Biomedical subjects

M Bauer

Publications and source records attributed to M Bauer.

At least 253 records · Page 14Linked to original sources

PubMed1998

The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor.

The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.

Animals↗

PubMed1998

Role of endothelins and nitric oxide in hepatic reperfusion injury in the rat.

We determined the functional role of nitric oxide (NO) and endothelins (ET), two potent vasoactive mediator systems in the liver, for the pathogenesis of sinusoidal perfusion failure and lethal hepatocyte injury after low-flow ischemia/reperfusion in the isolated perfused rat liver. NO synthase blockade with Nomega-nitro-L-arginine methyl ester (L-NAME) (10[-3] mol/L) before reperfusion prevented increased N02-/NO3- the final products of NO oxidation, which could be observed in the vehicle group. Epifluorescence microscopy revealed that the decrease in functional sinusoid density during reperfusion was much more profound compared with vehicle. This was associated with a lower surface PO2, a substantially higher number of nonviable hepatocytes, as assessed by in situ propidium iodide staining, and enhanced enzyme release into the perfusate compared with vehicle. In contrast, reperfusion in the presence of the endothelinA+B receptor antagonist bosentan (2 x 10(-4) mol/L) restored functional sinusoid density and surface PO2 to baseline values, resulted in a small reduction in the number of propidium iodide-positive hepatocytes, and caused similar increases in enzyme release as compared with vehicle. This indicates that hepatic generation of NO attenuates sinusoidal perfusion failure and improves liver tissue oxygenation, thus limiting hepatocyte injury during early reperfusion after hepatic low-flow ischemia. In contrast, endothelins counteract the microcirculatory effects of NO, i.e., mediate the no-reflow in hepatic sinusoids; however, the restoration of functional sinusoid density with bosentan resulted only in a small reduction in tissue damage, suggesting that additional components, which are independent of microcirculatory failure, contribute to hepatic reperfusion injury under these conditions.

Animals↗

PubMed1998

Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver.

Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXa, iron, and carbon monoxide. The HO-system consists of two isoenzymes, namely HO-2 and the inducible isoform HO-1, also referred to as heat shock protein (hsp) 32. Although both parenchymal and non-parenchymal liver cells participate in heme metabolism, the expression pattern of the isoenzymes in normal and stress exposed liver is unknown. To study this, rats underwent either endotoxin (lipopolysaccharide [LPS]) challenge, hemorrhagic hypotension, glutathione (GSH) depletion, or cobalt chloride injection, all known to provoke oxidative stress. HO-2 messenger RNA (mRNA) and protein were constitutively expressed in hepatocytes, Kupffer/endothelial-, and stellate (Ito-) cell enriched fractions. Although both non-parenchymal cell fractions expressed HO-1 transcripts, HO-1 immunoreactive protein was restricted to Kupffer cells in the normal liver. In contrast to HO-2, a significant increase in HO-1 on the whole organ level was noted by hemorrhagic hypotension, GSH depletion, and cobalt chloride injection. However, the distinct stress models led to a strikingly different cell-type specific and sublobular expression pattern of HO-1 gene expression. HO-1 was inducible in sinusoidal lining cells (hemorrhagic hypotension, LPS challenge), in periportal (cobalt chloride), or pericentral (GSH depletion, hemorrhagic hypotension) hepatocytes. The blockade of protein translation before hemorrhage by cycloheximide reduced upregulation of HO-1/hsp32 mRNA significantly (65.4% reduction, P < .05), whereas the inducibility of hsp70 transcript was maintained. In addition to transcriptional regulation, HO-1 seems to be subject to posttranscriptional control in particular in non-parenchymal cells.

Animals↗

PubMed1998

Primary malignant melanoma of the vagina: long-term remission following radiation therapy.

