Biomedical subjects

W Kuhn

Publications and source records attributed to W Kuhn.

At least 109 records · Page 6Linked to original sources

PubMed1998

3D Color Power Angio imaging: a new method to assess intracervical vascularization in benign and pathological conditions.

It is well known that angiogenesis is a fundamental event in the growth of tumors as well as in physiological conditions. In an ongoing prospective study involving eight women, we investigated the microvasculature within the cervix by the use of 3D Color Power Angio imaging. The ultrasound equipment was used in conjunction with specialized software providing high-resolution '3D-Angiomode'. The system provides the ability to visualize blood flow in small vessels that are undetectable by conventional color Doppler techniques and also to study the architecture and determine the number of blood vessels. Comparison of the vessels in the normal cervix with those in the cervix affected by carcinoma or bacterial or viral infection demonstrated that, in malignant tissue, there is a chaotic network of tortuous vessels traversing the tumor mass, whereas, in benign tissue or tissue that is inflamed as a result of infection, the course of the vessels has a regular structure.

Cervix Uteri↗

PubMed1998

Overexpression of the oncogene c-erbB-2 (HER2/neu) and response to chemotherapy in patients with ovarian cancer.

This study was designed to determine whether c-erbB-2 overexpression could be used as a marker to identify a subgroup of patients with ovarian cancer more likely than others to benefit from chemotherapy. Paraffin sections from tissue blocks from 208 patients with newly diagnosed untreated ovarian cancer were analyzed for c-erbB-2 overexpression. All patients underwent postoperative platin-based chemotherapy. Patients with c-erbB-2 positive tumors had a significantly worse prognosis as compared to patients with c-erbB-2 negative tumors (p = 0.0003). c-erbB-2 findings were not related to tumor stage or histologic findings. There was clear evidence of a dose-response effect with regard to survival in patients with c-erbB-2 negative tumors, which could not be seen in patients with c-erbB-2 positive tumors (p = 0.0341 vs p = 0.3775). We conclude that there is a significant total dose-response effect of platin-based chemotherapy in ovarian cancer patients without overexpression of c-erbB-2 but not in patients with c-erbB-2 overexpression. Overexpression of c-erbB-2 may be a useful marker to identify patients who are most likely to benefit from high-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Borderline tumors of the ovary: a clinico-pathologic and immunohistochemical study of 54 cases.

OBJECTIVE: To study EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, ras expression and ploidy in borderline tumors of the ovary by assessing their frequency, and relationship to histologic type, tumor recurrence and survival. METHODS: Fifty-four patients with borderline tumors were followed 3-140 months (median: 38 months). Paraffin-embedded sections were stained using monoclonal antibodies against EGF-R, HER-2/neu (p185), p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras. The immunohistochemical findings were correlated to histologic subtype, tumor recurrence, and survival. RESULTS: Positivity for EGF-R was found in 24% (13/54), in 22% (12/54) p185 was positive, 9% (5/54) of tumors were p53-positive, Mib-1 (Ki-67)-positivity was demonstrable in 46% (25/54). Expression of Bax, Bcl-2, and ras was found in 37% (20/54), 28% (15/54) and in 7% (4/54) of the cases, respectively. CONCLUSION: The data demonstrate expression of EGF-R, p185/HER-2/neu, p53, Mib-1 (Ki-67), Bax, Bcl-2, and ras in a subgroup of patients with ovarian borderline tumors. Further studies to evaluate their prognostic value are warranted.

Adult↗

PubMed1998

Interleukin-6 levels in cerebrospinal fluid inversely correlate to severity of Parkinson's disease.

INTRODUCTION: Several lines of evidence suggest that neuroimmune mechanisms may also be involved in neurodegeneration in Parkinson's disease (PD). The potential role of cytokines such as interleukin 6 (IL-6), in the interaction between neurons and immune system has been emphasized by recent findings. IL-6 induces acute phase protein synthesis, differentiation of neuronal cells and improves catecholaminergic and cholinergic cell survival in the brain. SUBJECTS AND METHODS: We determined levels of IL-6 in cerebrospinal fluid (CSF) of untreated parkinsonian patients and age- and sex-matched controls. Intensity of disease was evaluated by the Unified Parkinson's Disease Rating scale. RESULTS: Significantly elevated levels of IL-6 were found in the CSF of parkinsonian patients. Moreover a significant inverse correlation between severity of PD and IL-6 CSF levels appeared. DISCUSSION: Elevated IL-6 levels in the CSF of untreated parkinsonian patients may reflect the original condition in the course of disease. We speculate that an endogenous upregulation of IL-6 synthesis occurs in order to regenerate lesioned neurons probably at an early phase of the degenerative process in PD.

