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Biomedical subjects

E Fritschka

Publications and source records attributed to E Fritschka.

At least 19 recordsLinked to original sources

Hereditary premenopausal breast cancer.

Less than 1% of breast cancers occur between the age of 20 and 30 years, but more than 50% of breast cancers under the age of 30 years are hereditary. Breast cancer mainly occurs sporadically, however, in 5 to maximally 10% of cases a genetic predisposition is present. Mutations in the already sequenced tumor suppressor genes BRCA1 and BRCA2 account for 60-70% of these hereditary breast cancers. The chromosomal location of BRCA1 is 17q21 and that of BRCA2 is 13q12-13. Screening procedures and possible prevention strategies for women with mutations in the BRCA1 and BRCA2 genes are discussed. They include the use of tamoxifen.

Adult↗

An unusual case of systemic lupus erythematosus, lupus nephritis, and transient monoclonal gammopathy.

A 23-year-old female patient suffering from active systemic lupus erythematosus (SLE) was treated with azathioprine (2 mg/kg per day) and prednisone. Lupus nephritis class III with increasing proteinuria developed 28 months after disease onset. Treatment was switched to monthly pulse cyclophosphamide administered intravenously for 6 months (total dose 6.3 g), followed by oral azathioprine and low-dose prednisone to maintain partial remission. Eight months later, the patient developed an acute exacerbation of SLE with fever, proteinuria of 9.1 g/day, pancytopenia, and cerebral involvement with cephalgias and a grand mal seizure. She responded well to high-dose corticosteroids (500 mg prednisolone pulses over 3 days, i.v.) and was azathioprine switched from to methotrexate (12.5-15 mg per week). Under this treatment, lupus activity gradually decreased and the patient felt well again. Five years after the initial diagnosis of SLE, a rapidly increasing immunoglobulin G-kappa type (IgG-kappa) monoclonal gammopathy developed, reaching a maximal serum paraprotein concentration of 73.5 g/l. Bone marrow biopsy revealed 15% of moderately abnormal, highly differentiated plasma cells arranged in small clusters and expressing IgG-kappa. No bony lesions were detectable on skeletal radiographs. Pulses of dexamethasone (40 mg) were administered and led to a transient decrease of paraproteinemia to a minimum of 31.9 g/l, followed by an increase to 62 g/l. At that point, high-dose chemotherapy supported by autologous stem cell transplantation was considered. Due to an intermittent pneumococcal septicemia, methotrexate was discontinued and dexamethasone was replaced by 5-10 mg cloprednol. At this point, totally unexpectedly, the paraprotein decreased spontaneously without any further cytostatic treatment and was no longer detectable 1 year later. Concomitantly, plasma cell counts in bone marrow biopsies fell to below 5%. As SLE remained inactive, the patient became pregnant and gave birth to a healthy child. During late pregnancy, SLE activity flared up with rising proteinuria and blood pressure. Therefore, after delivery, cyclophosphamide (100 mg/day, orally) was readministered for 4 months, resulting in an improvement of kidney function with stable proteinuria of 1-2 g/l to date. Paraproteins are no longer detectable. In conclusion, this case report documents the rare event of transient paraproteinemia in a patient with SLE. A self-limiting regulatory defect in the control of a terminally differentiated B-cell clone may be the origin of this phenomenon.

Adult↗

Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial.

BACKGROUND: Calcium antagonists such as nitrendipine reduce the effects of cyclosporin on renal haemodynamics, however, their long-term efficacy has not been established. We did a randomised trial to investigate the effects of nitrendipine on renal function in renal-transplant patients treated with cyclosporin. METHODS: 253 renal-transplant patients were recruited: 52 normotensive patients (diastolic blood pressure <90 mm Hg) were assigned placebo and 57 nitrendipine 5 mg twice daily; 71 hypertensive patients (diastolic blood pressure >90 to <115 mm Hg) were assigned placebo and 73 nitrendipine 10 mg twice daily. Nitrendipine was increased to 20 mg twice daily if the target diastolic blood pressure (<90 mm Hg) was not achieved. The patients were seen once a month for 24 months; blood pressure and serum creatinine concentration were recorded at each visit. Analysis was by intention to treat. FINDINGS: 63 patients were withdrawn (35 nitrendipine, 28 placebo). The mean serum creatinine concentration at baseline was slightly higher in the nitrendipine group (146.7 micromol/L [SE 4.42]) than in the placebo group (137.0 micromol/L [3.54]. At the 24-month endpoint or at dropout, serum creatinine concentration was significantly higher in the 123 patients in the placebo group than the 130 patients in the nitrendipine group (160.8 [7.1] vs 148.5 [5.3], p for effect of treatment=0.025, analysis of covariance in a two-way classification; 95% CI for difference -1.77 to -22.98). At study entry, the blood pressures of the placebo and the nitrendipine groups were almost identical. At 24 months, blood pressure was higher in the normotensive patients given a placebo than in those patients given nitrendipine. By contrast, blood-pressure values were similar in those hypertensive patients given a placebo and those given nitrendipine at the end of treatment. INTERPRETATION: The calcium antagonist nitrendipine has no adverse effects on kidney function in renal-transplant patients with cyclosporin. The drug has a small but significant nephroprotective effect, that is independent of the drug's antihypertensive action.