OBJECTIVE: To describe the characteristics and clinical course of patients with primary vaginal melanoma treated at three large Austrian institutions. METHODS: The medical records of 14 patients treated at the Departments of Obstetrics and Gynecology of the Universities of Graz and Vienna and the Salzburg Women's Hospital between 1982 and 1996 were reviewed. RESULTS: The median age at diagnosis was 73 years. Presenting symptoms included vaginal bleeding in all patients. Three of seven patients (43%) with tumors < or = 3 cm survived longer than 5 years compared to none of seven patients with a tumor size > 3 cm. Three of nine patients (33%) who received radiotherapy either in addition to surgical excision or as primary treatment, survived for 5 years. Other potential prognostic factors such as age, location, FIGO stage, depth of invasion, Chung level, histology, cell type, mitotic count, vessel involvement, ulceration, p53 accumulation, type of surgery, type of radiotherapy, or chemotherapy did not seem to correlate with the patients' outcome. The median overall survival was 10 months (range 1-153). The 5-year disease-free and overall survival rates were 14 and 21%, respectively. All three long-term survivors recurred locally. CONCLUSION: All three patients who had long-term survival had lesions < or = 3 cm and received either primary radiotherapy (n = 2) or adjuvant radiotherapy after complete excision of the primary lesion (n = 1). In view of the poor overall survival rates, regardless of treatment, radiotherapy may be a limited valuable alternative or adjunct to surgery in patients with primary malignant melanoma of the vagina < or = 3 cm in diameter.

Adult↗

PubMed1998

[Managed care. Its impact on health care in the USA, especially on anesthesia and intensive care].

Managed care, i.e., the integration of health insurance and delivery of care under the direction of one organization, is gaining importance in the USA health market. The initial effects consisted of a decrease in insurance premiums, a very attractive feature for employers. Managed care promises to contain expenditures for health care. Given the shrinking public resources in Germany, managed care seems attractive for the German health system, too. In this review the development of managed care, the principal elements, forms of organisation and practical tools are outlined. The regulation of the delivery of care by means of controlling and financial incentives threatens the autonomy of physicians: the physician must act as a "double agent", caring for the interest for the individual patient and being restricted by the contract with the managed care organisation. Cost containment by managed care was achieved by reducing the fees for physicians and hospitals (and partly by restricting care for patients). Only a fraction of this cost reduction was handed over to the enrollee or employer, and most of the money was returned with profit to the shareholders of the managed care organisations. The preeminent role of primary care physicians as gatekeepers of the health network led to a reduced demand for specialist services in general and for university hospitals and anesthesiologists in particular. The paradigm of managed care, i.e., to guide the patient and the care giver through the health care system in order to achieve cost-effective and high quality care, seems very attractive. The stress on cost minimization by any means in the daily practice of managed care makes it doubtful if managed care should be an option for the German health system, in particular because there are a number of restrictions on it in German law.

Anesthesia↗

PubMed1998

[Anesthesia and perioperative immune function].

Innate and acquired immunity plays a pivotal role in the host defense response. Pain, stress, necrotic tissue and invading microorganisms are known modulators of the complex immune response of patients undergoing major surgery. Anaesthesia itself or perioperative interventions of the anaesthesiologist may substantially alter the immune function with potential impact on the postoperative course. For instance, transfusion of allogenic blood and administration of dopamine or metoclopramide may interfere with immunity. Stress and pain are associated with immune tolerance, increased susceptibility to infection and tumor spreading in animal models. Thus, anaesthesia may--through modulation of the neurohumoral stress response--indirectly affect immunity of the surgical patient. In particular epidural anaesthesia and/or administration of epidural or spinal opioids seem to attenuate the stress response with beneficial effects on cellular and humoral immunity. In addition, anaesthetics, such as etomidate, propofol, or thiopentone and opioid analgesics may directly affect function of immune competent cells. However, these actions may only be apparent with high or supraclinical concentrations and/or long-term exposure. Regarding the latter, evidence suggests that long-term sedation using thiopentone in neurosurgical patients is paralleled by infectious complications in a dose-dependent manner. At present, no data are available regarding the significance of the observed alterations associated with various anaesthetic procedures of the incidence of postoperative complications associated with impaired immunity, such as infection or metastatic spreading in oncological surgery.

Anesthesia↗

PubMed1998

[The effect of gamma-hydroxybutyrate (GHB) on proinflammatory cytokine gene expression in coronary surgical procedures].

