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Biomedical subjects

U Kuhlmann

Publications and source records attributed to U Kuhlmann.

At least 73 records · Page 4Linked to original sources
PubMed1990

Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry.

Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man.

Blood Platelets↗
PubMed1990

Uremic pruritus in patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). The role of plasma histamine and skin mast cells.

Fifty-four uremic patients (26 patients were maintained on continuous ambulatory peritoneal dialysis [CAPD] and 28 on hemodialysis [HD]) were screened for pruritus and plasma histamine. 50% of the patients on CAPD and 64.3% of patients on HD complained of current itching. The extent of itch, assessed by a score, was not significantly different between HD and CAPD patients. Plasma histamine levels showed no significant difference between CAPD and HD patients and no correlation between plasma histamine level and the extent of pruritus could be demonstrated. In six patients on CAPD and 9 patients on HD plasma histamine levels were determined before and three months after initiation of dialysis treatment; no substantial change could be observed. In some patients skin biopsies were obtained from the gluteal region in order to determine the number of skin mast cells. The number of mast cells did not show a significant difference between controls (n = 12), uremic patients before initiation of dialysis treatment (n = 8), patients on CAPD (n = 11) and patients on HD (n = 13). There was no relationship between the level of plasma histamine, the number of skin mast cells and the extent of pruritus in uremic patients.

Adult↗
PubMed1989

Multifactorial genesis of enhanced platelet aggregability in patients with nephrotic syndrome.

Platelet aggregation, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) release and thromboxane B2 (TxB2) formation in stimulated platelet-rich plasma were investigated in 13 patients with nephrotic syndrome who had normal serum creatinine levels (creatinine clearance greater than 70 ml/min/1.73 m2). In contrast to 13 sex- and age-matched controls, spontaneous platelet aggregation only occurred in patients with nephrotic syndrome with correlation to serum albumin and plasma fibrinogen levels. The EC50 (estimated concentration of aggregating agent to cause half maximum velocity of primary aggregation) for ADP and collagen and threshold concentration of arachidonic acid (threshold AA) were decreased in patients with nephrotic syndrome, reflecting a hyperaggregable state. In patients with nephrotic syndrome EC50 ADP values were significantly correlated to serum albumin, serum cholesterol and plasma fibrinogen, however, EC50 collagen or threshold AA did not correlate to these parameters. Plasma beta-TG levels were increased in patients, whereas plasma PF 4 levels were not significantly changed in patients compared to controls. In vitro TxB2 formation was elevated in patients only after stimulation with AA. Nevertheless, after stimulation with collagen and ADP, TxB2 formation was unchanged in patients compared to controls. Platelet hyperaggregability in nephrotic patients was confirmed in our study. However, unchanged thromboxane B2 formation after collagen stimulus as well as missing correlations between EC50 collagen or threshold AA and serum albumin were contradictory to the hypothesis that enhanced AA availability due to hypoalbuminemia is responsible for platelet hyperaggregability. Platelet hyperaggregability in terms of EC50 ADP being associated with serum albumin levels as well as to serum cholesterol and plasma fibrinogen indicate a multifactorial genesis.

Female↗
PubMed1989

Cure and improvement of renovascular hypertension after percutaneous transluminal angioplasty of renal artery stenosis.

In the present study we report our long-term experience in 82 patients with renovascular hypertension (48 with atherosclerotic stenosis, 34 with fibromuscular dysplasia) who were followed up for a mean observation period of 23.6 months after percutaneous transluminal angioplasty (PTA) of renal artery stenosis. Our results show a highly significant decrease in mean systolic and diastolic blood pressure. Cure rates were slightly higher in patients with fibromuscular dysplasia (41% cured, 47% improved) than in those with atherosclerosis (23% cured, 54% improved). Kidney function significantly improved in patients with cure, remained stable in those with improvement and worsened in cases classified as unimproved. These results document the good long-term effect of PTA on blood pressure and kidney function in patients with renal artery stenosis.

Adult↗
PubMed1989

Treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) with intraperitoneal cefazolin and gentamicin.

Between 1983 and 1988 57 peritonitis episodes in an unselected patient population were initially treated with intraperitoneal cefazolin and gentamicin. The loading dose consisted of 500 mg cefazolin/L dialysate and 40 mg gentamicin/L dialysate. The maintenance dosage was 125 mg cefazolin and 8 mg gentamicin per liter dialysate. Forty-five (78.9%) patients were primarily cured with this regimen (responder group = RG). Twelve patients (21.1%) did not respond to the initial therapy (nonresponder group = NG). Eight peritonitis episodes in the NG (14.0% of all patients) were caused by tunnel infections and 2 by diverticulitis (3.5%). The cure rate in patients without tunnel infection or bowel disease was 95.7%. A relapse occurred in 2 patients (3.5%). Duration of therapy was assessed by daily white blood cell count (WBC) in the effluent and treatment was discontinued when the WBC was less than 100/microliters for 3 days. The mean duration of therapy with cefazolin and gentamicin was 8.1 days in the RG and 6.0 days in the NG. Nonresponders were subsequently treated with a modified antibiotic regimen on an average 11.9 days.

