 18. Ferrlecit , sodium ferric gluconate complex, Package Insert. Watson Pharma, Inc. Morristown, NJ. 19. Venofer , iron sucrose, Package Insert. American Regent Laboratories. Shirley, NJ.

22 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Anemia in Longterm Care: A Common Occurrence

Binh Nhung Tran, Pharm.D

Abstract

Anemia is often underdiagnosed in long-term care facilities. In this paper, the types of anemia due to iron deficiency, chronic disease, or vitamin B12 deficiency are presented along with causes and diagnosis. Proper laboratory evaluation helps prevent the complications associated with this condition. Recommendations developed by the Council for Anemia Clinical Strategies provide useful tools for the treatment of anemia in nursing home residents.

Toùm Löôïc

Beänh thieáu maùu thöôøng khoâng ñöôïc chaån ñònh ñaày ñuû trong caùc vieän daønh cho ngöôøi cao nieân. Trong baøi naøy, caùc loaïi beänh thieáu maùu do thieáu chaát saét, do beänh maõn tính, hoaëc thieáu sinh toá B12 ñöôïc trình baày vôùi caùc nguyeân do vaø caùch chaån ñònh. Caùc keát quaû thöû nghieäm seõ giuùp ñònh beänh vaø chöõa trò sôùm, traùnh nhöõng dieãn bieán cuûa beänh. Nhöõng höôùng daãn cuûa Cô quan Thaåm ñònh Beänh thieáu maùu seõ giuùp caùc Döôïc só theo doõi beänh naøy taïi caùc vieän daønh cho ngöôøi cao nieân.

Reùsumeù

Le diagnostic de l'anemie ne s'est pas toujours effectueùen bonnes conditions dans les maisons de repos. Dans cet article, les types d'anemie sont decrits avec leurs causes, soit par deùficience du fer, soit par maladie chronique, ou par manque de vitamine B12. Les resultats des laboratoires aident au diagnostic de la maladie et acceùleørent le traitement en eùvitant les complications. Graâce aux recommendations du Conseil de clinique strategique pour l'Anemie, le traitement de la maladie chez les personnes ageùes sera plus aiseù.

nemia is very common in nursing home residents, and is associated with increased morbidity and mortality1. The condition is not a normal finding in older persons, and hemoglobin concentration should not be adjusted downward in this population2-3. Anemia is an independent risk factor for mortality over 5 years4 , frailty and mobility impairment. An increase in myocardial infarction and poor outcomes following an infarct are noted, and prolonged anemia results in left ventricular hypertrophy5. Anemia is also a risk factor for falls in older persons, and has been shown to lead to functional impairment. Quality of life is impaired, and a high level of fatigue is noted.

A

Vietnamese Pharmaceutical Journal No.5 - 23

DÖÔÏC KHOA THÖÏC HAØNH - Anemia in Longterm Care

CRITERIA FOR DETERMINING ANEMIA Hemoglobin and hematocrit values differ little between the healthy elderly population and the younger population. A hemoglobin concentration of less than 13g/dL in men and less than 12 g/dL in women defines anemia, according to World Health Organization (WHO) standards. While the WHO cutoffs for anemia may be reasonable, they should not be considered optimal hemoglobin concentration. Women with an Hb between 13-14 g/dL have better mobility and lower mortality compared to those with a hemoglobin concentration of less than 12 g/dL. From the third National Health and Nutrition Examination Survey (NHANES II), there is a significant increase in anemia with each decade of life over the age of 70, where the percentage of anemic patients is higher in men than in women, probably due to falling androgen levels. Sex differences in hemoglobin concentration result mainly from differences in testosterone concentration. Hypogonadism in older males (andropause) is commonly associated with approximately a 1 g/dL fall in hemoglobin concentration6. Men who have functional hypogonadism from pituitary adenomas are anemic7, and men with prostate cancer who are undergoing therapy with total androgen blockade are anemic8. Thus, anemia should be investigated and treated appropriately, irrespective of age. TYPES AND CAUSES OF ANEMIA While some of this anemia is due to deficiencies in iron, folate, or vitamin B12, the most common cause is anemia of chronic disease, much of which is associated with chronic kidney disease (CKD). Erythropoietin, or epoetin alfa, has been demonstrated to restore hemoglobin concentrations approaching normal in these persons. Darbepoetin alfa has a longer half-life than that of epoetin alfa, thus can be administered every other week. The Council for Anemia Clinical Strategies in long-term care recommends that the causes of anemia be aggressively sought and that appropriate treatment be given to correct underlying causes and restore hemoglobin concentrations to normal. The most common cause is anemia of chronic disease (3540%). Iron deficiency account for 8-15%, blood loss (7%), myelodysplasia (5%), and chronic kidney disease (6-8%). As in most studies of older persons, a large number of anemias had no diagnosis. Renal insufficiency accounts for the most in anemia of chronic disease (27%), where patients have an erythropoietin deficiency. Other causes include cancer (nonchemotherapy patients), congestive heart failure, hepatitis C, inflammation, diabetes, and rheumatoid arthritis. Patients can have more than one cause of anemia of chronic disease, for example iron deficiency, chronic kidney disease, and rheumatoid arthritis.

24 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Nutritional anemias including deficiency in iron, vitamin B12, or folate, and anemia due to blood loss and drug side effects should be excluded. SIGNS AND SYMPTOMS OF ANEMIA The picture of organs and systems affected is broad. One notices: - Cognitive impairment: depression; dizziness, headache, pallor of mucous membranes, dyspnea. - Systolic ejection murmur, hypotension, orthostasis, wide pulse pressure. - Palpitations, impotence, edema, decreased exercise tolerance, angina, tachycardia, cold intolerance. - Anorexia, fatigue, syncope. ERYTHROPOIESIS Normal hematopoiesis consists of the transformation of multipotential stem cells to committed progenitors and then into erythrocytes. See figure 1. Once a progenitor is committed to forming erythrocytes, it is stimulated by erythropoietin and testosterone, and inhibited by a variety of cytokines (eg. Tumor necrosis factor alpha, interferon gamma, and interleukin-6). Depending on the balance of the stimulus, the cells become mature erythrocytes or undergo an apoptotic death. Figure 1: Physiologic factors involved in the production of normal red blood cell

DIFFERENTIAL DIAGNOSIS OF ANEMIA Anemia can be due to failure of the bone marrow to manufacture adequate blood components, gradual or rapid blood loss from hemorrhage, or rapid breakdown of blood components from hemolysis. A. Anemias due to failure of the bone marrow The bone marrow fails to produce adequate nutrients (vitamin B12, folate, pyridoxine, or iron) necessary for blood production. In other cases, there is primary impairment of hemoglobin synthesis (hemoglobinopathy), or altered maturation of blood cells (myelodysplastic syndromes). Thus strategies for the differential diagnosis of anemia are devised as follows: A corrected reticulocyte count is useful to determine bone marrow function. Anemia associated with an increased reticulocyte count occurs when the bone marrow responds to red cell destruc-

Anemia in Longterm Care - PHARMACY PRACTICE

tion (hemolysis) or hemorrhage. The presence of elevated concentrations of unconjugated bilirubin and lactic dehydrogenase usually accompany hemolysis. If these concentrations are normal, a source of blood loss should be sought, including gastrointestinal bleeding, intracranial bleeds, hemoptysis, trauma, vaginal bleeding, and severe ecchymoses. Since gastrointestinal bleeding is the most common cause of occult blood loss, a stool occult blood test should be obtained. Absence of elevated lactate dehydrogenase (LDH) and indirect bilirubin only tells us that there is no hemolysis. Many conditions - not just blood loss - may be present. For example, myelodysplastic syndrome, which is on the rise in the elderly in the U.S., is associated with a normal LDH, normal bilirubin, and a low reticulocyte count. A low or normal corrected reticulocyte count in the presence of anemia indicates an inadequate bone marrow response. In presence of a low corrected reticulocyte count, determination of red cell morphology indices is useful. An elevated mean corpuscular volume (macrocytosis) suggests vitamin B12 or folate deficiency, hepatic disease, myelodysplasia, hypothyroidism, and alcoholism. Drug may cause either hemolysis or macrocytosis - notably, phenytoin, methotrexate, and azathioprine. B. Anemias due to Vitamin B12 and Folate deficiencies. Measurement of vitamin B12 and folate concentrations will determine anemia due to these causes in the majority of cases. Confirmation of nutritional deficiency in those patients who have values in the lower normal range should be obtained. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Homocysteine level will be elevated in both vitamin B12 and folate deficiencies, but a methylmalonic acid level will be elevated only in Vitamin B12 deficiency. Renal failure is the only other confounding cause of an elevated methyl-malonic acid concentration. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Myelodysplastic syndrome is a bone marrow failure state associated with varying degrees of pancytopenia. About Table 1: Comparison of iron deficiency anemia and anemia of chronic disease Mean corpuscular volume Serum iron Total iron-binding capacity Serum Ferritin Soluble transferrin receptor

half of these patients will also have neutropenia. An elevated mean corpuscular volume with abnormalities in red cell corpuscular has suggested myelodysplastic (MDS) anemia when nutritional deficiency, drugs, and chemotherapy have been excluded. A peripheral blood smear in patients with MDS may show hyposegmented nuclei in the neutrophils or abnormal granular content in the white cells. C. Anemia of chronic disease In persons with a low or normal mean corpuscular volume, the likely diagnoses include anemia of chronic disease, anemia of renal disease, iron deficiency anemia, or thalassemia minor. The differential diagnosis of iron deficiency anemia from anemia of chronic disease is given in Table 1. Persons with microcytosis, a low serum iron, and low ferritin concentrations have iron deficiency anemia. If the iron is low and the ferritin is high, this is suggestive of anemia of chronic disease. In the case other causes of anemia coexist, soluble transferrin receptor may be useful in determining the diagnosis. Circulating soluble transferrin receptors are a new tool in the diagnosis of anemia. They are elevated in iron deficiency anemia even in the presence of chronic disease, but normal or only slightly raised in anemia of chronic disease. Since ferritin concentrations are elevated in inflammation, liver disease, renal disease, cancer, and in some elderly women, soluble transferrin receptors can be of use in making the diagnosis of iron deficiency. Soluble transferrin receptors divided by the log of ferritin (<2.55) is the best method of differentiating anemia of chronic disease from anemia of chronic disease associated with iron deficiency anemia9. However, there does not appear to be much advantage of these newer, more expensive methods over measuring total iron-binding capacity10. Anemia of chronic disease is diagnosed by recognizing renal disease in association with a low erythropoietin level. If the serum creatinine is greater than 2mg/dL, it is unnecessary to measure erythropoietin. In older persons, there can be a declining glomerular filtration rate in presence of normal serum creatinine, due to loss of lean mass associated with aging. This is more marked in the nursing home resident with cachexia. The Cockcroft-Gault equation will demonstrate that the majority of female nursing home residents with a creatinine of 1.2 mg/dL or greater have severe renal impairment.

Iron deficiency Anemia Normal or decreased Decreased Increased Decreased Increased

Anemia of chronic disease Decreased or normal Decreased Normal to Decreased Increased Normal to Decreased

Vietnamese Pharmaceutical Journal No.5 - 25

DÖÔÏC KHOA THÖÏC HAØNH - Anemia in Longterm Care

Figure 2. Calculations in Diagnosing Anemia a. Reticulocyte Index patient's hematocrit Reticulocyte index = reticulocyte % x Normal hematocrit (45) b. Mean Corpuscular Volume (MCV) MCV (fL) = Hematocrit (L/L) Red blood cells /ML x 10 -9

greater than 2 mg/dL. A calculated creatinine clearance should be done to identify residents with chronic renal failure whose creatinine is less than 2mg/dL. - The long half-life of darbepoetin alfa is advantageous in long-term care where a once-or twice-a-month dosing regimen could be utilized. The dosing regimen of erythropoietin should lead to an increase of hemoglobin concentration by no more than 1g/dL in a 2-week period, and target hemoglobin concentration should not exceed 12g/dL. Transferrin saturation and ferritin concentration should be monitored and iron replaced, orally or intravenously, if iron deficiency develops. ROLE OF THE CONSULTANT PHARMACIST IN ANEMIA MANAGEMENT Monitoring for efficacy and toxicity end points with erythropoiesis-stimulating proteins is important11. Dosing adjustments need to be done at intervals of at least four weeks unless clinically indicated. If drug therapy requires dosage adjustment based on lab values and package insert guidelines, refer to clinical product algorithms. Adverse events such as hypertension will be noted. Causes of hypo-response range from missed doses, inadequate iron stores, drug/disease interactions (iron needs an acidic environment to be maximally absorbed), B12/ folate deficiencies, occult blood tests, infection, coexisting medical conditions such as malignancies, hematological disorders, and hemolysis. The pharmacist can take an active lead in educating nurses to become involved in recognizing anemia in the patients, facilitate the development of anemia protocol in the facility, and ensure that laboratory tests are monitored and adjusted as needed. Finally, the cost versus benefit factor should be put in perspective when assessing the use of erythropoietic stimulating proteins. The team approach when working with the physician and the nurse will reduce the risks of falls and injury, restore functional ability, resulting in better quality of life in older patients.

c. Cockcroft - Gault Equation to calculate creatinine clearance (multiply by 0.85 for women) Creatinine clearance (mL/min) = 140 - age in years x body weight (kg) 72 x serum creatinine Example: An 85-year old female nursing home resident with a hemoglobin of 10g/dL weighs 55 kg and has a serum creatinine of 1.3 mg/dL Creatinine clearance = 140 - 85 yrs x 55kg x 0.85 27.5 ml /min 72 x 1.3 mg/dL Thus, her anemia is due to chronic kidney disease. RECOMMENDATIONS OF THE COUNCIL FOR ANEMIA CLINICAL STRATEGIES IN LONG-TERM CARE The Council for Anemia Clinical Strategies in Long-Term Care developed recommendations for the treatment of anemia in long-term care. A hemoglobin concentration of less than 12 g/dL should be evaluated and treated when appropriate. - Treat anemia of chronic kidney disease, looking at positive clinical outcomes such as improved quality of life (physical and mental), and decreased hospitalization and mortality (secondary to decreased falls and fractures), and cardiovascular morbidity. - Increase awareness of chronic kidney disease in the elderly by using formulas to calculate the creatinine clearance. - Erythropoietin should be considered in all anemic residents with chronic kidney disease whose serum creatinine is

References:

1- Diagnosis and Management of Anemia in Long term care. Medical Education Resources, Supplement to Annals of Long-Term Care, August 2003. 2- Tran KH, Udden MM, Taffer GE, et al. Erythropoietin regulation of hematopoesis is preserved in healthy elderly people. Clin Res 1993; 41:116A. 3- Zauber NP, Azuber AG. Hematologic data of healthy very old people. JAMA 1987; 257:2181-2184. 4- Izaks GJ, Westendorp RGJ, Knook DL. The definition of anemia in older persons. JAMA 1999;28:1714-1717.

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Anemia in Longterm Care - PHARMACY PRACTICE

5- Kamenetz Y, Beloosesky Y, Zelter C, et al. Relationship between routine hematological parameters, serum IL-3, IL-6 and erythropoietin and mild anemia and degree of function in the elderly. Aging Clin Exp Res 1998;10:32-38. 6- Weber JP, Walsh PC, Peters CA, Spivak JL. Effect of reversible androgen deprivation on hemoglobin and serum immunoreactive erythropoetin in men. Am J Hematol 1991;36:190-194. 7- Ellagala DB, Alden TD, Couture DE, et al. Anemia, testosterone, and pituitary adenoma in men. J Neruosurg 2003;98:974-977. 8- Bogdanos J, Karamanolakis D, Milathianakis C, et al. Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement. Anticancer Res 2003;23:1757-1762. 9- Malope BI, MacPhail AP, Alberts M, Hiss DC. The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status. Br J haematol 2001;115:910:84-89. 10- Wians FH Jr, Urban JE, Keffer JH, Kroft SH. Discriminating between iron deficiency anemia and anemia of chronic disease using traditional indices of iron status vs transferrin receptor concentration. Am J Clin Pathol 2001;115910:112-118. 11- Binaso, KA, The Role of the Consultant Pharmacist in Anemia Management, in Raising the Bar of Anemia care in the Elderly. An ASCP educational program released on Nov 6, 2004.

Vietnamese Pharmaceutical Journal No.5 - 27

Laøm sao ñoïc ñöôïc keát quaû xeùt nghieäm BEÄNH THIEÁU MAÙU

DS Leâ-vaên-Nhaân Certified Geriatric Pharmacist, Clinical Laboratory Scientist

Abstract :

Using case studies, this article discusses the basic principles which will help the pharmacist interpret haematology laboratory results and to differentiate between various forms of anemia. These include anemia due to Iron and Vitamins insufficiencies, and erythropoietin deficiency because of chronic renal failure. A brief discussion on Thalassemia is also offered as it is one of the major causes of anemia in the Vietnamese population.

Lôøi noùi ñaàu:

Chöông trình ñaøo taïo döôïc só cuûa Phaùp vaø Vieät-nam ñeàu coù phaàn thöïc taäp xeùt nghieäm ñeám maùu ( CBC hay Cells Blood Count). Döôïc só Hoa-kyø khoâng caàn phaûi laøm xeùt nghieäm nhöng traùi laïi phaûi ñoïc ñöôïc keát quaû xeùt nghieäm vaø hieåu ñöôïc keát quaû xeùt nghieäm. Baøi naøy khoâng phaûi laø baøi giaùo khoa, maø chæ oân laïi moät soá ñieåm caên baûn, giuùp quyù ñoàng nghieäp bieát nhìn ôû ñaâu vaø phaùn ñoaùn nhö theá naøo ñeå hieåu roõ yù ñònh baùc só, giaûi thích cho beänh nhaân vaø theo doõi ñieàu trò. Ñieàu caàn ñeå yù laø ngöôøi baùc só duøng keát quaû xeùt nghieäm ñeå ñoái chieáu vôùi beänh söû, trieäu chöùng beänh trong khi chuùng ta chæ coù tôø giaáy xeùt nghieäm, neân phaûi deø-daët vì keát quaû xeùt nghieäm coù khi khoâng phaûn aûnh ñuùng tình traïng beänh. Trong xeùt nghieäm ñeám maùu, chuùng toâi chæ giôùi haïn phaàn hoàng caàu vaø chæ thaûo luaän phaàn thieáu maùu do thieáu saét, do thieáu sinh toá, do thieáu noäi tieát toá erythropoietin ôû thaän vaø löôùt sô beänh thieáu maùu thalassemia thöôøng gaëp ôû ngöôøi Vieät-nam.

Xeùt nghieäm ñeám maùu CBC :

YÙ nghóa caùc töø ngöõ trong xeùt nghieäm CBC: RBC : Red blood cells löôïng hoàng caàu trong mm khoái maùu tính baèng trieäu HGB : Hemoglobin hay huyeát saéc toá. Hemoglobin chuyeân chôû döôõng khí ñeán caùc teá baøo, neáu hemoglobin caáu taïo sai laïc nhö trong beänh thalassemia, seõ khoâng höõu duïng vaø cuõng gioáng nhö khi thieáu hemoglobin. Ngöôøi bình thöôøng, hemoglobin treân 14, nhöng chæ khi naøo xuoáng quaù thaáp döôùi 8 luùc ñoù môùi ñaùng quan ngaïi. HCT : hematocrit hay tyû soá huyeát caàu treân theå tích maùu, HCT thaáp khi huyeát caàu bò suy giaûm. HCT phuï nöõ thöôøng treân 40% vaø phaùi nam treân 45%. Ngöôøi suy thaän kinh nieân HCT giaûm xuoáng thöôøng döôùi 35% coù khi döôùi 30%. MCV : mean corpuscular volume hay theå tích trung bình cuûa hoàng caàu. Bình thöôøng MCV khoaûn 80 ñeán 90, neáu döôùi 80 thì xem nhö hoàng caàu teo laïi ( microcytic) vaø neáu lôùn hôn 100 thì xem laø phì ra ( macrocytic). Hoáng caàu nhoû hôn bình thöôøng khi bò thieáu saét hay bò beänh thalassemia. Hoàng caàu lôùn hôn bình thöôøng khi bò thieáu folate ( do uoáng röôïu chaúng haïn) hay thieáu sinh toá B-12.

28 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Ñoïc Keát Quaû Xeùt Nghieäm Beänh Thieáu Maùu - PHARMACY PRACTICE

MCH : mean corpuscular hemoglobin, löôïng hemoglobin trung bình trong moãi hoàng caàu. MCHC : mean corpuscular hemoglobin concentration hay tyû soá trung bình cuûa hemoglobin trong hoàng caàu. Khi tyû soá naøy thaáp töùc laø ngöôøi naøy thieáu saéc toá (hypochromic anemia). RDW : Red cell Distribution Width hay söï thay ñoåi hình daïng hoàng caàu. con soá naøy lôùn khi ngöôøi beänh ñang thieáu maùu hay saép bò thieáu maùu maëc daàu caùc soá ño khaùc vaãn bình thöôøng. Retic: reticulocyte count hay hoàng caàu maïng löôùi hay hoàng caàu non. Bình thöôøng hoàng caàu non ít khi xuaát hieän ôû ngoaïi vi, chæ taêng cao khi bò xuaát huyeát hay tieâm thuoác kích thích sinh huyeát nhö epoietin vaø cho thaáy heä sinh huyeát trong tuûy xöông bình thöôøng. Traùi laïi, khi RBC, HBG, HCT ñeàu thaáp maø retic cuõng thaáp, thì coù theå heä sinh huyeát bò truïc traëc hay thieáu chaát erythropoietin ôû thaän. Moät tröôøng hôïp thieáu maùu : thöû ñoïc keát quaû xeùt nghieäm sau: Möùc ñoä bình thöôøng RBC 4.93 3.85 - 4.91 HGB 12.0 11.9 - 14.9 HCT 38.0 35.0 - 44.5 MCV 77.1 81.5 - 98.0 MCH 24.3 27.6 - 33.8 MCHC 31.5 33.3 - 35.7 RDW 18.8 11.0 - 14.0% Chuùng ta thaáy löôïng hoàng caàu ôû möùc ñoä bình thöôøng, möùc ñoä HGB vaø HCT tuy coù hôi thaáp nhöng khoâng ôû möùc traàm troïng, MCV vaø MCHC thaáp hôn bình thöôøng thuoäc nhoùm hoàng caàu nhoû hôn bình thöôøng vaø thieáu saéc toá microcytic vaø hypochromic anemia. Ñieàu ñaùng ngaïc nhieân laø RDW raát cao, chöùng toû coù söï giao ñoäng ñöa ñeán chöùng thieáu maùu nhöng khoâng roõ nguyeân nhaân. Tröôøng hôïp naøy phaûi hoûi beänh nhaân beänh gì, ñang duøng thuoác gì, hay hoûi baùc só beänh traïng cuûa beänh nhaân, môùi coù theå giaûi thích roõ raøng vaø chính xaùc keát quaû xeùt nghieäm maùu naøy. Thieáu maùu do thieáu saét : Khi xeùt nghieäm ñeám maùu cho thaáy thieáu maùu vaø MCV thaáp, MCHC thaáp, baùc só coù theå nghi ngôø thieáu maùu do thieáu saét. Baùc só coù theå yeâu caàu thöû theâm nhöõng xeùt nghieäm sau : Serum iron: löôïng saét trong huyeát thanh. Saét do transferrin chuyeân chôû, neân xeùt nghieäm naøy coù theå sai khi löôïng transferrin xuoáng thaáp. Tranferrin : protein chuyeân chôû saét trong maùu TIBC ( Total Iron Binding Capacity ) : khaû naêng transferin coù theå nhaän theâm saét ñeå ñeán möùc baõo hoøa. TIBC lôùn khi thieáu saét vaø xuoáng thaáp khi coù thöøa saét. TSAT : transferrin saturation hay chæ soá cho bieát löôïng saét

döï tröõ saün saøng ñeå cung öùng cho söï thaønh laäp hoàng caàu. Chæ soá naøy phaûi töø 20% ñeán 50%. Ferritin : löôïng saét döï tröõ. Ferritin khoâng phuï thuoäc transferrin neân seõ cho moät keát quaû chính xaùc hôn laø ngöôøi beänh coù thieáu saét khoâng. Tuy nhieân xeùt nghieäm naøy ñaét tieàn hôn, neân thoâng thöôøng baùc só chæ cho thöû saét vaø TIBC. Thí duï RBC HGB HCT MCV MCH MCHC RDW Serum iron TIBC Ferritin 3.96 10.8 32.9 83.0 27.3 32.8 13.8 32 256 47 Möùc ñoä bình thöôøng 4.20 12.0 37.0 81.0 27.0 33.0 11.5 35 245 13 5.40 16.0 47.0 99.0 31.0 37.0 14.5 140 400 150

Trong tröôøng hôïp naøy chuùng ta thaáy RBC, HGB, HCT ñeàu xuoáng thaáp nhöng MCV vaø MCHC laïi bình thöôøng, neân goïi laø beänh thieáu maùu vôùi theå tích vaø saéc toá bình thöôøng normocytic vaø normochromic anemia. RDW cuõng ôû trong möùc bình thöôøng. Chuùng ta khoâng thaáy reticulocyte, neáu cao thì coù theå ñoaùn ñöôïc beänh nhaân bò maát maùu do xuaát huyeát. Löôïng saét thaáp vaø TIBC phuø hôïp vôùi thieáu saét, ferritin coøn ôû trong giôùi haïn nhöng gaàn ñeán möùc thieáu huït. Neáu xem hoà sô thuoác duøng, seõ thaáy beänh nhaân ñang duøng thuoác choáng ñoâng maùu. Thieáu maùu do thieáu sinh toá : Khi beänh nhaân thieáu maùu vaø MCV cao, baùc só seõ nghó laø macrocytic anemia vaø cho thöû löôïng acid folic vaø sinh toá B12 trong maùu. Acid folic thöôøng coù trong thöùc aên töôi, vaø ñöôïc theâm vaøo trong cereal hay boät nguõ coác neân ít khi bò thieáu tröø tröôøng hôïp ngöôøi beänh uoáng röôïu boû aên vaø duøng moät soá thuoác laøm thieáu acid folic nhö thuoác chöõa ñoäng kinh phenytoin (Dilantin). Khoâng neân töï tieän chöõa ngay baèng folic acid vì neáu ngöôøi beänh thieáu sinh toá B-12 trieäu chöùng bieán maát maø beänh vaãn coøn coù theå sinh bieán chöùng nguy hieåm. Thí duï : RBC HGB HCT MCV MCH MCHC RDW Folic acid Vit B-12 HIV 3.2 11.5 35.9 114 36.6 32.1 15.5 27.6 1,959 pos Möùc ñoä bình thöôøng 4.5 - 6.5 14.1 - 18.1 43.5 - 53.7 80 - 97 26 - 32 31.8 - 35.4 11.6 - 14.8 3.0 - 17.0 200 - 950

Chuùng ta thaáy ngöôøi naøy thieáu maùu, MCHC bình thöôøng töùc saéc toá bình thöôøng nhöng MCV cao töùc theå tích hoàng

Vietnamese Pharmaceutical Journal No.5- 29

DÖÔÏC KHOA THÖÏC HAØNH - Ñoïc Keát Quaû Xeùt Nghieäm Beänh Thieáu Maùu

caàu lôùn, goïi laø macrocytic, normochromic anemia. Ñieàu naøy phuø hôïp vôùi chöùng beänh nhieãm HIV. Ñieàu ngaïc nhieân laø löôïng sinh toá B-12 vaø folate raát cao, ñaùng lyù MCV phaûi bình thöôøng. Chuùng toâi khoâng ñuû döõ kieän ñeå tìm hieåu theâm, nhöng ñoaùn laø baùc só ñaõ cho duøng hai sinh toá treân roài môùi cho laøm xeùt nghieäm. Phaûi chôø ñôïi khoaûn 120 ngaøy cho hoàng caàu cuõ cheát thay baèng hoàng caàu môùi sinh, khi ñoù theå tích hoàng caàu môùi bình thöôøng trôû laïi. Beänh thieáu maùu do suy thaän maõn tính: Beänh thaän maõn tính thöôøng keøm theo beänh thieáu maùu. Thaän laønh maïnh saûn xuaát noäi tieát toá kích thích tuûy xöông sinh huyeát goïi laø erythropoietin hay EPO. Thaän suy seõ khoâng saûn xuaát ñuû EPO neân tuûy xöông seõ taïo ít hoàng caàu hôn. Ngoaøi ra, loïc maùu cuõng laøm maát hoàng caàu, vaø thieáu acid folic hay sinh toá B 12 do thieáu dinh döôõng cuõng laøm cho caøng thieáu maùu. Ngöôøi bò suy thaän vôùi Cr> 2mg/dl seõ xem laø thieáu maùu khi: - Phuï nöõ ôû tuoåi coù kinh nguyeät vaø HCT < 33% vaø HGB < 11 g/dl. - Ñaøn oâng hay phuï nöõ ôû tuoåi maõn kinh vaø HCT < 37% vaø HGB < 12 g/dl. - Beänh nhaân seõ ñöôïc tieâm epoitein ñeå giöõ cho HGB ôû möùc 11 ñeán 12 g/dl. Thí duï : RBC HGB HCT MCV MCH MCHC Iron TIBC Ferritin Albumin 3.11 9.3 27.9 88 30 34.1 31 159 261 3.0 Möùc ñoä bình thöôøng 4.60 14.0 42.0 80.0 27.0 32.0 65 228 27 3.5 5.20 18.0 52.0 100.0 31.0 36.0 170.0 428 377 4.5

duøng caùc thuoác maïnh trò ñau bao töû nhö nhoùm öùc cheá bôm proton laøm giaûm acid trong bao töû laøm sao hoøa tan heát saét ñöôïc! Thí duï 2: RBC HGB HCT Iron TIBC Retic Albumin Transferrin saturation 3.46 10.1 32.4 39 206 1.9 3.3 35 Möùc ñoä bình thöôøng 3.5 12.0 36 30 230 < 0.5 3.4 20 - 4.5 - 16.0 - 48 - 160 - 405 - 5.2 - 55

Cuõûng nhö tröôøng hôïp treân, ngöôøi naøy suy thaän, albumin thaáp neân khaù hôn neân möùc ñoä saét cao hôn maëc daàu TIBC vaãn thaáp vì vaãn chöa ñuû transferrin.. Retic 1.9 laø cao hôn bình thöôøng, do ñöôïc tieâm epoietin ñeå kích thích sinh huyeát. Beänh thieáu maùu thalassemia: "Thalas" laø bieån neân Thalassemia ñöôïc dòch laø thieáu maùu vuøng bieån. Neân hieåu bieån ôû ñaây laø Ñòa trung haûi vaø beänh thöôøng xaûy ra ôû caùc nöôùc gaàn Ñiaï Trung haûi nhö YÙ, Hy-laïp. Beänh naøy cuõng thöôøng xaûy ra ôû ngöôøi VN nhöng khoâng phaûi chæ ngöôøi ôû vuøng bieån môùi coù beänh naøy. Hemoglobin laø huyeát saéc toá caàn thieát ñeå chuyeân chôû oxy ñeán caùc teá baøo. Hemoglobin coù 2 chuoãi alpha vaø 2 chuoãi beta. Khi coù söï sai laïc trong caáu truùc cuûa caùc chuoãi naøy, hemoglobin maát khaû naêng chuyeân chôû oxy. Tuøy theo sai laïc ôû chuoãi alpha hay beta chuùng ta coù thalassemia alpha hay beta. Ñaây laø beänh di truyeàn vaø neáu ngöôøi con chæ nhaän coù 1 gene sai laïc töø cha hay meï, ngöôøi ñoù chæ coù thalassemia trait neân beänh nheï, thöôøng khoâng phaûi chuyeàn maùu, trong khi neáu bò caû hai gene töø cha vaø meï thì beänh naëng goïi laø "major" vaø phaûi chuyeàn maùu. Do hoàng caàu bò phaù vôõ do truyeàn maùu cao, nhöõng ngöôøi naøy thöôøng bò söng laù laùch vaø tích tuï nhieàu saét, ñoâi khi phaûi tieâm Desferral ñeå laáy bôùt saét ra khoûi cô theå. May maén laø ngöôøi VN phaàn nhieàu chæ coù "trait" neân khoâng caàn chuyeån maùu. Xeùt nghieäm maùu seõ thaáy gioáng nhö ngöôøi bò thieáu maùu do thieáu saét, nghóa laø hoàng caàu nhoû vaø thieáu saéc toá, nhìn döôùi kính hieån vi seõ thaáy maøu nhaït vaø coù moät chaám ñaäm ôû giöõa nhö hoàng taâm neân coøn goïi laø target cells. Sau ñaây laø moät soá ñieåm khaùc bieät giöõa beänh thieáu maùu do thieáu saét vaø thieáu maùu thalassemia: RDW RBC MCV HGB MCHC Thieáu maùu do thieáu saét cao thaáp thaáp hay bình thöôøng thaáp < 30% Thieáu maùu thalssemia bình thöôøng > 5 trieäu thaáp < 9 g/dl > 30%

Chuùng ta thaáy HGB vaø HCT raát thaáp do tuûy xöông khoâng sinh huyeát ñöôïc. Löôïng saét ño ñöôïc thaáp hôn bình thöôøng, do thieáu transferrin chuyeân chôû chöù khoâng phaûi thieáu thaät söï, vì ferritin cho thaáy löôïng saét döï tröõ vaãn cao. Neáu coù ñöôïc retic chuùng ta seõ thaáy retic thaáp vì maùu khoâng sinh theâm khi thieáu maùu. Tröôøng hôïp retic cao phaàn nhieàu do baùc só ñaõ cho chích epoietin ( Procrit hay Epogen) ñeå sinh huyeát. Neáu baùc só cho vieân saét keøm vôùi Procrit, thì phaûi hieåu duøng ñeå baûo ñaûm coù ñuû chaát saét trong khi sinh huyeát, chöù khoâng phaûi beänh nhaân thieáu saét. Vì saét ñöôïc taùi sinh khi hoàng caàu cheát,neân löôïng saét caàn ñöa vaøo cô theå raát nhoû. Maëc daàu saùch vôû baûo lieàu löôïng vieân saét laø 325mg ngaøy 3 laàn, nhöng ñoù laø tröôøng hôïp thieáu saét traàm troïng, duøng 3 vieân moät ngaøy cô theå khoâng söû duïng heát chæ gaây taùo boùn, vaø vieân saét ñeå trong nhaø khoâng ñaäy kyõ deã gaây tai naïn khi treû em toø moø laáy uoáng. Vieân saét cuõng caàn moâi tröôøng acid ñeå hoøa tan tröôùc khi haáp thuï vaøo maùu,

30 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Ñoïc Keát Quaû Xeùt Nghieäm Beänh Thieáu Maùu - PHARMACY PRACTICE

Ngoaøi ra neáu laøm ñieän dung seõ thaáy HB AØ 2 vaø HG F cao hôn ôû tröôøng hôïp thalassemia. Sau ñaây laø moät tröôøng hôïp thieáu maùu thalassemia cuûa moät phuï nöõ Vieät-nam: Möùc ñoä bình thöôøng RBC 4.90 4.80 - 10.80 HGB 10.1 12.0 - 16.0 HCT 33.0 36 - 48 MCV 67.3 81 - 99 MCH 20.6 26 - 33 MCHC 30.6 32 - 37 Morphology ( Hình daïng hoàng caàu ): - 1+ hypochromic - 1+ microcytic - 1+ target cells - 1+ anisocytosis ( hoàng caàu khoâng ñeàu nhau) Maëc daàu coù baûng so saùnh treân, chuùng ta khoù loøng phaân bieät giöõa beänh thieáu maùu do thieáu saét vaø thieáu maùu do thalassemia, neáu khoâng thaáy möùc ñoä saét vaø ferritin. Moät tröôøng hôïp thöù hai cuõng cuûa moät phuï nöõ VN bò thalassemia keøm theo chöùng rong kinh do xô hoùa töû cung (fibrosis) neân coâng thöùc maùu khoâng khaùc gì ngöôøi bò thieáu maùu do thieáu saét :

RBC HGB HCT MCV MCHC RDW Iron TIBC % saturation Ferrtin

4.02 10.7 33.0 82 32.4 20.1 43 429 10 7

Möùc ñoä bình thöôøng 4.4 - 5.8 13.5 - 16.5 40.0 - 50.0 80 - 98 32.0 - 36.0 0.0 - 15.5 59 - 158 228 - 428 20 - 50 15 - 408

Chuùng ta thaáy möùc ñoä hoàng caâØu, hemoglobin vaø HCT khoâng ñeán noãi thaáp laém vaø MCV cuõng bình thöôøng, nhöng RDW raát cao cho bieát ñang thieáu maùu naëng. Saét thaáp, TIBC cao vaø ferritin raát thaáp cho bieát thieáu saét. Neáu coù retic ôû ñaây leân cao chuùng ta môùi ñoaùn ñöôïc do xuaát huyeát, neáu khoâng, phaûi hoûi beänh nhaân hay coù baùc só cho theâm beänh söû môùi ñoaùn ñöôïc. Mong raèng baøi höôùng daãn treân seõ giuùp quyù ñoàng nghieäp treân phöông dieän haønh ngheà. Chuùc caùc baïn may maén.

Vietnamese Pharmaceutical Journal No.5- 31

Beänh thieáu maùu do thieáu folate vaø sinh toá B12 ôû nhoùm di daân VN vuøng nam California

BS Löông-Vinh Quoác-Khanh , BS Nguyeãn-thò Hoaøng-Lan

(Baøi naøy ñaõ ñaêng treân Southern Medical Journal soá 1, thaùng gieâng naêm 2000) Phieân dòch : DS Leâ-vaên-Nhaân

Abstract:

Background: Although the occurrence of iron deficiency anemia and hemoglobinopathies in Vietnamese immigrants has been reported, folate and vitamin B12 deficiencies have not. Proper diagnosis and effective treatment is necessary to achieve a complete correction of anemia. Methods: We retrospective analyzed the records of the Vietnamese immigrants seen in our medical clinic from 1991 to 1993. Fifty-nine anemic patients (48 females and 11 males) had low levels of red blood cell (RBC) folate and/or serum vitamin B12. Results: The patients' mean age was 37.7+17 years. Mean hemoglobin and hematocrit were 11.4+0.7 g/dL and 34.4+2.2%, respectively. Mean corpuscular volume (MCV) was normal in 40 patients (68%) (mean, 89.1+5 fL.) and low in 19 patients (32%) had low MCV values (mean, 69.7+6 fL.). Forty-four patients had low RBC folate levels (mean, 157.7+41.7 ng/mL). Twenty patients had low serum vitamin B12 levels (mean, 165.6+47 pg/mL)(normal value, 225-1000 pg/mL). Fourteen patients had ferritin levels less than 20%. Conclusions: Concomitant folate, vitamin B12 and iron deficiencies or hemoglobinopathies might have been responsible for either normal or low MCV in some of our anemic patients. In this ethnic group, RBC folate and vitamin B12 levels should be determined in anemic patients.

Toùm taét

Boái caûnh: maëc daàu beänh thieáu maùu do thieáu saét vaø beänh huyeát saéc toá ôû di daân VN ñaõ ñöôïc baùo caùo, chöa coù baùo caùo naøo veà beänh thieáu maùu do thieáu folate vaø sinh toá B12. Caàn chaån ñoaùn ñuùng caùch vaø ñieàu trò höõu hieäu ñeå söûa chöûa hoaøn toaøn chöùng thieáu maùu. Phöông phaùp: Chuùng toâi xem laïi hoà sô nhöõng beänh nhaân VN ñaõ ñeán phoøng maïch chuùng toâi töø naêm 1991 ñeán 1993. 59 beänh nhaân bò thieáu maùu ( 48 nöõ vaø 11 nam) vôùi folate trong hoàng caàu vaø sinh toá B-12 trong huyeát thanh thaáp. Keát quaû: Tuoåi trung bình cuûa beänh nhaân laø 37.7 +/- 17 tuoåi. Trò soá trung bình cuûa hemoglobin vaø hematocrit laø 11.4 +/- 11.07 g/dl vaø 34.4% +/- 2.2% theo thöù töï. MCV trung bình bình thöôøng ôû 40 beänh nhaân (68%) ( 89.1 +/- 5fL) vaø thaáp ôû 19 beänh nhaân (32%) trung bình 69.7 +/- 6fL. 44 beänh nhaân thaáp folate (155.7 +/- 41.7 ng/ml) 20 beänh nhaân thaáp sinh toá B12 ( 165.6 +/- 47 pg/ml). 14 beänh nhaân coù möùc ferrtin < 20%. Keát luaän: Moät soá beänh nhaân thieáu maùu cuûa chuùng toâi coù theå ñaõ coù nhieàu nguyeùn nhaân keát hôïp thieáu folate, sinh toá B12, thieáu saét vaø beänh huyeát saéc toá vôùi MCV bình thöôøng hay thaáp. Trong nhoùm di daân naøy, neân xem laïi nhöõng beänh nhaân thieáu maùu caùc yeáu toá folate trong hoàng caàu, sinh toá B12 trong huyeát thanh.

32 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Beänh thieáu maùu do thieáu folate vaø sinh toá B12 - PHARMACY PRACTICE

au khi chieán tranh VN chaám döùt naêm 1975, hôn 1 trieäu ngöôøi Ñoâng Nam AÙ taùi ñònh cö ôû Hoa-kyø. Phaàn lôùn bò thieáu maùu do thieáu saét vaø beänh huyeát saéc toá (hemoglobin E vaø thalassemia)2-4 Tuy nhieân, chuùng toâi khoâng thaáy baùo caùo naøo veà beänh thieáu folate vaø sinh toá B12 ôû nhoùm thieåu soá naøy. Folic acid vaø cobalamin ( sinh toá B12) giöõ vai troø quan troïng trong vieäc toång hôïp DNA ôû teá baøo ñang sinh soâi naåy nôû. Thieáu folate vaø sinh toá B12 ñöa ñeán chöùng thieáu maùu hoàng caàu lôùn ( megaloblastic anemia). Neáu khoâng chaån ñoaùn ñuùng caùch vaø chöûa trò höõu hieäu, thöôøng khoù ñaït ñeán söûa chöûa toaøn veïn chöùng thieáu maùu. Do ñoù, chuùng toâi baùo caùo tình traïng MCV bình thöôøng hay thaáp keát hôïp vôùi folate vaø sinh toá B12 thaáp trong nhoùm di daân Vieät-nam sinh soáng ôû mieàn nam California laø nôi ngöôøi Vieät-nam cö nguï nhieàu nhaát taïi haûi ngoaïi.

S

theå theâm ferritin thaáp hay khoâng. RDW chæ hôi cao ôû 15 beänh nhaân.

Bieän luaän:

Naêm 1934 Winthrobe5 coâng boá toång hôïp ño löôøng hoàng caàu ñeå ñònh beänh vaø phaân loaïi beänh thieáu maùu khoâng döïa vaøo hình theå huyeát caàu nhöng caên cöù vaøo chæ soá hoàng caàu. Chæ soá hoàng caàu duøng ñeå ñaùnh giaù sô khôûi beänh nhaân thieáu maùu: MCV cao laø chæ tieâu truyeàn thoáng cho beänh thieáu maùu do thieáu folate vaø sinh toá B12. Wheeler vaø coäng söï ñeà nghò neân ño möùc B12 khi MCV > 100fL. Griner vaø Oranberg khuyeân neân kieåm tra möùc folate vaø B12 khi MCV > 95fL. Tuy nhieân, beänh nhaân cuûa chuùng toâi coù MCV bình thöôøng hay thaáp. Hoï coù ferritin vaø löôïng baûo hoøa transferin thaáp cho thaáy thieáu saét. 11 beänh nhaân coù hoàng caàu nhoû hôn bình thöôøng ( microcytosis) vaø hoàng caàu cao ( erythrocytosis) (RBC> 5 x 1012/L) maëc daàu hemoglobin thaáp cho thaáy bò beänh veà huyeát saéc toá ( hemoglobinopathies)2. Coù leõ hoï bò thieáu maùu do thieáu saét ñoàng thôøi vôùi beänh huyeát saéc toá thöôøng gaëp ôû saéc daân Ñoâng Nam AÙ chaâu2-4 neân MCV môùi bình thöôøng hay thaáp. Thompson vaø coäng söï11baùo caùo 82% beänh nhaân coù möùc B12 thaáp gaëp ôû beänh vieän Bellevue New York coù MCV döôùi 95fL. Hoï ñeà nghò neân khaùm nghieäm theâm nhöõng ngöôøi nghi ngôø thieáu B12 maëc daàu MCV bình thöôøng. Craig vaø coäng söï thaáy MCV < 100fL trong 50 tröôøng hôïp thieáu B12 vaø folate trong moät khu chaêm soùc cho ngöôøi cao nieân trong thaønh phoá. Phaàn lôùn nhöõng beänh nhaân naøy khoâng coù trieäu chöùng thieáu folate hay B12. Ngoaøi ra, Seward vaø coäng söï tìm thaáy khoâng coù lieân heä chaët cheû giöõa trò soá MCV vaø keát quaû ñoaùn tröôùc veà beänh thieáu maùu ôû beänh nhaân naèm beänh vieän. Hoï cuõng ñeà nghò MCV laø moät daáu chöùng toài ñeå tìm beänh thieáu maùu do thieáu folate hay B12. RDW ( Red cell Distribution Width) hay tyû leä sai laïc kích thöôùc hoàng caàu duøng ñeå ño hoàng caàu khoâng ñeàu (anisocytosis) . Bessman vaø coäng söï 14 ñeà nghò neân caûi tieán phaân loaïi beänh thieáu maùu baèng trò soá MCV vaø RDW. Hoï baùo caùo nhöõng beänh nhaân thieáu saét, folate, cobalamin ñeàu cao RDW, gioáng nhö beänh nhaân vöøa thieáu caû saét vaø folate hay B12 ngay caû khi MCV vaø hemoglobin bình thöôøng. Phöông phaùp naøy giuùp phaân bieät beänh thieáu maùu thalassemia dò hôïp töû khoâng bieán chöùng ( uncomplicated heterozygous) vaø beänh thieáu maùu do thieáu saét. RDW cuõng laø moät chæ daáu nhaïy caûm nhöng khoâng ñaëc thuø cuûa beänh thieáu saét ôû beänh nhaân phaûi loïc thaän (dialysis) laâu daøi15. Trong moät nghieân cöùu beänh thieáu maùu aùc tính ( pernicious anemia) khoâng ñöôïc chöûa trò, RDW taêng cao trong 2/3 tröôøng hôïp. Tuy nhieân RDW chæ taêng sô trong 15 beänh nhaân thieáu maùu cuûa chuùng toâi. Thoâng thöôøng, möùc B12 <100pg/ml seõ xem nhö ñaùng keå vaø giöõ 100 vaø 200pg/ml seõ xem nhö trung bình17-18. Tuy nhieân, Thompson vaø coäng söï11 baùo caùo 75% beänh nhaân vôùi maãu

Vietnamese Pharmaceutical Journal No.5- 33

Beänh nhaân vaø phöông phaùp:

Chuùng toâi phaân tích hoài toá hoà sô nhöõng ngöôøi di daân ñeán khaùm taïi phoøng maïch töø 1991 ñeán 1993. 59 beänh nhaân thieáu maùu (48 nöõ vaø 11 nam; tuoåi töø 4 ñeán 82 tuoåi) möùc ñoä hoàng caàu, folate vaø sinh toá B12 thaáp. Taát caû beänh nhaân ñeàu ñöôïc ñeám maùu toaøn phaàn (CBC) vôùi chæ soá keå caû MCV vaø RDW ( Red cell Distribution Width). Xeùt nghieäm tìm xem coù thieáu maùu do thieáu saét goàm möùc ñoä saét, khaû naêng gaén saét toaøn phaàn (TIBC), soá phaàn traêm baûo hoøa tranferrin, möùc ñoä ferritin. RBC ( hoàng caàu), möùc ñoä folate vaø sinh toá B12 trong huyeát thanh ñeàu ñöôïc ño ôû moãi beänh nhaân. Döõ lieäu ñöôïc trình baøy nhö laø trung bình coïng ( mean) +/SD ( standard deviation). Söï khaùc bieät ñaùng keå giöõa caùc nhoùm ñöôïc ñaùnh giaù baèng traéc nghieäm Student 's t test 2 chieàu.

