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Biomedical subjects

Michael Bauer

Publications and source records attributed to Michael Bauer.

At least 55 records · Page 3Linked to original sources

Liver failure.

PURPOSE OF REVIEW: Liver failure is a rare but life-threatening condition affecting a multitude of other organ systems, most notably the brain and kidneys, following severe hepatocellular injury. Liver failure may develop in the absence ('acute') or presence ('acute-on-chronic') of liver disease with substantial differences in pathophysiology and therapeutic options. Within the last 12 months substantial progress has been made in identifying patients who will potentially benefit from extracorporeal support of their failing liver. RECENT FINDINGS: In addition to traditional 'static' laboratory tests to assess liver function, the significance of 'dynamic' tests, such as indocyanine green clearance, has been better defined, and these tests are becoming more easily available. Transplantation remains the treatment of choice for fulminant, acute and subacute liver failure with predicted unfavorable outcome according to King's College or Clichy criteria, most notably in the absence of pre-existing liver disease, and should be performed before extrahepatic complications emerge. Encouraging results have been obtained with the use of support systems in patients with acute and acute-on-chronic liver failure in relatively small patient collectives, making well-conducted randomized trials a necessity to define their role in this high-risk population. Current (pre)clinical data suggest that programmed cell death is an important mechanism for the pathogenesis of acute and acute-on-chronic liver failure and, thus, antiapoptotic strategies are promising pharmacologically. SUMMARY: Although mortality remains high, substantial progress has been made in 2004 regarding the understanding of pathophysiology, and the monitoring and support of the patient presenting with a failing liver.

Journal Article↗

Influence of heme-based solutions on stress protein expression and organ failure after hemorrhagic shock.

OBJECTIVE: Hemoglobin-based oxygen carriers (e.g., diaspirin-cross-linked hemoglobin [DCLHb] and hemoglobin glutamer-200 [HbG]) may have potential in the treatment of hemorrhagic shock. The nitric oxide scavenging and direct vasoconstrictive side effects of free hemoglobin of currently available preparations may increase organ injury after shock in contrast to non-oxygen-carrying heme solutions (e.g., hemin arginate [HAR]). However, both classes of substances might induce the protective enzyme heme oxygenase (HO)-1, particularly in the liver. The aim of the study was to assess the role of pretreatment with DCLHb, HbG, or HAR on HO-1 expression and organ injury after hemorrhagic shock. DESIGN: Prospective controlled laboratory study. SETTING: Animal research laboratory at a university hospital. SUBJECTS: Male Sprague-Dawley rats (200-300 g body weight, n = 5-12/group). INTERVENTIONS: Twenty-four hours after different doses of DCLHb, HbG (each 1, 2, or 3 g/kg of body weight), or HAR (5, 25, or 75 mg/kg of body weight), the protein expression of HO-1 and heat shock protein-70 in liver, kidney, heart, lungs, and aorta was determined. Twenty-four hours after pretreatment with DCLHb, HbG, or HAR, rats were subjected to hemorrhage (mean arterial blood pressure, 35-40 mm Hg for 1 or 2 hrs)/resuscitation (5 or 4 hrs, respectively). Animals treated with Ringer's solution (30 mL/kg of body weight) served as controls. In additional experiments, HO activity was blocked with tin mesoporphyrin-IX. MEASUREMENTS AND MAIN RESULTS: DCLHb, HbG, and HAR dose-dependently induced HO-1 protein but not heat shock protein-70. Pretreatment with DCLHb or HbG shortened the onset of decompensation in shock (DCLHb, 40 +/- 11 mins; HbG, 36 +/- 4 mins) compared with vehicle (68 +/- 4 mins, p < .05) and HAR pretreatment (81 +/- 7 mins, p < .05). High doses of DCLHb pretreatment increased mortality (2 hrs of shock, 80%; p < .05 vs. vehicle or HAR). Pretreatment with HAR led to higher shed blood volumes (p < .05) and higher hepatocellular ATP levels (2 hrs of shock, p < .05 vs. DCLHb and HbG). Blockade of HO activity by tin mesoporphyrin-IX abolished the protection mediated by HAR. CONCLUSIONS: Although DCLHb, HbG, and HAR induce HO-1 in the absence of an unspecific stress response, only HAR pretreatment protects against shock-induced organ failure. Although the underlying mechanisms of positive HAR priming are not completely understood, the induction of HO-1 expression and the lack of nitric oxide scavenging through HAR may play an important role.