Adult↗

Renal diseases in ankylosing spondylitis: review of the literature illustrated by case reports.

Ankylosing spondylitis (AS) can be accompanied by extraarticular manifestations in the cardiovascular, pulmonary, neurologic and renal organs. Secondary renal amyloidosis is the most common cause of renal involvement in AS (62%) followed by IgA nephropathy (30%), mesangioproliferative glomerulonephritis (5%) as well as rarely membranous nephropathy (1%), focal segmental glomerulosclerosis (1%) and focal proliferative glomeruleonephritis (1%). Treatment associated nephrotoxicity may result from non-steroidal anti-inflammatory drugs or disease modifying agents. The purpose of this paper was to alert for the possibility of renal damage in AS and to analyse the frequencies of different etiologies of renal involvement. Two typical case reports of renal involvement in AS are presented to illustrate the clinical course of such patients. Renal side effects and possible pre-existing renal diseases should be taken into account while choosing the appropriate medication for patients with AS.

Adolescent↗

Ambulatory infusion of noradrenaline for long-term treatment of Shy-Drager syndrome.

A 70-year-old female patient with advanced Shy-Drager syndrome exhibited severe orthostatic hypotension, low serum catecholamine levels, and autonomic dysfunction. She was bedridden despite oral medication with fludrocortisone, etilefrin, dihydroergotamine, L-dopa, yohimbine, and amezinium methyl sulfate. Only intravenous application of noradrenaline (30 ng/kg/min) provided complete mobilization. After implantation of a port-a-cath system, intravenous noradrenaline treatment could be continued on an outpatient basis. Over the following 5 years, the patient was throughout sufficiently mobile and did not show any significant side effects of this treatment. However, during the 5th year she suffered from nonhemorrhagic brain stem infarction due to cerebral hypoperfusion after orthostatic stress in the absence of noradrenaline infusion. We conclude that ambulatory noradrenaline infusion is a new valuable tool for long-term treatment of advanced Shy-Drager syndrome.

Ambulatory Care↗

Case report and review of the literature. Fatal pulmonary complication in ankylosing spondylitis.

A 44-year-old non-smoking patient with longstanding ankylosing spondylitis presented in marked respiratory distress with tachypnea, fever, cough, greenish sputum, night sweats, dyspnea and weight loss. Computed tomography showed traction bronchiectases and cavities associated with scarring. The findings were most pronounced in the upper lobes which contained multiple cavities up to 8 cm in diameter harboring fungus balls. The superior segment of the left lower lobe showed two additional cavities. Tuberculosis and atypical mycobacteria were ruled out. Antibiotic therapy resulted in transient improvement. Five months after this acute exacerbation the patient expired from massive haemoptysis. Pulmonary fibrosis is a rare manifestation of ankylosing spondylitis, may be complicated by infection and haemorrhage and determine the dismal prognosis of these patients.

Adult↗

Pharmacokinetics of the PDGF-antagonist trapidil in patients with and without renal impairment.

