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Biomedical subjects

W Kuhn

Publications and source records attributed to W Kuhn.

At least 127 records · Page 7Linked to original sources

Optimized differential diagnosis of breast lesions by combined B-mode and color Doppler sonography.

To optimize the sensitivity and specificity of gray-scale imaging and color Doppler in breast tumor diagnosis, alone and in combination, 89 women with palpable breast masses were scanned preoperatively and standard parameters were determined in both modes. Parameters significant for differentiation of benign and malignant tumors identified using univariate analysis were combined and weighted using multivariate analysis (multiple logistic regression). Histologically 59 tumors were malignant and 30 benign. Gray-scale sonography alone achieved a sensitivity of 88% and a specificity of 96% using the parameters of wall structure and posterior acoustic attenuation. Color Doppler achieved a sensitivity of 85% and a specificity of 79% using resistance index and pulsatility index as parameters. Combination of both methods yielded an accurate diagnosis in 84/87 patients (sonographic lesion correlates were absent in two cases), equivalent to a sensitivity of 97% and a specificity of 96%. Thus the individual diagnostic performance of gray-scale imaging and color Doppler sonography in palpable breast disease is further enhanced using multiple logistic regression to combine independently significant parameters.

Adult↗

[Metabolic characterization of ovarian tumors with positron-emission tomography and F-18 fluorodeoxyglucose].

PURPOSE: This study describes diagnostic accuracy of PET imaging in patients with ovarian tumours using histological diagnosis as gold standard. METHODS AND RESULTS: Pet studies were performed in 19 patients who were scheduled to undergo exploratory surgery for a suspicious ovarian mass and in 5 patients with suspected recurrence. The PET data were analyzed visually and quantitatively and compared to the histologic findings. 6 patients had ovarian cancer, while in 13 patients a benign tumour was found including inflammatory processes in 4 cases. All malignant tumours showed an enhanced FDG uptake with the exception of one false-negative borderline carcinoma. 4 cases with inflammatory processes as well as endometrial and follicular cysts revealed a high FDG uptake. A successful localisation of a recurrent tumour was possible in 4 out of 5 cases. Disseminated peritoneal carcinomatosis in two patients could not be detected by PET. CONCLUSIONS: Enhanced glucose metabolism of ovarian cancer enables PET diagnosis with a sensitivity of 83%. An intensive FDG uptake in inflammatory processes resulted in a specificity of only 54% in this study. The high sensitivity of PET for malignant tumours may be useful in the detection of recurrent ovarian cancer.

Adult↗

[Therapy of Parkinson disease. 1: Standard therapy of motor and non-motor symptoms].

Early diagnosis is important for satisfactory pharmacotherapy of idiopathic Parkinson's disease (PD). L-Dopa therapy is still the gold standard in the treatment of PD, but due to complications of long term L-Dopa application, a combination therapy of levodopa with various dopamine agonists and putative neuroprotective drugs, like e.g. selegiline, is becoming increasingly important and attracts more and more attention, especially in the early phases of PD. Moreover, disturbances of the autonomic nervous system and the mind have to be considered and treated besides pharmacotherapy of motor symptoms in idiopathic Parkinson's disease (PD). Hypersalivation, seborrhoea, dysregulation of the cardiovascular system and disturbances of gastrointestinal and bladder motility and sleep are common mainly in the context of autonomic failure in PD. Moreover, Parkinsonian patients often complain of psychopathological features like depression, dementia and psychosis, which may also be due to dopaminergic Parkinsonian therapy. This review surveys possible therapeutic approaches of these disturbances of the psyche and the autonomic nervous system in PD.

Antiparkinson Agents↗

[Therapy of Parkinson disease. 2: New therapy concepts for treating motor symptoms].

