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Acetazolamide for Monge's Disease
Acetazolamide for Monge's Disease
"Excessive erythrocytosis"
Published ahead of print on April 3, 2008
Am. J. Respir. Crit. Care Med. 2008, doi:10.1164/rccm.200802-196OC
Acetazolamide for Monge's Disease: Efficiency and Tolerance of a 6
Month Treatment
Jean-Paul Richalet1*, Maria Rivera-Ch2, Maxime Maignan3, Catherine
Privat2, Isabelle Pham4, Jose-Luis Macarlupu2, Olivier Petitjean5, and
Fabiola Leon-Velarde2
1 Laboratorie "Reponses cellulaires et fonctionnelles a l'hypoxie,"
EA2363, ARPE, UFR SMBH, Universite Paris 13, Bobigny, France; Service
de Physiologie et Explorations Fonctionnelles, Service de Pharmacie,
AP-HP, hopital Avicenne, Bobigny, France, 2 Facultdad de Ciencias y
Filosofia, Dpto. De Ciencias Biologicas y Fisiologicas, Laboratorio de
Fisiologia Comparada, Universidad Peruana Cayetano Heredia, Lima,
Peru, 3 Laboratorie "Reponses cellulaires et fonctionnelles a
l'hypoxie," EA2363, ARPE, UFR SMBH, Universite Paris 13, Bobigny,
France; pole Urgences, CHU Grenoble, La Tronche, France, 4 Laboratorie
"Reponses cellulaires et fonctionnelles a l'hypoxie," EA2363, ARPE,
UFR SMBH, Universite Paris 13, Bobigny, France; Service de Physiologie
et Explorations Fonctionnelles, AP-HP, hopital Jean Verdier, Bondy,
France, 5 Service de Physiologie et Explorations Fonctionnelles,
Service de Pharmacie, AP-HP, hopital Avicenne, Bobigny, France
* To whom correspondence should be addressed. E-mail:
richalet@smbh.univ-paris13 . fr .
Rationale:
Monge's disease is characterized by an excessive erythrocytosis,
frequently associated with pulmonary hypertension, in high altitude
dwellers. It has a considerable impact on public health in high
altitude regions. A preliminary study demonstrated the efficiency of
acetazolamide (250 mg/day for 3 weeks) in reducing serum
erythropoietin and hematocrit.
Objectives:
Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg
acetazolamide that could be chronically implemented and its effects on
pulmonary artery pressure and cardiac function.
Methods:
A two-phase study was performed in patients (hematocrit 63%) from
Cerro de Pasco, Peru (4,300 m). First phase: a double blind placebo-
controlled study in 55 patients who receive a single dose of either
250mg acetazolamide (n=40) or placebo (n=15) by daily oral
administration for twelve weeks. Second phase (open label): after a
four-week wash out period, all patients received 250mg acetazolamide
for twelve weeks. Hematocrit, blood gases, clinical outcome and
pulmonary artery circulation were evaluated.
Results:
First phase: acetazolamide decreased by 44% the number of polycythemic
subjects (p=0.02), decreased hematocrit from 69 to 64% (p<0.001) and
increased arterial O2 pressure from 42 to 45 mmHg (p<0.001). No severe
adverse effect, nor hypokalemia was recorded. The second phase
reproduced the effects observed during the first phase, without
cumulative effects on hematocrit. A four-week washout restored basal
hematocrit. Only patients who received Acz for 6 months showed a clear
reduction in pulmonary vascular resistance.
Conclusions:
Acetazolamide reduces erythrocytosis and improves pulmonary
circulation in Monge's disease without adverse effects. Its
implementation as a chronic treatment for this disease appears
efficient and safe. Registered at w w w .clinicaltrials.gov, ID#
NCT00424970
Key words: hypoxia, altitude, pulmonary hypertension, chronic mountain
sickness
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* tinyurl . com /2r2nkh
Man Is A Herbivore!
