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Biomedical subjects

H Toplak

Publications and source records attributed to H Toplak.

At least 55 records · Page 3Linked to original sources
PubMed1994

"Non-dipping" related to cardiovascular events in essential hypertensive patients.

About 1 third of all patients with essential hypertension reveal an impaired circadian pattern of blood pressure. This phenomenon called "non-dipping" (i.e. a lack of the normal nocturnal fall in blood pressure) is related to a higher incidence of end-organ damage such as left ventricular hypertrophy. It is the purpose of this study to evaluate, whether or not non-dipping of blood pressure may worsen the prognosis of hypertensive subjects. 116 consecutive hypertensives underwent an ambulatory blood pressure monitoring (ABPM) using the Spacelabs 2000 device. 2 groups were established: Group I (n = 87) were "dippers", group II (n = 29) "non-dippers" showing a diminished or even lack of nocturnal fall in blood pressure. No difference was seen concerning sex, mean 24-hour systolic blood pressure, systolic and diastolic causal blood pressure and heart rate. However, a significant difference in age and mean 24-hour diastolic blood pressure could be observed. In a follow-up investigation after approximately 31 months all patients and/or their physicians were contacted concerning cardiovascular events during the time since the ABPM was performed. In Group I only 1 transient ischemic attack occurred, but in group II 4 patients showed major cardiovascular events: 3 deaths occurred (2 of which caused by myocardial infarction, 1 by apoplexy), while 1 suffered from a transient ischemic attack (p < 0.001). Thus, in essential hypertension non-dipping of blood pressure is associated with an increased occurrence of cardiovascular events, and, therefore, the circadian blood pressure profile should be carefully monitored.

Adolescent↗
PubMed1994

[10-year-follow-up of patients with silent Cohn type 1 myocardial ischemia].

Prevalence of type 1 silent myocardial ischemia (SMI; completely asymptomatic patients) is reported to appear 2 to 4% of the general population. The prognosis of these patients is said to be similar to that of patients with angina pectoris. Our study investigated a 10-year follow up of silent myocardial ischemia detected by bicycle exercise testing in comparison to a comparable control group. 10 years later 127 patients were reinvestigated by bicycle ergometry, 33 patients out of the SMI-group (group A) and 84 patients out of the control group (group B). Mean age in group A was 62 +/- 7 years (range 42 to 71 years), in group B 56 +/- 7 years (range 29 to 69 years). After 10 years there was no statistical significant difference between the 2 groups on using beta-blockers, calciumchannel-blockers and nitrates, on arterial hypertension, diabetes mellitus, smoking history and positive family-history as well as in total cholesterol, HDL- and LDL-cholesterol, triglycerides, blood glucose and uric acid. 1 patient of A and 2 of B died from a sudden cardiac death, 2 of A and 7 of B survived a myocardial infarction, 11 of A and 11 of B developed angina pectoris (p < 0.05). A statistical significant difference was found in the ergometric working capacity (maximal workload in Watt) between the 2 groups (p < 0.001) that did not change over the 10 years, the control group worked better in both investigations. SMI type 1, detected by bicycle ergometry seems to be only a risk factor for developing "loud ischemia" (= angina pectoris) but not for "hard events". A routine screening of completely asymptomatic persons with bicycle ergometry seems to have no prognostic relevance.

Adult↗
PubMed1994

Cardiovascular risk factors in obesity. The effect of weight reduction on platelet size in overweight patients.

Platelet volume, indicating platelet activity has been proposed as a further independent risk factor for cardiovascular disease (CVD). It is well established that weight reduction reduces some of the risk factors for CVD in obese patients. We therefore retrospectively investigated the effects of weight reduction on platelet mass, platelet volume and serum lipid profile in patients undergoing an eight-week weight reduction therapy. During weight reduction, the body mass index (P < 0.005), serum total cholesterol (P < 0.05), LDL cholesterol (P < 0.01) and serum triglycerides (P < 0.01) were significantly reduced, while HDL cholesterol remained unchanged. On the other hand, platelet mass (P < 0.005) and platelet volume (P < 0.0005) increased significantly within the same period. We therefore conclude that fasting might alter the control of platelet size with a possible impact on platelet activity. This might result in an increased risk of thrombo-embolic ischaemic events in atherosclerotic patients.