New approaches in Parkinsonian pharmacotherapy may be (1) inhibition of catechol-O-methyl-transferase influencing the metabolism of dopamine, (2) the use of budipine, which is assumed to be neuroprotective, with an effect especially on tremor, (3) the application of NADH with the postulated stimulation of the endogenous dopamine synthesis and (4) the revival of stereotaxic surgery with the lesion or the stimulation of certain brain areas, enabled by the development of new and more sensitive methods. Neuroprotective, and/or neuroregenerative therapeutic approaches, like e.g. application or stimulation of growth factors and/or transplantation of neuronal dopaminergic cells, may redirect Parkinsonian therapy from present palliative, symptomatic therapeutic principles to acurative therapy in the future.

Antiparkinson Agents↗

2-[123I]-iodolisuride SPET visualizes dopaminergic loss in de-novo parkinsonian patients: is it a marker of striatal pre-synaptic degeneration?

The aim of this study was to assess the correlation between the functional integrity and density of striatal dopaminergic receptors and clinical data in 15 de-novo patients with idiopathic Parkinson's disease by single photon emission tomography (SPET) using 2-[123I]-iodolisuride (ILIS), a tracer based on the D2-dopamine receptor agonist lisuride. Deficient striatal uptake of ILIS correlated with the severity of the disorder, scored by the Unified Parkinson's Disease Rating Scale (UPDRS) (n = 15; ratio of ILIS uptake: basal ganglia/cerebellum [B/C] & UPDRS I-III, Spearman R = -0.562, P = 0.013), Beck's Depression Inventory (BDI) (n = 12; B/C & BDI, Spearman R = -0.825, P = 0.0009) and the ZUNG Depression Scale (ZDS) (n = 11; B/C & ZDS, Spearman R = -0.7425, P = 0.008). Experimental data indicate that lisuride shows a higher affinity for pre-synaptic dopaminergic autoreceptors than for post-synaptic D2-dopamine receptors under conditions of low applied ILIS concentrations as in this study. From the results of this study and these experimental data, we speculate that ILIS-SPET can visualize pre-synaptic striatal dopaminergic degeneration in Parkinson's disease.

Aged↗

Elevated serum levels of the c-erbB-2 encoded oncoprotein fragment in cases of pure preeclampsia and HELLP syndrome.

OBJECTIVE: During normal human ontogenesis an overexpression of the c-erbB-2 encoded oncoprotein p185 (HER2/neu) occurs in the placenta and on fetal epithelial cells. It is accompanied by the increase of a 105 kD fragment (p105) in both maternal serum and cord blood. We examined whether p105 levels in maternal serum are influenced by destructions of placental tissue, fetal growth disturbances and placental circulation disorders. METHODS: We analysed p105 serum concentrations in patients with abortion (n = 25), ectopic pregnancy (n = 5), intrauterine growth retardation (n = 9), pregnancy induced hypertension (n = 24) and compared them with normal pregnancies of a corresponding gestational age. RESULTS: Patients with abortions showed normal p105 values. Intrauterine growth retardation was associated with lower p105 levels (p < 0.05) whereas patients with pure preeclampsia (p < 0.001) and HELLP syndrome (p < 0.05) had significantly higher levels. CONCLUSION: The elevation of p105 in sera of preeclamptic women could be due to an increased fetomaternal transfer of p105.

Abortion, Missed↗

Distorted colour discrimination in Parkinson's disease is related to severity of the disease.

The Farnsworth-Munsell 100-hue test (FMT) may be used for measurement of colour discrimination and error scores of the FMT provide an unspecific biological marker for the distinction between parkinsonian patients (PP) and healthy controls. The aim of this study was to examine the possible association between distorted colour discrimination and disease severity in untreated "de novo" PP Error scores of the FMT were significantly (P<0.0001) elevated in PP compared to age- and sex-matched controls and correlated to severity of the disease. We conclude that impaired colour discrimination is related to pathophysiology of Parkinson's disease. But it remains unclear whether these alterations of colour vision reflect striatal dopamine deficiency or changes of retinal dopaminergic pathways in PP.

Adult↗

S-100 protein: serum marker of focal brain damage after ischemic territorial MCA infarction.