Keát quaû:

Tuoåæ trung bình cuûa 59 beänh nhaân laø 37.7 +/- 17 tuoåi. Nam beänh nhaân lôùn tuoåi hôn nöõ beänh nhaân ( 54.4 +/- 20 so vôùi 34 +/- 14 tuoåi p< 0.001). Phuï nöõ bò thieáu maùu nhieàu hôn nam vôùi tyû soá 5 treân 1. Döõ lieäu huyeát hoïc ñöôïc toùm taét thaønh 2 baûng ( khoâng trình baøy trong baøi naøy, nhöng coù trong nguyeân baûn). Möùc trung bình hemoglobin laø 11.4 +/- 0.7 g/dl vaø möùc trung bình HCT laø 34.4 +/- 2.2%. Möùc trung bình MCV bình thöôøng ôû 40 beänh nhaân (68% ôû 89.1 +/- 5 fL). 11 beänh nhaân coù hoàng caàu nhoû (microcytosis) vaø hoàng caàu > 5 x 1012 /L maëc daàu hemoglobin thaáp. 44 beänh nhaân bò folate trong hoàng caàu thaáp, trung bình 157.7 +/- 41.7 ng/ml. 20 beänh nhaân thaáp sinh toá B12 165 +/- 47 pg/ ml vaø beänh nhaân phaùi nam bò thieáu B12 nhieàu hôn phaùi nöõ ( 127.5 +/- 35.6 so vôùi 178.3 +/- 44pg/ml p< 0.001. Hai phuï nöõ vôùi möùc ñoä B12 thaáp coù möùc folate trong hoàng caàu cao. 6 beänh nhaân trong ñoù coù 3 phuï nöõ vaø nam keát hôïp folate trong hoàng caàu vaø B12 ñeàu thaáp. Vaøi beänh nhaân bò löôïng baõo hoøa transferrin thaáp coù

DÖÔÏC KHOA THÖÏC HAØNH - Beänh thieáu maùu do thieáu folate vaø sinh toá B12

tuûy baøo lôùn (megaloblastic marrow) hay keát quaû thöû nghieäm Schilling vôùi möùc B12> 100pg/ml trong huyeát thanh. Duøng phöông phaùp ño phoùng xaï ( radioassay) 20 beänh nhaân cuûa chuùng toâi coù möùc cobalamin thaáp. Ñaõ coù baùo caùo cho bieát phöông phaùp ño phoùng xaï cho keát quaû B12 cao hôn do protein R trong boä xeùt nghieäm 19-20 gaén khoâng ñaëc thuø vôùi caùc chaát töông töï B12. Kolhouse vaø coäng söï 20 trình baøy döõ lieäu vaø ñeà nghò laø phöông phaùp ño phoùng xaï khoâng tìm ñöôïc chöùng thieáu cobalamin khoaûn 20% beänh nhaân. Tuûy baøo megaloblastic cuõng ñöôïc moâ taû ôû beänh nhaân nghieän röôïu vôùi möùc ñoä folate vaø B12 bình thöôøng . Kristensen vaø Gormsen 22 nhaän thaáy khi B12 trong huyeát thanh thaáp phaûn aûnh chöùng chöùng thieáu B12, coù theå hieän dieän ngay khi tuûy xöông khoâng coù huyeát baøo ñöôïc xeáp vaøo loaïi megaloblast. Carmel vaø Karnaze 23 ñeà nghò beänh nhaân vôùi möùc B12 thaáp, keát quaû thöû nghieäm Schilling bình thöôøng, vaø khoâng bò chöùng thieáu maùu hoàng caàu lôùn (megaloblast) coù theå do bieán loaïn chuyeån hoùa B12 . Hôn nöõa, nhöõng beänh nhaân phaùi nam cuûa chuùng toâi lôùn tuoåi hôn vaø coù möùc B12 thaáp hôn phaùi nöõ. Nhöõng nhaän xeùt naøy phuø hôïp vôùi nhöõng nghieân cöùu khaùc24-25. Möùc folate trong huyeát thanh thaáp coù theå chæ cho bieát ngöôøi ñoù duøng ít thöùc aên coù folate trong vaøi ngaøy tröôùc ñoù26. Chæ daáu toát hôn ñeå bieát thieáu folate trong moâ baøo laø ño folate trong hoàng caàu27, vì möùc ñoä naøy khoâng thay ñoåi trong khi hoàng caàu löu thoâng trong maùu vaø cho ta bieát möùc ñoä folate 2 ñeán 3 thaùng tröôùc ñoù. Ngoaøi ra, möùc ñoä folate trong hoàng caàu thaáp töông öùng toát hôn vôùi möùc ñoä thay ñoåi megaloblast trong tuûy xöông hôn laø möùc ñoä folate trong huyeát thanh. Khi caùc chöùng sau ñaây cuøng hieän dieän thieáu saét, beänh gan, tuûy xöông taêng nhieàu (myeloproliferation) hay beänh huyeát saéc toá, möùc ñoä folate trong huyeát thanh vaø trong hoàng caàu coù theå bình thöông, vaø möùc B12 trong huyeát thanh coù theå bình thöôøng hay taêng cao, nhöng vaãn coù theå moâ thieáu sinh toá B12. Ñieàu naøy chæ coù theå chöùng minh qua subtle hypersegmentation hay thöû nghieäm loaïi boû deoxyuridine vaø ñöôïc xaùc minh sau khi chöûa trò baèng sinh

toá B1228. Moät thöû nghieäm khaùc laø giaûm khaû naêng gaén folate trong huyeát thanh ñeå tìm chöùng thieáu folate aån 29. 44 beänh nhaân thieáu maùu cuûa chuùng toâi coù möùc folate trong hoàng caàu thaáp, trong ñoù coù 6 ngöôøi thieáu maùu keát hôïp thieáu caûø folate vaø B12. Coù moät ñeà nghò lieân heä chuyeån hoùa giöõa folate vaø B12, vaø sinh toá B12 coù theå thaáp ôû beänh nhaân thieáu folate30. Ngöôïc laïi, möùc folate trong hoàng caàu thaáp ñöôïc baùo caùo ôû beänh nhaân thieáu B1231-32, vaø möùc ñoä folate trong hoàng caàu bình thöôøng trôû laïi khi chæ chöûa baúng cobalamin31. Nhöõng baèng côù khaùc cho thaáy chuyeån hoùa folate bò truïc traëc khi chæ thieáu cobalamin. Nöôùc tieåu thaûi quaù ñoä formiminoglutamic acid laø chæ daáu nhaïy caûm cho moät loaïi thieáu folate caän laâm saøng33, ñoâi khi gaëp trong chöùng thieáu maùu aùc tính 34. Hai beänh nhaân coù möùc folate cao trong hoàng caàu, coù theå do "methyl-folate" sinh ra bôûi thieáu B12. Vieäc chuyeån hoùa 5methyltetrahydro-folate thaønh tetrahydro-folate caàn homocystein-5-methyltetrahydrofolate transferase35, enzym naøy phuï thuoäc B12. Trong chöùng thieáu B12, söï tích tuï cuûa 5methylhydrofolate vaø folate coù theå xaûy ra26-36. Tuy nhieân, chuùng toâi khoâng theå loaïi boû tính khaû dó beänh nhaân chuùng toâi duøng thöùc aên chöùa nhieàu folate hay duøng lieàu acid folic cao cung caáp ñuû cho giai ñoaïn chuyeân chôû moät daïng naøo cuûa folate vaøo trong hoàng caàu, maëc daàu thieáu B12 . Cooper vaø Lowenstein31 cho thaáy hoaït ñoäng cuûa folate cuûa hoàng caàu thieáu B12 taêng moät phaàn naøo khi duøng moät löôïng lôùn acid folic.

Keát luaän:

Nhöõng ñieàu tìm thaáy ñöa ñeán keát luaän laø nhöõng beänh nhaân thieáu maùu cuûa chuùng toâi do keát hôïp thieáu folate, thieáu B12, thieáu saét vaø beänh huyeát saéc toá, do ñoù MCV môùi bình thöôøng hay thaáp. chæ soá MCV thöôøng chæ ôû möùc bình thöôøng maëc daàu thieáu folate vaø B12 ôû beänh nhaân thieáu maùu ngöôøi VN. Neân ño folate trong hoàng caàu vaø B12 trong huyeát thanh ôû nhoùm di daân naøy.

References:

1. US Committee for Refugees, Immigration and Refugee Services of America. Refugee Report 1995 : 12:10-11 2. Fiarbanks VF, Gilchrist GS, Brimhall B et al: Hemoglobin E trait reexamined: a cause of microcytosis and erythrocytosis.Blood 1979; 53: 109-115 3. Hurst D., Title B, Kleman KM et al: Aenemia and hemoglobinopathies in Southeast Asian Refugee children. J Pediatr 1983; 102: 692-697 4. Dode C, Berth A, Bourdillon F et al : hemoglobin disorders among Southeast Asian refugees in France : Acta heamatol 1987; 78: 135-136 5. Winthrobe MM: anemia-Classification and treatment on the basis of differences in the average value and hemoglobin content of the red corpuscules. Arch Intern med 1934; 54: 256-280 6. Wheeler LA, brecher G, Sheiner LB: Clinical laboratory use in the evaluation of anemia; JAMA 1977; 238: 2709-2714

34 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Beänh thieáu maùu do thieáu folate vaø sinh toá B12 - PHARMACY PRACTICE

7. Griner PF, Oranberg PR: predictive values of erythrocyte indices for tests of iron, folic acid and vitamin B12 deficiency; Am J Clin Pathol 1978; 70: 748-750 8. Croft RF, Streeter AM,O'Neil BJ: Red cell indices in megaloblastosis and iron deficiency; Pathology 1974 ; 6:107-117 9. Spivak JL: Masked megaloblastic anemia; Arch Intern Med 1982 ; 142: 2111-2114 10. Green R Kuhl W, Jacobson R et al, Masking of macrocytosis by alpha-thalassemia in blacks with pernicious anemia; N Engl J Med 1982 ; 307: 1322-1325 11. Thompson WG, Babitz L.,Cassino C. et al: Evaluation of current criteria used to measure vitamin B12 levels Am J Med 1987 : 82 : 291-294 12. Craig GM. Elliot C. Hughes KR: Masked vitamin B12 and folate deficiency in the elderly Br J Nutr 1985 : 54: 613-619 13. Seward SJ. Safran C. Marton KI. et al: does the mean corpuscular volume helps physicians evaluate hospitalized patients with anemia? J Gen Intern med 1990 : 5: 187- 191 14. Bessman JD, Gilmer PR.garner FH.: Improves classification of anemias by MCV and RDW Am J Clin Pathol 1983: 80: 322-326 15. Morgan DL.Peck SD.: The use of red cell distribution width in the detection of iron deficiency in chronic hemodialysis patients Am J Clin Pathol 1988: 89: 513-515 16. Saxena S. Weiner JM. Carmel R. : Red cell distribution width in untreated pernicous anemia. Am J Clin Pathol 1988: 89: 660-663

Vietnamese Pharmaceutical Journal No.5- 35

Beä n h Thaä n Kinh Nieâ n

(Chronic Kidney Disease)

DS. Trònh Nguyeãn Ñaøm Giang

Abstract

Chronic kidney disease progressively leads to chronic kidney failure. Irreversible deterioration of kidney functions that leads to a life-threatening condition will require dialysis and renal transplantation to sustain life. Early detection, which is extremely important in the treatment of kidney disease, may arrest its progress toward end-stage renal disease (ESRD). This article offers an overview of the chronic kidney disease as well as commonly adopted treatment options available to health-care providers.

Toùm taét

Beänh Thaän Kinh Nieân (BTKN) laø moät beänh tieán trieån, laøm maát daàn chöùc naêng cuûa thaän khoâng theå phuïc hoài ñöôïc. Tôùi moät tuoåi naøo ñoù moïi ngöôøi ñeàu bò maát daàn chöùc naêng cuûa thaän. Chöùc naêng cuûa thaän khi thoaùi hoùa quaù söùc thì seõ daãn ñeán moät tình traïng coù theå nguy hieåm ñeán tính maïng vaø ngöôøi beänh caàn phaûi coù söï trôï giuùp laøm thaåm taùch vaø toái haäu coù theå laø gheùp thaän khaùc thì môùi coù theå soáng ñöôïc thoaûi maùi hôn. Neáu ñöôïc khaùm phaù sôùm vôùi trò lieäu kòp thôøi thì coù theå laøm trì hoaõn ngöôøi beänh ñi vaøo giai ñoaïn cuoái cuûa beänh thaän (1) Baøi vieát naøy coù tính caùch toùm löôïc noùi toång quaùt veà beänh thaän kinh nieân , nhöõng nguyeân do gaây neân beänh, vaø nhöõng caùch chöõa trò thoâng duïng chuaån vôùi muïc ñích giuùp giôùi saên soùc söùc khoûe lieân heä coù moät caùi nhìn toaøn dieän veà beänh, khi coù tröôøng hôïp caàn bieát ñeán.

Beânh Thaän Kinh Nieân ä

B

eänh Thaän Kinh Nieân (chronic kidney disease/CKD) laø moät cuïm töø ñaët ra bôûi Hoäi Thaän Quoác Gia (The National Kidney Disease Foundation/NKD) ñeå chæ ñònh nhöõng beänh thuoäc ñöôøng thaän.

Neáu beänh ñöôøng thaän ñöôïc chaån ñoaùn sôùm trong giai ñoaïn môùi chôùm vaø ñöôïc baét ñaàu trò lieäu ngay thì coù nhieàu trieån voïng laøm chaäm ñöôïc beänh suy thaän (renal failure). Beänh Thaän Kinh Nieân (BTKN) laø moät beänh aâm æ (insidious), tieán trieån, laøm maát daàn chöùc naêng cuûa thaän khoâng theå phuïc hoài ñöôïc. Khi löôïng creatinine trong maùu cao hôn 1.5 mg/dL cho ñaøn baø vaø 2.0 mg/dL cho ñaøn oâng, hay khi heä soá thanh thaûi creatinine (creatinine clearance) thaáp hôn 60mL/phuùt/1.73m2, vaø keùo daøi laâu hôn ba thaùng thì coi nhö laø baét ñaàu bò beänh thaän kinh nieân. Toác ñoä tieán trieån beänh thay ñoåi tuøy theo beänh vaø söï hieän dieän cuûa protein trong maùu (1,2).

36 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Beänh Thaän Kinh Nieân - PHARMACY PRACTICE

Theo NKD, Beänh Thaän Kinh Nieân ñöôïc saép xeáp thaønh naêm giai ñoaïn nhö sau (3): Giai ñoaïn 0 I II III IV V Mieâu taû Vôùi yeáu toá ruûi Thaän hö haïi vôùi GFR bình thöôøng hay hôi thaáp Nheï (mild) Vöøa phaûi(moderate) Traàm troïng (severe) Thaän suy (kidney failure)

Beänh Cao Huyeát AÙp

Beänh thaän ôû ngöôøi lôùn tuoåi

Khi aùp suaát trong tieåu caàu thaän (glomerulus) taêng, noù seõ taïo neân beänh sô cöùng tieåu caàu Toác ñoä loïc qua thaän mL/min Glomerular Filtration rate/GFR thaän. Tuøy theo ñoä naëng nheï cuûa beänh cao huyeát aùp, trieäu >90 chöùng coù theå thay ñoåi. Protein trong nöôùc tieåu (proteinuria), >90 tieåu tieän ñeâm (nocturia), vaø nöôùc tieåu vaån ñuïc coù truï 60-89 (casts). Sau ñoù daàn daàn beänh 30-59 coù theå trôû thaønh beänh coù nitro 15-29 urea trong maùu (azotemia). <15 Thoáng keâ cho bieát ngöôøi da ñen coù nhieàu ruûi bò BTKN vì ñoä ruûi maéc beänh cao huyeát aùp nhieàu hôn gioáng da traéng (5). Beänh thuoäc tieåu caàu (glomerular disease) Beänh tieåu caàu aûnh höôûng ñeán tieåu caàu maïch (glomeruli), gaây neân bieán ñoåi ñoä thaåm thaáu cuûa maøng tieåu caàu, chöùc naêng, vaø cô caáu. Beänh tieåu caàu coù theå do thaän (vieâm tieåu caàu thaän) , hoaëc coù theå coù nguoàn goác khaùc do söï roái loaïn cuûa nhieàu cô quan trong cô theå, nhö beänh vieâm maïn tính moâ lieân keát (systemic lupus erythematosus). Beänh vieâm naøy coù theå khoûi maø khoâng ñeå laïi daáu veát seïo hay bieán chuyeån thaønh beänh sô cöùng (sclerosis), hay coù theå tieán haønh trôû neân sô cöùng hoaëc nhanh hoaëc chaäm. Protein trong nöôùc tieåu (proteinuria), maùu trong nöôùc tieåu (hematuria) hoàng huyeát caàu daïng baát bình thöôøng (dysmorphic red blood cells), vaø hoàng huyeát caàu ñoùng khuoân truï (red cells casts) trong nöôùc tieåu. Vieâm thaän keõ (interstitial nephritis) Gaây neân bôûi thuoác vaø kim loaïi naëng. Hö haïi oáng nhoû trong thaän laøm noàng ñoä nöôùc tieåu trôû neân baát bình thuôøng, pH vaø nhöõng chaát ñieän phaân (electrolytes) baát bình thöôøng, nhöng khoâng coù protein hay hoàng huyeát caàu trong nöôùc tieåu. Vieâm beå thaän kinh nieân (chronic pyelonephritis) Vieâm kinh nieân laøm vieâm khoaûng giöõa (interstitial) vaø hoaïi töû teá baøo oáng (tubular cell necrosis). Vieâm laøm taêng aùp xuaát trong nang bao thaän (kidney capsule). Khi aùp xuaát trong nang thaän cao hôn aùp suaát thuûy tónh (hydrostatic pressure), thì toác ñoä loïc qua oáng tieåu caàu thaän (GFR) giaûm xuoáng. Do nang, di truyeàn, baåm sinh (cystic/hereditary/congenital) Hoäi chöùng Alport, beänh thaän ña nang (polycystic kidney disease), beänh thaän tuûy nang (medullary cystic KD), dò daïng cuûa oáng daãn tieåu. Beänh do taéc ngheõn (obstructive disorders) Ñaù saïn, ung thö, phì lôùn tuyeán tieàn lieät laøm caûn trôû doøng löu cuûa nöôùc tieåu, laøm taêng aùp xuaát trong nang thaän so vôùi aùp suaát thuûy tónh (hydrostatic pressure) laøm giaûm GFR, gaây neân hö haïi cho nhöõng moâ quan troïng. Keát quaû cuûa beänh

Vietnamese Pharmaceutical Journal No.5- 37

Beänh thaän xuaát hieän ôû ngöôøi lôùn tuoåi laø chuyeän khoâng theå traùnh ñöôïc. Sau tuoåi 40, cöù moãi naêm trung bình moät ngöôøi seõ maát côõ 1 ml creatinine clearance (CrCl). Khi tôùi tuoåi 80, CrCl coù theå bò suy giaûm 50% so vôùi bình thöôøng. Söï baát ñieàu hoøa cuûa thaän coù theå baét ñaàu ngay caû khi serum creatinine (SrCr) trong maùu khoâng taêng vì ngöôøi giaø coù khuynh höôùng gia taêng tæ soá môõ so vôùi cô (fat-to-muscle). Creatinine laø moät saûn phaåm phuï (byproduct) cuûa cô cho neân moät ngöôøi coù khoái löôïng cô thaáp thöôøng coù SrCr thaáp. Ño löôøng CrCl raát caàn thieát ñeå phoûng chöøng beänh thaän ôû ngöôøi giaø (1,2,3)ø.

Nguyeân nhaân gaây Beänh Thaän Kinh Nieân

Nguyeân nhaân chính gaây beänh thaän kinh nieân laø do: * Beänh tieåu ñöôøng (Diabetes mellitus), vaø beänh cao huyeát aùp (hypertension) chieám 50-70% tröôøng hôïp. * Beänh vieâm thaän tieåu caàu (glomerulonephritis), beänh thuoäc baøng quang (cystic diseases), vaø beänh ñöôøng tieåu khaùc côõ 20- 25%. * Beänh khoâng tìm ñöôïc lyù do côõ 15% Beänh Tieåu Ñöôøng (Diabete Mellitus/DM) Beänh Tieåu Ñöôøng (DM) loaïi 1 vaø 2 taïo neân sô cöùng tieåu caàu thaän (glomerulosclerosis), ñaây laø moät beänh im laëng, baét ñaàu do maøng cô baûn daày leân daàn. Trong beänh DM, saûn phaån cuoái cuøng cuûa glucose (glucose-end-product) tích tuï ôû maøng cô baûn naøy, daàn daàn tieåu caàu maïch (glomerulus) maát tính choïn löïa baùn thaåm thaáu naøy vaø coù theå bò hôû (leak) gaây neân tình traïng vi ñaûn baïch trong nöôùc tieåu (microalbuminuria). Tình traïng naøy seõ daãn tôùi coù protein trong nöôùc tieåu vaø sau ñoù trôû thaønh hoäi chöùng thaän (nephrotic syndrome) (4). Beänh DM loaïi 2 haàu nhö trôû thaønh moät phaàn dòch boäc phaùt taïi Myõ, nhöõng nhoùm daân bò ruûi beänh nhieàu nhaát laø ngöôøi Myõ goác Phi chaâu, goác Meã Taây Cô vaø goác ngöôøi Myõ baûn xöù (African Americans, Mexican Americans, vaø Native Americans).

DÖÔÏC KHOA THÖÏC HAØNH - Beänh Thaän Kinh Nieân

naøy laø chöùng öù nuôùc trong thaän (hydronephrosis).

Yeáu toá nguy cô laøm beänh nhaân maéc beänh Thaän Kinh Nieân

Nhöõng beänh nhaân coù nguy cô cao nhaát laø nhöõng beänh nhaân bò tieåu ñöôøng (DM), cao huyeát aùp (HT). Duøøng thuoác choáng ñau nhöùc khoâng chöùa steroids (NSAIDs) cho BTKN, nhöõng beänh nhaân maéc beänh maäp phì, lipid trong maùu cao (hyperlipidemia), hay huùt thuoác coù theâm nguy cô veà beänh tim maïch; vaø noùi chung veà nguy cô toång quaùt phaûi keå tuoåi giaø, gioáng daân vaø aên quaù nhieàu protein.

WBCs: neáu soá baïch huyeát caàu nhieàu hôn 5 (> 5) cho bieát bò nhieãm truøng. Fat: Nhöõng theå baàu duïc cho bieát coù lipid trong nöôùc tieåu, nhö nhaän thaáy ôû trong hoäi chöùng hö thaän (nephrotic syndrome). Casts: Nhöõng truï khaùc nhau coù theå cho bieát nhöõng loaïi beänh thaän coù xuaát xöù khaùc nhau. Thí duï truï RBCs cho bieát thöông toån tieåu caàu thaän hay maïch maùu (glomerular hay vascular lesion), neáu WBCs thì laø do vieâm khoaûng giöõa trong thaän (interstitial nephropathies). Sieâu AÂm thaän (Renal ultrasound) Ñaây laø moät phöông phaùp ít toán keùm vaø tieän lôïi ñeå chaån ñoaùn beänh. Thöôøng duøng ñeå ñònh kích thöôùc cuûa thaän vaø loaïi boû nhöõng nghi ngôø laø beänh nhaân bò ngheõn thaän, bò chöùng öù nöôùc trong thaän (hydronephrosis), vaø beänh thaän ña nang (polycystic renal disease).

Nhaän ñònh, tìm vaø theo doõi beänh

Nhöõng nhoùm ngöôøi coù nguy cô cao caàn phaûi theo doõi kyõ löôõng nhöõng thöû nghieäm thoâng thöôøng nhö urea nitrogen trong huyeát (blood urea nitrogen), creatinine huyeát töông (serum creatinine), vaø phaân tích nöôùc tieåu. Thoâng soá bình thöôøng cuûa creatinine 0.6- 1.3 mg/dL, BUN 8-20 mg/dL, vaø heä soá thanh thaûi creatinine (CrCl) cho ñaøn oâng 97- 137 mL/phuùt, cho ñaøn baø 88- 128 mL/phuùt. Söï thanh thaûi creatinine (CrCl) CrCl laø thoâng soá quan troïng nhaát ñeå theo doõi chöùc naêng thaän. Creatinine laø saûn phaåm thoaùi hoùa cuûa phospho-creatinine, moät chaát döï tröõ naêng löôïng quan troïng cuûa cô. Creatinine ñaøo thaûi do loïc ôû tieåu caàu thaän. Khi chöùc naêng loïc cuûa tieåu caàu thaän giaûm, noàng ñoä creatinine trong huyeát töông taêng. Phöông phaùp thoâng duïng nhaát laø öôùc löôïng heä soá thanh thaûi cuûa creatinine baèng coâng thöùc Cockroft-Gault (6). Coâng thöùc tính trò soá cho nam giôùi nhö sau: CrCl = (140 - Tuoåi) x Caân naëng (Kg) 72 x Creatinine (mg/dL) (cho nöõ giôùi, nhaân keát quaû vôùi 0.85) Proteine trong nöôùc tieåu (Proteinuria) Neáu thaáy coù protein trong nöôùc tieåu thì tieåu maïch thaän (glomeruli) bò toån thöông vaø maát tính baùn thaåm thaáu choïn loïc. Löôïng protein pheá thaûi qua thaän lieân quan tröïïc tieáp ñeán toác ñoä suy yeáu cuûa thaän. Löôïng protein pheá thaûi haøng ngaøy neáu nhieàu hôn 150 mg/ngaøy thì ta caàn phaûi tìm hieåu lyù do (7). Chaát laéng caën cuûa nöôùc tieåu (urine sediment) Phaân tích chaát laéng caën trong nöôùc tieåu coù theå bieát theâm lyù do taïi sao thaän bò hö haïi. Moät vaøi keát quaû thöû nghieäm ñieån hình cho ta thaáy: Crystals: thuûy tinh theå thöôøng thaáy trong beänh saïn trong thaän hay beänh guùt/ thoáng phong (gout). RBCs: neáu soá hoàng huyeát caàu nhieàu hôn 5 (> 5) trong moät phaïm vi nhìn kính hieån vi cao ñoä (high power field) cho bieát coù theå coù thöông toån (lesion) trong tieåu caàu thaän.

Nhöõng haäu quaû sau khi bò Beänh Thaän Kinh Nieân

Thaän laø moät boä phaän quan troïng cuûa cô theå, söïï thoaùi hoùa cuûa thaän gaây aûnh höôûng ñeán nhieàu cô quan khaùc cuûa cô theå. Thieáu maùu Beänh nhaân coù theå bò thieáu maùu khi CrCl thaáp hôn 35 mL/phuùt vaø seõ tieáp tuïc xuoáng thaáp hôn. Lyù do chính laø do söïï saûn xuaát erythropoietin bò giaûm ñi do thaän bò hö haïi.Theâm vaøo nöõa, thôøi gian ñôøi soáng cuûa RBCs seõ giaûm ñi moät nöûa. Thieáu saét (Fe) cuõng raát thoâng duïng (8). Thieáu aên protein (protein malnutrition) Giaûm protein trong nöôùc tieåu (hypoproteinuria) coù theå do chöùng bieáng nhaùc aên (anorexia) vì bò BTKN, löôïng protein saûn xuaát giaûm vaø löôïng protein thoaùi hoùa taêng. Khi albumin xuoáng thaáp beänh nhaân thöôøng coù tieân löôïng raát keùm (poor prognosis). Beänh cao huyeát aùp (hypertension) Maëc duø beänh cao huyeát aùp laø lyù do thöù nhì sau beänh tieåu ñöôøng gaây neân BTKN, noù cuõng laø haäu quaû do thaän suy yeáu. Sodium pheá thaûi giaûm thieåu laøm cho theå tích taêng leân quaù ñoä. Heä thoáng renin-aldosterone bò kích thích vôùi söïï hieän dieän cuûa thaän ñang hö haïi hoã trôï angiotensin II taïo neân co maïch (vasoconstriction). Söïï gia taêng hoaït ñoäng cuûa heä thaàn kinh giao caûm laøm taêng theâm söïï saûn xuaát cuûa nhöõng chaát thuoäc heä thoáng thaàn kinh giao caûm (nhoùm chaát sinh lyù/catecholamines: epinephrine, norepinephrine, vaø dopamine). Löôïng saûn xuaát nhöõng chaát thuoäc prostaglandins giaûm taïo söï thích öùng heä thoáng thaàn kinh giao caûm. Khi thaän baét ñaàu suy yeáu, huyeát aùp trôû neân raát khoù kieåm soaùt ñöôïc, vaø thöôøng caàn phaûi uoáng nhieàu thöù thuoác khaùc nhau môùi coù theå laøm giaûm huyeát aùp. Beänh cao huyeát aùp laø beänh gaây neân beänh phì ñaïi taâm thaát traùi (left ventricular hypertrophy). Neáu huyeát aùp khoâng kieåm soaùt ñöôïc thì beänh suy thaän caøng xaûy ra mau choùng hôn (5).

38 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Beänh Thaän Kinh Nieân - PHARMACY PRACTICE

Nguy cô maéc beänh tim Nguy cô maéc beänh tim maïch ôû nhöõng beänh nhaân bò beänh ñöôøng thaän cuõng cao hôn, coù theå tôùi 20% cao hôn trong nhöõng nhoùm beänh nhaân khaùc maéc beänh tim maïch (5). Beänh loaïn döôõng xöông thaän (renal osteodystrophy) Khi CrCl xuoáng thaáp tôùi giöõa 30- 60 mL/phuùt thì söï ñieàu hoøa calcium vaø phospho bò thay ñoåi. Trong beänh thaän suy, phospho bò giöõ laïi trong cô theå. Phopho trong maùu cao (giaù trò bình thöôøng töø 2.4 - 4.7 mg/dL) laøm taêng söï pheá thaûi calcium. Khaû naêng chuyeån hoùa vit D sang daïng hoaït ñoäng vit D - 125 bò maát maùt. Khi vit D thieáu huït laøm ñöôøng ruoät khoâng haáp thuï ñöôïc calcium. Tình traïng thieáu huït calcium trieàn mieân naøy laøm tuyeán caän giaùp (parathyroid gland) bò kích thích vaø baét ñaàu tieát ra kích thích toá parathyroid hormone (PTH), chaát naøy laøm xöông tieát ra calcium, vaø sau cuøng laø beänh nhaân bò beänh loaïn döôõng xöông thaän (9).

quaày cuõng caàn phaûi caån thaän. Khi CrCl xuoáng thaáp hôn 50 mL/phuùt, nhöõng thuoác chuyeån hoùa vaø pheá thaûi qua ñöôøng thaän ñeàu phaûi giaûm löôïng thuoác xuoáng (14). Moäät vaøi thuoác caàn ñöôïc giaûm lieàu khi maéc beänh thaän laø beta-blockers, allopurinol, thuoác khaùng thuï theå H2, penicillins, cephalosporins, digoxin, morphine, fluorquinolones, morphine, vaø codeine. Moät soá thuoác neân traùnh khi CrCl thaáp hôn 30 mL/phuùt laø chaát laøm töông phaûn (contrast dyes), aminoglycosides, cimetidine, colchicine, probenecid, metformin, acarbose, vaø glyburide. Theo doõi ñoà aên vaø dinh döôõng Beänh nhaân thöôøng ñöôïc khuyeán caùo ñi vaán keá nhöõng chuyeân vieân veà aên uoáng kieâng cöõ (dietitian) (15). Uoáng nöôùc nhieàu ñeå traùnh maát nöôùc. Traùnh uoáng phuï trôï chaát khoaùng, traùnh magnesium. Thuoác boå toång hôïp chöùa nhieàu loaïi vit B vaø folate coù theå duøng ñeå giaûm löôïng homocysteine. Khoâng neân duøng nhöõng döôïc thaûo coù theå gaây ñoäc toá haïi thaän. Sodium neân haïn cheá töø 2 ñeán 4 g/moät ngaøy. AÊn nhaït cuõng toát. Saét (Fe). Neáu thöû nghieäm cho bieát thieáu saét thì neân loaïi boû nghi ngôø beänh nhaân bò maát maùu trong ñöôøng tieâu hoùa, roài sau ñoù cho beänh nhaân uoáng theâm thuoác phuï trôï saét. Phospho. Neân haïn cheá löôïng phospho töø 0.8 ñeán 1.2 g/moät ngaøy ñeå phoøng ngöøa thaëng dö phospho trong maùu (hyperphosphatemia), thieáu calcium trong maùu, vaø traùnh ñöôïc phì tuyeán caän giaùp. Neáu löôïng phospho trong maùu quaù cao thì phaûi duøng thuoác laøm dính phospho. Potassium cuõng caàn ñöôïc kieåm soaùt kyõ löôõng. Trò thieáu maùu vôùi Epoetin Alfa Sau khi theo doõi kyõ löôõng thöû nghieäm cho toaøn soá maùu (complete blood count/CBC), ferritin, saét, vaø khaû naêng dính saét toaøn phaàn (total iron binding capacity), neáu beänh nhaân bò thieáu maùu ñaúng caàu ñaúng saéc (normocytic normochromic anemia), thì epoetin thöôøng ñöôïc duøng ñeå trò thieáu maùu. Khi beänh nhaân duøng epoetin laâu thì coù theå bò thieáu saét, vì saét trong maùu ñaõ ñöôïc duøng ñeå taïo hoàng huyeát caàu. Khi beänh nhaân ñang trò lieäu vôùi epoetin , saét phuï trôï coù theå cung caáp baèng caùch truyeàn iron dextran (InFeD) vaøo tónh maïch hay duøng thuoác uoáng (16). Ñieàu trò beänh loaïn döôõng xöông thaän (renal osteodystrophy) Loaïn döôõng xöông thaän coù theå xaåy ra khi CrCl ôû möïc 5070 mL/phuùt. Ñeå traùnh beänh coù theå xaåy ra, löôïng phospho vaø calcium trong maùu phaûi ñöôïc theo doõi kyõ löôõng (17). Phosphorus: Neáu phospho trong maùu cao hôn möïc bình thöôøng (2.5- 4.6 mg/dL), b/n caàn phaûi uoáng loaïi thuoác dính phospho (phosphate binders) nhö calcium carbonate (thí duï nhö Tums), calcium acetate (PhosLo), hay sevelamer

Vietnamese Pharmaceutical Journal No.5- 39

Caùch ñieàu tri beänh thaän kinh nieân

Vì söï phöùc taïp do Beänh Thaän Kinh Nieân gaây neân, caùch ñieàu trò cuõng ña dieän vaø phaûi thích öùng vôùi töøng caù nhaân. Beänh cao huyeát aùp Cao huyeát aùp ôû giai ñoaïn cuoái cuøng cuûa beänh thaän (endstage renal disease/ESRD). Ñích cuûa huyeát aùp kieåm soaùt laø 130/85 mm Hg. Baát cöù döôïc phaåm naøo mang ñöôïc huyeát aùp xuoáng thaáp cuõng toát, neân ñöôïc duøng caû (10). Glucose trong maùu Löôïng glucose trong maùu kieåm soaùt chaët cheõ (Hemoglobin A1c <7.0) seõ laøm giaûm ñöôïc vi ñaûn baïch trong nöôùc tieåu. Duøng thuoác öùc cheá men chuyeån angiotensin (ACE-I) hay thuoác ngaên chaën thuï theå angiotensin II (ARB) Angiotensin-converting enzyme inhibitors (ACE-Is) vaø angiotensin II-receptor blockers (ARBs) laø loaïi thuoác ñaàu tieân duøng ñeå trò beänh nhaân bò tieåu ñöôøng, suy tim, lipid trong maùu cao, hay coù protein trong nöôùc tieåu. Thuoác nhoùm naøy laøm giaûm aùp huyeát, vaø laøm giaûm pheá thaûi protein, cuøng laøm giaûm aùp suaát trong tieåu caàu thaän vaø do ñoù laøm giaûm protein trong nöôùc tieåu (11). Tröôùc khi cho beänh nhaân duøng thuoác naøy, baùc só thöôøng phaûi coi kyõ xem beänh nhaân coù bò maát nöôùc hay khoâng. Caàn theo doõi ñoä potassium trong maùu, vaø möïc creatinine. Cuõng caàn phaûi theo doõi nhöõng taùc duïng phuï cuûa thuoác nhö gaây ho, phuø do thoaùt quaûn nöôùc qua thaønh maïch (angioedema). Ngoaøi ra, ARBs cuõng nhö ACE I, coøn ñöôïc duøng vôùi muïc ñích ñeå baûo veä thaän (12) Ñeå baûo veä toái ña chöùc naêng coøn laïi cuûa thaän, khi beänh nhaân bò nhieãm truøng ñöôøng tieåu (urinary tract infection) thì caàn ñöôïc chöõa trò ngay (13). Traùnh ñoäc toá haïi thaän (nephrotoxins) Caàn neân traùnh taát caû nhöõng chaát ñoäc toá haïi thaän nhö NSAIDs, goàm caû thuoác ngaên chaën Cox-2. Thuoác mua ngoaøi

DÖÔÏC KHOA THÖÏC HAØNH - Beänh Thaän Kinh Nieân

(Renagel). Lôïi ñieåm cuûa Renagel laø khoâng chöùa calcium neân khi duøng lieàu cao coù theå laøm giaûm bieán coá calci hoùa maïch maùu. Aluminum hydroxide (Amphojel) coù theå duøng trong moät thôøi gian ngaén haïn, nhöng neáu beänh nhaân phaûi uoáng phosphate binder laâu daøi thì khoâng neân. Phosphat binders laïi gaây taùo boùn (constipation), do ñoù beänh nhaân thöôøng phaûi duøng moät thuoác laøm meàm phaân (stool softener).

Calcium: möïc calcium neân duy trì trong voøng 9-11 mg/dL Khi beänh nhaân coù löôïng phospho bình thöôøng nhöng calcium thaáp hay coù möïc kích thích toá tuyeán caän giaùp cao (PTH) thì thuoác phuï trôï vitamin D nhö calcitriol (Rocaltrol) hay doxercalciferol (Hectorol) caàn phaûi ñöôïc duøng vôùi beänh nhaân ñaõ laøm thaåm taùch hay beänh nhaân coøn ñang ôû giai ñoaïn 3 hay 4 cuûa beänh thaän kinh nieân chöa caàn laøm thaåm taùch.

References:

1. Parmar M. Chronic renal disease. BMJ. 2002;325:85-90. 2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1-266. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002;39:S1-S246. http://www.kidney.org/professionals/kdoqi/guidelines_ckd/tables.htm 3. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med. 2003;139:137-147. 4. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2004;27:S15-S35. 5. AHA Scientific Statement. Kidney disease as a risk factor for development of cardiovascular disease. Circulation. 2003;108:2154-2169 6. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41 7. Johnson CA, Levey AS, Coresh J, Levin A, Lau J, Eknoyan G. Clinical practice guidelines for chronic kidney disease in adults: Part II. Glomerular filtration rate, proteinuria, and other markers. Am Fam Physician. 8. Kausz AT, Obrador GT, Pereira BJ. Anemia management in patients with chronic renal insufficiency. Am J Kidney Dis 2000;36(6 Suppl 3):S39-51 9. Hruska KA, Teitelbaum SL. Renal osteodystrophy. N Engl J Med 1995;333(3):166-74 10. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;39: S11-S68. 11. Manley HJ. Role of angiotensin-converting-enzyme inhibition in patients with renal disease. Am J Health-Syst Pharm. 2000;57(Suppl 1):S12-S18. 12. Giatras I, Lau J, Levey AS. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group. Ann Intern Med 1997;127(5):337-45 13. Cohen G, Haag-Weber M, Hörl WH. Immune dysfunction in uremia. Kidney Int 1997;52 (Suppl 62):S79-82 14. Bakris GL, Kern SR. Renal dysfunction resulting from NSAIDs. Am Fam Physician 1989;40(4):199-204 15. K/DOQI clinical practice guidelines on nutrition in chronic renal failure. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis.2000;35: S1-S140 16. Erslev AJ, Besarab A. Erythropoietin in the pathogenesis and treatment of the anemia of chronic renal failure. Kidney Int 1997;51(3):622-30. 17. Martinez I, Saracho R, Montenegro J, et al. The importance of dietary calcium and phosphorus in the secondary hyperparathyroidism of patients with early renal failure. Am J Kidney Dis 1997;29(4):496-502

40 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Thöû tìm hieå u ñeå so saù n h "Thieá u maù u " vaø "Huyeá t hö" trong Taây -y vaø Ñoâ n g-y

Mai Taâm Brossard, Fev-2004

Abstract:

Are anemia in western medine and "blood emptiness" in traditional Chinese medicine, the same hematological disorders? In this current issue of the Vietnamese Pharmaceutical Journal focusing on Anemia the author attempts to contrast the description of this "blood insufficiency" as defined by these two medicines. This disease has been shown to be rather widespread in the world and caused directly by generic inheritance, malnutrition, organ deficiencies or indirectly after long primary diseases or others... The purpose of this paper is to explain the proper significances of the medical terms used in eastern and western medicines and the rationalization of the pathogenesis. The author introduces some principles of treatment in Eastern medicine based on his concept and his particular reasoning, compares them to the treatment approaches in Western medicine for this disease. Without going to details, the author also proposes some practice points in acupuncture and the use of the traditional formulae in Chinese herbs which have shown efficacy in treating the disease.

Sommaire:

L'Aneùmie en Occident, et le "Vide de Sang" en Orient sont-ils, tous les deux, des troubles heùmatologiques similaires? Le journal VPhJ a donneù pour ce preùsent numeùro un theøme porteù sur l'aneùmie, l'auteur essaie de mettre en paralleøle ces deux meùdecines visant cette insuffisance sanguine qui s'aveøre plutoât reùpandue dans la population du monde, que ce soit heùreùditaire, par malnutrition, par deùficiences organiques ou indirectement apreøs de longues maladies primaires ou autres... Ce texte a pour but de deùpartager les significations propres des termes meùdicaux utiliseùs dans ces deux meùdecines entre l'Est et l'Ouest et leurs raisonnements respectifs en matieøre de pathologie. Ceci eùtant fait, l'auteur eùtale quelques principes de traitement en meùdecine orientale selon son concept et son raisonnement particulier, par rapport aø la meùdecine occidentale dans cette pathologie. L'auteur propose aussi en pratique quelques points d'acupuncture et l'utilisation des formules classiques en herbologie chinoise, lesquels ont fait des preuves avec le temps, mais sans trop approfondir pour ne pas surcharger inutilement ce texte.

T

hieáu maùu (anemia) laø moät nhoùm beänh lyù maø thoâng thöôøng ñaïi chuùng ñeàu coù moät khaùi nieäm khaù gaàn gioáng nhau, duø khoâng chính xaùc laém. Thí duï nhö hoï nhìn da maët ai hoàng haøo vöøa phaûi thì goïi laø ñaày ñuû. Khi xanh xao hay tai taùi thì goïi laø thieáu maùu... Vöøa vieát tôùi ñaây, chuùng toâi chôït nhôù tôùi moät chuyeän raát thöôøng xaûy ra trong luùc haønh ngheà Döôïc só, laø raát hay gaëp ngöôøi thuoäc chuûng toäc da ñen ñeán tham vaán veà beänh thieáu maùu naøy, maø vì mình khoâng quen maét neân nhìn hoï khoù thaáy ñöôïc caùi neùt tai taùi xanh xao cuûa ngöôøi "thieáu maùu". Theo kinh nghieäm haønh ngheà maáy chuïc naêm, chuùng toâi ñaõ coù caûm töôûng raèng hoï laø saéc daân tieâu thuï maïnh nhaát cyproheptadine (Periactin hay Vimicon) ñeå... leân caân vaø caùc döôïc phaåm chöùa saét vì... thieáu maùu. Baây giôø xem thoáng keâ cuûa Hoa-Kyø thì quaû thaät ngöôøi da ñen bò khieám khuyeát dieáu toá G-6-PD (Glucose-6phosphate dehydrogenase) do di truyeàn nhieàu hôn caùc saéc daân khaùc, nhaát laø phaùi nam, coù khoaûng 10-14% ñaøn oâng da ñen bò chöùng naøy, phía nöõ cuûa hoï cuõng coù theå bò, tuy ít hôn vaø tình traïng nheï hôn nhieàu. VPhJ kyø naøy coù chuû ñeà laø "anemia" neân Ban bieân taäp coù lôøi môøi chuùng toâi vieát moät baøi theo quan nieäm cuûa Ñoâng-y. Do ñoù, xin keå sô qua vaøi quan nieäm beänh lyù hoïc vaø phöông phaùp trò lieäu cuûa Ñoâng- y so vôùi Taây-y. Muïc ñích ñeå cho phaàn lôùn caùc ñoäc giaû khoâng quen coù theå tìm hieåu ñöôïc phaàn naøo phöông thöùc trò lieäu theo coå xöa naøy cuûa AÙ Ñoâng. Tuy coå xöa nhöng vaãn coøn thònh haønh moãi ngaøy ôû nhieàu quoác gia töø Ñoâng ñeán Taây treân theá giôùi.