Adult↗
PubMed1993

Cellular accumulation of amiodarone and desethylamiodarone in cultured human cells. Consequences of drug accumulation on cellular lipid metabolism and plasma membrane properties of chronically exposed cells.

Amiodarone (AMIO), a potent antiarrhythmic drug, is clinically widely used despite its frequent side effects after chronic administration. These side effects coincide with an intralysosomal accumulation of AMIO and its main metabolite desethylamiodarone (DEA) and may be causally related to the drug-induced intracellular storage of phospholipids (PL). Kinetics of cellular uptake and release of radiolabelled AMIO and DEA were studied following single and multiple exposures of cultured human skin fibroblasts to 5 and 10 microM drug concentrations. AMIO and DEA were efficiently taken up into cultured cells. The rate of uptake was slower than that of other cationic amphiphilic drugs. The intracellular steady state concentrations were in the millimolar range suggesting a lysosomal trapping. Repetitive exposures of cultures resulted in a cumulative and partly saturable drug uptake. The accumulation of DEA was higher than that of AMIO throughout. AMIO and DEA previously taken up into the cells during a 2 hr exposure were completely released into the washing media, suggesting an exchangeable form of the accumulated drugs. Following repetitive exposures only part of the drugs was released. Under chasing conditions using washing media containing non-labelled AMIO and DEA respectively or ammonium chloride the release of the chronically accumulated 14C-labelled drugs was increased. This suggested a drug storage in the form of complexes in acidic compartments. Phospholipid (PL) content as well as individual PL fractions were changed in whole cells and in isolated plasma membranes. PL accumulation is assumed to occur by inhibition of PL degradation due to formation of non-degradable drug-PL complexes or by inhibition of phospholipase activities. Cellular PL accumulation seemed to interfere with PL recycling. Changes in PL composition of purified plasma membranes were in part complementary to the ones in whole cells. The alterations in membrane PL composition may explain the changes in membrane fluidity and the decrease in beta-adrenoceptor density and in isoproterenol-stimulated cAMP formation. The results obtained provide an explanation for the pharmacokinetic, and possibly for the pharmacodynamic and also toxicological behaviour of AMIO and DEA in vivo.

Amiodarone↗
PubMed1993

Exposure to elevated D-glucose concentrations modulates vascular endothelial cell vasodilatory response.

The possible role of endothelial dysfunction in early stages of uncomplicated diabetes mellitus was investigated in porcine aortic endothelial cells. Prolonged exposure to various D-glucose concentrations resulted in concentration-dependent amplification of agonist-induced Ca2+ mobilization, whereas L-glucose and D-mannitol failed to mimic the effect of D-glucose. This stimulatory effect of high D-glucose on endothelial Ca2+ mobilization could be antagonized by coincubation with cytochalasin B, which prevented D-glucose uptake into the cells. In agreement with its effect on agonist-induced Ca2+ response, prolonged preincubation with pathological D-glucose concentrations amplified formation of endothelium-derived relaxing factor, which is well established to be strictly attributable to increases in endothelial free Ca2+. In contrast to endothelium-derived relaxing factor formation stimulated by receptor-interacting autacoids, preincubation with high D-glucose failed to modulate A 23,187-induced endothelium-derived relaxing factor formation, which is attributable to unphysiological increases in endothelial free Ca2+ by this ionophore. Similar to its effect on D-glucose-mediated amplification of agonist-stimulated Ca2+ mobilization, cytochalasin B abolished the stimulatory effect of high D-glucose on endothelium-derived relaxing factor formation. We therefore suggest that prolonged exposure to pathological high D-glucose concentrations results in an enhanced endothelium-derived relaxing factor formation caused by amplification of agonist-stimulated Ca2+ mobilization in endothelial cells. This mechanism may be of particular importance representing a possible basis of pathological vasodilation and reduced peripheral resistance in early stages of diabetes mellitus.

Animals↗
PubMed1993

[Eating behavior of patients with metabolic diseases and metabolically healthy probands in Austria. Results of a questionnaire survey at the Graz Autumn Fair 1991].

