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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 523 records · Page 29Linked to original sources
PubMed1995

Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction.

The aim of our study was to determine the prevalence of the factor V mutation (position 1691 G-->A) in patients with angiographically diagnosed coronary artery disease and myocardial infarction and, as a control, in blood donors. This mutation has already been proved to be the main genetic risk factor for venous thrombosis. In order to detect this mutation in exon 10 of the factor V gene we established a microtiter plate based hybridization assay for the specific detection of wild-type and mutant sequences in factor V gene segments, obtained after amplification by polymerase chain reaction. This test enables us to screen a large number of samples. The mutation was detected in 29 of 317 coronary artery disease (CAD) patients (9.1%) and 18 of 190 blood donors (9.5%) investigated. The mean activated protein C resistance ratios were 3.18 and 3.11, with nearly identical distribution. No increased prevalence of the factor V mutation was found in the CAD group. In 10 of 29 CAD patients (35%) with the factor V 1691 G-->A mutation and in 124 of 288 CAD patients without the mutation (43%) there was a history of myocardial infarction. From our data we conclude that there is no increased risk of developing coronary atheroma or consecutive myocardial infarction resulting from the factor V mutation with protein C resistance.

Adenine↗
PubMed1995

The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML--a comparative morphometric study on sequential trephine biopsies.

To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph(1+)-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.

Adolescent↗
PubMed1995

Course of patients diagnosed as having schizophrenia during first episode occurring under age 18 years.

Of 118 child and adolescent schizophrenic patients (ICD-9: 295.x; mean onset age 16.0 years), 97 (82.2%) could be completely investigated at follow-up (mean interval 7.4 years; mean age 23.1 years). At follow-up 30% of the patients were semi-dependent or dependent, 72% still required psychiatric treatment, 44% were at least moderately impaired with regard to educational/occupational functions and 58% with regard to social functions; 73% had experienced at least one further schizophrenic episode. Comparison with schizophrenia beginning in adulthood showed that the impairment in social function was much greater in the younger group of patients. These results support the belief that schizophrenic psychoses starting in adolescence have a worse outcome than those beginning in adulthood. The most efficient indicators for a worse outcome were long duration of inpatient treatment at first admission, a high number of symptoms and low social competence at discharge.

Adolescent↗
PubMed1995

Embryogeny of oxygen consumption in 13 altricial and precocial birds.

The embryogeny of O2 consumption (VO2) was examined in 6 altricial and 7 precocial bird species (egg mass: 1.13 to 330 g). The 13 species studied were measured in most cases daily, some of them were continuously measured for 24 hours. 10 of 13 species exhibited a clear plateau-phase in about the last fourth of their embryogeny. Mean total energy production during incubation period was 1.83 kJ/g in altricial and 1.77 kJ/g in precocial species. No marked differences concerning the occurrence of a plateau phase could be found in the general course between the two developmental modes. This may reflect the existence of a basically identical course of the embryonic VO2 in the examined bird species.

Animals↗
PubMed1995

A convenient in vitro assay for the inhibition of neurite outgrowth by adult mammalian CNS myelin using immortalized neuronal cells.

The adult mammalian CNS contains molecules which inhibit neurite outgrowth and which may be responsible for the lack of successful axonal regeneration after injuries in the brain and spinal cord. We describe an in vitro assay to measure the ability of primary and established lines of neuronal cells to produce neurites in the presence of CNS inhibitory molecules. The assay is suitable for identification of agents and treatments to overcome neurite growth inhibition. Assays are carried out in 96-well plates with CNS myelin substrates using NG108-15 cells, an immortalized cell line that can be induced to produce extensive neuritic growth. The inhibition of neurite outgrowth by CNS myelin observed in this assay is: (1) observed for NG108-15 cells and also PC12 cells and primary superior cervical ganglion neurons, (2) contact dependent, (3) half-maximal at 5 micrograms/cm2 of myelin, and (4) trypsin-labile. This assay is quantitative, rapid, highly reproducible, convenient and can be used to test compounds which have the potential to overcome the growth inhibitory molecules present in CNS myelin.

