Search PubMed⌕ Search

Biomedical subjects

F Skrabal

Publications and source records attributed to F Skrabal.

At least 37 records · Page 2Linked to original sources
PubMed1997

Essential hypertension in African Caribbeans associates with a variant of the beta2-adrenoceptor.

Populations of West African ancestry dwelling in Western communities exhibit greater prevalence of human essential hypertension and higher rates of end-organ damage. The sympathetic nervous system influences cardiac output, vascular tone, renal sodium reabsorption, and renin release and could be implicated in enhanced vascular responsiveness observed in African hypertensives. Such an effect could arise from genetic variants that alter agonist response of alpha-adrenoceptors, leading to enhanced vasoconstriction, or attenuate beta2-adrenoceptor-mediated vasodilatation. Indeed, there is evidence of a blunted vasodilator response to the beta-agonist isoprenaline in African Americans. A variant of the beta2-adrenoceptor gene that encodes glycine rather than arginine at position 16 (Arg16-->Gly) has been shown to confer exaggerated agonist-mediated receptor downregulation, which might attenuate vasodilator response. One hundred thirty-six unrelated hypertensives and 81 unrelated normotensives of African Caribbean origin were identified from primary care on the island of St Vincent. Genomic DNA from these subjects was analyzed for the presence of the Gly16 and Arg16 alleles by using an allele-specific polymerase chain reaction method. We report strong support for association of the prodownregulatory glycine 16 variant of the beta2-adrenoceptor gene with hypertension in African Caribbeans from St Vincent and the Grenadines (chi2=18.9, P=.000014, 1 df). This observation, coupled with reports of attenuated vasodilator responses to beta-agonists among people of West African ancestry, may provide a mechanism for enhanced vascular reactivity and identify a candidate gene for hypertension in this ethnic group.

Adult↗
PubMed1997

Effect of controlled extracorporeal blood cooling on ultrafiltration-induced blood volume changes during hemodialysis.

Considerable amounts of heat may be lost or gained through the extracorporeal circuit during hemodialysis and influence the hemodynamic stability of the dialysis patient. The effects of two levels of extracorporeal heat flux (Jtherm in W) on blood pressures and ultrafiltration-induced blood volume changes were studied in eight patients on conventional hemodialysis. Treatments were controlled automatically for mild to medium Jtherm of either -13.4 +/- 3.3 W (group A) or -30.2 +/- 3.7 W (group B) (1 W = 1 J/s = 3.6 kJ/h = 0.239 cal/s = 0.86 kcal/h) and repeated once. Values are given as mean +/- SD. With low blood flows (Qb = 251 +/- 21 ml/min), dialysate temperatures were automatically set at 37.3 +/- 0.3 degrees C (group A) and 35.3 +/- 0.2 degrees C (group B) for the two levels of Jtherm, respectively. Arterial blood temperatures increased by 0.4 +/- 0.4 degree C with mild extracorporeal cooling (group A), whereas arterial blood temperatures slightly decreased by -0.1 +/- 0.4 degree C in the group with medium negative heat flux (group B) (P < 0.01). Blood pressures tended to drop in the warm dialysate group and to remain unchanged in the cool dialysate group (P = NS). Relative blood volume changes calculated from on-line ultrasonic blood measurements were significantly larger with cool (-12.8 +/- 8.3 vol%) than with warm (-7.2 +/- 5.5 vol%, P < 0.05) dialysate, indicating reduced fluid removal from peripheral body compartments during cool hemodialysis ultrafiltration. Despite the larger reduction in intravascular volume, intradialytic hemodynamic stability was maintained with extracorporeal cooling and cool dialysate prescription.

Aged↗
PubMed1997

Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration.

OBJECTIVE: To evaluate a novel technique for on-line continuous glucose measurement in subcutaneous adipose tissue, and to investigate its accuracy for detection of hypoglycemia. RESEARCH DESIGN AND METHODS: The method combined an open-flow microperfusion of subcutaneous adipose tissue using a double lumen catheter and an extracorporeal sensor cell. An isotonic ion-free solution was perfused through the inner lumen of the catheter, equilibrated with the subcutaneous tissue fluid, and sampled through the outer lumen. The recovery was continuously monitored as the ratio between the measured sampled fluid conductivity and the subcutaneous tissue fluid conductivity (assumed to have a constant value of 1.28 S/m at 25 degrees C). Glucose concentration was calculated on-line from the measured glucose in the sampled fluid and the measured recovery in healthy volunteers during hyperglycemic glucose loads (n = 8), hypoglycemic hyperinsulinemic clamp (n = 6), and a 24-h monitoring period (n = 7). RESULTS: Subcutaneous glucose concentrations in the fasting state were 94% of the plasma glucose concentrations in arterialized venous samples. According to the error grid analysis, 96.9% of the on-line measured subcutaneous glucose concentrations during hyperglycemia and 96.3% during hypoglycemia were in accurate or acceptable zones. The mean differences between the measured subcutaneous glucose and the actual plasma glucose concentration were -0.06-3.3 mmol/l (hyperglycemia), and -0.6-1.1 mmol/l (hypoglycemia). CONCLUSIONS: By combining open-flow microperfusion, glucose sensor, and conductivity measurement, glucose concentration in the subcutaneous adipose tissue can be monitored on-line, extracorporeally, and continuously without any in vivo calibration, and gives accurate measurements during hyper- and hypoglycemia.

Adipose Tissue↗
PubMed1996

Thin-film microbiosensors for glucose-lactate monitoring.