Malnutrition as the cause of developing atherosclerosis is undoubtedly of major importance. For that reason, proper nutrition and eating habits among the population is of specific significance in preventive medicine. In order to establish a more pronounced food consciousness among the population of Styria, a questionnaire was issued to 1.354 persons attending the Graz Autumn Fair in 1991. The results showed above all that approximately 40% of the subjects investigated presented a disease due to malnutrition and metabolic disorder, mainly hyperlipidemia. The choice of various foods varied according to male and female tastes; roasted pork was more often a men's favourite dish (p < 0.001) while women had a prediction for vegetarian food (p < 0.001). There was, however, no difference in the choice of eating habits in persons with or without metabolic disorders. Thus, women in general do pursue a healthier consciousness was not so pronounced in man. Yet, it could not be established by means of the questionnaire that subjects with metabolic disorders showed different eating habits with respect to their disease.

Adult↗
PubMed1992

Increased IgM-anticardiolipin antibodies in patients with restenosis after percutaneous transluminal coronary angioplasty.

Increased anticardiolipin antibodies (acL) are often associated with arterial thrombosis in patients with autoimmune diseases. A mural thrombus at the site of percutaneous transluminal coronary angioplasty (PTCA) has been suggested as the initial cause for restenosis after primarily successful PTCA. In this study, IgM- and IgG-acL were determined in 65 men with coronary artery disease treated by PTCA; patients with infectious and autoimmune diseases were excluded from the study. Follow-up coronary angiography was performed 12 months after PTCA; restenosis was defined as greater than or equal to 50% reduction in diameter of the coronary vessel. The series comprised 2 groups: 34 patients (mean age 56 +/- 8 years) with (group A) and 31 (mean age 55 +/- 9 years) without (group B) restenosis. Medical history and laboratory findings were comparable in both groups. In patients with restenosis, IgM-acL were more often increased (9 of 34) than were those in patients without restenosis (2 of 31; p less than 0.05); IgG-acL values did not differ in both groups. Furthermore, there was no correlation between any vascular risk factors or laboratory findings, or both, with both IgM- and IgG-acL levels. Thus, IgM-acL appear to be independent indicators for an increased risk for restenosis after PTCA. Our observations suggest that an autoimmune mechanism may have a role in restenosis.

Adult↗
PubMed1992

Cultured human skin fibroblasts modify their plasma membrane lipid composition and fluidity according to growth temperature suggesting homeoviscous adaptation at hypothermic (30 degrees C) but not at hyperthermic (40 degrees C) temperatures.

Mammalian cell metabolism is responding to changes in temperature. Body temperature is regulated around 37 degrees C, but temperatures of exposed skin areas may vary between 20 degrees C and 40 degrees C for extended periods of time without apparent disturbance of adequate cellular functions. Cellular membrane functions are depending from temperatures but also from their lipid environment, which is a major component of membrane fluidity. Temperature-induced changes of membrane fluidity may be counterbalanced by adaptive modification of membrane lipids. Temperature-dependent changes of whole cell- and of purified membrane lipids and possible homeoviscous adaptation of membrane fluidity have been studied in human skin fibroblasts cultured at 30 degrees C, 37 degrees C, and 40 degrees C for ten days. Membrane anisotropy was measured by polarized fluorescence spectroscopy using TMA-DPH for superficial and DPH for deeper membrane layers. Human fibroblasts were able to adapt themselves to hypothermic temperatures (30 degrees C) by modifying the fluidity of the deeper apolar regions of the plasma membranes as reported by changes of fluorescence anisotropy due to appropriate changes of their plasma membrane lipid composition. This could not be shown for the whole cells. At 40 degrees C growth temperature, adaptive changes of the membrane lipid composition, except for some changes in fatty acid compositions, were not seen. Independent from the changes of the membrane lipid composition, the fluorescence anisotropy of the more superficial membrane layers (TMA-DPH) increased in cells growing at 30 degrees C and decreased in cells growing at 40 degrees C.

Adaptation, Physiological↗
PubMed1992

Microalbuminuria is no risk factor for restenosis following percutaneous transluminal coronary angioplasty.

