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Biomedical subjects

W Kuhn

Publications and source records attributed to W Kuhn.

At least 73 records · Page 4Linked to original sources
PubMed1999

Detection of tolcapone in the cerebrospinal fluid of parkinsonian subjects.

The cerebral availability of the peripherally and centrally acting catechol-O-methyltransferase (COMT) inhibitor tolcapone is not known in humans. Therefore, we determined the concentration of tolcapone in cerebrospinal fluid (CSF) of 12 parkinsonian subjects 1-4 h after oral application of 200 mg of the drug. The mean concentration was 56.4+/-35.5 nmol/l (mean +/- SD). This concentration was calculated to cause 75.2+/-15% (mean +/- SD) inhibition of COMT in CSF. Thus, tolcapone efficiently inhibits COMT after crossing the blood-brain barrier in humans.

Administration, Oral↗
PubMed1999

Generators of brain electrical activity in patients with Wilson's disease.

Electroencephalographic (EEG) generators were investigated in 13 patients suffering from hepatolenticular degeneration with and without neurological symptoms and in 13 healthy subjects for comparison by the use of FFT approximation. Quantitative assessment of motor deficits and psychiatric disturbances was correlated with EEG features. We found mainly an increase in delta activity, a decrease in alpha activity combined with a more posterior localisation of the EEG generators in the delta band and a more anterior one in the alpha band in patients compared with healthy controls. The localisation of the EEG generators in the patients with clinical apparent neurological symptoms were in all frequency bands more superficial compared with controls and patients without neurological symptoms. With longer duration of the disease, the lower the premorbid intelligence the more posterior was the delta EEG generator localised. Although the alpha EEG generator was more anteriorly localised with longer duration of the disease and more severe cognitive deficits, it was more superficial with more pronounced psychiatric symptoms, more severe cognitive deficits, lower premorbid intelligence and more pronounced motor disabilities. With more pronounced psychiatric symptoms and cognitive deficits, the beta EEG generator was more anteriorly localised. The present study demonstrated that a significant deviant EEG pattern exists between patients with and without clinical neurological symptoms and that stage-dependent alterations in psychiatric symptoms and cognitive ability are reflected on the EEG.

Adult↗
PubMed1999

Serum levels of neuron-specific enolase and s-100 protein after single tonic-clonic seizures.

Serum neuron-specific enolase (s-NSE) and s-100 protein (s-100) are sensitive markers of various brain diseases. We investigated both of these markers in nine patients within 5 min, 6 h, 12 h, and 48 h after a single tonic-clonic seizure. The mean peak s-NSE level was significantly higher after 5 min (11.97 +/- 8.56 microg/l) and 48 h (10.31 +/- 8.92 microg/l, P < 0.05) than the levels of seizure-free, age-matched controls. Five patients had increased s-NSE levels regarding the upper limit of normal as mean + 3 SD. s-100 was not detected either in controls or epileptic patients. These data indicate that s-NSE in contrast to s-100 may be an in vivo marker after generalized seizures in some patients.

Adult↗
PubMed1999

Analysis of the parkin deletion in sporadic and familial Parkinson's disease. Short communication.

Recently a mutation in the parking gene has been identified as the cause for an autosomal-recessively inherited form of early onset Parkinson's disease (EOPD). The disease causing minimal deletion has been defined as a homozygous exon 4 loss in the parkin gene among Japanese patients. We investigated 140 sporadic and familial EOPD patients of German ancestry for the exon 4 deletion in the parkin gene. None of our patients exhibited a homozygous deletion of exon 4, suggesting a minor role of this mutation for EOPD in Caucasians. Nevertheless a detailed mutation analysis is warranted to explore the overall significance of mutations in the parkin gene in EOPD.

Adult↗
PubMed1999

Limitations of the evaluation of adnexal masses by its macroscopic aspects, cytology and biopsy.

To investigate the relevance of intraoperative macroscopic evaluation of adnexal masses a prospective study was conducted from June 1st, 1993 to May 31st, 1994, which included 57 premenopausal and 60 postmenopausal women, who underwent laparotomy because of a cystic adnexal mass. The surgeons were asked to classify the tumor intraoperatively as benign or malignant and to assign to histologic groups. In addition cytology of the cyst fluid and a biopsy from the cystic wall were evaluated. Comparison of these items with the results of permanent section diagnosis revealed the tendency of the surgeons to underestimate adnexal masses depending on patients' age and the complexity of the tumor, despite of the knowledge of preoperative ultrasonographic findings. Sufficient cytolologic examination was possible in only one third of aspirates and only 21% of the examined postmenopausal malignant neoplasms have correctly been diagnosed by cytology. Evaluation of the biopsy specimens demonstrates a marked percentage of false negatives with respect to benign tumors (30% of non-functional benign neoplasms in the premenopause were assessed as functional cysts) as well as malignant neoplasms (only 72% were diagnosed correctly in the postmenopause group). In conclusion intraoperative subjective assessment, cytology and representative biopsies do not necessarily concur with the definitive histological diagnosis.

