Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension

OBJECTIVE: To test whether adding hydrochlorothiazide (HCTZ) (12.5 or 25 mg) to olmesartan 20 mg improves 24-h blood pressure in patients whose conventional diastolic blood pressure is inadequately controlled by olmesartan monotherapy. PATIENTS: Male and female patients > or = 18 years with mean sitting diastolic blood pressure (DBP) of 100-115 mmHg, mean sitting systolic blood pressure (SBP) greater than 150 mmHg, mean 24-h DBP of at least 84 mmHg, and at least 30% of DBP daytime readings > 90 mmHg. INTERVENTIONS: Four weeks of single-blind treatment with olmesartan 20 mg once daily, followed in non-responders by 8 weeks of randomized double-blind treatment with placebo or HCTZ (12.5 or 25 mg) once-daily, added to olmesartan. RESULTS: HCTZ 25 mg added to olmesartan 20 mg decreased mean daytime DBP significantly more (P = 0.0012) than placebo added to olmesartan 20 mg. Compared to olmesartan monotherapy, mean 24-h DBP and SBP were significantly reduced by combination therapy with olmesartan/HCTZ 20/12.5 mg (-1.9 mmHg, P = 0.0167 and -3.9 mmHg, P = 0.0018, respectively) and 20/25 mg (-3.7 and -7.4 mmHg respectively, P < 0.0001 for both). Mean 24-h DBP and SBP and mean night-time SBP reductions were significantly greater for HCTZ 25 mg than for HCTZ 12.5 mg. Response rates (mean daytime DBP assessed by ambulatory blood pressure measurement < or = 85 mmHg) approximately doubled following the addition of HCTZ (12.5 mg = 57.6% and 25 mg = 69.5%). CONCLUSION: Combination of olmesartan 20 mg with HCTZ provides significantly better 24-h blood pressure reduction than olmesartan monotherapy in patients with mild-to-moderate hypertension. Moreover, increasing the dose of HCTZ from 12.5 to 25 mg is a reasonable step to reach better daytime and night-time blood pressure control.     

Acid-base regulation of ion transport in rabbit ileum in vitro

Changes in acid-base balance have a major influence on ion transport in the ileum. The goals of the present study were to delineate (a) the specific transport processes most affected by changes in acid-base metabolism, (b) the individual roles of pH, PCO2, and concentration of HCO3- in modulating ion transport, and (c) the relationship between acid-base sensitive and other ion-transport systems. Ion transport and electrical parameters were measured in rabbit ilea in vitro under short-circuit conditions with systematic variations of pH, PCO2, and concentrations of HCO3-. Increasing HCO3- concentrations, with constant PCO2 and increasing pH, caused a decrease in electroneutral Na+ and Cl- absorption. At 5 mmol/L HCO3-, net fluxes of Na+ and Cl- were 5.9 +/- 1.4 and 4.5 +/- 1.1 microEq.cm-2.h-1, while at 50 mmol/L HCO3-, net Na+ and Cl- fluxes were 0.7 +/- 0.7 and 0.2 +/- 0.6 microEq.cm-2.h-1. Transepithelial HCO3(-)-gradient experiments suggested that serosal HCO3- was the principal factor. Changes in PCO2 showed a complex biphasic response, increasing net Cl- flux as PCO2 increased from 11-30 mm Hg in 5 mmol/L HCO3-; net Na+ flux increased as PCO2 was changed from 36 to greater than 100 mm Hg in 22 mmol/L HCO3-. In contrast, increasing pH in a bicarbonate-free N-2-hydroxyethylpiperazine-N'-2 = ethane sulfonic acid buffer did not significantly alter Na+ transport. Acid-base stimulated Na+ absorption was inhibited by 10(-3) mol/L amiloride, but not by bumetanide, consistent with the involvement of Na(+)-H+ exchange rather than Na(+)-Cl- cotransport. Epinephrine did not increase Na+ absorption under acid-base stimulated conditions, but glucose did, suggesting that the rate-limiting step for electroneutral absorptive processes under these conditions occurs at the apical rather than the basolateral membrane. Combining all experiments, a significant correlation existed between net flux of Na+ and HCO3- concentration (r = -0.72, P less than 0.05) and between net flux of Na+ and pH (r = -0.68, P less than 0.01). Chloride absorption was correlated with pH (r = 0.72, P less than 0.01). These results suggest a profound regulatory role for acid-base balance in electroneutral Na(+)-Cl- transport in rabbit ileum in vitro.     

