[Experiences in the control of foot-and-mouth disease during a primary outbreak].
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Biomedical subjects
Publications and source records attributed to M Hartmann.
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The insulin receptor gene is constitutively expressed, so the presence of insulin receptor proteins might be expected on all mammalian tissues, with the plasma membrane as the predominant site of receptor location. Results reviewed here indicate that insulin receptors are also present in all placental tissues and the placenta's progenitor tissues and cells, i.e., oocytes, spermatozoa, and preimplantation embryos, in most of the species studied. Receptor densities, however, vary among individual cells and cell types and at various developmental stages. Three aspects deserve emphasis. 1) In human placenta, the insulin receptor distribution pattern is characterized by a spatiotemporal change between first trimester and term. At the beginning of pregnancy, insulin receptors are found predominantly on the maternal side (apical membrane of syncytiotrophoblast, low density on cytotrophoblast); at term, however, they are on the fetal side (lining the fetal vessels). This suggests that, in the first trimester, maternal insulin regulates insulin-dependent processes, whereas, at term, it must be fetal insulin mainly controlling these processes. 2) The majority of insulin receptors is expressed on structures that are currently assumed to drive placental growth, i.e., syncytial sprouts and mesenchymal villi in first-trimester placentas and fetal endothelium at term. Therefore, we hypothesize a growth-promoting function, among others, of insulin on the placenta. 3) At present, no histologic evidence is available to demonstrate insulin receptors in structures commonly associated with receptor-mediated endocytosis. Whether placental insulin receptors are internalized, therefore, awaits clarification.
Using 26 restriction endonucleases, a cleavage site survey was undertaken for DNAs of several unrelated Streptomyces phages SH3, SH5, SH10 and SH13. Only EcoRI was found to produce single cleavage in SH3 and SH10 DNA. The complete maps were prepared for the 2, 9 and 11 fragments of SH10 DNA, as generated by EcoRI, KpnI and BglII, respectively. The evidence is presented that SH10 DNA contains cohesive ends. Moreover, a clear-plaque mutant of SH10 was shown to contain a deletion of 790 bp in the right part of the genome, including two KpnI sites.
The construct of expressed emotion is regarded as one of the most important predictors of the course of schizophrenia and has also proven to be a predictor of the course of depressive disorders, psychosomatic disorders and physical illness. Despite its clinical significance, the utility of the EE-construct has been limited since measurement by interview is time-consuming, and to date only applicable to psychotic illness. Questionnaires as a practicable alternative to the structured interview are also mostly applicable solely to psychotic disorders. One exception is the Family Emotional Involvement and Criticism Scale (FEICS, Shields et al.). This questionnaire allows a general assessment of EE and thus a practical application of EE to the general area of family research. In a sample of n = 202 patients, the German version of this instrument proved to be reliable in our research. The two-factor structure of the original American version was replicated. We found good correlation between the measured factors, and clinical and other diagnostic markers particular to family pathology. This questionnaire is therefore a brief, reliable and valid instrument for measuring EE in many disorders.
An instrument to measure quality of life in multicentric pediatric studies in German language was missing yet. The FMH measures the capability for daily life actions with 56 items like "can walk without aids" or "earns money". It was normalized with 971 persons (45.5% female) aging between 0 and 102 years resulting in age-dependent percentiles. The retest-reliability-coefficient is 0.99. The validity was tested in 10 brain tumor patients: there was a good agreement with the IQ (r = 0.7) and with a semiquantitative assessment by a physician (p < 0.001).
PROBLEM: Investigations to date on localization of placental insulin receptors (IR) at the ultrastructural level focused on the maternal facing side of the placenta but did not allow localization of IRs to intracellular compartments. METHOD: The ultrastructural localization of IR in placentae from early and term gestation was studied using the immunogold technique and a monoclonal antibody against the external domain of the IR (clone MA20). RESULTS: At 10 wk gestation, there were high levels of IR in both cytotrophoblast and syncytiotrophoblast, with sparse microvillous labeling. Fetal vessels contained various amounts of IR while stromal cells were also labeled. By 13 wk, this pattern was unchanged; however, at term, fewer IR were present in the syncytiotrophoblast, with more label on microvilli than before. Fetal vessels were well labeled, while stromal cells appeared unchanged. Intense labeling of fetal erythrocytes provided an internal positive control, while omission of the primary antiserum produced loss of binding. CONCLUSION: The data suggest a spatiotemporal alteration in placental IR distribution during pregnancy, possibly reflecting a shift in control of placental growth and metabolism from mother to fetus.
