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Biomedical subjects

M Bauer

Publications and source records attributed to M Bauer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Psychological and endocrine abnormalities in refugees from East Germany: Part II. Serum levels of cortisol, prolactin, luteinizing hormone, follicle stimulating hormone, and testosterone.

We investigated afternoon serum levels of cortisol, prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone in a group of 84 refugees who had fled from East to West Germany and suffered from psychiatric disorders within 6 weeks of their arrival in West Berlin. The mean hormone levels were compared with those of healthy control subjects. Cortisol levels were lower and LH levels were higher in the patients than in the control subjects, but only at trend levels of significance. No differences were found between the prolactin, FSH, or testosterone concentrations of the two groups. The patients with major depressive disorder (MDD) had a significantly higher mean cortisol level than the mean levels in the subgroups in whom posttraumatic stress disorder, dysthymia, and adjustment disorder were diagnosed. It can be concluded that the hypothalamic-pituitary-adrenal axis may "adapt" during severe long-term psychological stress and that long-term stress may be only one of the neurochemical mechanisms underlying the hypercortisolemia in patients with MDD.

Depressive Disorder↗
PubMed1994

Treatment of intractable non-rapid cycling bipolar affective disorder with high-dose thyroxine: an open clinical trial.

Six patients with very severe forms of non-rapid cycling bipolar affective illness whose symptoms had previously been refractory to all current antidepressant and/or prophylactic medications were treated with supraphysiological doses of thyroxine (250 to 500 micrograms/day) as an adjuvant to their previous medications. The mean follow-up period was 27.8 +/- 12.8 months (range 12 to 46). The mean number of relapses during the follow-up period of each patient declined from 5.3 +/- 3.1 to 0.8 +/- 0.8 and the mean duration of hospitalization from 10.0 +/- 5.6 to 0.8 +/- 1.2 months as compared to the same length of time for each patient before the start of treatment with high-dose thyroxine (T4). Three of the patients had no further relapses at all. Thus, for these patients, who had previously been severely ill and therapy-resistant, high-dose T4 administration proved to have excellent effects on the course of the illness. However, in five of these patients the effect of the T4 was strong enough only when it was administered in combination with a prophylactic and antidepressant and/or neuroleptic drug, of which in some cases high doses were also needed. The side effects were negligible. Mechanisms that may possibly underlie the beneficial effects of high-dose T4 in bipolar affective disorder are discussed.

Adult↗
PubMed1994

[Indications, technique and results of ultrasound guided punch biopsy in breast diagnosis (n=307)].

From May 1, 1992, to April 30, 1993, we performed 307 ultrasonic guided high-speed punch biopsies. In 119 of the 307 women, we dispensed with further surgical and histological procedures when the tentative diagnosis from complementary mammary diagnostic procedures revealed no pathological findings and concurred with the histological results of the punch biopsy. In 188 women, the biopsy was followed by surgical intervention and correlation of the histological findings. This group of patients showed a sensitivity of 98%, a specificity and positive prognostic value of 100%, and a negative prognostic value of 91%. If we combine the results of the complementary mammary diagnostic (including the punch biopsy), then the sensitivity, specificity, and positive and negative prognostic values for this surgically and histologically confirmed group of patients all reach 100%. In trained hands, the ultrasonic guided high-speed punch is a reliable means of determining the histological nature of lesions detected in ultrasonic scans. This technique has been perfected in our facility. Along with preoperative carcinoma detection, it permits us to avoid unnecessary operations when under defined conditions there are no pathological findings.

Adolescent↗
PubMed1994

Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS.

Treatment of cryptococcal meningitis with amphotericin B or fluconazole is often unsuccessful; in only 35%-40% of cases do CSF cultures become negative by 10 weeks after initiation of such therapy. We conducted a prospective, open-label clinical trial involving persons with AIDS to determine whether the rate of clinical success would improve when fluconazole (400 mg daily) was combined with flucytosine (150 mg/kg daily). At the conclusion of 10 weeks of therapy, 75% (95% confidence interval, 58%-87%) of 32 subjects' CSF cultures were negative. The Kaplan-Meier estimate of clinical success at 10 weeks was 63% (95% confidence interval, 48%-82%). The median time to negativity of the CSF culture was 23 days. Toxic side effects that were sufficiently severe to lead to the withdrawal of flucytosine were observed in nine subjects (28%). In this pilot study of fluconazole combined with flucytosine, the rate of clinical success at 10 weeks was greater than that previously reported with regard to the use of fluconazole alone or amphotericin B alone.

AIDS-Related Opportunistic Infections↗
PubMed1994

Treatment of neuroblastoma patients with antiganglioside GD2 antibody plus interleukin-2 induces antibody-dependent cellular cytotoxicity against neuroblastoma detected in vitro.