Animals↗

Plasma platelet-activating factor acetylhydrolase activity in critically ill patients.

OBJECTIVE: Platelet-activating factor (PAF) is a potent proinflammatory mediator in systemic inflammation and sepsis and is inactivated by the enzyme PAF-acetylhydrolase (PAF-AH). Recently, a large phase III clinical trial using recombinant PAF-AH to treat patients with severe sepsis was performed but failed to reduce 28-day mortality rate. To get more information on the activity of PAF-AH in sepsis, we repeatedly measured its activity in plasma in critically ill patients compared with healthy controls. DESIGN: Retrospective cohort study. SETTING: Intensive care unit. PATIENTS: Two hundred thirty-one patients who were admitted to an operative intensive care unit within 1 yr were enrolled and evaluated daily for American College of Chest Physicians/Society of Critical Care Medicine criteria. PAF-AH activity was measured as the release of [H]-acetate from [H]-acetyl-PAF. INTERVENTIONS: Analysis of plasma samples. MEASUREMENTS AND MAIN RESULTS: At the day of admission, PAF-AH activity of patients was below controls but markedly increased over time. Higher activities were seen in patients with severe sepsis or septic shock compared with those without organ failure. With respect to the clinical outcome, lower values were found in nonsurvivors only as long as they had not developed organ failure. In severe sepsis/septic shock, values of nonsurvivors exceeded those of survivors. PAF-AH activity was positively correlated with plasma levels of inflammatory mediators such as neopterine and tumor necrosis factor-alpha but not with acute phase reactants such as C-reactive protein, interleukin-6, or PCT. In addition, parenteral nutrition with lipid emulsions was seemingly associated with low PAF-AH activity compared with enteral nutrition. CONCLUSION: The data indicate severity- and time-dependent changes in PAF-AH activity and may help to explain the failure of recombinant PAF-AH treatment strategies that were not based on activity measurements.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Inhibitors of NADPH oxidase reduce the organ injury in hemorrhagic shock.

Reactive oxygen species contribute to the multiple organ dysfunction syndrome in hemorrhagic shock. Here, we investigate the effects of two chemically distinct inhibitors of NADPH oxidase on the circulatory failure and the organ dysfunction and injury associated with hemorrhagic shock in the anesthetized rat. Hemorrhage (sufficient to lower mean arterial blood pressure of 45 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure and in renal dysfunction and liver injury. Treatment of rats upon resuscitation with the NADPH oxidase inhibitors diphenylene iodonium (DPI, 1 mg/kg i.v.) reduced renal dysfunction and liver injury, whereas apocynin (3 mg/kg i.p.) did reduce the liver injury, but not the renal dysfunction caused by hemorrhagic shock. DPI and apocynin also attenuated the lung and intestinal injury (determined by histology) caused by hemorrhage and resuscitation. In the liver, DPI and apocynin abolished the increase in the formation of superoxide anions associated with hemorrhagic shock. However, neither DPI nor apocynin had a significant effect on the delayed circulatory failure caused by hemorrhage and resuscitation. In addition, DPI and apocynin did not reduce the increase in nitric oxide synthesis caused by hemorrhagic shock. Moreover, DPI reduced the activation of the transcription factor activator protein-1 caused by severe hemorrhage and resuscitation in the liver. Thus, we propose that an enhanced formation of superoxide anions by NADPH oxidase contributes to the liver injury caused by hemorrhagic shock, and that inhibitors of NADPH oxidase may represent a novel therapeutic approach for the therapy of hemorrhagic shock.

Acetophenones↗

Hallucinations in bipolar disorder: characteristics and comparison to unipolar depression and schizophrenia.