Catheters, Indwelling↗
PubMed1989

[Fluorescent formazans in flow cytometry. Studies of their oxygen sensitivity].

In order to supply the tetrazolium salt procedure to flow cytometry we have synthesized monotetrazolium salts which are converted into fluorescent formazans on reduction. In this preliminary study we investigated the "oxygen sensitivity" of four of our compounds and compared them to the commercially available nitrotetrazole blue (NBT). The amount of formazan produced by Ehrlich ascites tumour cells via the succinic dehydrogenase reaction during oxic and anoxic incubations was determined by elution technique. Under oxic conditions no NBT formazan but much cyano-di-chlorophenyl formazan (==CCPC) was generated. The yields of this formazan differed only slightly between oxic and anoxic incubations. Twice as much of the amount of the other three formazans cyano-ditolyl- (==CTC, Stellmach 1984), cyanodiphenyl- (==CPC), and cyano-dianisyl tetrazolium chloride (==CAC), were produced in nitrogen atmosphere as in oxygen. The amount of all formazans investigated increased both in oxic and in anoxic conditions if cyanide was present. All cyano-aryl formazans have the maximum of absorbance between 430 and 470 nm and fluoresce in the spectral range above 580 nm with CTC formazan being the brightest. The tetrazolium salts, i.e. in unreduced state, did not fluoresce in the visible part of the spectrum. The formazans could be applied to flow cytometry. After staining the nuclear DNA with the fluorochrome DAPI, we obtained detailed two-parametric distributions correlating the amount of formazan per cell with the DNA content. The results are a step to establish a method for automated identification of malignant cells.

Animals↗
PubMed1988

Pharmacokinetics and pharmacodynamics of nitrendipine in healthy subjects and patients with kidney and liver disease.

Nitrendipine [3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate] is a calcium antagonist with a dihydropyridine structure that has a great structural resemblance to nifedipine. Instead of a methyl group in position 3, it has an ethyl group and the NO2 group is in the meta instead of in the ortho position. These minor structural differences have a pronounced impact with respect to both the pharmacokinetics and pharmacodynamics of nitrendipine as compared to nifedipine. Based on equimolar plasma concentrations, nitrendipine is on average three times more potent than nifedipine with regard to the reduction of peripheral vascular resistance, arterial blood pressure, and increased leg blood flow. The terminal half-life is on average 8 h, and thus substantially longer than the terminal half-life of 2-3 h for nifedipine. Despite its almost complete absorption, bioavailability is on average 15-25% and shows great interindividual variability ranging from 7 to 40%. The systemic plasma clearance of the drug is on average 18 ml/min/kg and thus approaches the liver blood flow. In patients with liver cirrhosis, the half-life is prolonged to 19.6 h, the total plasma clearance is decreased by 50%, and the bioavailability is more than doubled to 54%. No data are available if liver disease alters the pharmacodynamic response of the drug. Kidney disease has some effect on the disposition of the drug. Systemic clearance is not changed but the terminal elimination half-life is slightly prolonged to 10.5 h. This increase in half-life is due to an increased volume of distribution. Bioavailability, which is 21.2%, is not grossly altered in renal failure.

Humans↗
PubMed1986

Renal venous renin determinations in renovascular hypertension. Diagnostic and prognostic value in unilateral renal artery stenosis treated by surgery or percutaneous transluminal angioplasty.

To assess the diagnostic and prognostic value of renal venous renin levels in renovascular hypertension, 95 patients with severe unilateral renal artery stenosis were studied. Surgery (n = 52) or percutaneous transluminal dilation (n = 43) were done irrespective of renal venous renin levels. Lateralization of renin secretion as assessed by the PRA ratio and the renin secretion index was found in the majority of patients (66% and 88%, respectively). Patients with fibromuscular hyperplasia had more frequently PRA ratios less than 1.5 than those with arteriosclerotic stenosis (p less than 0.05). The renin secretion index proved to have a higher sensitivity (92%) and predictive value (92%) for a successful outcome of both surgery and PTA than the PRA ratio (69% and 89%, respectively), while the specificity was the same with both parameters (42% and 43%, respectively). The contralateral suppression index was most specific in predicting an unfavorable outcome. However, with all ratios used, a considerable number of false-negative and false-positive tests were observed both with surgery and PTA, a finding limiting the value of the method in selecting patients for these interventions. Other factors, such as age of the patient, kidney function and the underlying arterial disease turned out to be equally important prognostic factors. Thus, although cure after both surgery and PTA is more likely in the presence of lateralized renin secretion and contralateral suppression, the method does not allow to exclude patients with severe renal artery stenosis, hypertension and negative renal venous renin tests from these interventions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Surgery, transluminal dilatation and medical therapy in the management of renovascular hypertension.

In the present retrospective study, the effect of various therapeutic procedures (surgery, percutaneous transluminal dilatation and antihypertensive drugs) was analyzed in 202 patients with renovascular hypertension. The results show that each of the three methods effectively lowers blood pressure. However, marked differences were observed in pretreatment clinical and laboratory data among the three groups. These differences were most probably caused by different selection criteria before submitting the patient to a given therapeutic regime. Our findings also demonstrate that on the basis of the present analysis a direct comparison between surgery, dilatation and medical therapy is not possible.

