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Biomedical subjects

B Heintz

Publications and source records attributed to B Heintz.

At least 37 records · Page 2Linked to original sources

Selenium deficiency and thyroid function in acute renal failure.

The lethality of acute renal failure exceeds 50% due to multiorgan dysfunction. In such critically ill patients a reduction of thyroid hormone concentrations without clinical symptoms or laboratory evidence of hypothyroidism frequently occurs. Selenium has recently been shown to play a major role in thyroid hormone metabolism. The aim of this study was to investigate the possible influence of selenium on thyroid hormone metabolism in acute renal failure. Changes in thyroid metabolism were related to the severity of multiorgan failure and to the clinical course. Thyroxine (T4), tri-iodothyronine (T3), free-T4, free-T3, thyrotropin (TSH), serum creatinine, and plasma selenium concentrations in 28 patients (mean age 60 +/- 13) with acute renal failure and multiple-organ dysfunction syndrome were determined initially, and every 3 days after hospital admission. The plasma selenium concentration was found to be reduced compared to normal controls (32 +/- 14 vs. 70-120 micrograms/L). T4 (56 +/- 15 nmol/L, normal range 64-148), T3 (1.31 +/- 0.38 nmol/L, normal range 1.42-2.46), free-T3 (3.1 +/- 1.0 pmol/L, normal range 4.7-9.0), and free-T4 (10.8 +/- 4.0 pmol/L, normal range 10.3-25.8) values were low in 50-70% of the patients at the time of presentation. Plasma TSH concentrations were within the normal range (0.59 +/- 0.79 mU/L, normal range 0.25-3.1), and no clinical symptoms of hypothyroidism were observed. T4 concentration was higher in patients who survived acute renal failure compared to nonsurvivors (62 +/- 22 vs. 51 +/- 16 nmol/L, p < 0.05). Plasma selenium concentration was lower in patients with a severe organ dysfunction syndrome (36 +/- 10 vs. 29 +/- 19 micrograms/L) and correlated with the number of organ failures in these patients (r = -0.247, p < 0.05). T4 and free-T4 values paralleled decreasing selenium concentrations (r = 0.35, p < 0.05). Thyroid hormone levels were reduced in patients with acute renal failure without an increase in TSH. An increase in T4 concentrations became apparent during treatment and may be related to a favorable outcome in acute renal failure. Thyroid hormone concentrations paralleled plasma selenium levels, indicating a possible influence of selenium on thyroid function in acute renal failure.

Acute Kidney Injury↗

Isolated cerebral aspergilloma--long-term survival of a renal transplant recipient.

A renal transplant recipient with isolated cerebral aspergilloma 4 months after allograft transplantation is reported. On admission cerebral computed tomography showed a ring-enhancing mass in the left frontal hemisphere and aspirated purulent material revealed A. fumigatus hyphae. He was cured by short-term antifungal therapy and neurosurgical removal of the well demarcated lesion. He is still alive more than two years later and the renal transplant is well functioning. This is the first report of a renal transplant recipient with isolated cerebral aspergillosis without any relapse and only the third patient who has survived longer than 3 months. Early diagnostic procedures with rapid confirmation of aspergillus infection are pivotal for a benign clinical course.

Amphotericin B↗

Blood pressure rhythm and endocrine functions in normotensive women on oral contraceptives.

