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Biomedical subjects

W Kuhn

Publications and source records attributed to W Kuhn.

At least 91 records · Page 5Linked to original sources

[Efficiency, safety and tolerability of recombinant human interleukin-3 (rhIL-3) as supportive therapy accompanying dose-intensive carboplatin containing chemotherapy in ovarian cancer with special regard to thrombocytopenia].

OBJECTIVE: In a prospective, randomized, placebo-controlled double-blind trial we evaluated to what extent a dose-intensification of adjuvant chemotherapy is possible with the help of Interleukin-3 (rhIL-3). MATERIAL AND METHODS: Following initial surgery, 12 patients with primary ovarian cancer have been treated with Carboplatin and Cyclophosphamide (dosage: AUC 4 according to Calvert). After randomisation, a group of 6 patients prophylacticly received rhIL-3 against myelosuppression on days 3-12 of the cycle, in contrast to a group of 6 patients who received placebo-injections. RESULTS: The patients treated with rhIL-3 showed less hematologic side-effects. Adherence to 4-weekly chemotherapy courses was more frequent in the rhIL-3-group (73% vs. 44%, p = 0.005). An intensification of the chemotherapy with 3-weekly courses did not succeed significantly. Observed side-effects of rhIL-3-therapy were headaches, fever, flu-like symptoms, rashes and blisters at the site of injection which excluded 2 of 6 patients from the study. CONCLUSIONS: Supportive rhIL-3 to adjuvant Carboplatin-based chemotherapy enables a better keeping of 4-weekly courses in contrast to the placebo-group due to faster recovery of hematologic parameters. Due to the side-effects, of IL-3, this cytokine cannot be recommended for routine clinical use.

Adult↗

Kleine-Levin syndrome and Parkinsonian symptoms--a case report.

We report the case of a 54-year-old male patient, who developed the symptoms of Kleine-Levin syndrome (KLS) at the age of fifty. Four years later Parkinsonian symptoms (PS) appeared. The possible relationship between both KLS and PS, e.g. regarding neuroendocrinological similarities, will be discussed to explain the subsequent onset of PS after the manifestation of KLS in this patient.

Humans↗

Selegiline as immunostimulant--a novel mechanism of action?

In clinical studies the MAO-B inhibitor selegiline appears to slow the progression of neurological deficits in Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease (AD). The mechanisms of action remain unclear. Several lines of evidence indicate an immune-mediated pathophysiology of PD and AD. According to animal trials, selegiline increases the survival rate of immune suppressed mice. Stimulation of the immune response to bacterial or viral infection or in chronic inflammatory processes in managed by an increased synthesis of the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6 (IL-6). Outcome of viral or bacterial infections in the brain highly correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha (TNF). The aim of our study was to characterize the influence of selegiline on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood mononuclear cells (PBMC) from healthy blood donors. After isolation and washing PBMC were cultured without and with selegiline in three different concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified atmosphere (7% CO2). Then cultures were centrifuged and supernatants were collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured PBMC with various concentrations induced an increased synthesis of IL-1 beta (ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results indicate, that the influence of selegiline on the cytokine biosynthesis may also contribute to its putative neuroprotective properties.

Adjuvants, Immunologic↗

[Neurologic consultation practice in a general hospital of a rural area].

The long-standing consultant service for neurological patients in a general hospital requires questions to about the dimensions and efficiency of being answered cooperation between a general hospital and a neighbouring neurological clinic with a casualty ward and neuroradiology. From 1987 to 1995, 1471 patients with neurological diagnoses were observed retrospectively. The small number of requested consultancies (4-5%) was conspicious related to the total member of patients treated in the general hospital. About 25% of the recommendations of the consultants were realized. The percentage of pensioners and housewives was distinctly higher (45%). With the help of the diagnosis "concussion of the brain" good cooperation was observed between the general physicians to whom the consultant's recommendations had been passed on and the neurological casualty ward. The results, tendencies and possibilities for improvement of interdisciplinary cooperation are discussed.

Adult↗

Colour vision abnormalities do not correlate with dopaminergic nigrostriatal degeneration in Parkinson's disease.

Sensory disturbances such as olfactory or visual dysfunctions are common in Parkinson's disease (PD). A possible relationship between distorted colour discrimination and the nigrostriatal dopamine deficit is still a matter of debate. We examined 31 de novo Parkinsonian patients with [123I]beta-CIT single photon emission tomography (SPECT). We used a single-head gamma-camera and calculated the binding ratio striatum/cerebellum (specific/nonspecific binding) of [123I]beta-CIT uptake. On the same day, we performed the Farnsworth-Munsell 100 Hue Test (FMT) in these patients and estimated the total error score, in order to investigate abnormalities of colour vision. Parkinsonian patients' total error score was higher compared with an age- and sex-matched control group (P = < 0.0001), whereas disability scores of the Hoehn and Yahr scale (P = 0.019, Spearman r = 0.419) and the Unified Parkinson's Disease Rating Scale (P = 0.039, Spearman r = 0.373) correlated with total error score. No significant association appeared between total error score (Spearman r = -0.119, P = 0.525) and [123I]P-CIT-SPECT ratio. Thus both total error scores of the FMT and [1231]beta-CIT-SPECT binding ratios have been found to reflect the severity of PD. However, only [123I]beta-CIT SPECT reflects degeneration of dopaminergic neurons of the basal ganglia, but does not reflect alterations of the visual system and/or extranigral lesions in PD. From our results, we speculate that FMT may be a valuable clinical method to measure extranigral lesions of the visual system in PD.

