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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 253 records · Page 14Linked to original sources
PubMed1998

Alterations of protein tyrosine phosphorylation in T cells of immunocompromised patients.

Activation of the T-cell receptor (TCR) results in recruitment of tyrosine kinases and changes of tyrosine phosphorylation levels. We quantitatively analyzed protein phosphorylation of resting and TCR stimulated T cells for healthy donors and immunocompromised patients using two-colour flow cytometry. Stimulation of T cells of healthy persons by OKT3 antibody led to a biphasic increase of phosphotyrosine levels with the first peak after 15 s and the absolute maximum occurring after 3-5 min. Levels remained high up to 30 min and returned to baseline levels afterwards. Compared to healthy blood donors, the phosphotyrosine baseline levels were 20-30% increased in patients after bone marrow transplantation (BMT). Using OKT3 to stimulate T cells of BMT patients led to strong increases in phosphotyrosine levels comparable to those of controls. In contrast, the response of T cells of human immunodeficiency virus-infected patients with acquired immune deficiency syndrome was severely impaired (P = 0.01). In conclusion, this flow cytometric methodology enables analyses of changes in cellular phosphotyrosine levels following TCR stimulation. The increased baseline levels in BMT patients and the observed unresponsiveness of T cells in AIDS patients could be of interest for the study of predictors of graft-versus-host reactivity and the clinical analysis of immune functions in AIDS patients, respectively.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Autologous and allogenic hybrid cell vaccine in patients with metastatic renal cell carcinoma.

OBJECTIVE: To evaluate the safety, acute and long-term toxicity and therapeutic activity of an allogenic and an autologous hybrid cell vaccine in patients with progressive metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Eleven patients were vaccinated with a lethally irradiated hybrid cell vaccine of allogenic RCC tumour cells fused with major histocompatibility complex class I-matched and class II-unmatched activated allogenic lymphocytes. These patients were then followed for a mean of 11 months. Another 13 patients were vaccinated with a hybrid cell vaccine of autologous tumour cells fused with allogenic activated lymphocytes and followed for a mean of 6 months. RESULTS: Six of the 11 patients receiving the allogenic vaccination showed an initial response, with two complete and two partial responses to date. Only three patients who received autologous vaccination responded to treatment. CONCLUSIONS: Hybrid cell vaccination is a promising new approach in the treatment of patients with advanced RCC.

Cancer Vaccines↗
PubMed1998

Pulsatility index in the fetal anterior tibial artery during the second half of normal pregnancy.

The objective of this prospective study was to establish reference values for the pulsatility index in the fetal anterior tibial artery during the second half of pregnancy. Pulsed Doppler waveform analysis of 203 fetuses at 23-42 weeks of pregnancy was performed, each fetus being examined just once. There were neither fetal nor maternal complications detectable at the time of the examination. In the first 14 fetuses from which recordings were taken, Doppler examination was performed on both fetal legs in order to evaluate systematic differences between the right and left legs. Intraobserver variability was analyzed by repetition of the measurements by the same examiner in the first 130 cases. There was no difference between right and left tibial circulation. The repeatability coefficient, defined as the 95% range for the difference in two repeat measurements, was 1.08. The pulsatility index of the anterior tibial artery (50th centile) increased slightly from 3.29 at 23 weeks of pregnancy to 4.09 at 42 weeks. The 5th and 95th centiles were calculated, as was the 95% confidence interval of the 5th and 95th centiles. Examination of the fetal peripheral circulation during the second half of pregnancy is possible with a high degree of precision. Whether there are changes in peripheral arterial circulation in compromised fetuses remains to be evaluated.

Female↗
PubMed1998

GBV-C/HGV in hemodialysis patients: anti-E2 antibodies and GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells.

Hepatitis G virus (GBV-C/HGV), a recently identified RNA virus adds to the risk of parenteral transmitted viral infections in hemodialysis patients. We studied the prevalence of GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells (PMNC) by reverse transcription-polymerase chain reaction (RT-PCR) and determined antibodies against the envelope protein E2 of GBV-C/HGV by ELISA. A total of 119 dialysis patients were studied. GBV-C/HGV-RNA was found in 16 of 119 patients (13%) as compared with 2% of healthy controls (P = 0.014). Two of the 16 GBV-C/HGV-RNA+ patients were co-infected with HCV, and none was positive for HBV-DNA. In 38% of serum GBV-C/HGV-RNA+ patients GBV-C/HGV-RNA was also detected in PMNC. In addition, GBV-C/ HGV-RNA was identified in PMNC of 2 patients negative for GBV-C/ HGV-RNA in serum. Twenty-four patients had anti-E2 antibodies in serum (20%), but were GBV-C/HGV-RNA-. In addition, two of the 16 GBV-C/HGV-RNA+ patients were concomitantly positive for anti-E2 antibodies. Only one of the 16 GBV-C/HGV infected patients had elevated aminotransferases; this patient was co-infected with hepatitis C virus. GBV-C/HGV-RNA positivity was independent on duration of hemodialysis, but GBV-C/HGV-RNA+ patients had received more units of blood in the past. Combined data of past contact, as assessed by anti-E2 antibodies, and present infection, documented by GBV-C/HGV-RNA, indicate a high overall exposure to GBV-C/HGV in dialysis patients.