DESIGN AND METHODS: Twenty-four hour blood pressure profiles were determined by non-invasive ambulatory blood pressure measurements in young normotensive women during the follicular and luteal phases of the menstrual cycle. Forty women participated, 20 of whom were on oral contraceptives (ethinyl-ethylestradiol 0.03 mg + levonorgestrel 0.15 mg) and 20 of whom were age- and weight-matched control individuals not on oral contraceptives. Data on systolic and diastolic blood pressure and heart rate were analyzed in each case by linear and rhythm analysis. Urine was collected day and night on each occasion on which ambulatory blood pressure measurements were recorded. RESULTS AND CONCLUSION: Daytime, night-time, and 24 h mean systolic and diastolic blood pressure and heart rate did not depend on the cycle phase. The nocturnal fall in blood pressure was preserved in both groups and during both phases. Rhythm analysis by partial Fourier series showed that, of 240 individual 24 h blood pressure profiles, only 12 (5%) did not exhibit a significant circadian rhythm. Linear and rhythm analyses revealed that during both phases of the menstrual cycle systolic and diastolic blood pressure were significantly higher throughout the 24 h, especially during the night, in women taking oral contraceptives. During both phases of the menstrual cycle urinary aldosterone excretion was significantly higher in women taking oral contraceptives. This increase could contribute to the night-time blood pressure elevations caused by oral contraceptives. The results suggest a modulating influence of sex steroids on the circadian blood pressure profile even in normotensive healthy volunteers.

Adult↗

Diffusion coefficient through the blood-aqueous barrier using a standard protocol.

AIMS/BACKGROUND: Comparison of the diffusion coefficient through the blood-aqueous barrier of healthy volunteers measured in different cities with identical fluorophotometers using a standardised protocol. METHODS: Healthy volunteers aged between 20 and 70 years were studied in seven European cities. The fluorescein concentration in the anterior segment of each eye was measured with a commercial scanning fluorophotometer 30 and 40 minutes after intravenous fluorescein. The decay of non-protein bound fluorescein concentration in blood plasma was determined with the use of three blood samples taken at 7, 15, and 55 minutes after injection. The diffusion coefficient through the blood-aqueous barrier was calculated from the ratio between the fluorescein concentration in the anterior chamber and the time integral of non-protein bound fluorescein concentration in plasma using specially developed software. RESULTS: The mean values of the diffusion coefficient (SD) (X10(-4) min-1) were 4.76 (1.51) (n = 20, Brussels), 5.48 (2.33) (n = 17, Coimbra), 3.47 (2.09) (n = 12, Cologne), 6.09 (2.77) (n = 21, Frankfurt), 3.85 (1.59) (n = 11, Ghent), 4.99 (1.69) (n = 23, Leiden), and 4.87 (1.05) (n = 20, Madrid). The values between centres were similar (Kruskal-Wallis test p > 0.05) except for Cologne and Frankfurt (p = 0.013). No differences were found when repeating measurements (four centres, interval time 1-8 months, Wilcoxon paired test p > 0.39). CONCLUSION: The diffusion coefficients had similar values and standard deviations. The concerted action demonstrated the usefulness of a standardised protocol.

Adult↗

Association between heparan sulfate proteoglycan excretion and proteinuria after renal transplantation.

The aim of the study presented here was to investigate whether, in patients showing immediate graft function after renal transplantation, cold-ischemia and reperfusion lead to damage of the glomerular basement membrane and consequently to a loss of heparan sulfate proteoglycans. Loss of these heparan sulfate proteoglycans is a major cause of proteinuria. Time-dependent changes in urinary excretion rates of heparan sulfate proteoglycans but also of total protein, albumin, low- and high-molecular-weight proteins were analyzed quantitatively and by polyacrylamid-gel-electrophoresis in eight patients. Immediately after renal transplantation, severe proteinuria with an excretion rate of up to 251 +/- 108 mg/min was apparent and rapidly declined within 24 h to 4.11 +/- 2.80 mg/min. The gel-electrophoretic pattern showed a nonselective glomerular and tubular proteinuria. The excretion rate of heparan sulfate proteoglycan was increased in this initial reperfusion phase (up to 7 h), most probably because of ischemia- and reperfusion-induced damage of the glomerular basement membrane. The initial nonselective glomerular proteinuria disappeared within 48 h, changing to a mild selective glomerular proteinuria. In this second phase (7 to 48 h), lower levels of heparan sulfate proteoglycan excretion were observed (0.54 +/- 0.54 microgram/min versus 1.66 +/- 1.93 micrograms/min, P < 0.05). However, during the repair process of the glomerular basement membrane, heparan sulfate proteoglycan is synthesized de novo, leading to an increasing heparan sulfate proteoglycan content of the glomerular basement membrane. This second phase is paralleled by the change from a nonselective to a selective glomerular proteinuria. In the third phase, when the heparan sulfate proteoglycan content of the glomerular basement membrane normalizes, glomerular proteinuria was abolished in most of the patients.

