Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24-h intragastric pH and serum gastrin in healthy subjects.

AIM: To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two-way crossover, clinical pharmacology study. METHODS: Twenty-four healthy subjects (14 men, 10 women; mean age 26.8 years) received rabeprazole 20 mg or esomeprazole 20 mg daily on days 1-5, with a 14-day 'wash-out'. Intragastric pH was recorded continuously, and serum gastrin measured, on days 0, 1 and 5. RESULTS: On day 0, mean intragastric pH AUC was significantly higher before the esomeprazole than before the rabeprazole treatment in four of the five time intervals analysed. On days 1 and 5, mean intragastric pH AUC was higher after rabeprazole than esomeprazole during 5-11, 14-24 and 0-24 h after dosing. Mean pH AUC in the first 5 h after dosing on day 5 was higher after esomeprazole than rabeprazole (P=0.012). On day 1, mean per cent times pH > 3 and > 4 were significantly greater after rabeprazole than esomeprazole during 0-14, 14-24 and 0-24 h. On day 5, mean serum gastrin AUC0-4 was higher (P = 0.017) after rabeprazole than esomeprazole (335 vs. 316 pg/mL.h). CONCLUSION: In this clinical pharmacology study, rabeprazole 20 mg daily was more effective than esomeprazole 20 mg daily in increasing intragastric pH and maintaining pH > 3 and > 4. On day 5, mean pH AUC was higher after esomeprazole than rabeprazole.

Transfusion-associated falciparum malaria successfully treated with red blood cell exchange transfusion.

Falciparum malaria is frequently associated with significant morbidity and mortality. The use of exchange transfusion as a therapeutic modality for severe cases of malaria has been described previously. We describe a case of a 49 year-old African American gentleman with a history of hemoglobin-SC disease who presented with a severe case of Plasmodium falciparum malaria 3 weeks after having received an infected blood transfusion. His peripheral smear showed the presence of numerous intraerythrocytic ring forms and "banana-shaped" gametocytes with a high-grade parasitemia, estimated at 18%. He was treated with antimalarial chemotherapy and also underwent a 12-unit red blood cell exchange transfusion, decreasing his parasite load to < 1%, as determined on repeat smear. It is prudent to be aware of the efficacy of this adjunctive treatment, especially with ever-increasing travel and a resultant increase in the prevalence of tropical diseases in the United States.

Role of nitric oxide in isoprenaline and sodium nitroprusside-induced relaxation in human hand veins.

AIMS: Recent reports, largely in animal models, have suggested that either inhibition of nitric oxide (NO) synthase or endothelium removal in arteries inhibits the response to isoprenaline, a beta-adrenoceptor agonist, and also enhances the response to sodium nitroprusside, a nitrovasodilator. This in vivo study was designed to determine whether N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, influences relaxation of human hand veins mediated by isoprenaline or by sodium nitroprusside. METHODS: Using the dorsal hand vein technique, full dose-response curves to bradykinin (0.27-278 ng min(-1), n=6), isoprenaline (2.12-271 ngmin(-1), n=8) and sodium nitroprusside (0.01-634 ng min(-1) n=7) were generated on separate occasions before and after L-NMMA co-infusion (50 microg min(-1)). RESULTS: In veins preconstricted with the alpha1-adrenoceptor-selective agonist phenylephrine, the three vasodilators induced maximal responses (Emax) of 119+/-35, 72+/-18 and 103+/-17%, respectively. L-NMMA inhibited relaxation to bradykinin by 64% (P=0.014) but did not influence relaxation induced by isoprenaline. The sensitivity to sodium nitroprusside was significantly enhanced by L-NMMA co-infusion (concentration shift of 2.3, P=0.031). CONCLUSIONS; We conclude that in human veins, spontaneously released NO does not play a major role in isoprenaline-induced relaxation. Our results also suggest that the effects of sodium nitroprusside in this vascular bed may be attenuated by endothelium-derived NO.

Inhibition of angiotensin-converting enzyme in human hand veins.

Conversion of angiotensin I to angiotensin II likely occurs in human veins, supporting the existence of endothelial angiotensin-converting enzyme (ACE) activity in these vessels. Using the dorsal hand vein technique, we investigated the effects of 2 ACE inhibitors, captopril (single oral dose of 6.25 mg) and enalaprilat (local infusion of 1 microgram/min), on venous responsiveness in healthy subjects. Orally administered captopril induced a marked decrease in angiotensin I- but not angiotensin II-induced venoconstriction. This blunted response persisted for at least 4 hours. Enalaprilat and captopril increased the sensitivity to bradykinin, decreasing the dose producing half-maximal response (ED50) of bradykinin 18-fold and 5-fold, respectively, without changing the maximal venodilatory response. These results confirm that there is substantial rapid metabolism of angiotensin I in human veins and suggest that a single dose of locally infused angiotensin I can be used with the dorsal hand vein technique to assess the time-course effect of vascular ACE inhibition after oral administration. Our findings also extend previous in vitro observations in human veins by showing that these agents potentiate the venodilatory effects of bradykinin in vivo.

Pseudotumour of the orbit: bilateral metachronous presentation.

A case is presented of a pseudotumour that developed in the left orbit 4 years after surgery and histological confirmation of a pseudotumour in the right orbit. There was no evidence of any thyroid pathology.