The pharmacokinetics of the PDGF-antagonist trapidil and its major metabolite desethyl-trapidil (M 1) were studied in patients with and without renal failure after a single dose of 200 mg and following 4-day treatment with 200 mg t.i.d. Twenty patients were classified according to their renal function as assessed by creatinine clearance (C(Cr)) in group A: 133.7 +/- 30.3 ml/min (n = 8), group B: 63.6 +/- 15.4 ml/min (n = 6) and group C: 17.9 +/- 6.1 ml/min (n = 6), patients on hemodialysis were not enrolled. After the first dose maximal plasma concentrations of trapidil with 5.99 +/- 1.60 (A), 5.76 +/- 1.46 (B) and 5.63 +/- 1.53 micrograms/ml (C) were not different between groups, but somewhat lower on day 4 with 4.96 +/- 0.78 (A), 5.78 +/- 1.78 (B) and 5.47 +/- 1.42 micrograms/ml (C). Similarly, AUC0-infinity-values on day 1 with 16.9 +/- 4.8 (A), 20.2 +/- 6.7 (B) and 22.2 +/- 11.2 micrograms/ml x h (C) showed only modest (NS) differences between groups, but decreased markedly on day 4 to 10.8 +/- 1.8 (A), 13.6 +/- 5.8 (B) and 14.4 +/- 4.3 micrograms/ml x h (C). Linear regression analysis between AUC and C(Cr) demonstrated no relationship between these parameters. For plasma concentrations of M 1 no significant differences were seen between groups. At steady state maximal plasma concentrations of M 1 occurred earlier and were slightly increased. In one patient (group B) receiving tamoxifen comedication markedly elevated plasma concentrations of trapidil and desethyltrapidil occurred, suggesting a pharmacokinetic interaction. Trapidil may be safely given to patients with impaired renal function, the apparent decrease of trapidil plasma concentrations may suggest autoinduction of metabolizing enzymes.

Administration, Oral↗

Elimination of amrinone during continuous veno-venous haemofiltration after cardiac surgery.

We studied the elimination of amrinone during continuous veno-venous haemofiltration (CVVHF) in three anuric patients after cardiac surgery. The patients had developed low cardiac output followed by acute prerenal failure. Plasma amrinone levels measured by HPLC were fitted to a two-compartment model. We found significant amrinone clearance, with a mean sieving coefficient (S) of 0.44%, which correlates with the protein-unbound, pharmacologically effective fraction of amrinone. The AUC of the arterial plasma concentration-time curve was decreased by 49.8%. All pharmacokinetic parameters showed wide interindividual variation. To ensure the therapeutic effect of amrinone and to avoid toxic adverse effects monitoring of plasma amrinone levels is necessary.

Amrinone↗

[Follow-up of plasma endothelin and serum interleukin 2 receptor level after liver transplantation].

In a prospective study levels of interleukin-2 receptors (Il-2-R) in serum and of endothelin (ET) in plasma were sequentially determined in 97 patients (39 women, 58 men) before and after liver transplantation (Ltx). The aim of the study was no evaluate the correlation and the time course of these two parameters after Ltx. The postoperative levels of Il-2-R and ET were higher in transplant recipients with no postoperative complications than in patients who had undergone operations to the liver. Patients suffering from acute rejection episodes after transplantation had more markedly increased Il-2-R and ET levels than those with an uneventful course, and this persisted for 3 months. A significant rise of Il-2-R concentrations 3-6 days before a biopsy confirmed rejection proved to have a sensitivity of 68% and a specificity of 68% respectively. A corresponding ET increase preceded rejection episodes confirmed by biopsy with a sensitivity of 62% and a specificity of 67%, respectively. These laboratory data can be obtained daily: they cannot undermine the "gold standard" of liver biopsy, but they are extremely beneficial in determining the timing and indication for the liver biopsy.

Adult↗

Teicoplanin pharmacokinetics and dosage recommendations in chronic hemodialysis patients and in patients undergoing continuous veno-venous hemodialysis.

Multiple-dose pharmacokinetics of teicoplanin, a glycopeptide antibiotic against gram-positive infections, were studied in 9 chronic hemodialysis (HD) patients and in 7 patients with an acute renal failure (ARF) treated by continuous veno-venous hemodialysis (CVVHD). After a loading dose of 800 mg i.v. the 400 mg maintenance doses were administered according to a target trough concentration of 5-15 mg/l. Using the Bayesian estimation method implemented in the computer program Abbottbase Pharmacokinetic System (PKS), we defined an open three-compartment kinetic model for teicoplanin and calculated the individual pharmacokinetics. The mean terminal elimination half-life was 176 +/- 41.3 h in the HD group and 99 +/- 22.3 h in the CVVHD group (p < 0.005). The total body clearance (CL) was 4 +/- 1.2 ml/min and 9.2 +/- 1.7 ml/min in the HD and CVVHD patients respectively (p < 0.001). The mean reduction of the serum levels during a HD session was 9.1% in the patients dialysed with a F8 filter and 20.2% with a high-flux F60 filter (p < 0.001). The resulting extraction rate was 10 +/- 3.6% (F8) which is similar to the unbound fraction. The elimination of teicoplanin during CVVHD therapy strongly depended on the ultrafiltration rate (UFR) (r = 0.923, p < 0.05). An UFR of 15.6 l/24 h resulted in a removal of 32%/24 h of a 400 mg dose and an UFR of 6.2 l/24 h in 9.5%/24 h respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

