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Biomedical subjects

R Krüger

Publications and source records attributed to R Krüger.

At least 55 records · Page 3Linked to original sources
PubMed1998

Spinocerebellar ataxia type 6: genotype and phenotype in German kindreds.

OBJECTIVE: Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia (ADCA) of which the mutation causing the disease has recently been characterised as an expanded CAG trinucleotide repeat in the gene coding for the alpha1A-subunit of the voltage dependent calcium channel. The aim was to further characterise the SCA6 phenotype METHODS: The SCA6 mutation was investigated in 69 German families with ADCA and 61 patients with idiopathic sporadic cerebellar ataxia and the CAG repeat length of the expanded allele was correlated with the disease phenotype. RESULTS: Expanded alleles were found in nine of 69 families as well as in four patients with sporadic disease. Disease onset ranged from 30 to 71 years of age and was significantly later than in other forms of ADCA. Age at onset correlated inversely with repeat length. The SCA6 phenotype comprises predominantly cerebellar signs in concordance with isolated cerebellar atrophy on MRI. Non-cerebellar systems were only mildly affected with external ophthalmoplegia, spasticity, peripheral neuropathy, and parkinsonism. Neither these clinical signs nor progression rate correlated with CAG repeat length. CONCLUSIONS: This study provides the first detailed characterisation of the SCA6 phenotype. Clinical features apart from cerebellar signs were highly variable in patients with SCA6. By comparison with SCA1, SCA2, and SCA3 no clinical or electrophysiological finding was specific for SCA6. Therefore, the molecular defect cannot be predicted from clinical investigations. In Germany, SCA6 accounts for about 13% of families with ADCA. However, up to 30% of SCA6 kindreds may be misdiagnosed clinically as sporadic disease due to late manifestation in apparently healthy parents. Genetic testing is therefore recommended for the SCA6 mutation also in patients with putative sporadic ataxia.

Adult↗
PubMed1997

Effects of fluvoxamine on depression, anxiety, and other areas of general psychopathology in bulimia nervosa.

The efficacy of fluvoxamine in maintaining improvement of general psychopathology (depression, obsessive-compulsive symptoms, anxieties, interpersonal trust, and body perception) was tested in a double-blind placebo-controlled study of 72 patients with bulimia nervosa who were being treated successfully with inpatient behavioral psychotherapy. Over a period of about 15 weeks (2-3 weeks inpatient titration phase, 12 weeks outpatient relapse-prevention phase), fluvoxamine or placebo were given. The relapse-prevention design was used to avoid potential confounding effects of other concomitant treatments. Assessments concerning general psychopathology were made on the basis of expert ratings (CGI, HDRS) and self ratings (HSCL, Eating Disorders Inventory (EDI)-subscales "ineffectiveness," "perfectionism," "maturity fears," "interpersonal distrust," and "interoceptive awareness"). Fluvoxamine had significant effects in preventing relapse as measured on the basis of the Clinical Global Impression (CGI) scale "severity of illness", and a positive trend for relapse preventing effects was observed for the HSCL "general symptomatic index". Further, a relapse preventing effect was observed for the HSCL subscale "obsessive-compulsive symptoms", but not for the EDI subscale "perfectionism". Various dependent variables measuring depression showed no significant relapse-preventing effects of fluvoxamine, but only positive trends. Fluvoxamine had no relapse preventing effects according to our results for dependent variables assessing anxieties, interpersonal trust, and body perception. During a final short (4-week) off-medication phase, no statistically significant effects of discontinuation of medication, but some trends in the expected directions, were observed.

Adult↗
PubMed1996

Selegiline stimulates biosynthesis of cytokines interleukin-1 beta and interleukin-6.

Several lines of evidence indicate an immune-mediated pathophysiology of Parkinson's disease (PD) and Alzheimer's disease (AD). In clinical studies the monoamine oxidase-B inhibitor Selegiline appears to slow the progression of neurological deficits in PD and the cognitive decline in AD. The immune response to bacterial or viral infection and in chronic inflammatory processes is stimulated by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequently interleukin-6 (IL-6). We investigated the influence of Selegiline on the synthesis of IL-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) from healthy blood donors cultured with or without Selegiline (10(-8)M, 10(-9)M or 10(-10)M) in a humidified atmosphere (7% CO2). Treatment of cultured PBMC with Selegiline significantly increased synthesis of both cytokines. The effect of Selegiline on cytokine biosynthesis may contribute to its putative neuroprotective properties.