BACKGROUND AND PURPOSE: Elevations of protein S-100 (S-100) in cerebrospinal fluid and serum have been reported after cerebral infarctions. The aim of our study was to evaluate the time course of serum S-100 concentrations after territorial middle cerebral artery (MCA) infarctions in correlation with clinical data and prognosis. METHODS: S-100 serum levels were serially determined in 26 patients with an acute infarction in the territory of the MCA at day 0 (within 12 hours after onset of symptoms), day 1 (24 hours after stroke onset), and days 2, 3, 4, 5, 7 or 8, and 10 after stroke and in 26 age- and sex-matched control subjects. S-100 assays were performed using a two-site radioimmunoassay technique. The clinical status was documented using the Scandinavian Stroke Scale. The functional deficit 4 weeks after stroke onset was scored by use of the modified Rankin scale. A cranial computed tomography (CCT) was performed initially and at day 4 or 5. RESULTS: Elevated concentrations of S-100 (> 0.2 microgram/L) were observed in 21 of 26 patients with MCA infarction but in none of the control subjects. S-100 levels peaked at days 2 and 3 after stroke. The S-100 concentrations in serum were significantly higher in patients with severe neurological deficits at admission, with extensive infarctions and a space-occupying effect of ischemic edema as compared with the rest of the population. S-100 values were not significantly correlated with the functional prognosis. CONCLUSIONS: Presence of S-100 in serum after ischemic stroke may be due to combined leakage out of necrotic glial cells and passage through an impaired brain-blood barrier, indicating severe ischemic cell injury. Therefore, S-100 in serum can be used as a peripheral marker of ischemic focal brain damage and may be helpful for therapeutic decisions in acute ischemic stroke.

Aged↗

In vivo effects of estrogens on c-erbB-2 oncoprotein levels in chorionic villous tissue and maternal serum.

The c-erbB-2-encoded oncoprotein p185 (HER2) is overexpressed in the fetal epithelium, the placenta and several carcinomas. Elevated serum levels of the released ectodomain (p105) were found in cancer patients and pregnant women at term. In cultured breast cancer cells estradiol inhibited p185 expression and induced growth arrest. These results prompted us to investigate the in vivo influence of serum estradiol and estriol on c-erbB-2 protein levels in pregnancy. We examined chorionic villous tissue extracts and maternal sera obtained from six legal abortions in the first trimester and 20 vaginal deliveries at term. For quantification of c-erbB-2 protein we employed an ELISA. In the first trimester maternal p105 serum levels were significantly (p < 0.0001) lower and p185 tissue levels significantly (p < 0.05) higher than in the third trimester. The highest p105 values were found in additionally examined cord blood. Interindividual regression analyses yielded inverse correlation between estradiol concentrations and placental p185 expression in the first (r = -0.58) and third trimester (r = -0.38) as well as p105 serum levels in the first trimester (r = -0.83). Estriol was correlated positively with p105 values in maternal and umbilical serum but not with placental p185 expression. We conclude that estradiol down-regulates p185 expression in pregnancy whereas the level of maternal p105 depends on the total amount of fetoplacental p185.

Chorionic Villi↗

Does an immunoscintigraphy with OC 125 affect the prognosis of ovarian cancer?

In a retrospective study, a total of 120 ovarian cancer patients were paired in terms of staging, grading, patent age, and operative and cytostatic therapy. Half of the patients underwent radioimmunoscintigraphy for diagnostic purposes. From the point of view of possible adjuvant immunological therapy, we investigated to what extent patients with treated ovarian cancer benefit from the application of OC 125 in terms of survival time. In our study we have been able to show that at favorable stages (FIGO II) the patient benefitted more from a radioimmunoscintigraphy than at prognostically unfavorable stages (FIGO IV). Even within FIGO stage III we have been able to show, thanks to the large number of cases, that patients with an NED situation benefitted significantly more form radioimmunoscintigraphy in terms of survival than those with residual tumors. Throughout FIGO stage III, patients with radioimmunoscintigraphy showed significantly superior 5-year survival rates (p < 0.05) than those without radioimmunoscintigraphy. These data would appear to justify prospective studies to establish to what extent ovarian cancer patients benefit from an adjuvant application of OC 125 in terms of the 5-years survival rate and the relapse-free interval.