OBJECTIVE: As there is very little research on the topic, we compared the frequency and the type hallucinations among hospitalized patients diagnosed with bipolar disorder (BPD) versus other major psychiatric illnesses. METHODS: At admission, all patients hospitalized at the Department of Psychiatry at the Freie Universität Berlin (1981-2001) underwent comprehensive assessments using the standardized Association for Methodology and Documentation in Psychiatry (AMDP) system. We used these data to compare risks and types of hallucinations and associated factors by bivariate and multivariate testing in patients diagnosed with BPD, major depression, or schizophrenia. RESULTS: At admission, the cross-sectional prevalence of current hallucinations among 4972 hospitalized subjects ranked: schizophrenia (61.1%), bipolar mixed (22.9%), bipolar manic (11.2%), bipolar depressed (10.5%), unipolar depressed (5.9%). The most frequent hallucinations across all patients were auditory, followed by somatic and visual hallucinations. There were only minor age or sex differences in risk of hallucinations. Compared with patients diagnosed with schizophrenia, hallucinations among patients with BPD were less severe, more visual and less often auditory. Characteristics of hallucinations were similar among manic and both bipolar- and unipolar-depressed subjects. Among patients with major affective disorders, those with hallucinations were less well-educated, had higher anxiety scores, less insight into the illness, and their hospitalizations averaged 17% longer. Across all diagnoses, hallucinations, particularly olfactory, were significantly associated with delusions. Hallucinations in BPD were most often accompanied by persecutory delusions; delusions of grandeur were least associated with hallucinations. CONCLUSIONS: This study provides detailed descriptive data regarding the frequency (cross-sectional) and characteristics of hallucinations in a large sample of patients with BPD, major depression or schizophrenia. Our results suggest a link of lower education and the presence of hallucinations in major affective disorders. The significance of this finding, as well as the role of anxiety in hallucinating patients, requires further study.

Adult↗

Epidemiology of bipolar disorders.

UNLABELLED: Bipolar, or manic-depressive, disorders are frequent and severe mental illnesses associated with considerable morbidity and mortality. Epilepsy and bipolar disorder could probably share some aspects of pathophysiology because manic as well as depressive symptoms are seen in patients with seizures, and a number of antiepileptic drugs are effectively used in the acute and prophylactic treatment of bipolar disorder. Epidemiologic research suggests a dimensional composition of bipolar illness at the population level. Apart from the DSM-IV diagnostic features of bipolar I (mania and depression) and bipolar II (hypomania and depression), the concept of bipolar spectrum disorders comprises a range of bipolar conditions with less obvious manifestations with estimated lifetime prevalence rates ranging from 2.8 to 6.5%. Expanding the definition of bipolar II disorders shows that half of the patients currently diagnosed with a unipolar depressive episode could suffer from unrecognized bipolar II disorder, and about the same number of mild depressive patients could be minor bipolars. Research efforts to refine the diagnostic criteria of bipolar disorder aim at an earlier and complete recognition of the disease to provide appropriate pharmacological and nonpharmacological treatment early in the course of the illness to anticipate individual suffering, suicidal behavior, and increased socioeconomic costs for society. This article also discusses risk factors, comorbid conditions, course of illness, as well as the individual and socioeconomic impact of bipolar disorders. CONCLUSIONS: The findings suggest reconceptualizing bipolar illnesses as highly recurrent, malignant disorders that occur far more frequently than previously thought. Interdisciplinary knowledge transfer could help to increase our understanding of the pathophysiology of these disorders as well as provide grounds for better recognition and treatment of patients with manic and/or depressive symptoms.

Age of Onset↗

Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.

BACKGROUND: Despite wide clinical use of mood-stabilizer combinations for long-term treatment of patients with bipolar disorder, research on risks and benefits of this practice is limited. We found 14 small, usually brief, clinical trials of maintenance treatment with lithium plus carbamazepine. These trials suggest added benefit of combination treatment over use of either agent alone but also indicate the need for further studies. METHOD: In a post hoc analysis, we reviewed the course of 46 patients with DSM-IV-diagnosed bipolar I disorder identified as not improving during long-term monotherapy in a mood disorders clinic, comparing days per year hospitalized in 3 consecutive time periods: before prophylactic treatment, during monotherapy with lithium (N = 31) or carbamazepine (N = 15), and during their combined use (N = 46). Secondary outcome measures were rates of hospitalization, time to first recurrence of an affective episode, use of adjunctive treatments, and adverse effects. We compared outcomes with nonparametric bivariate methods and tested predictive factors by multiple regression. RESULTS: Subjects showed significant reductions in hospitalized days per year during combination therapy, averaging a decrease of 55.9% (p = .004). Among secondary outcomes, hospitalizations per year fell by 36.1%, and median time to recurrence nearly doubled during combination therapy. Rates of adverse effects increased 2.5-fold, compared with monotherapy, and use of adjunctive psychotropic agents increased by 21.9%. CONCLUSION: Combining lithium with carbamazepine yielded substantial benefit but more adverse effects.

Adult↗

Design and effectiveness of a membrane-pump-driven ventilator for mice.