Humans↗
PubMed1996

Fluvoxamine in prevention of relapse in bulimia nervosa: effects on eating-specific psychopathology.

In a double-blind, placebo-controlled study of 72 patients with bulimia nervosa treated successfully with inpatient psychotherapy, the efficacy of fluvoxamine in maintaining improvement was tested. Fluvoxamine and placebo, respectively, were given over a period of about 15 weeks (2-3 weeks inpatient titration phase, 12 weeks outpatient relapse-prevention [maintenance] phase). The variables assessed concerned bulimic behavior and other aspects of eating disorders, global status, depression, anxieties, obsessive-compulsive behavior, and other aspects of psychopathology. Because the dropout rate was relatively high (N = 27 [33%]) and because it was considerably higher in the fluvoxamine group (19 out of 37 subjects), analyses were performed on the intent-to-treat sample (ideally including all 72 subjects). Results of the completer sample analyses (including only those subjects who finished the study) are briefly presented for comparison. In both the intent-to-treat and the completer analyses, the following scales showed fluvoxamine to have a significant effect in reducing the return of bulimic behavior: (1) self-ratings: Eating Disorder Inventory (EDI)-bulimia, urges to binge in previous week and the number of actual binges in the previous week; (2) expert ratings: Psychiatric Status Rating Scales for Bulimia nervosa, Structured Interview for Anorexia and Bulimia nervosa (SIAB)-"total score," SIAB-subscale "fasting," and SIAB-subscale "vomiting." Two further variables (EDI-total score and SIAB-subscale "bulimia") showed the superior relapse prevention effects of fluvoxamine compared with placebo for the completer sample, while they did not reach significance for group-by-time interactions in the intent-to-treat sample. During a final, short (4-week) off-medication phase, no effect of the discontinuation of medication was observed.

Adolescent↗
PubMed1995

[Viewpoints].

Explore the source record for details and available documents.

Eligibility Determination↗
PubMed1993

Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV.

Neuropeptide Y, peptide YY and pancreatic polypeptide share an evolutionary conserved proline-rich N-terminal sequence, a structure generally known to be inert to the attack of common proteinases, but a potential target for specialized proline-specific aminopeptidases. Purified human dipeptidyl peptidase IV (also termed CD 26) liberated N-terminal Tyr-Pro from both, neuropeptide Y and peptide YY, with very high specific activities and Km values in the micromolar range, but almost no Ala-Pro from pancreatic polypeptide. Other proline-specific aminopeptidases exhibited low (aminopeptidase P, liberation of N-terminal Tyr) or totally no activity (dipeptidyl peptidase II), as was also observed with less-specific aminopeptidases (aminopeptidase M, leucine aminopeptidase). When human serum was incubated with neuropeptide Y or peptide YY at micro- and nanomolar concentrations, Tyr-Pro was detected as a metabolite of both peptides. Formation of Tyr-Pro in serum was blocked in the presence of Lys-pyrrolidine and diprotin A (Ile-Pro-Ile), specific, competitive inhibitors of dipeptidyl peptidase IV. Incubation of neuropeptide Y or peptide YY with immunocytochemically defined, cultivated endothelial cells from human umbilical cord also yielded Tyr-Pro. Dipeptidyl peptidase IV could be immunostained on most endothelial cells by a specific antibody. We suggest that dipeptidyl peptidase IV might be involved in the degradation of neuropeptide Y and peptide YY to N-terminal truncated neuropeptide Y(3-36) and peptide YY(3-36). Since specific binding to Y1, but not to Y2 subtype of neuropeptide Y/peptide YY receptors requires intact N- as well as C-termini of neuropeptide Y and peptide YY, removal of their amino-terminal dipeptides by dipeptidyl peptidase IV inactivates them for binding to one receptor subtype.

Amino Acid Sequence↗
PubMed1993

[Malignant non-Hodgkin's lymphoma of the joint. Report of two cases, review of the literature and problems of classification].

