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Biomedical subjects

W Kaufmann

Publications and source records attributed to W Kaufmann.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

Natriuretic action of ANP is blunted by ACE inhibition in humans.

We investigated the impact of angiotensin I-converting enzyme (ACE) inhibition by enalapril (3 X 2.5 mg p.o.) on the renal action of acute intravenous (i.v.) infusion of atrial natriuretic peptide (1-28-hANP 0.1 micrograms/kg/min for 30 min) in 10 normal subjects. During the control infusion of ANP, urinary sodium excretion rose from 4.5 +/- 0.8 to 11.2 +/- 2.2 mEq/min and urine volume from 32 +/- 14 to 115 +/- 34 ml/30 min. This increment in urinary volume and sodium output during ANP infusion was almost completely reduced by ACE inhibition. ANP plasma levels before and during the infusion and stimulation of urinary cGMP excretion were unaltered by ACE inhibition. However, enalapril treatment reduced systolic blood pressure (SBP) from 112 +/- 3 to 106 +/- 3 mm Hg and diastolic blood pressure (DBP) from 71 +/- 2 to 66 +/- 3 mm Hg. The small rise in glomerular filtration rate (GFR) during the control infusion of ANP was not observed after pretreatment with enalapril. The study demonstrates the importance of the renin-angiotensin system for the natriuretic and diuretic action of ANP in normal humans.

Adult↗
PubMed1989

Detection of renal impairment in cases of chronic abuse of analgesics by administration of desamino-D-arginine vasopressin.

An early diagnosis of renal dysfunction is particularly important in patients with chronic abuse of analgesics. First morphological changes in cases of analgesic nephropathy are found in the renal medulla. Therefore, urinary osmolarity as well as the urinary excretion of cyclic adenosine monophosphate (AMP) and kallikrein were measured after application of desamino-D-arginine vasopressin (DDAVP) as parameters of the renal tubular function in 21 patients with normal creatinine clearance and a regular, excessive use of analgesics. The results were compared with those of 17 healthy volunteers and 8 patients with chronic renal insufficiency after analgesic nephropathy. In patients with analgesic nephropathy the urine osmolarity after 12 h of thirst was 367 +/- 28 mOsm/kg and did not increase after DDAVP. The results obtained from healthy volunteers were 781 +/- 39 mOsm/kg. Half of the patients with chronic misuse of analgesics had lower values of urine osmolarity after thirst and DDAVP compared to the reference area of healthy subjects. Similar results were found when the effect of DDAVP under conditions of water-loading was tested. The excretion of cyclic AMP as a second messenger of DDAVP and of kallikrein did not differ between patients with chronic abuse of analgesics and healthy volunteers. The excretion of kallikrein in patients with manifest analgesic nephropathy, however, was decreased. Thus the renal concentration test with DDAVP proved to be useful in early diagnosis of renal dysfunction caused by analgesics.

Adult↗
PubMed1988

Transforming activity of DNA from rat liver tumors induced by the carcinogen methyl(acetoxymethyl)nitrosamine.

Altered c-Ha-ras genes have been frequently detected in the DNA of spontaneous or chemically induced mouse liver tumors. To determine if ras gene mutation is a frequent event during liver carcinogenesis in rats, we examined the transforming activity of DNA from liver tumors that developed in rats injected with methyl(acetoxymethyl)nitrosamine (DMN-OAc) after a partial hepatectomy. Three weeks after the injection of DMN-OAc, rats were fed a diet containing phenobarbital. This carcinogen acts only on replicating liver cells. Six of eight tumor DNAs induced the transformation of NIH 3T3 cells. The transforming activity was stable upon a second round of transfection, and the transformants were tumorigenic in nude mice. Southern blot analysis of transformant DNAs showed that the transforming activity was not due to the acquisition of a ras (Ha, Ki, or N), neu, myc, A-raf, v-raf, erbA, or erbB gene of rat origin. Several transformants' restriction enzyme sensitivity was analyzed, and their activity indicated that similar transforming sequences were present in at least two tumors and that one tumor contained two different transforming sequences. These results suggest that during hepatocarcinogenesis induced in rats by DMN-OAc, alterations in the ras gene family occur infrequently or not at all and that several different genes (which are not homologous to common oncogenes) become activated and are capable of transforming NIH 3T3 cells.

Animals↗
PubMed1988

Relationship between plasma atrial natriuretic peptide and left atrial and left ventricular involvement in essential hypertension.

In order to investigate the role of cardiac hypertrophy in atrial natriuretic peptide (ANP) secretion in patients with essential hypertension, plasma levels of ANP were measured after overnight rest in 36 patients with untreated hypertension and in 31 normotensive controls. In the hypertensive subjects, plasma levels were correlated with left ventricular (LV) and left atrial abnormalities detected by chest X-ray, electrocardiogram (ECG) and M-mode echocardiography. Plasma ANP levels in patients with hypertension averaged 146 +/- 27 pg/ml compared to 46 +/- 7 pg/ml in the normotensive subjects (P less than 0.001). In patients with hypertension a significant correlation was found between ANP and supine systolic blood pressure (r = 0.54, P less than 0.001) and between ANP and diastolic blood pressure (r = 0.38, P less than 0.05). Furthermore, plasma ANP levels were correlated with total heart volume (r = 0.68, P less than 0.01), LV mass (r = 0.525, P less than 0.001), LV posterior wall thickness (r = 0.39, P less than 0.05), Sokolow-Lyon index (r = 0.721, P less than 0.001) and end-diastolic diameter of the left atrium (r = 0.334, P less than 0.05). The results suggest a contribution of LV and left atrial abnormalities to ANP secretion in essential hypertension.

Adult↗