Adult↗

PubMed1998

[123I]beta-CIT SPECT visualizes dopamine transporter loss in de novo parkinsonian patients.

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the basal ganglia, which may be visualized by single photon emission computed tomography (SPECT) in combination with the cocaine analog methyl-3-beta-(4-beta[123I]iodophenyl)tropane-2beta-carboxylate ([123I]beta-CIT). The aim of our study was to correlate findings of SPECT with clinical data of 34 previously untreated, idiopathic parkinsonian patients [age: 59.58+/-10.03 (mean+/-SD) years; Hoehn and Yahr Scale (HYS) mean range: 1.97+/-0.83, ranges I-III; Unified PD Rating Scale 3.0 (UPDRS, 30.64+/-18.68) and 15 healthy controls (age 47.93+/-10.47 years). SPECT scans were performed with a single-head gamma-camera 24 h after intravenous injection of [123I]beta-CIT. Comparison of the striatum/cerebellum (S/C) ratio of [123I]beta-CIT uptake of controls and parkinsonian subjects, subdivided according to their HYS range, was significant. No influence of age or sex was observed. Significant correlations were found between scores of the HYS, UPDRS parts I-III, part II, part III, and the S/C ratio of [123I]-CIT uptake. Moreover, SPECT with the radiotracer [123I]beta-CIT revealed side-to-side differences in parkinsonian patients and significant associations to contralateral clinical extrapyramidal symptomatology. Our data show that SPECT with [123I]beta-CIT is a valuable tool for estimating disease severity in PD.

Adult↗

PubMed1998

Elevated plasma levels of homocysteine in Parkinson's disease.

Significantly elevated plasma levels of homocysteine, but not cysteine and cysteinylglycine, were found in treated parkinsonian patients compared to controls. Elevated levels of homocysteine may be either caused by an unknown endogenous metabolic disturbance or by antiparkinsonian treatment, because no association to severity or duration of disease was found. Based on the results of this study one may speculate that homocysteine may be an independent risk factor for vascular disease in Parkinson's disease.

Aged↗

PubMed1998

Changes in plasma elastase during pregnancy and sub partu.

Elastase is produced and released by polymorphonuclear leukocytes (PNMs) during inflammatory processes. Thus, elastase is assumed to be a sensitive marker of infections similar to the well-established C-reactive protein (CRP). It is deactivated predominantly in tissues by alpha1-proteinase inhibitor which forms stable complexes with the elastase molecule (EAPI) that can be detected for several hours. Premature rupture of membranes is often correlated with an early increase in elastase, occurring earlier than the increase in leukocyte count or CRP. Elastase might be a sensitive marker of beginning amnion infection syndrome after premature rupture of membranes. For the present study, plasma EAPI levels of 335 healthy pregnant women as well as 47 healthy nonpregnant pre- and postmenopausal women were analyzed. No significant differences were found in the latter group or in pregnant women until the beginning of labor. Women at the beginning of labor but without rupture of membranes showed a significant increase in plasma EAPI from 97.7 to 338.3 ng/ml (p < 0.001). With opening of the os uteri to more than 2 cm, elastase concentrations decreased to values comparable to those before the beginning of labor (p < 0.001). The use of elastase as a marker for a rupture of membranes or beginning amnion infection syndrome as suggested by a number of studies might need some restriction. As a consequence, serial monitoring of plasma elastase to detect a persisting increase might give more reliable results. The increase in plasma elastase during beginning of labor may be explained by the role of PMNs in the physiology of delivery. However, serial monitoring to detect a persisting increase in plasma EAPI may be more helpful.

C-Reactive Protein↗

PubMed1998

High prevalence of parkinsonism after occupational exposure to lead-sulfate batteries.

Seven of nine postal workers exposed to lead-sulfate batteries over a period of up to 30 years developed parkinsonian symptoms. One of the remaining two showed left-hand bradykinesia and one was not available for examination. The high prevalence and cause of parkinsonism in these patients remains unexplained. Lead intoxication may play a role in the occurrence of parkinsonian symptoms, but involvement of sulfate and other sulfur compounds must also be considered.

