Search PubMed⌕ Search

Biomedical subjects

E Werner

Publications and source records attributed to E Werner.

At least 37 records · Page 2Linked to original sources

Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension.

BACKGROUND & AIMS: Angiotensin II receptor antagonists have been proposed as new drugs for portal hypertension. This randomized, placebo-controlled, double-blind study aimed to assess the effect of the angiotensin II receptor antagonist irbesartan on portal and systemic hemodynamics and renal function in patients with cirrhosis. METHODS: Thirty-six patients with cirrhosis and portal hypertension received 150 mg/d irbesartan or placebo for 1 week. Systemic hemodynamics, kidney and liver function parameters were recorded regularly; hepatic venous pressure gradient and plasma renin were assessed on days 0 and 7. RESULTS: Irbesartan reduced the hepatic venous pressure gradient by 12.2% +/- 6.6% (P < 0.05) and mean arterial pressure by 5.3% +/- 4.0% in 13 of 18 verum patients. In 4 (22%) verum patients, arterial hypotension, accompanied by significant renal impairment, required withdrawal of irbesartan. In these patients, baseline plasma renin (P < 0.002) and cystatin C (P < 0.001) levels were higher, and creatinine clearance (P < 0.02), serum sodium (P < 0.01), and albumin (P < 0.05) were lower than in patients who tolerated irbesartan. Four of five patients with baseline renin >900 microU/mL developed treatment-limiting hypotension. CONCLUSIONS: The angiotensin II receptor antagonist irbesartan is not advisable in patients with advanced cirrhosis and high plasma renin because it may induce arterial hypotension and only moderately reduces portal pressure.

Angiotensin Receptor Antagonists↗

[Management of a deaf-blind patient with a 12-channel cochlear implant].

A case study of a deaf-blind patient implanted with the COMBI40+ cochlear implant is presented. The patient is a 70-year-old woman who has been blind since the age of 40. Since 1977 the hearing loss continuously increased. Before surgery she had a very small residual hearing (with hearing aid: 40% speech intelligibility by four syllable numbers) and she used Braille and finger-spelling on her hand to communicate with other people. The patient has a high intelligence and so she did not have any problems when the speechprocessor was fitted and during the hearing therapy. After one month she had an open-set-speech recognition. The quality of her life is much better than before surgery. The communication by finger-spelling on her hand is not necessary any longer.

Aged↗

Kinetics of systemic ruthenium in human blood using a stable tracer.

The biokinetics of ruthenium after oral and intravenous administration has been investigated in two human subjects using the stable isotope 101Ru as a tracer. Tracer concentrations in blood plasma have been determined using activation analysis with protons. The results presented here prove that the stable tracer technique is a valuable tool for obtaining relevant information about the biokinetics of ruthenium in humans. From these pilot studies, it may be argued that the clearance of systemic ruthenium from plasma is significantly slower than the predictions of the biokinetic model currently recommended by the International Commission on Radiological Protection (ICRP). The experimental data for the orally administered tracer, which reflect the gastrointestinal absorption process, differ from the curve derived from the ICRP model, suggesting that the uptake into the systemic circulation may be lower than predicted. On the basis of these preliminary data, investigations on a larger number of subjects with improvements in the experimental design are scheduled.

Administration, Oral↗

The use of three-dimensional ultrasound for thyroid volumetry.

Conventional two-dimensional (2-D) ultrasound is the standard method for the investigation of thyroid morphology. Volume calculations need model assumptions and are observer dependent. The present study performed with a commercially available three-dimensional (3-D) system Freescan added to a conventional ultrasound scanner compares the accuracy of conventional thyroid volumetry to several methods of 3-D volume determination. In vitro measurements were performed on thyroid phantoms with known volumes. The standard deviation of the normalized differences was 8.0% (3-D segmentation) and 10.5% (conventional). For the accuracy of volume determination in human thyroids we performed a postmortem study. The thyroid volume was calculated conventionally by the ellipsoid model and by two 3-D methods (segmentation and the newly developed multiplanar volume approximation). The reference volume was determined after resection by submersion. The standard deviation of the normalized differences was 26.9% for the conventional method, 9.7% for 3-D segmentation and 11.5% for the multiplanar volume approximation, showing significant better results for both 3-D methods and no significant difference between the 3-D methods. The 3-D system, therefore, achieves a better accuracy for thyroid volumetry than the conventional volumetry using planar images. In addition, the 3-D images are stored electronically and can be used for follow-up studies.

Cadaver↗

Phagocytosis mediated by Yersinia invasin induces collagenase-1 expression in rabbit synovial fibroblasts through a proinflammatory cascade.