Adult↗

SPECT-evaluation of the monoamine uptake site ligand [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) in untreated patients with suspicion of Parkinson disease.

BACKGROUND: For a few years, data on SPECT-imaging of dopamine transporters with the cocaine derivate [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I] beta-CIT) have been reported mostly in healthy subjects or animals. This study reflects our preliminary results with SPECT-imaging of dopamine transporters using the cocaine analogue 123-beta-CIT in patients with untreated (de novo) parkinsonism. METHODS: In 33 patients with clinical suspicion of Parkinson disease and 5 healthy controls, SPECT-imaging of dopamine transporters was performed 1, 4, and 24 hours after injection of 180 MBq of 123I-beta-CIT, which was generated by iododestannylation. None of the patients or controls had been treated before with neuroleptical drugs or any other pharmaceuticals with known binding to the dopamine transporters. Clinical symptoms were staged by the scales Hoehn-Yahr (HYS), Unified Parkinson Disease Rating Scale (UPDRS), and the self-rating scale of Beck depression inventory (BDI). For evaluation, striatal/cerebellar ratios were calculated to every time point. RESULTS: Significant correlations of 123I-beta-CIT uptake could be stated compared to UPDRS, HYS, and BDI values (Spearman correlation, p < 0.05). The symptoms of rigor and akinesia showed a significant correlation with the beta-CIT uptake, whereas the symptom of tremor failed, which may be caused by the location of tremor symptoms out of the striatum. Comparing the controls, a significant (p < 0.01) decrease of tracer uptake in parkinsonian patients is stated on the images at 24 hours p.i. In our patients, tracer uptake does not depend significantly on duration of disease and age. CONCLUSION: 123I-beta-CIT seems to be a promising tool in imaging of untreated parkinsonian patient.

Adult↗

The clinical potential of Deprenyl in neurologic and psychiatric disorders.

This article reviews the results of clinical studies with Deprenyl in various neurologic and psychiatric disorders except Parkinson's disease. Promising results could be observed both in narcolepsy in a dose of at least 20 mg/day in three different trials and in one study of Tourette's syndrome including attention hyperactivity disorders using an average dosis of 8.1 mg/ day. Controversial results were reported for Alzheimer's disease. On the one hand significant improvement of cognitive functions was found by various authors. On the other hand in a more recent study no effect on the progression of the disease could be observed. For depression a higher dosage of deprenyl between 30 to 60 mg/day appears to be necessary for effective treatment. No positive results were found in amyotrophic lateral sclerosis and in tardive dyskinesias.

Adult↗

Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis.

Exogenous application of levodopa is conventionally used to equalize the striatal dopamine deficit in idiopathic Parkinson's disease (PD). The stimulation of endogenous biosynthesis of levodopa via activation of tyrosine hydroxylase (TH) has been proposed as new therapeutic concept in PD. This may be achieved by exogenous supply with the reduced coenzyme nicotinamide adenine dinucleotide (NADH). Aim of this open prospective study was to investigate (1) the efficacy of a new developed, parenteral application form of NADH on Parkinsonian symptoms and (2) the influence of bioavailability of levodopa. 15 patients, suffering from idiopathic PD (11 male, 4 female, age: 61.40[mean] +/- 10.27[SD] range: 44-74 years, Hoehn and Yahr stage: 3.03 +/- 0.69, range 2-4) received intravenous infusions of NADH (10 mg a' 30 min) over a period of 7 days in addition to conventional Parkinsonian pharmacotherapy. Parkinsonian symptoms were scored before (day 1) and after NADH treatment (day 8). Levodopa plasma levels were estimated over a period of four hours on the day before and on the first day of NADH application by HPLC. Parkinsonian patients showed a significant response, evaluated by the Unified Parkinson's Disease Rating Scale Version 3.0 (p = 0.025; Wilcoxon test). Moreover application of NADH significantly increased bioavailability of plasma levodopa (AUC, p = 0.035; Cmax p = 0.025). In conclusion NADH in used galenic form may be a potent stimulator of endogenous levodopa biosynthesis with clinical benefit for Parkinsonian patients.