Adult↗
PubMed1986

Fibromuscular hyperplasia: extension of the disease and therapeutic outcome. Results of the University Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia.

92 patients with fibromuscular hyperplasia (FMH) seen at the University Hospital Zurich were studied. Renovascular FMH was the most frequent manifestation of the disease (89%). FMH of the cerebral arteries was seen in 26%. The intestinal and subclavian arteries were involved in 9% each and the iliac arteries in 5% of the patients. In 2 patients each FMH of the abdominal aorta or the coronary arteries, respectively, was found. 26% of the patients had systemic disease with involvement of 2 or more arteries. Half of the patients with bilateral renovascular disease showed additional extrarenal FMH. All patients with renovascular FMH were hypertensive (mean blood pressure 194 +/- 34/119 +/- 18 mm Hg). Surgery, percutaneous transluminal angioplasty (PTA) and medical therapy were equally effective in controlling blood pressure. The cure rates were 52% in patients undergoing surgery and 50% in those treated with PTA. The complication rate, however, was higher with surgery (11%) than with PTA (3%). 62% of the patients treated medically were normotensive. Major side effects occurred in 4.8%. The outcome of curative interventions (surgery or PTA) was influenced by the extension of FMH. In unilateral disease the cure rate was significantly higher (62%) than in systemic FMH (28%; p less than 0.03). Patients with strict bilateral disease were cured in 50%. We conclude: (a) PTA seems to be the treatment of choice in renovascular FMH because of a high cure and a low complication rate and (b) the outcome of curative interventions seems markedly influenced by the extension of FMH in these patients.

Adult↗
PubMed1985

[Renovascular hypertension: surgery, dilatation or drugs?].

The effect of various therapeutic procedures (surgery, percutaneous transluminal dilatation and antihypertensive drugs) was analyzed in 161 patients with renovascular hypertension. The results show that each of the three methods effectively lowers blood pressure. However, marked differences in pretreatment clinical and laboratory data among the three groups were observed, which were most probably caused by different selection criteria before submitting the patient to a given therapeutic regime. The findings also demonstrate that, on the basis of the present analysis, a direct comparison between surgery, dilatation and medical therapy is not possible.

Adult↗
PubMed1985

[Fibromuscular renovascular hypertension: comparison of surgery, transluminal dilatation and drug therapy].

82 patients with fibromuscular renovascular hypertension have been studied. 33 patients were treated surgically (group I), 28 underwent transluminal dilation (group II) and 21 received drug treatment (group III). After a follow-up period of 2.5 (0.1-7) years, blood pressure in group I had decreased from 207 +/- 27/128 +/- 17 mm Hg to 135 +/- 15/85 +/- 9 mm Hg after surgery (p less than 0.001). 1.3 (0.1-4) years after dilation, group II showed a decrease of blood pressure from 174 +/- 25/107 +/- 13 mm Hg to 143 +/- 26/88 +/- 12 mm Hg (p less than 0.001). Blood pressure in group III decreased under drug therapy from 203 +/- 41/122 +/- 16 mm Hg to 146 +/- 19/92 +/- 8 mm Hg (p less than 0.001). 52% of the surgical patients and 50% of the dilated patients were cured, whereas 45% and 39% respectively were improved and 3% and 11% respectively did not improve. In group III, under antihypertensive drug therapy, blood pressure normalized in 62% of the patients, 33% showed better values and 5% did not improve. The complication rate was 11% in group I and 3.3% in group II. In two patients dilation was technically impossible. In group III one patient (4.8%) showed a massive but reversible increase of serum creatinine under captopril. In 70% of all patients the renal vein renin ratio was greater than or equal to 1.5. However, this ratio was unreliable as a parameter to predict the blood pressure decrease with curative methods. It is concluded from the above that all three methods offered good to very good results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

[Diuretics and antihypertensive agents in chronic kidney insufficiency: comparison of the effects of metolazone and furosemide].

Increasing dosages of two potent diuretic agents (5, 10, 20 mg metolazone or 40, 80, 160 mg furosemide) were compared in 35 patients with hypertension and chronic renal failure. In cases with insufficient blood pressure control, 10 mg pindolol was given as a second drug. Finally, patients not responding to a betablocker-diuretic combination received 100 mg hydralazine as a third drug. Both diuretics had comparable antihypertensive potency during a treatment period of up to 12 weeks. Maximal antihypertensive response was observed under 10 mg metolazone or 160 mg furosemide. However, only in 25% of our patients blood pressure was normalized with diuretic monotherapy (metolazone or furosemide). The remaining cases needed either an additional betablocker or a combination of three different antihypertensive agents. Under these conditions a substantial proportion of our patients (20%) did not reach the therapeutic goal (diastolic blood pressure less than 95 mm Hg). These results document the difficulties of hypertension management in chronic renal failure. An early change to the stepped-care approach should be made in all cases with insufficient blood pressure response to potent diuretics.

Adult↗