Adult↗
PubMed1998

Use of anxiolytics and hypnotics in gynecological, surgical and medical departments of general hospitals.

While several surveys have shown that patients in nonpsychiatric hospital departments frequently receive anxiolytics or hypnotics during hospitalization, and also receive discharge prescriptions for these drugs, as yet none has investigated the start of intake of these drugs during hospitalization in conjunction with an assessment of all types of psychiatric disorders. Therefore, we studied 728 patients in medical, gynecological, and surgical departments of two non-university general hospitals in Austria for the prevalence of anxiolytic and hypnotic drug use during hospitalization as compared to discharge prescriptions for such drugs. Altogether, 50.4% of all admitted patients were treated with anxiolytics or hypnotics during their stay in hospital, and 42.8% of those who had not taken such drugs before admission. Of the patients using these medications during hospitalization, 26.1% also received discharge prescriptions. The significant associations between psychiatric variables and both drug use during hospitalization and prescriptions at discharge, suggest that anxiolytic and hypnotic drugs are used aptly. However, considering that about half of the patients suffering from substance abuse disorders received discharge prescriptions, the risk of continued substance abuse must not be neglected. Overall, fewer patients received anxiolytics or hypnotics at discharge than had used them before admission.

Aged↗
PubMed1998

[Autofluorescence characteristics of lipofuscin components in different forms of late senile macular degeneration].

BACKGROUND: Lipofuscin is the main fluorophore of the human fundus. Because lipofuscin is the result of the accumulation of metabolic debris in pigmentepithelial cells (RPE), the autofluorescence can be interpreted as a clinical sign for the metabolic activity of the RPE. In order to get informations of RPE-function in different types of late AMD, the autofluorescence patterns in patients with late AMD were analyzed. MATERIAL AND METHOD: A prospective examination of the fundus-autofluorescence of 64 eyes of 52 patients with different types of late AMD was performed using a confocal scanning-laser-opthalmoscope. The autofluorescence images were categorized in respect to the type of late AMD according to the opthalmoscopic and fluoresceine-angiographic findings. RESULTS: Reduced autofluorescence was found in the centre of occult (78.6%) and classic (100%) choroidal neovascularisations (NV) as well as in the occult NV of RPE detachments. A loss of autofluorescence was related to the RPE free area of RPE-tears (100%) and to RPE-atrophy (88.9%) with sometimes increased autofluorescence at the rim. Increased autofluorescence could be seen at the surface of RPE-detachments (71.4%), in the area of the shrink age of RPE in RPE-tears (100%) as well as at RPE-proliferations in small occult NV (100%). Disciforme scars showed variable patterns of autofluorescence. CONCLUSION: The autofluorescence of the RPE can be analyzed clinically with the described method. Different patterns of autofluorescence could be revealed in different types of late AMD. Increased autofluorescence was found in lesions with proliferative or phagocytotic metabolic activity of the RPE like RPE-detachments, shrinked RPE in RPE-tears or occult NV with RPE-proliferations. The reduced autofluorescence in occult or classical choroidal NV can be interpreted as a sign of decompensation of the RPE and was also seen in areas with RPE-loss.

Aged↗
PubMed1998

Renal impairment in patients with long-standing cyanotic congenital heart disease.

Nephropathy is known to occur in patients with long-standing cyanotic congenital heart disease (CCHD). In order to assess the incidence, nature and degree of the problem among such patients, discriminating urine analyses were performed in 26 patients with CCHD, with a mean age of 22 (10-42) y. Ten patients showed reduced glomerular function, six of whom also had advanced glomerulopathy. Glomerular filtration rates were below normal in half of the patients and occurred with glomerular-type proteinuria in five, with tubular-type proteinuria in one and without pathological proteinuria in four. An elevated haematocrit and duration of cyanosis were identified as the main risks factors for the development of glomerulopathy. The risk of developing glomerular lesions rose sharply during the second decade of life. Nephropathy in CCHD is common and the dominant feature is glomerular damage, which is related to the duration of cyanosis and the extent to which the haematocrit is elevated.

