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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 37 records · Page 2Linked to original sources

[Psychological disorders after severe occupational accidents].

After severe accidents, a significant number of victims develop post-traumatic stress disorder (PTSD) and other psychiatric disorders, which lead to considerable impairment in work and daily life. Few studies exist which deal with the psychological consequences of industrial accidents. The Department of Psychiatry and Psychotherapy (University of Freiburg) in cooperation with the Department of Trauma Surgery (University of Freiburg) have therefore carried out a prospective study on the subject. 56 victims of an industrial accident were assessed immediately after the accident, and again six months later, using different instruments, e.g. structured clinical interviews (e.g. ADIS). The prevalence rates of psychiatric disorders in the follow-up assessment after six months were 12% PTSD, 11% subsyndromal PTSD (not all criteria of PTSD fulfilled) and 11% other psychiatric disorders. The patients with PTSD and subsyndromal PTSD were compared with the patients with other psychiatric disorders. The accidents of patients with PTSD/subsyndromal PTSD were more serious, and their injuries more severe. In addition, these patients reported that they had thought much more about their work before the accident and believed that their work was much more dangerous than that of patients with other psychiatric disorders. As early as the first day after the accident the patients with PTSD/subsyndromal PTSD were afraid of developing physical and work-related problems as a consequence of the accident. They also reported more symptoms of PTSD and depression and anxiety symptoms. Patients with PTSD/subsyndromal PTSD reported more limitations in daily life and that they were unfit for work for a longer period. After their return to work, they had more problems and were less resistant to stress.

Accidents, Occupational↗

[Algorithms for diagnosis and therapy of sleep disorders in general practice].

Complaints of insomnia, i.e. problems to fall asleep or maintain asleep and/or non-restorative sleep are very common in general practice. This article presents the clinical algorithm non-restorative sleep which was devised by the German Society for Sleep Research and Sleep Medicine. This algorithm presents a guideline for the diagnosis and the treatment of insomnia.

Age Factors↗

Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma.

PURPOSE: This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas Exotoxin (NBI-3001) in patients with recurrent malignant glioma. PATIENTS AND METHODS: A total of 31 patients with histologically verified supratentorial grade 3 and 4 astrocytoma were studied. Of these, twenty-five patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma (AA). Patients were over 18 years of age and had Karnofsky performance scores > or = 60. Patients were assigned to one of four dose groups in a dose-escalation fashion: 6 microg/ml x 40 ml, 9 microg/ml x 40 ml, 15 microg/ml x 40 ml, or 9 microg/ml x 100 ml of NBI-3001 administered intratumorally via stereotactically placed catheters. Patients were followed with serial MRI scans and clinical assessments every four weeks for the first 16 weeks and then every eight weeks until week 26. RESULTS: No drug-related systemic toxicity, as evident by lack of hematological or serum chemical changes, was apparent in any patients; treatment-related adverse effects were limited to the central nervous system. No deaths were attributable to treatment. Drug-related Grade 3 or 4 toxicity was seen in 39% of patients in all dose groups and 22% of patients at the maximum tolerated dose of 6 microg/ml x 40 ml. The overall median survival was 8.2 months with a median survival of 5.8 months for the GBM patients. Six-month survival was 52% and 48%, respectively. Gadolinium-enhanced magnetic resonance imaging of the brain showed areas of decreased signal intensity within the tumor consistent with tumor necrosis following treatment in many patients. CONCLUSIONS: NBI-3001 appears to have an acceptable safety and toxicity profile when administered intratumorally in patients with recurrent malignant glioma.

Adult↗

[Non-restorative sleep and insomnia. Diagnostic and therapeutic options for psychiatry and psychotherapy].

Over the last few years, a shift in paradigm has taken place in the diagnosis and therapy of insomnia. Traditionally, treatment focused on improving night sleep, i.e. shortening sleep latency and prolonging total sleep time. Modern approaches aim at improving or restoring the recuperative value of sleep and ensuring daytime functioning on a social, psychological and professional level. Based on the guidelines "Non-restorative Sleep" of the German Society of Sleep Research and Sleep Medicine, this article presents a clinical algorithm for the diagnosis and therapy of non-restorative sleep with predominant insomnia. The term "non-restorative sleep" permits us to view the restorative value of sleep and the resulting daytime functioning of the individual afflicted with insomnia as the focus for the diagnosis of and therapy for insomnia. This algorithm is suitable for the clinical practice of outpatient psychiatric and psychotherapeutic services as well as for psychiatric inpatients. The main features for psychiatrists and psychotherapists in the diagnosis and therapy of non-restorative sleep are underlying psychiatric-psychological factors or secondary psychiatric sequelae of chronic primary insomnias. For primary, organic and psychiatric insomnias, a broad spectrum of psychopharmacological and cognitive behavioral methods can be applied either alone or in combination.