Evaluation of splanchnic perfusion and oxygenation was performed by measurements of serosal tissue oxygen tension (PserO2) and intramucosal pH (pHi) in relation to subcutaneous oxygen tension (PscO2), subcutaneous carbon dioxide tension (PscCO2) and subcutaneous pH (pHsc) in pigs subjected to oleic acid-induced lung injury during ventilation with increasing levels of positive end-expiratory pressure (PEEP). Lung injury resulted in a general hypoxia and redistribution of perfusion away from the subcutaneous and splanchnic tissues, illustrated by a decrease in PaO2 from 93 to 37 mm Hg (p < 0.01), PscO2 from 45 to 17 mm Hg (p < 0.01), PserO2 from 80 to 30 mm Hg (p < 0.01) and pHi from 6.84 to 6.74 (p < 0.05) and a decrease of porta flow from 0.77 to 0.57 l/min. Application of PEEP up to 10-15 cm H2O resulted in an increase of portal vein oxygen tension (PportaO2) from 21 to 34 mm Hg (p < 0.01), PscO2 from 17 to 26 mm Hg (p < 0.05) and PserO2 from 30 to 55 mm Hg (p < 0.05). At PEEP 20 cm H2O PserO2 decreased to 47 mm Hg (p < 0.05). Porta flow decreased continuously with increasing levels of PEEP. PserO2 correlated with PportaO2 (r = 0.7, p < 0.001). pHi correlated poorly with PportaO2 (r = 0.2) and porta flow (r = 0.4). PscO2 and PserO2 correlated well (r = 0.8, p < 0.001). In summary, splanchnic perfusion and oxygenation was better reflected by serosal oxygen tension than pHi in the colon. Changes in serosal oxygenation of the colon paralleled changes in subcutaneous tissue oxygenation.
The fibrinolytic activity of the new plasminogen activator, recombinant staphylokinase, was compared to that of streptokinase and tissue-type plasminogen activator in the fibrin plate assay. The pattern of fibrinolysis by staphylokinase on fibrin plates differs from the other plasminogen activators. A number of mutants of staphylokinase with various amino acids in position 26 substituted for methionine in wild-type staphylokinase were compared with respect to their fibrinolytic potencies. Only the mutants with cysteine or leucine in this position have a fibrinolytic activity comparable to wild-type staphylokinase. The results on the fibrinolytic activities in the fibrin plate assay correlate with those of a plasmin generation assay, the latter is, however, less sensitive.
PURPOSE: Efavirenz (EFV) has been shown to be a highly effective HIV therapy in antiretroviral-naïve patients when used with nucleoside reverse transcriptase inhibitors. METHOD: The study participants were 314 patients, 45 of whom had not been previously treated with any antiretroviral medication. The other patients were heavily pretreated for about 3 years (1,047 days); 34 with two nucleoside reverse transcriptase inhibitors, 147 with triple therapy, and 88 with a quadruple regimen. RESULTS: Suppression of plasma HIV-1 RNA to <50 copies/mL and <500 copies/mL was achieved in 56% and 72% of the pretreated patients and in 82% and 91% of the naïve patients, respectively, at week 80 (intention-to-treat analysis: noncompleters = failure: 10% and 15% and 20% and 22%, respectively). The viral load reduction at week 80 was 0.7 log(10) for the pretreated patients and 2.6 log(10) for the naïve patients. CD4 cell counts increased from 386 to 474 cells/microL at week 80 in the pretreated group and from 264 to 431 in the naïve patients. 118 patients discontinued the treatment due to adverse events (37 patients due to nervous system symptoms and 15 patients because of exanthema). There were no AIDS-defining events in the group of antiretroviral-treated patients. CONCLUSION: EFV in combination with nucleoside reverse transcriptase inhibitors as antiretroviral therapy was potent and effective in reducing viral load, mainly in treating therapy-naïve patients and in preventing AIDS-defining events.