Adult↗

[Bioavailability of two verapamil formulations following repeated administration in steady-state conditions. An open, two-period, crossover study].

The relative bioavailability of a new formulation of verapamil (CAS 52-53-9, Veramex 40) in comparison to a standard formulation was investigated in an open two-period cross-over study in 16 healthy volunteers under steady state conditions of 7 days duration each. For the estimation of verapamil a selective HPLC-method was used with fluorescence detection after direct injection and enrichment by column switching enabling a simultaneous separation and analysis of verapamil and N-norverapamil. The bioavailability was estimated using areas under the concentration-time curves (AUC), maximum serum concentrations (Cmax) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVAlog). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference substance, thereafter slightly higher plasma levels up to 7 h were observed after the test substance. The individual plasma profiles had a similar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean relative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concentrations for verapamil and N-norverapamil were 50.0 and 49.7 ng/ml, respectively. After the standard formulation the corresponding values were 50.4 and 50.3 ng/ml. The mean PTF-values for verapamil and N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, respectively. The 90% confidence intervals for AUC, Cmax and PTF for verapamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, Cmax and PTF. Therefore bioequivalence between both formulations can be stated.

Adult↗

Age-related changes in the elastic properties of the aortic tree in normotensive patients: investigation by intravascular ultrasound.

The arterial wall structure degenerates with increasing age, elastin fibers decrease while collagen increases. We investigated the elastic properties of the aorta and iliac arteries to determine the relationship between aging and arterial mechanics. The regional elasticity of the aorta and iliac arteries was determined at five different sites in 40 normotensive patients aged 32 to 78 years. A combined procedure for arterial blood pressure measurement and arterial cross-sectional area determination was employed to calculate the parameters of compliance and pulse wave velocity. The descending thoracic and abdominal aorta showed significant correlations between age and elasticity. No correlation was observed at the aortic bifurcation. A significant correlation between age and pulse wave velocity was apparent in the common iliac artery, whereas compliance showed no significant correlation to age. In the external iliac artery as well, no significant correlation between age and elasticity could be found. Arterial elasticity decreases with age, but this process does not progress uniformly at all sites of the arterial system. The difference in elasticity between these basic types of arteries diminishes throughout life. At the aortic bifurcation, mechanical aging seems to proceed faster than at unbifurcated arterial segments.

Adult↗

Effects of blood pressure reduction on the elastic profile of the aortic tree in patients with coronary heart disease.

Decreased arterial compliance of large arteries in coronary heart disease has been reported. Using intravascular ultrasound it was demonstrated that arterial compliance decreases with increasing distance from the heart. Until now changes in the elastic profile have not been investigated after a stepwise blood pressure (BP) reduction induced by antihypertensive agents. The local viscoelastic properties of the aortic tree were analyzed before and after a mean arterial BP reduction of about 5 and 15 mm Hg below baseline by the steady-state infusion of increasing doses of nisoldipine in 15 patients with coronary artery disease. Intravascular ultrasound imaging combined with arterial pressure measurements were performed at five sites along the aortic tree to determine the viscoelastic profile before nisoldipine administration and again after the 5 and 15 mm Hg nisoldipine-induced blood pressure reductions. The elasticity parameters varied depending on the distance from the heart and on the BP level. At both BP reduction levels nisoldipine infusion led to an increase in arterial compliance at the abdominal aorta and at the aortic bifurcation. A dissociation between the 5 and the 15 mm Hg BP reduction was found at the common iliac artery and at the external iliac artery. Our results provide direct quantitative evidence that stepwise BP reductions exhibit different and, in part, contrary effects on the elastic profile, depending on the aortic tree location. The results also suggest that nisoldipine infusion can significantly ameliorate local viscoelastic properties at the abdominal aorta and at the aortic bifurcation, an effect that was associated or caused by a change in BP attributable to a decrease in peripheral resistance.