Vietnamese Pharmaceutical Journal No.5 - 41

DÖÔÏC KHOA THÖÏC HAØNH- "Thieáu maùu" vaø "Huyeát hö"

1) Thieáu maùu (anemia) theo Taây-y:

1a) Cô cheá vaø nguyeân do thieáu maùu theo Taây-y: Ñeå khoûi muùa rìu qua maét thôï, chuùng toâi chæ xin coá lieät keâ moät caùch ñôn giaûn, nhöng hy voïng khoâng thieáu, caùc yeáu toá chính nôi ñaây ñeå ñoäc giaû khoûi maát coâng nhôù laïi khi caàn so saùnh. Cuõng vì Ñoâng-y sôû tröôøng nhaát trong söï trò beänh do xaùo troän veà chöùc naêng (function), coøn khi caáu truùc (structure) ñaõ bò thay ñoåi traàm troïng thì hieäu quaû coù phaàn keùm ñi raát nhieàu, do ñoù beänh thieáu maùu maø chuùng toâi coù theå ñeà caäp ñeán moät caùch ích lôïi cho baøi vieát naøy laø söï thieáu maùu do tan huyeát (hemolytic anemia). Veà beänh do töï-mieãn-nhieãm (autoimmune), chuùng toâi nghó cuõng coù theå ñieàu hoaø trôû laïi ñöôïc, coøn beänh gaây ra söï thay ñoåi hình daïng hoàng huyeát caàu (sickle cell) khoâng phaûi laø ñòa haït deã trò, tuûy xöông coù vaán ñeà thì caøng khoù hôn nöõa! Phaàn baïch huyeát caàu thì coù veû thuoäc "veä khí" (khí baûo veä) hôn laø "huyeát" theo y-lyù Ñoângy (seõ coù giaûi thích ôû phaàn sau). Beänh thieáu maùu (anemia) laø chöùng roái loaïn veà huyeát thoâng thöôøng nhaát. Taïi Hoa Kyø, theo taøi lieäu cuûa Mayo Clinic thì coù ñeán 3.4 trieäu ngöôøi Myõ mang beänh naøy, trong soá ñoù ña soá laø phuï nöõ, nhöõng ngöôøi coù beänh daøi haïn (beänh maõn tính) hoaëc ngöôøi treân 65 tuoåi. Ngöôøi giaø yeáu thì deã hieåu. Coøn phuï nöõ thì raát deã bò thieáu maùu vì chæ caàn kinh nguyeät nhieàu hôn bình thöôøng hoaëc do thai ngheùn vaø sinh ñeû. Coøn beänh maõn tính coù theå keå ra raát nhieàu nhö: suy thaän maõn tính, tieåu ñöôøng, yeáu tim, ung thö, caùc chöùng vieâm kinh nieân nhö vieâm khôùp xöông do thaáp (rheumatoid arthritis) hay vieâm loeùt ñaïi traøng (inflammatory bowel disease), beänh nhieãm HIV... Ñoù laø chöa keå thieáu maùu khoâng do beänh maø do... trò beänh, nhö haäu öùng khi trò lieäu baèng döôïc phaåm, thí duï nhö thuoác trò soát reùt, caùc loaïi choáng vieâm NSAID, nitrofurantoin, trò ung thö baèng hoaù hoïc lieäu phaùp (chemotherapy), trò beänh AIDS baèng thuoác choáng sieâu vi nhö AZT chaúng haïn; trong tieán trình phaãu thuaät cuõng gaây maát maùu ít nhieàu. Nguyeân nhaân thieáu maùu ñöông nhieân cuõng bao goàm söï maát ñi, do taát caû caùc beänh gaây xuaát huyeát nhieàu khi raát aâm thaàm, hoaëc söï dinh döôõng khoâng ñem laïi ñaày ñuû chaát caàn thieát ñeå sinh huyeát. Hieän töôïng töï huûy quaù sôùm hoàng huyeát caàu bôûi heä mieãn nhieãm cuõng laø moät nguyeân nhaân khaùc. Söï ngoä ñoäc nhö ghieàn röôïu hay nhieãm moät loaïi saùn kyù sinh (fish tape worm, teania...) cuõng laøm löôïng huyeát trong cô theå thieáu huït moät caùch ñaùng keå. Cuoái cuøng cuõng neân keå theâm beänh thieáu maùu vôùi nguyeân nhaân di truyeàn, ngoaøi söï khieám khuyeát dieáu toá G-6-PD nhö ñaõ noùi beân treân, chuùng ta coù theå keå theâm beänh "thalassemia", do nhöõng gene trong söï toång hôïp caùc chuoãi globin alpha hay beta cuûa huyeát saéc toá (hemoglobin) bò khieám khuyeát hay laø dò daïng. Toùm laïi, thieáu maùu theo Taây-y coù theå do thieáu dinh döôõng hay söï keùm haáp thuï cuûa boä tieâu hoaù (saét vaø sinh toá B12, acid folic v.v...), maát maùu do xuaát huyeát, coù theå do moät cô quan bò moät chöùng beänh kinh nieân (nhö thaän khoâng coøn tieát ñaày ñuû "erythropoietin", trong bao töû khoâng ñuû "intrinsic factor"), do söï di truyeàn hay gene ñoät bieán. Beänh coù theå naëng

42 - Taäp San Chuyeân Nghieäp Döôïc Khoa

hay nheï, taïm thôøi hay keùo daøi. 1b) Caùc trieäu chöùng thieáu maùu theo Taây-y ta coù theå lieät keâ nhö sau: - yeáu ôùt, - maøu da lôït laït keå caû moâi, lôïi (nöôùu), moùng tay, moùng chaân v.v..., - nhòp ñaäp cuûa tim mau hôn bình thöôøng, - thôû hoån heån, - töùc ngöïc, - choùng maët, xaây xaåm, - deã noåi noùng, - chaân tay teâ hay laïnh, - nhöùc ñaàu. Tröø phi bò thöông hay moät côn xuaát huyeát caáp tính, caùc trieäu chöùng baét ñaàu raát töø töø khoù ñeå yù, vaø caøng ngaøy caøng naëng theâm. Lyù luaän theo khoa hoïc thieáu maùu laøm cho naõo boä beänh nhaân suy nghó khoâng ñöôïc minh baïch vì thieáu döôõng khí (oxygen). Duø ñoïc hay vieát chöõ cuõng thaáy khoù khaên, caùc sinh hoaït thöôøng nhaät ñöông nhieân cuõng bò trôû ngaïi. Cuõng vì soá hoàng huyeát caàu giaûm, söï chuyeân chôû döôõng khí cuõng giaûm thieåu cho moïi nôi trong cô theå, traùi tim phaûi ñaäp theâm ñeå buø vaøo söï thieáu huït naøy, do ñoù seõ khoâng traùnh khoûi sanh ra vaán ñeà cho tim veà laâu veà daøi. Thieáu maùu cuõng laøm cho hoaït ñoâng cuûa cô quan sinh duïc bò xaùo troän, ngöôøi phuï nöõ seõ thaáy kinh kyø khoâng ñeàu cuõng nhö löu löôïng kinh huyeát troài suït baát thöôøng, coøn boä phaän sinh duïc nam coù theå khoâng ñuû maùu vaøo caùc cô xoáp giuùp cô quan naøy cöông cöùng ñuùng möùc khi caàn thieát. Chæ sô löôïc bao nhieâu ñoù cuõng ñaõ cho chuùng ta thaáy söï quan troïng trong vieäc trò lieäu vaø nhaát laø phoøng ngöøa chöùng beänh naøy. Söï truyeàn maùu tuy raát höõu duïng trong moät soá tröôøng hôïp caáp tính nhaát thôøi nhöng caùch naøy khoâng phaûi deã daøng veà phöông dieän kyõ thuaät cuõng nhö khía caïnh tieáp lieäu. Nhaát laø caøng ngaøy caøng thaáy nhieàu vaán ñeà maø khoa hoïc chöa naém heát noåi trong vieäc truyeàn maùu, do ñoù vaïn cuøng baát ñaéc dó môùi neân nhôø ñeán phöông phaùp naøy. Ñoù laø chöa keå ñeán tröôøng hôïp coù ñaïo giaùo khoâng cho pheùp ngöôøi beänh nhaän maùu truyeàn!

2) Huyeát hö theo Ñoâng-y

2a) Sinh lyù hoïc cuûa huyeát theo Ñoâng-y (Quan nieäm Huyeát vaø Khí trong Ñoâng-y, theo Auteroche vaø Navailh) Trong baøi vieát naøy chæ xin ñeà caäp ñeán Huyeát vaø caùc Khí coù lieân heä ñeán Huyeát. Huyeát ñöôïc sinh ra nhôø 3 yeáu toá: 1. Tinh chaát trích bieán töø söï tieâu hoaù thöïc phaåm (hoaït ñoäng cuûa trung tieâu Tyø Vò) hoaù ñoû maø thaønh huyeát (Trung tieâu thoï khí thuû traáp, bieán hoaù nhi xích, thò vò huyeát -Linh Khu/thieân 30, Quyeát Khí) 2. Dinh khí, dinh coù nghóa laø dinh döôõng, khí naøy luaân löu trong caùc maïch vaø laø nguoàn naêng löôïng nuoâi döôõng taïng phuû cuøng cô theå, ñoái ngöôïc vôùi veä khí laø khí baûo veä che chôû

"Thieáu maùu" vaø "Huyeát hö" - PHARMACY PRACTICE

cho cô theå, veä khí chu löu beân ngoaøi maïch, coù theå bao goàm caû heä mieãn nhieãm theo khoa hoïc hieän ñaïi. Saùch Linh Khu coù vieát: Dinh laø tinh khí cuûa côm nöôùc. Con ngöôøi thuï khí ôû côm nöôùc, côm nöôùc vaøo daï daøy beøn truyeàn cho phoåi, chaûy traøn beân trong, san seû beân ngoaøi, phaàn tinh chuyeân noù vaän haønh trong kinh maïch ngaàm, thöôøng dinh döôõng khoâng ngöøng, cuoái cuøng trôû veà giai ñoaïn ñaàu". Coù nghóa laø maùu huyeát cuøng dinh khí troâi chaûy ôû trong maïch maùu trong moät söï tuaàn hoaøn khoâng ngöøng. (Dinh khí phaûi chaêng bao goàm huyeát töông ?) Veà dinh khí BS Nguyeãn Vaên Nghò, beân Phaùp, coù thöû tìm söï töông öùng vôùi Taây-y vaø ñaõ phaùt bieåu nhö sau: "Le Yong (Dinh khí) est l'eùleùment nutritif syntheùtiseù aø partir de la quintessence eùnergeùtique provenant de la digestion alimentaire, cet eùleùment sera conduit vers la citerne de Pecquet aø travers l'intestin greâle. Il suit ensuite le canal thoracique pour parvenir jusqu'aø la veine cave infeùrieure, d'ouø il atteint le Coeur, puis passe aux Poumons pour eâtre distribueù dans tout le corps... Cet eùleùment circule d'une part dans les vaisseaux sanguins avec le sang et d'autre part dans les vaisseaux lymphatiques..." (Meùdecine Traditionnelle Chinoise, Nguyen Van Nghi et Christine Recours-Nguyen, 1984, page 77). 3. Tinh cuûa tuûy: töùc laø tinh cuûa Thaän vì theo Ñoâng-y "Thaän sanh tuûy vaø naõo, chuû xöông coát, phaùt hieän ra toùc" (baây giôø khoa hoïc ñaõ baét ñaàu khaùm phaù ra vieäc naøy nhö erythropoietin, calcitriol trong thaän, vaø toùc ruïng hay moïc coù lieân heä ñeán hormon nhö androgen, xin ñoïc baøi "Taûn Maïn veà Thaän Suy vaø Suy Thaän" treân Nguyeät San Y Teá vaø Taäp San Y Só thaùng 1/2004, cuøng taùc giaû, ñeå hieåu Thaän theo Ñoâng-y coù theå laø "taát caû" caùc hormon)

2b) Nhieäm vuï cuûa Huyeát, coù 2 nhieäm vuï chaùnh: 2b1- Huyeát nuoâi döôõng: Nhö thieân thöù 10 trong saùch Toá vaán coù ghi: "Can thuï huyeát nhi naêng thò, tuùc thuï huyeát nhi naêng boä, chöôûng thuï huyeát

Ñoà hình Thaän sinh huyeát theo khoa hoïc so saùnh vôùi Ñoâng-y: nhi naêng oác, chæ thuï huyeát nhi naêng nhieáp" (Toá vaán/ Nguõ taïng sinh thaønh thieân) Löôïc dòch: "Gan nhaän ñöôïc huyeát ta môùi nhìn ñöôïc (maét do gan laøm chuû), chaân nhaän ñöôïc huyeát thì môùi ñi ñöôïc, tay nhaän ñöôïc huyeát thì môùi naém ñöôïc, ngoùn nhaän ñöôïc huyeát môùi co ñöôïc". Thieân 47 saùch Linh Khu coøn theâm: "Khi huyeát ñöôïc ñieàu hoaø thì gaân coát môùi coù söùc, caùc khôùp môùi

Vietnamese Pharmaceutical Journal No.5 - 43

DÖÔÏC KHOA THÖÏC HAØNH- "Thieáu maùu" vaø "Huyeát hö"

linh hoaït...). Traùi laïi, neáu huyeát khoâng ñaày ñuû (huyeát hö) thì maét nhìn keùm vaø khoâ, caùc khôùp xöông seõ cöùng ñô, tay chaân teâ, da khoâng nhuaän... Coâng naêng cuûa huyeát ngoaøi söï dinh döôõng caùc toå chöùc toaøn thaân, coøn chi phoái caûm giaùc cuûa bì phu. 2b2- Huyeát laø nôi nöông töïa cuûa "Thaàn": Thaàn laø thaàn minh, trí giaùc, moät hoaït ñoäng taâm linh ñaëc bieät cuûa con ngöôøi, khoâng ai thaáy tröïc tieáp ñöôïc, chuùng ta coù theå duøng töø "mental" ñeå dòch sang ngoaïi ngöõ cho deã hieåu. Thoâng duïng nhaát laø hai chöõ "an thaàn" duøng cho thuoác nguõ, vì maát nguû theo quan nieäm cuûa Ñoâng-y laø do thaàn khoâng yeân. Moät töø khaùc ñeå giuùp cho hieåu roõ laø "thaát thaàn", coù nghóa laø taâm thaàn cuûa ngöôøi ñoù ñang "maát", khoâng coøn suy nghó hay nhaän thöùc ñöôïc nhö ngöôøi bình thöôøng. 2c) Lieân heä giöõa Huyeát vaø Khí, "khí vi huyeát soaùi": Theo lieân heä AÂm Döông thì Huyeát thuoäc AÂm, ñoái vôùi Khí thuoäc Döông. Huyeát luaân löu khoâng ngöøng trong cô theå ñeå thi haønh nhöõng nhieäm vuï ñaõ keå treân. Söï luaân löu naøy phaûi nhôø söï thuùc ñaåy cuûa khí. Ngay trong huyeát quaûn, trong ñieàu kieän vaän haønh bình thöôøng, huyeát cuõng phaûi döïa vaøo khí. Do ñoù môùi coù caâu "khí vi huyeát soaùi" (soaùi coøn ñöôïc ñoïc laø suùy, khí laø vò töôùng chæ huy huyeát). Ñaây laø moät quan heä sinh lyù-beänh lyù. Söï vaän haønh cuûa khí huyeát nhaèm giöõ gìn moái töông quan ñoái laäp nhöng thoáng nhaát. Khí laø döông, laø ñoäng löïc; huyeát laø aâm, laø cô sôû vaät chaát. Dinh huyeát ôû trong kinh maïch sôû dó vaän haønh chu löu toaøn thaân laø nhôø vaøo ñoäng löïc cuûa khí. Khí haønh thì huyeát cuõng haønh, khí treä thì huyeát cuõng treä, cho neân môùi meänh danh raèng khí laø soaùi cuûa huyeát. Nhöng ñoái laïi, khí cuõng phaûi döïa vaøo dinh huyeát môùi phaùt huy ñöôïc taùc duïng, cho neân Ñoâng-y coøn noùi raèng huyeát laø meï cuûa khí. Moái quan heä cuûa hai yeáu toá naøy laø: huyeát dòch nuoâi naáng toå chöùc khí quan maø sinh ra cô naêng hoaït ñoäng, nhöng söï hoaït ñoäng chính thöôøng cuûa cô naêng laïi thuùc ñaåy cho huyeát dòch vaän haønh. Söï vaän haønh cuûa khí huyeát, nhö vaäy, theå hieän nguyeân lyù aâm döông hoã caên (aâm döông cuøng toàn taïi vôùi nhau, cuøng chung moät goác reã). 2d) Cô naêng giuùp huyeát löu haønh: Theo sinh lyù hoïc cuûa Ñoâng-y, trong söï löu haønh cuûa huyeát coù söï phoái hôïp khí cuûa caùc "Taïng" sau ñaây: 1- Taâm (tim) laø söùc ñaåy chính yeáu vaø caên baûn. 2- Pheá (phoåi) giuùp phaân phoái khaép cô theå (tuyeân) 3- Tyø (laù laùch vaø laù mía) ñeå giöõ huyeát trong maïch khoâng thoaùt ra ngoaøi (thoáng huyeát). 4- Can (gan) giuùp ñieàu hoaø löôïng huyeát, nhö moät nhaø kho döï tröõ löôïng dö thöøa, khi caàn thì cho ra (taøng huyeát). Neáu moät trong caùc cô naêng treân bò trôû ngaïi hoaëc maát quaân bình thì seõ sanh beänh veà huyeát. Thí duï nhö Tyø khí yeáu coù theå sanh ra chöùng xuaát huyeát (hemorrhage) vì khoâng coøn khaû naêng giöõ huyeát trong caùc maïch... 2e) Huyeát hö theo Ñoâng-y: Trong Ñoâng-y coù nhieàu chöùng beänh cuûa huyeát nhö huyeát öù,

44 - Taäp San Chuyeân Nghieäp Döôïc Khoa

xuaát huyeát, huyeát hö, huyeát nhieät, huyeát haøn v.v... Trong baøi naøy chæ chuù troïng ñeán "Huyeát hö". Chöùng naøy laïi coøn coù nhieàu daïng ñaëc bieät maø Taây-y chöa ñeå yù ñeán. Xin toùm taét nhö sau: - Huyeát hö laøm Khí hö theo (maùu bò thieáu tröôùc roài sanh ueå oaûi yeáu meät) - Khí Huyeát löôõng hö (gioáng nhö treân nhöng 2 beân naëng baèng nhau) - Tyø khí khoâng giöõ ñöôïc huyeát trong maïch (huyeát traøn ra khoûi maïch, nghóa laø xuaát huyeát do goác laø Tyø hö) - Taâm Huyeát hö (thieáu maùu nhöng aûnh höôûng nhieàu nhaát treân tim vaø "Thaàn", nhö tim ñaäp maïnh, maát nguõ...) - Can huyeát hö (aûnh höôûng nhieàu nhaát treân gan, gan khoâng ñuû huyeát (huyeát thuoäc aâm) seõ "noùng" leân, coù caùc chöùng thuoäc nhieät nhö taùo boùn, nhöùc ñaàu, tính tình noùng naûy; vì kinh nguyeät phuï nöõ tuøy thuoäc nhieàu vaøo Can kinh vaø Can huyeát neân coù theå coù chöùng ñau buïng khi coù kinh hay haønh kinh raát ít; maét do aûnh höôûng bôûi can neân seõ khoâ vaø thaáy khoâng roõ v.v...) - Can huyeát hö sanh phong (gioáng nhö treân nhöng "naëng" hôn vì nhieät ñaõ thaønh hoaû vaø hoaû cöïc ñaõ sinh "phong", caùc chöùng phong ngöùa (eczema) laø ñaây! Neáu aûnh höôûng treân gaân vaø baép thòt (gaân cô thuoäc gan) seõ thaønh "Can Phong sinh Noäi Ñoäng" töùc laø moät daïng cuûa kinh phong (seizure). - Huyeát nhieät (cuõng gaàn gioáng nhö treân nhöng do moät nguoàn nhieät vaøo huyeát chôù khoâng phaûi vì thieáu huyeát maø hieän ra "nhieät" moät caùch bieåu kieán nhö treân . Ví duï nhö phong ngöùa, noåi meà ñay do aên ñoà "noùng" hay thöïc phaåm "coù phong". Tôùi phaàn cuoái naøy thì khoâng coøn laø huyeát hö nöõa nhöng cuõng xin keå ra cho ñoäc giaû thaáy cuøng moät trieäu chöùng ngoaøi da nhö phong ngöùa coù theå laø "hö" (huyeát hö) hay laø "thöïc" (do thöïc nhieät laøm maùu "noùng" leân). Beänh huyeát coøn nhieàu thöù nhö ñaõ keå beân treân, nhieät coøn coù theå laø taø nhieät hay nhieät ñoäc (infections), haøn taø cuõng coù theå taán coâng vaøo huyeát maïch gaây beänh v.v... raát ñaùng cho caùc nhaø khaûo cöùu tìm hieåu, vì söï trò lieäu beân Ñoâng-y thaät ñaày ñuû vaø döïa treân nhöõng nguyeân taéc maø caøng ngaøy caùc khaùm phaù cuûa Taây-y ñaõ chöùng minh laø khoâng sai! Ngoaøi ra beänh huyeát hö cuûa Ñoâng-y, cuõng nhö caùc beänh khaùc, naèm trong moät tieán trình toång theå caùc beänh traïng, tröôøng hôïp naøy cuoái cuøng seõ sanh ra AÂm hö roài Döông hö, hay AÂm tuyeät roài Döông tuyeät töùc laø... gaàn cheát! Trong con ngöôøi, daây mô reã maù lieân laïc chaèng chòt, boä phaän naøy lieân quan ñeán cô quan kia, do ñoù khi naém vöõng Ñoâng-y seõ khoâng laáy laøm laï nhö maét keùm, maét khoâ coù theå do Can huyeát hö, tai uø do Thaän v.v... Keát quaû treân söï trò lieäu thöïc haønh ñeàu chöùng minh ñöôïc caùc söï kieän "kyø laï" naøy! Cuõng nhö ñaõ noùi beân treân, trong baøi naøy chuùng toâi chæ xin chuù troïng ñeán huyeát hö vì gaàn gioáng "anemia" vôùi caùc trieäu chöùng nhö: saéc maët, maøu saéc cuûa moâi, löôõi, moùng tay moùng chaân nhôït nhaït khoâng boùng, ñaàu choaùng, maét hoa,

"Thieáu maùu" vaø "Huyeát hö" - PHARMACY PRACTICE

2f) Taïm keát phaàn Ñoâng-y: Toùm laïi ta coù theå noùi laø, theo Ñoâng-y, Huyeát ñöôïc sanh ra do söï tieâu hoaù caùc thöïc phaåm bôûi Tyø Vò (coøn goïi laø Trung Tieâu) roài ñöôïc Tinh cuûa Thaän (Haï Tieâu) bieán thaønh. Sau khi thaønh laäp laø do Taâm Pheá (Thöôïng Tieâu) thuùc ñaåy löu haønh khaép cô theå chung vôùi Dinh Khí. Huyeát ñöôïc gìn giöõ trong huyeát maïch nhôø Tyø khí vaø ñöôïc döï tröõ trong Can ñeå ñieàu hoaø löu löôïng. Beân ngoaøi caùc maïch vaø cô theå laø söï luaân löu cuûa Veä Khí (ñoái vôùi Dinh Khí ôû trong) ñeå phoøng thuû baûo veä cô theå. Coøn neáu nhìn moät caùch toång quaùt thì Huyeát vaø Khí lieân laïc hoå töông vôùi nhau; Khí treä seõ laøm Huyeát khoù vaän haønh hoaëc öù keát; coøn Huyeát hö thì Khí khoâng coøn ñöôïc baûo döôõng seõ suy yeáu theo. Nhö theá, ta thaáy caùi nhìn bao quaùt veà Huyeát cuûa Ñoâng-y coù veû phöùc taïp hôn Taây-y raát nhieàu duø khoâng coù söï phaàn tích tæ mæ baèng Taây-y, vì Ñoâng-y khi noùi ñeán moät cô quan hay baát cöù moät phaàn naøo cuûa cô theå laø noùi ñeán chöùc naêng hôn laø caùi vaät chaát nhìn thaáy raát laø giôùi haïn duø phaân tích ñeán möùc naøo ñi nöõa. Do ñoù, ta coù caûm töôûng (coù theå raát ñuùng) laø "Huyeát" cuûa Ñoâng-y ngoaøi huyeát töông (Dinh Khí ?), hoàng huyeát caàu - hemoglobin, baïch huyeát caàu laïi laø moät phaàn cuûa Veä Khí (?)..., coøn ñöa ra theâm chöùc naêng thrombine cuûa gan, hormon erythropoietin cuûa Thaän, nguoàn goác vaø cô cheá sinh ra histamin trong maùu v.v... Ngoaøi söï nuoâi döôõng cô theå ra, huyeát coøn giuùp cho "Thaàn" ñöôïc an ñònh. Töø ñoù suy ra neáu huyeát hö seõ coù caùc trieäu chöùng trong caùc cô quan noù nuoâi döôõng, khoâng coøn söï toàn tröõ moät caùch ñaày ñuû trong gan vaø thaàn minh seõ bò xaùo troän. Muoán trò beänh huyeát hö phaûi bieát cô quan naøo bò vaán ñeà trong caùc thaønh phaàn phoái hôïp ñeå sanh ra huyeát nhö ñaõ neâu treân vaø giuùp huyeát löu haønh ñieàu hoaø. Do ñoù, ta thaáy trò beänh huyeát hö theo Ñoâng-y khoâng phaûi laø chuyeän laøm moø, vaø nhaát laø khoâng cöù phaûi "boå maùu" maø xong ñöôïc.

ñuùng theo höôùng cuûa nguyeân taéc trò lieäu ñaõ ñeà ra. Hoaëc söï roái loaïn cô naêng coøn coù theå ñöôïc phaûn hoài (reversible) vì caáu truùc (structure) chöa bò xaâm phaïm hay hö haïi quaù nhieàu. - Veà döôïc thaûo thì lieàu löôïng toa thuoác phaûi khoâng maïnh hoaëc yeáu quaù, ngöôøi laäp phöông chaån beänh chính xaùc vaø bieát roõ mình muoán gì, söï pha cheá phaûi ñuùng vaø thuoác phaûi... "toát"! Do ñoù, chuùng toâi xin chæ ghi ra vaøi nguyeân taéc trò lieäu theo caùc chöùng ñaõ keå nôi phaàn treân, taùc duïng chính cuûa moät soá huyeät ñaïo; cuõng nhö vaøi baøi thuoác coå ñieån caên baûn ñeå chöùng minh laø Ñoâng-y coù phöông thöùc ñeå trò ñöôïc bònh thieáu maùu. Chöù khoâng phaûi chæ laø nhöõng lyù thuyeát xuoâng, khoâng coù giaù trò gì veà phöông dieän thöïc haønh. 3a) Trò baèng döôïc thaûo Coù nhöõng thang thuoác boå noåi tieáng töø xöa vaãn ñöôïc söû duïng raát thöôøng xuyeân nhö: Baùt Traân Thang: laø phöông thuoác boå Khí, döôõng Huyeát do hai toa nhoû sau ñaây hôïp laïi maø thaønh: - "Töù Vaät Thang": döôõng huyeát, haønh huyeát, bình can Ñöông-qui (Radix Angelicae sinensis), Xuyeân-khung (Radix Ligustici wallichii), Baïch-thöôïc (Radix Paeoniae albae), Thuïc-ñòa-hoaøng (Radix Rehmanniae glutinosae praeparata), - "Töù Quaân Töû Thang": boài boå Tyø khí Nhaân-saâm (Radix Ginseng), Baïch-truaät (Rhizoma Atractylodis macrocephalae), Phuïc-linh (Sclerotium Poriae cocos), Chích Cam-thaûo (Radix Glycyrrhizea uralensis praeparata) Toa naøy treân thöïc teá coù gia theâm hai vò Sinh-khöông (Rhizoma Zingiberis officinalis) vaø Ñaïi-taùo (Fructus Ziziphi jujubae) nhöng khoâng keå neân vaãn coù teân laø "Baùt Traân Thang" Thaäp Toaøn Ñaïi Boå: gioáng nhö 8 vò ôû treân vaø gia theâm 2 vò cho ñuû 10: Hoaøng-kyø (Radix Astragali membranacei) vaø Nhuïc-queá (Cortex Cinnamomi cassiae) Nhöng khi vaøo chi tieát, neáu muoán laäp moät phöông thuoác döôõng huyeát cho ñuùng thì ngoaøi vieäc ñaàu tieân caàn phaûi chöùa caùc döôïc thaûo coù taùc duïng döôõng huyeát, vaø ñoù laø ñieàu kieän tieân khôûi, ngöôøi trò beänh coøn baét buoäc phaûi thích öùng vôùi tình traïng beänh lyù luùc ñoù cuûa beänh nhaân. Thí duï gaëp tröôøng hôïp "Taâm huyeát hö" khoâng nuoâi ñöôïc Taâm vaø Thaàn, gaây neân tim ñaäp nhanh, maát nguû, keùm trí nhôù, maïch teá nhöôïc thì thuoác phaûi chöùa döôïc thaûo coù khaû naêng döôõng Taâm vaø an Thaàn. Thí duï nhö "Quy Tyø Thang": kieän Tyø vaø Taâm, boå döôõng khí huyeát, döôõng naõo.

3) Trò lieäu:

Ñeán phaàn naøy chuùng toâi xin ñôn giaûn hoaù moät chuùt vì nhieàu lyù do. Thöù nhaát laø baøi vieát naøy khoâng coù muïc ñích chæ daãn veà Ñoâng-y thöïc haønh, duø laø chaâm cöùu hay laø söû duïng döôïc thaûo. Vaán ñeà trò lieäu thöïc haønh neân ñeå cho ngöôøi coù khaû naêng chuyeân moân... thöïc haønh! Ñeå traùnh tröôøng hôïp sai laàm coù theå gaây nguy hieåm cho ngöôøi muoán "thöû". Chuyeän naøy ñuùng cho döôïc phaåm, cho y khoa hieän ñaïi thì cuõng ñuùng cho Ñoâng-y! Hieäu quaû cuûa phöông phaùp trò lieäu theo Ñoâng-y tuøy thuoäc nhieàu yeáu toá: - Chaån beänh cho ñuùng - Tìm nguyeân taéc trò lieäu cho thích öùng vôùi beänh traïng vaø ngöôøi beänh - Veà chaâm cöùu thì söï phoái huyeät phaûi döïa treân moät caên baûn höõu lyù, nhaän huyeät cho ñuùng, thuû thuaät phaûi chính xaùc vaø hieäu quaû (ñaéc khí). Phaàn coøn laïi thì coøn do ngöôøi beänh coù hay coøn coù khaû naêng veà khí huyeát ñeå "ñaùp öùng" (reacting)

Vietnamese Pharmaceutical Journal No.5 - 45

DÖÔÏC KHOA THÖÏC HAØNH- "Thieáu maùu" vaø "Huyeát hö"

tim hoài hoäp, ñaùnh troáng ngöïc, baûi hoaûi keùm söùc, hoaëc chaân tay teâ daïi, maïch teá nhöôïc... Nhaân-saâm (Radix Ginseng) hay Ñaûng-saâm (Radix Codonopsis pilosulae) Hoaøng-kyø (Radix Astragali membranacei) Baïch-truaät ( Rhizoma Atractylodis macrocephalae) Ñöông-qui (Radix Angelicae sinensis) Phuïc-thaàn (Sclerotium Poriae cocos pararadicis) Toan-taùo nhaân (Semen Ziziphi spinosae) Long-nhaõn nhuïc (Arillus Euphoriae longanae) Vieãn-chí (Radix Polygalae tenuifoliae) Moäc-höông (Radix Saussureae) Chích Cam-thaûo (Radix Glycyrrhizea uralensis praeparata) Sinh-khöông (Rhizoma Zingiberis officinalis) Ñaïi-taùo (Fructus Ziziphi jujubae) Trong ñoù, Ñöông-qui vaø Long-nhaõn-nhuïc boå huyeát döôõng taâm coøn Toan-taùo nhaân, Phuïc-thaàn vaø Vieãn-chí laøm an dòu Taâm Thaàn. Coøn thí duï neáu gaëp tröôøng hôïp Taâm khí bò suy, ñaäp khoâng ñeàu vaø nhanh thì vieäc ñaàu tieân vaãn boå taâm döôõng huyeát nhöng phaûi coäng theâm boå khí vaø laøm ñieàu hoaø laïi nhòp tim. Toa thuoác tieâu bieåu cho tröôøng hôïp naøy laø: "Chích Cam-Thaûo Thang" (Glycyrrhiza Decoction), goàm coù: Chích Cam-thaûo (Radix Glycyrrhizea uralensis praeparata), Nhaân-saâm (Radix Ginseng) Ñaïi-taùo (Fructus Ziziphi jujubae) Sinh ñòa-hoaøng (Radix Rehmanniae), A-giao (Colla Corii Asini), Maïch-ñoâng (Radix Ophiopogonis), Hoaû-ma-nhaân (Semen Cannabis Sativae) Queá-chi (Ramulus Cinnamoni cassiae) Sinh-khöông (Rhizoma Zingiberis officinalis) Toa naøy khi xöa luùc saéc thuoác coù theâm röôïu, 40% röôïu, 60% nöôùc. Thôøi nay chæ saéc baèng nöôùc, sau khi xong theâm 10% röôïu traéng vaøo ñeå daãn thuoác (söù). Trong toa naøy, Camthaûo laø "quaân", 6 vò keá laø "thaàn", 2 vò cuoái laø "taù", "söù" laø röôïu trong luùc cheá bieán (saéc thuoác). Phaàn naøy xin keå theâm nhö vaäy vì chuùng toâi muoán nhaân tieän ñaây giaûi thích sô qua thaønh phaàn ñaày ñuû cuûa moät toa thuoác Ñoâng-döôïc, thöôøng phaûi coù boán phaàn: "quaân" (thuoác taùc duïng chính), "thaàn" (thuoác keøm thuoác chính nhöng khoâng quan troïng baèng), "taù" (thuoác coù taùc duïng hoå trôï, phuï thuoäc) vaø "söù" (thuoác daãn). Hai thí duï treân cho chuùng ta thaáy laø vieäc chaån beänh cho ñuùng, luùc naøo cuõng laø ñieàu caàn thieát ñeå chöõa trò moät caùch ñöùng ñaén. Theâm moät thí duï khaùc, chaúng haïn nhö gaëp tröôøng hôïp "Can-huyeát hö", trong beänh lyù coù theâm caùc chöùng nhö ñau vuøng buïng, maét môø hoaëc khoâ, haønh kinh lôït laït vaø raát ít, thì trò khoâng theå trò gioáng nhö laø "Tyø-khí hö" vì Tyø laø goác

haäu thieân cuûa khí huyeát neân trong tröôøng hôïp naøy khí huyeát ñeàu bò suy thoaùi raát traàm troïng, phaûi duøng lieàu löôïng raát maïnh ñeå boå khí sinh huyeát. 3b) Trò baèng chaâm cöùu: Veà phöông thöùc trò lieäu baèng chaâm cöùu cuõng khoâng khaùc! Huyeät ñaïo coù theå ñöôïc söû duïng trong vieäc ñieàu trò huyeát hö coù raát nhieàu. Nhöng khoâng phaûi laø cöù chaâm taát caû hay "caøng nhieàu caøng toát" laø hay! Treân thöïc teá chöùng minh khoâng phaûi nhö vaäy! Caâu "nhaát chaâm baù beänh" tuy quaù lyù töôûng, vaø coù theå laø khoâng töôûng, nhöng chaâm "töôùi hoät sen" thì chaúng coøn ra phöông phaùp gì caû. Söï phoái huyeät moãi kyø chaâm hay cöùu phaûi coù lyù do cuûa noù, vaø söï thay ñoåi huyeät ñaïo cho caùc kyø sau ñoù cuõng phaûi theo moät logic, döïa theo keát quaû coù ñöôïc, hay döïa theo yù muoán cuûa ngöôøi trò trong moät tieán trình ñaõ vaïch tröôùc, tuøy theo keát quaû chaån beänh, traïng thaùi cuûa beänh nhaân vaø söï tieán trieån hay thay ñoåi cuûa beänh traïng. Do ñoù, ñöôïc lieät keâ döôùi ñaây, laø caùc huyeät cuøng caùc taùc duïng ñaõ ñöôïc ñôn giaûn hoaù tôùi möùc toái ña, ñeå cho chuùng ta moät yù nieäm veà lyù thuyeát trong laâm saøng. Nhöng treân phöông dieän thöïc haønh, söï löïa choïn huyeät ñaïo theo kinh maïch, caùch phoái huyeät, thuû thuaät chaâm hay cöùu laø nhöõng ñieàu kieän chi phoái raát nhieàu cho keát quaû thu thaäp ñöôïc. Thí duï nhö beänh thieáu maùu coù chöùng nhöùc ôû ñænh ñaàu (vuøng huyeät Baù-hoäi, Du-20) thì ngöôøi trò beänh phaûi raønh veà kinh maïch ñeå bieát kinh Can bò aûnh höôûng, taïi vì Tuùc-Khuyeát-aâm Can kinh coù moät nhaùnh ñi leân, qua coå, vuøng maét roài leân ñænh ñaàu ñeå keát hôïp vôùi maïch Ñoác, duø trong saùch vôû thoâng thöôøng (khoâng vaøo saâu chuyeân moân) chæ veõ kinh naøy ñeán huyeät Kyø-moân (Liv-14) ôû söôøn ngöïc laø heát! Tröôøng hôïp naøy ñöông nhieân phaûi chuù troïng boå Can nhö phaûi theâm Khuùctuyeàn (Liv-8) laø huyeät hôïp, thuoäc thuûy sinh moäc, cuûa Can kinh. Sau ñaây laø lieät keâ caùc huyeät hay caùc nhoùm huyeät duøng chung vaø coâng naêng ñôn giaûn hoaù cuûa chuùng trong tröôøng hôïp trò huyeát hö: (See table.1)

4) Vaøi chöùng minh khoa hoïc:

Raát tieác laø cho tôùi nay coù quaù ít taøi lieäu ñöôïc phoå bieán moät caùch chaùnh thöùc, ghi laïi caùc nghieân cöùu vaø keát quaû cuûa döôïc thaûo cuõng nhö chaâm cöùu theo Ñoâng-y treân beänh thieáu maùu. Maø daàu cho coù chuùt ít thì söï chính xaùc cuõng khoâng ñöôïc ñaûm baûo nhö chuùng toâi seõ phaùt bieåu trong phaàn keát luaän cuoái baøi vieát naøy. Tìm maõi môùi thaáy hai phuùc trình veà döôïc thaûo töông ñoái caàn neân keå laïi: - Moät laø Novel Therapies for the Hemorrhaging Patient 2004, cho ngaønh... thuù-y, bôûi Lynelle Graham, DVM, Diplomate ACVA (University of Minnesota College of Veterinary Medicine, Veterinary Medical Center). Baøi naøy phuùc trình söï coâng hieäu cuûa moät ñaëc cheá coù teân treân thò tröôøng laø "Yunnan Bai Yao" trong taùc duïng laøm ngöng xuaát

46 - Taäp San Chuyeân Nghieäp Döôïc Khoa

"Thieáu maùu" vaø "Huyeát hö" - PHARMACY PRACTICE

Table.1: Baûng lieät keâ caùc huyeät hay caùc nhoùm huyeät duøng chung vaø coâng naêng ñôn giaûn hoaù cuûa chuùng trong tröôøng hôïp trò huyeát hö Kinh maïch vaø soá (Ngoaïi kinh) Baøng-quang kinh (Bl-15) (Bl-15) (Bl-17) Teân huyeät Ngö-yeâu Taâm-du Taâm-du Caùch du Coâng duïng trong chöùng huyeát hö trò nhöùc ñaàu vuøng phía sau hai maét, huyeät a-thò döôõng taâm-huyeát. cöùu baèng ngaûi ñeå boå taâm khí. ngoaøi taùc duïng taïi choã (trò co thaét caùch maïc), ñaây laø huyeät coù theå trò taát caû beänh veà huyeát cuûa Ñoâng-y nhöng vì ôû sau löng neân chæ ñöôïc duøng khi thuaän tieän. Caùc huyeät khaùc trò "goác" beänh neân ñöôïc öu tieân hôn. boå taâm, an thaàn thaêng khí leân ñænh ñaàu. boài döôõng taâm-huyeát, an thaàn boå Can huyeát. boài boå taâm-khí, an thaàn an thaàn raát maïnh cho tröôøng hôïp aâu lo khích ñoäng (anxiety) thaùi quaù. döôõng huyeát, an thaàn, boå döôõng töû cung laø moät huyeät boå khí toång quaùt coøn goïi laø Ñan-ñieàn, cuõng duøng ñeå boài boå vaø hoaït khí vuøng buïng döôùi boå Tyø, ñieàu huyeát, duøng khi coù xuaát huyeát quan troïng laøm bôùt ñau khi thoáng kinh trò beänh Tyø, Vò, boài boå khí huyeát (xem caùc nhoùm phoái huyeät) döôõng huyeát vaø boå khí.

(Bl-44) Ñoác-maïch (Du-20) Taâm kinh (H-7) Can kinh (Liv-8) Taâm-baøo kinh (P-6) (P-7) Nhaâm maïch (Ren-4) (Ren-6) Tyø kinh (Sp-1) (Sp-8) Vò kinh (ES-36) Nhoùm phoái huyeät (St-36 & Sp-6 & Bl-20) (St-36 & Sp-6) (Bl-18 & Bl-20) (Ren-12 & Bl-21) (Ren-14 & He-7) (Ren-14 & Ren-15) (Sp-4 & P-6)

Thaàn-ñöôøng Baù-hoäi Thaàn-moân Khuùc-tuyeàn Noäi-quan Ñaïi-laêng Quan-nguyeân Khí-haûi

AÅn Baïch Ñòa cô Tuùc-tam-lyù Tuùc-tam-lyù, Tam-aâm-giao, Tyø du Tuùc-tam-lyù vaø Tam-aâm-giao Can-du vaø Tyø-du Trung-uyeån vaø Vò-du Cöï-khuyeát vaø Thaàn-moân Cöï khuyeát vaø Cöu vó Coâng-toân vaø Noäi-quan

boài boå khí laãn huyeát, Tam-aâm-giao cuõng coù taùc duïng an thaàn. laø phoái huyeät ñeå boå Tyø sinh can huyeát ñeå kieän Tyø ích Vò an thaàn boài döôõng taâm-huyeát, an thaàn döôõng huyeát an thaàn

Vietnamese Pharmaceutical Journal No.5- 47

DÖÔÏC KHOA THÖÏC HAØNH- "Thieáu maùu" vaø "Huyeát hö"

huyeát. Ñaây laø moät ñaëc cheá neân coâng thöùc khoâng coù gì laø roõ raøng. Chuùng toâi chæ ñoaùn chaát taùc ñoäng chaùnh coù leõ laø Saâm Tam-Thaát, coù teân khoa hoïc laø Panax pseudoginseng hoaëc Radix notoginseng. Ñoäc giaû naøo muoán tìm hieåu coù theå vaøo internet theo ñòa chæ ñính keøm phía döôùi baøi. - Phuùc trình ñuùc keát thöù hai laø Treatment of Thalassemia with Chinese Herbs bôûi Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon. Baøi naøy keå laïi raèng töø naêm 1980, caùc nhaø nghieân cöùu cuûa Guang'anmen Hospital of the China Academy of Traditional Chinese Medicine (Beijing) vaø Hematology Institute of the Chinese Academy of Medical Sciences ñaõ töøng tìm caùch trò lieäu beänh Thalassemia. Duøng Bushen Shengxue Fang (Boå Thaän Sinh Huyeát phöông) hoaëc caùc toa töông töï ñeå söû duïng. Trong kyø Ñaïi Hoäi naêm 2000 taïi Baéc Kinh (2000 International Congress on Traditional Medicine) keát quaû ñaõ ñöôïc thoâng baùo laø raát thuaän lôïi, cuõng nhö xaùc nhaän ñöôïc lyù thuyeát cuûa Ñoâng-y veà "Thaän sanh Tuûy". Phaàn chaâm cöùu thì trong boä saùch "Traiteù d'Acupuncture" maø C. Roustan ñaõ dòch töø taøi lieäu chaùnh thöùc cuûa Vieän Chaâm-cöùu Thöôïng-Haûi (Trung-Hoa) coù ghi laïi vaøi thí nghieäm kieåm chöùng taùc duïng cuûa caùc huyeät chaâm cöùu treân heä tuaàn hoaøn. Chuùng toâi cuõng xin ghi laïi moät caùch toùm taét vaøi ñieàu ñaùng keå nhö sau: - Trong tröôøng hôïp bò giaûm baïch huyeát caàu (leucopenia) do hoaù hoïc trò lieäu vaø quang tuyeán trò lieäu, sau khi chaâm caùc huyeät: Ñaïi-chuøy (Du-4), Hieäp-coác (Li-4), Tuùc-tam-lyù (St36) ñaõ laøm taêng thaät nhanh soá löôïng baïch huyeát caàu. - Chaâm Cao-hoang (Bl-43) vaø Tuùc-tam-lyù (St-36) nôi ngöôøi bò thieáu hoàng caàu (pernicious anemia) sau 5 ngaøy soá hoàng huyeát caàu ñaõ taêng töø 1.000.000 leân 3.370.000/mm3. - Trong nhöõng tröôøng hôïp beänh lao gaây ho thoå ra huyeát, duøng "bì phu chaâm" (mai hoa chaâm) chung quanh vuøng coå beänh nhaân ñaõ laøm taêng soá löôïng tieåu caàu (thrombocytes) vaø giuùp bôùt xuaát huyeát. Ngoaøi ra trong saùch keå treân coøn ghi laïi nhöõng taùc duïng cuûa chaâm cöùu treân nhòp tim, söï co maïch vaø daõn maïch, heä baïch huyeát vaø keå caû treân huyeát aùp. Dó nhieân cuõng coù phaàn cho caùc boä phaän khaùc, nhö heä mieãn nhieãm, boä hoâ haáp, boä baøi tieát, heä noäi tieát v.v...

5) Keát luaän:

Trong tröôøng hôïp beänh "thieáu maùu" chuùng ta thaáy Ñoâng vaø Taây coù veû khaù "aên yù" vôùi nhau, ít ra laø trong caùc ñieåm chính yeáu cuûa Taây-y! Töø nguoàn goác beänh coù theå do dinh döôõng hay haáp thuï keùm, Vò hö hay baøi tieát khoâng ñuû intrinsic factor, töø Thaän tinh baát tuùc hay khoâng ñuû erythropoietin, do töø beänh laâu ngaøy nôi caùc cô quan khaùc v.v... Theâm vaøo ñoù, caùc trieäu chöùng moâ taû cuõng aên khôùp vôùi nhau phaàn lôùn nhö: yeáu ôùt, da moâi vaø moùng tay chaân lôït laït, nhòp ñaäp cuûa tim mau hôn bình thöôøng, thôû haøo heån, töùc ngöïc, choùng maët, xaây xaåm, deã noåi noùng, chaân tay teâ hay laïnh, nhöùc ñaàu, maïch yeáu v.v... Cuõng nhö ñoái vôùi chöùng beänh ñoù vaø caùc trieäu chöùng sinh ra töø ñoù, caû hai beân y-hoïc ñeàu coù caùch trò lieäu. Ñeå traùnh söï tranh luaän voâ ích, chuùng toâi ñaõ coá traùnh khoâng laïm baøn ñeán khía caïnh coâng hieäu cuûa caùc phöông thöùc trò lieäu. Duø sao, theá naøo cuõng coù thaønh coâng vaø thaát baïi trong caû ñoâi beân. Xin ñeå toaøn quyeàn cho ñoäc giaû vaø beänh nhaân töï tìm laáy keát luaän vaø caùc vò coù thaåm quyeàn veà y teá xeùt ñoaùn giaù trò caùc keát quaû cuõng nhö söï ñoái chieáu suaát ñoä (ratio) keát quaû, öùng vôùi chi phí veà y teá coäng ñoàng. Tuy nhieân veà phöông dieän sinh lyù hoïc, chuùng toâi nhaän thaáy nhieàu yeáu toá raát baát ngôø. Ví duï nhö ngöôøi xöa ñaõ bieát khaùi nieäm veà dò öùng naèm trong maùu (phong ngöùa, noåi meà ñay); nhö Thaän laø caùc nguoàn kích thích toá trong cô theå (xem baøi "Taûn Maïn veà Thaän suy vaø Suy Thaän"), coå nhaân ñaõ bieát vaø duøng caâu "Thaän sanh Tuûy" ñeå noùi veà vai troø Thaän tinh trong söï sinh huyeát vaøi ngaøn naêm tröôùc söï khaùm phaù ra erythropoietin. Nguyeân vaên ñuùng ra coå nhaân ñaõ noùi "Thaän sinh Tuûy vaø Naõo..."! Thì söï thaät cho thaáy laø môùi gaàn ñaây khoa hoïc cuõng ñaõ khaùm phaù ra söï sinh toång hôïp erythropoietin trong naõo khi naõo boä thieáu döôõng khí, nhö sau khi bò "truùng phong" (ñoät quî naõo hay "stroke") chaüng haïn. Ñoù laø chöa keå nhöõng trieäu chöùng khaùc nhö maát nguû, ñoäng kinh hay co giaät maø chöa thaáy Taây-y ñeà caäp moät caùch roõ raøng söï lieân laïc ñoái vôùi beänh thieáu maùu. Cuõng nhö nhöõng vaán ñeà ñieàu trò coù theå lieân heä ñeán hormon nhö trò beänh huyeát hö gaây taét kinh; hoaëc cuõng huyeát hö maø laïi vì "baêng laäu" (baêng coù nghóa laø kinh nguyeät quaù nhieàu, laäu thì huyeát ít hôn nhöng cöù keùo daøi dai daúng), maø söï trò lieäu cuûa Ñoâng-y ñoái vôùi caùc chöùng naøy raát laø coâng hieäu! Neáu tôùi ñaây ñoäc giaû ñaõ nhaän xeùt ñöôïc ñieàu quan troïng laø: tuy hai teân beänh coù veû moâ taû nhöõng trieäu chöùng khaù gioáng nhau maø trong vaán ñeà nghieân cöùu, neáu chæ ño hematocrit hay ñeám hoàng huyeát caàu roài laøm thoáng keâ ñeå chöùng minh hieäu quaû cuûa moät phöông thöùc trò lieäu theo Ñoâng-y thì khoâng coù gì goïi laø chính xaùc heát! Ñöôïc nhö vaäy thì ngöôøi vieát baøi naøy seõ töï nhuû laø ñaõ laøm ñöôïc moät ñieàu ích lôïi, laøm ñôõ maát coâng toán cuûa moät caùch thaät voâ ích veà chuyeän naøy.