In the Heidelberg study about psychoanalytic therapy with children and adolescents 133 cases have been studied in a naturalistic design. Up to now results were published on the basis of assessments of experts only. This follow-up study has investigated the stability of therapy outcomes from the perspectives of different raters. For that outcome has been rated five years after the end of treatment by experts, parents and children themselves. Good outcomes have been stabile and have shown even after five years. Single variables showed further improvement in the time of follow-up, for example the social communicative impairment with parents. Thus the high rate of successful longterm psychoanalytic therapies with children and adolescents could be confirmed from different rater perspectives.
We wanted to verity whether M2-PK is a useful marker in testicular cancer. In a prospective study of 20 consecutive patients, blood was drawn from the testicular and the cubital vein before semicastration and later. For the detection of M2-PK we used the Assay of ScheboTech. In the testicular vein M2-PK was 11.2 U/ml. In the cubital vein it was 6.2 U/ml before semicastration, increasing in the following days. There were no significant differences between testicular and cubital vein blood, between the non-metastasized patients and the metastasized stages and between the patients with seminoma and non-seminomatous tumors. There is no profit in the diagnosis of testicular cancer using Tu-M2-PK.
We combined 'in situ' high pressure microscopy with confocal laser scanning microscopy to directly study Ca2+ homeostasis in intact mammalian (murine) skeletal muscle fibres during high pressure exposure up to 35 MPa. Cytosolic Fluo-4 and mitochondrial Rhod-2 Ca2+ fluorescence were simultaneously monitored. To separate changes in Ca2+ and direct/indirect effects of pressure on the dye, experiments in permeabilized ('skinned') muscle fibres were performed at a fixed Ca2+ concentration. Normalized Fluo-4 fluorescence sharply declined up to 10 MPa but showed a plateau between 10 MPa and -35 MPa. In the intact fibre, Fluo-4 fluorescence exponentially decreased during pressurization to 35 MPa with a pressure constant of pi-5 MPa whereas mitochondrial Rhod-2 fluorescence exponentially increased with a four-fold larger pi. Holding the pressure at 35 MPa almost did not change Fluo-4 fluorescence. However, Rhod-2 fluorescence started to decrease after -40 min. Upon decompression, Rhod-2 and Fluo-4 fluorescence increased exponentially with similar pi. However, initial Fluo-4 fluorescence values were not restored. Our results are in agreement with pressure induced Ca2+ leakage from the sarcoplasmic reticulum. Ca2+ might then be taken up in large amounts by mitochondria preventing cytosolic increase in Ca2+. Prolonged pressure applications (-40 min at 35 MPa) seem to destabilize mitochondrial function with release of Ca2+ from mitochondria back into the cytosol and eventually mechanical activation resulting in irreversible contractures. The pressure induced disturbance of Ca2+ homeostasis might have important implications for the pressure exposure limits and/or dive profiles of deep sea mammals.
Semen analyses from 29 patients with testicular tumours were done, 19 were examined before and after orchidectomy but before any other treatment. There was no evident difference in both of these examinations. Therefore it is possible to obtain enough time for cryopreservation, because the stricken patients can be first treated by unilateral orchidectomy without loss in quality of the semen. Hendry et al. (1983) accepted for sperm freezing only samples with more than 10 mill/ml spermatozoa and more than 30% motility. 17 of our 29 patients (58.6%) fulfilled that condition. Thus, in more patients cryopreservation can be considered.
The potentials of nickel(II) and cadmium(II) to interfere with the repair of different types of deoxyribonucleic acid (DNA) lesions was investigated. Concerning the nucleotide excision repair pathway, nickel(II) has been shown to reduce the incision and the ligation frequency after ultraviolet (UV)-irradiation. When applying a gel mobility shift assay and HeLa nuclear cell free extracts, nickel(II) diminishes the specific binding of a protein to UV-damaged DNA, suggesting that nickel(II) interferes with the DNA-protein interactions involved in the damage recognition after UV-irradiation. Similarly, the incision frequency is reduced in the presence of low concentrations of cadmium(II). Concerning the repair of oxidative DNA damage induced by visible light, non-cytotoxic concentrations of nickel(II) caused a complete repair inhibition of DNA base modifications like 7,8-dihydro-8-oxoguanine (8-hydroxyguanine) and of DNA strand breaks. Since the repair of DNA damage is essential for the prevention of cancer, its inhibition may account for the carcinogenic action of the respective metal compounds.