Adult↗

Decreased glomerular basement membrane heparan sulfate proteoglycan in essential hypertension.

Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essential for maintenance of the selective permeability of the glomerular basement membrane. Recently, we isolated and characterized a novel small basement membrane-associated heparan sulfate proteoglycan from human aorta and kidney. Partial amino acid sequence data clearly show that this heparan sulfate proteoglycan is distinct from the large basement membrane-associated heparan sulfate proteoglycan (perlecan). Using specific monoclonal antibodies, we have shown that the novel heparan sulfate proteoglycan is located predominantly in the glomerular basement membrane and, to a lesser extent, in the basement membrane of tubuli. Turnover or, in the course of kidney diseases, degradation of heparan sulfate proteoglycan from glomerular basement membranes may lead to urinary excretion of heparan sulfate proteoglycan, which can be measured by a sensitive enzyme immunoassay. The aim of the present study was to analyze whether changes in the structure and function of glomerular basement membranes can be directly detected by measurement of the excretion of a component of this basement membrane, eg, heparan sulfate proteoglycan into urine. The excretion of this small heparan sulfate proteoglycan was compared after physical exercise in normotensive and hypertensive subjects. Normotensive subjects and treated, essential hypertensive patients underwent a standardized workload on a bicycle ergometer. Biochemical characterization of the urinary proteins and heparan sulfate proteoglycan was performed before and 15 and 45 minutes after exercises.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endothelin-1 potentiates ADP-induced platelet aggregation in chronic renal failure.

The effect of preincubation of heparinized whole blood with endothelin-1 (ET-1) on the ADP (adenosine diphosphate) and epinephrine-induced platelet aggregation was examined in 20 healthy donors compared with 20 patients with chronic renal failure (CRF). ET-1 significantly stimulated ADP-induced aggregation in CRF: EC (effective concentration)25 = 2.3 +/- 0.20 with ET-1 vs. 2.7 +/- 0.22 mumol/L without ET-1; EC50: 3.8 +/- 0.18 with ET-1 vs. 4.4 +/- 0.24 mumol/L without ET-1; and EC75: 5.7 +/- 0.22 with ET-1 vs. 6.4 +/- 0.21 mumol/L without ET-1). In healthy donors only the EC25 was significantly increased: EC25 = 2.5 +/- 0.13 with ET-1 vs. 2.8 +/- 0.20 mumol/L without ET-1. No significant influence of ET-1 in epinephrine-induced aggregation was observed in CRF or in healthy donors. The basal values of determined ET-1 were significantly elevated in CRF: 6.99 +/- 0.29 pmol/mL vs. 5.65 +/- 0.33 pmol/mL in healthy donors. The high endogenous level of ET-1 in CRF patients together with an observed higher endogenous plasma level of cAMP (58 +/- 5.2 nmol/L compared to 29 +/- 2.0 nmol/L in healthy donors) may explain the enhanced pharmacological interaction of ET-1 and ADP in CRF patients. The data suggest that positive agonist interaction between ET-1 and ADP may result from effects on the concentrations of cAMP within the platelet rather than from direct interaction on the membrane receptors or the transmembrane coupling mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Polyenylphosphatidylcholine improves the lipoprotein profile in diabetic patients.