48 - Taäp San Chuyeân Nghieäp Döôïc Khoa

"Thieáu maùu" vaø "Huyeát hö" - PHARMACY PRACTICE

References:

1- Novel Therapies for the Hemorrhaging Patient - 2004 http://www.mvma.org/Proceedings/anesthesia/Novel%20Therapy.html 2- Treatment of Thalassemia with Chinese Herbs by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon. http://www.itmonline.org/arts/thalassemia.htm 3- Medline Plus Encyclopedia (A service of the U.S. National Library of Medicine and the National Institutes of Health): http://medlineplus.gov/ 4- "Hoaøng Ñeá Noäi Kinh" baûn dòch cuûa Löông y Nguyeãn Ñoàng Di 5- "Hieåu bieát toùm taét Noäi Kinh", Löông y Nguyeãn Trung Hoaø 6- "Giaùo Trình Lyù Luaän Cô Baûn Y Hoïc Coå Truyeàn", Löông y Nguyeãn Trung Hoaø 7- "Nam Nöõ Khoa", Phoù Thanh Chuû, baûn dòch cuûa Ñoâng-y-só Ñònh Ninh Leâ Ñöùc Thieáp 8- "Le Diagnostic en Meùdecine Chinoise" de B. Auteroche et P. Navailh, Edition Maloine. 9- "Meùdecine Traditionnelle Chinoise", Nguyeãn Vaên Nghò, Christine Recours-Nguyen, Edition N.V.N., 1984. 10-"A Clinical Guide to Chinese Herbs and Formulae", by Chen Song Yu and Li Fei, Churchill Livingstone Edition. 11- "Grand Formulaire de Pharmacopeùe Chinoise", Eric Marieù, Ed. Paracelse. 12- "Traiteù d'Acupunture", Vol I, II, III, Traduction de C. Roustan, Edit. Masson 1987. 13- "The Practice Of Chinese Medecine, The Treatment of Diseases with Acupuncture and Chinese Herb", Giovanni Maciocia,Churchill Livingstone.

Vietnamese Pharmaceutical Journal No.5- 49

Thiu máu và TrÎ liOEu b¢ng các phÜÖng pháp t¿ nhiên

DS Traàn Vieät Höng, BS Traàn Quang Tuaán Anh

Abstract:

Anemia is the result of a marked reduction in the number red blood cell (RBC) in the blood or in a decrease in hemoglobin content of RBC. It is caused by excessive hemorrhage, excessive destruction of RBC or inadequate production of the RBC. Deficiency in iron, Vitamin B12, folic acid and vitamin C due to diet or gastrointestinal absorption disorders can lead to anemia. Natural remedies based on special diets, nutritional supplements and traditional herbs are discussed in depth.

ñåi cÜÖng :

hiu máu (Anemia) ÇÜ®c xem là moät tình trång trong Çó máu thiu các t bào hÒng cÀu (Red blood cell=RBC) hay thiu phÀn hemoglobin(chÙa s¡t) trong RBC. NhiOEm vø chính yu cûa t bào hÒng cÀu là chuyên chª oxy tØ ph°i Çn các mô t bào cûa cÖ th< Ç< trao Ç°i và lÃy Çi carbon dioxide. Các triOEu chÙng cûa bOEnh thiu máu , nhÜ mOEt mÕi quá ñoä, là bi<u hiOEn cûa tình trång mô t bào không có Çû oxygen cÀn thit và có s¿ tích lÛy carbon dioxide.. Có th< chia chÙng Thiu máu thành 3 nhóm chính: - Thiu máu do ª cÖ th< mÃt quá nhiSu máu. - Thiu máu do ª t bào hÒng cÀu (RBC) bÎ hûy hoåi quá mÙc. - Thiu máu do ª cÖ th< không ch tåo Çû RBC. 1- Thiu máu do ª cÖ th< mÃt quá nhiSu máu : Tình trång thiu máu có th< xÄy ra trong nhöõng trÜ©ng h®p mÃt máu cÃp tính ( diÍn tin nhanh) và mÃt máu kinh niên (diÍn tin chÆm nhÜng liên tøc). MÃt máu cÃp tính có th< nguy Çn tính mång nu cÖ th< mÃt hÖn 1/3 t°ng sÓ khÓi lÜ®ng máu (chØng 1.5 lít). MÃt máu cÃp tính không Çòi hÕi nhöõng chÄn Çoán khó khæn và thÜ©ng phäi cÀn Çn truySn máu. MÃt máu kinh niên, nhÜ mÃt máu do xuÃt huyt vì ung loét bao tº, bOEnh trï hay kinh nguyOEt ÇSu có th< gây chÙng thiu máu. CÀn phäi chÄn Çoán chính xác Ç< có th< ÇÜa ra phÜÖng thÙc trÎ liOEu cÀn thit. 2- Thiu máu do hÒng cÀu bÎ hûy hoåi quá mÙc : Nhöõng hÒng cÀu 'già', và nhöõng hÒng cÀu bÃt thÜ©ng, ÇSu bÎ tÿ (lá lách) loåi ra khÕi hOE thÓng tuÀn hoàn. Nu s¿ hûy hoåi các t bào này vÜ®t quá khÕi khä næng ch tåo các RBC m§i cûa cÖ th<, thì có th< ÇÜa Çn thiu máu. Ls do thÜ©ng g¥p nhÃt ÇÜa Çn s¿ hûy hoåi quá mÙc RBC là hình dång bÃt thÜ©ng cûa RBC. Moät sÓ vÃn ÇS khin RBC có hình dång bÃt thÜ©ng nhÜ : trøc tr¥c trong viOEc t°ng h®p hemoglobin (ví dø nhÜ trÜ©ng h®p bOEnh do di truySn sickle-cell anemia..); t°n thÜÖng cÖ hc do chÃn thÜÖng bên trong ñoäng måch; hÜ håi do di truySn vS các enzym liên hOE Çn RBC, Çn các vitamins và khoáng chÃt.. 3- Thiu máu do ª suy yu sän xuÃt RBC : ñây ÇÜ®c xem là trÜ©ng h®p thiu máu thông thÜ©ng nhÃt. Nhöõng ls do thÜ©ng g¥p nhÃt là do ª nhöõng khim khuyt vS dinh döôõng. Tuy s¿ thiu høt moät sÓ vitamins và khoáng chÃt có th< gây ra thiu máu, nhÜng 3 loåi thÜ©ng g¥p nhÃt là: thiu S¡t, Vitamin B12 và Folic acid..Thiu máu do thiu s¡t ÇÜ®c gi là microcytic anemia vì RBC trª thành rÃt nhÕ, trong khi Çó thiu máu do khim khuyt Vit B12 và Folic acid låi ÇÜ®c gi là macrocytic anemia vì RBC trª thành to l§n hÖn.

50 - Taäp San Chuyeân Nghieäp Döôïc Khoa

T

Thiu máu và TrÎ liOEu - PHARMACY PRACTICE

Các chÙng thiu máu

1-Thiu máu do thiu S¡t Thiu s¡t là ls do thÜ©ng g¥p nhÃt trong các chÙng thiu máu, tuy nhiên nhöõng triOEu chÙng thiu máu låi chÌ xuÃt hiOEn vào giai-Çoån cuÓi cûa thiu s¡t. Các nghiên cÙu tåi các QuÓc gia Çang phát tri<n ghi nhÆn các b¢ng chÙng cho thÃy có tình trång thiu s¡t nÖi tØ 30-50 % dân sÓ (1). Nhóm có nguy cÖ cao nhÃt trong vÃn ÇS thiu s¡t là trÈ em dܧi 2 tu°i, thiu nöõ 13-16, phø nöõ có thai và ngÜ©i cao niên. Tình trång thiu s¡t có th< do ª s¿ gia tæng trong nhu cÀu s¡t cûa cÖ th<, æn uÓng thiu chÃt s¡t, suy giäm hÃp thu hay sº døng, mÃt máu ho¥c do s¿ phÓi h®p giöõa các yu tÓ k< trên.(1,2). Tåi Hoa Kÿ, Ça sÓ các tình trång thiu S¡t là do ª cÖ th< thiu s¡t d¿ tröõ, khoäng 30 % phø nöõ MÏ không Çû s¡t d¿ tröõ: hemoglobin trong máu ª mÙc bình thÜ©ng, nên khi có thai hay khi Çau Óm..không có tröõ lÜ®ng s¡t Ç< bù trØ.. Nhu cÀu vS S¡t gia tæng trong giai Çoån tæng tröôûng nÖi trÈ em và lúc trÈ Çang trܪng thành, trong th©i kÿ mang thai và lúc cho con bú. HiOEn nay, phÀn l§n các phø nöõ có thai ÇÜ®c cho uÓng thêm S¡t. VÃn ÇS æn uÓng không Çû chÃt s¡t (trong th¿c phÄm) cÛng xäy ra tåi nhiSu nÖi trên th gi§i, nhÃt là tåi nhöõng vùng có nhiSu ngÜ©i æn chay. Th¿c ÇÖn cûa trÈ em tåi nhöõng nܧc công nghiOEp phát tri<n (æn nhiSu söõa và ngÛ cÓc cereal) cÛng chÙa ít chÃt s¡t. NgÜ©i l§n, nu chÌ æn các loåi th¿c phÄm vô b° (junk foods) cÛng së có nguy cÖ thiu s¡t. Tuy nhiên, nhóm có nguy cÖ cao vS thiu s¡t trong dinh döôõng là nhöõng vÎ cao niên có l®i tÙc thÃp(3). S¿ kiOEn này còn r¡c rÓi hÖn vì nÖi nhöõng vÎ cao niên, s¿ suy giäm hÃp thu s¡t là ÇiSu vÅn thÜ©ng xÄy ra (4). S¿ suy giäm hÃp thu s¡t thÜ©ng là do ª s¿ thiu bài tit acid hydrochloric trong bao tº (1,2) và tình trång này rÃt thÜ©ng xÄy ra nÖi ngÜ©i cao niên (3). Nhöõng ls do khác vS suy giäm hÃp thu s¡t bao gÒm tiêu chäy kinh niên, không hÃp thu ÇÜ®c s¡t, giäi phÅu c¡t bao tº và dùng các chÃt trung hòa acid (antacid)(1). MÃt máu là nguyên do thÜ©ng g¥p trong các trÜ©ng h®p thiu máu nÖi phø nöõ trong lÙa tu°i còn sinh nª, và thÜ©ng là do kinh nguyOEt quá nhiSu. Nhöõng nguyên do khác là xuÃt huyt trong bao tº, bOEnh trï và hin máu ( khi cho 1 pint hay 0.5 lit máu, cÖ th< së bÎ mÃt Çi 250 mg s¡t, và mÃt nhiSu tháng sau lÜ®ng s¡t này m§i ÇÜ®c bù Ç¡p låi ÇÀy Çû) (1,2). ViOEc chÄn Çoán thiu s¡t tÓt nhÃt là Ço nÒng ñoä ferritin trong huyt thanh (serum ferritin= protein tÒn tröõ s¡t) : và Çây là thº nghiOEm nhÆy nhÃt. Các phÜÖng thÙc Ço lÜ®ng s¡t tÒn tröõ nhÜ s¡t trong huyt thanh, khä næng nÓi kt s¡t t°ng coäng và hemoglobin trong t bào máu..kém nhÆy hÖn, nhÜng vÅn thÜ©ng ÇÜ®c thº nghiOEm Ç< giúp ÇÎnh bOEnh. Tình trång thiu s¡t kéo dài ÇÜ®c xác ÇÎnh bªi lÜ®ng t bào máu ÇÕ (RBC) xuÓng thÃp, hematocrit (KhÓi lÜ®ng RBC) xuÓng thÃp (còn 34-37%), t bào hÒng cÀu nhÕ Çi và mÙc ferritin trong huyt thanh xuÓng thÃp.(1)

2- Thiu máu do khim khuyt Vitamin B12 : Thiu Vitamin B12 thÜ©ng xÄy ra do moät s¿ khim khuyt vS hÃp thu hÖn là thiu B12 trong th¿c ÇÖn ÇÜa vào cÖ th<. ñ< có th< ÇÜ®c hÃp thu, B12 phäi ÇÜ®c phóng thích khÕi th¿c phÄm do tác døng cûa acid hydrochloric và kt nÓi v§i moät yu tÓ noäi tåi (intrinsic factor) có trong ruoät non(5). Yu tÓ này ÇÜ®c bài tit tØ các t bào ª vách trong (parietal) bao tº, các t bào này cÛng có trách nhiOEm trong viOEc tit hydrochloric acid. H®p chÃt phÙc tåp B12-Intrinsic factor ÇÜ®c hÃp thu nÖi ruoät non v§i s¿ tr® giúp cûa trypsin, moät enzym do tøy tång sän xuÃt. ñ< hÃp thu B12, cÖ th< phäi tit Çû hydrochloric acid và yu tÓ intrinsic, lÜ®ng các enzym cûa tøy tång phaûi ÇÀy Çû, nhÃt là trypsin, ÇÒng th©i còn cÀn có 'khúc ruoät ileum (khoäng ruoät non sau chót) nguyên vËn và lành månh. Tình trång thiu intrinsic factor ÇÜa Çn trång thái thiu máu, có th< gây tº vong (pernicious). S¿ khim khuyt intrinsic factor ít khi xÄy ra nÖi ngÜ©i dܧi 35 tu°i, và thÜ©ng xÄy ra nÖi nhöõng ngÜ©i gÓc Scandinavia, Anh, và Ái nhï Lan, và ít xÄy ra nÖi ngÜ©i Nam Âu, Á Çông và Da Çen. Thiu máu loåi aùc tính thöôøng xÄy ra kèm theo v§i thiu s¡t (6). S¿ thiu B12 do dinh döôõng thÜ©ng liên quan Çn nhöõng ngÜ©i æn chay chÌ æn rau quä. Vì nÖi cÖ th< bình thÜ©ng, lÜ®ng B12 tÒn tröõ có th< sº døng ÇÜ®c trong tØ 3 Çn 6 næm, s¿ thiu B12 thÜ©ng chÌ xuÃt hiOEn nÖi ngÜ©i æn chay sau nhiSu næm. Có moät vài trÜ©ng h®p thiu B12 nÖi trÈ sÖ sinh Çã ÇÜ®c ghi nhÆn là do ª bà mË æn chay, Çã không uÓng các vitamin trong th©i gian mang thai. ThÙc æn lên men nhÜ xì dÀu, miso và tempeh có chÙa moät lÜ®ng nhÕ B12 . ViOEc chÄn Çoán thiu B12 có th< ÇÜ®c xác nhÆn b¢ng cách Ço nÒng ñoä B12 trong máu. Tuy nhiên Ça sÓ các Bác sï chÌ theo dõi s¿ hiOEn diOEn cûa các t bào máu ÇÕ to hÖn bình thÜ©ng và các triOEu chÙng chuyên biOEt xÄy ra do thiu máu vì thiu B12 nhÜ s¡c diOEn xanh-tái, dÍ mOEt mÕi, høt hÖi, löôõi Çau, ÇÕ nhÜ thÎt bò, sÜng tiêu chäy, rÓi loån tim-hOE thÀn kinh (1,2). Các rÓi loån thÀn kinh do thiu B12 có th< nghiêm trng: nhÜ tê, cäm giác kin bò nÖi chân, cánh tay, trÀm cäm, nhÀm lÅn, mÃt cäm giác rung cÖ, mÃt phän xå giây gân.. NÖi ngÜ©i cao niên các triOEu chÙng này khin có th< bÎ nhÀm v§i bOEnh Alzheimer's. 3- Thiu máu do thiu Folic acid : Thiu folic acid là trÜ©ng h®p thiu vitamin thÜ©ng g¥p nhÃt trên th gi§i. Không nhÜ Vitamin B12, cÖ th< không d¿ tröõ nhiSu lÜ®ng folic acid dÜ thØa: folic acid tÒn tröõ trong cÖ th< chÌ Çû cho sinh hoåt bình thÜ©ng trong tØ 1 Çn 2 tháng. Tình trång thiu folic acid xÄy ra rÃt thÜ©ng nÖi ngÜ©i nghiOEn rÜ®u vì rÜ®u gây trª ngåi cho viOEc hÃp thø folic acid, gây rÓi loån cho tin trình bin döôõng và khin cÖ th< thäi folic acid ra ngoài. Tình trång thiu folic acid cÛng thÜ©ng g¥p nÖi phø nöõ có thai do ª nhu cÀu gia tæng. Folic acid tÓi quan trng cho viOEc tåo t bào nÖi phôi thai, nu thai không ÇÜ®c cung cÃp Çû folic acid, trÈ khi sinh ra, có th< bÎ khuyt tÆt nhÜ neural

Vietnamese Pharmaceutical Journal No.5 - 51

DÖÔÏC KHOA THÖÏC HAØNH - Thiu máu và TrÎ liOEu

tube defect. Phø nöõ có thai dÍ ª vào tình trång thiu folic acid do ª nhu cÀu cûa bào thai gia tæng. Nu uÓng nhiSu rÜ®u trong th©i kÿ mang thai, nÒng ñoä folic acid bÎ ru®u làm xuÓng thÃp, có th< ÇÜa Çn hoäi chÙng thai ngoä ñoäc do rÜ®u (fetal alcohol syndrome)(7). Ngoài rÜ®u, moät sÓ thuÓc khi uÓng vào cÖ th<, có th< gây ra tình trång thiu folic acid nhÜ các thuÓc trÎ ung thÜ, trÎ kinh phong, thuÓc tránh thai (1,2). Tình trång thiu folic acid rÃt thÜ©ng g¥p nÖi nhöõng bOEnh nhân tiêu chäy kinh niên hay bÎ rÓi loån hÃp thu nhÜ bOEnh coeliac, bOEnh Crohn's và bOEnh sprue nhiOEt ǧi.. và thiu folic acid låi ÇÜa Çn tiêu chäy và loån hÃp thu.. tåo thành moät cái vòng lÄn quÄn. Do Çó nÖi nhöõng bênh nhân bÎ tiêu chäy kinh niên, rÃt nên cho uÓng folic acid nhÜ moät biOEn pháp phòng ngØa.. Thiu folic acid ÇÜa Çn thiu máu giÓng nhÜ loåi thiu máu vì thiu B12 (macrocytic=t bào máu trª thành to hÖn). Thº nghiOEm nhÆy nhÃt Ç< tìm tình trång thiu folic acid là Ço lÜ®ng folic acid trong huyt thanh và trong RBC. Ngoài các triOEu chÙng thiu máu, thiu folic acid còn gây ra tiêu chäy, trÀm cäm và löôõi sÜng ÇÕ (1) . 4- Thiu máu liên hOE Çn Vitamin C : Vitamin C giúp gia tæng lÜ®ng s¡t hÃp thu nÖi ruoät tØ các nguÒn th¿c phÄm không phäi là thÎt, b¢ng phän Ùng khº và phÙc hóa (chelating) chÃt s¡t. ñ< có th< höõu hiOEu, cÀn phäi uÓng Vit C cùng moät lúc v§i S¡t. NÖi nhöõng bOEnh nhân thiu máu vì thiu s¡t, khi uÓng viên thuÓc S¡t chung v§i 100-200 mg Vit C lÜ®ng s¡t hÃp thuï gia tæng tØ 30-40 %. Vit C cuõng tham d¿ vào tin trình chuy<n folic acid sang dång có hoåt tính (trong cÖ th<), dihydrofolic acid. Trên th¿c t, thiu máu vì thiu Vit C có nhöõng triOEu chÙng gÀn tÜÖng t¿ nhÜ thiu folic acid.

lesterol và nhöõng vitamin tan trong dÀu (nhÜ Vitamin A..) ViOEc sº døng Gan hay Trích tinh Gan hiOEn không còn ÇÜ®c khuyn khích trong Y hc (dòng chính=mainstream) tåi Hoa Kÿ, nhÜng vÅn là phÜÖng thÙc höõu døng nhÃt trong Y hc trÎ liOEu b¢ng phÜÖng pháp t¿ nhiên (Naturopathic Medicine) vì Gan chÙa khá nhiSu yu tÓ có th< kích khôûi cÖ th< ch tåo các RBC, và cung cÃp thêm cho cÖ th< nhiSu vitamins và khoáng chÃt. Vài sÓ liOEu vS giaù trÎ dinh döôõng cûa GAN B¼ (sÓ lÜ®ng 3 oz, nÃu theo ki<u om chín=braised): (theo Prevention Magazine's Nutrition Advisor. 1993) - Calories - ChÃt béo - Bão hòa - Bão hòa 1 nÓi Çôi - Bão hòa nhiSu nÓi Çôi - Calories do chÃt béo cung cÃp - Cholesterol - Sodium - ChÃt Çåm - ChÃt boät (Carbohydrat) - Các chÃt dinh döôõng chính : - Vitamin B12 - Vitamin A - Riboflavin - Folate - S¡t - Niacin - Vitamin B6 - Këm - Vitamin C 64 mcg 9,011.7 RE (*) 3.5 mg 184.5 mcg 5.8 mg 9.1 mg 0.8 mg 5.2 mg 19.6 mg 137 4.2 g 1.6 g 0.6 g 0.8 g 27 % 331 mg 60 mg 20.7 g 3g

Các phÜÖng pháp trÎ liOEu

ViOEc ÇiSu trÎ bOEnh thiu máu tùy thuoäc vào s¿ chÄn Çoán cûa các Bác sï d¿a trên nhöõng thº nghiOEm lâm sàng liên hOE. ñiSu cÀn lÜu s là nên có nhöõng thº nghiOEm chuyên biOEt do các phòng thí nghiOEm chuyên môn th¿c hiOEn. Không nên chÃp nhÆn s¿ chÄn Çoán chung-chung nhÜ 'thiu máu', vì muÓn trÎ dÙt bOEnh cÀn phäi bit rõ nguyên do ÇÜa Çn thiu máu.. Các phÜÖng pháp trÎ liOEu theo thiên nhiên bao gÒm : h tr® dinh döôõng chung; ÇiSu trÎ thiu máu do thiu s¡t; do thiu Vit B12; do thiu folic acid và sº døng dÜ®c thäo.. 1- PhÜÖng pháp h° tr® dinh döôõng chung : Th¿c phÄm tÓt nhÃt giành cho ngÜ©i thiu máu, do mi nguyên nhân, có lë là gan bò. Gan bò không nhöõng chÙa nhiSu chÃt s¡t mà còn tÃt cä các vitamin trong nhóm B. Tuy nhiên cÀn thÆn trng, không nên dùng quá 100 gram mi ngày và liên tøc vì gan chÙa lÜ®ng khá cao Vitamin A. Trích tinh Gan Çã thûy giäi có lë tÓt hÖn vì có Çû tính chÃt dinh döôõng cûa gan nhÜng ÇÒng th©i không chÙa chÃt béo, cho-

(*) USDA dùng ÇÖn vÎ RE (Retinol equivalents) thay cho IU (International unit), nhu cÀu RE mi ngày cho moät ngÜ©i 25-50 tu°I ÇÜ®c ÇÎnh là 1000 RE. Nhöõng loåi rau có lá xanh løc l§n cÛng rÃt höõu døng cho ngÜ©i thiu máu do ª chÙa chlorophyl t¿ nhiên tan trong dÀu và nhöõng döôõng chÃt khác k< cä s¡t và folic acid. Phân tº chlorophyll rÃt tÜÖng ÇÒng v§i phân tº hemoglobin. Chlorophyll tan trong dÀu (không phäi loåi tan trong nܧc) có th< có tác døng nÖi ngÜ©i thiu máu loåi chlorophyll tan trong nܧc không ÇÜ®c hÃp thu nÖi ÇÜ©ng tiêu hóa, do Çó không có hoåt tính trong trÜ©ng h®p thiu máu. Ngoài ra, phÀn Çông bOEnh nhân thiu máu không tit Çû hydrochloric acid, do Çó rÃt nên thêm vào th¿c phÄm trong các böõa æn, chÃt acid này. 2- Thiu máu do thiu s¡t : Xin nh¡c låi: muÓn trÎ thiu máu cÀn phäi tìm ra nguyên nhân gây ra thiu máu. ñÓi v§i trÜ©ng h®p thiu máu do ª thiu s¡t, thÜ©ng phäi tìm cho ra nguyên nhân gây mÃt máu mãn tính hay ls do tåi sao cÖ th< không hÃp thu Çû s¡t tØ các

52 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Thiu máu và TrÎ liOEu - PHARMACY PRACTICE

th¿c phÄm æn vào S¿ thiu hydrochloric acid thÜ©ng là ls do giäi thích cho viOEc hÃp thu s¡t bÎ trª ngåi, nhÃt là nÖi ngÜ©i cao niên. Gia tæng thêm s¡t trong thÙc æn Çôi khi có th< giúp vÜ®t qua s¿ trª ngåi hÃp thu. Ngoài gan, sò huyt (oyster) và rau có lá xanh løc xÆm nhÜ spinach.., nhöõng th¿c phÄm khác có chÙa nhiSu s¡t nhÜ : Th¿c phÄm - Spinach nÃu chín - Sò huyt (sÓng) - Sauerkraut (Çóng hoäp) - ñÆu hòa lan (green pea), nÃu chín - Gan bò (chiên) - Brauchschweiger xúc sích - ñÆu lima, nÃu chín - ThÎt bò (steak) - Nܧc cÓt mÆn (prune) LÜ®ng cÀn Ç< cung cÃp ÇÜ®c 5mg saét 1 cup 1/4 cup 1 cup 1/3 2 cups 3 ounces(90 g) 2 khoanh 1 cup 5 ounces (150 g) 2 cups

TØ 1926, bOEnh thiu máu aùc tính (pernicious anemia) Çã ÇÜ®c ÇiSu trÎ b¢ng cách chích trích tinh gan. Không lâu sau Çó, các chÃt cô Ç¥c tØ gan có hoåt tính Çã ÇÜ®c dùng chích b¡p thÎt và dùng dܧi dång thuÓc uÓng, tuy nhiên viOEc dùng Gan dÀn dÀn bÎ quên lãng Ç< ÇÜ®c thay b¢ng B12 ÇÖn ñoäc: ñ< trÎ thiu máu loåi pernicious, tiêu chuÄn trÎ liOEu là chích B12 theo liSu 1mg/ ngày trong 1 tuÀn lÍ, tuy nhiên hiOEn nay Vitamin B12 dùng theo ÇÜ©ng uÓng, cÛng cho nhöõng kt quä trÎ liOEu tÜÖng ÇÜÖng ! Vitamin B12 thÜ©ng chÌ g¥p trong các th¿c phÄm gÓc ñoäng vÆt. NguÒn chÙa nhiSu B12 nhÃt là gan, thÆn rÒi Çn trÙng, cá, phô mai và thÎt. Nhöõng ngÜ©i æn chay tuyOEt ÇÓi (chÌ æn rau quä) thÜ©ng ÇÜ®c chÌ dÅn là các thÙc æn lên men nhÜ tÜÖng miso Tempeh chao là nhöõng nguÒn có th< cung cÃp B12, tuy nhiên lÜ®ng B12 trong các th¿c phÄm k< trên rÃt bin Ç°i và dång B12 trong th¿c phÄm lên men chÜa ch¡c Çã ÇÜ®c cÖ th< hÃp thuï (ñiSu này xÄy ra trong trÜ©ng h®p vài loåi rong bi<n, tuy chÙa B12 nhÜng khi Çun nÃu B12 låi bÎ bin dång không th< hÃp thuï) Có nhiSu dång B12: Dång thông døng nhÃt là Cyanocoba lamin. Tuy nhiên B12 chÌ có hoåt tính khi ª 2 dång Methylcobalamin hay Adenosylcobalamin (còn ÇÜ®c gi là Coenzym B12, Cobalamide, Cobinamide hay Dibencozide). Dång Methylcobalamin là dång B12 có hoåt tính duy nhÃt dùng tåi Hoa Kÿ dܧi dång thuÓc viên Trong khi Methylcobalamin có hoåt tính ngay sau khi ÇÜ®c hÃp thu, thì cyanocobalamin phäi ÇÜ®c cÖ th< chuy<n Ç°i thành methylcobalamin hay thành adenosylcobalamin, b¢ng cách lÃy Çi phân tº cyanide và thay vào Çó b¢ng nhóm methyl hay nhóm adenosyl. Tuy B12 thÜ©ng ÇÜ®c dùng b¢ng cách chích, nhÜng thÆt ra không nhÃt thit phäi chích: B12 có th< dùng dܧi dång uÓng, v§i liSu lÜ®ng thích h®p, (dù không kèm theo intrinsic factor) vÅn có th< làm tæng nÒng Çoä B 12 trong máu. Moät ÇiSu khá ls thú là cho Çn nay rÃt nhiSu Bác Sï vÅn chÜa bit ÇiSu này. Trong bài báo có t¿a ÇS '' Oral Cobalamin for Pernicious Anemia : Medicine's Best-Kept Secret '' Çæng trên J.A.M.A sÓ ngày 2 tháng Giêng næm 1991, tác giä F.A Lederly Çã xác quyt B12 có hoåt tính khi dùng uÓng và ghi nhÆn trong moät cuoäc thæm dò các BS noäi khoa (internists) tåi Hoa Kÿ 91 % Çã cho r¢ng B12 không th< ÇÜ®c hÃp thu ÇÀy Çû khi không có intrinsic factor, và 88% xác nhÆn së dùng B12 du§i dång thuÓc uÓng nu công hiOEu nhÜ thuÓc chích. Ls do ÇÜa Çn quan niOEm không dùng B12 uÓng ( vì không hiOEu nghiOEm) là do tØ sai lÀm trong các sách Y hc Çã cho r¢ng B12 khi uÓng hiOEu quä không Çoán ÇÜ®c (unpredictable). Sai lÀm này do US Pharmacopoeia Anti-Anemia Preparations Advisory Board ÇÜa ra vào næm 1959 d¿a trên liSu lÜ®ng B12 (dùng uÓng) mi ngày 100-250 mcg.. LiSu này tÜÖng ÇÓi thÃp Ç< Çåt ÇÜ®c kt quä cÀn thit. LiSu ÇÜ®c khuyn cáo nên dùng hiOEn nay là 2000 mcg(8). ñ< trÎ thiu máu loåi pernicious, Ça sÓ các sách y khoa khuyn cáo nên dùng 1000mcg (dång chích) mi tuÀn trong 8 tuÀn rÒi sau Çó 1000 mcg/ tháng trong suÓt Ç©i. Khi dùng

Vietnamese Pharmaceutical Journal No.5 - 53

(Theo G.Wardlaw-Perspectives in Nutrition pp467) Vitamin C Çã ÇÜ®c chÙng minh là có th< giúp cäi thiOEn s¿ hÃp thu s¡t (1) và gia tæng mÙc tÒn tröõ s¡t trong cÖ th<. LÜ®ng 500 mg Vit C dùng thêm trong mi böõa æn rÃt höõu hiOEu cho công viOEc nêu trên. NhiSu thÙc æn và nܧc uÓng, ngÜ®c låi, có th< chÙa các chÃt Ùc ch s¿ hÃp thu s¡t nhÜ trà, cà phê, cám håt mì, lòng ÇÕ trÙng.. Sº døng quá nhiSu chÃt chÓng acid và calcium cÛng gây giãm hÃp thu s¡t..

Các dång chÃt s¡t :

Có 2 dång chÃt s¡t (dinh döôõng) : s¡t-heme (heme-iron) và s¡t-không heme (non-heme iron). S¡t heme là s¡t kt nÓi v§i các proteins liên kt v§i oxygen : hemoglobin và myoglobin. ñây là dång s¡t ÇÜ®c hÃp thu tÓt nhÃt . T> lOE hÃp thu cûa các chÃt s¡t (dinh döôõng) không-heme, nhÜ Ferrous sulfate và Ferrous fumarate là 2.9 % khi bøng Çói và 0.9% khi uÓng chung v§i th¿c phÄm, trong khi Çó t> lOE hÃp thu cûa s¡theme, nhÜ trong gan, lên Çn 35 %, ngoài ra s¡t heme không gây nhöõng phän Ùng phø nhÜ s¡t không heme, nhÜ gây buÒn nôn, ÇÀy hÖi và tiêu chÄy. S¡t không-hem không kt nÓi, cÛng có khuynh hܧng tåo thành nhöõng gÓc t¿ do hÖn là s¡t heme. Tuy s¡t-heme có nhiSu Üu Çi<m hÖn, nhÜng s¡t không-heme vÅn là dång h° tr® dinh döôõng thÜ©ng ÇÜ®c dùng nhÃt : ls do là s¡t-heme dù có t> lOE hÃp thu cao hÖn nhÜng vÅn có th< gia tæng lÜ®ng s¡t không heme Ç< Çåt ÇÜ®c sÓ lÜ®ng cÀn thit (ví dø dùng 3 gram s¡t-heme, mÙc hÃp thu së tÜÖng ÇÜÖng v§i 50 mg s¡t không heme). Dång s¡t không heme tÓt nhÃt là ferrous succinate. 3-Thiu máu do thiu Vitamin B12 :

DÖÔÏC KHOA THÖÏC HAØNH - Thiu máu và TrÎ liOEu

uÓng có th< dùng 2000 mcg/ ngày trong suÓt 1 tháng rÒi giäm xuÓng 1000 mcg mi ngày. 4- TrÎ thiu máu do thiu Folic acid : Trong trÜ©ng h®p thiu máu do thiu folic acid, phÜÖng thÙc dinh döôõng cÀn nhaém vào nhöõng th¿c phÄm chÙa nhiSu folic acid nhÜ: Gan, Mæng tây (asparagus), ÇÆu håt (bean), men bia, rau có lá xanh và ngÛ cÓc. Vì folic acid dÍ bÎ hûy hoåi do nhiOEt và ánh sáng, do Çó nên æn rau sÓng hay chÌ trÀn sÖ qua thÎt, söõa, trÙng rau có cû chÙa tÜÖng ÇÓi ít folic acid. ñ< cÖ th< có th< tÒn tröõ ÇÀy Çû folic acid, cÀn uÓng mi ngày 1000 mcg (1 mg) folic acid liên tøc trong 1 tháng. Các dång folic acid thÜ©ng g¥p gÒm folic acid (hay folate) và folinic acid (5- methyl-tetra-hydrofolate). CÖ th< cÀn chuy<n bin folic acid thành tetrahydrofolate rÒi sau Çó g¡n thêm moät nhóm methyl tåo ra folinic acid Ç< có th< hÃp thu : do Çó nu uÓng th£ng folinic acid së giúp cÖ th< hÃp thu nhanh hÖn (8). 5- DÜ®c thäo trÎ thiu máu : ñông và Tây Y có sº døng moät sÓ dÜ®c thäo Ç< trÎ thiu máu. Do ª quan Çi<m khác biOEt , nên các cây cÕ và cách dùng cÛng khác nhau. Các cây thuÓc dùng trong ñông Y c° truySn Çã ÇÜ®c DS Mai Tâm trình bày trong các thang thuÓc trong bàì 'ñông Y và Thiu máu'.. ñông Y : Sau Çây là vài dÜ®c liOEu và cây thuÓc ÇÜ®c dùng trong DÜ®c hc Trung Hoa.. hiOEn Çåi : (Thiu máu và nhöõng rÓi loån vS máu ÇÜ®c gÒm chung trong các chÙng 'Tiêu huyt= Hollowness of the blood). A-giao (Gelatin trích tØ da lØa, Equus asinus). Thành phÀn hoåt chÃt chính gÒm các aminoacids và Calcium Ca2+. Các thº nghiOEm lâm sàng tåi Trung Hoa ghi nhÆn dÜ®c liOEu có moät sÓ tác døng, nhÃt là sinh huyt (hematopoiesis) : kích thích s¿ ch tåo hÒng cÀu và hemoglobin nÖi tûy xÜÖng, ngoài ra còn có tác døng cÀm máu, nhÜng không gây thay Ç°i th©i gian Çông máu. DÜ®c liOEu còn có thêm tác døng trên s¿ bin döôõng Ca2+ : gia tæng s¿ hÃp thu Ca2+ nÖi ruoät và giäm s¿ bài tit Ca2+ theo nܧc ti<u. Theo Bän thäo CÜÖng møc, A giao có tác døng chÌ huyt trong các trÜ©ng h®p ti<u ra máu, ói ra máu, phân có máu, kinh nguyOEt không ÇSu và xuÃt huyt sau khi sanh nª (9). Kê huyt Ç¢ng (Ji Xue Teng), Çt khô Spatholobus soberectus (Leguminosae) Thành phÀn chính gÒm friedelin, taraxerone và các h®p chÃt loåi alcohol. DÜ®c liOEu có tác døng làm chÆm nhÎp tim và hå huyt áp.DÎch chit baèng nܧc có hoåt tính kích thích s¿ co bóp tº cung. LiSu cao gây co giÆt. ñông Y c° truySn dùng làm thuÓc b° huyt, giúp huyt lÜu thông, giäm cÙng, sÜng kh§p xÜÖng. TrÎ các chÙng thiu båch cÀu, suy dinh döôõng và thiu máu do xuÃt huyt. LiSu thÜ©ng dùng tØ 60-120 gram, dång thuÓc s¡c, uÓng mi

54- Taäp San Chuyeân Nghieäp Döôïc Khoa

ngày.(9) (Tåi ViOEt Nam, Spatholobus harmandii cÛng gi là Kê huyt Ç¢ng hay Huyt rÒng, ÇÜ®c cho là có tác døng b° khí-huyt, thông kinh låc, månh gân cÓt dùng làm thuÓc b° huyt, hoåt huyt, thông kinh..) Nöõ Trinh tº (Nu zhen zi)= quä cûa Ligustrum lucidum Quä chÙa các hoåt chÃt loåi glucoside nhÜ nuzhenide, oleanolic acid, ursolic acid.. DÜ®c liOEu cho thÃy có tác døng giúp gia tæng båch cÀu, tr® tim và giúp l®i ti<u. Ngoài ra còn có thêm tác døng kháng sinh. Các nghiên cÙu m§i ghi nhÆn tác døng chÓng u-bܧu b¢ng cách gia tæng th¿c bào và kích thích hoåt ñoäng cûa t bào sát thû lymphokine. Nöõ trinh tº ÇÜ®c dùng Ç< trÎ leukopenia, sÜng ph°i kinh niên. DÜ®c Çi<n Trung Hoa chÌ ÇÎnh dùng b° thÆn, bÒi b° khí huyt, döông Can và giúp sáng m¡t (9). Tåi ViOEt Nam, có các cây Lingustrum indicum = Râm và L. sinense = Râm Trung quÓc dùng làm thuÓc thanh nhiOEt, diOEt khuÄn, giäm Çau. Båch dÜ®c tº (Bei Yao zi) = Reã xÓp phÖi khô cûa Stephania cepharentura Reã chÙa nhiSu alkaloids gÒm cepharanthine, cycleamine, isotetrandrine, berbamine và cepharamine.. DÜ®c thäo có tác døng kích thích s¿ sinh sän båch cÀu trong tûy xÜÖng, giúp gây tái tåo hÒng cÀu và hemoglobin; ngoài ra còn có khä næng kháng sinh nhÃt là chÓng vi trùng lao. Có th< có tác døng nhÜ chÃt chÓng ñoäc tÓ v§i ñoäc tÓ cûa vi trùng uÓn ván (tetanus) và båch hÀu (diphteria). Cepharanthine tác døng trên t bào B nÖi ngÜ©i nhÜ moät tác nhân kích Ùng hOE miÍn nhiÍm và gia tæng tác ñoäng kháng sinh cûa metylglyoxal-Bis trên Staphyloccocus aureus; Cepharanthine cÛng gây nghÎch Çäo moät phÀn s¿ kháng vincristine nÖi t bào glioma cûa ngÜ©i, giúp cäi thiOEn tác døng trÎ liOEu cûa 5 FU b¢ng cách giúp tæng nÒng ñoä 5FU bên trong t bào ung thÜ. Båch dÜ®c tº ÇÜ®c dùng Ç< trÎ leukopenia, Viêm gan cÃp tính, trÎ xuÃt huyt và th° huyt (9). Tåi ViOEt Nam có các cây Stephania rotunda = Bình vôi; S. sinica = Bình vôi tán ng¡n..có nhöõng tác døng an thÀn, döôõng huyt thÜ©ng dùng làm thuÓc ngû, an thÀn và làm thuÓc b° cho ngÜ©i lao l¿c.

DÜ®c thäo trÎ thiu máu theo Naturopathic Medicine :

Khoa Thiên nhiên trÎ liOEu dùng moät sÓ dÜ®c thäo Ç< trÎ các trÜ©ng h®p thiu máu chung nhÜ : Angelica, Gentiane.. 1- RÍ Angelica : Các cây Angelica ÇÜ®c dùng : tåi Âu châu : Angelica archangelia (A. officinalis) còn có các tên nhÜ Root of the Holy Ghost (Anh), Racine d'angelique (Pháp)..; tåi Hoa Kÿ

Thiu máu và TrÎ liOEu - PHARMACY PRACTICE

: Angelica atropurpurea ,hay Wild Celery, Masterwort..và tåi Trung Hoa :A. sinensis (ñÜÖng Qui).. Hoåt chÃt chính gÒm nhöõng tinh dÀu deã bÓc hÖi chÙa các monoterpenes, sesquiterpenes; các chÃt Ç¡ng loåi macrolic lactones, trên 20 loåi furanocoumarins, chuy<n hóa chÃt cûa caffeic acid. Các hoåt chÃt cûa RÍ Angelica Çã ÇÜ®c dùng tåi Âu châu tØ xa xÜa Ç< làm thuÓc b° kích thích s¿ bài tit dÎch vÎ và dÎch tøy tång kiOEn vÎ và là thành phÀn trong các loåi rÜ®u khai vÎ Ç¡ng nhÜ Bénédictine, Chartreuse. Kommission E cûa ñÙc cho phép dùng làm thuÓc trÎ æn kém ngon, Çau th¡t bao tº, ÇÀy hÖi (BAnz no 101, Published June 1,1990). (10) Nhöõng nghiên cÙu tåi Trung Hoa vS ñÜÖng quy (A.sinensis) ghi nhÆn tác døng làm tæng sÓ lÜ®ng HÒng cÀu và giúp kích thích s¿ hoåt ñoäng cûa các t bào gan (11) :Các tác giä Wang,Y và Zhu, B (1996) Çã ghi nhÆn ÇÜ®c tác døng cûa các polysaccharide trong A. sinensis gây kích khªi s¿ sinh sän và phát tri<n cûa các t bào gÓc tåo lÆp hÒng cÀu trong cÖ th< (Chung Hua I Hsueh Tsa Chih 1996, 76:363-66). Tåi ViOEt Nam có nhöõng loåi Angelica Dahuricae= Båch chÌ,; A. sinensis= ñÜÖng quy và A. pubescens=ñoäc hoåt. ñÜÖng quy ÇÜ®c dùng Ç< trÎ các chÙng thiu máu xanh xao, cÖ th< suy nhÜ®c, trong Thang TÙ vÆt thang' gÒm ñÜÖng quy 8g, Thøc ñòa 12g, Båch thÜ®c 8g và Xuyên khung 6g, s¡c v§i 600 ml nܧc. 2- RÍ cây Gentiane (Gentiana lutea) :

Gentiane, tuy không còn ÇÜ®c ghi trong USP nhÜng hãy còn ÇÜ®c chính thÙc sº døng tåi Âu châu, ghi trong Ch dÜ®c thÜ Anh=BP, Kommission E cûa ñÙc vÅn ghi nhÆn là moät vÎ thuÓc. Thành phÀn chính trong Gentian là nhöõng hoåt chÃt Ç¡ng loåi secoiridoid nhÜ Gentiopicrin, gentiin, gentiamarin, gentisin (hay gentianin =gen tianic acid). Màu vàng cûa RÍ là do nhöõng s¡c tÓ loåi xanthone. Gentiane ñöôïc xp vào loåi các chÃt b° Ç¡ng, có tác døng kích thích tiêu hóa, kiOEn vÎ, giúp gia tæng bài tit nܧc bt dùng làm tæng cäm giác ngon miOEng. Gentiane là chÃt tåo vÎ cho rÜ®u Vermouth (12). RÍ Gentian khi pha loãng ª nÒng ñoä 1/12,000 vÅn còn vÎ Ç¡ng! Nên dùng gentian nºa gi© trܧc khi æn. Tåi ñÙc, cây Gentian (Enzianwurzel) ÇÜ®c xp vào loåi ÇÜ®c bäo vOE ch¥t chë, tÃt cä mi dÎch vø xuÃt nhÆp ÇSu ÇÜ®c ki<m soát bªi German Federal Ordinance on the Conservation of Species (BArtSchV). Tåi ViOEt Nam và Trung Hoa: Gentiana scabrae hay Long Ǫm thÜ©ng ÇÜ®c dùng làm thuÓc b° gan, chÓng sÜng trÎ thÃp kh§p. 3- Cây Dandelion (Taraxacum officinale ): Dandelion chÙa khá nhiSu Vitamin, S¡t và các khoáng chÃt cùng nhiSu protein và döôõng chÃt khác, Çã ÇÜ®c dùng tØ lâu Ç©i trong dân gian Ç< trÎ thiu máu.(8)

References:

1- Krause, M.V và Mahan, K.L Food, Nutrition and Diet The rapy, 7th ed., W,B Saunders, Philadelphia PA 1984. 2- Petersdorf, R et Al Harrison's Principles of Internal Medi cine McGraw-Hill, NewYork NY 1983. 3- Morley J.E Nutritional status of the elderly Am.J.Med 1986,81 pp 679-95. 4- Jacobs A.M and Owen GM The effect of age on iron absorption. J.Gerontol 1969, 24 pp 95-96. 5- Bedwoda W, Charlton R, Bothwell T 'The importance of gastric hydrochloric acid in the absorption of non-heme iron' J.Lab.Cli.Med 1978, 92 pp 108-116. 6- Carmel R, Weiner J.M and Johnson C.S 'Iron deficiency occurs frequently in patients with pernicious anemia' J.A.M.A 1987, 257 pp 1,081-83. 7- Davis R.E and Nichol D.J 'Folic acid' Int. J. Biochem. 1988, 20 pp 133-39. 8- Murray M. and Pizzorno J Encyclopedia of Natural Medicine, Revised 2nd Edition. Prima Publishing pp 233-41 9- Huang Kee Chang The Pharmacology of Chinese Herbs, 2nd Edition, CRC Press pp 339-41. 10-Wichtl Max Herbal Drugs and Phytopharmaceuticals 3rd Edition, CRC Press pp 38-41. 11- Castleman M. The Healing Herbs, Bantam Books New York 1995 pp 66-71 12- Fetrow C W and Avila J R Professional's Handbook of Complementary & Alternative Medicines, SpringHouse PA 1999 pp 272-74

Vietnamese Pharmaceutical Journal No.5 - 55

What Does the Future Hold for Acute and Chronic Anemia?