Microalbuminuria is known to be associated with an increased risk for cardiovascular disease. It is detectable in acute myocardial infarction and could therefore also be a risk factor for reocclusion after percutaneous transluminal coronary angioplasty (PTCA). In our study follow-up coronary angiography was performed in 50 consecutive patients with a mean age of 56 years (38-70) on average 14 months after successful PTCA. Restenosis was defined as a decrease in diameter of 25% or more of the original result and one of at least 50% in vessel diameter. In the restenosis group there were 23 patients, and 27 showed no restenosis. The family history and anamnestic risk profile, results of the initially performed coronary angiography, and laboratory risk factors were comparable in the two groups. Median microalbumin was 11.2 mg/g creatinine in those with restenosis and 9.8 mg/g creatinine in those without. Using a cut-off of 10.0 mg/g creatinine, 12 of 23 patients with restenosis (52%) and 10 of 27 patients without (37%) were positive for microalbuminuria (NS). The incidence of microalbuminuria was higher in both groups compared to historical controls. Thus, in the restenosis group the incidence of microalbuminuria tended to be higher than in the nonrestenosis group, but since this difference did not reach statistical significance, it cannot be used to predict the risk of reocclusion after PTCA.

Adult↗
PubMed1992

Specific and non specific stimulation of prostaglandin release by human skin fibroblasts in culture.--Are changes of membrane fluidity involved?

In order to study a bidirectional relationship between changes of membrane fluidity and prostaglandin synthesis, the arachidonic acid cascade was stimulated in cultured human skin fibroblasts by unspecific stimuli (hypotonicity, low calcium concentrations) and by the specific stimulus, bradykinin. Fluorescence anisotropy of trimethylammoniumdiphenylhexatriene was used to measure membrane fluidity in cell monolayers. Hypotonicity or low calcium concentrations induce membrane fluidisation and prostaglandin synthesis. However, after specific stimulation of prostaglandins with bradykinin (at normocalcic and isotonic conditions) a rigidification of plasma membranes was observed in living cells. Fluidisation of membranes and bradykinin activate phospholipase A2 and induce prostaglandin synthesis. Although in cell membrane preparations increased phospholipase A2 activity leads to fluidisation, in our model a membrane fluidisation was not observed after stimulation of phospholipase with bradykinin. This suggests that in living cells a fluidizing effect of lysolecithin resulting from phospholipase A2 activation may be rapidly counteracted by its removal. A decrease of phosphatidylcholin content and consequently a rigidification of the membrane may ensue. Thus, the cell culture model using two different ways of stimulating phospholipase activity, helps to define the directional relationship between changes of membrane fluidity and activation of phospholipase and the arachidonic acid cascade in living human cells.

Bradykinin↗
PubMed1992

Fibrinogen values in patients with and without restenosis following percutaneous transluminal coronary angiography.

Fibrinogen has turned out to be an independent risk factor for coronary heart disease (CHD). It is not known whether or not this parameter could be a prognostic factor for restenosis following percutaneous transluminal coronary angioplasty (PTCA), which represents the main problem limiting the long-term efficacy of this procedure. Therefore, we studied fibrinogen concentrations in a series of 50 males (mean age: 55, range: 38-70 years) with CHD and successful PTCA. Follow-up coronary angiography was performed 12 months following PTCA. Twenty-two patients had restenosis, and 28 patients were without restenosis. Both groups did not differ significantly in medical history (smoking habits, hypertension, positive family history for cardiovascular diseases), in routine lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoproteins A1 and B). Fibrinogen values were 405 +/- 128 mg/dl (range: 202-725) in patients with restenosis and 352 +/- 94 mg/dl (range: 187-568) in patients without restenosis (not significant). Elevated fibrinogen levels of more than 400 mg/dl were found in 8 patients in each group. Although fibrinogen is a proven marker for CHD in men, fibrinogen is not a risk factor for restenosis following PTCA.

Adult↗
PubMed1991

[Silent myocardial ischemia. Current concepts of pathophysiology and diagnosis].

Silent myocardial ischemia (SMI) is divided into 3 groups: type I: completely asymptomatic patients, type II: patients after acute myocardial infarction with SMI, type III: patients with angina pectoris (AP) and SMI. Pathophysiology on the lack of pain-perception and the cause for high tolerance against pain in SMI-patients has not yet been cleared up. It is most likely that more than one mechanism is involved in every patient, e.g. generally lower pain-perception in SMI-patients, physically counter-regulation in pain, duration and strength of myocardial ischemia. Diagnosis of SMI can be made by exercise- and long-term-ECG, thalliumszintigraphy and coronary angiography, in doing so the pros and cons of the 4 established methods have to be noted. The summary of the findings together with the lack of pain leads to the diagnosis of SMI.