OBJECTIVE: To determine the influence of gamma-hydroxy-butyrate (GHB) on spontaneous and lipopolysaccharide (LPS)-stimulated release of tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interleukin-10 (IL-10) in whole blood from patients undergoing coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC). In addition, the pharmacological modulation on lipopolysaccharide (LPS)-stimulated cytokine release by GHB (GHB-Na and GHB-ethanolamide) was characterized in a separate in vitro-assay. METHODS: In a prospective, randomized, double-blinded study, 12 patients undergoing elective CABG were assigned to receive either saline (control) or GHB-Na (25 mg/kg as loading dose followed by 25 mg/kg/h) intraoperatively. Blood samples were obtained (A) preoperatively, (B) 20 min after ECC and (C) 24 h after ECC. Plasma levels (spontaneous release) as well as LPS-stimulated cytokine secretion were measured in a whole blood culture system ex vivo and correlated with mRNA-expression in peripheral blood mononuclear cells (PBMC). In addition, the dose-response characteristics of modulation of the cytokine response by GHB was studied in vitro in the same assay. RESULTS: Plasma IL-6 and IL-10 levels were significantly elevated after CABG, while TNF and IL-1 beta were detectable only occasionally in both groups. Expression of all cytokines studied was significantly reduced upon ex vivo LPS-stimulation at time point B. Despite maintained expression of TNF and IL-1 beta mRNA-transcripts upon ex vivo LPS-stimulation in patients treated with GHB, release of the cytokines in the supernatant was decreased to a similar degree as in the control group. Cytokine response upon LPS-stimulation was restored 24 h after CABG for the group mean, however, with substantial individual heterogeneity. In vitro, pharmacological doses of GHB-Na (2 mg/ml) attenuated LPS-induced IL-1 beta release. However, application of the GHB-receptor antagonist NCS-382 caused a nearly complete cessation of IL-1 beta release in vitro (to 2.5% of control). GHB-ethanolamide (LK 544) did not influence the LPS-stimulated release of the cytokines studied. CONCLUSION: The results suggest a biphasic response of stimulated PBMC cytokine gene expression during CABG with an initial tolerance to LPS-stimulation shortly after termination of ECC. However, whether or not PBMC express functional GHB receptors remains unclear in light of contradictory effects of the different ligands. In spite of the ex vivo and in vitro results, application of GHB-Na in doses which are primarily based on its use as an anesthetic agent do not seem to modulate the release of the cytokines studied.

Adult↗

PubMed1998

[Thyroid gland function in lithium treatment].

Lithium is widely used in the acute and prophylactic treatment of affective disorders. Lithium affects thyroid hormone metabolism via different mechanisms. In patients this leads to a compensatory increase in pituitary thyroid stimulating hormone (TSH) which usually maintains the euthyroid status. This is probably the reason for the relatively high prevalence of goitre in lithium-treated patients; however, the enlargement of the gland is only moderate in most cases. Due to its immunostimulating effects lithium may support the appearance of thyroid auto-antibodies and the development of thyroiditis, which may be the reason for a higher prevalence of hypothyroidism in patients receiving lithium. However, also cases of hyperthyroidism in such patients have been reported repeatedly. Therapeutic recommendations for the treatment of disturbances of thyroid function during lithium treatment are given.

Affective Disorders, Psychotic↗

PubMed1998

[High dosage thyroxine treatment in therapy and prevention refractory patients with affective psychoses].

The following review summarizes current knowledge on the treatment of therapy-resistant patients with affective disorders with supraphysiological doses of thyroxine (T4). Several groups have reported independently of each other that administration of 200-500 micrograms T4/day has excellent effects in 50-65% of patients a) with bipolar disorder, with or without, "rapid cycling" course, who were previously resistant to all prophylactic drugs and b) in the treatment of therapy-resistant depression. T4 is effective only in combination with an antidepressant or a prophylactic drug. Side effects are minimal, even when T4 is administered over several years. These results now justify to recommend high dose T4-augmentation as "last-resort" treatment also beyond research purposes, i.e. in psychiatric wards and in private practice. Recommendations for clinical applications are given and hypotheses on possible mechanisms underlying the efficacy of T4 treatment are discussed.

Bipolar Disorder↗

PubMed1998

Statistical pattern detection in univariate time series of intensive care on-line monitoring data.

OBJECTIVES: To determine how different mathematical time series approaches can be implemented for the detection of qualitative patterns in physiologic monitoring data, and which of these approaches could be suitable as a basis for future bedside time series analysis. DESIGN: Off-line time series analysis. SETTING: Surgical intensive care unit of a teaching hospital. PATIENTS: 19 patients requiring hemodynamic monitoring with a pulmonary artery catheter. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Hemodynamic data were acquired in 1-min intervals from a clinical information system and exported into statistical software for further analysis. Altogether, 134 time series for heart rate, mean arterial pressure, and mean pulmonary artery pressure were visually classified by a senior intensivist into five patterns: no change, outlier, temporary level change, permanent level change, and trend. The same series were analyzed with low-order autoregressive (AR) models and with phase space (PS) models. The resulting classifications from both models were compared to the initial classification. Outliers and level changes were detected in most instances with both methods. Trend detection could only be done indirectly. Both methods were more sensitive to pattern changes than they were clinically relevant. Especially with outlier detection, 95% confidence intervals were too close. AR models require direct user interaction, whereas PS models offer opportunities for fully automated time series analysis in this context. CONCLUSION: Statistical patterns in univariate intensive care time series can reliably be detected with AR models and with PS models. For most bedside problems both methods are too sensitive. AR models are highly interactive, and both methods require that users have an explicit knowledge of statistics. While AR models and PS models can be extremely useful in the scientific off-line analysis, routine bedside clinical use cannot yet be recommended.

