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Biomedical subjects

J Kindler

Publications and source records attributed to J Kindler.

At least 19 recordsLinked to original sources
PubMed2002

Coexistence of antitopoisomerase I and anticentromere antibodies in patients with systemic sclerosis.

BACKGROUND: Antibodies targeting DNA topoisomerase I (ATA) or centromere proteins (ACA) are associated with clinical subsets of patients with systemic sclerosis (SSc). The occurrence of those autoantibodies is considered to be mutually exclusive. OBJECTIVE: To describe the clinical and immunogenetic data of three patients who are co-expressing both antibodies, and then review previous publications. METHODS: Both antibodies were detected by different methods, including indirect immunofluorescence technique, enzyme linked immunosorbent assay, immunodiffusion, and immunoblot. Patients were HLA typed by serological and molecular genetic methods. Data were extracted from published reports for comparison. The search for published studies was through Medline and other database research programmes. RESULTS: During routine laboratory diagnostics over several years three patients with scleroderma and coincidence of ATA and ACA were identified: patient 1 with diffuse SSc, Raynaud's phenomenon, puffy fingers and fingertip necrosis, contractures, and calcinosis; patient 2 with diffuse SSc, Raynaud's phenomenon, oedema of the hands, and interstitial calcinosis of hands, knees, and shoulders, and pulmonary fibrosis; patient 3 with scleroderma of hands, forearms, and face, Raynaud's phenomenon, puffy fingers, finger contractures, fingertip necrosis, and calcinosis. All three patients studied were carriers of HLA alleles known to be associated with these autoantibodies. In serial measurements the concentrations of the two antibodies showed independent or even reverse fluctuations. Screening of 100 patients with ACA for ATA and vice versa disclosed no further patients with coincidence of these antibodies. Twenty eight cases of ACA/ATA coexistence in 5423 patients (0.52%) with SSc or SSc associated symptoms were found in an analysis of published studies. CONCLUSION: The expression of ATA and ACA is not totally mutually exclusive, but coincidence is rare (<1% of patients with SSc). Patients with both autoantibodies often have diffuse scleroderma and show immunogenetic features of both antibody defined subsets of SSc.

Adult↗
PubMed1998

Coronary vasculopathy in polycythemia vera.

Thrombosis is a common complication in polycythemia often causing death. In coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is mostly discussed as the origin of the infarction. We discuss the case of a 30-year-old male patient, with polycythemia, who died of myocardial infarction. On autopsy the vessels showed neither ateriosclerotic changes nor thrombotic occlusions. Instead, a marked intima proliferation was found leading to multiple occlusions whereas media and adventitia were unchanged. This pattern of a coronary vasculopathy has not been described before, and can be interpreted as an alternative mechanism for vascular occlusion in polycythemia. Similar histopathological changes have already been found in skin lesions in erythromelalgia, a common symptom in polycythemia.

Adult↗
PubMed1997

[Small cell bronchial carcinoma and pleural empyema after pneumonectomy for tuberculosis].

We report the case of a 60-year-old man with a destructive ipsilateral bronchial carcinoma after pneumonectomy performed for tuberculosis several decades previously. The diagnosis steps in this case report are demonstrated and the correlations between the two diseases are discussed. The early diagnosis of malignant processes after thoracotomy performed because of tuberculosis is emphasized.

Carcinoma, Small Cell↗
PubMed1995

Long-term ciclosporine A treatment in adults with minimal change nephrotic syndrome or focal segmental glomerulosclerosis.

To evaluate the efficacy and safety of long-term ciclosporine A (CSA) treatment in idiopathic nephrotic syndrome, we prospectively followed immunosuppressive therapy in 22 nephrotic adults for a median of 32 months (range 7-91 months) and obtained repeat renal biopsies. CSA induced complete remission in 60.0% and 14.3% of patients with minimal change nephrotic syndrome (MCNS) (n = 7), respectively. In addition, partial remissions were achieved in 20.0% of patients with MCNS and in 42.9% of patients with FSGS. Resolution of proteinuria was strictly CSA-dependent and no sustained remission occurred following withdrawal, thereby requiring long-term treatment in 18 patients. In 10 patients CSA was administered for more than 43 months. During maintenance therapy the antiproteinuric effect of CSA was preserved and renal function as well as blood pressure remained stable in patients with MCNS, whereas renal function deteriorated in two patients with FSGS due to progression of the underlying renal disease. Renal biopsies revealed slight signs of CSA toxicity in four patients. However, in no case loss of renal function was attributable to these lesions. In conclusion, the present data suggest that long-term maintenance treatment of MCNS with CSA is efficacious and safe at least for a period of up to 43 months. In contrast, CSA has some effect on proteinuria in FSGS, but the results are less favorable.