Angina Pectoris↗
PubMed1991

[Silent myocardial ischemia. Current concepts of prognosis and therapy].

Type-I-patients with silent myocardial ischemia (SMI) have a 2-4fold higher longterm-risk for coronary-events than healthy people. With increasing gravity and duration of ischemia type-II-patients have an increased event-risk. Reliable statements about prognosis of type-III-patients are very difficult. Therapy of SMI is equivalent to therapy of "loud" ischemia and comprises: 1) treatment of cardiovascular risk-factors (nicotine, arterial hypertension, hyperlipidemia, adiposis), 2) nitrates as effective straight at the coronary stenosis, 3) beta-blockers, which influence the circadian ischemic rhythm, 4) calcium-channel-blockers with especially for nifedipine little effect, 5) thrombocyte-aggregation inhibitors and 6) invasive therapeutical methods (percutaneous transluminal coronary angioplasty [PTCA] and aorto-coronary bypass grafting [ACBG]).

Angina Pectoris↗
PubMed1990

Effects of culture and incubation conditions on membrane fluidity in monolayers of cultured cells measured as fluorescence anisotropy using trimethylammoniumdiphenylhexatriene (TMA-DPH).

Membrane fluidity of coverslip attached living cells was measured as fluorescence anisotropy using 5 microM trimethylammoniumdiphenylhexatriene (TMA-DPH) as fluorescent probe. Fluorescence anisotropy is inversely related to membrane fluidity. Cells were grown on glass coverslips that were inserted and directly incubated in quarz cuvettes. The coverslips were fixed with special holders at an angle of 30 degrees in respect to the incident light. Effects of incubation temperature, of cell growth and densities and of the ionic and nonionic composition of the incubation medium on membrane fluorescence anisotropy were measured. Membranes of growing cells were more fluid than those of stationary cells, while cell densities had no effect except at very low cell numbers. Calcium concentrations increasing from 0 to 8 mmol/l in the incubation medium proportionally decreased membrane fluidity. Hypotonicity of the incubation media increased membrane fluidity while hypertonicity compared to normotonicity had no effect. Differentiated human fibroblasts from different origins exhibited similar membrane fluidities. They were, however, different from those of rat cells. Membrane fluidity of rat brain tumor cells increased with age in culture while membrane fluidity of primary differentiating rat brain cells decreased in with age in culture. Measurement of fluorescence anisotropy in living cells attached to glass coverslips is a convenient tool to study effects of culture--as well as of environmental--conditions on membrane fluidity.

Animals↗
PubMed1990

[Insulin-sulfonylurea combination therapy in secondary therapy failure with sulfonylurea compounds. Randomized study between evening and morning intermediary insulin administration using the Novo Pen semi-automatic insulin injector].

In 28 type II diabetics with secondary failure of sulfonylurea treatment, the efficacy and safety of combined therapy with insulin and glibenclamide were investigated. Patients were randomized in two groups and treated for 16 weeks either with insulin Novo Protaphan HM Penfill (100 IU/ml "bed time") and 10 mg of glibenclamide in the morning (group A), or with insulin Novo Actraphan HM Penfill 100 IU/ml in the morning combined with two 5 mg doses of glibenclamide at lunchtime and in the evening (group B). Subsequently a dropout trial of sulfonylurea was performed in half of the patients. Mean blood glucose levels were lowered in the whole group of patients from 13.5 +/- 1.8 mmol/l to 8.8 +/- 2.3 mmol/l after 8 weeks and 8.7 +/- 1.8 mmol/l after 16 weeks, and the HbAlc from 10.1 +/- 1.2% to 8.4 +/- 1.0% and 7.8 +/- 1.0% respectively. After a glibenclamide dropout period of one or two weeks in 14 of the patients, the mean blood glucose level rose significantly by 2.8 +/- 2.6 mmol/l. Only 2 patients did not show this increase. The mean insulin consumption was 13 +/- 3 IU after 8 weeks and 14 +/- 5 IU after 16 weeks respectively, and the incidence of hypoglycemia one in 12 weeks of treatment. The combination of glibenclamide and insulin (administered with the Novo Pen injector) is a safe and effective form of therapy in secondary failure of sulfonylurea, and is well accepted due to the mild start into insulin therapy.

Adult↗