Antiparkinson Agents↗

PubMed1998

Thrombomodulin, a receptor for the serine protease thrombin, is decreased in primary tumors and metastases but increased in ascitic fluids of patients with advanced ovarian cancer FIGO IIIc.

The human ovarian cancer cell line OV-MZ-19, established from a patient with cystadenocarcinoma of the ovary, expressing thrombomodulin (TM), a cell surface receptor for the serine protease thrombin, interacts with monoclonal and polyclonal antibodies having different specificity for TM. These antibodies detect TM antigen by means of flow cytofluorometry, laser scanning microscopy, immunocytochemistry, and ELISA. Therefore a highly sensitive ELISA for TM antigen was established using two different monoclonal antibodies to quantify TM in tissue extracts and biological fluids, e.g. peritoneal malignant ascites. Primary malignant ovarian tumors and metastases of the omentum and intestine contain TM antigen as determined by ELISA but in significantly lower concentrations than benign ovarian tumors (p=0.0056). In contrast, malignant ascitic fluid of patients with advanced ovarian cancer (FIGO IIIc) contain significantly elevated concentrations of soluble TM than benign peritoneal exudates (p=0.0003). Immunoaffinity purified ascites-derived TM efficiently activates protein C. Protein C activation of ascites-derived TM as well as TM expressed by the tumor cells is inhibited by the monoclonal antibodies. TM abrogates the procoagulant activity of thrombin, reduces pericellular thrombin via internalization, accelerates the thrombin-mediated inactivation of pro-uPA, and the EGF domains of TM exhibit mitogenic activity towards fibroblasts and tumor cells. Both, thrombin and pro-uPA play important roles in tumor invasion and metastasis. Therefore, downregulation and/or release of TM into ascitic fluid may play an important role in the malignant behavior of tumor cells.

Antibodies, Monoclonal↗

PubMed1998

Disease-adapted relapse therapy for ovarian cancer: results of a prospective study.

Primary therapy of advanced ovarian cancer is standardized, the therapy in relapsed ovarian cancer however is still controversial. In a prospective study the benefit of secondary surgery and/or second-line chemotherapy were evaluated. 139 patients with relapsed ovarian cancer were stratified according to a treatment plan: patients with early relapse (recurrence-free interval 12 months) or primary progression during chemotherapy (n=43) were treated chemotherapeutically with etoposide (p.o. vs. i.v.). Patients with late relapse (recurrence-free interval >12 months, n=96) were referred, if possible, to a secondary debulking operation, followed by a platinum-based chemotherapy. Remission-rate, toxicity and survival time were analyzed. Median survival time in the group was 15 months compared to 30 months in patients with late relapse (p=0.0004). Within the group patients with secondary debulking and chemotherapy (n=59) had a statistically significant survival advantage compared to patients who had only chemotherapy (n=37) (38 vs. 12 months, p<0.0001). The unfavorable group of patients with early relapse should be treated chemotherapeutically, whereas in patients with late relapse a secondary debulking seems to improve prognosis.

Adult↗

PubMed1998

[Soluble adhesion molecules in patients with pre-eclampsia].

Plasma concentrations of the circulating adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106) were determined in 31 women with pre-eclampsia, 9 women with HELLP syndrome, and 13 women with transient pregnancy induced hypertension (PIH). Data were compared with a control group of 157 healthy pregnant women of the same gestational age. Furthermore, concentrations of circulating E-selectin (CD62E), P-selectin (CD62P), and PECAM-1 (CD31) were determined in a subpopulation of 17 women with pre-eclampsia. Plasma concentrations of circulating ICAM-1, VCAM-1, E-selectin, and PECAM-1 were significantly elevated in women with pre-eclampsia compared to healthy control pregnant women. Circulating ICAM-1 and VCAM-1 levels were also significantly elevated in the pre-eclampsia group compared to women with PIH. Concentrations of circulating P-selectin varied strongly in all experimental groups (SD > 70% of the mean), most likely reflecting various degrees of thrombocyte degranulation in the individual samples. Finally, longitudinal profiles of cICAM-1 and cVCAM-1 concentrations were determined in 123 healthy pregnant women between the 16th and the 42nd week of gestation. This analysis identified cICAM-1 and cVCAM-1 as tightly regulated plasma parameters that varied in a small concentration range. Concentrations of cICAM-1 and cVCAM-1 did not vary during pregnancy and the determined concentrations corresponded to the reported reference levels of nonpregnant individuals.

