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Biomedical subjects

M Wagner

Publications and source records attributed to M Wagner.

At least 343 records · Page 19Linked to original sources
PubMed1998

The public health versus clinical approaches to maternity services: the emperor has no clothes.

This paper explores the conflict between practice based on science, or based on peers, and between the recommendations of public health agencies and the recommendations of organizations of clinicians, with specific reference to maternity services. The WHO European Regional Office, as a public health agency, has been bringing to the attention of the public and of governments two serious problems brought about by the present hegemony of the clinical approach: (1) The reliance on standards of practice rather than scientific evidence, and (2) Having doctors decide health policy, leading to the failure to honour the self-determination of the individual and family and basic human reproductive rights.

Decision Making, Organizational↗
PubMed1998

Coding of time-varying hormonal signals in intracellular calcium spike trains.

In a variety of cell types extracellular hormonal stimuli varying in time are transfered across the cell membrane into repetitive spikes of the intracellular calcium concentration ([Ca2+]i). Distinct temporal patterns of [Ca2+]i spikes are capable of regulating the function and structure of target cells. Here, we investigate the ability of transmembrane signaling to encode time-varying hormonal stimulations (bandlimited Gaussian white noise) in a model of receptor-controlled [Ca2+]i oscillations. The encoding of hormonal signals in [Ca2+]i spike trains is quantified by using an information-theoretic approach allowing to estimate the hormonal stimulus from [Ca2+]i spike trains. Our results suggest that intracellular [Ca2+]i spike trains convey faithful information on temporal variations of extracellular hormonal concentrations at scales of 30-200 sec, corresponding to cut-off frequencies between 5 and 30 mHz of the random hormonal stimulation.

Animals↗
PubMed1998

[Bilateral ischemic optic neuropathy secondary to acute ergotism].

We report a case of a 31 year-old man who presented a bilateral ischemic optic neuropathy associated with headaches and severe systemic hypertension. This episode appeared after administration of ergotamine tartrate and macrolides. This medication probably led to a vasospasm which occurs in patients with hypertension. The cardiovascular and serum lipid evaluations were normal. A migraine optic neuropathy can be evoked.

Adult↗
PubMed1998

[MRI aspects of spinal cord abscesses. Report of 5 cases and review of the literature].

The spinal canal is an uncommon site for abscess formation resulting from bloodstream disseminated infection. Prognosis is often unfavorable. Rapid treatment is essential for satisfactory neurological recovery. Abscesses within the spinal canal are thus diagnostic and therapeutic emergencies. The neuro-infectious and inflammatory manifestations and laboratory findings vary considerably and are insufficient for diagnosis. MRI plays a decisive role. The most commonly reported signs are the presence of an intramedullary collection giving a low-intensity signal on T1-weighted images and a high-intensity signal on T2-weighted images with peripheral contrast uptake and generally extended adjacent medullary edema. We report here five cases of spinal canal abscesses diagnoses with MRI at different stages of development (pre-suppurative myelitis in two cases, constituted abscess in three cases). For each case we reviewed the clinical course and describe the details of the imaging findings. In our series, the collected abscesses presented as round lesions within the canal with contrast uptake. It is noteworthy that the periependymal gray matter adjacent to the lesion also took up the contrast agent in all patients with a collected abscess. This sign has not been described previously and appears to be a going argument orienting the diagnosis towards an infectious rather than tumoral formation.

Abscess↗
PubMed1998

[Uveitis in Whipple disease: Identification of Trophyrema whippelii by PCR].

Whipple's disease is a multisystem bacterial disease usually characterized by malabsorption, diarrhea and polyarthritis. Ocular manifestations include uveitis, vitreitis, retinis, myositis, papilledema and optic atrophy. We report a case of a chronic bilateral vitreitis in a 63 year-old man who had been treated for a Whipple's disease with gastrointestinal involvement 30 years before. The jejunal biopsy was negative but the polymerase-chain-reaction (PCR) revealed the presence of Trophyrema Whippelii in the vitreous prelevement of both eye. This new, original strategy of PCR is specific and more sensitive than histological diagnosis.

Actinomyces↗
PubMed1997

Fast visual evoked potential input into human area V5.

Studies of the human visual cortex have demonstrated that an area for motion processing (V5) is located in the lateral occipito-temporal cortex. To study the timing of arrival of signals in V5 we recorded multi-channel visual evoked potentials (VEPs) to checkerboard stimuli. We then applied dipole source analysis which was computed on a grand average of 10 subjects, and on five individual subjects, respectively. We demonstrate an early VEP component with onset before 30 ms and with a peak around 45 ms, located in the vicinity of V5. This early component was independent of a second activity, which started around 50 ms and peaked around 70 ms, and was located within the striate cortex (V1). These results provide further evidence for a very fast input to V5 before activation of V1.