[Interstitial nephritis in typhus].

A 58-year-old man developed continuous fever of around 40 degrees C and a macular rash on the trunk and limbs one week after an eight-day visit to the island of Rhodos. Typhus was diagnosed on the basis of the clinical findings, the characteristic rash and a rise in antibody titre against Rickettsia prowazekii and mooseri (1:1280). The fever subsided and the patient's general state markedly improved within three days of starting antibiotic treatment with doxycycline. Five days after hospital admission renal function deteriorated, serum creatinine rising from 1.7 to maximally 8.7 mg/dl. Renal biopsy on the eighth day of illness revealed, in concordance with the diagnosis of a rickettsial infection, acute granulomatous interstitial nephritis. Doxycycline administration was continued for a total of 18 days and renal function improved. Two weeks after discharge serum creatinine had fallen to 1.8 mg/dl and to 1.2 mg/dl after 6 months. The antibody titre against Rickettsia prowazekii had fallen to 1:20 about 12 weeks after discharge. Early antibiotic treatment of typhus is of importance to avoid irreversible renal damage.

Antibodies, Bacterial↗

[Increased plasma endothelin concentrations in patients after liver transplantation and in liver cirrhosis].

Endothelin, one of the most potent vasoconstrictors known today, is released by the vascular endothelium. Patients after liver transplantation and patients with liver cirrhosis show significantly higher plasma endothelin concentrations and significantly reduced results in the quantitative liver function tests (ICG-HL, GEC, Lidocaine-HL, MEGX) compared with healthy control persons. The plasma endothelin concentrations were better correlated with the more liver bloodflow dependent function tests (ICG-HL, Lidocaine-HL) than with the more metabolic-capacity dependent function tests (GEC, MEGX). As cyclosporine A in vitro can increase the liberation of endothelin, we conclude that in patients after liver transplantation an endothelin mediated cyclosporine induced hepatotoxicity might be the reason for the demonstrated association.

Endothelins↗

Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure.

The pharmacokinetics and pharmacodynamics of the ACE inhibitor quinaprilat have been studied in six chronic haemodialysis (HD) patients and in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after a single oral dose of 2.5 mg quinapril. Mean tmax and Cmax values (SEM) for quinaprilat in interdialytic HD patients were 4.0 (0) h and 84 (8.4) ng.ml-1 respectively, and they did not differ significantly from those in CAPD patients (4.7 (0.7) h and 64 (5.7) ng.ml-1). Elimination half lives were 30 (10.1) h (HD) and 34 (7.3) h (CAPD). Cmax, tmax, t1/2, and AUC were increased and CL was decreased compared to data reported previously after giving 2.5 mg to healthy subjects. Peritoneal clearance was calculated as 0.1 (0.1) ml.min-1, thus less than 0.5% of the dose were removed within 24 h by CAPD. ACE activity was suppressed by more than 93% between 4 and 24 h postdose (P < 0.001). It decreased in both groups with increasing plasma quinaprilat levels. Angiotensin II concentration compared to baseline was significantly decreased at 4 hours (-30.4 +/- 10%) and 24 h (-30 +/- 9.9%) (P < 0.05, n = 11), while active plasma renin concentration was still significantly increased at 48 h postdose (+ 60.2 +/- 14.5%, P < 0.01). Mean arterial pressure 24 h postdose was significantly (P < 0.05) decreased in HD (-12 mmHg) and CAPD patients (-20 mm Hg). Only two patients reported unwanted effects (fatigue, dizziness, nausea, and weakness). In conclusion, due to its long lasting effect on ACE activity and on blood pressure in terminal renal failure a starting dose of quinapril 2.5 mg o.d. may be used in hypertensive HD and CAPD patients.

Adult↗