We show that the interaction of the Yersinia surface protein, invasin, with rabbit synovial fibroblasts mediates bead phagocytosis and induces expression of interleukin 1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha) and MMP-1/collagenase-1 (CL-1). Presentation of invasin as a ligand on the surface of 4.5 microm beads induced phagocytosis and increased CL-1 expression 20-fold after 24 hours. By contrast, presentation of invasin as a spreading substrate did not induce CL-1 expression. CL-1 induction following phagocytosis of invasin-coated beads was mediated by a mechanism dependent on high-affinity binding to beta1 integrins and the function of the small GTPase RhoA. Expression of a function-perturbing mutant, RhoAN19, abrogated bead-induced CL-1 expression. RhoA activation coupled bead phagocytosis with signal transduction because expression of constitutively active mutant RhoV14 was sufficient to trigger CL-1 expression. The signal-transduction cascade elicited by bead phagocytosis triggered NFkappaB activation, stimulating a proinflammatory cellular response with transient increases in TNF-alpha production that peaked at 2 hours and induction of IL-1alpha that was sustained for at least 10 hours. Inhibition of IL-1alpha function by blocking antibodies or IL-1 receptor antagonist showed that IL-1alpha is the autocrine intermediary for subsequent CL-1 induction.

Adhesins, Bacterial↗

Determination of biokinetic parameters for ingestion of radionuclides of zirconium in animals using stable tracers.

Exposure to the radioactive isotope 95Zr, as in nuclear accidents, and to stable zirconium, due to its use in industry, has increased the interest in the biokinetics of this element. Information has been derived mainly from tests performed on animals by means of radioactive tracers. Due to the fact that extrapolation from animals to humans is always open to question, there is an increasing need of a methodology which allows data to be obtained directly from humans. The use of stable tracers, being ethically justifiable, is a powerful tool for providing this information. As two tracers of the same element must be utilized in order to evaluate gut absorption, an analytical technique which is capable of distinguishing and measuring simultaneously different isotopes of zirconium in biological samples is required. Preliminary tests on laboratory animals were performed in order to assess the feasibility of the double tracer technique combined with proton activation analysis.

Animals↗

First hints for a correlation between amplification of the Int-2 gene and infection with human papillomavirus in head and neck squamous cell carcinomas.

Infection with human papillomavirus (HPV) and alterations in certain genes have frequently been proposed as mechanisms in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we investigated 47 HNSCC for the presence of HPV and, by fluorescence in situ hybridisation, for amplification of Int-2 and Hst-1 in the search for a possible correlation. The highest frequency of HPV infection was found in hypopharyngeal carcinomas, while amplification of Int-2 or Hst-1 was distributed more equally among the different localisations. Amplification of Int-2 was detectable (7 of 9 cases) in 78% of the HPV-positive carcinomas, whereas no virus infection could be found in the five cases with amplified Hst-1 only. In spite of the rather low number of infected tumour samples, our results suggest a correlation between HPV infection and amplification of Int-2.

Adult↗

Internal biokinetic behaviour of molybdenum in humans studied with stable isotopes as tracers.

Although molybdenum is considered to be an essential trace metal for humans, the knowledge about its metabolism is rather limited. The present study was aimed at the assessment of biokinetics following intravenous injection of trace amounts of 95Mo or 96Mo into five healthy volunteers. In a total of 11 investigations, the plasma clearance up to eight hours and the urinary excretion for at least three days after the injection were evaluated. The tracer concentrations were determined by proton nuclear activation analysis in blood plasma and by thermal ionization mass spectrometry in urine samples respectively. In all subjects, the plasma clearance is much faster than expected from the literature. The data obtained for the plasma clearance of the tracer can reasonably be fitted by a two exponential equation. The half times of the fast component range between 4 and 70 minutes and for the slow component between 3 and 30 hours. The urinary excretion of the injected tracer seems also to be faster than expected and the fractions lost are higher for larger doses administered. For the smallest dose given, 34% of the injected tracer were excreted within one day whereas for the four times larger dose about 60% were lost. These findings on urinary excretion are in agreement with recently published results.

Adult↗

A novel chimeric mitochondrial RNA localized in the nucleus of mouse sperm.

Six identical cDNA clones corresponding to an RNA of 1685 nucleotides that is enriched in mouse sperm compared with testis were isolated from a mouse testis cDNA library. The sequence of these clones corresponds to the 16S mitochondrial RNA plus an inverted repeat of 120 bp covalently joined to the 5' end of the RNA. By RT-PCR, it was demonstrated that this transcript, referred to as chimeric RNA, was present in mouse sperm, testis, liver, kidney, brain, and spleen. The absence of an equivalent sequence in mitochondrial DNA or as a mitochondrial pseudogene in total DNA extracted from sperm, testis, and somatic tissues suggests that the chimeric RNA is a post-transcriptional product, maybe resulting from a trans splicing reaction. The chimeric RNA was found by RT-PCR in total RNA extracted from purified sperm heads. This result was confirmed by in situ hybridization, which showed clear staining of the sperm nucleus with probes corresponding to sequences of the mitochondrial 16S RNA and the inverted repeat.

Animals↗

Internal dose for ingestion of molybdenum radionuclides based on a revised biokinetic model.