Adult↗

PubMed1998

In vivo and in vitro investigations of hydration effects of beauty care products by high-field MRI and NMR microscopy.

AIM: Data obtained from in vivo and in vitro measurements on human skin and skin samples are presented. METHODS: In vivo measurements, using a 3-Tesla magnetic resonance system, on the forearm of three female volunteers show an increase of signal intensity, after application of cream, between 30% and 58%, depending on the cream type. In-plane resolution was 90 microm, with slice thickness of 2 mm. Chemical-shift-selective in vitro microimaging studies were performed on a 9.4-T spectrometer using human skin samples from the abdomen. In these experiments, in-plane resolution was 4 microm and slice thickness was 100 microm. RESULTS: The results demonstrate clearly the moisturising effect of beauty care products on the stratum corneum, which can be identified in in vitro experiments. No ingress into the skin of the lipid components of the emulsions could be observed in vitro. However, skin occlusion and consequently a long-lasting moisturising effect cannot be excluded. CONCLUSIONS: These results prove the capability of magnetic resonance imaging to investigate human skin in vivo and in vitro, and to follow the skin penetration of beauty-care products and pharmaceutical ointments.

Adult↗

PubMed1997

Disgust implicated in obsessive-compulsive disorder.

Psychiatric classificatory systems consider obsessions and compulsions as forms of anxiety disorder. However, the neurology of diseases associated with obsessive-compulsive symptoms suggests the involvement of fronto-striatal regions likely to be involved in the mediation of the emotion of disgust, suggesting that dysfunctions of disgust should be considered alongside anxiety in the pathogenesis of obsessive-compulsive behaviours. We therefore tested recognition of facial expressions of basic emotions (including disgust) by groups of participants with obsessive-compulsive disorder (OCD) and with Gilles de la Tourette's syndrome (GTS) with an without co-present obsessive-compulsive behaviours (GTS with OCB; GTS without OCB). A group of people suffering from panic disorder and generalized anxiety were also included in the study. Both groups with obsessive-compulsive symptoms (OCD; GTS with OCB) showed impaired recognition of facial expressions of disgust. Such problems were not evident in participants with panic disorder and generalized anxiety, or for participants with GTS without obsessions or compulsions, indicating that the deficit is closely related to the presence of obsessive-compulsive symptoms. Participants with OCD were able to assign words to emotion categories without difficulty, showing that their problem with disgust is linked to a failure to recognize this emotion in others and not a comprehension or response criterion effect. Impaired recognition of disgust is consistent with the neurology of OCD and with the idea that abnormal experience of disgust may be involved in the genesis of obsessions and compulsions.

Adult↗

PubMed1997

[Non-motor symptoms of Parkinson disease. Significant impact on quality of life--using possible treatments].

In patients with idiopathic Parkinson's disease, not only the motor disorders, but also disturbances of the autonomic nervous system and the psyche need to be treated. With respect to the autonomic nervous system, such symptoms as hypersalivation, seborrhea, dysregulation of the cardiovascular system, disturbances of the gastrointestinal tract and bladder motility, as also sleep disorders predominate. Also seen in Parkinson's disease are such psychiatric complaints as depression, dementia and psychoses, which latter in particular may also be a consequence of dopaminergic replacement therapy. A number of therapeutic concepts are available for the treatment of these disorders, which are often extremely stressful for the patient and therefore require early treatment.

Autonomic Nervous System Diseases↗

PubMed1997

[Current therapy of idiopathic Parkinson disease. 1: Diagnosis, therapeutic guidelines, standard pharmacotherapy and physical therapy].

The necessary prerequisite for adequate medical and physical treatment are early diagnosis and differential diagnosis. The gold standard for medical treatment of Parkinsonism continues to be the administration of L-dopa. However, in view of the complications associated with the long-term use of L-dopa, combination treatment with dopamine agonists and substances presumed to have a neuroprotective effect, for example selegiline, administered at the onset of the disease is currently gaining importance and finding increased interest.

Antiparkinson Agents↗

PubMed1997

[Current therapy of idiopathic Parkinson disease. 2: Recent and alternative therapies].