Biopsy↗
PubMed1999

Pulsatile vs. continuous parenteral tocolysis: comparison of side effects.

Bolus tocolysis has been developed to reduce the dose of fenoterol compared to continuous tocolysis. Whereas the high efficacy of pulsatile application of fenoterol has been shown, the proof of reduced side effects is still lacking. A total of 59 patients with preterm labor were divided in three groups: (1) continuous tocolysis and oral application of magnesium (n=19), (2) continuous tocolysis and parenteral application of magnesium (n=20), (3) pulsatile tocolysis (bolus tocolysis) and oral application of magnesium (n=20). Heart rate, systolic and diastolic blood pressure, serum K+ and serum Mg++ were quantified before tocolysis and after 2, 8 and 24 h. Beta-blockers and water balance were recorded over 24 h. Subjective side effects were quantified using a questionnaire with scales graduated covering palpitations, tremor, diaphoresis, thirst, precardialgia and nausea/vomiting. The analysis of the data revealed significantly fewer side effects concerning heart rate, plasma K+ level and the subjective side effects among patients treated with bolus tocolysis than among those treated with continuous tocolysis. Between the latter two groups, no significant difference was found. Concerning blood pressure and need for beta-blockers, no significant differences were found between the three groups. The results of the present study show that especially the side effects subjectively found to be disagreeable by the patients are reduced by pulsatile tocolysis, whereas other side effects show only slight differences between the study groups.

Adrenergic beta-Antagonists↗
PubMed1999

Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc.

Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low- and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from individualized therapy protocols.

Adult↗
PubMed1999

Colour vision abnormalities and movement time in Parkinson's disease.

Visual system dysfunction has been reported in Parkinson's disease (PD). The objective of the present study was to evaluate a putative association of distorted colour vision and delayed initiation and execution of movement in PD. We performed the Farnsworth-Munsell 100-hue test and estimated the total error score in 30 previously untreated parkinsonian patients and 30 age- and sex-matched controls. We then determined slowness in motor readiness and motor programming in the parkinsonian subjects on the same day. Subjects were asked to press a start button and release it after the randomized appearance of a visual stimulus and to move their right index finger to a reaction button as quickly as possible. Reaction time was considered as elapsed time between onset of the stimulus light and release of the start button, movement time was the time period between release of the start button and the pressing of the reaction button. Significant differences appeared between parkinsonian patients' and controls' reaction times (P = 0.007), movement time (P = 0.001) and total error score (P = 2.23E-08). A significant relation (Spearman R = 0.473, P = 0.008) was found between movement time and total error score, but not between reaction time and total error score (Spearman R = 0.259, P = 0.166). We conclude, that visual dysfunction and execution of movement are more influenced by altered dopaminergic neurotransmission in PD in comparison to the initiation of movement.

Adult↗
PubMed1999

Thrombophilic state in breast cancer.

Tumor cell metastasis and thrombosis are the major causes of death in cancer patients. Thrombosis in cancer patients may occur when physiologic antithrombotic systems are defective or when prothrombotic activities defeat normal physiologic antithrombotic mechanisms. Malignancies by themselves may already predispose to a hypercoagulable state in cancer patients. Tumor cells can either directly activate the blood clotting system or indirectly stimulate mononuclear cells to synthesize and express various procoagulants, subsequently leading to prothrombin activation, fibrin formation, and generation of a thrombus. In addition, other comorbid predisposing factors effecting thrombosis in cancer patients have to be considered, including surgery, bed rest, infection, long-term indwelling central venous catheters, anticoagulation, and chemotoxic or steroidal anticancer drugs used in adjuvant or palliative cancer treatment. Reliable information on the incidence of thromboembolism in cancer patients is available for breast cancer; less data have been reported for other malignancies. Chemo- and/or hormone therapy in patients with primary or metastatic breast cancer is associated with an increased thromboembolic risk, although the benefits of treatment far outweigh the risks. The current literature discussing the effect of chemo/hormone therapy on blood clotting factors and the associated risk of thrombosis is reviewed, with emphasis on new developments in the area of tissue-specific SERMs (selective estrogen receptor modulators). SERMs are employed as adjuvant therapy in primary breast cancer and in the palliation of advanced breast cancer and may be clinically useful as potential substitutes for long-term hormone replacement therapy, in the treatment of osteoporosis, and for cancer prevention therapy.

Antineoplastic Agents↗
PubMed1999

Delayed motor response correlates with striatal degeneration in Parkinson's disease.

