Biomedical subjects

B Jilma

Publications and source records attributed to B Jilma.

95 records · Page 6Linked to original sources

PubMed1994

In vivo study of the effect of exogenous estradiol on alpha-adrenoceptor responsiveness of human veins.

Based on previous experimental and epidemiologic findings, we hypothesized that 17 beta-estradiol (E2) could decrease the alpha-adrenergic responsiveness in venous smooth muscle cells (VSMC), thereby decreasing venous tone and contributing to the pathogenesis of varicose veins. To test this hypothesis, the effect of an acute increase in E2 serum concentrations on venous alpha-adrenergic responsiveness to norepinephrine (NE) was studied in young healthy men. We conducted a double-blind, randomized, placebo-controlled cross-over study in 23 male volunteers; 96 +/- 2 h after a single intramuscular (i.m.) injection of 10 mg estradiol valerate or placebo, we quantified the pharmacologic effects of estradiol on alpha-adrenergic responsiveness of superficial hand veins by venous compliance technique (VCT) and on resting blood pressure (BP). After administration of estradiol, E2 serum levels increased 9.97 +/- 7.54-fold (mean +/- 1 SD, p < 0.001) to within the range of premenopausal preovulatory women. No significant difference was observed in mean dose of NE required for half-maximal venoconstriction (ED50, p = 0.224), however, or in the maximal effect of NE (Emax, p = 0.796) after administration of E2 as compared with placebo. A significant difference in diastolic BP (DBP) (p = 0.039) was observed after E2 administration (64.6 +/- 7.7 mm Hg) as compared with placebo (68.3 +/- 7.6 mm Hg); BP (SBP) was not affected (p = 0.786). Our findings do not support the concept that E2 reduces alpha-adrenoceptor responsiveness of SMC in superficial veins.

Adult↗

PubMed1994

Effects of 17 beta-estradiol on circulating adhesion molecules.

The effects of 17 beta-estradiol (E2) on the serum levels of the circulating endothelial-leukocyte, intercellular, and vascular adhesion molecules [ELAM-1, ICAM-1 (CD54), and VCAM-1] were evaluated in healthy male volunteers after single im injection of 10 mg E2 valerate. In addition, a time course of the effects of E2 on circulating adhesion molecules (AMs), cortisol serum levels, differential blood counts, and surface expression of the lymphocyte function-associated antigen-1 (CD11a/CD18), CD3, CD4, CD19, and CD25 on leukocytes was studied in another group of volunteers. A 5% decrease in circulating ICAM-1 (P = 0.045 vs. placebo) was found when a single time point (96 h after E2 injection) was studied. However, this decrease was smaller than the intrasubject (day to day) variability observed, and there was no consistent and time-dependent effect of E2 on circulating AMs. Circulating neutrophils increased 2.3-fold over baseline after E2 treatment (P = 0.0008 vs. placebo). The mean coefficients of variation for the intrasubject (day to day) and intersubject variability of circulating AMs were between 5.4-7.5% and 20-29%, respectively. Our findings indicate that the effect of E2 on circulating AMs is not distinguishable from the intrasubject variability observed after placebo treatment. Thus, an effect of E2 on adhesion molecules is unlikely to contribute to the antiatherogenic-cardioprotective effect of E2. The pronounced E2-mediated increase in neutrophils deserves further studies to elucidate its (patho-)physiological implications.

Adult↗

PubMedDate not supplied

Immunoglobulin administration to fetuses with anemia due to alloimmunization to D.

BACKGROUND: The purpose of this study was to examine fetal tolerance of high-dose intravenous immunoglobulin (IVIG), given directly at the time of intravascular transfusion, and its effects on fetal hemolysis and pregnancy outcome in the setting of alloimmunization to D. STUDY DESIGN AND METHODS: Thirteen consecutive D+ fetuses requiring transfusion for maternal alloimmunization received high-dose IVIG (1.0 g/kg) and red cell transfusions. Twenty-four previous, consecutive fetuses with maternal anti-D served as controls. The schedules for subsequent transfusions were the same in the two groups. RESULTS: High-dose IVIG was well tolerated by all fetuses. In the IVIG group, daily decreases in hematocrit were smaller than those in controls after the second administration of IVIG (mean hematocrit decrease, 0.72 percent/day vs. 1.45 percent/day; p = 0.007). No significant difference was found in the total number of fetal transfusions, the gestational age at delivery, the duration of neonatal intensive care, the number of neonates requiring postnatal transfusion therapy, and perinatal mortality. CONCLUSION: In this small pilot study, direct administration to fetuses of IVIG with red cell transfusions was well tolerated and appeared to have a beneficial effect on fetal hemolysis.

Female↗

PubMedDate not supplied

Heparin blunts endotoxin-induced coagulation activation.

BACKGROUND: Lipopolysaccharide (LPS) is a major trigger of sepsis-induced disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is known about the effects of clinically used anticoagulants in this setting. Therefore, we compared with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on LPS-induced coagulation. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. In the placebo group, activation of coagulation caused marked increases in plasma levels of prothrombin fragment F(1+2) (P<0.01) and polymerized soluble fibrin, termed thrombus precursor protein (TpP; P<0.01); TF-positive monocytes doubled in response to LPS, whereas levels of activated factor VII slightly decreased and levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decreased activation of coagulation caused by LPS, as F(1+2) and TpP levels only slightly increased; TF expression on monocytes was also markedly reduced by UFH. TF pathway inhibitor values increased after either heparin infusion (P<0.01). Concomitantly, factor VIIa levels dropped by >50% at 50 minutes after initiation of either heparin infusion (P<0.01). CONCLUSIONS: This experimental model proved the anticoagulatory potency of UFH and LMWH in the initial phase of experimental LPS-induced coagulation. Successful inhibition of thrombin generation also translates into blunted activation of coagulation factors upstream and downstream of thrombin.

Adult↗

PubMedDate not supplied

Rofecoxib exerts no effect on platelet plug formation in healthy volunteers.

OBJECTIVE: Although rofecoxib has very high selectivity for cyclo-oxygenase 2 (COX-2), supratherapeutic rofecoxib concentrations (> 1000 mg) inhibit purified human COX-1 in vitro and TXB2 formation in vivo. It is therefore possible that higher doses of rofecoxib may affect platelet function. This could be important if rofecoxib is given to thrombocytopenic patients. In these cases, already moderate inhibition of platelet function could precipitate bleeding complications. We therefore set out to investigate the influence of rofecoxib on platelet function in healthy volunteers. METHODS: We set up a balanced-randomised, double-blind, placebo-controlled, two way cross-over study. Peripheral blood was withdrawn from 42 healthy volunteers before and 3 hours after intake of 50, 250, 500 mg of rofecoxib or placebo (n = 14 per group). Platelet function was assessed by a platelet function analyzer (PFA-100) which measures collagen-epinephrine induced closure time (CEPI-CT) under shear stress. RESULTS: CEPI-CT increased by 14% (p = 0.002) and 11% (p = 0.003) three hours after intake of placebo and rofecoxib at dosages of up to 500 mg, respectively. The increase in CEPI-CT versus baseline was not significantly different in the placebo period compared with the active treatment periods (n = 42, p > 0.05). CONCLUSIONS: Rofecoxib does not impair platelet function. Thus, rofecoxib appears to be a valuable analgetic and antipyretic agent in the therapy of patients at risk for bleeding.

Adult↗