Administration, Oral↗
PubMed1993

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↗
PubMed1993

Torasemide in advanced renal failure.

In patients with advanced renal failure, high doses of loop diuretics are required to promote negative sodium and water balance and to treat hypertension. Torasemide is a new loop diuretic that has a high bioavailability of 90% and a plasma half-life of 3-5 hours, which remains unchanged in chronic renal failure. Even in patients with advanced renal failure, intravenous and oral high-dose torasemide proves effective in increasing fluid and sodium excretion in a dose-dependent manner. A number of studies in renal failure patients provide evidence that, on a weight-by-weight basis, the ratio of diuretic potency between torasemide and furosemide is 1:2.5 after oral dosing and 1:1 after intravenous administration. The lack of a substantial calciuretic effect of torasemide in chronic renal disease needs further confirmation. Two controlled multicenter clinical trials comparing high oral doses of furosemide and torasemide in patients with end-stage renal disease requiring maintenance hemodialysis demonstrated a substantial increase in urinary volume and electrolyte excretions in patients receiving 100 or 200 mg oral torasemide once daily. A dose of 200 mg oral torasemide appears equally natriuretic to oral furosemide 500 mg, whereas the antihypertensive effect of torasemide is more pronounced. Neither torasemide nor furosemide in the above doses has a negative influence on the neurological status of hemodialysis patients.

Administration, Oral↗
PubMed1992

Serial kidney biopsies in patients with nephrotic syndrome treated with cyclosporin.

A total of 21 patients with severe steroid-resistant or steroid-dependent nephrotic syndrome have been treated with cyclosporin (CsA) over a period of 6 to 71 months. A permanent treatment was started in patients with complete [c] (proteinuria less than 0.3 g/day) or partial [p] (0.3 to less than 3.0 g/day) remission. In four cases proteinuria was markedly reduced but still greater than 3 g/day. Informed consent was obtained and all patients agreed to further control biopsies. Out of 14 patients treated for longer than 6 months, a fall in creatinine clearance was seen in three cases, including two patients with focal sclerosis who required dialysis treatment. Control biopsies were performed once in 11 and twice in seven patients. In two cases definite CsA-related damage was diagnosed after 1 and 24 months of treatment. Possible CsA-induced damage could not be excluded in three additional cases. In all other biopsies no CsA-related alterations could be demonstrated up to 47 months of treatment. The mean values of the creatinine clearance showed no deterioration. The drop off in a few cases has been related to the basic disease.

Adolescent↗
PubMed1990

[The effect of various factors on the progression of kidney insufficiency cause by analgesic nephropathy].

In a retrospective study of 33 patients the influence of different anamnestic, clinical and laboratory parameters on the progression of renal failure was investigated. The analysis of progression of renal failure was evaluated in terms of a reasonable criterium intuitively suggesting itself which is based on a non-linear fitting of the serum creatinine profile. Follow-up serum creatinine levels showed that renal function became worse in 28 cases, with terminal renal failure developing in 6 cases. In 5 patients significant improvement in kidney function was observed. The variables systolic and diastolic blood pressure, total amount of ingested analgesics, continued abuse and cessation of analgesics, frequency of urinary tract infections and amount of proteinuria had no significant influence on progression of renal failure. However, a strong relationship between the initial serum creatinine level and the progression of renal failure could be established. In conclusion our results indicate that long-term prognosis of analgesic nephropathy mainly depends on early diagnosis.

Adult↗
PubMed1989

Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency.

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1-2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5-15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15-40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40-80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Fournier's gangrene in hypersensitivity vasculitis.

