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Biomedical subjects

Michael Bauer

Publications and source records attributed to Michael Bauer.

102 records · Page 6Linked to original sources
PubMed2002

Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression.

Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressant were assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P.M. and CRH stimulation at 3 P.M. on the next day). Twenty-four patients were re-assessed after response was determined or, in cases of non-response, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton Depression Rating Scale (HDRS 17-item version). Response was defined as a DeltaHDRS of > or =50% and an endpoint score of < 10. Patients had a significantly higher ACTH and cortisol response to CRH stimulation during lithium augmentation compared with the values at baseline. There was no difference in ACTH and cortisol reaction between responders and non-responders to lithium augmentation. This increase is in contrast to the known normalization of HPA-axis overdrive after treatment with a tricyclic antidepressant like amitriptyline. Because the effect was independent of response status we suggest that this increase reflects an effect of lithium that is independent from the psychopathological state or its change. This effect might be explained by the serotonergic effects of lithium.

Adolescent↗
PubMed2002

Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in the stress-exposed rat liver.

Heme oxygenase (HO)-1 is up-regulated after ischemia/reperfusion and contributes to maintenance of hepatic perfusion and integrity. Blockade of HO-1 leads to an increased portal pressor response in the stress-exposed liver. We tested whether the increase in portal pressure reflects unmasking of a concomitant up-regulation of the vasoconstrictor endothelin (ET)-1. Hemorrhagic shock induced messenger RNAs encoding HO-1 (16-fold) and ET-1 (9-fold) with a similar time course in the liver. At maximum induction of both mediators, rats received either vehicle or the endothelin ET(A/B) antagonist bosentan (10 mg/kg intravenously). Subsequently, the HO pathway was blocked in all animals by tin-protoporphyrin (SnPP)-IX (50 micromol/kg intravenously). Portal and sinusoidal hemodynamics were measured using microflow probes and intravital microscopy, respectively. Blockade of the HO pathway led to a significant increase in portal resistance (sham/SnPP-IX, 0.17 +/- 0.046 mm Hg. min. mL(-1); shock/vehicle/SnPP-IX, 0.57 +/- 0.148 mm Hg. min. mL(-1); P <.05) and a decrease in sinusoids conducting flow (shock/vehicle/SnPP-IX: baseline, 28.3 +/- 0.85 sinusoids/mm; 10 minutes after SnPP-IX, 23.1 +/- 1.09 sinusoids/mm; P <.05). Intravital microscopy showed narrowing of failing sinusoids colocalizing with stellate cells after blockade of the HO pathway. Blockade of ET(A/B) receptors attenuated the increase in portal resistance (shock/bosentan/SnPP-IX, 0.29 +/- 0.051 mm Hg. min. mL(-1)) and prevented sinusoidal perfusion failure (shock/bosentan/SnPP-IX: baseline, 28.2 +/- 0.97 sinusoids/mm; 10 minutes after SnPP-IX, 28.8 +/- 1.18 sinusoids/mm) as well as sinusoidal narrowing. In conclusion, a functional interaction of the up-regulated vasodilatory HO system and the vasoconstrictor ET-1 on the sinusoidal level exists under stress conditions. Both mediator systems affect sinusoidal diameter via direct action on hepatic stellate cells in vivo.

Animals↗
PubMed2002

Hepatic redox regulation of transcription factors activator protein-1 and nuclear factor-kappaB after hemorrhagic shock in vivo.

Ischemia and reperfusion result in a hepatocellular stress gene response, characterized by a zonal heterogeneity with pericentral hepatocytes being the primary target. In the present study, we assessed cell type-specific and zonal pattern of activation of redox-sensitive transcription factors nuclear factor-kappaB (NFkappaB) and activator protein-1 (AP-1) in a graded model of hemorrhage and their modulation by the antioxidants trolox and tempol. Hemorrhagic hypotension (35-40 mm Hg) up to 3 h without subsequent resuscitation led to an only moderate activation of NFkappaB and AP-1. In contrast, fluid resuscitation after 1 or 2 h of hemorrhage induced a profound activation of AP-1 within the first hour of reperfusion. Consistent with a regulation by oxygen free radicals, activation of AP-1 was substantially attenuated by antioxidants. The faint activation of NFkappaB with various intervals of hemorrhage was unaffected by antioxidants and did not exceed activation with sham operation. Immunohistochemistry for the AP-1 subunit c-Jun revealed a predominant expression in nuclei of pericentral and midzonal hepatocytes. These data suggest activation of AP-1 in hepatocytes most susceptible to injury and reprogramming of gene expression in low-flow ischemia. Whereas activation of NFkappaB is weak in this model and is not modulated by either reperfusion or antioxidants, regulation of AP-1 after hemorrhage and subsequent resuscitation seems to depend on oxygen free radical formation because it requires reperfusion and is inhibitable by antioxidants.

