[Immunointervention in newly diagnosed type 1 diabetes].
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Biomedical subjects
Publications and source records attributed to M Walter.
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BACKGROUND AND OBJECTIVE: Living donor liver transplantation (LDLT) has been gaining importance in the treatment of end-stage liver disease in adults as a partial solution to the growing organ shortage. Thus far, only few empirical studies have been published on the situation of donors who are faced with the risk of medical complications after resection of the right hepatic lobe. PATIENTS AND METHODS: 87 potential donors were preoperatively assessed in the years 2000 and 2001 at the Charité Berlin. 41 potential donors were excluded, 46 donors (31 women, 15 men, mean age 41 [19 - 67] years) underwent liver surgery and were re-assessed 6 months after the operation. The frequency of postoperative complications and the course of psychosocial parameters were investigated. Donors' moods were analysed with the Berlin Mood Questionnaire, the physical complaints were assessed with the Giessen Complaint Questionnaire. The preoperative interviews of 20 potential donors were analysed according the current social qualitative research methods. RESULTS: In 11 % (n = 10) of potential donors transplantation was not recommended for psychosocial reasons because they showed a marked ambivalence towards the operation. After operation, 22 % (n = 12) of donors had postoperative complications. Most relevant single causes of severe impairment were temporary and reversible biliary leakages from the cutting edge. There were no long- term complications. 26 % (n = 10) of donors showed postoperative high values for anxious depression and physical complaints. CONCLUSIONS: The resection of the right hepatic lobe holds promise of a good psychosocial outcome for most donors, irrespective of donation-related complications. The psychosocial impairment and physical complaints of some donors after transplantation are yet not clearly understood. Further psychosocial studies will be necessary to develop criteria for an evidence based medical care of living donors.
We present here the clinical, molecular and biochemical findings from 238 limb-girdle muscular dystrophy type 2A (LGMD2A) patients, representing approximately 50% (238 out of 484) of the suspected calpainopathy cases referred for the molecular study of the calpain 3 (CAPN3) gene. The mean age at onset of LGMD2A patients was approximately 14 years, and the first symptoms occurred between 6 and 18 years of age in 71% of patients. The mean age at which the patients became wheelchair bound was 32.2 years, with 84% requiring the use of a wheelchair between the age of 21 and 40 years. There was no correlation between the age at onset and the time at which the patient became wheelchair bound, nor between the sex of the patient and the risk of becoming wheelchair bound. Of the cases where the CAPN3 gene was not affected, approximately 20% were diagnosed as LGMD2I muscular dystrophy, while facioscapulohumeral muscular dystrophy (FSHD) was uncommon in this sample. We identified 105 different mutations in the CAPN3 gene of which 50 have not been described previously. These were distributed throughout the coding region of the gene, although some exons remained free of mutations. The most frequent mutation was 2362AG-->TCATCT (exon 22), which was present in 30.7% of the chromosomes analysed (146 chromosomes). Other recurrent mutations described were N50S, 550DeltaA, G222R, IVS6-1G-->A, A483D, IVS17+1G-->T, 2069-2070DeltaAC, R748Q and R748X, each of which was found in >5 chromosomes. The type of mutation in the CAPN3 gene does not appear to be a risk factor for becoming dependent on a wheelchair at a determined age. However, in the cases with two null mutations, there were significantly fewer patients that were able to walk than in the group of patients with at least one missense mutation. Despite the fact that the results of phenotyping and western blot might be biased due to multiple referral centres, producing a diagnosis on the basis of the classical phenotype is neither sufficiently sensitive (86.7%) nor specific (69.3%), although western blot proved to be even less sensitive (52.5%) yet more specific (87.8%). In this case LGMD2I was a relevant cause of false-positive diagnoses. Considering both the clinical phenotype and the biochemical information together, the probability of correctly diagnosing a calpainopathy is very high (90.8%). However, if one of the analyses is lacking, the probability varies from 78.3 to 73.7% depending on the information available. When both tests are negative, the probability that the sample comes from a patient with LGMD2A was 12.2%.
For perioperative anesthesia in a case of shoulder arthroscopy, a continuous interscalene plexus block according to Meier was performed in a 51-year-old female patient. The catheter was placed after stimulator-assisted punction and application of a local anesthetic. A few minutes after a further dose of local anesthetic was given via the catheter, the patient had to be intubated and ventilated with signs of total spinal anesthesia. The cervical CT showed the intrathecal displacement of the catheter, reaching the spinal canal near the root of the 7th spinal nerve. Blind advancement and deep placement increase the risk of an abnormal catheter position. Intraspinal misplacement should be reliably excluded.