Fournier's gangrene in IgE positive hypersensitivity vasculitis demands concurrent high dose immunosuppression, radical surgery and intensive treatment of septic sequelae. Even extended autologous skin grafting is possible with immunosuppression. A case of fulminant necrotizing infection of the genitalia, perineum and abdominal wall during the acute generalization phase of IgE positive hypersensitivity vasculitis is described. Apart from the radical surgical approach, medical treatment demands a different strategy than in classical Fournier's gangrene. The favorable outcome in a 21-year-old man after several months of intensive care could be realized only by close cooperation of internal specialists, urologists and plastic surgeons.

Adult↗
PubMed1989

Single-dose pharmacokinetics of recombinant human erythropoietin in patients with various degrees of renal failure.

The pharmacokinetic profile of recombinant human erythropoietin (rHuEpo) was studied after a single intravenous dose of 150 U/kg in ten patients with various degrees of renal function: group I, creatinine clearance greater than 80 ml/min, n = 2; group II, creatinine clearance 10-50 ml/min, n = 6; group III, creatinine clearance less than 3 ml/min (patients undergoing haemodialysis) n = 2. Erythropoietin concentrations in serum and urine samples obtained over 48 h were measured by RIA. rHuEpo was cleared from circulation in an exponential fashion, the half-life ranged from 6.5 to 12.7 h (mean 9.03 h) and was not different between the groups. The apparent volume of distribution varied from 0.041 to 0.099 l/kg (mean 0.070 l/kg) this corresponds to 1.5 times the plasma volume and was unrelated to kidney function. Renal clearance (groups I, II) accounted for less than 3% of total body clearance, both parameters were unaffected by decreasing renal function. These results indicate that, in accordance with animal data, the elimination of rHuEpo occurs mainly through non-renal mechanisms.

Adult↗
PubMed1989

Steady-state kinetics of ramipril in renal failure.

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 23 hypertensive patients with various degrees of renal insufficiency. During a 2-week treatment period, each subject took daily a 5-mg tablet of ramipril. Serum profiles and urinary excretion of the parent compound and ramiprilat, the active metabolite, were then evaluated. Peak concentrations of ramipril were slightly greater in patients with severe renal insufficiency; however, most of the ramipril was metabolized in the liver. The drug concentration-time curve was almost independent of renal function and no accumulation was observed after multiple dosing. In contrast, ramiprilat kinetics were significantly influenced by renal function. Initial apparent half-lives (8-16 h), mean trough concentrations (5-19 ng/ml), and absolute accumulation all increased with worsening renal function, and renal clearance of ramiprilat was significantly correlated with creatinine clearance. The subsequent long terminal phase at low ramiprilat serum concentration represents the slow dissociation of the angiotensin converting enzyme (ACE)-bound drug. This study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min), smaller doses of ramipril will be required than in patients with normal or borderline normal renal function.

Adult↗
PubMed1989

Therapeutic efficacy and tolerance of ramipril in hypertensive patients with renal failure.

In an open trial, the antihypertensive and hormonal effects of ramipril, a new nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, were studied in 23 hypertensive patients with various degrees of renal failure: group I, creatinine clearance 5-15 ml/min, n = 10; group II, creatinine clearance 15-40 ml/min, n = 7; group III, creatinine clearance 40-80 ml/min, n = 6. In a 2-week placebo run-in period, antihypertensive agents were reduced or discontinued. During the treatment phase, patients received a 5-mg tablet of ramipril once daily for a period of 2 weeks. Concomitant medication remained unchanged. In all groups, ramipril significantly decreased mean arterial blood pressure. Blood pressure response was not different in the three groups, although plasma ramipril levels were higher in patients with severe renal failure. In patients with high plasma renin activity (PRA), reduction of blood pressure was greater than in subjects with low PRA. Plasma ACE activity was suppressed to less than 20% of its initial value in all groups during the whole treatment period, and the suppression was more marked and lasted longer in patients with severe renal failure. A strong correlation between the plasma ramiprilat levels and the inhibition of plasma ACE activity was noted for all groups. Mean serum creatinine did not increase significantly; serum potassium levels rose from 4.5 to 4.9 mmol/L on day 14 (p less than 0.01). In conclusion, in patients with various degrees of renal failure, ramipril represents an effective and well-tolerated antihypertensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