Animals↗
PubMed1995

Synthesis and processing of the rubella virus p110 polyprotein precursor in baculovirus-infected Spodoptera frugiperda cells.

In order to study the processing of rubella virus (RV) structural proteins (capsid protein, of 33 kDa; E2 of 42-47 kDa; and E1 of 58 kDa) in Spodoptera frugiperda (fall armyworm) cells, a 24S cDNA encoding the polyprotein precursor, p110, was inserted under the transcriptional regulation of the polyhedrin gene promoter of the Autographa californica nuclear polyhedrosis virus (AcNPV) and expressed during viral infection. By immunoblot analysis using antibodies directed against whole RV and the individual structural proteins, evidence is presented that polypeptides similar to those synthesized in RV-infected B-Vero cells are expressed in this lepidopteran insect cell line infected with the recombinant baculovirus, VL1392-RV24S. The identity of the recombinant proteins was further confirmed using human convalescent sera. By expressing the recombinant proteins in the presence and absence of tunicamycin, we have further demonstrated that the 24S transcription-translation unit of RV, is expressed and proteolytically cleaved similarly, if not identically, in Sf9 cells as compared to B-Vero cells.

Animals↗
PubMed1995

Estrogen and progesterone receptor content of GnRH analogue pretreated and untreated uterine leiomyomata.

OBJECTIVES: The steroid receptor concentration and the histological morphology of uterine leiomyomata in premenopausal patients undergoing myomectomy therapy with and without a preoperative GnRH analogue, was analysed to evaluate whether the GnRH analogue therapy leads to important hormonal receptor changes, histomorphological changes and a significant shrinkage of the leiomyomata. STUDY DESIGN: Sixty-one GnRH analogue pretreated leiomyomata and 28 untreated leiomyomata were analysed. To determine the estrogen and progesterone receptor concentrations, immunohistochemical techniques were used and quantified with the immuno-reactive score (IRS-score). The leiomyomata were divided into cellular rich, normal, hyaline or cystic degenerated and necrotic according to their histology. RESULTS: The GnRH analogue pretreated leiomyomata group showed higher levels of estrogen and progesterone receptors than the untreated group (37.7% of the GnRH analogue group had a high positive and 29.5% a moderate positive estrogen receptor status whereas high levels of estrogen receptor could be found in only 14.3% of the untreated group). The leiomyomata of both groups with the exception of the necrotic ones, were estrogen and progesterone receptor positive. CONCLUSIONS: Our study suggests that pretreatment of uterine leiomyomata leads to a significant increase in the hormonal receptor concentration of these benign tumors. If pretreated leiomyomata are not removed surgically immediately after the therapy, a rapid regrowth can occur and again cause clinical symptoms.

Antineoplastic Agents, Hormonal↗
PubMed1995

Prognostic significance of DNA ploidy in oral squamous cell carcinomas. A retrospective flow and image cytometric study with comparison of DNA ploidy in excisional biopsy specimens and resection specimens, primary, tumors, and lymph node metastases.

Deoxyribonucleic acid ploidy was determined in paraffin-embedded tumor tissue from 116 patients with primary oral squamous cell carcinomas (including 5 carcinomas of the lip and 14 of the tongue) by means of flow cytometry. One hundred six cases were suitable for evaluation (91%). Sixty-eight percent of the cases (n = 72) showed a nondiploid nuclear DNA content. Nondiploidy correlated significantly with presence of lymph node metastases (p < 0.02) but not with tumor stage, grading (World Health Organization), or relapse-free and overall survival. Carcinomas of the lip and tongue turned out to be diploid more frequently than other oral squamous cell carcinomas (p = 0.002). In the 21 cases in which a comparison of DNA content of excisional biopsy specimens and subsequent resection specimens was possible a difference in DNA ploidy was found in one case only. The comparison of primary tumors and their lymph node metastases in 30 cases revealed a discrepancy of DNA content in five cases (17%), which was connected with a shift from nondiploidy to diploidy in four out of five cases. Fifty cases studied in parallel by means of image cytometry with Feulgen-stained tissue sections exhibited a concordance of the ploidy status in 87% and a significant correlation of the DNA index values obtained with both methods (p < 0.01). These results demonstrate that DNA ploidy in oral squamous cell carcinomas is distributed rather homogeneously within the tumors and remains rather stable in the lymph node metastases. Despite a significant correlation between nondiploidy and presence of lymph node metastases, ploidy failed to be a statistically significant parameter for prognosis in oral squamous cell carcinomas in our investigation.