Adult↗
PubMed1997

Influence of freeze-concentration effect on proteinase-catalysed peptide synthesis in frozen aqueous systems.

Freezing of the reaction mixture is a powerful tool in proteinase-catalysed peptide synthesis. In this study, the considerable yield-increasing effect of freezing has been analysed by physical and analytical methods. 1H-NMR relaxation time measurements have been used to determine the amount of unfrozen water in partially frozen systems thus quantifying the extent of the 'freeze concentration effect' for the first time. Comparative studies in ice and at room temperature verify the importance of freeze-concentration which, however, is not sufficient for a complete understanding of the observed effects. Furthermore, the phase behaviour of frozen systems is discussed.

Catalysis↗
PubMed1997

The CDK-activating kinase CAK1 can dosage suppress sporulation defects of smk1 MAP kinase mutants and is required for spore wall morphogenesis in Saccharomyces cerevisiae.

Mitogen-activated protein (MAP) kinase pathways are evolutionarily conserved kinase cascades that are required for the response of eukaryotic cells to a wide variety of environmental stimuli. MAP kinase pathways are also required for the execution of developmental and differentiative programs in a variety of cell and tissue types. SMK1 encodes a developmentally regulated MAP kinase in yeast that is required for spore wall morphogenesis. Cyclin-dependent kinase-activating kinases (CAKs) phosphorylate a conserved threonine residue in the activating loop of cyclin-dependent kinases. CAK1 encodes the major CAK activity in yeast and is required for cell cycle progression. The work presented here demonstrates that CAK1 functions positively in the spore wall morphogenesis pathway. First, CAK1 has been isolated as a dosage suppressor of a conditional smk1 mutant that is defective for spore wall morphogenesis. Second, CAK1 mRNA accumulates during spore development contemporaneously with SMK1 mRNA. Third, cak1 mutant strains have been isolated that are able to complete meiosis I and II but are specifically defective in assembly of the spore wall. These results show that cell cycle progression and morphogenetic pathways can be regulated by a single gene product and suggest mechanisms for coordinating these processes during development.

Alleles↗
PubMed1997

Human herpesvirus-6 (HHV-6)-associated necrotizing encephalitis in Griscelli's syndrome.

We report a male caucasian German pediatric patient of no Arab or Mediterranean ancestry with virus associated CNS lesions in Griscelli's syndrome (GS; McKusick No. 214450). The boy presented with recurrent infections, and meningitis with subsequent progressive signs of increased intracranial pressure leading to death at 32 weeks of age. At autopsy, various sites of the CNS revealed necroses in gray and white matter. CNS histology revealed numerous and massive predominantly perivascular CD8 positive lymphohistiocytic infiltrates. These findings were associated strictly with the presence of human herpesvirus-6 (HHV-6) genome or the HHV-6 specific late antigen H-AR 3, found in neurons, oligodendrocytes, and astrocytes. The search for HHV-6 replication dependent antigen, HHV-7 DNA, CMV, adenovirus, Coxsackie B1, B2, and B4-antigens, and mycobacteria was not successful. Detection of viruses was attempted using immunohistochemistry, in situ hybridization or nested polymerase chain reaction, respectively. Lymphocyte typing was carried out immunohistochemically. In GS, virus induced CNS damage does not seem to require necessarily active virus replication. It may also appear as a consequence of an immune reaction triggered by antigen expression.

Antigens, Viral↗
PubMed1997

Pharmacokinetic/pharmacodynamic evaluation of systemic effects of flunisolide after inhalation.

The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of charcoal. A placebo group was used to assess the endogenous cortisol, granulocyte, and lymphocyte baseline levels. Flunisolide plasma levels were determined by high-performance liquid chromatography using a tandem mass spectrometer as detector (HPLC/MS/MS). Cortisol plasma levels and differential white blood cell counts were obtained over 12 hours. An integrated pharmacokinetic/pharmacodynamic (PK/PD) model was applied to link the flunisolide plasma concentrations with the effects on lymphocytes, granulocytes, and cortisol. Maximum concentration levels of 3 to 9 ng/mL of flunisolide were observed after 0.2 to 0.3 hours for all of the investigated doses. The terminal half-life ranged from 1.3 to 1.7 hours. There was no statistical difference between treatments in the presence or absence of orally administered charcoal. The pharmacokinetic/pharmacodynamic (PK/PD) models satisfactorily described the time-courses of the effects on granulocytes, lymphocytes, and cortisol suppression. The resulting E50-values (concentrations to induce 50% of the maximum effect) concurred with the reported values of in vitro receptor binding affinities. The duration of the systemic effects were short because of the short half-life of the drug. Cumulative cortisol suppression increased with dose administration and ranged from 20% to 36%. The PK/PD simulations resulted in a smaller degree of cortisol suppression for the drug administered at 10 PM. The cumulative change from baseline was slightly smaller for the effects on granulocytes and lymphocytes than those on cortisol. This information promotes the comparison with other inhaled glucocorticoids.