Adolescent↗
PubMed1998

Aerosol bolus dispersion in patients with bronchiolitis obliterans after heart-lung and double-lung transplantation. The Munich Lung Transplantation Group.

Bronchiolitis obliterans (BO) is one of the main late complications in patients after lung transplantation. Because BO is located in small airways, conventional lung function tests are supposed to be rather insensitive to detect early stages of this disease. In this study, the capability of the aerosol bolus dispersion test to detect BO was tested in 12 subjects with heart-lung and double-lung transplantation. Four of these patients had histological evidence of BO. The broadening (dispersion) of inhaled boluses consisting of monodispersed inert test particles during respiration was repeatedly measured in each subject. Additional measurements of spirometric and bodyplethysmographic measurements were performed. Patients with evidence of BO showed significantly increased aerosol bolus dispersion and significantly reduced maximal airflow parameters. Calculation of receiver operating characteristics (ROCs) revealed that from all lung function parameters under consideration, aerosol bolus dispersion divided by the maximum expiratory flow rate at 50% of vital capacity (MEF50) and MEI50 had the highest sensitivity and specificity for the detection of BO. Both parameters showed a sensitivity and specificity of 100%. Therefore, it may be speculated that even in early stages of disease, the combination of MEF50 measurement with aerosol bolus dispersion measurements may be a powerful tool for the detection of BO in patients with lung transplantation.

Adolescent↗
PubMed1998

Phase II study with cisplatin and paclitaxel in combination with weekly high-dose 24 h infusional 5-fluorouracil/leucovorin for first-line treatment of metastatic breast cancer.

Results from our previous phase II study demonstrating high efficacy and low toxicity for a weekly schedule of 5-fluorouracil (5-FU)/leucovorin in intensively pretreated patients with metastatic breast cancer prompted addition of paclitaxel and cisplatin to this regimen for a phase II study of outpatient first-line treatment of metastatic breast cancer. (MBC). Twenty-eight patients with metastatic breast cancer have been evaluated. Pretreatment comprised adjuvant CTX in 24 out of 28 patients, but no prior CTX for MBC. Patients were treated with 5-FU 2 g/m2 (24 h infusion) plus leucovorin 500 mg/m2 (2 h infusion prior to 5-FU) weekly for 6 weeks (days 1, 8, 15, 22, 29 and 36); in addition, paclitaxel 175 mg/m2 (3 h infusion) was administered on days 0 and 21, and cisplatin 50 mg/m2 (1 h infusion) on days 1 and 22 prior to 5-FU/leucovorin, repeated every 50 days. All patients were treated as outpatients using Port-a-Cath systems and portable pumps. Aside from common total alopecia, neutropenia was common but only of short duration. No episodes of febrile neutropenia occurred. Non-hematologic toxicities (NCl CTC grade, percent of patients) consisted of mild to moderate diarrhea (2+3, 47%), mucositis (2, 14%), and nausea and vomiting (2+3, 60%). Out of 28 patients with bidimensionally measurable disease 25% (seven out of 28) achieved a CR, 57% (16 out of 28) achieved a PR, 11% (three out of 28) had a SD and 7% (two out of 28) had a PD. Overall RR was 82% (95% confidence interval 66-100%). Median remission duration was 8 months, median time to progression 9 months and median survival time 28 months with a median follow-up of 21 months. We conclude that the combination of paclitaxel, cisplatin and 5-FU/leucovorin is an effective non-anthracycline-containing regimen for the first-line treatment of MBC.

Adult↗
PubMed1998

Phase II study of continuous 120 h infusion of mitomycin C as salvage chemotherapy in patients with progressive or rapidly recurrent colorectal cancer.

We evaluated the therapeutic activity and safety of continuously infused mitomycin C in patients with metastatic colorectal cancer who had recurred (less than 3 months) or progressed following first- or second-line 5-fluorouracil-based chemotherapy. Treatment consisted of mitomycin C 20 mg/m2 i.v. given over 120 h (5 days) followed by a 3 week rest period. Fifty-two consecutively enrolled patients were assessable for toxicity and 49 for response evaluation (three patients evaluable but not measurable), completing at least one full course of chemotherapy. Previous chemotherapy regimens consisted of bolus 5-fluorouracil/folinic acid (5-FU/FA) (Machover) n=26 (50%) or continuous (24 h) 5-FU+/-FA+/-interferon n=26 (50%). Forty-two percent of patients had received one previous chemotherapy regimen and 58% more than one. One partial remission (2%) lasting 7 months and 11 disease stabilizations (23%) with a median duration of 3.2 months (range 1-8) were achieved in 49 patients. Median survival time since start of mitomycin C was 4.7 months (1.2-28.1) resulting in a 6 month survival rate of 36%. The progression-free interval was 10 weeks (range 4-36). Delayed and cumulative thrombo- and leukocytopenia (WHO grade III/IV) were observed in 19 and 6%, and anemia in 2% of patients. WHO grade I/IV mucositis, diarrhea and fever/infection occurred each in 6% of patients. Treatment delays and dose reductions were necessary in 11 (21%) and 21 (40%) patients, respectively. In three cases treatment was stopped due to cumulative thrombocytopenia (6%). Continuous infusion of single-agent mitomycin C displays modest activity in heavily pretreated 5-FU refractory colorectal cancer patients combined with a low toxicity level.