PURPOSE: To compare image contrast and lesion conspicuity of enhancing intracranial lesions obtained with T1-weighted and magnetization transfer T1-weighted spin-echo sequences after administration of standard (0.1 mmol/kg body weight) and triple doses of gadobutrol. METHODS: Twenty-four patients with a total of 34 enhancing intracranial lesions were studied with T1-weighted and magnetization transfer T1-weighted spin-echo MR imaging. An incremental dose technique was used with intravenous injections of 0.1 and 0.2 mmol/kg body weight gadobutrol. Lesion-to-white matter contrast and white matter-to-edema contrast were calculated. RESULTS: The lesion-to-white matter contrast of the magnetization transfer T1-weighted studies was significantly higher than that of the T1-weighted studies when identical doses of gadobutrol were compared. The lesion-to-white matter contrast was not significantly different on the triple-dose T1-weighted study and the standard-dose magnetization transfer T1-weighted study. Two lesions were visible only on the standard-dose magnetization transfer T1-weighted and the triple-dose studies. CONCLUSION: Standard-dose magnetization transfer T1-weighted and triple-dose T1-weighted spin-echo MR studies are equally well suited to increase the lesion-to-white matter contrast in patients with enhancing intracranial lesions. Triple-dose magnetization transfer T1-weighted studies further increase lesion-to-white matter contrast but do not show additional lesions.
Acid inhibitory therapy has long been considered of no benefit for upper GI bleeding. The reason was that achlorhydria in the stomach could not be achieved with any single or combination of acid inhibitory drugs. The introduction of proton pump inhibitors has, for the first time, allowed the physician to temporarily achieve achlorhydria by large doses of intravenously applied proton pump inhibitors. The first placebo-controlled clinical trials have shown that, indeed, an intragastric pH of near 7 can significantly improve the clinical outcome of upper GI bleeding. Pharmacokinetic studies with proton pump inhibitors have shown that a bolus of 80 mg pantoprazole or omeprazole followed by immediate continuous infusion of eight mg per hour will result in an intragastric pH of 7 within 20 minutes. This intragastric pH optimizes the different steps of hemostasis in the stomach.
The introduction of H2-receptor antagonists in the mid-1970s provided, for the first time, acceptable medical therapy for acid-related diseases. Their short duration of action and single receptor targeting, however, limited satisfactory treatment of patients. Today the control of gastric acid secretion can be effectively achieved by direct inhibition of the H+, K(+)-ATPase. Inhibition of the proton pump suppresses acid secretion independent of the route of stimulation. Two classes of drugs are able to inhibit the proton pump. First, the substituted benzimidazoles (proton pump inhibitors [PPIs]), which, due to their pKa of about 4, accumulate in the acidic secretory canaliculus of the stimulated parietal cell. Following conversion to a cationic sulfenamide, they react with cysteines on the extracytoplasmatic face of the H+, K(+)-ATPase subunit. Second, acid pump antagonists (APAs) acting by K(+)-competitive and reversible binding to the gastric proton pump, which is the final step for activation of acid secretion in the parietal cell. One possible class of APAs are imidazopyridines. BY841 was selected from this class and is chemically a (8-(2-methoxycarbonylamino-6-methyl-phenylmethylamino )-2,3-dimethyl-imidazo [1,2-a]-pyridine). In pharmacological experiments such as pH-metry in the conscious, pentagastrin-stimulated fistula dog, BY841 proved to be superior to both ranitidine and omeprazole by rapidly elevating intragastric pH up to a value of 6. The duration of this pH elevation in the dog was dose-dependent. As was predicted by the above-mentioned dog model, available clinical phase I data confirm dose-dependent pharmacodynamics of BY841 in man. Using both acid output and continuous 24-hr pH measurements, a pronounced antisecretory effect of BY841 has been found. Actually, a single 50 mg oral dose of BY841 immediately elevated intragastric pH to about 6. Higher doses caused a dose-dependent increase in duration of the pH-elevation, without any further increase in maximum pH values. Twice daily administration was more effective than once a day administration of the same daily dose. With both regimens, the duration of the pH-elevating effect of BY841 further increased upon repeated daily administration. This demonstrates lack of tolerance development, the latter being a well-known disadvantage of H2-receptor antagonists. In comparison with the standard dose of omeprazole, BY841 administered at a dose of 50 mg or 100 mg twice daily is markedly more effective on Day one of treatment, and both doses are at least as potent as omeprazole following repeated daily administration.