Single-chamber ventricular pacing increases markers of left ventricular dysfunction compared with dual-chamber pacing.

AIMS: Large randomized trials comparing DDD with VVI pacing have shown no differences in mortality, but conflicting evidence exists in regard to heart failure endpoints. Here we evaluated the effect of pacing mode on serum levels of brain natriuretic peptide (BNP) and amino-terminal-proBNP (NT-proBNP). Methods Forty-one patients (age 73 +/- 10 years) with dual-chamber pacemakers were included in a prospective, single-blind, randomized crossover study evaluating the impact of DDD(R)/VDD versus VVI(R) mode on objective and functional parameters. Data were collected after a 2-week run-in phase and after 2 weeks each of VVI(R) and DDD(R)/VDD pacing or vice versa. Results BNP and NT-proBNP levels during DDD(R)/VDD stimulation (151 +/- 131 and 547 +/- 598 pg/mL) showed no change compared with baseline (154 +/- 130 and 565 +/- 555 pg/mL), but a significant 2.4-fold increase was observed during VVI(R) mode [360 +/- 221 and 1298 +/- 1032 pg/mL; P < 0.001 compared with DDD(R)/VDD]. The assessment of functional class, the presence of pacemaker syndrome [49% in VVI(R) mode] and the patients' preferred pacing mode showed significant differences in favour of DDD(R)/VDD pacing. CONCLUSION: Patients can differentiate between DDD(R)/VDD and VVI(R) pacing, and prefer the former. Compared with DDD(R)/VDD pacing, VVI(R) stimulation induces a two- to three-fold increase in serum BNP and NT-proBNP levels.     

The inhibitory effect of aspirin on fibrinolysis is reversed by iloprost, a prostacyclin analogue

The reduced fibrinolytic response after aspirin intake may be due to prevention of prostacyclin production. The effect of iloprost (a stable prostacyclin analogue) was tested on the fibrinolytic activity (euglobulin lysis area on fibrin plate [E.L.A.], t-PA antigen, PAI activity and PAI-1 antigen) of plasma drawn after venous stasis test from six healthy male volunteers, who each received all the following treatments according to a single-blind randomized cross-over design: placebo, iloprost, aspirin + placebo, aspirin + iloprost. The mean E.L.A. value after venous occlusion was significantly higher than the basal level after every treatment but aspirin. Within each treatment group the t-PA antigen levels in response to venous stasis were significantly higher than the basal ones. PAI-1 antigen levels did not change significantly before and after venous stasis either within or among the treatment groups. These data are consistent with the hypothesis that the mechanism related to aspirin's effect on fibrinolysis is mediated by suppression of vessel wall prostacyclin production. Aspirin's inhibitory effect on fibrinolysis was in fact prevented by replacing endogenous prostacyclin with iloprost. Iloprost enhances fibrinolytic activity reduced by aspirin, but not by promoting t-PA release or by inhibiting release of the specific inhibitor, PAI-1.     

Gender, equity: new approaches for effective management of communicable diseases

This editorial article examines what is meant by sex, gender and equity and argues that these are critical concepts to address in the effective management of communicable disease. Drawing on examples from the three major diseases of poverty (HIV, tuberculosis [TB] and malaria), the article explores how, for women and men, gender and poverty can lead to differences in vulnerability to illness; access to quality preventive and curative measures; and experience of the impact of ill health. This exploration sets the context for the three companion papers which outline how gender and poverty shape responses to the three key diseases of poverty in different geographical settings: HIV/AIDS in Kenya; TB in India; and malaria in Ghana.     

Sustained effectiveness of chronic prazosin therapy in severe chronic congestive heart failure

Twelve patients with severe chronic congestive heart failure (CHF) (NYHA class III and IV) resistant to digitalis and diuretics were treated with the postsynaptic alpha-blocking agent prazosin (PZ) (3 to 20 mg/day). In 11 patients oral PZ treatment was well tolerated; the agent was discontinued in the remaining patient because of orthostatic dizziness. After 4 weeks of PZ, total systemic vascular resistance decreased from 2245 ± 792 to 1603 ± 355 dyn sec cm^?5, mean blood pressure declined from 100 ± 15 to 90 ± 14 mm Hg, and pulmonary capillary wedge pressure decreased from 29 ± 8 to 25 ± 9 mm Hg. Cardiac index increased from 1.92 ± 0.63 to 2.30 ± 0.41 l/min/m². The increase of stroke volume index correlated with the fall in peripheral vascular resistance (r = ?0.79, p < 0.01) and the decline in pulmonary capillary wedge pressure (r = ?0.75, p < 0.05). In parallel, exercise tolerance increased significantly. Four patients improved from functional class IV to II, four from class IV to III, and one from class III to II, while two patients were unchanged. In the eight patients followed for 6 months, the beneficial effects of ambulatory PZ were maintained throughout the expansive observation period. Three patients died as their disease process progressed during the study (sudden death, pneumonia, and post-PZ withdrawal pump failure). Prazosin is a valuable vasodilator for long-term treatment of otherwise refractory congestive heart failure with the agent given in sufficient individualized dosage.     

Expression of glycoprotein hormone alpha-subunit by endocrine cells of the oxyntic mucosa is associated with hypergastrinemia

Previous studies have shown that hyperplastic endocrine cells of the oxyntic mucosa in patients with atrophic gastritis may express immunoreactivity for the alpha-subunit of human chorionic gonadotropin (alpha-HCG, common to all glycoprotein hormones). Since this endocrine proliferation is regarded as dependent on the trophic effect of the concomitant hypergastrinemia, the relation between immunohistochemical expression of alpha-HCG by oxyntic endocrine cells and serum levels of gastrin were investigated. The study was performed on endoscopic gastric biopsies of the oxyntic mucosa from 49 patients subdivided into the following groups: A) with histologically normal mucosa and normogastrinemia (22 cases), B) with atrophic gastritis and normogastrinemia (12 cases), C) with normal mucosa and hypergastrinemia (Zollinger-Ellison syndrome, retained antrum) (7 cases) and D) with atrophic gastritis and hypergastrinemia (with or without pernicious anemia) (8 cases). The alpha-HCG immunoreactive cells were found in all hypergastrinemic patients (groups C and D), regardless of the concomitant pathological condition of the mucosa. These cells accounted for 7.8% to 44.7% of the number of Grimelius argyrophil cells in consecutive serial sections. In contrast, alpha-HCG-containing cells were exceptional or absent in most normogastrinemic patients. Their number was sizable in only two cases of group A and three cases of group B, where it ranged from 2.5% to 14.8% of the number of argyrophil cells. It was concluded that expression of alpha-HCG is another feature of oxyntic endocrine cells associated with hypergastrinemia in addition to those previously recognized such as development of hyperplasia and/or carcinoid tumors.