Adult↗
PubMed1998

Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome.

OBJECTIVES: The acute respiratory distress syndrome (ARDS) is a frequent complication of severe sepsis and a major cause of death in patients with hematologic malignancy during chemotherapy-induced leukocytopenia. Inflammatory mediators are important modulators of host response to injury and have been found to be increased in the bronchoalveolar lavage (BAL) fluid of nonleukocytopenic patients with ARDS. Since inflammatory cytokines in plasma of nonleukocytopenic patients seem to be efficient predictors of the course of ARDS, we examined this hypothesis in leukocytopenic patients with septic shock-induced ARDS. DESIGN: Prospective, observational study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Nineteen patients with leukocytopenia (white blood cell count of <1/nL) following cytoreductive chemotherapy for malignant disorders and severe sepsis with shock-induced ARDS (Murray score of >2.5). INTERVENTIONS: BAL and plasma sampling and ICU management. MEASUREMENTS AND MAIN RESULTS: The proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were measured in the BAL aspirates and in plasma samples, both obtained within 18 hrs after onset of ARDS. Hemodynamic and oxygen metabolism data were measured immediately before plasma samples were taken and BAL was performed. Of the 19 patients studied, nine patients responded to ICU treatment (e.g., mechanical ventilation as indicated by PaO2/FIO2, FIO2, shunt volume, and course of pulmonary infiltrates), whereas ten patients did not respond. BAL cytokine concentrations were significantly increased in nonresponders in comparison with responding patients (TNF-alpha, p = .021; IL-6, p = .008; IL-8, p = .019). In contrast, we did not observe any differences between the groups in terms of plasma cytokine concentrations. CONCLUSION: Determination of cytokine concentrations in BAL samples may be useful for evaluation of severity and course of ARDS in leukocytopenic patients, whereas measurement of plasma cytokines is not helpful.

Adult↗
PubMed1998

Transjugular intrahepatic portosystemic shunt and cardiac arrhythmias.

The approach to the liver for a transjugular intrahepatic porto-systemic shunt (TIPS) is through the venous system. Because catheter and guidewire system traverses the heart, cardiac arrhythmias may be expected during the procedure. We have prospectively investigated the incidence of such dysrhythmias during TIPS implantation. Twelve consecutive patients, 4 women and 8 men aged 26 to 75 years (mean, 58 +/- 13 years), were studied. Before and on the day of TIPS implantation, a 24-hour Holter recording was performed. Transjugular intrahepatic portosystemic shunt implantation was performed under local anesthesia (lidocaine) and sedoanalgesia (midazolam and fentanyl). None of the patients had concomitant cardiac disease or electrolyte disturbances. In all patients except one, TIPS implantation was successful without any technical complications. A mean of 43 +/- 5.3 hours of Holter recording was performed before and after TIPS implantation. All recordings obtained during this control period were considered inconspicuous. The mean heart rate was significantly higher during the implantation procedure of 136 +/- 37 minutes' duration (83 +/- 20 beats per minute vs 70 +/- 19 beats per minute; p < 0.01). Nine of the 12 patients experienced episodes of nonsustained supraventricular tachycardias, and one patient had two sustained supraventricular tachycardias. Frequent episodes of nonsustained ventricular tachycardias developed in 75% of the patients. It seems clear that TIPS implantation is frequently associated with supraventricular and ventricular tachyarrhythmias even in patients with apparently good cardiac condition at the beginning of the procedure. Thus close cardiac monitoring with resuscitation equipment immediately available throughout the procedure is mandatory.

Adult↗
PubMed1998

Treatment of pruritus in chronic liver disease with the 5-hydroxytryptamine receptor type 3 antagonist ondansetron: a randomized, placebo-controlled, double-blind cross-over trial.