OBJECTIVE: Studies on reaction time have suggested a selective deficit of slowness in motor readiness and motor programming in Parkinson's disease (PD). Objective of this study was the putative relation between delayed initiation and execution of movement and the striatal dopamine deficiency in PD. MATERIAL AND METHODS: We investigated 32 idiopathic, previously untreated parkinsonian patients to evaluate dopaminergic nigrostriatal degeneration by single photon emission tomography in combination with the radiotracer [123I]-beta-CIT and performed a simple reaction time paradigm on the same day. RESULTS: Significant relations between the [123I]-beta-CIT-SPECT-ratio striatum/cerebellum and reaction--and movement time appeared. Reaction time and movement time of parkinsonian patients were significantly longer compared to age-matched controls. CONCLUSIONS: We conclude that reaction- and movement-time is related to the dopaminergic nigrostriatal degeneration in untreated parkinsonian subjects.

Adult↗
PubMed1999

Basal ganglia alterations and brain atrophy in Huntington's disease depicted by transcranial real time sonography.

OBJECTIVES AND METHODS: Transcranial real time sonography (TCS) was applied to 49 patients with Huntington's disease and 39 control subjects to visualise alterations in the echotexture of the basal ganglia. For comparison T1 weighted, T2 weighted, and fast spin echo MRI was performed in 12 patients with Huntington's disease with and in nine patients without alterations of the basal ganglia echotexture as detected by TCS and T1 weighted, T2 weighted, and fast spin echo MRI. Furthermore, the widths of the frontal horns, third ventricle, and the lateral ventricles were depicted in TCS examinations and correlations examined with corresponding CT slices. RESULTS: Eighteen out of 45 (40%) of the patients with Huntington's disease with adequate insonation conditions showed hyperechogenic lesions of at least one basal ganglia region. In 12 patients TCS depicted hyperechogenic lesions of the substantia nigra; in six patients the head of the caudate nucleus was affected. The lentiform nucleus (n=3) and the thalamus (n=0) were less often affected or spared. Hyperechogenic lesions were significantly more frequent in patients with Huntington's disease than in 39 control subjects, who had alterations of the echotexture in 12.8% (4/39) of the examinations. The number of CAG repeats and the clinical status correlated with the identification of hyperechogenic lesions of the substantia nigra (p<0.01). Hyperechogenic lesions of the caudate nucleus were associated with an increased signal intensity in T2 weighted MR images (p<0.05). All TCS parameters indicating brain atrophy correlated with CT findings (p<0.0001). CONCLUSIONS: TCS detects primarily abnormalities of the caudate nucleus and substantia nigra in Huntington's disease. These changes in the echotexture may represent degenerative changes in the basal ganglia matrix and are partially associated with CAG repeat expansion and the severity of clinical findings.

Adult↗
PubMed1999

Impaired visual function in focal idiopathic dystonia.

Visual dysfunctions have previously been reported in Parkinson's disease and Huntington's chorea. To further characterize the pathophysiology of vision in basal ganglion diseases, we studied visual functions in focal dystonic syndromes. Colour discrimination and visual contrast perception were investigated in 37 patients with focal idiopathic dystonia (ID; 20 spasmodic torticollis, 17 blepharospasm) and in age- and sex-matched healthy volunteers using the Farnsworth-Munsell 100-hue test and stationary contrast targets (Vistech plates). The mean total error score as well as the partial scores for the 'red-green' and the 'blue-yellow' axes in the Farnsworth-Munsell 100-hue test of the patients with ID were significantly elevated as compared to controls (spasmodic torticollis mean total error score 90.9 +/- 67.6, controls: 16.6 +/- 10.2; blepharospasm mean total error score 119.4 +/- 78.6, controls: 22.7 +/- 7.9). Additionally, the spatial contrast sensitivity was impaired in patients as compared to controls. The results indicate that the visual system is affected in ID. The visual disorder may be related to an imbalance of certain neurotransmitters in the visual system of patients, e.g. in the catecholaminergic pathways.

Adult↗
PubMed1999

First-line chemotherapy with epirubicin, paclitaxel, and carboplatin for advanced ovarian cancer: a phase I/II study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group.

PURPOSE: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the "third drug" into first-line regimens for advanced ovarian cancer. PATIENTS AND METHODS: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m2) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. RESULTS: Dose-limiting toxicity occurred at dose level 2 (75 mg/m2 epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m2 (E) combined with a 3-hour infusion of paclitaxel 175 mg/m2 (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. CONCLUSION: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation. A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated.

Adult↗
PubMed1999

HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.

In a collective of 112 node-negative breast cancer patients, we compared the prognostic impact of HER-2/neu gene amplification (AMP) determined by fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still alive at time of analysis was 7 years. Automated FISH and IHC were performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu AMP significantly predicted both disease-free (DFS) and overall survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate analysis of all analyzed prognostic factors, HER-2/neu AMP was the only independent predictive factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7-year median follow-up: patients with low levels of both uPA and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group assessment. In addition to its prognostic strength, the significant impact of HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic therapy.

Adult↗