Administration, Inhalation↗
PubMed1997

Dependency of cortisol suppression on the administration time of inhaled corticosteroids.

Endogenous cortisol suppression is one of the major systemic side effects of inhaled corticosteroids in the treatment of asthma. A previously developed pharmacokinetic/ pharmacodynamic approach was used to evaluate the influence of administration time on the cumulative cortisol suppression (CCS) after single doses of the inhaled corticosteroids flunisolide and fluticasone propionate. Administration time-dependent simulations of CCS were performed with drug-specific pharmacokinetic and pharmacodynamic parameters obtained from previous clinical trials. Both drugs showed similar diurnal variation in CCS, dependent on the administration time, with maximum suppression when administered in the early morning at approximately 3 AM. The optimum administration time for minimized CCS was in the afternoon but was shifted from 3 PM for fluticasone propionate to later time points around 7 PM for flunisolide, probably because of the shorter terminal elimination half-life of flunisolide. Regarding peak to trough fluctuation, however, CCS after fluticasone propionate showed only half the administration time dependency as after flunisolide. Therefore, the ratio between CCS after flunisolide and after fluticasone propionate also followed administration time-dependent variations. This led to the conclusion that administration time has to be considered as a pivotal influential factor in clinical studies comparing CCS among different inhaled corticosteroids.

Administration, Inhalation↗
PubMed1997

Is OVX1 a suitable marker for endometrial cancer?

The single most common cause leading to the diagnosis of endometrial cancer is postmenopausal bleeding. Although most patients with early-stage disease (FIGO stage I and II) can be cured, prognosis worsens considerably with increasing stage. While serum CA 125 levels are elevated only in a significant proportion of patients with advanced disease, recently a new serum marker (OVX1) for the detection of early-stage endometrial cancer was reported. Serum OVX1 levels were measured using an OVX1 radioimmunoassay (RIA) or enzyme immunoassay (EIA) in 192 patients with endometrial cancer. CA 125 levels were measured in 112 patients using the CIS ELSA CA 125 kit. Apparently healthy females had mean serum OVX1 levels measured with the OVX1-EIA of 1.34 +/- 0.74 U/ml, while patients with endometriosis had mean OVX1 serum levels of 3.15 +/- 2.45 U/ml. The mean OVX1 serum level for endometrial cancer patients was 2.00 +/- 1.32 U/ml. These values were 2.76 +/- 1.62, 6.10 +/- 4.66, and 5.37 +/- 3.49, respectively, using the OVX1-RIA assay. Applying a cutoff value of 2.8 U/ml, serum OVX1-EIA levels in endometrial cancer patients were increased in 25 of 127 patients (19.7%) with stage I disease, 5 of 17 patients with stage II (29.4%), 5 of 22 patients (22.7%) with stage III, and 4 of 11 patients (36.4%) with stage IV disease. Using the OVX1-RIA and a cutoff of 7.2 U/ml, serum levels were increased in 22 of 127 (17.3%) stage I, 6 of 17 (35.3%) stage II, 5 of 22 (22.7%) stage III, and 6 of 11 (54.5%) stage IV patients. Serum CA 125 levels, determined in a total of 112 patients, were elevated above 35 U/ml in 12 of 79 patients (15.2%) with stage I, 4 of 12 patients (33.3%) with stage II, 8 of 13 patients (61.5%) with stage III, and all of 8 patients (100%) with stage IV disease. While a good correlation between serum CA 125 levels and the clinical stage of the disease was found, no correlation could be detected for OVX1 and stage.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1997

[99mTc-MDP-SPECT for detection of subclinical mandibular infiltration of squamous epithelial carcinoma].