BACKGROUND: Recently, the serotonin antagonist ondansetron has been reported to have a positive effect on cholestasis-associated pruritus. OBJECTIVES: To study the effect of orally administered ondansetron on pruritus in chronic liver disease in a randomized, placebo-controlled, double-blind, cross-over study. METHODS: Subjective severity of pruritus was assessed using a visual analogue scale (VAS) recorded four times daily by the patients. After a one week pretreatment baseline period the patients were randomized to receive ondansetron tablets 8 mg tds or placebo tablets tds for one week. Following a one week wash-out period patients were switched to the other treatment for one week. The study was ended by an additional follow-up week without medication. For each day peak VAS values were determined and the mean value of the last five days of each week was calculated and referred to as the composite peak VAS score. RESULTS: We observed a significant but moderate reduction of the composite peak VAS score of 1.34 points (CI(95%): 0.12-2.56; P=0.033) during treatment with ondansetron as compared to placebo (treatment effect). In addition, a period effect was observed: a reduction of composite peak VAS score by 1.26 points (C1(95%): 0.04-2.48; P=0.044) was seen in the second treatment period as compared to the first period, irrespective of the kind of treatment. Although under treatment with ondansetron a significant improvement of itching as assessed by the VAS score was demonstrated, this treatment was not preferred over placebo by the patients. CONCLUSIONS: The 5-hydroxytryptamine receptor type 3 antagonist ondansetron has a small, but significant positive effect on pruritus in chronic liver disease as compared to placebo.

Administration, Oral↗
PubMed1998

Effects of testosterone suppression on serum levels of hepatitis B surface antigen and HBV-DNA in men.

AIMS/BACKGROUND: There is epidemiological evidence that progression of hepatitis B virus (HBV)-induced liver disease is adversely influenced by male gender. Furthermore, in male transgenic mice, HBsAg levels increase after puberty, resulting in 4- to 10-fold higher HBsAg levels than in female transgenic mice. Castration reduces HBsAg levels by 90-95%, while substitution of testosterone to castrated animals rapidly increases HBsAg concentrations. We hypothesized that suppression of endogenous testosterone levels may have similar effects on HBsAg serum levels in men, as observed in male mice. METHODS: To test our hypothesis, we studied the influence of reversible testosterone suppression by the LHRH-analog triptorelin on serum concentrations of HBsAg and HBV-DNA. Eight male patients, who were chronically infected with HBV, were studied in a prospective interventional study. RESULTS: Triptorelin decreased serum testosterone levels to castration levels for several weeks. However, this reversible testosterone suppression had no effect on HBsAg or HBV-DNA serum concentrations (p > 0.05). CONCLUSIONS: Suppression of endogenous testosterone levels had no effect on HBsAg levels in men, which points to a different regulation of HBsAg expression in men compared with transgenic mice.

Adult↗
PubMed1998

Absence of effect of rufloxacin on theophylline pharmacokinetics in steady state.

Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1. 02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events.

Adult↗
PubMed1998

Transient and long-term feeding by means of percutaneous endoscopic gastrostomy in neurological rehabilitation.

In 28 patients of a neurological rehabilitation unit of a hospital the use of enteral nutrition via percutaneous endoscopic gastrostomy (PEG) tubes was reviewed. During a total observation period of 5,172 days no life-threatening complications occurred. Minor complications were observed in 12 patients (43%) in the first 2 weeks after the insertion and in 5 patients (18%) afterwards. The nutritional status stabilized in all subjects. Transient PEG feeding was performed in 11 patients (39%) with a mean duration of 150 days. We conclude that hesitation in the application of PEG feeding in neurological rehabilitation should be abandoned. The timing and monitoring of PEG feeding in patients undergoing neurological rehabilitation for acute remitting neurological disorders is discussed.

Adolescent↗
PubMed1998

Predictive value of tubular markers for the development of microalbuminuria in adolescents with diabetes.

The predictive value of tubular proteinuria and/or enzyme excretion for the development of microalbuminuria in patients with diabetes mellitus was investigated over a period of 7.5 years in 64 children and adolescents without microalbuminuria at baseline. An abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) preceded the increase of albumin excretion in all 8 patients (12.5%) developing microalbuminuria during this period (positive/negative predictive value 0.2 and 1.0, respectively). Also both, the actual as well as the long-term glycemic control (HbAlc) up to the onset of abnormal NAG excretion were predictive for the development of microalbuminuria. Fifty percent of those patients with both an elevated NAG excretion and an HbAlc > or = 9% developed micro-albuminuria within the next 5 years. Therefore, periodic monitoring of urinary NAG excretion should be incorporated into the follow-up of patients with type 1 diabetes mellitus.

Acetylglucosaminidase↗