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Biomedical subjects

W Kaufmann

Publications and source records attributed to W Kaufmann.

At least 19 recordsLinked to original sources
PubMed1992

Di-(2-ethylhexyl) phthalate: a short-term repeated inhalation toxicity study including fertility assessment.

In a study of the 28-day inhalation toxicity of di-(2-ethylhexyl) phthalate (DEHP) aerosols, 9-wk-old Wistar rats, 27 males (mean weight 226 g) and 17 females (mean weight 155 g) per group, were exposed in head-nose inhalation systems to DEHP aerosols of respirable particle size (mass median aerodynamic diameter < or = 1.2 microns) or air (controls). Exposure for 6 hr per day, 5 days per wk for 4 wk to target concentrations of 0, 0.01, 0.05 and 1.0 mg/litre gave estimated doses of 230, 11 and 2.3 mg/kg/day for the males, and 360, 18 and 3.6 mg/kg/day for females, on the assumption of 100% deposition and absorption. Clinical investigation and blood chemistry parameters did not reveal any treatment-related effects. At the end of exposure a statistically significant (16%) increase in relative lung weights, accompanied by increased foam-cell proliferation and thickening of the alveolar septi, was found in the males of the highest dose group. Absolute liver weights were significantly (8.75%) increased in females and relative liver weights were increased in both sexes in the highest dose group, but there were no corresponding histological effects. All these effects were reversed during the 8-wk post-exposure period. No testicular toxicity was observed histologically and no impact on mating performance and male fertility was detected after two matings of treated males with untreated females, 2 and 6 wk after the end of exposure. Electron microscopic examination of liver samples from two male and two female rats per group at the end of exposure and after the 8-wk post-exposure period did not reveal clear substructural changes that could be attributed to exposure or to peroxisome proliferation. The no-observed-effect level for all exposure-related findings was 0.05 mg/litre under the conditions used.

Administration, Inhalation↗
PubMed1991

[Disordered alpha 2-adrenoreceptor function in hemodialysis patients with renal anemia--a possible cause of increased blood pressure in relation to recombinant human erythropoietin?].

Nine patients on maintenance hemodialysis and transfusion-demanding renal anemia (group A) were treated with rHuEPO 120 IU/kg i.v. three times per week. Hemoglobin-content was raised from 7.2 +/- 0.9 to 10.4 +/- 0.8 g/dl. In all patients blood pressure rose, three patients developed arterial hypertension. Mean diastoloic blood pressure was 66 +/- 12 and 78 +/- 16 mmHg (p less than 0.001) before and after rHuEPO. Rise in blood pressure was accompanied by a significant fall in plasma-noradrenaline-levels (from 498 +/- 100 to 383 +/- 75 pg/ml; p less than 0.05) and alpha 2-adrenoceptor-density (from 574 +/- 76 to 384 +/- 49; p less than 0.05). Compared to nine patients on maintenance hemodialysis and hematocrit over 30% (group B), patients with severe renal anemia (group A before treatment) had higher densities of alpha 2-adrenoceptors (574 +/- 76 vs. 218 +/- 32; p less than 0.001) despite higher plasma-noradrenaline-levels (498 +/- 100 vs. 399 +/- 63; n.s.). We suppose a anemia-related disturbance of alpha 2-receptor-function with the result of abolished receptor down-regulation and impaired vascular reagibility to vasoconstricting stimuli. With the correction of anemia receptor-function improves, receptor down-regulation as well as vascular reagibility is re-established resulting in augmented vascular resistance and higher blood pressure.

Adult↗
PubMed1991

Changes in the alpha adrenergic system and increase in blood pressure with recombinant human erythropoietin (rHuEpo) therapy for renal anemia.

Recombinant human erythropoietin (rHuEpo) is effective in correcting renal anemia with the development of hypertension as the most frequent side-effect. Compared to hemodialysis patients with normal hemoglobin concentration, nine examined patients with transfusion-dependent renal anemia had low blood pressure in the context of high alpha 2-receptor densities and high plasma levels of catecholamines. This constellation can be explained by a defective receptor-ligand-interaction. During treatment with rHuEpo all patients showed an increase in blood pressure due to increased peripheral resistance, accompanied by a significant fall in plasma noradrenaline and alpha 2-receptor-density. There was a significant negative correlation between hemoglobin concentration and alpha 2-receptor density. We conclude that correction of renal anemia abolishes anemia-mediated disturbance of alpha 2-receptor function with the consequence of receptor down-regulation and increased vasoconstriction, which contributes to the rise in arterial blood pressure.