METHODS: In this study we investigated the anesthesiological module of a clinical pathway. We chose the pathway of "laparoscopic prostatectomy" as an example for time-consuming minimally invasive surgery and 40 patients were randomly assigned to 2 groups receiving either total intravenous anesthesia (TIVA) using propofol/ remifentanil or balanced minimal flow anesthesia using desflurane/ remifentanil. During this module the indicators of quality such as vigilance, pain, postoperative nausea and vomiting (PONV) and mobilization were measured. Costs were evaluated and analyzed by a bottom-up procedure. RESULTS: There were no anesthesia-related deviations from clinical pathways and both forms of anesthesia management were equally well tolerated by the patients. No significant difference was observed regarding hemodynamic measurements or PONV. The patients in the desflurane/ remifentanil group recovered more rapidly (p=0.037) and had more pain. The amount of analgesic agents given immediately following anesthesia was significantly higher than in the TIVA group (p=0.017). The median anesthesia costs per minute for laparoscopic prostatectomy in the propofol group were 2.79 EUR (minimum cost 2.41 EUR, maximum cost 3.21 EUR) and in the desflurane group 2.68 EUR (minimum cost 2.45 EUR, maximum cost 3.39 EUR). The total anesthesia costs for both groups were within the proceeds matrix range for diagnosis-related groups (DRG). However, the cost analysis for medication was slightly higher than the proceeds matrix range for DRGs. CONCLUSION: Both forms of anesthesia can be implemented for time-consuming surgical procedures and allow a cost-effective anesthesia management. Anesthesiological procedures must go hand-in-hand with the type of anesthesia selected. The prophylactic use of analgetics for desflurane/ remifentanil anesthesia should be given earlier and in higher doses than in propofol/ remifentanil anesthesia. The prophylactic use of antiemetics following laparoscopic procedures of long duration is indicated. Optimizing anesthesiological procedures could lead to a continuous improvement in the quality of therapeutic pathways.
Cardiac resynchronization therapy (CRT) has significant positive effects on the quality of life, enables patients to cope more efficiently with cardiopulmonary stress and leads to a reduction of total mortality in patients suffering from congestive heart failure NYHA classes III and IV, reduced ventricular function and left bundle branch block with a QRS complex wider than 150 ms. In a large number of patients suited for CRT, an additional defibrillator function seems to work out well concerning an additional prognostic improvement by means of reducing sudden cardiac death. Due to partially contradictory study outcomes, it still remains to be discussed whether all patients suited for CRT really need an ICD.
BACKGROUND: Psychosocial stress can not only be considered as a result of chronic alcohol abuse, but also as a cause of high alcohol consumption and it maintains as a distress syndrome the subsequent course of the alcohol use disorder. METHODS: This review summarises empirical research results concerning the interrelations between psychosocial stress and alcohol consumption. The effects of psychosocial stress are regarded as an ideal-typical process leading to an increased alcohol intake and later to chronic alcohol abuse, often ending in alcohol dependence. The aim of the study is to demonstrate the relevance of stress and distress for diagnostics and therapy of alcohol- related disorders. RESULTS: At the starting point of high alcohol consumption psychological relief due to the stress-reducing effects of alcohol is often assumed. A vicious circle begins, perpetuating psychosocial distress and reinforcing the anxious or depressive symptoms related to emerging distress syndromes. Associated frequent comorbidities during the progression are other substance- related disorders, anxiety and affective disorders. Following alcohol dependence severe somatic and psychosocial consequences have to be anticipated. CONCLUSIONS: Psychosocial stress, distress and psychological effects can be understood as an important psychopathological developmental process of prolonged alcoholism. Symptoms of distress may be a first relevant evidence of high and hazardous alcohol consumption. Alcoholic patients should be motivated early to attend psychiatric and psychotherapeutic treatments to improve their chances for a positive development. Positive results can be achieved with stress management programs in alcohol dependent patients. These interventions appear to have comparable effects to other treatments.