Therapy of neuroblastoma patients with interleukin (IL)-2 activates effector cells capable of lysing tumor cells in vitro. When tumor cells are pretreated with certain monoclonal antibodies (MoAb), these in vivo activated effectors show augmented tumor lysis via antibody-dependent cellular cytotoxicity (ADCC). This study presents immunological analyses of serial blood samples from two refractory neuroblastoma patients who received combined in vivo therapy with murine anti-ganglioside GD2 monoclonal antibody 14.G2a and IL-2. These studies were designed to determine whether conditions that induce ADCC in vitro can be generated in vivo by combined therapy with IL-2 and MoAb. As shown previously, administration of IL-2 dramatically augments the ability of peripheral blood mononuclear cells (PBMC) to mediate ADCC. In addition, we demonstrate here that sera, obtained 1 h after infusion of 14.G2a, provides an effective source of functional antibody for ADCC mediated by PBMC from healthy donors. Finally, effective ADCC-mediated killing of neuroblastoma target cells was also achieved in vitro following IL-2 plus 14.G2a treatment when patients' effector cells were combined with patients' serum, as the source of 14.G2a antibody. These results indicate that this combination of IL-2 and 14.G2a generates conditions within the peripheral blood of pediatric neuroblastoma patients that enable their own lymphocytes to mediate antibody-dependent cellular cytotoxicity sufficient to effectively kill neuroblastoma cells in vitro.

Antibodies, Monoclonal↗
PubMed1994

Phase I study of tumor necrosis factor-alpha and actinomycin D in pediatric patients with cancer: a Children's Cancer Group study.

In preclinical studies, synergy was observed between tumor necrosis factor-alpha (TNF-alpha) and agents that interact with DNA topoisomerase II, such as actinomycin D (Act D). Based upon this, a Phase I study was conducted in pediatric patients utilizing an escalating dose of recombinant TNF (rTNF) in combination with a fixed dose of Act D. Act D (15 micrograms/kg/day) was administered daily by intravenous push immediately followed by intravenous rTNF daily for 5 consecutive days. Thirty-three patients with refractory malignancies were entered in the study, of whom 28 patients could be evaluated for toxicity. Malignancies included sarcomas (16), Wilms' tumor (6), leukemias (3), and others (3). The starting dose for rTNF was 40 micrograms/m2/day x 5 and was escalated in subsequent patient groups until nonhematopoietic, dose-limiting toxicity occurred. At 240 micrograms/m2/day of rTNF, three of six patients experienced grade 4 toxicity consisting of hypotension, hemorrhagic gastritis, and renal and liver biochemical abnormalities. Evidence of antitumor response was observed in two patients: one with metastatic Ewing's sarcoma and one with Wilms' tumor. We conclude that the maximum tolerated dose of rTNF when combined with Act D is between 200 and 220 micrograms/m2/day x 5 for pediatric patients.

Adolescent↗
PubMed1994

Dose-related pattern of sinusoidal leukocyte adhesion in sublobular regions of the liver after systemic endotoxin challenge in the rat.

The unique arrangement of large numbers of fixed tissue macrophages, endothelial, and parenchymal cells along hepatic sinusoids as well as their key role in the acute phase response makes the liver a primary target organ in endotoxemia. Pathogenesis of hepatic failure in endotoxemia is incompletely understood, but microcirculatory failure as well as leukocyte-endothelial interaction in response to inflammatory mediators may relate to it. Using intravital fluorescence microscopy, sinusoidal widths, leukocyte flow velocity, and sublobular leukocyte (white blood cell (WBC)) adhesion characteristics 1 h after randomized intravenous application of 0, 0.1, 1, or 5 mg/kg b.w. Escherichia coli endotoxin O 111 B4 (ETX) were evaluated in female Sprague-Dawley rats (n = 6-8/group). Whereas the bolus injection of ETX caused only minor concurrent macrohemodynamic effects, a significant increase of permanent WBC adhesion especially in periportal areas (0 mg, 2.1 +/- 0.7%; 0.1 mg, 16.2 +/- 3.6%**; 1 mg, 15.5 +/- 1.0%**; 5 mg, 13.2 +/- 2.3%* (**p < .01, *p < .05, compared to vehicle)) was found in all groups 60 min after ETX challenge. In contrast, an increase of WBC margination in midzonal and pericentral regions was only seen with the higher doses of 1 or 5 mg/kg ETX, respectively. The sublobular pattern of WBC margination is consistent with the concept of regulation of WBC adhesion by inflammatory mediators released by lipopolysaccharide-stimulated Kupffer cells in vivo. We propose that overwhelming the detoxifying capacity of predominantly periportally located Kupffer cells with large amounts of ETX may lead to activation of pericentral-located resting macrophages paralleled by a rise of adhering leukocytes.