Recent investigations with human volunteers showed that the model recommended by ICRP for the description of the biokinetics of molybdenum radionuclides is not able to describe some characteristic features, like the clearance from the transfer compartment and the urinary excretion profile. Therefore, a revision of the model was presented in a previous paper. In the current work, dose coefficients for ingestion of radionuclides of molybdenum from members of the public have been calculated according to the ICRP guidelines, but using the revised biokinetic model. The results obtained for the effective dose do not differ remarkably from the ICRP estimates. However, considerable deviations are observed for the equivalent dose to some individual organs; for example, the dose coefficient for colon after ingestion of 99Mo in solid form is about 7 times higher than the ICRP value, whereas for other organs the new estimates are about one tenth of the ICRP ones. This fact could be of importance with respect to deterministic effects to particularly radiosensitive organs.

Adult↗

Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis.

Sialorrhoea is a socially disabling problem in bulbar amyotrophic lateral sclerosis (ALS). Botulinum toxin A (BoNT/A) was injected into the salivary glands in five patients with bulbar ALS and sialorrhoea. The effect of BoNT/A was measured by the number of paper handkerchiefs used each day and by salivary gland scintigraphy. BoNT/A ameliorated sialorrhoea and quality of life without major adverse effects. BoNT/A may be a relatively safe and effective treatment for sialorrhoea in selected patients.

Aged↗

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg].

AIM: In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. PATIENTS AND METHODS: In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. RESULTS: 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). CONCLUSION: A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

Adult↗

Detection of myocardial viability by low-dose dobutamine Cine MR imaging.

The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for predicting recovery of regional myocardial contractility after revascularization. Cardiac wall motion abnormalities are due to either non-viable and/or scarred, or viable, but hibernating, myocardial tissue. Dobutamine stress leads to increased systolic wall thickening only in viable myocardium. Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress (10 microg/kg/min). Patients were re-examined at rest 3, and in case of persisting wall motion defects, 6 months after revascularization. Criterion of viability was increasing end-systolic wall thickening during stress and/or at follow-up. Akinetic regions related either to the LAD (n = 19) or to the RCA (n = 6) were judged viable if > or = 50% of the affected segments improved. MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms. Sensitivity, specificity, and positive predictive value for the prediction of myocardial viability were 61%, 90%, and 87% for the segment-related analysis, and 76%, 100%, and 100% for the patient-related analysis based on coronary artery distribution, respectively. Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity.

Adult↗

Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants.

OBJECTIVE: To study the pharmacokinetics of flunitrazepam (used for sedation in neonates and infants), to determine the influence of both gestational and postnatal age on the pharmacokinetic parameters, and to analyze the relationship between the hemodynamic parameters and flunitrazepam plasma concentration. METHODS: Flunitrazepam was infused for 20 minutes as a single dose (0.2 mg x kg(-1)) and as multiple doses (0.1 mg x kg(-1)). Six to eight 1-mL blood samples were collected per patient. Flunitrazepam plasma concentration was measured by gas chromatography-mass spectrometry. RESULTS: Thirty-one patients (25 neonates and six infants) were included in the study. Only three of them received multiple doses. After the single dose (n = 28), half-life was 22.6 +/- 7.3 hours, clearance was 0.15 +/- 0.14 L x kg x h(-1), and volume of distribution was 4.6 +/- 4.1 L x kg(-1) (mean +/- SD). Plasma clearance and volume of distribution significantly increased with postnatal age (P < .05), but no pharmacokinetic parameter varied significantly with gestational age. Diastolic blood pressure significantly decreased with increasing flunitrazepam plasma concentrations (P < .05). CONCLUSION: Postnatal age but not gestational age influenced flunitrazepam pharmacokinetic parameters in neonates and infants. Diastolic blood pressure was inversely correlated to flunitrazepam plasma concentration.

Age Factors↗

[Drug therapy of sleep apnea syndromes: results of short-term treatment with theophylline].

BACKGROUND: In the treatment of obstructive sleep apnoea syndrome (OSA) nasal ventilation therapy (nCPAP) and various surgical strategies like uvulopalatopharyn-goplasty proved effective. However, not all patients can be successfully treated with these therapies. In our study we investigated the effects of oral theophylline taken at night in patients with OSA. PATIENTS AND METHODS: 50 patients with polysomnographically verified OSA were enrolled in two groups in this study. In the therapy group we administered 300-500 mg of oral theophylline at night for 4-22 weeks. In all patients nCPAP therapy was indicated in the beginning of the trial. RESULTS: We found a positive effect of theophylline treatment in patients with a comparatively low apnoea-hypopnoea index, low overweight and inconspicuous status of the upper airways. In 5 cases the initially indicated nCPAP treatment could be cancelled. In the therapy group the number of apnoea and hypopnoea was reduced by 17.08%. The mean apnoa duration and the time of sleep with an oxygen saturation below 90% was reduced by 8.41% and 19.58%, respectively. In the control group we found an increase in apnoeas and hypopnoeas by 10.48%. Apnoea duration and desaturation time increased by 4.71% and 11.04%, respectively. Comparison of the effects between the two groups using the Wilcoxon 2-sample test proved to be statistically significant. Besides these positive effects we found 27.2% non-responders. CONCLUSION: Theophylline has a short-term relevant beneficial effect only on patients with mild OSA. Because of the limited beneficial effects, permanent theophylline treatment has to be monitored regularly via control polysomnography. Under certain conditions noctural oral administration of theophylline may supplement conventional therapy strategies.

Administration, Oral↗