Adult↗

Visual hallucinosis: the major clinical determinant of distorted chromatic contour perception in Parkinson's disease.

Recently distorted chromatic contour perception has been demonstrated in Parkinson's disease (PD). The aim of our study is to determine the clinical factors which influence chromatic contour perception in PD. Chromatic and achromatic contour perception, colour discrimination and clinical data were evaluated in 73 patients with PD. We used a computer-aided method to determine the chromatic fusion time (CFT) which indicates the acuity of monochromatic contour perception. Chromatic CFT was generally shortened in patients as compared to controls (p < 0.01), whereas achromatic CFT was not significantly different. Variance analysis revealed the ability of colour discrimination and the risk of visual hallucinations as statistically significant (p < 0.05) variables influencing contour perception of certain stimuli. In contrast, disease stage, disease duration and disease severity have no relevant effect on chromatic contour perception in Parkinson's disease. On the basis of those properties one may suggest that distorted chromatic contour perception is due to an impairment at a central stage of visual processing in PD and an imbalance of the serotonergic system. Whether CFT is a reliable method to predict the individual risk of hallucinosis in PD has to be evaluated.

Aged↗

Sustained-release of levodopa: single dose study of a new formulation.

Motor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promising, effective solution of this problem. Therefore we performed a 4-fold, cross-over double-blind trial with a new SR preparation, tested in healthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian subjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacokinetic behaviour and their clinical effects. The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100 mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formulation the pharmacokinetic behaviour of the SR preparations showed no initial sharp peak, but more continuous and longer maintaining plasma concentrations of levodopa. Due to the small numbers of cases and the missing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical response were observed. But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinson's disease (prolongation of dosage intervals, reduction of motor fluctuations).

Aged↗

The motor performance test series in Parkinson's disease is influenced by depression.

The Motor Performance Test Series (MPTS) is widely used for treatment control in Parkinson's disease (PD). To elucidate the possible influence of depression on the fine motor skills in PD, 54 patients with idiopathic PD were investigated with the MPTS. 27 patients with major intensity of depression were compared to 27 age and motor disability matched patients with minor symptoms of depression, evaluated by the Zung depression scale. As determined by the subtest aiming, a significant lower ability for precise, quick complex arm-hand movements in depressed Parkinsonian patients was found. This result may be explained partly by motivation deficits in depressed patients with PD. On the other hand impairment of special motor loops including frontal lobe projections to specific thalamic subnuclei or to the caudate nucleus may cause disturbances of the subtest aiming in depressed Parkinsonian patients. On the basis of these findings impaired aiming may be explained by diminished ability for complex, semivoluntary movements in depressive Parkinsonian patients. The influence of psychiatric comorbidity on MPTS subtest aiming has to be considered in further therapy studies using evaluation of motor deficits by MPTS.

Adult↗

Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients.

Death of dopaminergic neurons in Parkinson's disease (PD) may partially be caused by synthesis and accumulation of endogenous and exogenous toxins. Because of structural similarity to MPTP, beta-carbolines, like norharman and harman, have been proposed as putative neurotoxins. In vivo they may easily be formed by cyclization of indoleamines with e.g. aldehydes. For further elucidation of the role of beta-carbolines in neurodegenerative disorders harman and norharman levels in cerebrospinal fluid (CSF) were measured in 14 patients with PD and compared to an age- and sex-matched control group (n = 14). CSF levels of norharman and harman in PD were significantly higher compared to controls. These results may suggest a possible role of harman and norharman or its N-methylated carbolinium ions in the pathophysiological processes initiating PD. However the origin of increased levels of these beta-carbolines remains unclear. On the one hand one may speculate, that unknown metabolic processes induce the increased synthesis of harman and norharman in PD. On the other hand a possible impact of exogenous sources may also be possible.

Adult↗