To perform mechanical ventilation of mice in the absence of highly expensive commercially available devices, we developed a membrane-pump-driven respirator and studied its practicability. The continuous airflow generated by the membrane pump was changed into an intermittent flow by using a multifunction timer. Tidal volume was adjusted by a rotary dimmer regulating the electric power onto the pump. The expiration air left the circuit through openings at the tube connection. Mice were ventilated with room air for 5 h with a tidal volume of approximately 200 muL. In group 1 (n = 6), ventilation was performed with a frequency of 110 min-1, in group 2 (n = 6) with a frequency of 150 min-1. Spontaneously breathing anesthetized mice (n = 6) served as controls. In addition we performed single-lung open-chest ventilation for 1 h in two animals. The parameters of arterial blood gas analyses were within the normal range except for moderate hyperventilation in group 2. Single-lung ventilation led to a significant decline (P < 0.05) of pO2 and SO2, whereas the pCO2 remained within the normal range. Respiratory rate, tidal volume and pressure limitation can be adjusted for optimal ventilation. In addition, the device provides a minimalized dead space and impedes potential alveolar damage caused by negative pressure generated by spontaneous inspiration during positive-pressure ventilation.

Animals↗

Long-term lithium treatment and thyroid antibodies: a controlled study.

OBJECTIVE: Because the role of thyroid autoimmunity in the development of lithium-induced thyroid dysfunction remains controversial, we compared the prevalence of thyroid autoantibodies in patients with affective disorders receiving long-term lithium maintenance therapy with that of age- and sex-matched controls. METHODS: We conducted a cross-sectional study with 100 adult patients with major affective disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised (DSM-III-R), who were undergoing lithium therapy for 6 months or more at a specialized lithium university clinic and 100 age- and sex-matched controls with no history of an axis I psychiatric disorder. Serum autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and TSH receptors (TRAb) were measured. RESULTS: TPOAb were found in 7 patients and 11 controls, and TgAb were found in 8 patients and 15 controls. TRAb were not found in either group. CONCLUSIONS: In this sample of patients with affective disorders, long-term lithium treatment did not increase the prevalence of thyroid autoimmunity.

Adult↗

Glucose utilization in the medial prefrontal cortex correlates with serotonin turnover rate and clinical depression in alcoholics.

We measured the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF), regional cerebral glucose uptake (rCMRglc) as assessed with positron emission tomography in the medial prefrontal cortex (PFC) and severity of clinical depression (Beck's Depression Inventory, BDI) in detoxified male alcoholics and age-matched healthy men. In alcoholics, the severity of clinical depression was negatively correlated with rCMRglc in the medial PFC and positively with CSF 5-HIAA concentrations. A voxel-based analysis showed that the strongest correlation between CSF 5-HIAA levels and rCMRglc was found in alcoholics in the left orbitofrontal and medial PFC (BA10 and BA11); no significant correlations were observed among healthy control subjects. This pilot study indicates that a dysfunction of medial PFC may interact with central serotonin turnover and negative mood states during early abstinence.

Alcoholism↗

Effects of portal vein arterialization on regeneration and morphology in liver transplantation: investigations using the rat model.

BACKGROUND: Portal vein arterialization (PVA) has been proposed as a technical variant in liver transplantation in the case of non-recanalizable thrombosis. The present study investigates the effects of the arterialized portal vein on the function, morphology, and regenerative behavior of the liver. METHODS: Different PVA techniques, including orthotopic liver transplantation, were used in a rat model. Portal blood flow was measured using a ultrasonic flowmeter. The regeneration capacity was determined on the basis of the increase of liver weight and the proliferating cell nuclear antigen index. The amount of hydroxyproline and the transcript levels of procollagen I were measured to determine the degree of fibrosis. The extracellular matrix was visualized with Picro-Sirius staining. RESULTS: The measurements obtained with an ultrasonic probe revealed a significant increase in portal blood flow after PVA. The regeneration capacity in the groups after PVA with no flow reduction was comparable to that of the control. Liver transplantation and PVA with no flow reduction was followed by a significant increase (four- to sixfold) in the amount of hydroxyproline and the level of the mRNA for procollagen I. In the Picro-Sirius staining, periportal and perivascular fibrosis with incipient formation of septa was seen. After reduction of the portal blood flow, these effects were significantly less pronounced. CONCLUSIONS: These operative techniques represent an excellent small animal model for studying the mechanism of liver regeneration and the genesis of fibrosis in liver and vessel tissue. The presenting findings indicate that the negative effects of "overarterialization" may be largely avoided by reducing portal blood flow. This implies that permanent PVA in clinical liver transplantation should be performed only in conjunction with a down-regulation of portal flow.