Patients with diabetes mellitus commonly exhibit pathological lipoprotein profiles and concomitant cardiovascular or peripheral atherosclerotic complications. Thirty non-insulin-dependent diabetics with secondary hyperlipidemia received 2.7 g 3-sn-polyenylphosphatidylcholine (PPC) or placebo daily, orally over a 2-month period under randomized, double-blind trial conditions, to investigate the efficacy and tolerance of the treatment. This period was followed by a one-month observation phase without investigational medication. Serum LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides were determined on days 1, 14, 28, 56 and 84. After 56 days of treatment with PPC, the primary variable of effectiveness, LDL cholesterol, decreased significantly (p = 0.0174) by 17% from 191 +/- 31 to 159 +/- 36 mg/dl, whereas values did not change in the placebo group. Total cholesterol (TC) in serum decreased by 16% from 303 +/- 22 to 255 +/- 23 mg/dl with PPC. In the placebo group, only a slight decrease from 292 +/- 27 to 289 +/- 41 mg/dl occurred. Mean serum triglyceride (TG) levels fell by 9% from 194 +/- 32 to 177 +/- 27 mg/dl in the PPC group. In the control group, values increased from 193 +/- 34 to 202 +/- 41 mg/dl. The differences in LDL, TC and TG between the treatment groups were statistically significant; p = 0.0014, p = 0.0001 and p = 0.007, respectively. HDL cholesterol in serum increased 12% from 50 +/- 10 to 55 +/- 13 mg/dl after PPC application. The control group did not show any alteration of mean HDL cholesterol level at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Pharmacodynamics and pharmacokinetics of oral nitrendipine solution in hypertensive patients with advanced renal failure.

Nitrendipine solution 5 mg.ml-1 in the dose of 5 mg was given orally to 20 patients with chronic renal failure and elevated diastolic blood pressure (> or = 110 mmHg), of whom 10 were on maintenance haemodialysis (endogenous creatinine clearance < 5 ml.min-1) and 10 were at the predialysis stage (endogenous creatinine clearance 5-20 ml.min-1). The aim of the study was to investigate the influence of kidney function and/or dialysis treatment on the pharmacokinetic and pharmacodynamic profile of a solution of nitrendipine and to assess its antihypertensive efficacy. After 10 min there was a significant reduction in blood pressure from 188/113 to 173/100 (patients not dependent on dialysis) and from 197/112 to 161/94 mmHg (patients dependent on dialysis). The maximum fall in blood pressure (approximately 30%) was attained after 90 min in the dialysis patients and after 120 min in the non-dialysis group. Blood pressure increased again about 3 h after the administration of nitrendipine but it was still below baseline after 12 h. The terminal elimination half-life (4.1 h in the dialysis patients and 3.6 h in non-dialysis patients) was similar to that observed in patients with normal renal function. The pharmacokinetics of nitrendipine did not differ between the dialysis and non-dialysis groups. There was a correlation between plasma concentration and the blood pressure reduction. The maximum plasma concentration of nitrendipine was reached after 0.5 h (median) and did not differ between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Response of vasoactive substances to intermittent ultrafiltration in normotensive hemodialysis patients.

The changes in blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), parathyroid hormone (PTH), arginine vasopressin (AVP) and the cyclic nucleotides cAMP and cGMP were measured during a fluctuating BV cycle in 15 patients with end-stage renal failure maintained on chronic hemodialysis (HD). HD consisted of 4 periods of about 60 min each. The first half of each HD period consisted of ultrafiltration (UF) greater than 1,000 ml/h, and the second half consisted of no UF. Changes in relative BV were measured using continuous hemoglobinometry. Total BV at the end of treatment was 74.3 +/- 6.9% of the pretreatment volume. A significant positive correlation between BV and the levels of ANP, PTH, Epi and cGMP and an inverse correlation between BV and PRA, Aldo, AVP and NE were demonstrated. While mean values of NE and AVP levels were directly related to actual changes in BV, individual values did not homogeneously reflect this relationship. The cyclic nucleotides cGMP and cAMP did not follow immediate BV changes, but showed a significant decrease correlated with diminished BV. Based on a pre-postdialysis analysis, significant changes in PRA and Aldo were missing. It seems possible that vascular stability in dialysis patients may be maintained by the response of NE and AVP, and not by the renin-aldosterone system. The changes in ANP and cGMP values correlated most significantly (r = 0.38 and r = 0.51, p < 0.005) with the changes in BV, but no single variable could explain the blood pressure regulation during HD with intermittent rapid UF.