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DEAD PEOPLE WALKING
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"Excessive erythrocytosis"
Published ahead of print on April 3, 2008
Am. J. Respir. Crit. Care Med. 2008, doi:10.1164/rccm.200802-196OC
Acetazolamide for Monge's Disease: Efficiency and Tolerance of a 6
Month Treatment
Jean-Paul Richalet1*, Maria Rivera-Ch2, Maxime Maignan3, Catherine
Privat2, Isabelle Pham4, Jose-Luis Macarlupu2, Olivier Petitjean5, and
Fabiola Leon-Velarde2
1 Laboratorie "Reponses cellulaires et fonctionnelles a l'hypoxie,"
EA2363, ARPE, UFR SMBH, Universite Paris 13, Bobigny, France; Service
de Physiologie et Explorations Fonctionnelles, Service de Pharmacie,
AP-HP, hopital Avicenne, Bobigny, France, 2 Facultdad de Ciencias y
Filosofia, Dpto. De Ciencias Biologicas y Fisiologicas, Laboratorio de
Fisiologia Comparada, Universidad Peruana Cayetano Heredia, Lima,
Peru, 3 Laboratorie "Reponses cellulaires et fonctionnelles a
l'hypoxie," EA2363, ARPE, UFR SMBH, Universite Paris 13, Bobigny,
France; pole Urgences, CHU Grenoble, La Tronche, France, 4 Laboratorie
"Reponses cellulaires et fonctionnelles a l'hypoxie," EA2363, ARPE,
UFR SMBH, Universite Paris 13, Bobigny, France; Service de Physiologie
et Explorations Fonctionnelles, AP-HP, hopital Jean Verdier, Bondy,
France, 5 Service de Physiologie et Explorations Fonctionnelles,
Service de Pharmacie, AP-HP, hopital Avicenne, Bobigny, France
* To whom correspondence should be addressed. E-mail:
richalet@smbh.univ-paris13 . fr .
Rationale:
Monge's disease is characterized by an excessive erythrocytosis,
frequently associated with pulmonary hypertension, in high altitude
dwellers. It has a considerable impact on public health in high
altitude regions. A preliminary study demonstrated the efficiency of
acetazolamide (250 mg/day for 3 weeks) in reducing serum
erythropoietin and hematocrit.
Objectives:
Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg
acetazolamide that could be chronically implemented and its effects on
pulmonary artery pressure and cardiac function.
Methods:
A two-phase study was performed in patients (hematocrit 63%) from
Cerro de Pasco, Peru (4,300 m). First phase: a double blind placebo-
controlled study in 55 patients who receive a single dose of either
250mg acetazolamide (n=40) or placebo (n=15) by daily oral
administration for twelve weeks. Second phase (open label): after a
four-week wash out period, all patients received 250mg acetazolamide
for twelve weeks. Hematocrit, blood gases, clinical outcome and
pulmonary artery circulation were evaluated.
Results:
First phase: acetazolamide decreased by 44% the number of polycythemic
subjects (p=0.02), decreased hematocrit from 69 to 64% (p<0.001) and
increased arterial O2 pressure from 42 to 45 mmHg (p<0.001). No severe
adverse effect, nor hypokalemia was recorded. The second phase
reproduced the effects observed during the first phase, without
cumulative effects on hematocrit. A four-week washout restored basal
hematocrit. Only patients who received Acz for 6 months showed a clear
reduction in pulmonary vascular resistance.
Conclusions:
Acetazolamide reduces erythrocytosis and improves pulmonary
circulation in Monge's disease without adverse effects. Its
implementation as a chronic treatment for this disease appears
efficient and safe. Registered at w w w .clinicaltrials.gov, ID#
NCT00424970
Key words: hypoxia, altitude, pulmonary hypertension, chronic mountain
sickness
Who loves ya.
Tom
Jesus Was A Vegetarian!
* tinyurl . com /2r2nkh
Man Is A Herbivore!
* tinyurl . com /a3cc3
DEAD PEOPLE WALKING
* tinyurl . com /zk9fk