Alanine Transaminase↗

Mechanism of the delay phenomenon: tissue protection is mediated by heme oxygenase-1.

Induction of the "delay phenomenon" by chronic ischemia is an established clinical procedure, but the mechanisms conferring tissue protection are still incompletely understood. To elucidate the role of heme oxygenase-1 [HO-1 or heat shock protein-32 (HSP-32)] in delay, we examined in the skin-flap model of the ear of the hairless mouse, 1) whether chronic ischemia (delay) is capable to induce expression of HO-1, and 2) whether delay-induced HO-1 affects skin-flap microcirculation and survival by either its carbon monoxide-associated vasodilatory action or its biliverdin-associated anti-oxidative mechanism. Chronic ischemia was induced by transsection of the central feeding vessel of the ear 7 days before flap creation. The flap was finally raised by an incision through four-fifths of the base of the ear. Microcirculatory dysfunction and tissue necrosis were studied with the use of laser Doppler fluxmetry and intravital fluorescence microscopy. HO-1 protein expression was determined with Western blot analysis. Seven days of chronic ischemia (delay) induced a marked expression of HO-1. This was paralleled by a significant improvement (P <0.05) of microvascular perfusion and a reduction (P <0.05) of flap necrosis when compared with nondelayed controls. Importantly, blockade of HO-1 activity by tin protoporhyrin-IX completely blunted the protection of microcirculation and the improvement of tissue survival. Additional administration of the vitamin E analog trolox after blockade of HO-1 to mimic exclusively the anti-oxidative action of the heat shock protein did not restore the HO-1-associated microcirculatory improvement and only transiently attenuated the manifestation of flap necrosis. Thus our data indicate that the delay-induced protection from tissue necrosis is mediated by HO-1, predominantly through its carbon monoxide-associated action of adequately maintaining nutritive capillary perfusion.

Animals↗

Intracellular localization of Arabidopsis sulfurtransferases.

Sulfurtransferases (Str) comprise a group of enzymes widely distributed in archaea, eubacteria, and eukaryota which catalyze the transfer of a sulfur atom from suitable sulfur donors to nucleophilic sulfur acceptors. In all organisms analyzed to date, small gene families encoding Str proteins have been identified. The gene products were localized to different compartments of the cells. Our interest concerns the localization of Str proteins encoded in the nuclear genome of Arabidopsis. Computer-based prediction methods revealed localization in different compartments of the cell for six putative AtStrs. Several methods were used to determine the localization of the AtStr proteins experimentally. For AtStr1, a mitochondrial localization was demonstrated by immunodetection in the proteome of isolated mitochondria resolved by one- and two-dimensional gel electrophoresis and subsequent blotting. The respective mature AtStr1 protein was identified by mass spectrometry sequencing. The same result was obtained by transient expression of fusion constructs with the green fluorescent protein in Arabidopsis protoplasts, whereas AtStr2 was exclusively localized to the cytoplasm by this method. Three members of the single-domain AtStr were localized in the chloroplasts as demonstrated by transient expression of green fluorescent protein fusions in protoplasts and stomata, whereas the single-domain AtStr18 was shown to be cytoplasmic. The remarkable subcellular distribution of AtStr15 was additionally analyzed by transmission electron immunomicroscopy using a monospecific antibody against green fluorescent protein, indicating an attachment to the thylakoid membrane. The knowledge of the intracellular localization of the members of this multiprotein family will help elucidate their specific functions in the organism.

Arabidopsis↗

Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study.

BACKGROUND: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database. METHODS: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4 (mean dose=416 mcg/d) therapy. RESULTS: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T4, with higher doses being positively correlated with the percentage decline of BMD. LIMITATIONS: Relatively small sample size, no bone density assessment prior to treatment with L-T4, no patient control group with mood disorders who did not receive L-T4 treatment, and bone density follow-up intervals were variable. CONCLUSIONS: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed.

Absorptiometry, Photon↗

Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo.