Aneuploidy↗
PubMed1995

A comparative study of the BBL crystal enteric/nonfermenter identification system and the biomerieux API20E and API20NE identification systems after overnight incubation.

The BBL Crystal Enteric/Nonfermenter (Crystal, Becton Dickinson Microbiology Systems) is a new multi-test identification system for Gram negative rods requiring no oil overlay or addition of reagents. One hundred and three selected Gram negative rod isolates from routine clinical specimens were tested in parallel using the appropriate API20E or API20NE (BioMerieux) reading after overnight incubation. The isolates included in the study, and the number tested, were as follows: Acinetobacter sp, 8; Aeromonas hydrophila, 1; Citrobacter diversus, 1; Citrobacter freundii, 1; Escherichia coli, 13; Enterobacter aerogenes, 10; Enterobacter agglomerans, 2; Enterobacter cloacae, 6; Klebsiella oxytoca, 6; Klebsiella pneumoniae, 12; Morganella morganii, 2; Proteus mirabilis, 6; Pseudomonas aeruginosa, 21; Salmonella sp, 2; Salmonella typhi, 1; Serratia marcescens, 1; Shigella sonnei, 2; Shigella sp, 2; Vibrio metschnikovii, 1; Xanthomonas maltophilia, 3; and, Yersinia enterocolitica, 2. The API20E and API20NE systems combined identified 74.8% (77/103) and the Crystal 97.1% (100/103) of isolates. Twenty six isolates required repeat and/or additional tests for correct identification with the API systems compared to 3 with the Crystal. Crystal is more convenient than API for routine clinical use because it requires fewer repeat and/or extra tests, and is easier and less time consuming to use.

Bacterial Typing Techniques↗
PubMed1995

Exogenous surfactant application in respiratory failure due to chronic obstructive pulmonary disease.

Recent results of basic research on regulation of surfactant secretion and surfactant physiology not only in the alveolus but also in peripheral small airways allow the conclusion that disorders in surfactant homeostasis may contribute to the pathophysiology of airway obstruction and hyperinflation. We therefore hypothesized that patients with respiratory failure due to obstructive lung disease may benefit from exogenous surfactant. Here we report a case that indicates the clinical situation to be considered for treatment with exogenous surfactant. The benefit for the patient was successful weaning from the ventilator. Improvements in effective compliance, resistance and blood gas parameters were observed following surfactant application.

Aged↗
PubMed1995

Cardiorespiratory responses to acute hypoxia and hyperoxia in adult and neonatal spontaneously hypertensive and normotensive rats.

The aim of this study was to investigate whether there are differences between particular characteristics of breathing regulation in primary hypertensive and normotensive states which might indicate significant differences in arterial chemoreceptor reflex function. Under air-breathing conditions, minute ventilation was similar in adult spontaneously hypertensive rats (SHR) (50 +/- 2ml/min x 100 g) and in Wistar-Kyoto rats (WKY) (54 +/- 3 ml/min x 100 g) but significantly lower in randomly bred normotensive Wistar rats (NWR) (39 +/- 1 ml/min x 100 g). In seven-day-old rats minute ventilation was 10.5 +/- 1.2ml/min x 10 g in SHR and 10.2 +/- 1.4 ml/min x 10 g in WKY. Our data indicate that there is no elevation of the ventilatory drive under air-breathing conditions which can be unequivocally associated with primary hypertension in adult and neonatal animals. Acute inhibition of ventilation caused by hyperoxia indicated that oxygen dependent peripheral chemoreceptor activity during air-breathing was similar in SHR and normotensive controls both in the unanesthetized neonatal state and in anesthetized adult animals. No well defined association between the characteristics of the hypoxic ventilatory response and primary hypertension could be demonstrated although responses in adult anesthetized SHR tended to be faster and of higher amplitude than in normotensive controls.