"The Case for Artificial Blood"

Chat V. Dang, MD, 2Alan B.C. Dang, MS3 1 Charles Drew University College of Medicine, Los Angeles, CA 2 UCSF School of Medicine, San Francisco, CA

1

Abstract:

"Chronic blood shortage and the threat of infectious disease drive the search for an artificial blood substitute for the last twenty years. Two types of oxygen carriers have been investigated: perfluorcarbons and cell-free hemoglobin. Side effects including hypertension, complement activation, anaphylactoid reactions and limited oxygen carrying capacity have hampered the success of perfluorcarbons (Fluosol and Oxygent). Recent research has focused on cell free hemoglobin. Although several hemoglobin products are being tested clinically none of the products is allowed for human use yet. Oxyglobin produced by Biopure Corp. is the only approved product for use in veterinary anemia treatment." For many patients with chronic anemia due to chronic renal failure, HIV or cancer therapy, recombinant erythropoeitin (Epogen®, Procrit®) has markedly improved the quality of life. However the hormone has no role in acute unanticipated blood loss, the lethality of which can only be mitigated by banked donor blood. In time of disaster or war, increased demand for blood causes shortages. The U.S. is currently experiencing a shortage of blood, but only volunteer donors are accepted and even then, only 4 to 5% of eligible donors do so. To address this situation, and in part due to the threat of HIV, efforts have been made to reduce the need for donor blood such as preoperative autologous donation, intraoperative hemodilution, or autotransfusion1. Still, these techniques do not apply in the trauma setting, and consequently there is increasing interest in the development of red cell substitutes. The ideal red cell substitute should: 1. Require no compatibility testing 2. Have improved biologic half-life 3. Have improved safety profile 4. Have prolonged shelf life 5. Have reduced cost. Three classes of blood substitutes have been investigated: perfluorocarbons (PFC), cell-free hemoglobin, and liposome encapsulated hemoglobin. Encapsulated hemoglobin, essentially an artificial RBC, remains in the early research phase because of the complexity of its synthesis2.

Pioneering Efforts: Perfluorocarbons

P

erfluorocarbons made news in 1966, when mice were shown to survive several hours immerged in oxygenated PFC. Perfluorocarbon compounds are similar to Teflon® or Gore-Tex®, but in liquid form. They dissolve 30 to 100 times more O2 than plasma3. However, they are not water-soluble and need to be emulsified for use. Perfluorocarbons are cleared from the circulation by the reticuloendolthelial system, and ultimately eliminated through the lungs. The first generation PFC Fluosol®, developed by the Green Cross Corporation of Japan, did not live up to expectations as there were no demonstrated benefit from Fluosol infusions in patients with profound anemia. In addition, Fluosol® caused hyperten-

56 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Acute and Chronic Anemia - PHARMACY RESEARCH

sion and complement activation, resulting in hepatosplenomegaly and possible life-threatening anaphylactoid reactions. Normally, the amount of oxygen dissolved in plasma is less than 1% of the total oxygen content in arterial blood, even with significant anemia. By contrast, a second generation PFC such as perflubron (Oxygent® made by Alliance Pharmaceutical Corporation4) can increase dissolved oxygen to approximately 10-15% of the total arterial oxygen content. The clinical applicability of PFC is limited by the requirement of ventilation with 100% FiO2, and the complicated process of preparing solutions for administration5. Thus, active research has shifted to hemoglobin solutions.

blood of managed bovine herds to minimize the risk of prion disease. It has an 8-hour half-life, and its effectiveness is limited to 24 hours. Hemopure® was the first product approved for human use: in 2001, South Africa approved it for use in adult surgical patients who are acutely anemic9. In the US, the company planned to complete its clinical trials and submit a comprehensive written response to FDA scrutiny by June 30, 2004. However, after the close of the markets on Christmas Eve, December 24, 2003, Biopure announced a potential SEC inquiry for securities fraud and, for the first time, disclosed substantial problems with its Hemopure® product and the FDA approval process. Polyheme® and Hemolink® are manufactured from outdated human donor blood. The FDA issued a "refusal to file" to Northfield Laboratories Inc., manufacturer of Polyheme®, and Hemosol Inc., maker of Hemolink®, because of the substandard quality of the data submitted. Hemosol's share price had fallen into penny stock range as it made a decision in 2003 to halt trials of Hemolink®. In the spring of 2004, Northfield Labs remains the only company with a believable stock value10, closing at $17.20 on April 12, 2004. Oxyglobin® (hemoglobin glutamer-200 (bovine), or HBOC301), produced by Biopure Corp., is the first and only oxygen therapeutic to receive marketing clearance from the U.S. FDA and the European Commission for veterinary treatment of canine anemia11.

The Hope of Cell-Free Hemoglobin

Acute hemolysis releases cell-free hemoglobin, dreaded for its nephrotoxicity and vasoactivity. Current research aims at preventing toxic effects (renal, hepatic, GI, vascular), and increasing persistence of cell-free hemoglobin in the circulation. Three sources of hemoglobin have been studied: 1. Human from outdated banked blood 2. Bovine with the possible risk of "mad cow disease" 3. Recombinant/transgenic pig, E. coli, currently inefficient and costly6 The resulting products are referred to as a hemoglobin-based oxygen carrier (HBOC). The toxicity of HBOC solutions comes from the tendency of the native tetrameric hemoglobin to dissociate to a non-functional dimeric form, toxic to the kidney and GI tract (nausea, vomiting, dysphagia, abdominal pain), and causing hypertension. Vasoconstriction is believed to result from the binding of endogenous nitric oxide by HBOC smaller molecules that leak into the interstitial space7. This side effect may be beneficial in septic shock as the HBOC molecule could be used as a nitric oxide scavenger8. Currently, the most significant limitation of HBOC solutions is their short circulatory half-life of about 8-12 hours. Hemopure® (hemoglobin glutamer-250 (bovine), or HBOC201) manufactured by Biopure Corporation, comes from the

Conclusion: The case for artificial blood

In 2003-2004, the biotech companies currently developing "oxygen therapeutics" face serious financial difficulties12. It is hoped that their pioneering effort will continue. In their current form, HBOC solutions are not ready to replace allogeneic blood transfusion. However, once commercially developed, they will certainly have a role in the resuscitation of soldiers injured in hostile actions or patients after masscasualty incidents such as terrorist bombings or massive earthquakes. Once favorable clinical experience has been accumulated, the next logical step for research would be to investigate the potential therapeutic role of blood substitutes in chronic anemias resulting from hemoglobinopathies.

References:

1- Rhee P. Hemoglobin substitutes, ready for prime time? Trauma & Critical Care 2003 syllabus:109-115. March 24-26, 2003, Las Vegas, Nevada. 2- Sarteschi LM, Sagripanti A, Carpi A, Menchini-Fabris F. Rationale for the development of red-cell substitutes and Status of the research. Intern Med 2001(9):36-44. http://www.pacinimedicina.it/PdfFiles/IM/2001/9-1/Sarteschi.pdf Accessed April 13, 2004 3- Leone BJ Artificial Blood: What Is It? Will I Use It? Accessed March 18, 2004 http://www.dcmsonline. org/jax-medicine/1998journals/december98/artificialblood.htm 4- Alliance Pharmaceutical Corporation website. http://www.allp.com/Oxygent/OX_STAT.HTM Accessed March 28, 2004 5- Yowler C. Transfusion and Autotransfusion. Emedicine online textbook. http://www.emedicine.com/med/topic3215. htm Accessed April 13, 2004

Vietnamese Pharmaceutical Journal No.5 - 57

DÖÔÏC KHOA NGHIEÂN CÖÙU - Acute and Chronic Anemia

6- Brown University Division of Biology and Medicine. Accessed March 23, 2004, April 15, 2004 http://biomed.brown.edu/Courses/BI108/BI108_2000_Groups/Blood_Substitutes/hboc.html 7- Chang TMS. Future generations of red blood cell substitutes. J Intern Med 2003(253)527-535 http://www.med.mcgill.ca/physio/pdf_files/tchang/2003JIMChang.pdf accessed April 12, 2004 8- Dong Q, Stowell C. Blood substitutes: What they are and how they may be used. Clinical Lab Reviews. MGH-Harvard. 2001;(8):1-5. http://www.mgh.harvard.edu/labmed/res/clr/CLR%208-4.pdf Accessed April 12, 2004. 9- Orfinger B. South Africa approves first blood substitute. American Red Cross In the News. April 2001. http://www.redcross.org/news/bm/intl/010419sub.html Accessed April 12, 2004 10- Steyer R. Quest for Blood Substitute a Costly One for Investors. http://www.thestreet.com/_yahoo/stocks/robertstey er/10149805.html Accessed March 29, 2004 11- Biopure Corporation website. Accessed March 26, 2004, April 13, 2004 http://www.biopure.com/shared/home.cfm?CDID=2&CPgID=54 12-Feuerstein A. Struggling Alliance Puts Oxygent on Hold. http://www.thestreet.com/tech/adamfeuerstein/10039961.html Accessed March 28, 2004, April 13, 2004.

58 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Treatment of Severe Anemia Using Blood Substitutes

Nguyen D. Kien, PhD, DABNM

Professor - Department of Anesthesiology and Pain Medicine University of California Davis Medical Center, Sacramento, California 95817

Abstract:

R

ecent research has focused on the delivery of oxygen to the ischemic tissues as well as the vascular factors that regulate oxygenation. There are two principle types of blood substitutes: Hemoglobin (Hgb)-based oxygen carriers and perfluorocarbons (PFC). Hgb is the protein in the red cells that is responsible for transporting oxygen. When infused into the circulation in the extract form, Hgb molecules break down into dimers that are rapidly filtered through the glomerulus leading to renal toxicity. The dimer formation has been prevented by modifying Hgb structure using either chemical or recombinant DNA processes. A chemical reaction provides a cross-link binding the dimers and restoring the oxygen affinity of the cell-free hemoglobin. Cross-linking is also obtained by recombinant DNA technology or soluble polymers to produce recombinant tetrameric hemoglobin or conjugated Hgb of high molecular weight, respectively. PFC compounds with high oxygen solubility are emulsified in lipids to form particles that are dispersed in the blood stream for improving oxygenation. Blood substitute solutions can be produced in large quantity, have long shelf life, are free of blood-borne diseases and do not require blood typing. However, the use of blood substitutes encounters various obstacles including O2 radicals as byproducts, a decrease in nitric oxide that leads to vasoconstriction and a loss of cellular water due to oncotic pressure gradient. New developments have effectively addressed these issues and preliminary studies suggest that Hgb-based oxygen carriers are safe and effective for clinical management of patients with severe anemia. Synthetic oxygen carriers are especially promising considering the problems associated with whole blood transfusion and when blood is not available or blood transfusion is contraindicated.

Overview:

Anemia is a clinical condition in which the hemoglobin (Hgb) concentration falls below a normal value. This normal value varies with the person's age, sex, living environment, and coexisting diseases. The Hgb concentration in children varies significantly in accordance to growth and development until they reach adulthood. The Hgb level in women is approximately 2 g/dl lower than the 14-18 g/dl range seen in men. Individuals living at high altitude have higher Hgb concentrations than those at sea level. Anemia is usually asymptomatic until the Hgb concentration is less than 8 g/dl. However, patients who are in a higher Hgb range can exhibit signs and symptoms of anemia when their Hgb levels are well above the 8 g/dl limit.

Vietnamese Pharmaceutical Journal No.5 - 59

DÖÔÏC KHOA NGHIEÂN CÖÙU - Treatment of Severe Anemia

Thus, Hgb concentration alone does not characterize anemia unless it is accompanied by other symptoms including fatigue, dyspnea, tachycardia, and headache (1)... The values of hematocrit calculated from the red cell count and the mean corpuscular volume have also been used to gauge anemia. These values, although can be measured by simple methods, do not reflect a direct measurement of Hgb or more importantly the oxygen carrying capacity. Anemia is generally caused by excessive blood loss or an imbalance between the production and destruction of red cells that precipitates in a persistent decline in Hgb concentration. Deficiency of iron, folate, vitamin B12, thalassemia or erythropoetin... impairs the production and maturation of red cells in the bone marrow leading to anemia. Furthermore, pregnancy, chronic hemolysis, drug or alcohol abuse are recognized as common factors contributing to anemia. Certain hemolytic disorders such as intracorpuscular or extracorpuscular defects cause abnormal loss of red cells. Sickle cell anemia is an example of the intracorpuscular defect. The mutation of the ß-globin gene transforms the amino acids in the heme portion of the Hgb molecule distorting the cell membrane and producing a sickle shape. As the sickled cells become dehydrated and rigid, they impede blood flow and oxygen transport that cause tissue infarcts. Excessive blood loss due to hemorrhage is a life threatening situation that requires urgent clinical attention. Acute blood loss triggers certain physiological responses to compensate for reduced intravascular volume. The combination of increased cardiac output and peripheral vasoconstriction provides a first line of defense by maintaining normal perfusion to vital organs at the expense of peripheral circulation. Fluid is mobilized from the extravascular compartments to replenish the intravascular volume. Since the replacement of red cells takes several weeks, blood becomes diluted with compensated or resuscitated fluids revealing the state of anemia. When oxygen transport is a concern, transfusion of red cells seems to provide an immediate and effective solution for managing anemia. At an Hgb concentration of 7 g/dl, oxygen delivery is believed to remain sufficient in most individuals. Therefore, transfusion of blood is usually indicated for improvement of inadequate oxygenation when Hgb concentration falls below 6 g/dl (2). Blood transfusion comprises of administration of either whole blood or only red cells. Although whole blood can be used when volume replacement is also needed, the benefit of whole blood transfusion is challenged by the increased risk of reactions due to blood components other than red cells. Except for some possible advantages in using whole blood in pediatric open heart surgery, since 1970 there has been a consensus that red cells and specific components should be given separately as indicated. Normally, transfusion of red cells is required to enhance oxygenation and prevent cell death from hypoxia when severe anemia occurs. In chronic anemia or symptomatic anemia, red cell

transfusion decreases viscosity induced by anemia thus improves circulation and augments oxygen delivery through changes in oxygen affinity of Hgb at the cellular level. It is clear that blood transfusion is necessary to improve tissue oxygenation to the oxygen deprived organ tissue when anemia becomes severe. However, the transfusion of blood has been known to cause multiple adverse effects which seriously overshadow the benefit of transfusion itself. Facing a continuous shortfall of blood supply and the risks of contracting blood-borne pathogens, there has been a thriving interest in searching for an oxygen carrier for blood replacement. The purpose of this article is to review recent developments in substituting blood with bio-synthetic compounds that can effectively deliver oxygen in combating anemia.

Adverse Effects of Blood Transfusion:

Blood transfusion is associated with supply shortage and high costs in addition to common medical problems including transmission of infectious pathogens, systemic reactions, modulation of the immune system, and other side effects (3). Each unit of blood costs approximately $150. Additionally, there are other indirect costs and the expenses to treat the transfusion related complications (4). Blood is readily available in large hospitals where refrigeration and preservatives increase the shelf life to 42 days. In order to resolve intermittent shortage problems, frequent blood drives are necessary to supply the need for blood in trauma and surgical patients. But in the event of mass casualty due to war or natural disaster, the quantity of blood in regular storage is inadequate to meet the demand for transfusion. Due to rigorous screening of donors the risk of contracting blood-borne diseases such as human immunodeficiency virus and hepatitis via blood transfusion has diminished substantially in recent years in industrialized countries. However, it remains to be a significant threat in developing nations. Although the transmission of common cytomegalovirus can be manageable in healthy individuals, it is life threatening in patients with severely compromised immune system. Screen tests are needed for the newly identified hepatitis G and human herpes viruses and the fatal Creutzfeld-Jakob disease. Bacterial infection and transmission of parasites remain a concern associated with transfusion. Elderly patients who receive blood during hip surgery have a 35% and 52% greater risk of bacterial infection and contracting pneumonia, respectively, than those without transfusion. The great risk of infection in this group of patients is related to the reduced resistance against bacterial invasion in addition to the immunosuppressive effect of hemorrhage itself (5). The effects of transfusion on the immune system are complex and vary among different types of patients which in

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Treatment of Severe Anemia - PHARMACY RESEARCH

turn complicate the task of substituting blood. Blood transfusion can have varying effects on the immunologic responses in different patient groups. For instance cancer patients with blood transfusion exhibit a higher rate of tumor recurrence (6). On the other hand, transfusion can reduce or delay the immune responses and thus decreases the rejection in patients with kidney transplant. Other adverse effects of blood transfusion include systemic reactions to red cells. Whereas the reaction to incompatible blood may be fatal, transfusion of hemolytic blood, although rare, is also life threatening. Other reactions including hypotension, tachycardia, chill, fever or skin allergic reactions have previously been reported in association with blood transfusion (7).

that avert molecular breakdown of Hgb by providing a chemical bond between the alpha and beta chains. Oxygen affinity can be altered by forming a single cross-link between the two alpha chains or the two beta chains of deoxygenated or oxygenated Hgb (9). Reagents including glutaraldehyde and ?-raffinose have been used successfully for binding hemoglobin molecules to form a more stable chain called polyhemoglobin. Biopure Corp cross-links bovine hemoglobin with glutaraldehyde and tests its products in trauma and surgical patients in a Phase III clinical trial. Also using glutaraldehyde as a reagent for cross-linking with hemoglobin, Northfield is entering a Phase III testing of its polyhemoglobin. The linkage of human hemoglobin with ?-raffinose provides Hemosol Ltd with products currently being studied in a Phase II clinical trial in dialysis and surgical patients undergoing hip or knee surgeries. An intramolecularly cross-link tetrameric hemoglobin of Baxter Healthcare has been reported to encounter significant side-effects from which serious concerns of its safety have been raised. Hgb can also be cross-linked to soluble polymers to form conjugated Hgb such as polyethylene glycol, polyoxyethylene, or Dextran. Apex Bioscience has a product using polyoxyethylene that is currently on clinical trial for septic shock. Enzon Inc is testing a cross-link product from bovine hemoglobin and polyethylene glycol in animals and cancer patients. Future generation of modified Hgb: The next generation of Hgb based oxygen carrier incorporates various biochemical substances and pharmacological treatments to maximize the efficacy of oxygenation. For instance, new product will contain specific enzymes with the ability to protect against cellular injuries induced by ischemia or reperfusion. The next generation of blood substitutes incorporates cross-linking of Hgb with an active vasodilator to improve microcirculation through eliminating peripheral hypertension due to the inhibition of nitric oxide production. It appears that Hgb can be obtained in great quantity from large animals or specifically bred animals through transgenic manipulation (10). Recent development of liposome-encapsulated hemoglobin, called the Neo Red Cell (NRC), provides significant improvement in oxygen transport efficiency and prolongation of circulation time. It has been postulated that NRC may block the reticuloendothelial system and interfere with the biodistribution of Hgb. However, this issue remains to be investigated. Currently, nanotechnology is being used to encapsulate hemoglobin and enzymes within biodegradable membrane microcapsules in diameter less than one micron (11). Several other issues including the mechanism of oxygen delivery; physiological responses and clinical consequences of blood substitution, prolongation of circulation time, and sources of hemoglobin...have attracted significant attention in the design of future generation products (12).

Vietnamese Pharmaceutical Journal No.5 - 61

Synthetic oxygen carriers:

Synthetic oxygen carriers are being developed to substitute blood based on the understanding of the efficacy of blood as an oxygen carrier as well as the morbidity of blood transfusion (3). Current products are being designed with different properties to address the long-term physiological effects in addition to the concerns of efficacy and safety. Synthetic products are separated into two different types based on the mechanism by which oxygen is delivered.

Hemoglobin-based oxygen carriers:

Hgb is the protein in the red cells that has the highest oxygen binding capacity among most biological substances. It functions as a carrier of oxygen and carbon dioxide between lungs and organ tissues. In the capillary bed, oxygen molecules are unloaded from Hgb to defuse into intracellular mitochondria and prevent cellular hypoxia. When fully saturated with oxygen at ambient air pressure, 1 g of Hgb contains 1.39 ml of oxygen. Each hemoglobin molecule consists of four twisted globin chains (a pair of alpha and a pair of beta arranged symmetrical across an axis) wrapping four heme groups (each chain is capable of binding to a centrally located molecule of oxygen). One alpha is tightly bound to one beta chain forming the alpha-beta dimer. The interface between the dimers is responsible for the binding with oxygen and plays an important role in the design of blood substitutes. The affinity for oxygen varies according to the transition between deoxygenation and oxygenation. When infused in the native form extracted from red cells, Hgb tetramers are broken down forming dimers which are rapidly removed from systemic circulation by renal clearance. However, excessive glomerular filtration of dimers causes tubular obstruction due to Hgb precipitates in the ascending limb of the loop of Henle leading to acute renal failure. The design of blood substitutes focuses on modifying Hgb structure to prevent the dimer formation, and to enhance its ability for carrying oxygen. The modification of hemoglobin structure can be achieved using either chemical or recombinant DNA technology (8). Crossed-link Hgb is constructed using chemical reactions

DÖÔÏC KHOA NGHIEÂN CÖÙU - Treatment of Severe Anemia

Development of Perfluorocarbons (PFC) as blood substitutes:

Clark in 1966 reported that mice survived for an extended period of time when immersed in a PFC solution. These animals were able to inhale the liquid solution that provided adequate oxygenation for sustaining life (13). Subsequent experiments showed that PFCs maintained cerebral function for hours and successfully replaced blood with good recovery in rats. These data led to the development of Fluosol-DA 20 which was the first blood substitute approved by FDA for use in coronary angioplasty (14). PFCs are chemically inert compounds that serve as oxygen solvents due to their high solubility for oxygen molecules. When emulsified with surfactants, PFCs can be injected into the blood stream and deliver the dissolved oxygen to organ tissues (15). The use of this product has been limited by the low oxygen carrying capacity, storage instability, prolonged uptake by the reticuloendothelial system, and interference with surfactant function causing pulmonary hyperinflation. The next generations of PFCs such as perfluorooctylbromide and perfluorodichlorooctane have a considerable improvement in oxygen carrying capacity and stability. However, some fundamental limitations still remain including optimal capacity for carrying oxygen and systemic reactions. The oxygen content of PFCs is a linear function of oxygen concentration in the alveoli. Therefore, patients should inhale pure oxygen for optimal oxygenation, a condition that may not be available in pre-hospital and several hospital settings. Additionally, the administration of PFCs is associated with cytokine release leading to flu-like symptoms such as headache, fever, chill, nausea, and peripheral vascular reactions. Cerebrovascular perturbation has also been noted in some patients following PFC administration that elevates the concerns about the safety of this group of blood substitutes.

surgical procedures with major blood loss; blood substitutes can provide an important alternative to red cell transfusion for routine surgical use. Additionally, blood substitutes are being proposed for organ preservation, tumor therapy, treatments of septic shock, acute vital organ ischemia, and anemia... Current phase III clinical trials include products from three different companies. PolyHeme, from Northfield Laboratories, is being studied for treatment of acute blood loss in trauma patients. Biopure Corporation introduces Hemopure for human in addition to their Oxyglobin that has been approved for routine animal use in canine anemia. In April 2001, Hemopure was approved for acute anemia therapy in South Africa marking the first Hgb-based oxygen carrier approved for human use. Hemolink of Hemosol Incorporated has recently gone through clinical trials and awaits regulatory approval for clinical application. Blood transfusion is refused in Jehovah's Witnesses even in cases of life threatening hemorrhage since a 1945 church ruling. Clinical management of this patient group is particular challenging even with the availability of an effective substitution of blood. Products from either Biopure or Northfield have been shown effective in treating severe anemia in Jehovah's Witness patients. Hgb concentrations as low as 3.1 g/dl increased significantly following administration of synthetic oxygen carriers without initial changes in hematocrit. Patients were discharged with Hgb concentrations higher than 7.8 g/dl without signs of neural deficit. Apparently, blood substitutes can provide an attractive alternative when the standard life-saving transfusion is prohibited by a religious conviction (17, 18).

Conclusion:

Current data reveal promising evidence that supports the preliminary use of certain blood substitutes in the treatment of severe anemia particularly when blood is not available or its transfusion is contraindicated. These products provide a complimentary mean for oxygen transport that offer significant therapeutic benefits. Although further testing is mandatory for understanding of the full potentials of blood substitutes, the lack of observed toxicity confirms that the quest for a safe and efficacious replacement of blood so far is on the right track.

Clinical applications for blood substitutes:

Potential applications for blood substitutes have been outlined for both prehospital and hospital settings. Blood substitute products appear to have a significant role in battlefield resuscitation and prehospital management of trauma patients with severe hemorrhage (16). They can be used effectively as adjuncts to hemodilution or autologous blood donation. Also, most red cells are transfused during many

References:

1. Rossi EC. Red cell transfusion therapy in chronic anemia. Hematol Oncol Clin North Am 1994;8(6):1045-52 2. Practice guidelines for blood component therapy. A Report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology 1996;84:732-47 3. Span DR, Casutt M. Eliminating blood transfusion: new aspects and perspectives. Anesthesiology 2000;93:242-55 4. Vamvakas EC, Carven JH. Allogeneic blood transfusion, hospital charges, and length of hospitalization: A study of 487 consecutive patients undergoing colorectal cancer resection. Arch Pathol Lab Med 1998;122:145-51

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Treatment of Severe Anemia - PHARMACY RESEARCH

5. Goodnough LT, Shander A, Brecher ME. Transfusion medicine: looking to the future. Lancet 2003;361(9352):161-9 6. Landers DF, Hill GE, Wong KC, Fox IJ. Blood transfusion-induced immunomodulation. Anesth Analg 1996;82:187-204 7. Blumberg N, Chuang-Stein C, Heal JM. The relationship of blood transfusion, tumor staging and cancer recurrence. Transfusion 1990;30:291-4 8. Christou NV, Meakins JL, Gotto D et al. Influence of gastrointestinal bleeding on host defense and susceptibility to infection. Surg Forum 1979;30:46-7 9. Winslow RM. Hemoglobin-based red cell substitutes. Baltimore: John Hopkins University Press 1992 10. Gould SA, Sehgal LR, Sehgal HL et al. The development of hemoglobin solutions as red cell substitutes. Transfus Sci 1995;16:5-17 11. Chang TSM. Is there a need for blood substitutes in the new millennium, and what should we expect in the way of safety and efficacy [editorial]? Artif Cells Blood Substit Immobil Biotechnol 2000;28:i-vii 12. Dietz NM, Joyner MJ, Warner MA. Blood substitutes: fluids, drugs, or miracle solutions. Anesth Analg 1996;82:390-405 13. Clark LC, Gollan F. Survival of mammals breathing organic liquids equilibrated with oxygen at atmospheric pressure. Science 1966;152:1755-6 14. Kerins DM. Role of the perfluorocarbon Fluosol-DA in coronary angioplasty. Am J Med Sci 1994;307:218-21 15. Keipert PE. In: Chang TMS, ed. Blood substitutes: principles, methods, products and clinical trial. Karger, Basel, Switzerland / Landes Georgetown, Texas, 1998; 2:101-21 16. Gould SA, Moore EE, Hoyt DB et al. The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. Am Coll Surg 2002;195(4):445-52 17. Shander A, Lui J, Alalawi R et al. Use of hemoglobin-based oxygen carrier as an adjunct in a therapeutic regimen for severe anemia. Anesthesiology 2003;99:B52 18. Cothren C, Moore EE, Offner PJ et al. Blood substitute and erythropoietin therapy in a severely injured Jehovah's Witness. N Engl J Med 2002;346:1097-8

Vietnamese Pharmaceutical Journal No.5 - 63

Pure red cell aplasia associated with recombinant DNA erythropoietin treatment

Tue H. Nguyen, Ph.D.

Pharmaceutical R&D,Genentech Inc.

This article summarizes a series of email communications on the Vietnamese Pharmacy Forum prompted by a question from Mr. Nguyen Huu Duc, Pharmacist, School of Pharmacy in Saigon and relayed to the Forum by Mr. Le Van Nhan, registered Pharmacist. It includes contributions and comments from Thuy C. Duong, Pharm.D., Bich-Lien Nguyen, M.D., Terrie T. Nghiem, Pharm.D., Giang N. Trinh, D.Ph., Binh- Nhung Tran, Pharm.D. and Tue H. Nguyen, Ph.D. Sau phaàn khaùi nieäm veà Erythropoetin-alfa, taùc giaû baøn veà caùch chaån nghieäm vaø caùc phöông caùch ñieàu trò. ít xaåy ra, phaûn öùng khaù traàm troïng khi phaùt hieän. Epoetin laø moät thuoác caàn thieát trong nhieàu tröôøng hôïp, caàn ñöôïc xöû duïng vôùi söï theo doõi caån thaän ñeå giaûm thieåu caùc phaûn öùng dothuoác gaây neân. Baøi naøy toùm löôïc caùc tin trao ñoåi treân Dieãn Ñaøn Döôïc khoa töø moät caâu hoûi veà Phaûn öùng hoànghuyeát caàu khoângtaùi taïo (aplasia) do xöû duïng Epoetin.

Background

uman recombinant Erythropoietin (rhu-EPO) has been a well established treatment for anemia associated with chronic renal failure and chemotherapy for the last fifteen years. It induced effective erythropoiesis with minor to moderate side effects. Since 1998, a small but increasing number of reported cases of pure red cell aplasia (PRCA) have triggered several investigations by the scientific communities and warnings from health authorities (1, 7).

H

The products

Erythropoietin-alfa (EPO-alpha) is a 165 amino acid protein secreted by the kidney to induce maturation of red blood cells (2). It was first cloned and developed as a therapeutic agent by Amgen, Inc. (Epogen). Johnson and Johnson produced the protein under Amgen's license and distributed it world wide through its multiple subsidiaries under the trade name Procrit in the U.S. and Eprex in Europe and Canada. Hoffman La Roche produced EPO-beta (NeoRecormon) which differs from EPO-alfa only by the composition of post -translational carbohydrate (3). The later has a longer elimination half life in vivo due to its increased sialic acid content. The most recent entry is Darbepoietin (Aranesp) by Amgen (4). Five mutations in the primary structure of EPO were introduced to add 2 additional glycosylation sites, thus further increase the in vivo half life of the protein and resulting in less frequent injection. Table 1 summarizes the relevant characteristics of the product. Epogen was formulated in a human serum albumin (HSA) containing buffer (5), so was Procrit and the initial Eprex formulation. Following a request from the European Health authority, Eprex was reformulated without HSA, in 1998. Tween 80 and glycine were added as stabilizers (1). NeoRecormon formulation contains Tween 20 and five different amino acids as well as urea and calcium chloride (12); Darbepoietin was formulated in a non HSA formulation and also contains a small amount of Tween 80 (6).

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Pure Red Cell Aplasia - PHARMACY PRACTICE

Eprex Manufacturer Cell line Molecule J&J E. coli EPO-alpha glycosylated

Procrit J&J E. Coli EPO-alpha glycosylated

Epogen Amgen E. Coli EPO-alpha glycosylated

Neorecormon Roche CHO EPO-beta glycosylated, Increased sialic acid content Tween 20 Urea Sodium chloride Sodium phosphate Calcium chloride Glycine Leucine Isoleucine Threonine Glutamic acid Phenylalanine SC Ex-US

Aranesp Amgen CHO Darbepoietin Mutated for increased carbohydrate content Tween 80

Formulation

Tween 80 Glycine Sodium chloride Sodium phosphate Sodium citrate

Sodium citrate Sodium chloride HSA

Sodium citrate Sodium chloride HSA

Route of administration Distribution

SC now IV Ex- US

IV US

IV worldwide

SC worldwide

Pure Red Cell Aplasia:

PRCA is a progressively developing anemia characterized by a sudden onset and complete absence of red blood cell precursors in an otherwise normal bone marrow (7). Red blood cell production ceases completely reflecting in a blood reticulocyte count of less than 10 000/mm3 and a rate of Hemoglobin decline of ~0.1 g/dl/day corresponding to the life span of red blood cell. There are several causes for PRCA. but Epoietin induced PRCA is diagnosed based on the presence of neutralizing antibody to EPO in the patient serum detected by ELISA and in vitro bioassay. European investigators reported 13 cases of PRCA between 1998 and 2000. Shortly after, the FDA reported 82 cases between 1997 and 2001. Up to March 2003, J&J registered 163 cases of PRCA, 142 in patients exposed to Eprex and 21 patients exposed to another erythropoietic agents other than Eprex. The incidence per 10 000 treated patient years was 0.03 from 1989-1997 but increased to 1.24 from 19982002 for Eprex (9). It is 0.12 for Epoietin beta, 0.02 for Epogen, and 0.5 for Darbepoietin (1). The data suggest a clear association with the subcutaneous injection of Eprex after reformulation in 1998 (1,7). It is also worth noting that Epoietin-beta and Darbopoietin also exhibit noticeably higher level of immunogenicity than Epogen and Eprex pre-1998. This is probably related to the fact that the later two were indicated for IV usage initially. Neutralizing antibodies are produced by a quick immune reaction to a new antigen or a slower break down of the

immune tolerance to self antigen. Epoietin induced PRCA appeared to be the later case (8). B cells directed to self antigen are produced continuously. In normal human, tolerance is induced by either receptor editing which negates immunogenic activity or by functional anergy in the presence of physiological concentration of circulating self antigen. Tolerant B cells can be activated by exposure to a higher concentration of the self antigen (i.e. injection of exogenous cytokines) combined with a danger signal such as bacterial endotoxin . The presentation of antigen in virus like array also triggers immunogenic reaction (8). This can occur when the protein denatures and aggregates. A study by Hermeling et al. (9) suggests that Tween 80 at the concentration used in Eprex forms mixed micelles with EPO-alpha displaying the protein molecules on the surface of the particles and rendering them immunogenic. Prefilled syringes need to be siliconized to aid in the manufacturing process and enhance the gliding of the stopper / plunger during drug administration. The siliconization process is a delicate operation. Excess silicon oil applied to the container can be extracted into the formulation and acts as an adjuvant similar to vaccine (10). Stoppers used in vials and prefilled syringes are elastomers and contain a complex mixture of stabilizers and residual chemicals from the polymerization reaction. Small quantities of these compounds can leach into the formulation and react with the protein. A recent report by J&J suggested that these leachables contribute to the immunogenicity of Eprex. (10). The company has switched to Fluorotec coated stopper and recalled all Eprex formulated in non-coated stopper. It reports a leveling off in reported cases of PRCA related to Eprex.

Vietnamese Pharmaceutical Journal No.5 - 65

DÖÔÏC KHOA NGHIEÂN CÖÙU - Pure Red Cell Aplasia

Initially Epogen and Eprex were indicated for IV administration. The switch to SQ injection of Eprex new formulation corresponded to the increase in PRCA (11). The skin is the body's first line of defense. A host of immune cells such as the dendritic cells reside in the epidermal and dermal space sampling neo-antigens and sending signal to the humoral immune system. It is well-known that SQ injection of vaccine elicits stronger immunogenic response. An interesting case was reported in the Journal of the American society of Nephrology (12) in which the patient developed wheals at the site of Eprex injection long before the manifestation of PRCA.. Subsequent IV injection of other EPO products also induced skin reaction at the sites of former EPO injection.

EPO-beta and Darbepoietin, treatment with epoietin should be stopped immediately when PRCA is suspected. Immunosuppressive treatment includes various regimens of corticosteroids, cyclophosphamide, Azathiodine, Rituximab and immunoglobulin therapy. These treatments have met with various degree of success. Cessation of EPO treatment alone rarely re-establishes erythropoiesis. Blood transfusion is used in severe cases of anemia. Subcutaneous injection of EPO-alpha has been contraindicated for patients with chronic renal failure (13,14). Optimization of the manufacturing process and changes in container closure system by the manufacturer are good preventive measures.

Diagnosis and Treatment

Some of the causes of PRCA include ferropenia, hemolytic anemia, lymphoproliferative disorders, undetected digestive hemorrhage, viral infection (Parvo virus), systemic autoimmune diseases (systemic lupus), drug toxicity (Chloramphenicol). The diagnosis of EPO induced PRCA is based on the absence of red cell precursors in bone marrow biopsy and the presence of neutralizing antibody to EPO in the serum. Since the antibodies cross react with

Conclusion

EPO induced PRCA is a rare but serious disease. Because of the low incidence, it is unlikely that a systematic investigation of the root cause can be performed. The drug offers significant improvement to the quality of life of millions of patients, with careful preventive measures and patient monitoring, PRCA can be managed adequately. The risk benefit ratio is clearly favorable for this important medicine.

References:

1-F. Locatelli F.,Vecchio LD. Pure Red Cell Aplasia Secondary To Treatment With Erythropoietin, J. Nephrol. 2003; 16:461 - 466 2-Miyake T, Kung CK, Goldwasser E. Purification Of Human Erythropoietin. J. Biol. Chem. 1977;252:5558-5564 3-NeoRecormon 4-Egrie JC, Browne KJ. Development And Characterization Of Novel Erythropoiesis Stimulating Protein. Nephrol. Dial. Transplant 2001;57:237-45 5-Physician Desk Reference, 2004 582-586, 3052 -3055 6-Physician Desk Reference, 2004 7-Eckardt KU, Casadewall N. Pure Red Cell Aplasia Due To Erythropoietin Antibodies. Nephrol. Dial. Transplant. 2003; 18:865-869 8-Schellekens H. Relationship Between Biopharmaceutical Immunogenicity Of Epoetin Alfa And Pure Red Cell Aplasia. Current Medical Research and Opinion. 2003; 19:433-434 9-Hermeling S, Skelletens H, Crommelin DJA, Jiskoot W. Micelle-Associated Protein in Epoetin Formulations: A risk Factor for Immunogenicity?. Pharm. Res. 2003 20:1903-1907. 10-Bader FG. Interaction Between A Formulation And Container/Closure And How They Can Affect Immunogenicity Of Biotherapeutic, 2004 IBC conference in pre-clinical development of biotherapeutics. San Diego 11-Casadevall N, Nataf J, Viron B, Kolta A, Kiladjian JJ, Martin-Dupont P, Michaud P, Papo T., Ugo V, Teyssandier I, Varet B, Mayeux P. Pure Red Cell Aplasia And Anti-Erythropoietin Antibodies In Patient Treated With Recombinant Erythropoietin. N Engl J Med. 2002;346:469-475 12-Haselbeck A. Epoietins: Differences And Their Relevance To Immunogenicity. Current Medical Research and Opinion. 2003;19:430-432 13-French Health Authority Letter. Issued 2 December 2002 http://afssaps.sante.fr/htm/3/3000/htm/ 14-Eprex Summary of Product Characteristics. Janssen Cilag Ltd. UK. Issued 17 July 2002 http://www.Janssen Cilag.com.cg/pdf/prof/ceprexprof.pdf Additional Websites: 1- http://www.swissmedic.ch 2- http://www.hc-sc.ca/hpfb-dgpsa/tpd-dpt/eprex3_hpc_e.html/ 3- [email protected] 4- http://www.medscape.com/viewarticle/466208 5- http://www.jnj.com/news/jnjnews/

66 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Beän h Thaën g Dö Saé t Moâ

Hemochromatosis

Giang Nguyeãn Trònh, R.Ph., D.Ph.

Abstract:

Hemochromatosis, the most common form of iron overload disease, is an inherited disorder that causes the body to absorb and store too much iron. The excess iron builds up in organs and damages them. Without treatment, the disease can cause these organs to fail.

Toùm taét:

Beänh thaëng dö saét moâ laø moät bieán loaïn di truyeàn laøm cho cô theå haáp thuï quaù nhieàu saét hôn möùc caàn thieát. Neáu khoâng ñöôïc ñieàu trò, löôïng saét tích tuï cao trong cô theå coù theå laøm toån haïi nhöõng cô quan thieát yeáu vaø nhöõng khôùp cuûa cô theå, ñoâi khi coù theå gaây töû vong.

T

rong cô theå saét giuùp söï thaønh laäp vaø duy trì hoàng caàu, giuùp chuyeân chôû oxygen ñi khaép cô theå. Cô theå caàn caân baèng hoùa soá löôïng saét caàn thieát baèng caùch haáp thuï moät soá vöøa ñuû ñeå cung öùng soá löôïng vöøa tieâu thuï. Khi cô theå tröõ saét nhieàu hôn nhu caàu, saét tích tuï trong teá baøo, trong moâ, trong caùc cô quan nhö gan, tuïy taïng, tim, da, vaø naõo boä, coù theå gaây hö haïi cho moâ vaø nhieàu cô quan khaùc trong cô theå.

Nguyeân nhaân gaây thaëng dö saét (Iron Overload) ê

Coù hai loaïi thaëng dö saét Loaïi thaëng dö saét do di truyeàn qua di theå (hereditary hemochromatosis) vaø thaëng dö saét phuï thuoäc (secondary iron overload). Thaëng dö saét moâ di truyeàn lieân quan ñeán HFE C282Y/C282Y ñoàng hôïp töû (C282Y homozygotes) C 282Y/H63D hoãn hôïp dò hôïp töû (heterozygotes) TDSM di truyeàn coù lieân heä ñeán moät tyø veát treân di theå HFE, moät di theå coù nhieäm vuï ñieàu hoøa löôïng saét haáp thuï töø thöïc phaåm. Coù hai loaïi ñoät bieán trong HFE, mang teân C282Y vaø H63D. C282Y quan troïng hôn. Khi moät ngöôøi thöøa höôûng C282Y cuûa caû hai ngöôøi boá laãn meï, seõ mang C282Y/C282Y, saét seõ ñöôïc haáp thuï quaù ñaùng vaø coù theå gaây neân bieán chöùng TDSM. Taøi lieäu cho bieát trong nöôùc Myõ, 85% ngöôøi bò TDSM coù hai aán baûn cuûa di theå ñoät bieán C282Y thöøa höôûng di truyeàn cuûa moät töø cha moät töø meï. Di theå ñoät bieán H63D thöôøng ít gaây gia taêng saét haáp thuï, nhöng ñoâi khi TDSM coù theå xaåy ra cho moät ngöôøi coù moät hoãn hôïp C282Y töø moät ngöôøi (cha hay meï) vaø H63D töø ngöôøi thöù hai (meï hay cha). Nhöng noùi chung, haàu heát nhöõng ngöôøi naøy chæ laø ngöôøi taûi beänh naøy suoát ñôøi maø thoâi. Ngoaøi ra coøn coù moät loaïi di theå ñoät bieán thöù ba raát ít thaáy laø S65Cø.

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Khuyeát taät trong di theå gaây TDSM hieän dieän töø khi môùi sinh, nhöng trieäu chöùng ít khi phaùt hieän ñeán taän tuoåi tröôûng thaønh. Thaëng dö saét moâ phuï thuoäc coù theå do nhieàu nguyeân nhaân * Thaëng dö saét do truyeàn maùu Beänh nhaân bò beänh thieáu maùu neáu cho truyeàn maùu nhieàu quaù coù theå bò nhieãm chöùng hemosiderin (hemosiderosis) vì löôïng saét cung caáp trong maùu ñöôïc truyeàn coù theå quaù thaëng dö vaø seõ tích tuï trong heä löôùi noäi moâ (reticuloendothelial system- RSE) cuûa nhöõng cô quan nhö gan, tuïy taïng, vaø tim. Löôïng saét quaù taûi naøy coù theå laøm suy giaûm chöùc naêng cuûa nhöõng cô quan lieân heä. * Thaêng dö saét khoâng do truyeàn maùu Nhöõng ngöôøi bò beänh thieáu maùu vuøng bieån (thalassemia), nhu caàu raát cao cho saét trong tuûy xöông laøm cho hoï haáp thuï saét trong thöïc phaåm nhieàu hôn soá löôïng caàn thieát. * Beänh gan kinh nieân: nhö gan vieâm B vaø C, beänh gan do uoáng röôïu, beänh gan môõ khoâng phaûi do uoáng röôïu, roái loaïn chuyeån hoùa porphyrin xuaát hieän treã treân da (porphyria cutanea tarda) * Saét thaëng dö do thöùc aên * Nhöõng nguyeân do khaùc: nhö saét thaëng dö ôû ngöôøi gioáng Phi chaâu, saét thaëng dö ôû treû sô sinh, v.v...