Adult↗
PubMed1991

[Principles and perspectives of clinical pharmacology].

Basic research led to the clarification of the mechanisms of action of numerous pharmacotherapeutic agents. Experimental and clinical pharmacology has a key position in the formulation and introduction of effective and safe medications. The investigation of pharmacokinetic and pharmacodynamic effects must use reproducible quantitative methods, such as controlled clinical trials. However, the complexity of medical, ethical and legal problems inherent in controlled clinical trials may explain why few pharmacological studies have been performed in intensive care medicine conditions. A particular problem is undoubtedly the need for a multimodal treatment, as this might well lead to drug interactions in the critically ill. We generally have to distinguish between pharmacokinetic interactions, i.e. resorption, distribution, altered interaction between metabolism and elimination of a drug, and pharmacodynamic interactions due to synergistic or antagonistic affects at the same receptor or target organ. In recent decades clinical pharmacology has developed in a dualistic manner. Whereas the correlation between plasma level and therapeutic effects is considered to be of primary importance, the correlation between dosage and relevant pharmacodynamic effects is thought to be of only secondary relevance. Pharmacokinetics and pharmacodynamics should not be seen as rival approaches, but rather as complementary methods in clinical pharmacology.

Critical Care↗
PubMed1990

[Pregnancy outcome with intensified insulin therapy in manifest diabetes].

In 1981, the intensified insulin therapy for achievement of euglycaemia in pregnant diabetics was introduced at the University Department of Obstetrics and Gynaecology in Cologne. This study compares the results of 112 pregnancies in women with overt diabetes monitored before (1971-1980) or after (1981-1988) changing the therapeutic regimen. In the period from 1981 to 1988, the proportion of euglycaemic patients (preconceptionally 19%, before delivery 79%) was clearly higher than from 1971 to 1980 (n = 42; 7% and 9%, respectively). The tight blood glucose control resulted in a doubling of hypoglycaemic episodes during pregnancy. The proportion of preterm deliveries was reduced from 47% to 24%. The rate of caesarean sections was nearly constant (1971-1980: 38%, 1981-1988: 34%). The marked success of therapy was the decrease of perinatal mortality from 20.9% to 2.9%. The perinatal morbidity also diminished, as shown by the decreasing rates (30-90%) of foetopathy, macrosomy, respiratory distress syndrome, birth trauma, hypoglycaemia, hypocalcaemia and polycythaemia. The malformation rate, however, remained high (1971-1980 = 7%, 1981-1988 = 11%). The results demonstrate the necessity of a strict blood glucose control during pregnancy, beginning before the time of conception.

Adult↗
PubMed1990

Isradipine: a new calcium antagonist with strong vasodilatory but negligible cardiodepressive effects.

To assess the effects of intravenous isradipine (0.5 mg) on left ventricular function in patients pretreated with the beta-blocker propranolol (0.1 mg/kg i.v.), 10 patients were studied during cardiac catheterization for suspected coronary artery disease (confirmed in 6). All patients had normal ejection fractions at rest. Following propranolol, isradipine significantly reduced mean aortic pressure (baseline: 112 mm Hg; propranolol: 107 mm Hg; isradipine: 92 mm Hg) and left ventricular systolic pressure (149 vs. 144 vs. 117 mm Hg, respectively). Propranolol alone significantly decreased heart rate, which then increased after isradipine (75 vs. 66 vs. 70 beats/min, respectively). Cardiac index was depressed with propranolol but normalized with isradipine (3.8 vs. 3.0 vs. 3.7 L/min/m2, respectively) as was mean pulmonary artery pressure (16 vs. 18 vs. 16 mm Hg, respectively). Left ventricular contractility decreased significantly during beta-blocker infusion and reached baseline values with isradipine (2,270 vs. 2,080 vs. 2,320 mm Hg/s, respectively). Parallel to dP/dtmax, systolic wall tension decreased as a consequence of the reduction of left ventricular volume and afterload (1,223 vs. 1,332 vs. 905 units, respectively). It is concluded that isradipine effectively reduces cardiac afterload with no sign of intrinsic cardiodepression.

Adrenergic beta-Antagonists↗
PubMed1990

Hemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans.