Algorithms↗

Is the antidepressive effect of sleep deprivation stabilized by a three day phase advance of the sleep period? A pilot study.

Sleep deprivation (SD) induces a rapid amelioration of mood in about 60 % of depressed patients. After the next night of sleep, however, most patients experience a relapse. Previous studies demonstrated that a six day sleep-phase advance protocol prevents relapses in about 60 % of patients who responded positively to SD. We investigated whether also a three day phase advance of the sleep period might be able to maintain the antidepressant effects of SD. Twenty-eight medicated depressed inpatients, who had a significant improvement after a SD in one night were recruited for this study. The phase advance protocol began on the first day after SD with a bed time from 5:00 p. m. to 12:00 p. m. on the first, from 7:00 p. m. to 2:00 a. m. on the second and 9:00 p. m. to 4:00 a. m. on the third day after SD. Three patients dropped out because of protocol violations. Only ten of the remaining 25 SD responders had a relapse during the three days of phase advance treatment or during the two days after it. Two of the relapsers improved again until day 6, i. e. 68 % showed an improvement of at least 30 % six days after the beginning of the treatment. This study indicates that even a three day phase advance protocol may help to prevent relapses after successful SD.

Circadian Rhythm↗

Proposition of treatment of cancer cells by nuclear protein mixtures from embryonic cells.

Several kinds of cancer cells are shown to revert to normal state by action of chemical or biochemical differentiation agents. The analogy between cancer and embryonic cells, with regard to the expression of oncogenes, and the presence, in young embryos, of regulating factors, lead to the proposition of treatment of cancer cells by extracts of nuclei from embryo cells. Preliminary experiments with these extracts, on hepatoma cells in culture, have shown growth and DNA synthesis inhibitions, without cell toxicity, and a prolongation of survival of rats injected with the treated cancer cells.

Animals↗

Sleep and manipulations of the sleep-wake rhythm in depression.

OBJECTIVE: Disturbed sleep is typical for most depressed patients and complaints about disordered sleep are the hallmarks of the disorder. Polysomnographic sleep research has demonstrated that besides impaired sleep continuity, sleep in depression is characterized by a reduction of slow wave sleep and a disinhibition of random eye movement (REM) sleep, with a shortening of REM latency, a prolongation of the first REM period and increased REM density. METHOD: Our own experimental work has focused on the reciprocal interaction hypothesis of non-REM and REM sleep regulation as a model to explain the characteristic features of depressed sleep. RESULTS: In agreement with the major tenet of this model, administration of cholinomimetics provoked shortened REM latency in healthy subjects and led to an even stronger REM sleep disinhibition in depressed patients. Manipulations of the sleep-wake cycle, such as sleep deprivation or a phase advance of the sleep period, alleviate depressive symptoms. CONCLUSION: These data indicate a strong bidirectional relationship between sleep, sleep alterations and depression.

Cholinergic Agents↗

Successful unrelated cord blood transplantation in two children with severe combined immunodeficiency syndrome.

We describe the successful unrelated cord blood transplantation in two patients affected by a Zap-70 deficiency and an Omenn-like syndrome, respectively. The patients were hospitalised for recurrent infections at the age of 13 and 2 months, respectively. An unrelated cord blood unit was found for each. The conditioning regimen was cyclophosphamide, busulfan and antithymocyte globulin. The total number of infused cells was 15.1 x 10(7)/kg and 17 x 10(7)/kg, respectively. Neutrophil engraftment was achieved on days +15 and +23, and platelet count >50 x 10(9)/l was achieved on days +21 and +52, respectively. One patient presented acute Graft-versus-host disease (GVHD) grade I and the other grade III. Chimerism was mixed and full donor. Normal lymphoproliferative response to mitogens and alloantigens was detectable at 6 months for both. No chronic GVHD was observed in either. The patients are alive and well at 53 and 15 months after transplantation. In conclusion, umbilical cord blood represents a valid alternative source of haemopoietic stem cells.

Antilymphocyte Serum↗

Ex vivo expansion of autologous PB CD34+ cells provides a purging effect in children with neuroblastoma.