Adult↗

Plasma levels of R- and S-salsolinol are not increased in "de-novo" Parkinsonian patients.

An augmented synthesis of tetrahydroisoquinolines, such as salsolinol (SAL) or an increased N-methylation of these compounds has been addressed by various investigators as putative pathophysiologic mechanisms in Parkinson's disease (PD). Aim of this study was (1) to investigate putative relations between plasma levels of dopamine and R- and S-enantiomers of SAL and (2) whether these metabolic precursors of the neurotoxic N-methylated-SAL (NMSAL) are elevated in untreated "de-novo" Parkinsonian patients compared to age- and sex-matched healthy controls. Plasma levels of R- and S-SAL and dopamine did not significantly (R-SAL: p=0.61, S-SAL: p=0.51, dopamine: p=0.84) differ in both groups. Parkinsonian patients' R-SAL plasma levels were inversely related to intensity (p=0.03, r =-0.42) and duration of PD (p=0.03, r=-0.43) in contrast to S-SAL and dopamine. Dopamine levels were not associated to R-SAL (p=0.88, r2=0.0008) and S-SAL (p=0.088, r2=0.12) neither in Parkinsonian patients nor in controls. We conclude, that an upregulation of N-methylation of tetrahydroisoquinolines takes place in PD by enzymes such as neutral N-methyltransferase specific for R-SAL. The activity of this enzyme has been found elevated in parkinsonian lymphocytes. This increased N-methylation by the N-methyltransferase specific for R-SAL leads to the known augmented levels of neurotoxic R-NMSAL in Parkinsonian patients compared to controls in the cenral nervous system especially in the beginning of PD.

Adult↗

Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

OBJECTIVE: Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. STUDY DESIGN: Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). RESULTS: A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p < 0.05). The extent of hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p < 0.02). CONCLUSIONS: Serum levels of hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.

Adult↗

Sonomorphology of endometriotic cysts.

OBJECTIVE: The aim of the study was to evaluate prospectively the sonomorphological feature of histologically verified endometriotic cysts. METHODS: Transvaginal sonography was performed in 122 patients. Age distribution of the patients, and size and sonomorphology of the lesions were analyzed. RESULTS: Eighty-one percent of the endometriotic cysts occurred in patients between 31 and 50 years old with a peak of 29% between 31 and 35 years. Most of the cysts (81%) ranged between 30 and 59 mm in diameter. Forty-three percent of the endometriotic cysts were observed as monolocular cysts with internal echoes. More than half of the findings were observed to be multilocular, partially without any internal echos, partially even with solid parts or purely solid. CONCLUSION: The so-called 'typically' monolocular smooth-walled endometriotic cyst with internal echoes was only found in 43% of the cases. However, data from the literature show that one cannot assume even this special entity to represent endometriomas. Regarding all monolocular cysts with homogeneous internal echoes, one has to be aware of a great amount of functional cysts and a non-calculable residual risk of malignancy.

Adult↗

Activated protein C resistance and factor V Leiden in patients with hemolysis, elevated liver enzymes, low platelets syndrome.

OBJECTIVE: Hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is characterized by a distinct activation of the coagulation system. A mutation of the gene coding for coagulation Factor V (Factor V Leiden) has been identified as the most frequent risk factor for thrombosis. To identify risk factors for HELLP syndrome, we determined coagulation parameters and the Factor V Leiden mutation in women who previously had developed HELLP syndrome. METHODS: Coagulation parameters (activated protein C resistance, antithrombin, protein C, protein S) were determined in 21 women 6 months to 9 years after they had developed HELLP syndrome in the third trimester. In addition, these women were analyzed for the presence of the Factor V Leiden mutation. RESULTS: Of these analyzed women, 33% (seven of 21) had an activated protein C resistance (activated protein C ratio less than 2.0). Another 38% of the women had subnormal activated protein C ratios (2.0-2.3). Only 57% of the women with an activated protein C resistance were identified as heterozygous carriers of the Factor V Leiden mutation (four of seven). CONCLUSION: Women with HELLP syndrome have a higher incidence of Factor V Leiden mutations. This increased incidence does not, however, account fully for the increased frequency of activated protein C resistance in these patients.

Adult↗

Evaluation of ovarian tumors in postmenopausal women by transvaginal sonography.