Acute Disease↗
PubMed1995

The nuclear membrane-associated honeycomb structure of the unicellular organism Amoeba proteus: on the search for homologies with the nuclear lamina of metazoa.

In the protozoon Amoeba proteus, a complex and highly organized structure with the morphology of a honeycomb is associated with the nucleoplasmic surface of the nuclear membrane. We have tested whether this structure exhibits similarity to the nuclear lamina of metazoic organisms. First, we have shown that the honeycomb layer is composed of 3 to 5 nm thick protein fibrils resistant to treatment with detergent, high salt, and digestion with nucleases, thus possessing properties typical for karyoskeletal elements. However, in contrast to the meshwork of lamin filaments in somatic cells of metazoic organisms, the honeycomb layer is not tightly anchored to the nucleoplasmic side of pore complexes, or to the inner nuclear membrane. Second, in microinjection experiments we investigated whether fluorescently labeled lamins of Xenopus laevis (lamins A and LI) and Drosophila melanogaster (lamin Dmo) were able to associate in vivo with the Amoeba proteus honeycomb structure. In microinjected amoeba these three lamins were efficiently transported into the nucleus, but did not associate with the nuclear envelope. Our results suggest that the Amoeba proteus nuclear envelope, including the honeycomb layer, does not contain proteins exhibiting high homologies to lamins of metazoan species thus preventing the localized assembly of microinjected lamins along the nuclear periphery.

3T3 Cells↗
PubMed1995

Navoban (tropisetron) alone and in combination with dexamethasone in the prevention of chemotherapy-induced nausea and vomiting: the Nordic experience. The Nordic Antiemetic Trial Group.

To evaluate the efficacy and safety of Navoban (tropisetron) three different Nordic multicentre trials were conducted during the period 1988-92. In all, 1050 patients were recruited from 15 centres. In the first study, Navoban monotherapy was compared with a high-dose metoclopramide cocktail. In the second, Navoban +/- dexamethasone was evaluated for those patients not fully protected by Navoban alone. In the third trial, Navoban was evaluated for various chemotherapy regimens, for long-term efficacy, and for various risk groups of patients. Spontaneous intercycle variations were also evaluated. Navoban was found to be as effective as the antiemetic cocktail but with a more favourable spectrum of side effects and a simpler schedule of administration. Navoban was more effective during the acute than the delayed phase. Addition of dexamethasone significantly improved prevention of both acute and delayed emesis. Long term efficacy seemed to be stable up to 10 cycles of chemotherapy. Patients treated with noncisplatin regimens showed significantly higher protection rates than patients treated with cisplatin. Various cancer diagnoses and cytostatic agents were also evaluated. Gender and age were important risk factors. Navoban was found to be an efficacious antiemetic agent, especially regarding acute nausea and vomiting. Addition of a corticosteroid significantly improved the effect during highly emetogenic chemotherapy. The role of Navoban for delayed emesis must be evaluated in future trials. The two most common side effects were headache and constipation. Overall, Navoban was well tolerated and patient compliance with the drug was high.

Antiemetics↗
PubMed1995

[Sarcoidosis of the lung: clinical course and inflammatory activity].

On the whole, sarcoidosis of the lung has a good prognosis with the exception of a few cases where it takes a progressive course. In such instances it would be useful to enable a prognosis already at the time of diagnosis by means of clinical parameters or inflammation markers. We examined a number of cell-biological inflammation parameters in the serum and bronchoalveolar lavage fluid of 72 patients in the x-ray stages I and II with and without Löfgren's syndrome (phenotyping of lymphocytes, interleukin-1 alpha, soluble interleukin-2 receptors [sIL-2R], interleukin-6, interleukin-8, platelet-derived growth factor, procollagen-3 peptide) and followed up these patients for one year by clinical parameters. It was found that markers of the active lymphocytic inflammation were mostly associated with spontaneous remission during the follow-up period. Hence, acute lymphocytic inflammation is a favourable prognostic sign and should not prompt premature treatment with cortisone.