Aged↗

PubMed1998

Acute pancreatitis due to pyritinol: an immune-mediated phenomenon.

A 23-year-old man experiencing three episodes of acute pancreatitis of undetermined etiology is described. Repeated questioning revealed that all three events had occurred after intake of the drug pyritinol. Controlled rechallenge with a single dose of the drug led to a fourth episode of acute pancreatitis. Skin testing was negative, but lymphocyte stimulation tests and double fluorescence analysis detected pyritinol-activated CD4 and CD8 lymphocytes. Together with the clinical observation that the intervals between drug intake and start of symptoms of acute pancreatitis became shorter with repeated exposure, the data are consistent with an immune-mediated origin of the pancreatitis. Pyritinol has to be added to the list of drugs capable of inducing acute pancreatitis.

Acute Disease↗

PubMed1998

Differential regulation of hepatic arterial and portal venous vascular resistance by nitric oxide and carbon monoxide in rats.

Nitric oxide (NO), a gaseous mediator that accounts for the biological activity of endothelium-derived relaxing factor, has been shown to play an important role in the reduction of basal vascular tone in multiple vascular beds, including the hepatic circulation. On the other hand, recent studies have provided first evidence that endogenously generated carbon monoxide (CO) may exert vasodilatory effects in the hepatic portal vein and within sinusoids. Thus, we defined the differential role of NO and CO in the regulation of vascular resistance in the two inflows to the liver in the normal rat in vivo. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium and surgically instrumented in order to study the change in hepatic arterial (Rha) and portal venous vascular resistance (Rpv) in response to intravenous bolus administration of either the NO-synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (1 mg/kg; n = 7 animals) or of tin protoporphyrin-IX (SnPP-IX) (50 micromol/kg), a specific inhibitor of the CO-generating enzyme heme oxygenase (n = 8 animals). While L-NAME caused a substantial increase in Rha, Rpv increased only slightly under these conditions. In sharp contrast, SnPP-IX did not affect Rha, but caused a profound increase in Rpv. In conclusion, Rha and Rpv are differentially regulated by NO and CO in the normal rat liver in vivo, i.e., NO serves as a potent vasodilator in the hepatic arterial circulation, but exerts only a minor vasodilatory effect in the portal venous vascular bed. In contrast, while there is no intrinsic CO-mediated vasodilation in the hepatic artery, CO acts to maintain portal venous vascular tone in a relaxed state.

Animals↗

PubMed1998

Reproducibility of 1H-NMR integrals: a collaborative study.

The quantitative use of NMR spectroscopy was investigated by a reproducibility study of 1H-NMR integrals involving five laboratories. A significant laboratory effect was found confirming the difficulty to obtain very precise data by integration of complex signals. The reproducibility of any NMR assay measurement, which requires a high precision should be validated by an interlaboratory study.

Evaluation Studies as Topic↗

PubMed1998

An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles.

Dissolution efficiency (D.E.), the area under a dissolution curve between defined time points, and the fit factors (f1 and f2) have been compared for the characterisation of dissolution profiles, using data from three batches of a product in nine different packs stored under two conditions. The factors f1 and f2 offer ease of calculation and a simple measure of similarity between pairs of dissolution profiles. This is well suited to the qualitative determination of 'similarity' as required by the FDA's SUPAC Guide. However, they do not provide information on individual batches, including their consistency. In contrast, D.E. does provide such information is well-suited to making quantitative comparisons amongst batches. Because D.E. has a simple physical meaning, it is easier to interpret D.E. data then corresponding f1 and f2 results. The confidence limits in D.E. values provide a useful measure of the variability in batch dissolution and allow the statistical significance of difference in D.E. between pairs of batches to be determined. Both of the above measures lead to the same conclusions regarding the similarity in protective power amongst the nine packs under test and to the value of added desiccant in maintaining the dissolution profile of the product when stored under high humidity conditions. It is concluded that D.E. offers a suitable alternative to the single point dissolution measurement for QC of immediate release products.