In our studies, we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intra-arterially (40-6,050 pM/kg) and was infused intra-arterially (40-6,050 pM/kg/min). The investigations were performed in 21 normotensive and 15 hypertensive patients. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol of Na/day), salt loading (300 mmol of Na/day), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 X 1 mg), indomethacin (2 X 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure in a dose-related manner by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, beta-adrenoceptors, histamine-1 receptors, and prostaglandins. ACE inhibitors protentiate the blood pressure-lowering effect of bradykinin approximately 20- to 50-fold. In the case of intra-arterial injection of bradykinin, only 2-5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From these experiments, a pulmonary clearance rate of bradykinin of over 95% can be calculated. In the pulmonary arteries, bradykinin has no effect on vascular resistance. In patients suffering from primary or renovascular hypertension, the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism, bradykinin caused the same blood pressure lowering effect as in the normotensives.

Adult↗
PubMed1990

T-lymphocyte subsets in the duodenal lamina propria of patients infected with the human immunodeficiency virus type 1 and influence of high-dose immunoglobulin therapy.

T-lymphocyte subsets in duodenal biopsies of human immunodeficiency virus type 1 (HIV-1)-infected patients were studied by immunocytochemical staining to determine the alterations of CD4- and CD8-cell subsets in comparison with HIV-1 antibody-negative controls and to examine the association with stage, gastrointestinal symptoms, and peripheral lymphocyte subsets and the influence of high-dose intravenous immunoglobulins. A significant decrease in duodenal CD4 cells (p less than 0.001) and CD4/CD8 ratio (p less than 0.001) follows HIV-1 infection when compared to HIV-1-negative controls, more accentuated both in patients of stage WR6 and suffering from diarrhea than in those of stages WR1-5 or without diarrhea. In addition, a significant increase in CD8 cells (p less than 0.01) could be found in HIV-1-infected patients, again with lower levels in patients of stages WR6 than WR1-5. A strong correlation was found between the intestinal and peripheral CD4/CD8 ratio (R = 0.80), but the correlation was weak if HIV-1-negative persons were excluded from analysis (R = 0.29). Treatment with high-dose intravenous immunoglobulins improved diarrhea in four of five patients; two patients gained weight. Diffuse lymphocytic infiltration of the lamina propria, villous atrophy, CD4- and CD8-cell percentage, and CD4/CD8 ratio were not influenced.

Adult↗
PubMed1990

[Malnutrition--a clinically relevant problem in HIV-1 infection?].

Until now, recommendations for nutrition therapy of HIV-infected subjects can only be regarded as preliminary, because of the lack of scientific results regarding the interactions between HIV-infection and nutrition. HIV-infected patients have a high risk to become malnourished during the course of the disease, as a consequence of multiple pathogenetic factors--similar to the nutritional problems of tumor patients. At the moment, the following procedure is recommended in order to treat or prevent HIV-associated malnutrition: The nutritional status and history should be assessed in each HIV-positive subject as early as possible. Independent of the actual nutritional status, each patient should obtain a nutrition education. A continuous nutrition therapy becomes necessary in the case of evident or imminent malnutrition. Nutrients should be applied by oral access as long as possible. But especially for patients with opportunistic infections of the GI-tract accompanied by malabsorption, total parenteral nutrition may be the only effective way of nutrition.

Enteral Nutrition↗
PubMed1989

[Diagnosis and therapy of malignant peritoneal mesothelioma].

Malignant peritoneal mesothelioma is an uncommon tumor with great diagnostic and therapeutic problems. Symptoms, clinical features and course of the disease are described in three patients which were seen at our hospital within the last years. At the beginning there are often severe weight loss, malaise and sometimes fever of unknown origin. Abdominal pain, increased abdominal girth or nausea indicate advanced tumor stages in most cases. Ultrasonography and computed tomography of the abdomen can give important information during the diagnostic approach. Nevertheless, the definite diagnosis can only be established by laparoscopy or open surgery with biopsy for a histological examination. Despite intern and extern radiotherapy as well as systemic and/or local chemotherapy the prognosis of malignant peritoneal mesothelioma remains unfavourable. Mean survival time ranges from six to 18 months.

Aged↗
PubMed1989

Therapeutic value of calcium antagonists in autonomous hyperaldosteronism.