Animals↗
PubMed1994

Hepatic intercellular communication in shock and inflammation.

The liver is well recognized as a target for injury during low flow or inflammatory states. Functionally, the result is both metabolic and host defense dysfunction. Although the liver is clearly responsive to changes in systemic levels of various mediators, it is becoming apparent that substantial changes occur within the liver that are not directly dependent on extrahepatic factors. This is the result of complex interactions among the various cell types that exist in a highly organized arrangement within the functional subunit of the liver. The purpose of this review is to summarize the structural relationships which form the basis for this system of cell-cell communication and their functional implications both in the normal liver and during both low-flow and normal-flow inflammatory states.

Animals↗
PubMed1994

Nucleotide sequence of the Wolinella succinogenes flagellin, which contains in the antigenic domain two conserved regions also present in Campylobacter spp. and Helicobacter pylori.

Wolinella succinogenes possesses one polar flagellum, which shows a characteristic surface pattern of parallel lines along the axis of the filament in electron microscopic images. We determined the gene sequence of the Wolinella flagellin, which is, as in most other bacteria, the only structural component of the filament. Sequence comparison with other members of the Proteobacteria revealed two highly conserved regions in the central part of the flagellin molecule among Campylobacter spp. and Helicobacter pylori, an area that had previously been described as highly variable. Similar surface patterns are found in related polarly flagellated bacteria, but not in Escherichia coli and Bacillus subtilis, which also lack these conserved regions.

Amino Acid Sequence↗
PubMed1994

ET-1 induced alterations of hepatic microcirculation: sinusoidal and extrasinusoidal sites of action.

Using epifluorescence microscopy, we investigated the dynamic changes in hepatic sinusoidal hemodynamics in vivo during continuous infusion of endothelin-1 (ET-1) in pentobarbital-anesthetized rats. ET-1 was infused for 20 min at rates of 2 or 10 pmol/min either systemically or into the portal vein, followed by a 90-min recovery period. In contrast to systemic application of ET-1 that did not cause a consistent hepatic microvascular effect, we observed two different patterns of microcirculatory alterations during portal application. Infusion of 2 pmol/min elicited a rapid, reversible decrease in sinusoidal diameter that was paralleled by a slight increase in red cell velocity, resulting in conservation of volumetric flow and sinusoid density. Infusion of 10 pmol/min resulted in a biphasic narrowing followed by transient increase in sinusoidal diameter and a profound and lasting decrease in red cell velocity, leading to an almost complete cessation of hepatic microvascular blood flow. These results indicate that ET-1 is a potent constrictor in the liver microcirculation in vivo and acts at both extrasinusoidal and sinusoidal sites, although the sinusoidal sites appear to be more sensitive to lower concentrations.

Animals↗
PubMed1994

Psychopathology and long-term adjustment after crises in refugees from East Germany.

OBJECTIVE: In this study we examined psychopathology, diagnoses, social adjustment and the course of symptoms over two and a half years in East German refugees who suffered a crisis immediately after migrating to West Berlin just prior to or shortly after the breaching of the Wall in autumn 1989. METHODS: One hundred and twenty two refugees seeking crisis intervention in a psychiatric outpatient unit after arrival were investigated. Six months later 59% and two and a half years after migration 30% of the patients were re-examined. RESULTS: The patients had been exposed to prolonged stress situations in East Germany and were suffering from anxious-depressive syndrome with vegetative complaints. Sixty patients required more than one crisis intervention during the first six months after resettlement. During the follow-up period symptoms decreased significantly. At the second follow-up interview 81% of the patients had a satisfactory job, and 89% acceptable accommodation. CONCLUSIONS: Satisfactory classification of the psychiatric disorders induced in East German refugees by prolonged stress was not possible according to the DSM-III-R criteria. Initial crises are not necessarily associated with poor long-term adjustment after migration.

Acculturation↗
PubMed1994

Endothelin-1 as a regulator of hepatic microcirculation: sublobular distribution of effects and impact on hepatocellular secretory function.