UNLABELLED: A prospective study was performed to compare the sensitivity and accuracy of ultrasound (US), computed tomography (CT), and single photon emission computed tomography (SPECT) as a bone scan to detect subclinical invasion of the mandible by squamous cell carcinoma of the oral cavity and floor of mouth. METHODS: The present study reports data on 35 patients with squamous cell carcinoma of the oral cavity. SPECT, mandibular orthopantomography (OPG), US, CT and magnetic resonance imaging (MRI) were performed as well as histologic examination of resected mandibles. Transverse slices of 12 mm thickness were reconstructed for SPECT and semi-quantitative assessment of radionuclide uptake was performed with a scoring system based on comparisons of tracer uptake in the mandible to that in an unaffected part of the mandible. Lesion to non-lesion count ratios in the mandible in 3 h SPECT images were calculated. OPG, US and CT were evaluated for comparison. RESULTS: In 12/35 patients, histologic examination showed carcinoma infiltrating mandibular bone. SPECT correctly predicted mandibular invasion in 11/12 cases, with no false-positive results. CT detected correctly 3/12 lesions, while OPG and ultrasound each demonstrated 2/12 tumors. CONCLUSION: Bone SPECT was found to provide an accurate means for assessing tumor invasion to the mandible by intraoral squamous cell carcinoma. As a complementary study to one of the other imaging modalities it was shown to have a high specificity, indicating that it should be performed routinely in patients with suspect mandibular bone involvement by causes.

Adult↗
PubMed1997

[Dementia in the very elderly. Results of the Berlin Aging Study].

The frequency of dementia in very old subjects, the risk factors and the consequences of the disease were investigated in the Berlin Aging Study in an age- and gender-stratified design (ages 70-103 years, n = 516). Psychiatrists diagnosed a dementia syndrome according to DSM-III-R, applying the GMS-A and HAS interviews. The dementia frequency steeply increases until the 90-94 year group, but there is no further exponential increase for the 95+ group--instead for men the data show a plateau of dementia prevalence. Low education level turned out to be a risk factor, which explains the gender effect in a logistic regression analysis. The apolipoprotein E4 genotype was confirmed as a risk factor--however, only for the older subjects (85+). Dementia was a major reason for institutionalization. The 2-year mortality was no higher in dementia than for age-matched non-demented controls. The results gave a detailed picture of dementia in the very old. This is a prerequisite for planning facilities for psychiatric diagnostics and therapy as well as nursing care.

Aged↗
PubMed1997

Inverse localization of electric dipole current sources in finite element models of the human head.

The paper describes finite element related procedures for inverse localization of multiple sources in realistically shaped head models. Dipole sources are modeled by placing proper monopole sources on neighboring nodes. Lead field operators are established for dipole sources. Two different strategies for the solution of inverse problems, namely combinatorial optimization techniques and regularization methods are discussed and applied to visually evoked potentials, for which exemplary results are shown. Most of the procedures described are fully automatic and require only proper input preparation. The overall work for the example presented (from EEG recording to visual inspection of the results) can be performed in roughly a week, most of which is waiting time for the computation of the lead field matrix or inverse calculations on a standard and affordable engineering workstation.

Cerebral Cortex↗
PubMed1997

Dynamic blood cell contact with biomaterials: validation of a flow chamber system according to international standards.

The increasing number of patients requiring prosthetic substitution of segments of the vascular system strongly supports the need to optimize a relevant, standardized testing panel for new materials designed for synthetic vascular prostheses. The ISO gives the standard requirements for testing biomaterials provided for implantation. Our primary interest was the establishment of a reliable in vitro panel as a useful and relevant screening system for vascular implant devices to evaluate blood/device interactions under flow conditions. The aim of the present study was to evaluate influences of different flow conditions on blood cell-biomaterial interactions with special emphasis on the interactions of human granulocytes (PMN) and polymeric surfaces. PMN were isolated and vital cells were quantified by flow cytometrical analysis directly before, as well as immediately after the experiments. The viscosity of the final cellular suspension was analysed by using a computerized cone-plate rheometer. As reference materials we used FEP-teflon, PVC-DEHD, PU, PP and PE. Dacron and ePTFE synthetic vascular protheses were tested in a comparative way to those references. The adhesion processes were observed over a period of 40 minutes under arterial (shear stress 0.74 Pa) and venous (shear stress 0.16 Pa) flow conditions in a parallel plate flow chamber system under highly standardized conditions and laminar flow. The cells were observed with the help of inverse light microscopy. Cell behaviour was recorded and analysed in both analogue (video) and digital (imaging system) modes. Samples of the cell suspensions were obtained at regular time intervals and analysed by enzyme linked immuno sorbent assay (ELISA) to quantify LTB4 release. Irrespective of the material, approximately 3 to 4 times more PMN adhered to the biomaterial surfaces under venous flow conditions compared to the arterial. Shear intensity did not influence the running order of biomaterials with respect to cell numbers. This response in descending order at the end of the experiments was as follows: PU, PVC-DEHD, PP, PE and ePTFE. The biochemical analyses indicate that in the system used only a weak effect on LTB4 release induced by the different materials could be determined. A significant effect caused by flow conditions was not observed. Further experiments, both static as well as dynamic, must be performed for multiple, relevant parameters of haemocompatibility, for potential biomaterials as well as those currently in use in vascular prostheses.

Journal Article↗