Atrial natriuretic factor and cyclic guanosine monophosphate: ion transport in rat colon in vitro and in vivo.

The role of atrial natriuretic factor receptors in the colon is uncertain. Accordingly, the effects of atrial natriuretic factor in vivo and in vitro were studied. In vivo perfusion of the colon in Sprague-Dawley rats was used to measure Na+, K+, Cl-, and water transport, while atrial natriuretic factor was infused into the jugular vein at 0.5 or 1.0 micrograms.kg-1.min-1. In vitro experiments in Ussing chambers measured short-circuit current and ion fluxes before and after atrial natriuretic factor administration. Because cyclic guanosine monophosphate is thought to be a second messenger for atrial natriuretic factor, short-circuit current was also determined before and after exposure to 8-Br-cyclic guanosine monophosphate. Plasma atrial natriuretic factor (atriopeptin III) levels were determined by radioimmunoassay. The in vivo transport of water, sodium, and chloride and the secretion of potassium were not altered by atrial natriuretic factor infusion. In vitro studies showed no change in Na+ or Cl- transport or change in short-circuit current. Plasma atrial natriuretic factor concentrations increased from 139 +/- 55 pg/mL to 1385 +/- 396 pg/mL during infusion, and urine output increased from 12.6 +/- 0.5 microL/min to 37.4 +/- 2.9 microL/min (P less than 0.05). In contrast, 8-Br-cyclic guanosine monophosphate in vitro caused a significant (P = 0.0004) increase in short-circuit current from 1.2 +/- 0.2 to 2.9 +/- 0.3 microEq.cm-2.h-1.     

Anomaly of the vena cava inferior with paracaval venous aneurysm and renal collateralisation

Aneurysms of the great venous vessels represent anatomical rarities. Most malformations of the venous system published so far concern mainly the inferior vena cava and arise in different formations. Reports of malformations of the renal veins are limited to a few case reports and may lead to diagnostic and therapeutic difficulties. We report on an case of a asymptomatic, aneurysmatic venous malformation of the vena cava inferior With consideration of the entire findings we preferred a conservative treatment of the patient.     

Secretory diarrhea

Opinion Statement Because diarrhea is a symptom and not a disease, the choice of therapies depends on the ability to determine a specific etiology or the necessity to resort to a nonspecific antidiarrheal approach. Attention to diet and lifestyle may provide clues to the etiology of diarrhea that can obviate complex work-ups and therapies. There are myriad tests to evaluate chronic diarrhea; perhaps the most frequently neglected is a timed collection of stool volume. Results from this test can help direct further work-up parsimoniously. Secretory diarrhea caused by neuroendocrine tumors is rare, but may respond well to specific therapies. Nonspecific therapies are very effective in controlling symptoms when no individual diagnosis is at hand. A judicious use of diagnostic options and therapies can lead to a successful outcome for most cases of chronic diarrhea.     

Antagonism of ethanol-induced depressant effects by 4-aminopyridine in the central nervous system of the rat

Intraperitoneal injection of ethanol (2 g/kg) produced significant motor impairment in rats, as measured by performance on the tilting plane. Administration of 3 mg/kg 4-aminopyridine (4-AP) antagonized the depressant effect of ethanol on motor performance. Using slices of hippocampus, in vitro, 4-aminopyridine (10-100 microM) also antagonized the ethanol-induced depressant effect on orthodromically-elicited population spikes in the CA1 pyramidal cell layer. This antagonism appears to result from the ability of 4-aminopyridine to enhance release of transmitter in both excitatory and inhibitory neurones. Due to a number of unwanted side effects, further evaluation of 4-aminopyridine and its analogues needs to be done before it can be considered useful in the management of acute intoxication with ethanol.