This paper gives a survey of malignant Non-Hodgkin lymphomas (NHL) of joints. Primary and secondary malignant lymphomas of joints are rare. Our analysis of 6 years', new entries in the lymph node register in Kiel, covering 37.367 cases of malignant lymphomas, revealed only 20 cases (0.05%) with infiltration of joints. Slightly more men than women (1.18:1) are actually affected by articular lymphomas. In addition to 34 articular lymphomas of joints described in the literature between 1974 and 1992, we analyse 2 cases seen in our own institute and the 20 cases taken from the Kiel lymph node register. The peak incidence is between 40 and 60 years of age. One of our own cases, a woman of 92, is the oldest person ever affected. The most frequent localizations of NHLs are the knee, hip, and shoulder joints, with low-grade lymphomas predominating. Osteolytic lesions on radiographs are of decisive clinical and diagnostic significance for malignant articular lymphomas with affected bones. Lymphomas of joints are treated almost exclusively by radiation and chemotherapy, and sometimes a combination of both. Decisive prognostic significance attaches to the grade of malignancy and the fact of primary or secondary infiltration of the synovium and of the bone. The average survival time for patients with low-grade NHLs is 19 months with infiltration of the synovium and 27 months with infiltration of joint forming bones only, whereas the average survival time for patients high-grade lymphomas is 8 months with infiltration of the synovium and 11 months with infiltration only of joint-forming bones.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[New battery-powered equipment for continuous measurement and monitoring of blood pressure and body temperature].

This study reviews two newly developed battery-powered monitors for the accurate and invasive measurement of arterial blood pressure and body temperature. Their way of functioning is described in detail. Both devices allow a close monitoring of blood pressure, pulse rate and body temperature and a suitable intervention during the transport of critically ill patients and organ donors. Both monitors have high accuracy and stability, simplicity of operation and are robust. They are also relatively small and light. In addition, the devices are very suitable for measurement not only in humans but also in small animals like rats. The temperature monitor shows high accuracy in a range from -20 to 100 degrees C and is well suited for momentary and continuous temperature measurement in many other fields of application.

Blood Pressure Monitors↗
PubMed1989

Kinetics of antipyrine and sulfamethazine in patients recovered from dihydralazine-hepatitis.

Pharmacokinetic studies with sulfamethazine (500 mg) and antipyrine (15 mg/kg) were performed in 27 hypertonic patients (16 females, 11 males, 37-78 years) who had recovered from a dihydralazine-induced hepatitis, and 21 patients with essential hypertension (13 females, 8 males, 18-74 years) treated with antihypertonics excluding dihydralazine. 20 patients of the hepatitis group (74%) and 12 patients of the control group (57%) were slow acetylators. With regard to the pharmacokinetic parameters no differences were found in both slow and rapid acetylators between the sulfamethazine group and the antipyrine group.

Acetylation↗
PubMed1986

Comparison of the metabolism of the three antidepressants amitriptyline, imipramine, and chlorimipramine in vitro in rat liver microsomes.

The metabolism of the tricyclic antidepressants amitriptyline (AMI), imipramine (IMI), chlorimipramine (CMI) and some of their metabolites was studied in vitro in isolated liver microsomes of female Spraque-Dawley rats. Nine metabolites of AMI, seven metabolites of IMI, and 11 metabolites of CMI were quantitatively determined with high-performance liquid chromatography. The main metabolic reactions, mediated by an NADPH generating system, were hydroxylation, demethylation, and N-oxidation. The ratio of these reactions was different for the three drugs. AMI was hydroxylated more than CMI and CMI more than IMI. The order for demethylation was CMI greater than AMI = IMI, the order for N-oxidation IMI greater than CMI less than or equal to AMI. The substrate dependence of metabolism was investigated. Demethylation and N-oxidation increased proportionally to increasing substrate concentrations, whereas formation of hydroxylated metabolites became saturated (in the concentration range of 10(-6)-10(-5) M). The in vitro metabolism was compared with the in vivo metabolism in humans, reflected by the plasma concentrations of these drugs and their metabolites. A good agreement in metabolic pathways was found.

Amitriptyline↗