* baát löïc * taét kinh nguyeät sôùm * saéc toá cuûa da taêng laøm da troâng xaùm hay coù maøu nhö maøu ñoàng * suy yeáu tuyeán giaùp * nhöôïc tuyeán yeân, giaûm chöùc naêng tuyeán yeân * nhieãm truøng

Chaån Ñònh Beänh

Beänh TDSM thöôøng ít khi ñöôïc chaån ñònh vaø chöõa trò sôùm, vì nhöõng trieäu chöùng cuûa beänh naøy thöôøng khoâng chuyeân bieät. Khi beänh nhaân ñeán khaùm beänh vaø than phieàn veà beänh nhö ñau khôùp, beänh gan, beänh tim hay tieåu ñöôøng thì baùc só chæ nghó tröôùc tieân laø ñieàu trò nhöõng beänh naøy, vaø ít khi nghó laø beänh do löôïng saét toàn tröõ quaù ñaùng trong moâ vaø cô quan. Chæ sau khi laøm nhöõng thöû nghieäm maùu thoâng thöôøng, neáu keát quaû cho thaáy thí duï nhö coù baát bình thöôøng trong nhöõng thoâng soá cuûa chöùc naêng gan, vaø sau khi nhöõng cô cheá cuûa toàn tröõ saét khoâng coù tính caùch di truyeàn nhö thieáu maùu thalassemia hay thieáu maùu hoàng caàu lieàm (sickle cell anemia) ñöôïc loaïi boû thì thöû nghieäm chuyeân bieät tìm TDSM môùi ñöôïc cho laøm. Hieän nay, nhöõng cô quan, hieäp hoäi lieân quan ñeán beänh ñöôøng ruoät, ñau khôùp, tieåu ñöôøng, tim maïch coù nhaéc nhôû baùc só neân nghó ñeán vieäïc cho thöû nghieäm chuyeân bieät tìm beänh TDSM cho nhöõng ngöôøi coù beänh ñau khôùp, baát löïc, meät moûi quaù söùc, beänh tim, enzym gan taêng, vaø tieåu ñöôøng. Thöôøng thì beänh söû, khaùm toång quaùt, vaø thöû nghieäm maùu thoâng duïng giuùp cho vieäc loaïi ra nhöõng ñieàu kieän coù theå gaây neân nhöõng trieäu chöùng beänh nhaân than phieàn. Nhöng nhöõng thöû nghieäm maùu thoâng thöôøng khoâng cho bieát ñöôïc beänh, maø beänh nhaân caàn phaûi coù ít nhaát laø hai thöû nghieäm chuyeân bieät veà maùu ñeå ñònh beänh TDSM. Serum transferrin saturation (TS). Transferrin baõo hoøa trong maùu: ño löôïng saét keát dính vôùi moät protein (transferrin) coù nhieäm vuï mang saét trong maùu. Neáu transferrin saturation > 45 % thì coi nhö quaù cao. Serum ferritin (SF). Ferritin trong maùu do löôïng saét döï tröõ trong toaøn cô theå. Caùch tính TS: Beänh nhaân khoâng ñöôïc duøng nhöõng saûn phaåm phuï trôï saét trong 24 giôø. Sau khi nhòn ñoùi ít nhaát laø 12 giôø, laáy maùu ñeå laøm boán thöû nghieäm: Saét trong huyeát thanh (Serum IronSI), Toång soá khaû naêng saét keát dính (Total iron binding capacity-TIBC), % baõo hoøa (% of saturation), vaø Ferritin trong huyeát thanh (Serum ferritin). Caùch ño % baõo hoøa (ST): muoán coù soá phaàn traêm cuûa ñoä baõo hoøa thì laáy saét trong huyeát thanh (SI) chia cho Toång soá khaû naêng saét keát dính (TIBC) vaø nhaân cho 100%. TIBC/Serum Iron x 100% = transferrin baõo hoøa Taàm an toaøn cho Transferrin baõo hoøa (TS) hay % baõo hoøa

Yeáu toá maéc beänh

TDSM di truyeàn laø moät beänh di truyeàn veà maùu thoâng thöôøng nhaát ôû Myõ. Cöù côõ 5 trong 1,000 ngöôøi coù theå mang hai di theå ñoät bieán C282Y naøy. Beänh ít thaáy ôû ngöôøi Myõ goác Phi-Chaâu, goác AÙ-Chaâu, goác Taây-Ban-Nha, vaø ngöôøi Myõ da ñoû. Maëc duø caû hai phaùi nam vaø nöõ ñeàu coù theå mang di theå ñoät bieán, nhöng thoáng keâ cho thaáy ñaøn oâng deã bò aûnh höôûng veà beänh naøy hôn vaø beänh thöôøng thaáy phaùt hieän sôùm hôn. Ñaøn baø vì nhôø maát maùu qua kinh nguyeät, qua sinh nôû vaø thôøi kyø coù söõa neân thöôøng phaùt hieän treã hôn sau khi taét kinh.

Trieäu Chöùng

Ñaëc tröng laâm saøng goàm ñau khôùp, yeáu ñuoái, meät moûi, khoâng coù sinh löïc, ñau buïng, maát höùng laøm tình, maát kinh ôû ñaøn baø, vaø khoù thôû. Trieäu chöùng xaåy ra sôùm hôn ôû ñaøn oâng trong tuoåi töø 30 ñeán 50, vaø ñaøn baø thì töø ngoaøi tuoåi 50. Cuõng coù ngöôøi do tình côø maø chaån ñònh ra coù beänh duø chaúng coù trieäu chöùng gì ñaùng keå. Neáu beänh khoâng ñöôïc khaùm phaù ra sôùm vaø trò lieäu, saét tích tuï trong moâ vaø caùc cô quan nhö gan, tim, tuyeán tuïy taïng coù theå gaây neân nhieàu bieán chöùng traàm troïng nhö: * * * * beänh khôùp xöông, vieâm khôùp beänh gan nhö gan to, xô gan, suy gan vaø ung thö gan hö haïi tuïy taïng coù theå gaây neân beänh tieåu ñöôøng tim coù theå coù nhöõng baát thöôøng nhö nhòp tim khoâng ñieàu hoøa, suy tim

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laø töø 12 ñeán 44%. Taàm an toaøn cuûa Ferritin trong huyeát thanh (SF) laø töø 5 ñeán 150 ng/mL Neáu hai thöû nghieäm treân cho thaáy % baõo hoøa (ST) > 40% vaø SF >150ng/mL (ferritin > 300 ng/mL ôû ñaøn oâng, vaø > 200 ng/mL ôû ñaøn baø) thì coi nhö ngöôøi beänh naøy ñang maéc beänh TDSM di truyeàn vaø caàn phaûi laøm theâm moät soá thöû nghieäm khaùc.

Neáu sinh thieát gan cho thaáy coù trieäu chöùng bò sô gan, ngöôøi beänh caàn ñöôïc theo doõi thöôøng xuyeân ñeå tìm beänh ung thu gan vôùi CAT scan vaø alpha-fetoprotein (AFP) cöù moãi saùu thaùng.

Ñieàu trò

Ñieàu trò beänh TDSM thöôøng döôùi söï theo doõi cuûa baùc só trong ngaønh chuyeân veà gan, chuyeân veà ñöôøng ruoät, hay huyeát hoïc. Ngoaøi ra baùc só trong ngaønh tim maïch, noäi tuyeán, hay chuyeân veà thaáp khôùp (rheumatologist) vaø ngay caû baùc só noäi khoa cuõng thuoäc vaøo ñoäi chuyeân gia trò lieäu. Caùch ñieàu trò thì raát giaûn dò, khoâng toán keùm vaø an toaøn. Phöông phaùp ñoå bôùt maùu (phlebotomy) laø caùch laáy bôùt maùu ra khoûi cô theå. Khi maùu cô theå giaûm, thì cô theå seõ laáy saét döï tröõ trong cô theå vaø chuyeån hoùa noù ñeå buø vaøo löôïng saét thieáu huït trong maùu. Soá löôïng maùu ruùt ra khoûi cô theå nhieàu ít tuøy thuoäc vaøo soá löôïng thaëng dö saét trong maùu. Möùc ferritin trong maùu ñöôïc ño löôøng thöôøng xuyeân. Beänh nhaân neáu ñöôïc theo doõi kyõ löôõng, ñieàu trò haïn kyø ñeàu daën, ñoâi khi trò lieäu keùo daøi caû naêm, thì coù theå soáng bình thöôøng. Muïc ñích caàn ñaït laø giöõ cho möïc ferritin trong huyeát thanh maõi maõi ôû döôùi 20 ng/mL. Neáu tình traïng khoâng ñieàu trò keùo daøi beänh nhaân coù theå bò xô gan vaø suy gan. Tröôùc ñaây, soá maùu laáy ra töø ngöôøi bò TDSM ñeàu bò coi nhö maùu xaáu vaø ñöôïc tieâu huûy. Nhöng baét ñaàu töø naêm 1999, FDA ñaõ cho pheùp nhöõng ngaân haøng maùu ñöôïc pheùp duøng maùu naøy sau khi thoâng qua ñöôïc tieâu chuaån do FDA ñaët ra.

Thöû nghieäm DNA

Trong taát caû moïi tröôøng hôïp, laøm moät thöû nghieäm DNA cho di theå ñoät bieán HFE Cys282Y vaø His63G treân nhieãm theå soá 6. Thöû nghieäm naøy coù theå laøm töø moät maãu moâ (tissue sample) hay maãu maùu.

Thöû nghieäm chöùc naêng gan

Taát caû beänh nhaân nghi ngôø bò beänh TDSM ñeàu caàn cho thöû ALT, AST, SGOT, GGPT. Neáu nhöõng thöû nghieäm naøy coù keát quaù cao ñaùng keå, thì caàn laøm moät sinh thieát gan ñeå xaùc ñònh ñoä hö haïi cuûa gan. Vôùi nhöõng beänh nhaân coù chöùc naêng gan bình thöôøng vaø ñaõ xaùc nhaän laø bò TDSM qua thöû nghieäm DNA thì neân cho ñieàu trò ngay maø khoâng caàn phaûi laøm sinh thieát gan.

Tieâu chuaån ñeå laøm sinh thieát gan

Sinh thieát gan caàn phaûi laøm khi: Serum ferritin > 1000 ng/mL vaø ngöôøi beänh lôùn hôn 30 tuoåi Thöû nghieäm chöùc naêng gan cao ñaùng keå. Keát quaû cuûa CT, MRI, hay sieâu aâm cho thaáy to gan hay baát cöù baát bình thöôøng naøo cuûa gan. So saùnh nhöõng phöông phaùp CT, coäng höôûng töø quang aûnhMRI hay sieâu aâm thì MRI cho hình aûnh toát nhaát ñeå xaùc ñònh vò trí cuûa saét tích tuï trong gan vaø noù cung caáp moät phoûng ñònh toaøn löôïng saét trong gan, so vôùi sinh thieát gan chæ cho thaáy maãu cuûa moät phaàn cuûa gan. CT ít nhaïy caûm hôn, vaø sieâu aâm thöôøng khoâng phaûn aûnh ñöôïc söï toàn tröõ saét trong gan.

Tieân Löôïng

Tieân löôïng cho nhöõng ngöôøi bò beänh TDSM tuøy thuoäc vaøo söï hö hoûng cuûa cô quan lieân heä. Moät thí duï ñieån hình laø neáu beänh phaùt giaùc sôùm vaø trò lieäu thöïc hieän ngay thì coù theå ngaên ngöøa ñöôïc söï tieán trieån cuûa beänh gan. Neáu phaùt hieän sau khi beänh nhaân ñaõ bò xô gan thì duø cho löôïng maùu trong cô theå ñaõ ñöôïc duy trì ôû möïc bình thöôøng, beänh nhaân vaãn coù theå coù nguy cô bò ung thö gan.

References:

1- Niederau C, Erhardt A, Haussinger D: Haemochromatosis and the liver. J Hepatol 1999; 30 Suppl 1: 6-11 2- Tavill AS. Diagnosis and management of hemochromatosis. Hepatology 2001 May;33(5):1321-8. 3- Phatak PD, Sham RL, Raubertas RF: Prevalence of hereditary hemochromatosis in 16031 primary care patients. Ann Intern Med 1998 Dec 1; 129(11): 954-61 4- Burke W et al: Consensus Statement: Hereditary hemochromatosis. Gene discovery and its implications for population-based screening. JAMA 280:172, 1998 5- Cogswell ME et al: Iron overload, public health, and genetics: Evaluating the evidence for hemochromatosis screening. Ann Intern Med 129:971, 1998

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6- Beutler E, Gelbart T, West C, et al. (1996) Mutation analysis in hereditary hemochromatosis. Blood Cells Mol Dis 22:187-94. 7- Bonkovsky HL, Rubin RB, Cable EE: Hepatic iron concentration: noninvasive estimation by means of MR imaging techniques. Radiology 1999 Jul; 212(1): 227-34 8- Howard JM, Ghent CN, Carey LS: Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology 1983 Feb; 84(2): 209-15 9- Siegelman ES, Mitchell DG, Semelka RC: Abdominal iron deposition: metabolism, MR findings, and clinical importance. Radiology 1996 Apr; 199(1): 13-22 10- Gandon Y, Guyader D, Heautot JF: Hemochromatosis: diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology 1994 Nov; 193(2): 533-8 11- Howard JM, Ghent CN, Carey LS: Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology 1983 Feb; 84(2): 209-15 12- Kawamoto S, Soyer PA, Fishman EK: Nonneoplastic liver disease: evaluation with CT and MR imaging. Radiog raphics 1998 Jul-Aug; 18(4): 827-48

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Phuï Ñính

Beä n h Thaë n g Dö Saé t Moâ ÔÛ Ngöôø i Vieä t

Giang Nguyeãn Trònh, R.Ph., D.Ph.

Abstract:

Hereditary hemochromatosis is thought to be prevalent in Caucasians of Northern European origin. Recently, a case of HH in a Vietnamese patient was reported in the literature. However, in this case gene mutation occurs at a different location than those previously reported in the Caucasian population. Thus, although rare, hemochromatosis does occur in Asians.

Toùm taét:

Beänh thaëng dö saét moâ (TDSM) laø beänh raát thöôøng thaáy ôû ngöôøi da traéng, nhaát laø nhöõng ngöôøi coù nguoàn goác töø vuøng Baéc AÂu. Gaàn ñaây coù baùo caùo veà moät tröôøng hôïp TDSM ôû ngöôøi Vieät. Thöû nghieäm cho thaáy ñoät bieán xaåy ra ôû moät di theå khaùc vôùi tröôøng hôïp ôû ngöôøi da traéng. Toùm laïi, TDSM tuy hieám nhöng cuõng coù theå xaåy ra cho ngöôøi goác AÙ ñoâng.

B

eänh thaëng dö saét moâ laø moät beänh raát thoâng duïng ôû ngöôøi da traéng, nhaát laø nhöõng ngöôøi coù nguoàn goác töø vuøng Baéc AÂu-chaâu. Vaøo naêm 1988, baùo New England Journal of Medicine coù baøi vieát cho bieát keát quaû thöû nghieäm treân maãu maùu cuûa 11,605 ngöôøi ñöôïc coi laø bình thöôøng thì cöù moät trong 200 ngöôøi laø bò beänh thaëng dö saét moâ - TDSM. Ngöôøi Myõ bò beänh naøy nhieàu hôn moät soá beänh khaùc coäng laïi nhö beänh xô hoùa nang (cystic fibrosis), beänh Huntington, vaø roái loaïn cô (muscular dystrophy).

Lòch söû beänh TDSM

Beänh TDSM ñöôïc khaùm phaù ra bôûi moät baùc só ngöôøi Phaùp teân laø Armand Trousseau vaøo naêm1865 sau khi oâng khaùm vaø chöõa moät ngöôøi ñaøn oâng 28 tuoåi bò beänh tieåu ñöôøng traàm troïng maø luùc ñaàu Trousseau nghó laø ngöôøi naøy bò ba thöù beänh coäng laïi tieåu ñöôøng, xô gan, vaø saéc toá da. Khi laøm giaûo nghieäm töû thi thì gan raát lôùn vaø raát laï. Naêm 1889, baùc só Von Recklinghausen ñaët teân hieän töôïng beänh naøy laø hemochromatosis. Naêm 1935, baùc só Josep H. Sheldon vieát moät töôøng trình noåi tieáng veà moät treû sô sinh bò beänh loaïn bieán döôõng gaây hö haïi nhieàu cô quan thieát yeáu. Thöû nghieäm ño löôïng saét trong maùu baét ñaàu vaøo naêm 1925. Thöû nghieäm toång soá khaû naêng saét keát dính (TIBC) baét ñaàu vaøo naêm 1944. Trò lieäu ñôn giaûn baèng caùch ñoå maùu ñi (bloodletting) baét ñaàu ñöôïc aùp duïng vaøo trong khoaûng nhöõng naêm 1950. (Moät tröôøng hôïp trò beänh baèng caùch ñoå maùu laøm cheát toång thoáng Myõ George Washington ñaõ laøm soâi noåi dö luaän vaø ngaønh y khoa vaøo theá kyû thöù 18).

Vietnamese Pharmaceutical Journal No.5- 71

DÖÔÏC KHOA NGHIEÂN CÖÙU - Beänh Thaëng Dö Saét Moâ

Thöû nghieäm Ferritin baét ñaàu vaøo naêm 1956 Di theå ñoät bieán cho beänh TDSM ñöôïc haõng Mercator genetics, Inc (baây giôø laø Progenitor), Menlo Park, California chính thöùc thoâng baùo qua baøi vieát treân tôø Nature Genetics soá thaùng Taùm 1996. Tröôøng hôïp beänh TDSM ôû moät ngöôøi Vieät Trong baøi vieát veà beänh Thaëng Dö Saét Moâ coù noùi ñeán thaëng dö saét di truyeàn gaây neân bôûi hai loaïi hôïp töû thöôøng thaáy laø C282Y vaø H63D, vaø S65C HFE. Nhö ñaõ vieát haàu heát caùc tröôøng hôïp beänh TDSM laø do ñoàng hôïp töû C282Y/C282Y. Hoãn hôïp dò hôïp töû C282Y/H63D thöôøng ít khi gaây beänh maø nhöõng ngöôøi mang noù thöôøng khoûe maïnh vaø chæ laø nhöõng ngöôøi mang taûi di theå naøy maø thoâi. Vì beänh thöôøng thaáy ôû ngöôøi da traéng goác Baéc AÂu, vaø raát ít thaáy ôû nhöõng gioáng daân khaùc neân cho ñeán taän naêm 2001, khoâng coù moät nghieân cöùu naøo noùi ñeán beänh ôû nhöõng gioáng daân khaùc. Vaøo thaùng ba, naêm 2002, moät töôøng trình ñaàu tieân trong baùo Gastroentology noùi veà tröôøng hôïp moät ngöôøi ñaøn oâng Vieät Nam bò maéc beänh TDSM maø sau khi doø tìm hieåu veà di theå ñoät bieán thì khoâng thaáy ba loaïi ñaõ ñöôïc bieát ñeán töø laâu (C282Y, H63D, S65C). Moät loaïi di theå ñoät bieán môùi ñöôïc khaùm phaù ra vaø ñöôïc ñaët goïi laø IVS5+1 G-->A. Ñaây laø tröôøng hôïp ñaàu tieân tìm thaáy ôû moät ngöôøi ñaøn oâng Vieät Nam coù di theå ñoät bieán IVS 5+ 1G-->A. Moät töôøng trình khaùc cho hay nhöõng ngöôøi AÙ chaâu vuøng Ñoâng Nam bò beänh thaêng dö saét di truyeàn laø do IVS5+1 G-->A vaø H63D HFE ñoät bieán. Noùi toùm laïi, beänh thaëng dö saét moâ coù theå xaåy ra cho ngöôøi AÙ Chaâu, vaø tuy beänh hieám xaåy ra, baùc só sau khi tìm maõi vaãn chöa chöõa trò ñöôïc ñuùng beänh thì phaûi neân nghó ñeán beänh thaëng dö saét moâ vaø neân cho laøm thöû nghieäm chuyeân bieät nhö thöû nghieäm saét trong maùu, toång soá khaû naêng saét keát dính (TIBC), vaø ferritin. Taøi lieäu tham khaûo: 1- Wylie Burke et al. "Hereditary Hemochromatosis. Gene Discovery and its Implications for Population-Based Screening." JAMA 280 (2): 172-8. 2- Gastroenterology. 2002 Mar;122(3):789-95. A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin. 3- Blood Cells Mol Dis. 2003 May-Jun;30(3):302-6. Hemochromatosis gene (HFE) mutations in South East Asia: a potential for iron overload.

John Steinbeck IV (1945-1991) vaøø Beänh Thaëng Dö Saét Moâ Nhaø vaên John Steinbeck IV (1945-1991) con trai cuûa vaên haøo John Steinbeck (The Grapes of Wrath) thöøa höôûng hai beänh di truyeàn cuûa boá ñeå laïi, ñoù laø nghieän röôïu vaø beänh thaëng dö saét moâ. John Steinbeck IV bò sô gan ngay töø khi môùi 34 tuoåi, nhöng beänh thaëng dö saét moâ chæ ñöôïc khaùm phaù ra vaøo naêm 1984, khi Steinbeck IV 39 tuoåi. Suoát cuoäc ñôøi, oâng phaûi tranh ñaáu vôùi nghieän ngaäp töø ma tuùy khi oâng ôû Vieät Nam vaø röôïu. John Steinbeck IV vieát hoài töôûng veà Vieät Nam trong In Touch vaø nhaän moät giaûi thöôûng Emmy khi hôïp taùc vôùi CBS vieát veà taøi lieäu The World of Charlie Company. John Steinbeck IV cheát naêm 1991 vì bò beå ñóa (rupture disc), vaø khoâng soáng soùt sau giaûi phaãu. Cuoán saùch The Other Side of Eden- Life with John Steinbeck do vôï John, Nancy Steinbeck vieát tieáp vaø xuaát baûn naêm 2001. Moät tröôøng hôïp beänh hemochromatosis Vieát veà hemochromatosis phaûi keå ñeán moät tröôøng hôïp ñaõ gaây chuù yù cho giôùi chuyeân gia trong ngaønh huyeát hoïc. Trong baùo John Hopkins Advanced Studies in Medicine soá thaùng Hai, 2003 coù moät baøi trong phaàn Clinical Red Flags noùi veà moät tröôøng hôïp beänh thaëng dö saét moâ -TDSM (hemochromatosis). Ñaây laø tröôøng hôïp moät ngöôøi ñaøn oâng da traéng 30 tuoåi, bò meät moûi, maát ham muoán tình duïc vaø duïc tính (loss of libido), ñau nhöùc khôùp ñuû moïi nôi ñaõ caû naêm vaø leân 40 lbs. Sau khi beänh nhaân ñöôïc chaån ñònh laø bò beänh thaëng dö saét moâ vaø ñöôïc chöõa trò baèng phuï trôï testosterone vaø laáy bôùt maùu ra khoûi cô theå (phlebotomy); beänh TDSM thuyeân giaûm nhöng beänh nhaân vaãn bò ñau khôùp vaø laïi naëng theâm 25 lbs nöõa. Moät soá thöû nghieäm maùu tieáp tuïc tìm theâm beänh ñaõ cho bieát beänh nhaân coù möïc hormone sinh tröôûng raát thaáp ôû trong maùu, ñoù laø moät bieán chöùng baát thöôøng hieám thaáy cuûa beänh thaêng dö saét trong moâ. Beänh nhaân ñöôïc cho trò lieäu theâm vôùi hormone taêng tröôûng, sau nhieàu thaùng beänh nhaân ñaõ suùt caân nhieàu, bôùt meät nhöng ñau nhöùc khôùp xöông vaãn coøn dai daúng. BS D.W. Schlott, taùc giaû baøi vieát cho bieát maëc duø testosterone seõ ñöôïc duøng maõi maõi, oâng khoâng chaéc laø hormone taêng tröôûng seõ ñöôïc duøng bao laâu cho beänh nhaân naøy, lí do vì coù theå khi laáy bôùt saét trong cô theå ra roài thì söï roái loaïn chöùc naêng cuûa tuyeán yeân seõ giaûm bôùt. Taùc giaû keát luaän trong tröôøng hôïp moät beänh nhaân bò beänh TDSM meät moûi quaù ñoä, leân caân thì baùc só neân nghó ñeán beänh nhaân coù theå bò thieáu hormone taêng tröôûng khi trò lieäu baèng caùch loaïi bôùt chaát saét moâ ra khoûi cô theå qua caùch laáy bôùt maùu ra, khoâng ñaït ñöôïc keát quaû toát.

72 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Beänh Thaëng Dö Saét Moâ - PHARMACY RESEARCH

Taøi lieäu tham khaûo: 1- Barton, J. D. (2000). Hemochromatosis. Cambridge: Cambridge University 2- Press.Schlott, D. W., & Berkenblit, G. (2003). Hemochromatosis and a seldom-considered complication. Advanced Studies in Medicine, 3 (2), 112-113.

http://www.collectmedicalantiques.com/bloodletting.html

Vietnamese Pharmaceutical Journal No.5- 73

Environmental Exposure and Anemia

Bui Quoc Quang, MD.

Director Toxicology Genencor International Inc., Palo Alto, CA 94304

Abstract

The Author

The author graduated from the School of Pharmacy, Saigon University in 1970 and currently holds a doctorate degree in Pharmacology & Toxicology. He is Board certified in toxicology and is currently with Genencor International in Palo Alto, CA. His previous positions included Howard University College of Medicine, Office of Pesticide Programs, USEPA; Unocal 76 and Elf Atochem

Application of pesticides in the agricultural sector has contributed significantly to the economic growth and human health by the elimination of numerous parasitic diseases and by the production of abundant, nutritive and inexpensive food crops. Undoubtedly, without agricultural pesticides hunger and famine would still rampage worldwide. Unfortunately, the widespread use and misuse of pesticides are not without health and environmental consequences including rare hematological condition such as aplastic anemia. A review of the literature suggests an association between pesticide exposure and aplastic anemia, which is more prevalent in third world countries, lower socioeconomic status and child-laborers.

Toùm Löôïc

AÙp duïng thuoác coân truøng trong noâng nghieäp laø moät ñoäng cô quan troïng cho söï phaùt trieån kinh teá vaø cho söùc khoûe cuûa con ngöôøi. Moät soá lôùn beänh taät do kyù sinh truøng ñaõ ñöôïc dieät tröø; thöïc phaåm noâng nghieäp ñöôïc saûn xuaát doài daøo vaø vôùi giaù reû. Neáu khoâng coù nhöõng thuoác dieät coân truøng naøy, naïn ñoùi keùm nhaát ñònh vaãn coøn hoaønh haønh khaép theá giôùi. Tuy nhieân vieäc söû duïng thuoác dieät coân truøng roäng raõi vaø khoâng ñuùng caùch ñaõ ñöa ñeán nhöõng haäu quaû khoâng toát veà moâi sinh vaø trong vaøi tröôøng hôïp hieám coù, ñaõ gay ra beänh thieáu maùu. Moät soá taøi lieäu khaûo cöùu ñaõ chöùng minh söï lieân heä giöõa vieäc söû duïng thuoác dieät coân truøng vaø beänh thieáu maùu nhaát laø ôû caùc nöôùc chöa môû mang, caùc taàng lôùp ngöôøi ngheøo hoaëc ôû caùc true em laøm vieäc taïi noâng tröôøng.

Introduction

P

esticides were introduced in the 1930s. In 1939, there were 32 pesticides registered with the US Department of Agriculture (USDA). Sixty years later, in 1990, there were over 800 active-ingredient pesticides and over 20,000 commercial products containing pesticides registered with the US Environmental Protection Agency (EPA). By 1995, sales of pesticides in the USA alone amounted to over 1 billion pounds to control pests. Over 150,000 cases of pesticide exposures are reported annually to the US Poison Control Centers, 90% of which involves home uses. Exposure to pesticides occurs in several ways - by ingestion of residues in food crops and drinking water, by inhalation through spray drift and household applications, and by dermal absorption of leftover products from household uses. Pesticide exposure may result in adverse effects ranging from acute, chronic health effects, reproductive toxicity, neurotoxicity, carcinogenicity, to target organ damage. Adverse health effects may also be caused by impurities or by-products from manufacturing processes, such as dioxins and ethylene thiourea. Several reports have linked pesticide-occupational exposure to anemia and the purpose of this review is to assess whether pesticide-exposure could be one of the etiologic factors.

74- Taäp San Chuyeân Nghieäp Döôïc Khoa

Environmental Exposure and Anemia - PHARMACY RESEARCH

Aplastic Anemia - The Implication

Relatively little is known about aplastic anemia, especially its possible etiologies and risk factors. Aplastic anemia is a bone marrow failure syndrome characterized by peripheral blood pancytopenia and bone marrow hypocellularity. It has been documented that aplastic anemia is rare in the West and is more common in Asia (1). Indeed, the annual incidence in Thailand and China is 20 cases per million compared to 2 to 6 per million in the US and 1.4 per million in France. Known risk factors for aplastic anemia include medications such as chloramphenicol, chemicals such as benzene, and viral infection such as HBV. However, 40 to 70% of the cases are still of unknown etiology. Other possible etiologic associations include drugs, such as penicillamine, carbamazepine, and gold compounds, along with agricultural pesticide exposure and low socioeconomic status. The pesticides commonly alleged are the organochlorine and organophosphate insecticides (2).

and recently from the war in Iraq as potential biological chemicals. In the past two decades, the herbicides represent the fastest growing section of the agricultural pesticide business. Most common herbicides are 2,4 D and 2,4,5-T containing the infamous contaminant TCDD or dioxin. The extensive spray of Agent Orange, a 50:50 mixture of the nbutyl esters of 2,4-D and 2,4,5-T as a defoliant during the Vietnam war raises the possible adverse health effects among exposed US service personnel and the Vietnamese population. Of all the fungicides, hexachlorobenzene is the most well known due to an epidemic poisoning involving over 4000 people in Turkey where people consumed treated grain (3). Given the enormous use of pesticides worldwide, especially in developing countries, the possible etiologic association with aplastic anemia becomes important in the prevention of this rare hematological disorder.

Pesticides - The Alleged Causative Agents

No one can doubt the efficacy of pesticides for the protection of crops, thereby providing us with abundant, inexpensive, wholesome, and attractive fruits and vegetables. The medical miracles accomplished by pesticides are many including the suppression of typhus in Naples, Italy by DDT; the control of river blindness in West Africa by Temephos; the control of malaria in Vietnam and all over Asia by a variety of insecticides and most recently the control of the Mediterranean fruit fly in California by air sprays of organophosphates. However, the widespread use and misuse of pesticides create an awareness of the potential health hazards leading to the promulgation and passage of stricter regulations and legislations worldwide. It is noteworthy to emphasize that, despite the development of second and third generation derivatives of the early pesticides, all pesticides must be inherently toxic otherwise they would not be effective. There is no such thing as a safe pesticide, but all pesticides can be used safely when applied according to the label's instructions. Many of the public concerns about pesticides are related to "older" chemicals, these having entered the market in the 1950s and 1960s without extensive toxicity and environmental impact studies to support registration. Pesticides form a huge group of varied chemicals and are classified based on application such as insecticides (25-30%), herbicides (60-70%), fungicides (1015%), and rodenticides (<5%). Insecticides, in general, are neurotoxicants and the most famous is the organochlorine DDT. Another organochlorine derivative that pharmacists are quite familiar with is Lindane, a component of a pediculicide shampoo for head lice. The organophosphate insectides are also known as anticholinesterase agents based on their mechanism of action. Anticholinesterase agents have received plenty of publicity during the Desert Storm operation in Saudi Arabia

The Human Implication - Case Reports and Epidemiology Studies

Over three hundred cases of aplastic anemia associated with pesticide exposure are reported in the literature. The majority of these cases involves young persons with a history of occupational exposure to pesticides especially the organochlorines (e.g., DDT). This is not surprising because the organochlorines are the oldest and the most widely used pesticides. They are lipophilic and can persist in the adipose tissue for a lifetime. A population based case-control epidemiology study of aplastic anemia has been conducted in Thailand since 1989. The study was completed in 1999 and the results revealed positive associations with occupational exposure and agricultural pesticides (4). In Brazil, numerous cases of severe aplastic anemia were linked to low socioeconomic status and exposure to agricultural pesticides (5). In Tanzania, a randomized controlled trial of insecticide-treated areas suggested pesticide-induced malaria (6) and numerous reports indicated that the extensive use of insecticides and herbicides may be associated with the development of Hodgkin's disease, non-Hodgkin's lymphoma, and aplastic anemia and child laborers are mostly vulnerable (7). Aplastic anemia, pure red cell aplasia, leukemia, lymphoma and other hematological disorders are found in association with the pesticide pentachlorophenol (PCP). Owing to widespread contamination of the environment by PCP and its dioxin-dibenzofuran contaminants, its contributory role cannot be refuted scientifically. Aplastic anemia, porphyrias, porphyrinurias have been observed after exposure to hexachlorobenzene, chlorinated dioxins, polychlorinated biphenyls. Based on the above review of the medical literature, a possible etiologic association exists between pesticide exposure and aplastic anemia in humans.

Vietnamese Pharmaceutical Journal No.5 - 75

DÖÔÏC KHOA NGHIEÂN CÖÙU - Environmental Exposure and Anemia

The Occupational Implication

The International Labor Office has estimated that there are 250 million child laborers (5-14 years old) worldwide with more than half of these working full time. Most come from families ravaged by poverty, live in poor sanitation conditions and inadequate nutritious food. Working children are vulnerable to anemia and other health problems. However, the issue of child labor is complex. Child labor is an economic and social reality in many developing countries in Asia and Africa. Children may provide 25% or more of a family's total income yet child labor violates children' rights and exposes them to increased health risks. There are numerous immunotoxic and hematotoxic consequences of occupational exposures. Aplastic anemia may occur after exposure to organochlorine pesticides. Megaloblastic anemia has been noted in subjects exposed to chlordane. Methemoglobinemia is induced by aromatic nitro and amino compounds. Hemolytic reactions are caused by methyl chloride. Leukemia and lymphoma are noted after exposure to PCP. With regard to possible etiologic factors, there are strong and significant positive associations with occupational exposure to pesticides. However, household pesticide exposure is not associated with anemia; a fact related to low level exposure.

ufacture of pesticides, dyes, and industrial solvents. There were decreases in erythrocyte count, hemoglobin and hematocrit and increases in spleen weights - parameters characteristics of regenerative anemia (10). In a study with phenylurea herbicides in rats, the authors concluded that exposure to the herbicides resulted in increases in methemoglobinemia and changes in the morphology of erythrocytes (11)

The Conclusion

Since their introduction, pesticides have provided economic benefits, contribute significantly to the fight against famine and have become integral to our way of life. Unfortunately, many pesticides cause unintentional adverse effects, including human toxicity. In many countries, health officials have raised alarm over the increasing number of farmers and occupational laborers afflicted with aplastic anemia and allege to pesticide exposure. This has served as a basis lobbying for stricter legislations and regulations on pesticides. In this review, an evaluation of the published medical literature, including basic science literature, suggests a possible etiologic association between pesticide exposure and aplastic anemia. Only an association can be indicated since it has been very difficult to study aplastic anemia using traditional epidemiologic methods to establish causal relationships (12). It is plausible that pesticides may cause anemia in certain persons in certain circumstances. However the elimination of pesticide use might lead to dramatic consequences worldwide. For example, the elimination of the use of DDT to control malaria has resulted in more than a million new cases in Sri Lanka recently. In conclusion pesticides, as a group, have led to remarkable advances in disease control and agriculture, but this has not been without its own costs in human and environmental health. There is no safe pesticide but pesticides can be used safely.

The Basic Science Implication - Animal Data Evidence

The potential toxicologic effects of 1,3 dichloropropene, a soil fumigant, was investigated in dogs. Hypochromic and microcytic anemia were noted with partial reversal of the anemia noted during the recovery period (8). In mice treated with the chlorinated insecticide hexachlorocyclohexane, anemia was reported after chronic exposure (9). In 1994, the National Toxicology Program conducted several chronic and carcinogenicity studies with p-nitrobenzoic acid in rodents. p-Nitrobenzoic acid is an intermediate in the man-

References:

1. Young NS et al., 1984. Br J Hematology, Vol 62, 1-6. 2. Fleming LE and Timmny W., 1993 J Occup Med Vol 35, 1106-1116 3. Ecobichon D., 2000. In Cassarett & Doull's Toxicology. McGraw Hill Companies, Inc. 4. Issaragrisil S., 1999. Int J Hematol Vol 70(3), 137-140 5. Fonseca TC and Paquini R., 2002. Rev Assoc Med Bras, Vol 488(3), 263-267 6. Fraser-Hurt N et al., 1999. Trans R Soc Trop Med Hyg Suppl 1, 47-51 7. Woolf AD, 2002. J Toxicol Clin Toxicol Vol 40 (4), 477-482 8. Stebbins KE et al., 1999. Reg Toxicol Pharmacol Vol 30, 233-243 9. Shouche S and Rathore HS, 1997. Indian J Med Sci Vol 51(4), 120-122 10. National Toxicology Program 1994, Technical Report No. 442 11. Wang SW et al., 1993 Food Chem Toxicol Vol 31(4), 285-295 12. Issaragrisil S., 1999. IX Congress of ISH-Asian Pacific Division, Bangkok, Thailand

76 - Taäp San Chuyeân Nghieäp Döôïc Khoa

MEDICAL NEWS

Vaø i Tröôø n g Hôïp Beä n h Thieá u Maù u Ñoû

Nguyeãn Taøi Mai, MD.

Abstract

Anemia is very hard to diagnose sometime, and it is important to consider all possibilities when treating cases of chronic anemia. The author discusses two real life examples in the following cases.

Toùm löôïc

Ñònh beänh thieáu maùu ñoâi khi raát khoù, vaø caàn xem taát caû caùc yeáu toá noäi, ngoaïi thöông coù theå gaây ra beänh maõn tính. Taùc giaû baøn ñeán hai tröôøng hôïp ñaõ xaåy ra trong vieäc haønh ngheà chuyeân khoa huyeát hoïc.

Ñ

ònh beänh thieáu maùu ñoâi khi raát khoù. Caù nhaân toâi coù leõ ñaõ laáy hôn 1500 - 2000 mL tuûy xöông trong khoaûng 20 naêm qua. Trong vaøi nghìn tham khaûo veà thieáu maùu, coù ñoä 100 tröôøng hôïp ñaõ laøm ñuû caùc thöû nghieäm maø vaãn khoâng bieát vì sao beänh nhaân bò thieáu maùu. Nhöõng tröôøng hôïp naøy toâi ñeàu göûi ñeán caùc ñoàng nghieäp chuyeân khoa hhuyeát hoïc taïi caùc ñaïi hoïc khaùc nhöng vaãn chöa ñònh beänh ñöôïc roõ raøng. Tuy caùc tröôøng hôïp naøy raát nguy hieåm, toâi nghó neáu theo doõi laâu daøi thì cuoái cuøng cuõng coù theå ñònh beänh ñöôïc. Giaûi thích cho beänh nhaân raèng: beänh nhö taûng nuôùc ñaù ôû bieån, chæ môùi thaáy choûm hieän leân, daàn daàn seõ thaáy toaøn boä khoái nuôùc ñaù. Coù vaøi beänh nhaân bò laáy tuûy xöông 4 laàn trong voøng 4 naêm. Trong moät tröôøng hôïp sau, thaáy u tuûy soáng (myeloma), coøn caùc tröôøng hôïp khaùc thì ñeàu laø loaïn saûn tuûy (myelodysplasia). A. Moät beänh nhaân vöøa qua ñôøi vì suy tim sung huyeát (congestive heart failure). Hai naêm tröôùc ñaõ ñöôïc moät baùc só huyeát hoïc khaùm maø khoâng roõ taïi sao Hct chæ ôû khoaûng 30%. Khi baùc só noäi khoa chuyeån hoà sô sang phoøng maïch chuùng toâi ñeå hoûi yù kieán, laøm laïi tuûy xöông, thì thaáy ñeán 50% tuûy xöông ñaõ bò u tuûy soáng thaám nhaäp. Vò baùc só huyeát hoïc ñaàu tieân ñaõ khoâng laáy tuûy xöông, maø cho raèng beänh nhaân bò " Thieáu maùu kinh nieân - Anemia of chronic disease". Toâi chöõa baèng Melphalan Prednisone ñoä 8 thaùng, sau ñoù chuyeån sang Thalidomide. Tính duøng Velcade, nhöng Platelet chæ ôû khoaûng 8000/mm3, vaø phaûi truyeàn maùu moãi tuaàn (Hct 22%). B. Moät tröôøng hôïp khaùc xaãy ra cho thaân nhaân moät giaùo sö tröôûng khu huyeát hoïc taò moät ñaïi hoïc lôùn trong vuøng. Toâi coù noùi chuyeän qua ñieän thoaïi, vaø göûi pheát tuûy xöông cho oâng xem, oâng cuõng ñoàng yù. Nhöng beänh nhaân khoâng tin lôøi ngöôøi chaùu duø laø Professor - Chief Hematologist, ñeán khaùm moät baùc só huyeát hoïc thöù ba, roài thöù tö ôû New York nhöng khoâng ai bieát laø beänh gì. Cho neân beänh thieáu maùu khoâng deã truy; phaûi khaùm beänh laïi töø ñaàu, vaø nghó ñeán caùc beänh noäi, ngoaïi thöông ngoaøi ñòa haït beänh huyeát hoïc.

Vietnamese Pharmaceutical Journal No.5 - 77

Trình Baà y Moä t Truôø n g Hôï p Beä n h

BS Nguyeãn Taøi Mai

B

eänh nhaân laø moät nguôøi ñaøn oâng Vieät Nam 60 tuoåi do chuyeân vieân giaûi phaãu göûi ñeán sau khi sinh thieát (biopsy) haïch ôû coå (cervical lymphadenopathy). Moät tuaàn truôùc (25/th3/2002) sinh thieát haïch naøy cho thaáy "ung thö chuyeån di ñeán haïch coå, teá baøo lôùn phaân huôùng ung thö keùm (poorly differentiated large cell ), coù choã thaáy gioáng ung thö teá baøo vaåy (focally with squamous cell CA features). Truôùc ñoù, ngaøy 1/th 3/2002 ñaõ laøm CAT scan vuøng coå cho thaáy haïch noåi lôùn ôû caû hai beân coå, haïch lôùn nhaát ño duôïc khoaûng 20 mm, saâu trong vuøng baép thòt SCM (sterno-cleido-mastoid muscles). Phoûng vaán beänh nhaân vôùi söï hieän dieän cuûa vôï vaø con gaùi cho thaáy beänh nhaân ñaõ phaùt giaùc ra haïch coå ôû beân traùi khoaûng thaùng 9/2001 vaø ñaõ than phieàn vôùi gia ñình, tuy nhieân vì hôi khoù khaên trong vieäc noùi chuyeän vôùi BS gia ñình (moät BS nguôøi Caucasian) cho neân beänh nhaân chaàn chöø, maõi ñeán ñaàu thaùng 3/2002 , khi haïch ñaõ khaù lôn, môùi quyeát ñònh ñeán thaêm BS gia ñình. BS naøy sau khi khaùm, chuyeån ngay sang BS giaûi phaãu. Beänh nhaân hoaøn toaøn khoâng coù trieäu chöùng gì: khoâng ñau ôû coå hoïng, khoâng ho, khoâng soát, khoâng suït caân. Beänh nhaân ñang keát hoân, caùc con ñaõ truôûng thaønh. Beänh nhaân vaø gia ñình di daân sang Hoa Kyø thaùng 1/1992. Boá meï beänh nhaân ñeàu ñaõ maát. Cha maát khoaûng giöaõ 50 tuoåi (ruôïu); meï maát 79 tuoåi ("giaø"). Beänh nhaân laø con thöù 5 trong moät gia ñình coù 8 anh chò em; coù 4 anh chò em ñaõ cheát khi coøn raát nhoû tuoåi ; caùc anh chò em coøn laïi ñeàu khoeû maïnh. Khoâng coù beänh söû ung thö, lao, beänh di truyeàn, beänh maùu, ñaùi ñuôøng, buôùu coå, suyeãn ... trong gia ñình . Khi ôû VN, beänh nhaân ôû trong quaân ñoäi caû thaûy 13 naêm cho ñeán 1975, vaøo traïi tuø caûi taïo cho ñeán 1981. Trong thôøi ôû Hoa Kyø, beänh nhaân laøm thôï haøn trong moät haõng ñieän töû, vaø khoâng coù lòch söû tieáp xuùc vôùi hoaù chaát. Beänh nhaân khoâng uoáng ruôïu, nhöng coù huùt thuoác cho ñeán 1989 thì ngöng, luùc ñaàu 1-2 ñieáu moät ngaøy, luùc cuoái 1 goùi /ngaøy; caû thaûy khoaûng 10-

12 goùi-naêm (pack-year). Beänh söû noäi thuông: beänh nhaân uoáng Beta blocker töø 1991 (taêng aùp huyeát). Khoâng coù lòch söû dò öùng (no known allergies). Khaùm beänh nhaân cho thaáy veát moå ôû coå beân traùi ñaõ laønh, ôû coå beân phaûi, ôû tam giaùc truôùc coå (anterior cervical area) coù moät haïch lôùn khoaûng 1.5 - 2.0 cm. coù vaøi haïch coå nhoû hôn ôû caû hai beân. Khoâng thaáy haïch ôû chung quanh tai (periauricular), ñaèng sau coå (posterior cervical), treân xuông quai xanh ( supraclavicular lymphadenopathy) naùch (axillary), haùng (inguinal), khuyûu tay (trochlear), nhuôïng chaân (popliteal). Gan vaø tyø taïng khoâng söng lôùn (no hepato-splenomegaly). Da vaø coå hoïng khoâng coù bì baát thuôøng, haïch haïnh nhaân (tonsils) khoâng söng. Nghe phoåi vaø tim: khoâng coù gì ñaùng keå (unremarkable). Beänh nhaân ñuôïc göûi ngay sang chuyeân vieân tai muõi hoïng ñeå soi (endoscopic examination): taát caû bình thuôøng. Soi ñuôøng tieâu hoaù (EGDEsophagoGastricDuodenoscopy) : bình thuôøng. Ngaøy 13/th4/2002: CAT scan ñaàu, ngöïc, buïng, chaäu (pelvis) : khoâng coù gì ñaùng keå. PET (Positron Emission Tomography) scan ngaøy 23 thaùng 4, 2002 cho thaáy tuï ôû coå beân phaûi (increase accumulation in the region of the R neck) . Caùc thöû nghieäm: ñeám maùu toaøn dieän (complete blood count - CBC), cô naêng gan (liver function tests), thaän (BUN/Creatinine) taát caû bình thuôøng. Baïn seõ chöaõ nhö theá naøo ? Lôøi baøn: Ñaây laø moät truôøng hôïp "ung thö chuyeån di khoâng bieát nguoàn goác" (Ung thö khoâng roõ nguoàn UTKRN) ("tumor of unknown primary", hoaëc "Cancer of unknown primary site" (ô? Hoa Kyø, caùc oncologists thuôøng noùi taét : "unknown primary"-

78 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Trình Baày Moät Truôøng Hôïp Beänh - MEDICAL NEWS

tieáng Phaùp: "Cancers d'origine indeùtermineùe" ). UTKRN chieám khoaûng 2% cuaû taát caû caùc ung thö (Tham khaûo -TK 1). Chöùng naøy chæ ñuôïc moâ taû roõ reät töø ñaàu naêm 1980 trôû ñi (TK 2) Trong moät taøi lieäu goàm 220 beänh nhaân, chæ coù 32 beänh nhaân tìm ra ñuôïc nguoàn goác cuaû ung thö ( TK 3). Duø coù coá gaéng ñi tìm nguoàn ung thö caån thaän ñeán theá naøo chaêng nöaõ, chæ tìm thaáy nguoàn goác trong 13 % truôøng hôïp (TK 2, trang 1562). Ngay caû ñeán giaûi phaãu töû thi, trong 22% truôøng hôïp cuõng khoâng tìm ra nguoàn goác (TK 2, trang 1562). Ñieåm quan thieát laø xem xeùt caån thaän döôùi kính hieån vi. Trong truôøng hôïp naøy, ñaây laø moät ung thö carcinoma, teá baøo lôùn, vaø coù choã thaáy gioáng teá baøo vaåy. Vôùi beänh lyù moâ hoïc (histopathology) nhö vaäy thì chæ coù vaøi nôi xuaát phaùt: ung thö phoåi, muõi hoïng, thöïc quaûn... Trong truôøng hôïp naøy, vì theá ta seõ chöaõ trò theo döï ñoaùn raèng ung thö coù leõ töø phoåi hoaëc töø hoïng (head and neck tumor) vaø seõ duøng caùc hoaù chaát coù hieäu quaû cho caùc loaïi ung thö naøy cuøng vôùi trò lieäu baèng tia X (radiotherapy). Hieän nay caùc hoaù chaát coù hieäu quaû nhaát trong truôøng hôïp naøy laø Taxol, CarboPlatin. Toâi ñaõ baét ñaàu chöaõ ngay baèng hôïp chaát : Taxol 175 mg/M2, CarboPlatin AUC 6 - (AUC: area under the curve), Ifosfamide 1000 mg/M2 cuøng vôùi Mesna (ñaây laø hôïp chaát cho ung thö ñaàu vaø coå : thanh quaûn - laryngeal) (TK 4). Hôïp chaát (combination) naøy coù lôïi vì hai chaát Taxol vaø CarboPlatin raát hieäu quaû trong ung thö phoåi . Ñaëc bieät

CarboPlatin (hoaëc CisPlatinum) coù hieäu öùng toát trong Ung thö loaïi teá baøo vaåy. Beänh nhaân naøy cuõng ñuôïc göûi ñi chöaõ baèng tia X (2 chu kyø hoaù hoïc trò lieäu sau ñoù baét ñaàu chöaõ baèng Tia X). Sau khi beänh nhaân chöaõ xong tia X thì hoaù hoïc trò lieäu chu kyø (cycle, course) thöù 3 phaûi hoaõn laïi vì beänh nhaân bò lôû naëng ôû cuoáng hoïng vaø naám moïc khieán beänh nhaân khoâng aên ñuôïc (chæ nuoát ñuôïc duôùi 500 calories/ngaøy). Vieäc naøy khieán phaûi göûi beänh nhaân trôû laïi giaûi phaãu ñeå ñuïc loã vaøo bao töû (Gastric tube) ñeå nuoâi, hieän nay vôùi luôïng laø 2000 calories/ngaøy. Hoâm nay beänh nhaân vöaø xong chu kyø thöù 3 veà trò lieäu hoaù chaát (moãi chu kyø caùch nhau khoaûng 4 tuaàn - khoâng keå thôøi gian chöaõ Tia X) . Döï haäu trong UTKRN raát keùm, ñieåm giöaõ soáng soùt (median survival) chæ khoaûng 9 thaùng (TK 5). Ñieåm hieän nay khoâng roõ laø hoaù hoïc trò lieäu seõ keùo daøi bao laâu (toâi thuôøng cho 1 naêm) - 12 chu kyø) vaø nhieäm vuï cuaû giaûi phaãu sau thôøi gian aáy (coù neân trôû laïi moå ôû coå, vaø loïc boû taát caû caùc haïch ôû coå) (radical neck dissection) khoâng. Vieäc naøy thuôøng ñuôïc laøm ôû ung thö ñaàu vaø coå (head and neck) nhö ung thö thanh quaûn (laryngeal). Neáu chæ coù MOÄT haïch ung thö ôû coå thì coù leõ neân laøm (TK 6) , nhöng truôøng hôïp naøy CAT scan vaø khaùm beänh nhaân cho thaáy ung thö ôû caû hai beân coå.