Animals↗
PubMed2002

Heme oxygenase-1: redox regulation and role in the hepatic response to oxidative stress.

Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXalpha, free divalent iron, and carbon monoxide (CO). Among the three isoenzymes cloned to date, only HO-1 can be induced by a variety of seemingly disparate stimuli, most of which are linked by their ability to provoke oxidative stress. Although constitutive expression of HO-1 in the liver is restricted to Kupffer cells, the gene is inducible in nonparenchymal as well as in parenchymal liver cells. HO-1 induction potentially confers protection against oxidative stress in a variety of experimental models, such as liver ischemia/reperfusion secondary to transplantation or hemorrhage/resuscitation. Induction of HO-1 may protect the cell against oxidative injury by (a) controlling intracellular levels of "free" heme (a prooxidant), (b) producing biliverdin (an antioxidant), (c) improving nutritive perfusion via CO release, and (d) fostering the synthesis of the Fe-binding protein ferritin. Although protective effects of up-regulation of the HO pathway--presumably through production of bile pigments and CO--have been reported for a variety of cells and tissues, including the liver, evidence suggests that the protective action might be restricted to a rather narrow threshold of overexpression. High levels of HO-1 may even sensitize the cell to oxidative stress, e.g., through release of reactive iron. Transcriptional activation of the HO-1 gene is an integral part of the cellular response to oxidative stress, but its induction seems to be neither exclusively cytoprotective nor exclusively cytotoxic.

Animals↗
PubMed2002

Impact of alloantigens and storage-associated factors on stimulated cytokine response in an in vitro model of blood transfusion.

BACKGROUND: Transfusion of blood may contribute to immunosuppression in major surgery. The authors assessed the impact of alloantigens and storage on function of peripheral blood mononuclear cells cultured in their physiologic environment. METHODS: Blood units (whole blood, packed erythrocytes) were prepared with or without prestorage leukodepletion and stored for 24-26 days. Blood samples were coincubated with allogeneic fresh blood, autologous, or allogeneic stored blood. Endotoxin-stimulated release of tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) was measured after 24 h of culture by enzyme-linked immunosorbent assay. RESULTS: Coincubation with equal amounts of allogeneic fresh blood showed almost no influence on TNF-alpha (-12%, not significant) and IL-10 (+11%, not significant) release. Stored allogeneic whole blood resulted in a significant TNF-alpha depression (-61%) and IL-10 induction (+221%). These effects were diminished but not prevented by prestorage leukodepletion (TNF-alpha -42%, IL-10 +110%) and required the presence of soluble factors (TNF-alpha suppression) and cellular components (IL-10 induction). TNF-alpha decrease and IL-10 increase were in the same order of magnitude (-40%, +134% with, -65%, +314% without leukodepletion) after coincubation with autologous blood. In contrast, allogeneic erythrocytes had only little effects (TNF-alpha -6%, IL-10 +36%) even at this high transfusion equivalent. CONCLUSION: These data suggest that banked whole blood has an immunosuppressive effect that is largely attributable to storage-dependent factors. These factors are partially removed by prestorage leukodepletion, while the contribution of alloantigens is of minor significance. Immunosuppressive effects are least apparent with leukodepleted erythrocytes, suggesting that the presence of plasma during storage is required for the immunosuppressive effect to develop.

Blood Preservation↗
PubMed2002

How long should the lithium augmentation strategy be maintained? A 1-year follow-up of a placebo-controlled study in unipolar refractory major depression.

There is compelling evidence from placebo-controlled studies that lithium augmentation is an effective strategy in the acute and continuation treatment of refractory unipolar major depression. Authors prospectively investigated the 1-year outcome of 22 subjects diagnosed with unipolar major depression who had participated in a 4-month placebo-controlled, double-blind continuation study of lithium augmentation without relapse. At the end of the double-blind phase, the blinded medication (lithium in 14 patients, placebo in 8 patients) was tapered off over a 1-week period, while the antidepressant was continued at the same dosage for another 4 weeks. Subsequently, the antidepressant was gradually discontinued over a 4-week period. Clinical status was assessed at regular follow-up visits. During the open 6-month follow-up period, seven subjects suffered an affective recurrence, five of whom had received lithium during the placebo-controlled, double-blind phase of the study. Study data suggest that active medication should be maintained for at least 1 year after successful lithium augmentation in patients with unipolar major depressive disorder.

Adult↗
PubMed2002

Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass.

We investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (CPB). Whole blood of nine patients undergoing CPB and 25 patients with severe sepsis was stimulated ex vivo with LPS (E. coli O111:B4) or with Staphylococcus aureus Cowan strain I (SAC-I) lysate in the absence or presence of inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), or protein-tyrosine phosphatase (PTP). Both toxins stimulated a TNF-alpha response through PTK signaling. Although suppression of the cytokine response was similar for LPS and SAC-I after CPB, it was significantly more pronounced for SAC-I in sepsis. Inhibition of PTP failed to increase TNF-alpha upon LPS, whereas a moderate increase was observed with SAC-I. Impaired TNF-alpha responses occur in sepsis and after CPB. Although this has primarily been reported for gram-negative stimuli, our data suggest that this is even more pronounced for gram-positive stimuli in severe sepsis. Although PTK was the predominant signaling pathway, inhibition of PTP only partially restored the TNF-alpha response to SAC-I. Our results suggest that cellular mechanisms underlying monocyte deactivation are different in sepsis or following CPB and are discriminate for gram-positive and gram-negative toxins.

Adult↗
PubMed2002

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and continuation treatment of major depressive disorder.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). This first part of the guidelines covers disease definition, classification, epidemiology and course of unipolar depressive disorders, as well as the management of the acute and continuation-phase treatment. These guidelines are primarily concerned with the biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Adolescent↗
PubMed2002

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with the biological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Adolescent↗
PubMed2002

Effectiveness and feasibility of a standardized stepwise drug treatment regimen algorithm for inpatients with depressive disorders: results of a 2-year observational algorithm study.

BACKGROUND: The goal of the Berlin Algorithm Project is to establish a standardized stepwise drug treatment regimen (SSTR) for the treatment of inpatients with depressive disorders. We are reporting on the first of 3 subsequent study phases evaluating effectiveness and feasibility of the SSTR in a naturalistic clinical setting. METHOD: Patients with depressive disorders (International Classification of Diseases, Ninth Revision criteria) admitted to an academic medical center for inpatient treatment were enrolled in the SSTR protocol that comprised an algorithm-guided sequential treatment process (including pharmacologic washout period, sleep deprivation, antidepressant monotherapy, lithium augmentation, monoamine oxidase inhibitor treatment, and electroconvulsive therapy) dependent on the scores of a standardized assessment of treatment outcome, the Bech Rafaelsen Melancholia Scale (BRMS). RESULTS: Of 248 patients with depression, 119 (48%) were enrolled in the SSTR protocol. One hundred twenty-nine patients (52%) were not included, mostly due to individualized treatment procedures. An intent-to-treat (ITT) analysis showed that 38% of enrolled patients achieved remission (BRMS score < or = 5), 34% achieved "classic" response (deltaBRMS score > or = 50%), 15% achieved "low" response (deltaBRMS score 26% to 49%), and 13% did not respond. The overall response rate (remitters and classic responders) of SSTR treatment was 72% of the ITT sample. Twenty-one patients (18%) dropped out from the SSTR as nonresponders and 19 patients (16%) dropped out as low responders due to protocol deviations. CONCLUSION: The acceptance of the antidepressive treatment algorithm among physicians not specifically trained was moderate, resulting in a relatively low enrollment rate. However, once patients were enrolled into the study, adherence to the algorithm-based rules resulted in a low dropout rate. Most importantly, algorithm-guided antidepressive treatment showed a favorable response in those depressed patients who were treated according to the SSTR protocol.

Algorithms↗
PubMedDate not supplied

Association between response to lithium augmentation and the combined DEX/CRH test in major depressive disorder.

Although lithium augmentation is the foremost and most well-documented treatment strategy for treatment resistant depression, knowledge of factors related to response remains scanty. Findings with the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are associated with response to treatment with a tricyclic antidepressant. This study investigated the potential predictive value of the DEX/CRH test for lithium augmentation response in major depressive disorder. The DEX/CRH test was conducted prior to lithium augmentation in 30 patients with a major depressive episode who had not responded to an antidepressant monotherapy trial of at least 4 weeks. Response status was assessed weekly using the Hamilton Rating Scale for Depression. For multivariate prediction, a logistic regression analysis was performed. Eleven (37%) patients responded to lithium augmentation within 4 weeks. Responders showed higher ACTH response and lower cortisol response in the DEX/CRH test, but results were not statistically significant. However, non-responders had a statistically significant higher cortisol/ACTH peak ratio (3.43+/-1.75) compared to responders (2.18+/-1.38) (P=0.027). This ratio is an indicator for the sensitivity of the adrenal cortex to ACTH. A cortisol/ACTH peak ratio of 1.8 was identified as the best cutoff point to differentiate responders from non-responders. In conclusion, results suggest a more sensitive adrenal cortex in non-responders to lithium augmentation. The findings would be in line with the assumption of a more chronic course of depression with more pronounced biological alterations in the non-responder group, because chronic depression is known to cause enlargement of the adrenal gland with a subsequent hypersensitivity to ACTH. Results of this study should be confirmed in a larger study group.

Adrenocorticotropic Hormone↗