Adult↗
PubMed1995

[Conventional arthrography in comparison with magnetic resonance tomography and arthroscopy in internal knee joint injuries: are there specific indications?].

Twenty-one patients with suspected internal knee joint lesions were examined prospectively. In all patients an MRI was carried out first and was followed within two weeks by an arthrography and an arthroscopy. Lesions of the menisci, cruciate ligaments, hyaline cartilage, and synovial tissues were evaluated. Arthroscopy findings were defined as the "gold standard". MRI achieved an accuracy of 96.4%, a sensitivity of 93.6%, and a specificity of 92.5%, whereas arthrography achieved an accuracy of 67.8%, a sensitivity of 66.6%, and a specificity of 71.4%. These statistical data as well as the single findings revealed no special indications for arthrography in suspected knee joint lesions.

Acute Disease↗
PubMed1995

Acquired protein C dysfunction but not decreased activity of thrombomodulin is a possible marker of thrombophilia in patients with lupus anticoagulant.

Lupus anticoagulants (LAs) are acquired antiphospholipid antibodies, and the occurrence of LA is associated with an increased risk of developing thrombosis. In a population of 46 patients with LA with or without LA-associated thrombophilia, it was analyzed whether the concentration of LA could be correlated to the individual thrombotic risk in patients with LA. No significant difference was found in the concentrations of LA measured by routinely used functional and immunologic assays in patients with LA with thrombophilia when compared with patients with LA without thrombophilia. Inhibition of thrombomodulin (TM) activity by LA has been postulated to be one of the major pathogenic mechanisms causing thrombophilia in LA. Therefore the inhibition of endothelial cell-dependent TM activity by LA was analyzed by using a protein C (PC) activation assay. Reduced rates of PC activation were found in only 2 out of the 46 cases, ruling out that inhibition of TM activity is a common phenomenon in patients with LA. However, anionic phospholipids are necessary to ascertain the anticoagulant activity of activated PC (APC). To prove the hypothesis that the anticoagulant activity of APC is inhibited by LA, the anticoagulant response of purified APC added to LA-containing plasma was measured through the amount of factor VIII inactivation. Thirteen out of 14 patients with recurrent thrombotic events and 10 out of 19 patients with one single episode of thrombosis showed an APC response outside the mean--2 SD range of normal human controls. In contrast, among 13 patients with LA without symptoms, only one showed an abnormal APC response. From these data it is concluded that LA inhibits the APC anticoagulant activity and that this type of acquired APC dysfunction may contribute to the pathogenesis of LA-associated thrombophilia. Moreover, the APC anticoagulant response assay may prove to be a useful marker to identify patients with LA with a high thrombotic risk.

Adult↗
PubMed1995

Thyroid testing using the Cobas Core immunoassay system. A multicentre study.

The random access immunoanalyzer Cobas Core and the Cobas Core Thyroid Assays were assessed as to their clinical usefulness in the analysis of different thyroid diseases. Four centres participated in this study measuring the following five thyroid tests per sample on the instrument: thyrotropin, free thyroxine, thyroxine, triiodothyronine and free triiodothyronine. The assessment was based on studies of precision and clinical samples. Within- and between-series precisions showed a mean CV over all assays of 4.3 and 6.1%, respectively. Comparison of the test results with clinical data demonstrated that the Cobas Core results are in accordance with diagnosed thyroid diseases. A good discrimination between normal and disease status and between untreated and treated status was found. Furthermore, 370 sera measured with Technicon Immuno-1 TSH and FT4 assays were compared to the respective Cobas Core EIAs). A good correlation between the assays was demonstrated.

Evaluation Studies as Topic↗