References:

1) F. Greco & J. Hainsworth: Cancer of unknown Primary site, trang 2537 trong quyeån V.T. DeVita: "Cancer: principles and pracitce of oncology", 2001, 3235 trang. 2) D. Casciato: Metastasis of unknown origin, trang 1556 trong quyeån: Haskel: "Cancer Treatment", 2001, 1682 trang. 3) Saùch ñaõ daãn: DeVita, trang 2548. 4) Shin et al: Jnl clin. Oncol 16: 1325-1330, 1998. 5) Lortholary A et al: "Cancers d'origine indeterminee: aø propos de 311 cas" Bulletin du Cancer 01 Jun-2001 88(6): 619-27. 6) Zurr CL et al: "Diagnosis and treatment of isolated neck metastases of adenocarcinomas" Eur J Surg Oncol 2002 Mar: 28(2): 147-52.

Vietnamese Pharmaceutical Journal No.5- 79

Sieâ u Vi Cuù m H 5 N 1

Tieán Só Nguyeãn D. Thaùi, Ph.D.

Thaân göûi quí thaân höõu DDYK:

S

ieâu vi cuùm H5N1 hoaønh haønh ôû Vieät Nam vaø nhieàu nöôùc Chaâu AÙ ñang laø moät ñeà taøi thôøi söï vaø khoa hoïc noùng boûng keå töø ñaàu naêm nay. Vieän Pasteur Vieät Nam vöøa thieát laäp ñöôïc trình töï (sequence hay coøn ñöôïc goïi laø giaûi maõ) cuûa gene H5N1 vaø thaønh quaû naøy coù taàm quan troïng ñang ñöôïc phoå bieán roäng raõi trong nöôùc vaø ñöôïc söï löu taâm ôû nhieàu nôi. Nhaân dòp naøy, DDYK phoûng vaán TS Nguyeãn D. Thaùi veà yù nghóa cuûa keát quaû naøy, ñaëc bieät cho vieäc phaùt trieån sinh hoïc ôû Vieät Nam. TS Nguyeãn D. Thaùi laø moät chuyeân gia veà sinh hoïc phaân töû (SHPT) vaø laø ngöôøi ñöôïc bieát nhieàu trong coäng ñoàng y khoa Vieät Nam do phaùt hieän gene TIGR, di theå ñaàu tieân cuûa beänh Glaucoma. DDYK: Xin anh Thaùi cho bieát dieãn tieán veà vieäc giaûi maõ gene sieâu vi beänh cuùm H5N1 ôû Vieät Nam vaø taàm möùc quan troïng cuûa vieäc naøy. TS NDT: Ñaàu tuaàn qua vieän Pasteur Vieät Nam cho loan baùo ñaõ giaûi maõø ñöôïc baûn ñoà gene cuûa sieâu vi dòch cuùm H5N1. Keát quaû naøy do TS Cao Baûo Vaân, tröôûng phoøng nghieân cöùu sinh hoïc phaân töû (SHPT) cuûa vieän Pasteur, ñaûm nhieäm. Maãu phaåm sieâu vi H5N1 ñöôïc laáy töø beänh nhaân ôû Vieät Nam. Moät soá kyõ thuaät SHPT ñöôïc thöïc hieän treân maãu phaåm naøy goàm ly trích gene, vaø vì soá löôïng virus thöôøng raát nhoû neân caàn khuyeách ñaïi DNA cuûa gene baèng phaûn öùng PCR (polymerase chain reaction), vaø sau ñoù laäp trình töï baèng maùy giaûi maõ (sequencer). Moài cuûa phaûn öùng PCR ñöôïc söï hôïp taùc töø Nhaät Baûn. Duø trình töï cuûa sieâu vi H5N1 ñaõ ñöôïc bieát töø laâu

vaø do nhieàu nhoùm, tuy nhieân vieäc thieát laäp trình töï sieâu vi naøy töø maãu phaåm beänh nhaân Vieät Nam vaãn caàn thieát vì caùc chuûng sieâu vi cuùm, goàm H5N1, thöôøng taùi toå hôïp; coù nghóa laø caùc trình töï cuûa sieâu vì coù theå thay ñoåi theo töøng muøa vaø theo töøng vuøng. Trình töï H5N1 do TS Cao Baûo Vaân thieát laäp töø beänh nhaân ngöôøi Vieät ñaõ cho thaáy coù söï khaùc bieät naøy. Vieäc phaân tích söï khaùc bieät ñoù seõ coù nhöõng öùng duïng quan troïng cho vieäc chuaån ñoaùn cuõng nhö choïn löïa trong töông lai vaccine chuyeân bieät hôn cho beänh cuùm do sieâu vi H5N1 ôû Vieät Nam. Theo ñoù, keát quaû treân coù taàm möùc quan troïng ñeå ñaùp öùng nhu caàu y teá cuûa Vieät Nam, ñaëc bieät tröôùc bieán coá beänh dòch cuùm gaø hieän nay. Ngoaøi ra, keát quaû naøy coøn mang laïi uy tín cho ngaønh SHPT ôû Vieät Nam. Vieäc giaûi maõ H5N1 ñöôïc hoaøn thaønh trong 4 ngaøy, coù nghóa laø Vieät Nam hieän ñaõ coù trang thieát bò caên baûn vaø moät khaû naêng höõu hieäu ñeå thöïc hieän moät soá nghieân cöùu SHPT. Neáu öùng duïng tieàm naêng naày sôùm hôn, Vieät Nam coù theå ñaõ laø moät trong nhöõng nöôùc ñaàu tieân giaûi maõ gene cho tröôøng hôïp beänh SARS. DDYK: Xin anh cho bieát giaù trò kyõ thuaät cuûa vieäc giaûi maõ vaø töông lai cuûa kyõ thuaät naøy ñoái vôùi nghieân cöùu ôû Vieät Nam. TS NDT: Giaûi maõ laø moät kyõ thuaät caên baûn cuûa SHPT. Vieäc giaûi maõ giuùp cho nhöõng ngöôøi laøm nghieân cöùu sinh hoïc xaùc ñònh vaø phaân loaïi ñöôïc hình daïng cuûa gene. Nhieàu ngöôøi nghó raèng vôùi söï giaûi maõ cuûa Boä Gene Ngöôøi coâng boá naêm 2001, thì vieäc giaûi maõ gene khoâng coøn laø nhu caàu caàn thieát. Thöïc ra, cuõng nhö trong xaõ hoäi con ngöôøi, boä gene coù nhieàu loaïi vaø nhieàu hình daùng, vaø nhöõng hình daùng naøy cuõng coù theå thay ñoåi theo chuûng toäc, moâi tröôøng vaø thôøi gian. Cho neân kyõ thuaät giaûi maõ luoân laø phaàn troïng yeáu cuûa moät phoøng thí nghieäm SHPT. Ngaøy nay vieäc giaûi maõ thöôøng ñöôïc thöïc hieän raát nhanh, khoaûng vaøi chuïc ngaøn trình töï DNA (nucleotide sequence) baèng caùc maùy gia toác. Vieäc giaûi maõ cuõng coù theå thöïc hieän treân moät soá lôùn vaøi chuïc ngaøn daáu aán gene (gene marker) baèng phöông phaùp gene chips vaø kyõ thuaät SNPs (single nucleotide polymorphisms). Treân thöïc teá, vieäc giaûi maõ gene ngoaøi tin töùc veà hình daïng cuûa gene, ngöôøi laøm nghieân cöùu kinh nghieäm, coøn coù theå bieát ñöôïc raát nhieàu veà nhöõng ñaëc tính khaùc cuûa gene nhö chöùc naêng, beänh lyù vaø trò lieäu.

80 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Sieâu vi cuùm H5N1 - MEDICAL NEWS

Tuy chöa ñöôïc chöùng mình moät caùch heä thoáng, coù nhieàu döõ kieän di truyeàn vaø sinh hoïc cho thaáy daân toäc Vieät Nam laø moät chuûng toäc khaù thuaàn chuûng. Ñieàu naøy coù nghóa laø ngöôøi Vieät chuùng ta coù nhöõng thay ñoåi veà caáu truùc moät soá gene so vôùi nhöõng chuûng toäc khaùc. Theo nghóa ñoù, kyõ thuaät giaûi maõ seõ coù moät giaù trí ñaëc bieät ñeå giuùp tìm hieåu nhöõng khaùc bieát naøy. Ví duï, phaàn lôùn ñoät bieán cuûa caùc gene beänh di truyeàn ñöôïc tìm thaáy ôû caùc nöôùc Taây Phöông, vaø caùc ñoät bieán naøy chæ coù taàng soá (incidence) raát thaáp hoaëc khoâng coù ôû ngöôøi Vieät. Cho neân, muoán xöû duïng höõu hieäu caùc gene naøy ñeå chuaån ñoaùn, chuùng ta caàn tìm kieám ñoät bieán môùi trong chuûng toäc ngöôøi Vieät Nam. Ñieàu naøy caàn söï öùng duïng cuûa kyõ thuaät giaûi maõ, hoaëc nhöõng kyõ thuaät töôïng töï nhö gene chips, SNPs v.v. DDYK: Xin anh Thaùi cho bieát kinh nghieäm sinh hoaït khoa hoïc cuûa anh ôû Vieät Nam vaø anh thaåm ñònh khaû naêng Sinh Hoïc Phaân Töû cuûa Vieät Nam hieän nay ra sao. TS NDT: Ngöôøi Vieät chuùng ta coù hai baûn tính caàn thieát cho vieäc phaùt trieån khoa hoïc ñoù laø söï thoâng minh vaø loøng caàu tieán. Nhôø hai ñöùc tình naøy maø trong nhöõng naêm qua nhöõng ngöôøi laøm nghieân cöùu sinh hoïc ôû Vieät Nam ñaõ khaéc phuïc ñöôïc nhöõng khoù khaên vaø ñaït ñöôïc moät soá thaønh quaû toát ñeïp. Tröôùc thaäp nieân 1990 ôû Vieät Nam, boä moân sinh hoïc noùi chung ít ñöôïc löu taâm vaø SHPT môùi chæ laø khaùi nieäm ôû moät soá tröôøng ñaïi hoïc vaø cô sôû nghieân cöùu. Song song vôùi vieäc môû cöûa veà phaùt trieån kinh teá, vieäc tieáp nhaän vaø giao löu khoa hoïc ñaõ ñöôïc roäng raõi tieáp nhaän töø nhöõng nöôùc kyõ ngheä. Töø ñoù boä moân SHPT ñöôïc phaùt ñoäng ôû nhöõng cô quan giaùo duïc ñaàu naõo mieàn Nam nhö Tröôøng Ñaò Hoïc Y Döôïc TP HCM, beänh vieän Chôï Raãy, vieän Pasteur...vaø ôû mieàn Baéc nhö Vieän Nghieân Cöùu Sinh Hoïc Quoác Gia, beänh vieän Baïch Mai, Vieän Veä Sinh Dòch Teã, Vieän Nghieân Cöùu Nhieät Ñôùi vaø Noâng Nghieäp, Vieän Ñaò Hoïc Baùch Khoa, Trung Taâm Coâng Ngheä Cao Hoaø Laïc....Vieäc caáp thôøi giaûi maõ gene H5N1 cuûa dòch cuùm gaø phaùt hieän ôû Vieät Nam laø moät thaønh quaû raát khích leä vaø caàn thieát. Ngoaøi vieän Pasteur,

nhieàu nhöõng cô quan neâu treân cuõng coù khaû naêng giaûi maõ caùc gene. Khoâng nhö caùc nöôùc khaùc maø chuùng toâi coäng taùc ôû AÙ Chaâu, ñaõ coù nhieàu khoù khaên trong vieäc sinh hoaït SHPT ôû Vieät Nam vì thoâng tin kyõ thuaät vaø tieáp lieäu trong gia ñoaïn ñaàu raát haïn heïp. Khoaûng caùch naøy ñaõ ñöôïc ruùt ngaén raát nhieàu trong vaøi naêm vöøa qua vaø hieän nay caùc sinh hoaït quoác teá ñaõ mang laïi nhöõng kyõ thuaät tieán boä, vaø caùc saûn phaåm sinh hoïc ñaõ ñöôïc thöông maïi hoùa bôûi caùc haõng nöôùc ngoaøi vaø coù caû trong nöôùc saûn xuaát. Ñaëc bieät kyõ thuaät ñôn giaûn vaø höõu dung nhö PCR ñöôïc phoå bieán roäng raõi tôùi caùc tænh thò nhoû ñeå duøng cho vieäc chuaån ñoaùn dich teã vaø beänh lyù. Caùc chuaån ñoaùn beänh lyù ôû Viet Nam nhö soát reùt, lao, vieâm gan, thalassemia, AIDS, SARS....ñaõ ñöôïc thöïc hieän nhôø kyõ thuaät naøy. Trong thaäp nieân qua, caùc nhaø nghieân cöùu sinh hoïc Vieät Nam ñaõ chöùng minh cho thaáy hoï coù theå haáp thu vaø öùng dung kyõ thuaät SHPT cho moät soá vaán ñeà veà y teá, canh noâng vaø moâi tröôøng ôû Vieät Nam. Tuy nhieân ngaønh SHPT tôùi nay vaãn chöa ñöôïc söï löu taâm vaø yeåm trôï caàn thieát cuûa chính phuû Vieät Nam nhö ñaõ daønh cho nhöõng ngaønh coâng ngheä thoâng tin, ñieän töû. Ñaây laø moät thöû thaùch môùi ñoøi hoûi caùc nhaø nghieân cöùu sinh hoïc Vieät Nam noã löïc nhieàu hôn nöõa. Hy voïng raèng söï phaùt trieån kyõ thuaät sinh hoïc hieän nay nhieàu nôi ôû Vieät Nam, vaø nhöõng thaønh tích nhö vieäc giaûi maõ sieâu vi cuùm H5N1 vöøa qua, seõ mang laïi cho ngaønh nghieân cöùu sinh hoïc Vieät Nam nhieàu söï yeåm trôï vaø tieán boá caàn thieát. Vôùi tieàm naêng sinh hoïc cuûa Vieät Nam, SHPT seõ mang laïi nhöõng giaù trò lôùn lao veà y teá vaø kinh teá khi ñöôïc khai trieån cao ñoä. DDYK: Xin caûm ôn anh Thaùi vaø mong raèng chuùng ta seõ coù dòp trao ñoåi theâm veà boä moân khoa hoïc raát lyù thuù vaø ñöôïc coi laø haøng ñaàu cuûa theá kyû naøy. TS NDT: Xin caûm ôn DDYK vaø thaân chaøo.

Vietnamese Pharmaceutical Journal No.5- 81

TIN Y DÖÔÏC

Vioxx Recall

Giang N Trinh, R.Ph., D.Ph.

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Return of Vioxx

n September, 30, 2004, Merck & Co., Inc. announced a voluntary worldwide withdrawal of Vioxx (rofecoxib), its arthritis and acute pain medication. The company's decision is based on new, three-year data from a prospective, randomized, placebo-controlled clinical trial, the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial, which indicates that rofecoxib increases the incidence of acute myocardial infarction and sudden cardiac death. An article written in June 2000 on Cox 2 Inhibitors, "In search of Safer NSAIDS: Are Selective Cox-2 Inhibitors the answer?" was published in The Vietnamese Pharmaceutical Journal, Vol 1, No 1, April 2001. At that time, the results of two studies of gastrointestinal outcomes were just reported: the Vioxx Gastrointestinal Outcomes Research (VIGOR) and the Celecoxib Long Term Arthritis Safety Study (CLASS). The cardiovascular risks of these drugs were not mentioned in the article. Results of the VIGOR study, released in March 2000, demonstrated that the risk of gastrointestinal toxicity with Vioxx was less than with naproxen, but indicated an increased risk of cardiovascular events versus naproxen In this trial, the rate of serious gastrointestinal events among those receiving rofecoxib was half that among those receiving a traditional NSAID, naproxen 2 percent, as compared with 4 percent. However, a five-fold increase in the incidence of myocardial infarction was observed. Although this increase was a source of concern, it was argued that the small number of events reflected the play of chance or that naproxen was actually cardioprotective. However, epidemiologic studies of possible cardioprotection afforded by naproxen have proved inconclusive. In the CLASS trial, celecoxib was compared with ibuprofen or diclofenac, celecoxib appeared to have a more favorable gastrointestinal-side-effect profile, and no increase in cardiovascular risk was revealed. The APPROVe trial, which is being stopped, was designed to evaluate the efficacy of Vioxx 25 mg in preventing recurrence of colorectal polyps in patients with a history of col82 - Taäp San Chuyeân Nghieäp Döôïc Khoa

O

orectal adenomas. In this study, there was an increased relative risk for confirmed cardiovascular events, such as heart attack and stroke, beginning after 18 months of treatment in the patients taking Vioxx compared to those taking placebo. The results for the first 18 months of the APPROVe study did not show any increased risk of confirmed cardiovascular events on Vioxx, and in this respect, are similar to the results of two placebo-controlled studies described in the current U.S. labeling for Vioxx. Merck & Co has also mentioned that the results of clinical studies with one molecule in a given class are not necessarily applicable to others in the class. Therefore, the clinical significance of the APPROVe trial, , for the long-term use of other drugs in this class, consisting of COX-2 specific inhibitors and other NSAIDs, is unknown. Just when the Vioxx recall was thought to be permanent, on February 18, 2005, a Food and Drug Administration expert advisory panel narrowly voted in favor of allowing the arthritis painkiller Vioxx back on the market under strict conditions. Pharmaceutical manufacturer Merck & Co. said on the same day it could put its painkiller Vioxx back on the market if a federal advisory panel concludes the benefits of the drugs outweigh an increased risk of heart attacks and strokes. Merck's announcement came as an advisory committee of the Food and Drug Administration considered the risks associated with taking Cox II Selective Non-Steroidal AntiInflammatory Drugs (NSAIDs), which also include the painkillers Celebrex and Bextra. Back to the question "In search of Safer NSAIDS: Are Selective Cox-2 Inhibitors the answer?". Given what is now known, it would seem that selective inhibitors of COX 2 remain a rational choice for patients with a low cardiovascular risk who have had serious gastrointestinal events, especially while taking traditional NSAIDS. It would also seem prudent to avoid coxibs in patients who have cardiovascular disease or who are at risk for it.

MEDICAL NEWS

Vaøi Suy nghó veà Thuoác môùi

Ds Leâ-vaên-Nhaân

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gaøy 30.09.2004 coâng ty Merck thoâng baùo thu hoài thuoác rofecoxib vôùi teân bieät döôïc VIOXX. Doanh thu cuûa thuoác naøy cho ñaïi coâng ty döôïc phaåm laø 2.25 tyû Myõ kim moãi naêm, neân khoâng phaûi töï nhieân coâng ty töï thu hoài, maø phaûi do aùp löïc cuûa FDA vaø nhöõng chöùng côù thuoác gaây ñoäc haïi cho ngöôøi tieâu duøng. Neáu tieáp tuïc coâng ty seõ phaûi ñoái phoù vôùi nhöõng vuï kieän maø toán phí coù theå leân quaù möùc doanh thu vaø aûnh höôûng ñeán uy tín cuûa coâng ty.Chuùng ta cuõng nhôù laïi laø sau khi Vioxx ra thò tröôøng, ñaõ coù nhöõng nghieân cöùu vaø yù kieán thuoác naøy haïi tim, nhöng ñeàu bò nhaø saûn xuaát baùc boû. Luùc ñaàu, thuoác choáng vieâm khoâng steroid ñöôïc xem laø öùc cheá khoâng choïn loïc cyclo-oxygenase ôû caû 2 thuï theå COX1 vaø COX-2. COX-2 chæ xuaát hieän khi ñaõ bò vieâm, trong khi COX-1 coøn coù tính chaát baûo veä cho caùc moâ nhö moâ daï daøy ruoät. Ngöôøi ta phaân bieät thuoác choáng vieâm khoâng steroid tuøy theo thuoác naøy coù aùi löïc nhieàu hay ít vôùi COX-2 so vôùi COX-1 nhö vieân meloxicam ít haïi daï daøy do tyû soá aùi löïc COX-2/COX-1 cao. Nhöng sau khi celecoxib ( Celebrex ) ra ñôøi, caùc nhaø saûn xuaát baûo -coxib laø moät nhoùm hoaøn toaøn khaùc vôùi nhoùm choáng vieâm khoâng steroid vôùi teân laø -xicam, neân khoâng theâ duøng baát cöù thuoác naøo thuoäc nhoùm -xicam thay theá nhoùm -coxib ñöôïc. Ngaøy 19.11.04 tôø baùo Science ñaêng baøi khaûo cöùu cuûa nhoùm nghieân cöùu ñaïi hoïc y khoa Pensylvania caàm ñaàu bôûi baùc só Garrett Fitzgerald, cho thaáy duøng rofecoxib ñeå ngöøa u böôùu ruoät taêng gaáp ñoâi nguy cô nhoài maùu cô tim vaø ñoät quî. Baùc só Fitzgerald baûo 1 acid beùo ñöôïc taïo ra qua trung gian cyclo-oxygenase-2 hay COX-2, baûo veä ñoäng maïch khoâng bò cöùng. Khi duøng thuoác ngaên chaën COX-2, acid naøy khoâng saûn xuaát ñuû , tieán trình taïo xô vöõa ñoäng maïch coù theå xaûy ra. Khoâng nhöõng rofecoxib maø 1 thuoác môùi khaùc laø Bextra cuõng taùc duïng nhö vaäy, neân ngöôøi ta nghi ngôø taùc duïng laøm cöùng ñoäng maïch ñöa ñeán nguy cô tim maïch laø phaûn öùng nghòch cho toaøn nhoùm -coxib. Moät ñieàu ñaùng chuù yù khaùc laø estrogen giuùp COX-2 hoaït ñoäng, neân phuï nöõ treû ít bò beänh tim hôn phuï nöõ sau khi taét kinh. Estrogen cuõng giuùp COX-2 taïo ra PG12, moät acid beùo choáng hoaït ñoäng cuûa tieåu caàu, neân seõ giaûm taùc duïng sinh huyeát khoái taïo ra nguy cô tim maïch. Merck laø moät coâng ty döôïc phaåm noåi tieáng an toaøn veà maët kinh doanh, vaø ñaây laø laàn ñaàu tieân coâng ty naøy phaûi thu hoài

thuoác, aûnh höôûng ñeán giaù trò coå phieáu. Chuùng toâi cuõng nghi ngôø uy tín cuûa coâng ty naøy quaù maïnh, khieán FDA khoâng ñieàu tra kyõ ngay töø tröôùc khi cho thuoác naøy ra thò tröôøng.Ngoaøi ra, maëc daàu vieân Vioxx 50 mg chæ coù chæ ñònh duøng trong vaøi ngaøy cho phuï nöõ tröôùc khi coù kinh, nhieàu baùc só vaãn muoán duøng lieàu cao Vioxx ñeå trò ñau nhöùc baát chaáp nhaéc nhôû cuûa giôùi döôïc só. Hieän nay chöa coù nghieân cöùu naøo chöùng minh thuoác -coxib coâng hieäu hôn hay maïnh hôn thuoác choáng vieâm khoâng steroid , nhöng do quaûng caùo quaù maïnh, neân baùc só vaãn keâ ñôn -coxib nhieàu hôn laø NSAID. Moät ñieàu ñaùng suy nghó thöù hai laø baûn quyeàn trí tueä cho nhöõng thöù thuoác caàn thieát cho nhaân loaïi ñeå cöùu soáng sinh maïng haøng traêm trieäu ngöôøi taïi caùc quoác gia ngheøo ñoùi ôû Phi chaâu, AÙ chaâu vaø nam Myõ, nhö thuoác choáng HIV/AIDS vaø thuoác choáng soát reùt. HIV/AIDS cuõng ñe doïa söùc khoeû daân caùc nöôùc kyõ ngheä phaùt trieån vaø laøm toán khaù nhieàu ngaân saùch y teá caùc nöôùc naøy, neân coù nhieàu thuoác môùi ra ñôøi. Nhöng beänh soát reùt chæ xaûy ra ôû caùc nöôùc nhieät ñôùi, thuoác soát reùt khoâng baùn ñöôïc ôû caùc nöôùc kyõ ngheä phaùt trieån, neân raát ít phaùt minh thuoác môùi veà beänh naøy maëc daàu kyù sinh ñeà khaùng thuoác ngaøy caønh nhieàu. Chuùng ta cuõng ñaõ bieát ñeán thuoác artemisinin töø caây thanh hao hoa vaøng (artemisia annua) coù nhieàu höùa heïn chöûa ñöôïc beänh soát reùt, ñaõ thöû nghieäm laâm saøng taïi Vieät-nam vaø Trung quoác. Vaán ñeà laø khoâng coù ñuû döôïc lieäu ñeå trích 700 taán chaát naøy haøng naêm cho nhu caàu ñieàu trò treân theá giôùi, vaø hoùa chaát naøy cuõng ñaõ ñöôïc nghieân cöùu toång hôïp, nhöng giaù ñaét moãi lieàu khoaûng 40 USD daân ngheøo caùc nöôùc ñang phaùt trieån khoâng mua noãi. Moät yù kieán môùi phaùt sinh taïi ñaïi hoïc UC Berkeley laø ñöa gene taïo artemisinin trong caây thanh hao vaøo gene khuaån E. coli vaø baét vi khuaån naøy sinh ra artemisinin, gioáng nhö phöông phaùp baøo cheá insulin nhaân taïo. Vaán ñeà ñaët ra laø gene artemisinin ñaõ ñöôïc khaùm phaù tröôùc ñaây vaø ñaõ coù moân baøi saùng cheá, neáu mua baûn quyeàn thì thuoác seõ quaù ñaét. Do ñoù nhoùm nghieân cöùu ñaõ xoay qua moät höôùng khaùc, laø mua nhöõng maûnh taùch rôøi cuûa artemisinin vôùi giaù reû hôn nhieàu, roài duøng phöông phaùp khueách ñaïi PCR (polymerase chain reaction) taïm dòch laø chuoãi phaûn öùng polymerase. Hoï ñaõ may maén taïo ñöôïc gene toång hôïp saûn xuaát artemisinin coøn toát hôn gene goác trong thieân nhieân 142 laàn.

Vietnamese Pharmaceutical Journal No.5 - 83

TIN Y DÖÔÏC - Vaøi suy nghó veà thuoác môùi

Böôùc keá tieáp laø laøm sao ñöa ñöôïc gene naøy vaøo plasmid cuûa vi khuaån. Hoï ñaõ thaønh coâng trong yù ñònh naøy vaø taêng khaû naêng saûn xuaát artemisinin theâm 30 laàn nöõa. Ñieàu ñaùng ngaïc nhieân laø thay vì duøng artemisinin nhö laø thuoác uoáng choáng soát reùt, thì hoï laïi nghó ñeán vieäc baøo cheá thuoác chuûng, vaø ñang hôïp taùc vôùi 2 coâng ty khaùc ñeå laøm sao haï giaù thaønh vaø thöû nghieäm nhöõng vaán ñeà an toaøn caàn thieát cho döôïc phaåm. Chuùng toâi hoan ngheânh saùng cheá naøy höôùng ñeán daân ngheøo ôû caùc nöôùc nhieät ñôùi. Nhöng ñieàu chuùng ta suy nghó laø nhaø khoa hoïc phaûi ñöôïc baûo veä taùc quyeàn trí tueä nhöõng gì hoï tìm ñöôïc, nhöng trong tröôøng hôïp naøy ñaõ caûn trôû nhöõng saùng cheá khaùc giuùp daân ngheøo. Coù caùch gì vöøa baûo veä taùc quyeàn trí tueä vöøa höôùng tôùi sinh maïng cuûa raát nhieàu ngöôøi treân toaøn theá giôùi khoâng? Vieät-nam coù theå saûn xuaát ñuû artesunat ñeå trò soát reùt, lieäu coù caàn thuoác chuûng baøo cheá baèng kyõ thuaät sinh hoïc khoâng? Ñoù laø caâu hoûi chuùng ta caàn giuùp cho nhöõng ngöôøi laõnh ñaïo y teá Vieät-nam quyeát ñònh.

Hieän nay caùc ñaïi coâng ty döôïc phaåm ñeàu coù maët taïi Vieätnam nhö Sanofi-Aventis, Pfizer, Merck, Glaxo. Vôùi tieàn cuûa doài daøo, hoï dö söùc thuyeát phuïc boä y teá Vieät-nam cho nhaäp nhöõng thöù thuoác khoâng caàn thieát hay coù tieàm naêng gaây ñoäc haïi nhö tröôøng hôïp VIOXX. Muoán giuùp cho Vieät-nam traùnh ñöôïc phí phaïm ngoaïi teä vaø nhöõng nguy hieåm keå treân, ngaønh thoâng tin döôïc phaåm phaûi maïnh ñeå giöõ ñöôïc tính voâ tö. Nhöõng ngöôøi ñang laøm taïi caùc beänh vieän ôû Hoa-kyø, Canada, Phaùp, UÙc neân cung caáp thoâng tin ñeàu ñaën cho Dieãn ñaøn döôïc khoa, giuùp caùc ñoàng nghieäp taïi VN coù ñuû thoâng tin baùo caùo vôùi caùc baùc só, nhaát laø khi coù nghi ngôø veà tính an toaøn cuûa thuoác. Chuùng toâi chôø söï ñaùp öùng cuûa quyù vi. Vieát taïi Saigon ngaøy 28.11.04

84 - Taäp San Chuyeân Nghieäp Döôïc Khoa

ARTICLES REVIEW

Phaàn goùp yù

Beänh thieáu maùu do thieáu folate vaø B12 ôû ngöôøi Vieät-nam

DS Leâ Vaên Nhaân

Lôøi noùi ñaàu:

Baùc só Traàn-maïnh-Ngoâ ñaõ ñöa leân DDDK baûng toùm taét baøi naøy ñaõ ñaêng treân tôø Southern Medical Journal naêm 2000, nhöng coù leõ ít ai chuù yù vì phaàn chuùng ta hoïc hoûi ñöôïc laø phaàn bieän luaän (discussion) khoâng coù trong baøi toùm taét. Baûn dòch tieáng Vieät toaøn baøi ñaõ ñöôïc ñaêng treân soá baùo chuyeân ñeà veà beänh thieáu maùu cuûa hoäi DSVN taïi Hoa-kyø. Chuùng toâi chæ xin trieån khai nhöõng ñieåm hay trong baøi naøy maø thoâi.

thay vì möùc glucose thay ñoåi nhieàu laàn trong ngaøy. Phöông phaùp ño folate trong hoàng caàu coù theå tìm trong baøi baùo cuûa Hoffbrandt AV, Newcombe BFA, Mollin DL : Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency trong Journal of Clinical Pathology naêm 1966; 19:17-28. 5. Theo saùch vôû, beänh thieáu maùu thalassemia khoâng coù thuoác chöûa, neáu naëng quaù chæ coù theå truyeàn maùu. Nhöng vì beänh thieáu maùu cuûa ngöôøi Vieät-nam do nhieàu nguyeân nhaân khaùc nhau, neân vaãn coù hy voïng giuùp cho ngöôøi beänh, söûa chöõa thieáu maùu do saét, do folate hay B12 neáu coù, cuõng ñaõ caûi thieän ñöôïc tình traïng beänh nhaân raát nhieàu vaø ñaây laø ñieåm tích cöïc cuûa baøi naøy. 6. Vì phaûi laøm screening cho ngöôøi beänh thieáu maùu VN xem coù thieáu folate hay B12 khoâng, baùc só coù theå yeâu caàu ño möùc folate vaø B12 maëc daàu MCV bình thöôøng. Ñaây laø thoâng tin caùc baùc só neân duøng ñeå giaûi thích cho haõng baûo hieåm khi coù thaéc maéc vaø giuùp chuùng ta hieåu ñöôïc lyù do baùc só muoán ño folate vaø B12. Chuùng toâi cuõng ñöa ra moät tröôøng hôïp moät nöõ döôïc só Vieätnam ôû tuoåi maõn kinh bò thalassemia vaø thieáu maùu ôû möùc ñoä baùo ñoäng vì hemoglobin ñaâu khoaûng 8g/dl vaø HCT xaáp xæ 30. Baø ta bò thieáu saét keå caû ferritin, nhöng ngöôøi beänh laø döôïc só, khoâng theå baûo baø ta khoâng bieát aên uoáng. Baùc só chuyeân khoa veà huyeát hoïc ñaõ chuyeån ngöôøi beänh cho baùc só chuyeân moân veà phuï khoa vaø khaùm phaù ra baø naøy bò rong kinh do thieáu estrogen. Sau khi duøng moät loaïi thuoác ngöøa thai vôùi möùc estrogen thaáp (duøng ngoaøi chæ ñònh khoâng phaûi ñeå ngöøa thai) chöùng xuaát huyeát chaám döùt vaø hemoglobin taêng leân khoaûng 12g/dl vaø möùc saét trôû laïi bình thöôøng. Chuùng toâi hy voïng baøi naøy giuùp caùc döôïc só cho moät lôøi khuyeân tích cöïc cho caùc beänh nhaân khi hoï ñöôïc baùc só thoâng baùo coù beänh thalassemia vì vaãn coù hy voïng.

Nhöõng yù chính trong baøi:

Döïa treân 59 maãu maùu taïi phoøng maïch, taùc giaû ñaõ ñöa ra nhöõng nhaän xeùt sau : 1. Beänh thieáu maùu cuûa ngöôøi Vieät-nam khoâng ñôn thuaàn, maø laø moät hoãn hôïp cuûa beänh thieáu maùu do sai laïc caáu taïo huyeát saéc toá nhö beänh thalassemia, vaø thieáu maùu do thieáu saét, thieáu folate hay thieáu sinh toá B12. 2. Chính söï hoãn hôïp beänh naøy ñaõ laøm cho keát quaû xeùt nghieäm bò sai laïc vì caùc yeáu toá boå khuyeát cho nhau. Thoâng thöôøng khi thieáu folate hay B12 MCV phaûi cao ñeå chöùng toû coù hoàng caàu lôùn hôn binh thöôøng (macrocytosis), nhöng caùc maãu maùu cuûa ngöôøi Vieät-nam phaàn lôùn coù MCV bình thöôøng. 3. Taùc giaû ñeà nghò neân phoái hôïp MCV vaø RDW (Red Cell distribution Width) ñeå phaân loaïi caùc beänh thieáu maùu moät caùch chính xaùc hôn. 4. Nhöõng xeùt nghieäm hieän nay thöôøng ño folate trong huyeát thanh (serum folate) chæ phaûn aûnh vieäc tieâu thuï thöùc aên coù folate vaøi ngaøy tröôùc ñoù . Taùc giaû ñeà nghò ño folate beân trong hoàng caàu (red blood cell folate) phaûn aûnh möùc folate trong suoát ñôøi soáng cuûa hoàng caàu töùc khoaûn 120 ngaøy. Quan nieäm naøy cuõng töông töï nhö khi ta ño hemoglobin A1C phaûn aûnh löôïng glucose trong khoaûng 120 ngaøy tröôùc ñoù

Vietnamese Pharmaceutical Journal No.5 - 85

ÑIEÅM BAÙO

BIEÄN LUAÄN - DISCUSSION

Beä n h Thieá u Maù u ôû Beä n h Nhaâ n Vieä t Nam

Baùc só Nguyeãn vaên Ñích

S

au khi doïc baøi giôùi thieäu cuûa Bs Traàn maïnh Ngoâ, caâu hoûi cuûa Bs Traàn Huøng vaø yù kieán cuûa döôïc só Leâ vaên Nhaân, toâi ñaõ tìm ñoïc baøi cuûa baùc só Löông Vinh Quoác Khanh vaø Nguyeãn thi Hoaøng Lan trong Southern Medical Journal vaø coù moät soá yù kieán nhö sau: 1- Qua phaân tích caùc keát quaû xeùt nghieäm veà maùu cuûa 59 beänh nhaân Vieät nam bò thieáu maùu, caùc taùc giaû nhaän thaáy raèng coù theå coù nhieàu nguyeân nhaân gaây thieáu maùu xaûy ra treân cuøng moät ngöôøi beänh khieán phaûi thaän troïng khi giaûi thích keát quaû, thí du. MCV coù theå töông ñoái "thaáp" ôû ngöôøi voán bò thalassemia maø laïi bò thieáu folate, hoaëc "bình thöôøng" ôû ngöôøi thieáu saét nhöng cuõng thieáu cobalamin. 2- Keát luaän veà giaûi thích vaø söû duïng xeùt nghieäm ruùt ra töø söï phaân tích naøy laø ñuùng vaø ñaùng chuù yù, noù cho thaáy tính chaát phöùc taïp cuûa beänh nhaân Vieät nam qua boái caûnh kinh teá xaõ hoäi maø ngöôøi di daân Vieät nam ñaõ traûi qua tröôùc khi sang ñeán Hoa kyø. 3- Vì laø moät hoài cöùu (retrospective study), döïa treân moät soá nhoû beänh nhaân trong moät khoaûng thôøi gian do ñoù khoâng neân toång quaùt hoaù cho taát caû caùc beänh nhaân thieáu maùu Vieät nam. Coù theå vì lyù do thöïc teá moät soá gia ñình thaân thuoäc ñaõ tuï taäp ñònh cö gaàn nhau neân ta coù 11 ngöôøi bò thalassemia trong soá 59 ngöôøi bò thieáu maùu. 4- Trong thöïc teá thieáu maùu vì maát maùu vaãn laø nguyeân nhaân haøng ñaàu, 44 beänh nhaân nöõ so vôùi 11 beänh nhaân nam xaùc ñònh ñieàu ñoù. 5- Baø beänh nhaân maø döôïc só Leâ vaên Nhaân keå voán bò thalassemia heterozygote, ñeán moät giai ñoaïn bò rong kinh, trôû neân coù trieäu chöùng vì chaûy maùu, sau khi kieåm soaùt ñöôïc rong kinh baø laïi trôû veà tình traïng thieáu maùu nheï, vaø sinh hoaït bình thöôøng.

6- Taïi Vieät nam, nguyeân nhaân thieáu maùu thoâng thöôøng nhaát trong soá caùc nguyeân nhaân maát maùu tröôùc vaø sau 1975 laø do giun moùc (ankylostomia). Sau 1975, thieáu maùu do giun moùc laïi caøng trôû neân phoå bieán vaø traàm troïng. Chuùng toâi ñaõ thaáy haøng ngaøn con giun moùc baùm vaøo thaønh ruoät non (duodenum), huùt maùu. Nhieàu beänh nhaân chæ coøn treân döôùi 1 trieäu hoàng caàu, bò giaûm ñaïm (hypoprotidemia) ñeán möùc bò söng phuø, tim lôùn vaø suy tim vì thieáu maùu laâu ngaøy. Cho soå giun vaø aên uoáng ñaày ñuû, beänh nhaân trôû laïi bình thöôøng coù theå khoâng caàn truyeàn maùu (VN khoâng coù nhieàu maùu). Ñòeàu ñaùng buoàn laø khi traû hoï veà moâi tröôøng cuõ, hoï laïi bò laïi ! 7- Tæ leä beänh huyeát saéc toá (thalassemia...) chöa ñöôïc bieát roõ, coù leõ coù nhieàu hôn ôû vuøng bieân giôùi Vieät -Hoa (?) 8- Tröôùc 75 vaø sau 75 chuùng toâi cuõng löu yù ñeán Hoäi chöùng Giaûm Haáp thu (malabsorption syndrome), caùi maø ngaøy xöa ngöôøi Phaùp goïi laø Sprue Tropical (chöùng tieâu chaûy nhieät ñôùi) vaø nhaän thaáy daáu hieäu thieáu folate ôû nhöõng ngöôøi bò beänh ñöôøng ruoät. Hoäi chöùng naøy do nhieàu nguyeân nhaân, coù theå laø do nhieãm truøng, vaø kyù sinh truøng.... 9- Sau chieán tranh, trong thôøi kyø caám vaän, tröôùc khi "ñoåi môùi", tình traïng thieáu dinh döôõng traàm troïng (protein malnutrition), nhieàu treû em sinh thieáu thaùng, nhieàu treû em, caû ngöôøi lôùn ñaõ cheát vì thieáu söùc ñeà khaùng do thieáu dinh döôõng. Ñoïc baùo caùo cuûa baùc só Löông Vinh Quoác Khanh vaø Nguyeãn Thò Hoaøng Lan, ñoái chieáu vôùi nhöõng gì ñaõ xaûy ra, toâi tin raèng nhöõng con soá aáy phaûn aûnh thöïc teá cuûa moät giai ñoaïn. 10- Vì tæ leä nhieãm H.Pylori cao neân ta cuõng coù theå lieân heä thieáu maùu do thieáu cobalamin ôû Vieät nam vôùi vieâm daï daøy maõn tính (gastritis) do H.Pylori.

86 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Special Thanks

to

Amerisource Bergen

Represented by

Tami Vega

Account Manager, Retail Southwest Region

H.D SMITH

Wholesale Drug Co. Barnes Division Represented by

Senior Territory Manager

Stan Shapino

Cardinal Health

Represented by Retail Sales Consultant

Marina Keator

for their continued support of VPhA-USA

Vietnamese Pharmaceutical Journal No.5- 87

Thuaät Ngöõ

I. Prefix/suffix Preùfixe/suffixe:

Hemat- /Hemato- /HemoLeuko-emia -phobia -phile -genesis -lysis -meter -uria Heùmat- /Heùmato- /HeùmoLeucoeùmie phobie phile geneøse lyse meøtre urie Huyeát Traéng, baïch huyeát, trong huyeát,trong maùu sôï, choái,kî öa, deã,aùi sinh tan (huyeát),ly giaûi keá, maùy ño trong nöôùc tieåu

II. Terminology Terminologie:

Anemia Aplastic Anemia Hemolytic Anemia Hypochromic Anemia Iron Deficiency Anemia Macrocytic Anemia Microcytic Anemia Normocytic Anemia Megaloblastic Anemia Parasitic Anemia Pernicious Anemia Drepanocytic Anemia Sickle cell Anemia Aneurysm Angiography Angioplasty Atherosclerosis Betablockers Hematology Heme Hematocyte/Hemocyte Hematoglobulin/Hemoglobin Hematophilia/Hemophilia Hematopoiesis Hemoglobinuria Hemoglobinometer Leukemia Platelet/Thrombocyte Red Blood Cell /Erythrocyte

88 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Aneùmie Aneùmie aplastique Aneùmie heùmolytique Aneùmie hypochrome Aneùmie ferriprive Aneùmie macrocytaire Aneùmie microcytaire Aneùmie normocytaire Aneùmie meùgaloblastique Aneùmie parasitaire Aneùmie pernicieuse Dreùpanocytose/Aneùmie falciforme Aneùmie aø heùmaties falciformes Aneùvrisme Angiographie Angioplastie Atheùroscleùrose Beùtabloquants Heùmatologie Heøme Heùmatocyte/Heùmocyte Heùmatoglobuline/Heùmoglobine Heùmatophilie/Heùmophilie Heùmatopoieøse Heùmoglobinurie Heùmoglobinomeøtre Leuceùmie Plaquette sanguine/Thrombocyte Globules Rouge/EÙrythrocyte

Beänh thieáu maùu - khoâng taùi taïo - tan huyeát - giaûm saéc toá - do thieáu saét - ñaïi baøo hoàng caàu - tieåu baøo hoàng caàu - hoàng caàu bình thöôøng - ñaïi phoâi baøo - do kyù sinh - aùc tính, ñoäc tính - teá baøo hình lieàm - teá baøo hình lieàm phình maïch chuïp hình maïch maùu taïo laäp maïch maùu xô vöõa ñoäng maïch thuoác ngaêën chaën thuï theå beâta huyeát hoïc hem huyeát baøo huyeâát saéc toá beänh öa chaûy maùu sinh huyeát nöôùc tieåu coù huyeát saéc toá maùy ño huyeát saêéc toá ung thö baïch caàu tieåu huyeát caàu hoàng huyeát caàu

DÒCH THUAÄT DANH TÖØ Y DÖÔÏC

White Blood Cell/Leukocyte Stem cell Pluripotent Stem cell Blast cell Thalassemia Vena (pl Venae)/Vein

Globules Blanche/Leucocyte Cellule souche Cellule souche pluripotentielle Cellule blaste Thalasseùmie Veine

baïch huyeát caàu teá baøo maàm teá baøo maàm ña naêng phoâi baøo beänh thieáu maùu coù teá baøo hình lieàm tónh maïch

III. Abbreviation - Abreùviation - Teân taét:

[AIDS] [SIDA] [HIV] [VIH] [RNA] [ARN] [DNA] [ADN] Acquired Immune Deficiency Syndrome Syndrome d'Immuno Deùficience Acquise Human Immunodeficiency Virus Virus de l'Immuno-Deùficience Humaine Ribonucleic Acid Acide Ribonucleùique Deoxyribonucleic Acid Acide Deùsoxyribonucleùique Parameøtres eùrythrocytaires Heùmoglobine Hematocrit Heùmatocrite Red Blood Cell Count Nombre de globules rouges Cell Hemoglobin Concentration Mean Concentration Heùmoglobinique Corpusculaire Moyenne Mean Corpuscular Hemoglobin Teneur Globulaire Moyenne en Heùmoglobine Mean Corpuscular Volume Volume Globulaire Moyen Nom Glossaire Vocabulaire Dictionnaire Terminologie Nomenclature Constante Analyse Meùdicament orphelin Reùsonance Magneùtique Nucleùaire (RMN) teân töï ñieån thuaät ngöõ ngöõ vöïng töï ñieån thuaät ngöõ danh muïc khoâng ñoåi phaân tích thuoác moà coâi (loãi thôøi) coäng höôûng töø haït nhaân MCV MCH CMHC RBC HCT AIDS hay SIDA HIV RNA DNA Thoâng soá hoàng caàu Hb

Erythrocyte Parameters [Hb] [Hb] [HCT] [Hm] [RBC] [GR] [CHCM] [CHCM] [MCH] [TGM] [MCV] [VGM] Name Glossary Vocabulary Dictionary Terminology Word List Constant Analysis Orphan Drug Nuclear Magnetic Resonance (NMR) Hemoglobin

Vietnamese Pharmaceutical Journal No.5 - 89

VAÊN HOÏC NGHEÄ THUAÄT

Thô Song Ngöõ

Muoân Tuoåi Thanh Xuaân

Tuoåi anh muoân tuoåi thanh xuaân Caøng nhieàu ngaøy thaùng caøng say meâ ñôøi Say maây, say ñaát, say trôøi Say möa, say naéng, say ngaøy, say ñeâm Moät ngaøy laø vaïn thieân thu Boán muøa Xuaân Haï Thu Ñoâng naéng hoàng Trôøi xa phæ chí tang boàng Boán phöông Nam Baéc Taây Ñoâng laø nhaø Trôøi cao bieån hoïc meânh mang Luyeän reøn kinh söû ñieåm trang cho ñôøi Xoâng pha ñua söùc tranh taøi Moät tay khai phaù, moät ñaøi hieån danh Queâ höông giöõa buoåi töông phuøng Naøng Xuaân töôi thaém tình thô noàng naøn Yeâu em trôøi ñaát roän raøng Laõng queân thieân haï, meâ say tình hoàng Thaùi-Sôn NDT

Long-lasting Youthfulness

I feel long-lasting youthfulness Intensifying as time goes by Loving clouds, earth and heaven Rain and sun, day and night. Each day equals ten thousand years The sun shines through the four seasons Unabated is the taste for adventure I am at home in all compass directions. Lofty is the sky, world knowledge, immense Honing the tools for study and betterment For healthy competition From early discovery to great results On a happy day visiting the country In spring, nature melts with poetry Loving you in a wonderful world I forget everything, in passion for you. English version by Bình Nhung

March 2005

Xuaân 2005

90 - Taäp San Chuyeân Nghieäp Döôïc Khoa

LITERATURE AND ART

Em vaø Gioù vaø Maây laø moät

Thaû tình theo gioù nuùi Nuùi cuùi ñaàu thaàm laëng Thaû tình theo gioù bieån Rì raøo soùng ñaïi döông Thaû tình leân cao vuùt Mong baét naøng maây traéng Cuøng naøng deät coõi mô Trong vuõ truï trôøi xanh Tình yeâu nhö gioù thoaûng Tình yeâu nhö boùng maây Laøm sao giöõ laïi ñöôïc boùng maây Laøm sao giöõ laïi ñöôïc côn gioù? Ñuoåi theo côn gioù sôùm Baét ñöôïc ngoïn gioù tröa Ñuoåi theo côn gioù chieàu Maëc gioù cuoán hoàn ta Gioù maây vaãn coøn ñoù Gioù maây cho cuoäc tình Gioù maây cuûa muoân kieáp Bao giôø baét ñöôïc nhau...