Adult↗

Multiple-dose pharmacokinetics of ramipril in patients with chronic congestive heart failure.

Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple doses (14 days) of ramipril (5 mg once daily); the concentrations of ramipril and ramiprilat in plasma, as well as ramipril, ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine were measured at various times for 14 days. One patient dropped out after the first day due to hypotension and another who accidentally received another ACE inhibitor additionally was excluded, so that 11 patients completed the study. Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and ramipril and its metabolites in urine were measured by gas chromatography in the laboratories of Hoechst AG. Peak concentrations of the active substance ramiprilat were reached after about 4 h and amounted to 22.3 +/- 11.1 ng/ml after the first dose, and a peak concentration of 26.6 +/- 10.0 ng/ml was observed 2.5 +/- 1.4 h on average after administration on day 14. Practically no accumulation was observed for ramiprilat; the AUD (0-24 h) values increased from 191.3 +/- 83.1 ng.h/ml for the first study day to 238.3 +/- 98.0 ng.h/ml for day 14. As expected, only very small fractions of the dose were excreted with urine as unchanged ramipril and ramipril glucuronide. Ramiprilat is excreted with urine to a larger extent than is rampiril--on average 6.6 +/- 3.0% on the first day and 12.2 +/- 3.8% on day 14. The total amount excreted increased by 34% on average, and was mainly due to an increased ramiprilat excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Evaluation of segmental elastic properties of the aorta in normotensive and medically treated hypertensive patients by intravascular ultrasound.

DESIGN AND METHODS: Local elastic properties of the descending aorta at different levels were evaluated by means of intravascular ultrasound images and pressure measurements. For this purpose, 30 normotensive patients and 30 age-matched medically treated patients with essential hypertension, all undergoing diagnostic cardiac catheterization, were studied. RESULTS: Hypertension was well controlled in the essential hypertensives (137.1 +/- 6.79/74.5 +/- 2.65 mmHg). Systolic but not diastolic blood pressure in the hypertensive patients was significantly different from that of the normotensives (118.8 +/- 4.38/69.7 +/- 1.65 mmHg). The continuous loss of volume compliance with increasing distance from the heart was significantly higher in the hypertensives than in the normotensive patients [normotensives (1.45 +/- 0.19) x 10(-10) m5/N at the thoracic aorta, (0.08 +/- 0.05) x 10(-10) m5/N at the external iliac artery; hypertensives (0.81 +/- 0.09) x 10(-10) and (0.05 +/- 0.01) x 10(-10) m5/N at the corresponding sites]. Similarly, the hypertensives had an elevated elastic modulus proximal to the aortic bifurcation compared with the normotensives (244.47 +/- 44.06 versus 108.10 +/- 17.76 m/s, respectively). The decrease in buffering function of the vessel at this site is presumably caused by a turbulent flow pattern. Compared with the normotensives, the treated hypertensives had a significantly higher elastic modulus at each site where this was measured, whereas volume compliance and sectional compliance were lower. CONCLUSION: The differences in elastic modulus and compliance between hypertensive and normotensive patients seem disproportionate to the difference in systolic blood pressure (within the normal range in both the treated hypertensives and the normotensives). Therefore, normalization of high blood pressure by long-term antihypertensive treatment may not fully reverse changes, caused by arterial hypertension, in the viscoelastic properties of the arterial wall.

Adult↗