Endothelin-1 is a potent vasoconstrictor in the portal circulation causing sinusoidal constriction as well as presinusoidal resistance changes. Using in vivo videomicroscopy we studied the sublobular differences in dose response characteristics of sinusoid constriction at 10-13 min into continuous infusion of 5, 1.0, 3.0, and 5.0 pmol of endothelin-1 (ET-1)/100 g body weight/min in pentobarbital anesthetized rats. In addition, bile flow was monitored to estimate parenchymal secretory function. ET-1 evoked a profound constrictor effect in both sublobular regions studied. However, the maximal decrease of sinusoidal width in periportal inflow region (zone 1; 1 pmol/100 g/min: 4.8 +/- .1 microns) was reached at slightly lower concentrations of the peptide than in pericentral outflow region (zone 3; 3 pmol/100 g/min: 6.2 +/- .3 microns) compared to respective baseline values (zone 1: 7.1 +/- .1 microns; zone 3: 10.2 +/- .1 microns), suggesting upstream binding and clearance of the peptide. The constrictor response in zone 1 was biphasic and at higher concentrations of the peptide (5 pmol/100 g/min: 5.5 +/- .2 microns) sinusoidal widths increased again compared to the maximal response with the 1 pmol. Secretory function as reflected by the bile flow was maintained or even slightly increased with the lower doses (.5 and 1 pmol) of ET-1 and during the first 10 min into infusion of the higher doses (3 and 5 pmol). Subsequently, an approximately 20-25% decrease in bile flow accompanied the infusion of higher doses of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Involvement of platelet activating factors in pathologic leukocyte-endothelium interactions in the liver after hemorrhagic shock].

INTRODUCTION: Microcirculatory disturbances and increased adhesion of leukocytes to the hepatic endothelium immediately following hemorrhagic shock have been observed. It is currently discussed, that mediators released by activated macrophages may have regulative functions for these alterations. The aim of the study performed was to investigate the effects of platelet activating factor (PAF) by application of PAF-receptor antagonists in respect to disorders of liver microcirculation and leukocyte adhesion following hemorrhagic shock. METHODS: Sprague-Dawley rats, anesthetized with pentobarbital, were exposed to hemorrhagic shock by depression of the mean arterial blood pressure (MABP) to 40 mmHg for 60 min by controlled blood removal. Three hours following adequate volume replacement together with blood retransfusion (60%) and at normalized MABP as well as supranormal cardiac output levels, the livers of the animals were investigated by intravital microscopy in respect to leukocyte adhesion and microcirculation. Evaluation of the microcirculation of 5 liver lobules/animal was performed on SVHS recorded images using a computer-assisted image analysis system. Three shock groups (n = 6 rats) and one sham-operated control group (n = 8) were compared. Shock/NaCl group received 0.1 ml NaCl 0.9% 15 min prior to shock induction and 1 min prior to shock therapy i. v., respectively. Shock/BN group received a total of 10 mg/kg of the PAF-antagonist BN 52021 (Dr. Braquet, Paris) and Shock/WEB group 2 mg/kg of the PAF antagonist WEB 2086 (Boehringer, Ingelheim), respectively in 2 injections with identical volume. RESULTS: The course of hemodynamic parameters MABP and cardiac output were comparable in all 3 shock groups. Metabolic parameters such as acid-base state and hematocrit values did not reveal differences. Evaluation of liver microcirculation indicated in all shock groups a reduction of sinusoidal diameters and a slight increase of velocity of leukocytes. The significantly increased temporary adhesion of leukocytes with an adhesion time shorter than 20s in the shock/NaCl group (adhesion index 154.1 +/- 63.2s/100 leukocytes; mean +/- SD) was reduced significantly by the PAF antagonists BN 52021 (82.2 +/- 24.2) and WEB 2086 (86.0 +/- 30.0). Permanent adhesion with an adhesion time longer than 20s was increased significantly particularly in zone I of the liver acinus (portal region) in all shock groups without specific effects of the PAF antagonists. CONCLUSIONS: Liver microcirculation following adequately treated hemorrhagic shock was disturbed, as indicated by narrowed sinusoids and increased adhesion of leukocytes. PAF seems to have no effect on sinusoidal narrowing in this period, however, it seems involved in temporary adhesion of leukocytes. The relevance of these early changes following hemorrhagic shock in respect to the development of organ dysfunction should be further addressed.

Animals↗
PubMed1994

Clozapine treatment after agranulocytosis induced by classic neuroleptics.

Despite its potentially fatal side effect--agranulocytosis--clozapine has become an important drug in antipsychotic treatment. With this in mind, this report presents the case of a 23-year-old schizophrenic who had suffered from agranulocytosis after simultaneous short-term treatment with butyrophenone and phenothiazine neuroleptics 3 years ago. After nonresponse to two other classic neuroleptics, the administration of high-dose clozapine led to a full recovery without the recurrence of hematologic disorders during 24 months of follow-up examinations. Although patients with a known history of agranulocytosis are usually excluded from treatment with clozapine, we propose that, in very severe or otherwise therapy-resistant cases, clozapine be administered and then white blood cell counts monitored very stringently. Although a single case can prove little, our case provides further evidence for the presumption that noncross-reactivity exists between clozapine and other neuroleptic drugs in the induction of agranulocytosis.

Adult↗