You, the Wind and Clouds

Along the mountain wind, love is spread In silence, the mountain bends its head Sowing love along the sea wings Rhythmically on the shore, waves break. Blowing love up the sky I hope to catch the white clouds Weaving dreams with you In the firmament so blue. Love is like a soft zephyr The shadow of fleeting clouds How to hold on the evanescence How to keep the breeze? Chasing you early in the day I find you at noon only Searching the afternoon blast You reign on my soul at last. The wind and clouds are still there Companions for love Nurturing sentiments for ever When can we see each other?

Ñaøm Giang

English version by Bình Nhung

Le Vent, Les Nuages et Toi

Sur le vent de la montagne, l'amour s'envole En silence, la montagne courbe son front Sur le vent de la mer Les vagues chantent sur la greøve. Sur le haut du ciel Espeùrant de saisir les nuages blancs Un reâve avec toi, je tisserai Dans le firmament azureù L'amour est leùger comme le zeùphyr Fugace comme l'ombre des nuages Comment garder la peùnombre Comment retenir la brise? Cherchant le vent du matin Je trouve le vent du midi AØ la poursuite du vent du soir Tu reøgnes sur mon aâme, pourquoi? Le vent et les nuages sont encore laø Complices pour notre amour Preùsence eùternelle Quand pourrai-je te voir? Traduit par Binh Nhung

Vietnamese Pharmaceutical Journal No.5 - 91

PHARMACY ACTIVITIES

Vietnamese American Pharmacy Students Association in USC Activities

2005 TET Health Fair

by Vinvia Vu

o celebrate the year of the Rooster, the Vietnamese American Pharmacy Student Association (VAPSA) from the University of Southern California (USC) School of Pharmacy conducted an annual health screening on the 12th and 13th of February 2005 at Garden Grove Park (in the Tet Festival). Our mission is to promote health awareness of different disease states such as diabetes mellitus (DM), hypertension (HTN), osteoporosis, hyperlipidemia, STD and Hepatitis B among the Vietnamese community. VAPSA also intends to establish a meaningful and continuous presence in the annual Tet Health Fair to promote the role of the pharmacist as a caregiver and a community health educator. Additionally, our annual Tet Health Fair enables student volunteers to immerse in the festive Tet culture, while participating in a unique and worthwhile health project beneficial to the large Vietnamese community in Orange County. This year, the Tet Health Fair was a success despite the rain and mud thanks to the great support and cooperation from the following organizations: Vietnamese Pharmacist Association in the USA (VPhA-USA), APAG (Sav-On Drugs), Walgreens, Rite Aid, Union of Vietnamese Student Association (UVSA), and 108 motivated student volunteers from USC and 25 from Western University of Health Sciences School of Pharmacy. With thousands of people visiting our DM, HTN, and information booths, we courteously and professionally screened and counseled patients on their disease states. Over the 2 day-period, we performed 327 screenings for HTN and 329 for DM (see graphs). Patients with abnormal screening results were referred to the onsite pharmacists or their physicians for further evaluation. Patients with normal results were congratulated on their great achievement and encouraged to continue their healthy lifestyles. Besides the two types of screenings, we also provide patient education through poster boards and health pamphlets available in both English and Vietnamese languages. As a young organization, VAPSA is proud to provide free health care screenings and consultations to the Vietnamese community in Southern California. We will continue promoting health and culture awareness as we grow. Together with VPhA-USA, we are dedicated to serve the

T

Vietnamese community in future projects, such as the annual Immunization and Tet Health Fairs. Graph 1. The majority of patients have normal blood glucose level (<120 mg/dl). However, a few outliers have extremely high values (> 200mg/dl)

Graph 2. This bar graph shows that out of the total of 327 patients screened for HTN only 30% are have normal value, whereas 70% have values higher than normal.

Vietnamese Pharmaceutical Journal No.5 - 95

Vietnamese Pharmacists Associations in the Free World

Report of General Assembly Meeting December 29, 2004 - Sydney, Australia

Attendance:

- Tuong Anh Nguyen, Vice President of the IFVPA, Maryland, USA - Binh Nhung Tran, General Secretary, IFVPA - Mai Tam, Committee for Communications and Publications, IFVPA - Hong van Cao, President of the Vietnamese Pharmacists Association in Toronto, Canada - Jason Chau, Member, Vietnamese American Health Professional Association, New South Wales, Australia - Hieu Tam Doan, Adelaide, Australia - Linh Doan, Adelaide, Australia - Serena Tran, Goldfield Pharmacy, Girrawheen, WA - Rose Huynh, Goldfield Pharmacy, Girrawheen, WA - Phuc van Pham, Sydney, Australia - Quang Xuan Tran, Sydney, Australia The General Assembly Meeting of the International Federation of Vietnamese Pharmacists Associations in the Free world took place at 11:30 AM in the Tumbalong theater 2, Convention Center, Sydney, Australia, after completion of the morning part of the Pharmacy CE program with speakers Binh Nhung Tran and Tim Chen. I. REVIEW OF PREVIOUS MEETING Mrs Binh N. Tran, Secretary of the Federation, summarized the findings of the meeting on August 11, 2002 at the 4th International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free World in Anaheim, California. Mr. Mai Tam, on behalf of Mrs. Kim Do, Treasurer, reported on the finances of the Federation. US$ 5,262 were left in the account. A main project Mrs Kim is putting much effort in is the publishing of the Vietnamese Pharmacy Book to record the main events occurring in the field of Pharmacy. With the participation of all faculty members, pharmacy graduates and students from over the world, the book will have an invaluable historical value.

II. PROCEEDINGS AT THE 5TH CONVENTION Mr. Hieu Tran, President, could not attend the 5th Convention in Sydney, and has designated the following Board Members to represent the Federation at the Convention: - Pharmacist Tuong Anh Nguyen - Pharmacist Binh Nhung Tran - Pharmacist Mai Tam Vice-President Bui thi Hao from the Vietnamese Pharmacists Association in Northern California was not present. Mrs. Tuong Anh reviewed the events at the Convention since the first day of the Convention on December 28, 2004. At the Opening ceremony, Dr. Thuy Dinh Tran, President of the Vietnamese Medical Association of the free world and Mrs. Tuong Anh came on stage to declare the Opening of the Convention. III. HISTORY OF THE FEDERATION Mr. Mai Tam gave an overview of the formation of the International Federation of Vietnamese Pharmacists Association in the Free World since the Convention in Montreal. Through many terms and meetings to coincide with the International Conventions of Vietnamese Physicians, Dentists and Pharmacists in the Free World, the mission of the Federation is to rally pharmacists from all countries to realize a strong Vietnamese Pharmacists Community across the world. The thrust now is to involve the younger pharmacists graduating from schools outside of Vietnam to carry on that task. Lively discussions ensued on ways to achieve the optimal participation of the young members. IV. ELECTION OF THE EXECUTIVE BOARD FOR THE NEW TERM Due to the absence of representatives from France and other countries, there were not enough members to meet the quorum. The present members, along with Mr. Hong van Cao, President of the Vietnamese Pharmacists Association in Toronto, Canada, voted to extend the term of the current Executive Board until the next Convention.

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SINH HOAÏT DÖÔÏC KHOA

Thus, the Executive Board for the term 2005-2007 is composed of the current members: - Hieu Duc Tran, R.Ph., President - Tuong Anh Nguyen, P.D., Vice-President - Hao thi Bui, R.Ph.. Vice-President - Binh-Nhung Tran, Pharm.D., General Secretary - Kim thi Do, R.Ph., Treasurer Committee for Publications and Communications: - Mai Tam, R.Ph - Viet Thuc Truong, Pharm. Assistant to Mr. Hieu D. Tran: - Thuy Thanh Le, a pharmacy graduate from Monash University in Melbourne in 1999, currently works at a Medical Centre in Melbourne. A formal announcement was prepared for Dr. Tuong Anh to deliver at the Closing Ceremony on December 30, 2004. The contents of the message were: To rally pharmacists residing in all parts of the world, and foster communication among members. Regarding the Executive Board, the current term members will stay until the next Convention, with the addition of pharmacist Thuy Thanh Le to represent the young members. IV. ADJOURNMENT The meeting was adjourned at 12:30 PM. Although the attendance is not as high as one would expect from an international meeting, the members present showed much enthusiasm in carrying the objectives of the Federation. Several young pharmacists have attended all activities at the Convention, reinforcing the commitment to build a strong pharmacist community across the borders. Let's all keep the flame burning. Our deep thanks to the Organizing Committee at the 5th Convention for a thorough planning and superb execution of the programs for the enjoyment of all attendees. Reported by Binh Nhung Tran San Diego, California January 10, 2005

Report of the Vth International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free World The Vth International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free World was held on December 28 to 30, 2004 in Sydney, Australia. This was the first time the International Convention was held in the Land Down Under, and the event was the culmination of two years of preparation for the Organizing Committee.

At 6:05 PM, the Opening ceremony was started. Co-masters of the well- organized event were Dr. Cuong Bui from Brisbane, Queensland, and Dr. Katherine Lieu, daughter of Dr. Binh Lieu and Xuyen Tran from Sydney, and core members of the Organizing committee. The Vietnamese Physicians Association of the Free World (VPAFW) sponsored the Literary Awards for the year 2004 in several categories. Author Hoang N. Tuan from Australia won an award for his book on "Contemporary and post contemporary Vietnamese Literature". At 7:05 PM, Dr. Thuy D. Tran, President of the (VPAFW) and Dr. Tuong Anh Nguyen, Vice-President of the Vietnamese Pharmacist Associations in the Free World declared the Opening of the Convention. About 400 colleagues, members, and guests attended the event. The evening was continued with a cruise on the harbor aboard the Lady Rose boat, where the reception took place. Many pictures were taken for members who had been communicating via e-mail during the many months of preparation and finally got to see each other. The next day was spent on CE activities. Attendees went to three separate room areas to listen to the Medical, Dental or Pharmacy presentations. For pharmacy, there were two topics during the morning session: - Challenges and Rewards in Pharmaceutical Care presented by Binh Nhung Tran, Pharm.D., and - Home medication review: An Australian Model for achieving the quality use of medicines by Tim Chen, Ph.D., Professor at the Sydney University School of Pharmacy. After the meeting of the International Federation of Vietnamese Pharmacists in the Free World (see report in this issue), in the afternoon, pharmacists attended a session in the Medical part: - Clinical Risk Assessment, voluntary counseling and testing for HIV, Hepatitis and early detection of HI, Hepatitis

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PHARMACY ACTIVITIES

B & C in the Vietnamese Australian Community was presented by Phi Huynh-Do, M.D. Dr. Tuong Anh Nguyen moderated all the three talks, which were well received by the audience. In the evening was a reunion dinner for all promotion classes of physicians. The two MCs were pharmacist Quang X. Nguyen, who recently went through an eye operation, but still attended to the final touches for the program, and Dr. Xuyen Tran, a multi-talented physician. Both excelled in a variety of skits and entertaining talks for the audience On the last day, at the Youth Forum discussion, topics discussed were: - Volunteer work in Vietnam: what does it involve?; - Research and publications by young Australians; and - That having a Vietnamese background need not be relevant to my practice as a Health Officer in a country outside Vietnam, a most lively debate. Three young members were in each team, debating the pro and con aspect. Since both sides presented powerful statements and illustrated their points with brilliant examples, the result was a tie. The following section on the Open Meeting of the Vietnamese Physicians Association of the Free World was reported from an e-mail posting on the Vietnamese Pharmacy Forum by Pharmacist Phuc van Pham, Sydney Press Representative. The Meeting was held from 11:15 AM to 1:35 PM for physicians-members of the five countries. Presiding were Drs. Thuy Dinh Tran, Lien Duc Nguyen and Xuyen thi Tran. After a report of activities and financial status over the past two and a half years, the discussions centered on the location and time for the VIth International Convention. The time will be in 2008 instead of 2006. Proposed sites were:

Canada or Norway. If these two countries do not accept, the place will be Melbourne, Australia. The choices will be presented during the Gala dinner. The current term will last for eight more months, and the new 2005-2008 term will be elected at a Special meeting to be organized in France, Canada or the USA. This will be announced and association members including the Dental and Pharmacy sections will be notified. The Gala dinner was very entertaining. More than 500 members, relatives and friends were present. The White Coat Choir of Southern California performed very well. The consensus of decisions made by the Vth International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free World during the past days were formally announced. Please see the Vietnamese text at the end of the report. A distinctive gift of appreciation was presented to special members. For the promotion and dissemination of Convention news in the United States, and participation as speakers in the various programs, Dr. Duc van Nguyen and Binh Nhung received posters imprinted with the distinctive logo of the Convention: a koala bear perched on a branch of eucalyptus, with the signatures of 17 members of the Organization Committee. The Convention provided a great occasion to meet colleagues and friends whose contacts have been lost for several years. The Organizing Committee has realized an exceptional agenda, providing updates in professional fields as well as entertaining activities for the enjoyment of all attendees. Binh Nhung Tran, Pharm.D. San Diego, January 15, 2005

98 - Taäp San Chuyeân Nghieäp Döôïc Khoa

A Career In Industrial Pharmacy:

Interview between Dr. Tue Huu Nguyen and Binh Nhung Tran May 16, 2000

BNT: Dr Tue, I have met you first during the 1993 International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free world in San Jose, California. At that time, you were working at Genentech already. What brought you to work there? THN: First, I was trained as a pharmacist in Vietnam, graduating in 1973. When I came to the United States, I tried to get in the field where I have always wanted to work in, that is Industrial Pharmacy. I was admitted to the graduate program in Industrial Pharmacy at St. John University in 1976 after two semesters of remedial study in Pharmacokinetics, supplemental Mathematics, Physical Chemistry, etc. I got my Master's degree there, and went to work for Syntex Labs. I quickly realized that, in order to move up in a Research and Development environment, I had to finish Graduate School. Thus, I joined the Department of Pharmaceutical Chemistry at Kansas University, and obtained my Ph.D. there in 1984. It was the year when the first few protein drugs were successfully tested in the clinical setting and getting ready for marketing, and Pharmaceutical Development of Protein Drugs was the field to go into. I was lucky enough, probably due to my professor's reputation, to get a position with Genentech, and have stayed with the company since then. It has been a rewarding career scientifically, professionally, and I must say financially as well. BNT: Please tell us about your work. What are the areas of emphasis? THN: What do we do? My department is called Pharmaceutical Research and Development. I have a group of 45 people: 20 with Ph.D. degrees in a variety of fields, such as pharmaceutics, biochemistry, biology, chemical engineering, analytical chemistry, and biophysics; the other 25 persons are professionals with BS and MS degrees in the same fields. About two-thirds of the department are involved in development work. We take the protein after it is purified, and develop analytical methods to characterize the molecule's physical and chemical properties (primary, secondary and tertiary structures of proteins

mainly), design the formulation and drug delivery systems for that molecule, and develop the manufacturing processes to prepare products for clinical testing and marketing. The other third of the department is involved in research, working with Research and Discovery teams to select the best molecule candidates for further development. Their function is to determine the absorption and transport properties of drug molecules in various cell monolayers which are used as models for epithelial barriers, and to test various drug delivery concepts in animal models. Emphasis is placed on studying the pharmacokinetics profile, the bioavailability, and efficacy of the novel product. BNT: I have worked in Research and Development of Clinical Diagnostics at Miles Laboratories in Elkhart, Indiana for six years. The company was affiliated with Bayer Pharmaceuticals in the 80's. Subsequently, I moved to Hybritech Diagnostics in San Diego, California. This city is the hub of biotechnology firms. What do you think of the future of biotechnology companies in your area? THN: When I joined Genentech, there were only a handful (three or four to be exact) biotech companies in the Bay area. Now, there must be at least 100 (a number I often hear is 200) start-up biotech companies in this area. Most of them are more research labs than pharmaceutical companies, but many have drugs in clinical trials, and will be full-fledged companies in the near future. BNT: Would you encourage young pharmacists to go into Biotechnology? What are the academic requirements to get in the field? And what are the career opportunities? THN: Most of the pharmacists and Pharm.D.s are employed at Genentech and other pharmaceutical companies in the Drug Information, Drug Safety, and Customer services areas. With some advanced clinical training, some Pharm.D.s are employed in our Clinical Affairs Department. The job in Drug Information and Drug Safety entails interaction with customers, who are mainly hospital

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SINH HOAÏT DÖÔÏC KHOA

pharmacists and physicians, to answer questions regarding drug preparation, admixtures, and drug stability. They also record and analyze adverse event reports for follow-up action. Pharm.D.s with extensive clinical training work with physicians to help design clinical trial protocols and monitor their progress. Additionally, some pharmacists with Master of Business Administration degrees work in the Marketing department performing market research, analyzing clinical and market trends, studying the competition, estimating the market size for the new drug, and looking for future therapeutic areas for the company to invest research resources. These are rewarding career opportunities not widely known to the practicing pharmacist. Professionally, it is also rewarding to participate in the introduction of new drugs, which are targeted for

unmet medical needs and have the potential to affect patients' lives. BNT: Thank you very much for your time. Your answers will help pharmacists and Pharmacy students in charting a path for their careers. THN: I hope that I have answered your questions. Please don't hesitate to contact me if you have other questions. End of the interview Binh Nhung Tran May 16, 2000.

96 - Taäp San Chuyeân Nghieäp Döôïc Khoa

TWO WEEKS IN AUSTRALIA:

A LIFE-TIME OF MEMORIES

Binh Nhung Tran, Pharm.D

It has been two weeks of unforgettable significance, the culmination of two years of preparation for the Organizing Committee of the Fifth International Convention of Vietnamese Physicians, Dentists and Pharmacists in the Free World to occur in Sydney, Australia from December 28 to 30, 2004. For members living in the United States traveling to the Land Down Under for the first time, the trip provided a lore of wonders for all to enjoy, as well as the sense of urgency and fragility of existence. So many colleagues and family members have escaped the tsunami tragedy by a hair when shortening or canceling their vacation in Phuket, Thailand.

AN EVENTFUL START

W

e left San Diego on Sunday December 26, 2004, to board the overnight United Airlines flight to Sydney in company of our son Tony, his wife Trang and son Thi Lan. The flight was reasonably smooth; the crew was serving breakfast one hour before landing, so that the passengers are fully awake. Suddenly, we began to experience turbulences. We were holding on to our trays when the plane dipped suddenly. All breakfast trays in the cabin were catapulted high in front of our bewildered eyes, and landed upside down, spattering food and beverages all over. Someone's food was on our trays. I quickly retrieved the binder for the Pharmaceutical Care talk that I just assembled before the flight. Luckily, the coffee spills could be wiped out from the plastic cover, but the tainted pages inside will serve as a memento of this historic flight years after. Later on, our little grandson said: "I thought two planes were colliding".

SYDNEY, FABULOUS CITY AND CONVENTION SITE

After getting to Sydney, our first visit was to the Opera House, a stunning architecture with the shape of shells. During the tour of the facilities, we attended a rehearsal of the musical West Side Story, just before the real performance. Late in the evening, we attended the Opening ceremony, a well organized event from start to end. Co-masters of ceremony were Dr. Cuong Bui from Brisbane, Queensland, and Dr. Katherine Lieu, daughter of Dr. Binh Lieu and Xuyen Tran from Sydney, and core members of the Organizing committee. The Vietnamese Physicians Association of the Free World (VPAFW) sponsored the Literary Awards for the year 2004 in several categories. Author Hoang N. Tuan from Australia won an award for his book on "Contemporary and post contemporary Vietnamese Literature". Dr. Thuy D. Tran, President of the VPAFW, and Dr. Tuong Anh Nguyen, Vice-President of the Federation of Vietnamese Pharmacists Association in the Free World declared the Opening of the Convention.

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SINH HOAÏT DÖÔÏC KHOA - A Life-Time of Memories

The evening was continued with a cruise on the harbor aboard the Lady Rose boat. The next day was spent on CE activities. Attendees went to three separate room areas to listen to the Medical, Dental or Pharmacy presentations. There were two topics during the morning session: Challenges and Rewards in Pharmaceutical Care presented by Binh Nhung Tran, and Home medicines review by Dr. Tim Chen, Professor at the Sydney University School of Pharmacy. After the meeting of the International Federation of Vietnamese Pharmacists in the Free World (see report in this book), in the afternoon, Dr. Phi Huynh-Do spoke on Clinical Assessment and early detection of HIV diseases in the Vietnamese Australian Community. In the evening, we attended a reunion dinner for all promotion classes of physicians. The two MC were pharmacist Quang X. Nguyen, who recently went through an eye operation, but still attended to the final touches for the program, and Dr. Xuyen Tran, a multi-talented physician. Both excelled in a variety of skits and entertaining talks for the audience. Mrs. Tam Thuong, who injured her ankle during a pre-Convention trip, was present on stage in spite of the pain. On the last day, I attended the Youth Forum discussion, and saw many young members full of enthusiasm. Topics discussed were: Volunteer work in Vietnam: what does it involve?; Research and publications by young Australians; and a most lively debate on the theme: That having a Vietnamese background need not be relevant to my practice as a Health Officer in a country outside Vietnam. Three young members were in each team, debating the pro and con aspect. Since both sides presented powerful statements and illustrated their points with brilliant examples, the result was a tie. During the presentation, I was sitting next to pharmacist Ngoc Anh Nguyen, a resident of Melbourne, and member of the Vietnamese Pharmacy Forum and the Vietnamese Medical Forum, and so was glad to get the addresses of some colleagues in Melbourne and other areas. The Gala dinner was very entertaining. More than 500 members, relatives and friends were present. I met pharmacist Minh Nguyet Pham, and her husband, relatives of Dr. Toan Tran of the VPhF. The White Choir of Southern California performed very well. Several reports have been done on their program. A distinctive gift of appreciation was presented to special members. For the promotion and dissemination of Convention news in the United States, and participation as speakers in the various programs, Dr. Duc van Nguyen and Binh Nhung received posters imprinted with the distinctive logo of the Convention: a koala bear perched on a branch of eucalyptus, with the signatures of 17 members of the Organization Committee. There was nothing more meaning102 - Taäp San Chuyeân Nghieäp Döôïc Khoa

ful than the symbol of Australia, delivered by a group of most dedicated professionals in a superb program for the enjoyment of all attendees. On the last day in Sydney, we visited the Blue Mountains, a wonderland trek, besides other sites. New Year's eve was spent watching the famous fireworks shot from the Sydney Harbour Bridge, a spectacular view for all. This was the first time we welcomed the new year Down Under, and were ahead of most friends and family living many time zones behind.

MELBOURNE WITH THE FAMILY

On January 1st, 2005, we flew to Melbourne, and for five days, reconnected with family members whom we have not seen for almost a quarter century. We stayed at their house while they were vacationing in Thailand and Vietnam. MyNgoc Vo, a niece and member of the VPhF was supposed to go to Phuket resort during the Christmas holidays, but had breathing problems, so did not go. This was how she and other members escaped the Tsunami tragedy, as Dr. Minh Ho and his family did. A whole program of sight seeing was orchestrated by Peter and his family, who are of the same age range as our son Tony's. The following morning, we toured the city by car and train, visiting the National Gallery of Victoria (free entry), St Paul Cathedral where the children lit candles to the victims of the Tsunami earthquake and disaster. We had lunch at the Arts Centre, strolled down the Botanical Gardens, and enjoyed the nice scenery by the Yarra River bank. Dinner at the Daikyo Korean Restaurant was superb with sashimi and beef and seafood barbecue. On Monday 1/3, we went to Lorne Beach, a bustling seaside resort about 1 and 1/2 hours from Melbourne. We packed lunch and ate on the beach. Most enjoyed going in the water, while Binh sat under the eucalyptus trees, reading. Back in the city, we visited the Royal Botanical Gardens, renowned for its fine landscaped gardens. We strolled amid the beautiful lawns, watching eels and other fishes swimming in the tranquil lakes. We ended by visiting Footscray, the Vietnamese section of town, came by pharmacy Le Thi, and stopped for a quick dinner at Ha Long Restaurant. On Jan 4, we drove West, and rode on the Australia's favourite steam train Puffing Billy through the magnificent Dandenong Ranges from Belgrave to Emerald Lake Park. Some people took a one-way trip, with part of the family driving to the end of the train ride, and picking up their family there. We had the opportunity to feed parrots with our hands. The children were very delighted. The next day, we went to Phillip Island. At Wildlife Wonderland, we saw kangaroos in the natural habitat, fed

A Life-Time of Memories - PHARMACY ACTIVITIES

them, and watched koalas perched high in the eucalyptus trees. On the windy cliffs at the southern most part of Australia, we saw the penguin holes with part of their tails showing. Much to our regrets, we could not stay overnight to watch the nightly procession of the small penguins coming from the ocean to rejoin their families onshore, and then go back to the water at dawn. According to friends who witnessed the scene, the night march was a unique spectacle. After a picnic near the beach, the children flew kites. During the drive back, we discussed on Kim van Kieu's epic masterpiece by Nguyen Du, other literary works and folkloric verses. These intercalating days of long and short trips were made possible by renting a 12 seat bus, with coordinated team work and nice cooperation from the weatherman. As the saying goes: "If you do not like the Melbourne weather, just wait 15 minutes". You may see the complete opposite! On Jan 6, we went to Victoria Market, a popular spot for all purpose shopping. Lunch was dim sum in Richmond, the Asian district of Melbourne. Afterwards, we strolled to Park Fitzroy to watch the fountains and luscious flowers in the Conservatory. A wedding party was taking pictures there, with the bridesmaids in a symphony of hydrangea pink hues. Naturally, we took lots of pictures, framed by the multi-colored hanging fuchsia baskets. A stop by the St Patrick's Church, driving on St Kilda Street busy with bars and coffee shops ends up at the beach right in town at Portabello, where Peter used to work at the Commonwealth Bank many years ago. Dinner was a wonderful experience at Oanh's Kitchen in Kew, a suburb of Melbourne. The family renovated the place three years ago into a stunningly elegant restaurant suitable for state dinner guests. We were treated to a 7 course dinner with a superb array of oysters, an assorted fresh and fried rolls, salmon sashimi, salad with cigales de mer - sea bug- toâm voù", fish with dill Thang Long style, grilled scallops and shitake mushrooms..., duck fillet in five-spice olive sauce, and finishing with goat curry. Dessert, as with all the dishes, was artistically decorated as masterpieces. The host and hostess took turn visiting with all the guests, who at times have been refused service because they did not book ahead in the 30 seats restaurant. The atmosphere was also superb. Flowers were arranged in tall glass containers grouped by the entrance. A dozen more crystal and ceramic vases and ceramic were displayed on shelves on the opposite wall. An impressionist sea scape oil painting was the main decoration on another wall.

On Friday, Jan 7, Binh Nhung joined pharmacist Le Thi and Ngoc Anh for lunch at the same place where we had most of our meals - Ha Long restaurant. What a nice surprise when Drs. Le Thanh Canh and Nghiem Xuan Tuan and their spouses came along. Conversation sprang lively as the spouses also knew each other. After lunch, we visited Dr and Mrs Canh Le at their house in Toorak, one of the most prestigious areas of town, where sweet mangoes were served. As a surprise, Mrs. Le Thi brought an elegant tiramisu cake for all to enjoy while listening to four hand piano playing by Mrs. Canh and Binh Nhung, amid celebrity photo snapshots.

LASTING IMPRESSIONS

We cannot thank enough family and friends who have opened their houses and hearts in Sydney and Melbourne. At the Convention entrance hall on the first day, Dr. Binh Lieu and the registration committee welcomed every one of us. Dr. Bao Quy Nguyen Phuoc greeted me like a family member. Dr. Dong Quoc Tran, brother of pharmacist Thuy Lan Tran, has come from Melbourne to meet the guests who just came to the Convention site. Later, in Melbourne, Dr. Dong has invited us for dinner, but we could not accept because of constant sightseeing. Pharmacist Phuc Pham, a member of the VPhForum and professional reporter for the Nhan Quyen weekly newspaper and other publications, was a dynamic member, always trying to put colleagues in contact with classmates and friends. Dr. Binh Lieu, editor of the Medicine and Modern Life bi-monthly Vietnamese Health magazine, gave me all the year's issues in a bound book. Dr Phuoc Vo ensured that all the presentations were run smoothly. Thank you to all the Organizing Committee members for their untiring efforts to prepare for this most memorable 5th Convention in Australia. We would also like to thank all family members for a wonderful stay in Melbourne, for their hospitality, resourcefulness as guides and coordinators of all the outings, for wonderful sharing of dining experience, conversation, and to the children for their ingenuous and enlightening talks during the car trips. You are all invited to come to San Diego any time. San Diego, 01/10/05

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Tö vaán Y khoa mieãn phí:

Giôùi thieäu Paltalk vaø "Chöông trình Vaán ñaùp SOÁNG KHOÛE"

Giaùo Sö Nguyeãn Quyeàn Taøi

Florida, Hoa Kyø

"Thöa Baùc só, toâi bò chaûy nöôùc maét soáng töø hôn hai tuaàn nay. Chæ coù maét phaûi bò thoâi, coøn maét traùi khoâng coù. Toâi cuõng thaáy loám ñoám tröôùc maét. Khoâng bieát coù phaûi toâi coù bò beänh maét cöôøm khoâng?"

saün, hay thieát laäp moät nhoùm hoäi thaûo môùi cho nhoùm baïn höõu cuûa chuùng ta. "Chöông Trình Vaán Ñaùp SOÁNG KHOÛE": Moät nhoùm baùc só y khoa, döôïc só vaø chuyeân vieân ñieän toaùn Vieät Nam ñaõ söû duïng Paltalk ñeå thieát laäp moät chuông trình tö vaán y khoa cho quaàn chuùng. "Chöông trình Vaán Ñaùp SOÁNG KHOÛE" naøy môû roäng cho ngöôøi Vieät Nam ôû khaép nôi treân theá giôùi vaøo döï thính. Thính giaû coù theå ñaët caâu hoûi veà nhöõng vaán ñeà y khoa vaø söùc khoûe, vaø ñöôïc caùc baùc só vaø döôïc só giaûi ñaùp ngay. Chöông trình naøy baét ñaàu hoaït ñoäng ñeàu ñaën töø thaùng 1, 2004, moãi tuaàn moät laàn, vaøo 8 giôø saùng Chuû Nhaät (giôø Vieät Nam, töùc 8 giôø toái Thöù Baûy taïi mieàn Ñoâng, Baéc Myõ). Trong lôøi giôùi thieäu ñöôïc phaùt thanh lieân tuïc treân Paltalk vaø trong phaàn môû ñaàu moãi kyø phaùt thanh, Ban phuï traùch Chöông trình Vaán ñaùp SOÁNG KHOÛE löu yù ngöôøi döï thính laø nhöõng caâu giaûi ñaùp cuûa baùc só vaø duôïc só chæ coù taùnh caùch khaùi quaùt, giuùp thính giaû bieát theâm veà tình traïng söùc khoûe cuûa mình, vaø khuyeân beänh nhaân ñeán gaëp baùc só ôû ñòa phöông cuûa mình ñeå ñöôïc khaùm vaø ñieàu trò kòp thôøi vaø ñuùng möùc. Trong giai ñoaïn ñaàu, Chöông trình Vaán ñaùp SOÁNG KHOÛE chöa ñöôïc nhieàu ngöôøi bieát ñeán, neân soá ngöôøi vaøo döï thính haèng tuaàn chöa leân ñeán 100. Ña soá ngöôøi tham döï chöông trình vaø ñaët caâu hoûi laø ngöôøi Vieät ôû haûi ngoaïi. Nhieàu ngöôøi ôû Hoa Kyø, nhöng cuõng coù thính giaû raûi raùc ôû khaép nôi, nhö Canada, Thuïy só, Phaùp, Hoàng Koâng, UÙc, v.v.. Ñieàu naøy cuõng deã hieåu, vì tyû leä soá ngöôøi ôû Vieät Nam coù maùy ñieän toaùn caù nhaân vaø coù phöông tieän lieân laïc qua Maïng Löôùi coøn raát thaáp so vôùi soá ôû haûi ngoaïi. Tuy nhieân, ngöôøi vieát baøi naøy nhaän thaáy soá ngöôøi ôû Vieät Nam tham gia Chöông trình ngaøy caøng gia taêng, chöùng toû ñaõ coù theâm nhieàu ngöôøi ôû Vieät Nam bieát ñeán vaø söû duïng Chöông trình Tö vaán mieãn phí naøy. Moät soá caâu hoûi ñöôïc ñaët ra lieân quan ñeán nhöõng vaán ñeà söùc khoûe ñaëc bieät ôû Vieät Nam hay nhöõng thuoác men thöôøng duøng ôû trong nöôùc.

N

göôøi beänh 70 tuoåi naøy khoâng ôû trong phoøng khaùm beänh cuûa moät baùc só, maø ôû caùch xa baùc só haèng ngaøn daëm. Khi ñaët caâu hoûi treân, beänh nhaân ñang ôû Vieät Nam, vaø baùc só ñang ôû Hoa Kyø. Nhöng duø ôû xa hay gaàn, khoaûng caùch khoâng gian ñaõ khoâng thaønh vaán ñeà cho vieäc tö vaán söùc khoeû, vaø Baùc só ñaõ coù theå phaàn naøo giaûi ñaùp ngay thaéc maéc cuûa Beänh nhaân, nhôø moät kyõ thuaät truyeàn thoâng caøng ngaøy caøng ñöôïc nhieàu ngöôøi söû duïng: ñoù laø Paltalk. Töø khi maùy ñieän toaùn caù nhaân ñöôïc thoâng duïng, ñieän thö (e-mail) ñaõ trôû thaønh phöông thöùc gôûi chuyeån thö tín deã daøng vaø nhanh choùng qua Maïng Löôùi (Internet). Sau ñoù, nhöõng dòch vuï Gôûi Thö tín Caáp kyø (Instant Messager) cuûa nhöõng haõng AOL, Yahoo, ICQ, v.v. giuùp cho vieäc lieân laïc ñöôïc thöïc hieän caáp kyø, töùc nhöõng haøng chöõ vöøa ñöôïc gôûi ñi thì ngöôøi nhaän ñaõ thaáy noù hieän ra tröôùc maét treân maøn aûnh maùy ñieän toaùn cuûa mình. Khoâng nhöõng theá, caùc dòch vuï treân coøn giuùp chuùng ta lieân laïc vôùi nhau baèng lôøi noùi, khoâng khaùc gì ñieän thoaïi. Nhöõng phoøng troø chuyeän (chat room) thieát laäp qua nhöõng dòch vuï keå treân ñaõ ñöôïc nhieàu giôùi söû duïng ñeå taùn gaãu hay hoäi thaûo vôùi nhau. Gaàn ñaây, dòch vuï Paltalk ra ñôøi vaø ñang ñöôïc haèng chuïc trieäu ngöôøi treân theá giôùi söû duïng.

Paltalk laø gì?

Paltalk laø moät phöông tieän lieân laïc caáp kyø qua Maïng Löôùi. Duøng Paltalk, chuùng ta coù theå thaûo luaän vôùi nhau baèng lôøi noùi, tieáng noùi ñöôïc truyeàn qua maùy nghe roõ khoâng keùm gì ñaøm ñaïo qua ñieän thoaïi. Ñeå söû duïng Paltalk, ngoaøi maùy ñieän toaùn chuùng ta caàn coù theâm moät caùi loa vaø moät maùy vi aâm (microphone). Sau khi chuyeån xuoáng (download) chöông trình Paltalk vaø laøm thuû tuïc ghi danh, chuùng ta coù theå môû Paltalk ra vaø vaøo trong moät nhoùm hoäi thaûo ñaõ coù

104 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Tö Vaán Y Khoa Mieãn Phí - PHARMACY ACTIVITIES

Laøm sao thieát trí Paltalk treân maùy? Ban Phuï traùch Chöông trình Vaán ñaùp SOÁNG KHOÛE ñaõ bieân soaïn baûn chæ daãn sau ñeå giuùp ñoàng baøo thieát trí Paltalk trong maùy ñieän toaùn cuûa mình: Quí baïn vaøo Trang löôùi www.paltalk.com a. Goõ vaøo muïc "Sign up" (Ghi teân) hay "Register" (Ñaêng kyù) ñeå thieát laäp moät Account (Chöông muïc) mieãn phí vôùi Paltalk. b. Trong phaàn ghi danh, quí vò haõy töï choïn cho mình moät bieät danh (nickname), khaåu leänh (password), vaø hoaøn taát thuû tuïc ghi danh. Ghi danh xong, quí vò coù theå chuyeån hoà sô chöông trình Paltalk vaø laép nhu lieäu naøy vaøo maùy. Quí vò seõ caàn cho bieát ñieän chæ (e-mail address) cuûa quí vò. c. Laép nhu lieäu Paltalk xong, quí vò seõ phaûi caàn coù moät maät maõ (code) tröôùc khi coù theå baét ñaàu söû duïng. Quí vò haõy môû dòch vuï ñieän thö (e-mail service) cuûa quí vò. Quí vò seõ nhaän ñöôïc moät böùc thö töø Paltalk cho bieát maät maõ (code) daønh cho quí vò. d. Quí vò haõy trôû laïi chöông trình thieát keá Paltalk, ghi theâm maät maõ (code) vaøo, vaø hoaøn taát vieäc thieát keá. e. Quí vò haõy goõ vaøo muïc Giuùp ñôû (Help) vaø Thöû AÂm thanh (Audio test) vaø theo nhöõng chæ daãn cuûa Paltalk ñeå thöû loa (speaker) vaø maùy vi aâm (microphone). Neáu muoán bieát theâm veà caùch thöùc söû duïng Paltalk, quí vò coù theå goõ vaøo muïc "Support" trong Trang Chaùnh (Home page) cuûa Paltak treân Maïng Löôùi. Laøm sao vaøo "Chöông trình Vaán ñaùp SOÁNG KHOÛE" treân Paltalk? Sau khi môû Paltalk, quí vò baám vaøo hình Groups thì seõ thaáy moät loaït teân caùc "Nhoùm" (groups) ñang thaûo luaän. Quí vò haõy goõ vaøo nhoùm "By Language: Asia & the Far East" thì seõ thaáy moät loaït teân caùc "Phoøng (room)" treân maøn aûnh

(ña soá baèng Vieät ngöõ). Khi thaáy phoøng "Chöông trình Vaán ñaùp SOÁNG KHOÛE", chuùng ta baám vaøo ñaáy thì seõ thaáy hieän ra maøn aûnh cuûa "phoøng" Chöông trình Vaán ñaùp SOÁNG KHOÛE. Phoøng "Chöông trình Vaán ñaùp SOÁNG KHOÛE" môû cöûa khoaûng 15 phuùt tröôùc giôø khai maïc. Chöông trình tröïc tieáp vaán ñaùp baét ñaàu luùc 8 giôø saùng Chuû Nhaät (giôø Vieät Nam, töùc toái Thöù Baûy taïi Baéc Myõ) vaø thöôøng keát thuùc vaøo khoaûng 10 giôø 30. Coù khi chöông trình keùo daøi hôn neáu coù nhieàu thính giaû coøn muoán ñaët caâu hoûi vaø ñieàu kieän cho pheùp. Ñoäc giaû coù theå vaøo trang löôùi songkhoe.crctvn.org cuûa Chöông trình Vaán ñaùp SOÁNG KHOÛE ñeå bieát theâm veà thaønh phaàn caùc baùc só vaø döôïc só trong Ban Tö Vaán, vaø ñeå ñaët caâu hoûi. Nhöõng caâu hoûi naøy seõ ñöôïc giaûi ñaùp trong hoäp thô vaø nhöõng kyø phaùt thanh sau ñoù. Haèng ngaøy, thính giaû cuõng coù theå vaøo Phoøng "Chöông trình Vaán ñaùp SOÁNG KHOEÛ" trong Paltalk ñeå nghe nhöõng chöông trình ñaõ qua ñöôïc phaùt thanh laïi.

Toùm löôïc:

Chöông trình Vaán ñaùp SOÁNG KHOÛE laø moät coá gaéng coøn raát khieâm nhöôøng cuûa moät nhoùm baùc só, döôïc só vaø chuyeân vieân ñieän toaùn Vieät Nam. Caùc vò naøy duøng Paltalk, moät phöông tieän lieân laïc taân kyø treân Maïng Löôùi ñeå ñem thieän chí, kieán thöùc vaø kinh nghieäm cuûa mình phuïc vuï ñoàng baøo Vieät Nam ôû moïi nôi treân theá giôùi. Ngöôøi vieát baøi naøy hy voïng Chöông trình Vaán ñaùp SOÁNG KHOÛE ñöôïc nhieàu ngöôøi bieát ñeán vaø söû duïng, vaø seõ coù theâm nhieàu baùc só, döôïc só vaø caùc chuyeân vieân khaùc tham gia phuï traùch Chöông trình ñeå nhöõng ñoàng baøo thieáu phöông tieän tö vaán baùc só coù theå hieåu bieát theâm veà nhöõng vaán ñeà söùc khoeû, vaø bieát caùch baûo veä söùc khoeû cuûa mình höõu hieäu hôn.

Vietnamese Pharmaceutical Journal No.5 - 105

IN MEMORIAM

Dr. Nguyeãn Ñaït Toân

Doctor in Pharmacy from the University of RENE DESCARTES PARIS V, France. Passed away on June 19, 2004 in California at the age of 87 years. Although a graduate of Saigon University from an earlier generation, Dr. Nguyen had a young mind and was a model of scholarship. After 1975, he studied for the Doctor of Pharmacy degree in France, passed the Foreign Pharmacy graduate Equivalency Examination in the USA, and has published research work in acupuncture.

**********

Mr. Nguyeãn Taát Ñaït

Former Co-Founder of the Vietnamese Pharmacists Association in the USA. Graduate from the Saigon University School of Pharmacy, class of 1967 Passed away on June 28, 2003 in Orange County, California, at the age of 64 years. Professor Toâ Ñoàng, members of the VPhA-USA Board of Directors and Twenty-five classmates have expressed their sympathy for a dedicated member of the pharmacy family: From the Washington DC area: Phan Nguyeät-AÙnh, Nguyeãn Phuùc Cöôøng, Huyønh Anh Ñöùc, Vuõ Ngoïc Dieäp, Ngoâ Sôn Haûi, Ngoâ Kim Lieân, Traàn Kim Long, Trònh Bích Phöông, Nguyeãn Ñöùc Thuïy, Nguyeãn Maäu Trinh. From Houston, Texas: Nguyeãn Ngoïc Bình, Hoaøng Thò Minh Chaâu, Ñaøo Minh Taâm, Ñaøo Thò Myõ Leâ, Phaïm Nhö Haø, Phan Hoàng Kieân, Nguyeãn Thò Voïng, Nguyeãn Thò Vui, Phan Thò Baïch Mai, Höùa Thò Ngoïc Söông, Leâ Phi Uyeån, Haø Thò Ngoïc, Haø Vaên Chöông, Phan Quoác Chöông, Ngoâ Minh Chaâu.

106 - Taäp San Chuyeân Nghieäp Döôïc Khoa

IN MEMORIAM

We deeply regret

Dr. Nguyeãn Vaên Trang

Former Professor of the University of Saigon School of Pharmacy Who passed away on May 16, 2005 in Los Angeles, California at 85 years of age And wish to express our condolences to Mrs. Nguyeãn Vaên Trang (Pharmacist Nguyeãn Thò Hai) and the family. Many generations of pharmacists will remember having been students of Professor Trang.

The Vietnamese Pharmacist Associations in the Free World The Vietnamese Pharmacists Association in the USA L'Amicale des Pharmaciens du Quebec The Vietnamese Pharmacy Forum Former students of the Saigon School of Pharmacy

Vietnamese Pharmaceutical Journal No.5- 107

Special Thanks

to

Bristol-Myers Squibb Company

Represented by

Mary Ann Moss

Cardiovascular Risk Special Representative & Sr. Territory Business Manager Hepatitis-Virology

Kathleen Suler

Schering Oncology Biotech

Represented by

Hepatitis Business Developement Manager

Bal Villanueva

for their continued support of VPhA-USA

108 - Taäp San Chuyeân Nghieäp Döôïc Khoa

Special Thanks

to

AMGEN

Represented by

Ariane An, Pharm.D., FCSHP

for their financial contribution to this VPhJ issue and for their continued support of VPhA-USA

The Vietnamese Pharmacists Association in the USA

Information

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