The chronic effect of the calcium antagonist nitrendipine was investigated on blood pressure (BP), plasma aldosterone concentration (PAC), plasma renin activity (PRA), and serum potassium in six patients with primary aldosteronism, either due to an (unilateral) aldosterone-producing adenoma (APA; n = 3; age, 44 +/- 4 years; PAC, 312 +/- 96 pg/ml; PRA, less than 0.1 ng/l.h; serum potassium, 2.8 +/- 0.3 mmol/l) or to bilateral idiopathic hyperaldosteronism (IHA; n = 3; age, 49 +/- 1 years; PAC, 212 +/- 32 pg/ml; PRA, 0.1 +/- 0.1 ng/l.h; serum potassium, 3.3 +/- 0.2 mmol/l). After withdrawal of antihypertensive medications at least 3 weeks prior to the study, nitrendipine was given orally in a daily dosage of 40 to 60 mg. BP, PAC, PRA, and serum potassium were determined before (see data above) and after 4 weeks of nitrendipine therapy. After 4 weeks, BP was significantly reduced (178 +/- 10 to 165 +/- 6 mmHg systolic, 109 +/- 7 to 101 +/- 6 mmHg diastolic) in three patients with APA and in two with IHA. No significant changes of PAC, PRA, and serum potassium were observed in these patients. However, one patient with clinical characteristics of IHA and a long-term history of diuretic therapy showed a complete normalization of BP, PAC, PRA, and serum potassium, suggesting that the etiology of autonomous hyperaldosteronism in this patient might differ from typical primary aldosteronism. From these findings we conclude that calcium antagonists may be helpful in lowering BP in those patients with primary aldosteronism who develop intolerable side effects under treatment with spironolactone or trilostane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1989

Impact of acute and chronic sodium loading on atrial natriuretic peptide and renin in man.

The relationship between the renin-angiotensin system and the atrial natriuretic peptide and its contributions to the control of sodium balance is not clarified. We therefore studied plasma renin concentration (PRC) and plasma levels of atrial natriuretic peptide (ANP) in normal subjects during acute and chronic salt loading. Acute intravascular volume expansion by iv infusion of 2000 ml of normal saline resulted in sharp rise in plasma ANP from 122 +/- 24 to 405 +/- 141 pg/ml (p less than 0.05). This increase was only transient with plasma ANP returning to control levels after 240 min. In contrast, reduction in plasma renin concentration was less pronounced, however it was persistent for up to 240 min paralleled by a reduction in plasma protein. Reciprocal changes in ANP plasma levels and PRC were observed during dietary modification in sodium intake. At the end of low sodium diet over 4 days, supine plasma ANP averaged 49 +/- 7 pg/ml and levels increased to 128 +/- 38 pg/ml after 6 days of high sodium intake in 11 healthy subjects (p less than 0.05). In contrast, PRC values averaged 69.8 +/- 19.8 microU/ml and 14.4 +/- 6.5 microU/ml during low and high sodium diet respectively (p less than 0.01). The inverse relation between PRC and ANP was seen after prolonged dietary sodium loading over 15 days in 8 additional subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Renal and adrenal resistance against atrial natriuretic peptide in congestive heart failure: effect of angiotensin I-converting-enzyme inhibition.

We compared the natriuretic and diuretic effect of an intravenous infusion of 1-28 human atrial natriuretic peptide (hANP) (0.1 micrograms/kg/min over 30 min) in 10 patients with congestive heart failure (CHF) and in 10 control subjects of similar age and sex. In the controls, urine volume rose from 36.8 +/- 8.55 to 115.6 +/- 34.2 ml/30 min and urinary sodium excretion from 4.55 +/- 0.8 to 11.2 +/- 2.24 mEq/30 min before and during the infusion of ANP, respectively. In patients, baseline urine volume and sodium output were similar, however, rise in urine volume and urinary sodium was greatly reduced during the infusion of hANP. In patients with CHF, baseline plasma ANP levels (604.1 +/- 135.3 vs. 39.4 +/- 5.85 pg/ml; p less than 0.005) and urinary excretion of cyclic GMP (cGMP) (41.8 +/- 5.22 vs. 15.2 +/- 4.19 nmol/30 min; p less than 0.05) were significantly elevated compared to controls. The absolute and relative rise in cGMP excretion, however, was blunted in patients with CHF. In the controls, angiotensin I-converting-enzyme (ACE) inhibition by enalapril significantly reduced the urinary output of sodium and water after ANP infusion. Plasma ANP levels and urinary cGMP remained unaltered by ACE inhibition. Furthermore, treatment with enalapril resulted in a rise in renin and a drop in aldosterone levels. The reduction of plasma renin and serum aldosterone by ANP was maintained after ACE inhibition. In the patient group, administration of enalapril (3 X 2.5 mg every 6 h) reduced ACE activity in the serum from 84.7 +/- 16.9 to 2.13 +/- 0.88 U/l. Arterial blood pressure was lowered from 114.7 +/- 6.69 to 106.1 +/- 7.25 mm Hg systolic and from 76.9 +/- 3 to 69.2 +/- 3.7 mm Hg diastolic. However, natriuresis and diuresis and creatinine clearance following infusion of ANP remained unaltered.

Adrenal Glands↗