Peripheral blood CD34+ cell samples from eight children with advanced neuroblastoma and from 10 healthy adult donors were seeded at 5 x 10(4) cells/ml in stroma-free, serum-free medium with FL, SCF, MGDF (100 ng/ml each), G-CSF, IL6 (10 ng/ml each) and IL3 (5 ng/ml), and incubated for 10 days. The levels of expansion of PBCD34+ cells observed in neuroblastoma patients, with up to 214-fold expansion for total nucleated cells, 39-fold for CD34+ cells, 79-fold for CFU-GM and nine-fold for LTC-IC were identical to those obtained with PBCD34+ cells of healthy donors (P>/=0.5). All samples from patients with neuroblastoma and five donor's PBCD34+ cell samples contaminated with IMR-32 neuroblasts, were screened for the number of tyrosine hydroxylase (TH) mRNA transcript using LightCycler software. In all samples, progressive 1.9-4.4 log decreases in the number of TH transcripts were observed between days 0 and 10 of expansion. Our results show that in extensively pretreated children with neuroblastoma, the culture conditions that were effective for BM and CB cell expansion can generate an expansion of PBCD34+ cells and provide a purge of tumour cells.

Antigens, CD34↗

Pharmacokinetics and tolerability of a new intravenous immunoglobulin preparation, IGIV-C, 10% (Gamunex, 10%).

BACKGROUND AND OBJECTIVES: A new intravenous immunoglobulin (IGIV) process has been developed that integrates efficient inactivation of enveloped virus, using caprylate, with immunoglobulin G (IgG) purification and caprylate removal by column chromatography. Two clinical studies were conducted to compare the pharmacokinetics of the new product, IGIV-C, 10% (Gamunex, 10%), formulated with glycine, with the licensed solvent-detergent (SD)-treated intravenous immunoglobulin IGIV-SD, 10% (Gamimune N, 10%), formulated with glycine, and IGIV-C, 5%, formulated with 10% maltose. MATERIALS AND METHODS: Both studies were randomized, multicentre crossover trials of 18 and 20 (respectively) adult patients with primary humoral immune deficiency in which patients received one IGIV product for three consecutive periods (3-4 weeks) before crossing over to the other product. Pharmacokinetic parameters were determined after the third infusion of each product. RESULTS: IGIV-C, 10% was bioequivalent to IGIV-SD, 10%, with half-lives (t1/2) of 35 and 34 days, respectively. IGIV-C, 5%, was bioequivalent to IGIV-C, 10%, with t1/2 of 35 and 36 days, respectively. The products had comparable safety profiles. CONCLUSIONS: The pharmacokinetic profiles observed in these trials indicate that IGIV-C, 10% may replace, and be administered in a manner similar to, IGIV-SD, 10%.

Adult↗

Hormonal and developmental regulation of the mouse aldose reductase-like gene akr1b7 expression in Leydig cells.

The akr1b7 gene encodes an aldose reductase-like protein that is responsible for detoxifying isocaproaldehyde generated by the conversion of cholesterol to pregnenolone. The regulation of gene expression by human chorionic gonadotropin (hCG) was first investigated in the MA-10 Leydig tumor cell line. The akr1b7 gene was constitutively expressed and accumulation of its mRNA was increased in a dose- and time-dependent manner by treatment with hCG. akr1b7 mRNA accumulation was sharply increased in the presence of 0.25 nM hCG and it reached a fivefold increase within 2 h. AKR1B7 protein accumulation was delayed compared with that of the corresponding mRNA. In agreement, hCG significantly increased the levels of mRNA and protein of akr1b7 in primary cultures of adult mouse Leydig cells, thus suggesting that LH potentially regulates akr1b7 gene expression in vivo. Expression of akr1b7 was developmentally regulated in the testis. Unexpectedly, levels of akr1b7 mRNA increased from embryonic day 15 to the day of birth and declined until adulthood while AKR1B7 protein levels followed an inverse pattern, suggesting an important role for translational mechanisms.

Aldehyde Reductase↗

Patient education - evaluation of a complex intervention.

Diabetes education or self-management programmes are complex interventions. Their evaluation is difficult because of problems in identifying and separately assessing the effect of the various components of the intervention. A phased approach defining sequential stages of a continuum of increasing evidence has been proposed as a framework for the design and evaluation of such complex interventions. As an example we present the available evidence for diabetes treatment and teaching programmes implemented in Germany. Evidence is compiled for structured group treatment and teaching programmes for Type I diabetes, non-insulin dependent Type II diabetes, and hypertension according to the following sequential stages of increasing evidence: (i) preclinical or theoretical phase; (ii) modelling the components of the intervention; (iii) exploratory trials; (iv) randomized controlled trials; (v) phase of implementation including replication and transfer to different settings. Evidence for most of these phases has been generated for the three programmes, although individual studies do not fulfill all important quality criteria by today's standards. The time span for gathering the evidence from the theoretical phase to surveillance after implementation was about 20 years. It can only be speculated which parts of the programmes are the most active ones. The presentation of a continuum of increasing evidence for diabetes education or self-management programmes could provide useful information for the appraisal of such complex interventions. Since this evidence cannot be readily extracted from databases we suggest that other research groups present their data in a similar way.

Diabetes Mellitus, Type 1↗