A miniaturized device for simultaneous measurement of glucose and lactate levels was produced by means of photopatterning of enzyme-containing photosensitive membrane precursors. This device shows no cross-talk and a lifetime for both the glucose and the lactate sensors of more than 2 weeks when continuously operated in undiluted bovine serum. Linear response ranges of up to 40 mM for glucose and 25 mM for L-lactate, in combination with 95% response times of < 30 s, were realized. The devices are mass produced by means of thin-film technology on flexible carriers to give catheter-type multisensing devices for in vivo applications. Ex vivo experiments, performed with human volunteers, where the device was continuously operated in an extracorporeal, undiluted, heparinized blood stream for 6 h, gave a correlation of r > 0.98 with respect to laboratory techniques. Subcutaneous measurements of glucose levels in pigs were close to the corresponding blood levels obtained without in vivo calibration.

Adult↗
PubMed1996

Portable device for continuous fractionated blood sampling and continuous ex vivo blood glucose monitoring.

The objective of the study was to develop and evaluate a portable device for continuous fractionated blood sampling and continuous ex vivo monitoring of blood glucose. The inner lumen of a double lumen catheter (18 gauge x 45 mm) was placed in a peripheral vein and perfused with heparin solution (1.4 U min-1). The outer lumen was used to collect heparinized blood into 48 vacuum tubes at programmable sample volumes and time intervals (0.2-2 ml in 2.5-30 min). A sensor flow chamber with an internal volume of 1 mm3 incorporating a miniaturized thin-film amperometric glucose sensor was placed in the sampling line for continuous ex vivo blood glucose monitoring. Blood glucose and plasma insulin were measured during a frequently sampled intravenous glucose tolerance test (250 mg kg-1) and a subsequent oral glucose tolerance test (150 g) over 6 h in eight healthy volunteers (BMI 24.5 +/- 3.2 kg m-2). Additionally, in four experiments blood glucose was measured on-line using the glucose sensors. The overall correlation coefficients for whole blood glucose and plasma insulin between the manually drawn samples and the vacuum tubes were 0.73 and 0.87, respectively (p < 0.001). The miniaturized glucose sensor exhibited a linear measuring range of 25 mmol-1 glucose concentration and 95% response times of less than 30 s. Sensor readings and laboratory analyser results for the blood glucose measurement correlated between 0.93 and 0.98 (p < 0.001). In summary, continuous fractionated blood sampling and ex vivo blood glucose monitoring in ambulatory subjects is possible with a portable device.

Adult↗
PubMed1995

Numerical approximation of mathematical model for absorption of subcutaneously injected insulin.

A pharmacokinetic model is modified to enable quantitation of subcutaneous insulin absorption following insulin injections of soluble insulin and monomeric insulin analogues. The model for soluble insulin includes diffusion, equilibration between hexameric and dimeric insulin and absorption of dimeric insulin molecules. Numerical approximation is carried out by modelling the whole system as a capacitor-resistor network with lumped elements and discrete sources and sinks. By means of the analytical solution for monomeric-insulin absorption, it can be shown that the approximation scheme yields sufficiently accurate results. The modified model for soluble insulin demonstrates dose- and concentration-dependent insulin absorption within the range of therapeutic concentrations and volumes. Additionally, parameters are estimated from published glucose-clamp data. The results of the data fitting indicate that the model presented is adequate for pharmacological studies. The model is suitable for individual parameter estimation from the time course of plasma insulin or from the disappearance curves of radiolabelled injected insulin.

Humans↗
PubMed1994

Salt and asthma.

Explore the source record for details and available documents.

Asthma↗
PubMed1992

Beta 2-adrenoceptor density in fibroblast culture correlates with human NaCl sensitivity.

To study salt sensitivity in humans and its relation to expression of adrenoceptors, 20 male normotensive Caucasians were investigated on a diet of 180 mmol NaCl/day followed by 60 mmol NaCl/day over 2 wk and again by 180 mmol NaCl/day over 2 wk, and blood pressure changes were assessed by long-term oscillatory blood pressure monitoring under basal conditions. Individual cell cultures of skin fibroblasts from skin biopsies were also established, and alpha 2- and beta 2-adrenoceptors were measured. Seven subjects were salt sensitive, and the remainder were salt resistant. Cultured skin fibroblasts in salt-sensitive subjects express less than half the number of beta 2-adrenoceptors compared with salt-resistant subjects (65 +/- 12.7 vs. 173 +/- 14.8 fmol/mg, P less than 0.001), and there is a correlation between the absolute rise of blood pressure on a high-salt diet and the density of beta 2-adrenoceptors (r = -0.67, P less than 0.01). It remains to be established whether a reduced in vitro density of beta 2-adrenoceptors in cultured cells is causally related to salt sensitivity in normotensive humans.

Binding Sites↗
PubMed1991

[Further advances in the salt sensitivity hypothesis in man].

The hypothesis, proposed by us since 1981, that genetically determined salt sensitivity exists in the normotensive population has been confirmed by other groups. We propose that in salt sensitive subjects an augmented upregulation of alpha-2 combined with simultaneous downregulation of beta-2 adrenoceptors by a high salt diet (resulting in an increase in the "operative" adrenoceptor ratio) is responsible for the rise of blood pressure. In salt resistant subjects the "operative alpha-2/beta-2 adrenoceptor ratio" does not increase on a high salt intake. The adrenoceptor changes in salt sensitive subjects probably lead to an increased central sympathetic outflow (through receptor changes in certain brain areas) and to simultaneous enhanced end-organ response in resistance vessels and in the kidney, causing enhanced vasoconstriction and enhanced sodium reabsorption. Long term follow up of salt sensitive normotensives will show, whether they develop "essential hypertension" in the future.

Absorption↗