OBJECTIVE: The aim of the present study was the evaluation of simple reproducible sonomorphological criteria for the preoperative evaluation of ovarian tumors in postmenopausal women by use of transvaginal sonography. STUDY DESIGN: Postmenopausal women (> or =1 year of secondary amenorrhea) with ovarian tumors (n=378; tumors > or =3 cm and <3 cm but with solid parts) were examined in a prospective study by transvaginal sonography prior to surgery between 1987 and 1993. The sonomorphological criteria were correlated with the histological findings of the tumors. RESULTS: Of all ovarian tumors in postmenopausal women, 6.3% were functional cysts (follicular or corpus luteum cysts). Almost all of them were detected within the first 5 years of postmenopause. The other ovarian tumors were diagnosed as retention cysts (17.5%), benign neoplasms (39.4%), and malignant tumors (36.8%). Simple ovarian cysts (monolocular, smooth inner wall) represented sonomorphologically the second most frequent type of ovarian tumors in postmenopausal women (35.7%). Of these tumors, 9.6% were diagnosed as malignant. CONCLUSIONS: Simple reproducible sonomorphological criteria proved to be a useful clinical parameter in the preoperative evaluation of ovarian tumors.

Adult↗

Expression of the c-erbB-2-encoded oncoprotein p185 (HER-2/neu) in pregnancy as a model for oncogene-induced carcinogenesis.

Although oncogenes are involved in tumor development and progression, their activation during human ontogenesis is inseparably associated with normal fetal development. The c-erbB-2-encoded oncoprotein p185 (HER-2/neu) is overexpressed on fetal epithelial cells, in the placenta, and in several human carcinomas. In patients with p185-overexpressing tumors and in pregnant women at term, increased serum levels of a 105 kDa proteolytic breakdown product corresponding to the extracellular domain of oncoprotein p185 are detectable. Estrogens have been described to be potent inhibitors of p185 expression in human breast cancer cells and to influence also p105 serum levels in females. Regarding the significantly poorer prognosis of patients with c-erbB-2-positive tumors, we discuss common features and differences between c-erbB-2 oncoprotein overexpression in pregnancy and in carcinogenesis.

Cell Transformation, Neoplastic↗

Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer.

Drug resistance is one of the most important clinical problems in the treatment of ovarian cancer. This study was designed to determine whether expression of p53 could be used as a marker for predicting the response to chemotherapy of ovarian cancer. Tissue blocks were obtained from 187 patients with diagnosed untreated ovarian cancer. Paraffin sections from the primaries were immunohistochemically analysed for p53 expression. All patients underwent platinum-based chemotherapy after surgery. We analysed whether the number of chemotherapy cycles was related to survival in women with p53 positive and p53 negative ovarian cancer. 27/187 cases were p53 positive. Expression of p53 was associated with other factors of unfavourable prognosis. Patients with p53 positive tumours had a significantly worse prognosis compared with patients with p53 negative tumours (P = 0.037). There was a statistically significant dose-response effect of platinum-based chemotherapy in patients with p53 negative tumours, which could not be seen in patients with p53 positive tumours (P = 0.01 versus P = 0.553). This could also be observed in patients with residual tumour after surgery (P = 0.0001 versus P = 0.8866). Expression of p53 may be an additional useful marker in predicting response to chemotherapy. Thus, it is possible to identify a subgroup of patients who may benefit from alternative therapy regimens.

Adult↗

Platelet monoamine oxidase B activity in "de novo" and l-dopa treated parkinsonian patients and controls.

OBJECTIVE: Previous studies demonstrated controversial results regarding monoamine oxidase B (MAO-B) activity in platelets in the periphery in parkinsonian patients (PD). SUBJECTS AND METHODS: Therefore we determined platelet MAO-B activity in three age- and sex-matched groups of 17 untreated, so called "de novo" patients with Parkinson's disease (PD), 17 parkinsonian patients, receiving levodopa, and 17 controls by a radio enzymatic assay. RESULTS: No significant differences of MAO-B activity appeared. CONCLUSION: This result suggests that phenotypic determination of MAO-B activity in platelets may not be used as peripheral marker in PD and that levodopa treatment does not alter MAO-B activity in the periphery.

Aged↗

Fenoterol increases erythropoietin concentrations during tocolysis.

AIMS: The present study was carried out to assess the effect of the selective beta2-adrenoceptor agonists on erythropoietin (EPO) production. METHODS: Routine tocolysis with fenoterol (using the regular rate of 2 microg min[-1]) was used as a clinically easily accessible model. RESULTS: EPO concentrations had doubled 24 h after the start of tocolysis (P < 0.001). This increase lasted over the entire observation period of 48 h. Potassium concentrations fell significantly during the first hours of fenoterol infusion. There was no increase of human placenta lactogen during the period of EPO increase. CONCLUSIONS: The data confirm our earlier results that fenoterol increases EPO concentrations following haemorrhage. In this model it was not necessary to stimulate EPO production prior to pharmacological treatment.

Adrenergic beta-Agonists↗