New possibilities in the medical treatment of Parkinson's disease are offered by the MAO-B inhibitor, selegiline, and L-dopa preparations with strongly accelerated or retarded kinetics. Possible new approaches to drug treatment might be, firstly, inhibition of the enzyme catechol-o-methyl-transferase, which influences the breakdown of dopamine, and secondly, administration of NADH with the aim of stimulating the body's own synthesis of dopamine. A third approach might be the reintroduction of stereotactic surgery with coagulation or stimulation of certain areas of the brain, that has now been made possible by the development of new and more subtle techniques. Neuroprotective and/or neuro-regenerative approaches, such as, for example, the administration or stimulation of growth factors and/or transplantation of neuronal dopaminergic cells might lead the treatment of Parkinson's disease from the palliative symptomatic approach it is today, to a future curative approach.

Antiparkinson Agents↗

PubMed1997

Circulating endothelial cell adhesion molecules as diagnostic markers for the early identification of pregnant women at risk for development of preeclampsia.

OBJECTIVE: The aim of the current study was to determine levels of circulating endothelial cell adhesion molecules during preeclampsia and to assess their predictive value as diagnostic markers for the early identification of pregnant women at risk of developing preeclampsia. STUDY DESIGN: Plasma samples were obtained from women with preeclampsia; the syndrome of hemolysis, elevated liver enzymes, and low platelets; uncomplicated pregnancy-induced hypertension; and women with normal pregnancy. In addition, longitudinal plasma profiles of pregnant women were randomly collected to determine individual profiles of circulating endothelial cell adhesion molecules. A sandwich enzyme-linked immunosorbent assay technique was used to quantitate concentrations of soluble intercellular adhesion molecule-1 (CD54), vascular cell adhesion molecule-1 (CD106), E-selectin (CD62E), platelet endothelial cell adhesion molecule (CD31), and P-selectin (CD62P). RESULTS: Plasma levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and platelet endothelial cell adhesion molecule-1 were significantly elevated in women with preeclampsia compared with healthy control pregnant women. Longitudinal analysis of soluble plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels during pregnancy revealed that these molecules (1) show little variation in healthy pregnant women, (2) do not vary during normal pregnancy, and (3) are significantly elevated in women with preeclampsia and the syndrome of hemolysis, elevated liver enzymes, and low platelets compared with control pregnant women and those with uncomplicated pregnancy-induced hypertension. Analysis of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels in longitudinal profiles of pregnant women identified significantly elevated levels of these molecules in the plasma of preeclampsia-prone women 3 to 15 weeks before the onset of clinical symptoms. CONCLUSION: Elevated soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 measurements during pregnancy can be considered as major risk factors. Elevated levels of these substances in the plasma of pregnant women with preeclampsia support the concept of a primary endothelial cell involvement in the pathogenesis of preeclampsia. Although currently based on a limited database, significantly elevated levels of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the plasma of otherwise healthy pregnant women suggest a very high predictive value of these molecules for the earliest identification of women at risk of developing preeclampsia.

Biomarkers↗

PubMed1997

Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: a new prognostic factor.

Ovarian cancer is the leading cause of death in gynecological cancers. To date, there are no prognostic factors in ovarian cancer that adequately account for tumor biology and the course of the disease. In recent years, some reports have described the prognostic significance of the amplification and overexpression of the oncogene c-erbB-2 (HER2/neu) in various human cancers, including ovarian cancer. The c-erbB-2 proto-oncogene is located on the long arm of chromosome 17. It encodes a 185 kD transmembrane glycoprotein receptor (p185HER2) that has sequence similarities with the epidermal growth factor receptor (EGF-R). In ovarian cancer, the percentage of c-erbB-2 positive cases varies from 9 to 32%. Correlation with tumor stage and the degree of histological differentiation was not observed. The overexpression of c-erbB-2 is a new and statistically independent prognostic factor. The overexpression of oncogene c-erbB-2 in ovarian cancer can-be detected by immunohistochemistry staining for the protein p185 and characterizes a group with unfavorable tumor biology and a significantly worse prognosis. Elevated serum levels of the c-erbB-2 oncoprotein have been identified in patients with various cancers known to overexpress the c-erbB-2 oncogene. The detection of a p185 oncoprotein fragment in the sera of ovarian cancer patients was recently published by our group. Antiproliferative effects of monoclonal antibodies directed against p185 have been demonstrated in breast cancer patients. This may lead to a new approach in ovarian carcinoma therapy, too, over and above the diagnostic aspects.

Female↗