BACKGROUND/AIMS: The heme oxygenase (HO) system contributes to the maintenance of hepatic perfusion and integrity. It was the objective of this study to determine the influence of isoflurane (ISO) on hepatic HO-1 induction and its impact on hepatic hemodynamics. METHODS: Rats were pretreated with or without ISO for 5h. After hemodynamic measurements by pressure-, laser doppler-, and ultrasound based techniques, the liver was harvested. HO-1 was analyzed by an HO activity assay, Northern- and Western blotting. RESULTS: ISO pretreatment induced hepatic HO-1 mRNA and protein resulting in an increase of HO activity. No effect on hsp-27, hsp-70 and hsp-90 mRNA could be observed. ISO lowered portal resistance. HO inhibition by tin protoporphyrine IX increased portal resistance in ISO pretreated animals up to control levels. This was associated with an increase in portal pressure and a reduction of portal flow. Microvascular flux was also impaired after HO blockade and ISO. However, hepatic arterial and systemic hemodynamics remained unchanged, indicating a specific effect within the portal vascular bed. CONCLUSIONS: ISO pretreatment induces hepatic HO-1 mRNA and protein followed by an increase in HO activity, thereby reducing portal resistance. These findings indicate a beneficial effect of ISO on hepatic hemodynamics in vivo.

Anesthetics, Inhalation↗

Strategies for brain shift evaluation.

For the analysis of the brain shift phenomenon different strategies were applied. In 32 glioma cases pre- and intraoperative MR datasets were acquired in order to evaluate the maximum displacement of the brain surface and the deep tumor margin. After rigid registration using the software of the neuronavigation system, a direct comparison was made with 2D- and 3D visualizations. As a result, a great variability of the brain shift was observed ranging up to 24 mm for cortical displacement and exceeding 3 mm for the deep tumor margin in 66% of all cases. Following intraoperative imaging the neuronavigation system was updated in eight cases providing reliable guidance. For a more comprehensive analysis a voxel-based nonlinear registration was applied. Aiming at improved speed of alignment we performed all interpolation operations with 3D texture mapping based on OpenGL functions supported in graphics hardware. Further acceleration was achieved with an adaptive refinement of the underlying control point grid focusing on the main deformation areas. For a quick overview the registered datasets were evaluated with different 3D visualization approaches. Finally, the results were compared to the initial measurements contributing to a better understanding of the brain shift phenomenon. Overall, the experiments clearly demonstrate that deformations of the brain surface and deeper brain structures are uncorrelated.

Brain Neoplasms↗

Prophylaxis of schizoaffective disorder with lithium or carbamazepine: outcome after long-term follow-up.

OBJECTIVES: This study was conducted (1) to assess the prophylactic efficacy of lithium and carbamazepine in the maintenance treatment of schizoaffective disorder (SAD) with long-term follow-up, (2) to find predictors of the success or failure of prophylaxis, and (3) to search for differences in outcome between schizoaffective patients diagnosed according to either ICD-10 or DSM-IV. METHODS: Participating patients met the ICD-10 and/or DSM-IV criteria for schizoaffective disorder. Outcome was assessed using the Morbidity Index and time elapsed until the first recurrence during prophylaxis. Predictor variables were age at onset of illness, gender, and family history, as well as the following parameters prior to prophylaxis: time between onset of illness and start of prophylactic treatment (latency), severity of illness (hospitalization rate), number of hospital admissions and polarity of schizoaffective disorder (schizobipolar vs. schizounipolar). The time spent in the hospital per year was used to compare the course of illness before maintenance therapy to the time during maintenance therapy. Co-medication was taken into account. The clinical data during prophylaxis were ascertained prospectively. RESULTS: Forty-nine patients met the ICD-10 criteria for schizoaffective disorder, 34 of whom also met the DSM-IV criteria. All 49 patients underwent prophylactic therapy with either lithium (n=41) or carbamazepine (n=8) for an average of 6.8 years. After initiating prophylaxis, the number of days spent in the hospital declined dramatically from an average of 71 days to 11 days per year. No independent variable proved to be a consistent predictor of the course of treatment. In regard to the subgroup of patients diagnosed according to DSM-IV, no significant differences were observed when this subgroup was compared to the whole sample. LIMITATIONS: As this is a naturalistic study it does not allow for exact quantitative measures of effectiveness. CONCLUSIONS: This study is the first of its kind to investigate the efficacy of maintenance therapy in SAD over such an extended period of time. The results of the study show that lithium and carbamazepine appear to be highly effective in treating patients with schizoaffective disorder. However, it remains unclear how many schizoaffective patients will respond to mood stabilizer treatment and whether predictors of clinical relevance exist. In our sample, differences in the ICD-10 and DSM-IV diagnostic criteria for schizoaffective disorder were not related to significant differences in clinical outcome.

Adult↗