Models, Chemical↗

PubMed1998

Treatment of refractory depression with high-dose thyroxine.

In an open clinical trial we investigated whether addition of supraphysiological doses of thyroxine (T4) to conventional antidepressant drugs has an antidepressant effect in therapy-resistant depressed patients. Seventeen severely ill, therapy-resistant, euthyroid patients with major depression (12 bipolar, five unipolar) were studied. The patients had been depressed for a mean of 11.5 +/- 13.8 months, despite treatment with antidepressants and, in most cases, augmentation with lithium, carbamazepine, and neuroleptics. Thyroxine was added to their antidepressant medication, and the doses were increased to a mean of 482 +/- 72 micrograms/day. The patients' scores on the Hamilton rating Scale for Depression (HRSD) declined from 26.6 +/- 4.7 prior to the addition of T4 to 11.6 +/- 6.8 at the end of week 8. Eight patients fulfilled the criteria for full remission (a 50% reduction in HRSD score and a final score of < or = 9) within 8 weeks and two others fully remitted within 12 weeks. Seven patients did not remit. The 10 remitted patients were maintained on high-dose T4 and followed up for a mean of 27.2 +/- 22.0 months. Seven of these 10 remitted patients had an excellent outcome, two had milder and shorter episodes during T4 augmentation treatment, and one failed to profit from T4 treatment during the follow-up period. Side effects were surprisingly mild, and no complications were observed at all. In conclusion, augmentation of conventional antidepressants with high-dose T4 proved to have excellent antidepressant effects in approximately 50% of severely therapy-resistant depressed patients.

Aged↗

PubMed1998

Purity as an issue in pharmaceutical research and development.

In the third EUFEPS Nuremberg Conference, three important aspects in the purity area were extensively covered. The first one dealt with the setting up of practical strategies to establish specifications during the complete R&D process. An industrial strategy on how this goal could be reached was presented. A safety evaluation aspect reflecting the discussion between ten pharmaceutical companies was given and the regulatory point of view was presented. The second one focused on the physical aspect of the purity issue (polymorphism, crystallinity...). The scientific background of this problem was presented and the necessity to cover this problem during the early phases of an industrial R&D project was outlined. Regulatory aspects were covered and the necessity to perform in certain cases bioequivalence studies was pointed out. The last session raised the particularity of biotechnological products. The contributors stressed that the impurity limits should be based on safety evaluation as well as the necessity to review carefully the production methods. Finally, a review was done on the current progress of the ICH guidelines establishment.

Biotechnology↗

PubMed1998

Successful surgical treatment of a giant aneurysm of the right coronary artery.

We describe the case of a 46-year-old female patient, who was referred to us under the suspicion of an acute type-A aortic dissection. After perusal of the computer tomogram and subsequent transesophageal echocardiography, we decided to operate, albeit under the assumption of the existence of a pericardial cyst. Intraoperatively a strikingly large aneurysm of the right coronary artery presented itself, which was successfully treated through resection and end-to-end anastomosis.

Anastomosis, Surgical↗

PubMed1998

[Economic aspects of anesthesia. I. Health care reform in the German Republic].

Implications for Hospitals and Departments of Anaesthesiology. This article outlines the new German health care laws and their impact on the statutory health care system, hospitals and anaesthesia departments. The German health care system provides coverage for all citizens, although financial support from the public sector is on the downgrade. Hence, pressure to reduce public sector health care spending is likely to continue in the near future. Hospital costs account for one-third of total health care spending in Germany, and hospitals are facing increasing economic constraints: the volume and the charges for specific medical treatments are negotiated between the hospitals and the insurance agencies (or sickness funds) in advance. Only part of hospital care is still reimbursed on the basis of a per diem rate, and an increasing number of services are based on fixed payments per case or treatment. Reducing the costs for this treatment is therefore of utmost importance for hospitals and hospital departments. The prospective payment system and the pressure to contain costs demand a controlling system that allows for cost accounting per case. However, an economic evaluation must include comparative analysis of alternative therapeutic options in terms of both costs and outcome. Economic aspects challenge the traditional relationship between physicians and patients: doctors are still the advocates of their patients, but also act as agents for their institutions. Nevertheless, not only economic issues, but also ethical priorities and the value of an anaesthetic practice must be considered in the era of cost containment. Anaesthetists must be actively involved in providing high-quality care with its obvious benefits for the patient and be able to resist efforts to cut out expensive treatment modalities regardless of their benefits.

Anesthesia↗