Hexamerins are high molecular-weight proteins found in the hemolymph of insects and have been proposed to function as storage proteins. In previous studies, two Musca domestica hexamerins, designated Hex-L and Hex-F were characterized. Hex-L is synthesized exclusively by the larval fat bodies, is secreted into the hemolymph and likely provides a source of amino acids and energy during metamorphosis. Hex-F synthesis is induced by a proteinaceous meal and occurs only in the adult insect fat bodies. Hex-F also is secreted into the hemolymph and it has been suggested that in females it may be an amino acid reservoir to be used during the final stages of egg formation. Genomic clones containing full-length copies of the genes MdHexL1 and MdHexF1, encoding subunits of the larval and the adult female hexamerin, respectively, were isolated. Complete nucleotide sequences, including the 5'-end untranscribed regions, were determined and analyzed for each of the genes. Comparisons of the conceptual translation products of the cloned genes indicated that MdHexL1 and MdHexF1 are related to the larval serum proteins (LSP) 1 and 2 of Calliphora vicina and Drosophila melanogaster. DNA fragments containing the putative promoters of the two hexamerin genes were compared and cloned into a plasmid vector so as to drive the expression of the GFP reporter gene. The constructs were assayed in vitro in transfected S2 Drosophila melanogaster cells demonstrating that the cloned M. domestica DNA fragments exhibit promoter activity.
Nine New Zealand native white-rot fungi were studied for their ability to grow and survive on different substrates formulated from bark, wheat straw, sawdust, apple pomace and maize products in order to identify their pentachlorophenol (PCP) biodegradation potential and to select a fungal carrier for bioaugmentation of polluted soils. Isolates were also evaluated to mineralize (14)C-PCP in liquid culture and in soil. The American fungus Phanerochaete chrysosporium outgrew the native fungi on the substrates tested, but the high colonisation did not result in superior PCP dechlorination as measured by chloride release. Whilst Trametes versicolor inocula produced on wheat straw and SCS (sawdust-corn meal-starch-mix) gave the highest chloride release, colonization of these two substrates as measured by biological potential was lower compared to the pomace and pomace-sawdust-mix. Neither lignin peroxidase nor manganese peroxidase production were measured for New Zealand white-rot fungi during the experiments. Laccase was the only enzyme detected. In liquid culture, the mineralisation rate was higher for T. versicolor isolates compared to P. chyrysoporium. Very little to no pentachloroanisole (PCA) was captured in the volatile fraction of T. versicolor isolates, whereas 75% of the volatile fraction of P. chrysosporium consisted of PCA. The soil microcosms studies, using contaminated soil from a timber treatment site, clearly showed that the New Zealand T. versicolor isolates mineralized PCP. Degradation of PCP in non-sterile soil was higher in the presence of white-rot fungi than in soil without white-rot fungus. This demonstrates that viable white-rot fungus is necessary for significant PCP degradation and that T. versicolor isolates showed PCP remediation potential. Wheat straw and SCS could be suitable carriers for New Zealand native T. versicolor isolates for bioremediation of PCP polluted soil sites.
OBJECTIVES: The introduction of the living donation in organ transplantation introduces important new psychological conflicts and ethical questions in the transplantation process. Operation related risks, as well as dependencies in the family structure, generate considerable pressure on potential donors. The aim of the study was to reconstruct the determinants of willingness to donate before transplantation. METHODS: Evaluation of 20 taped and transcribed interviews oriented to current approaches in qualitative interview research. The approach used is based on grounded theory, qualitative content analysis, and the concept of the ideal type. RESULTS: Before surgery, "openly motivated" donors push for an operation, leaving no room for ambivalence in the evaluation process. They idealise the relationship with the recipient, and link their donation with the individual-partly in subconscious expectations and wishes. In contrast, "openly ambivalent" donors formulate their anxieties and express arguments against donation. CONCLUSIONS: Statements that claim ambivalence towards donation or utterance of arguments against donation indicate earlier coercion. Before transplantation, potential donors should have the opportunity to discuss their emotional situation to help their decision making process.
The general form of the multiparticle photofragmentation matrix element in dipole approximation is derived. Using two noncolinear momentum vectors to create a coordinate system enables the extraction of shape amplitudes depending only on lengths and mutual angles of the momentum vectors, i.e., on body fixed quantities, defining the fragmentation configuration. This is in contrast to previous parametrizations and, in particular, allows selection rules to be derived in a simpler and more transparent way.
AIM/HYPOTHESIS: Type 1 diabetes (T1D) is an autoimmune disease with multiple susceptibility genes. The aim of this study was to determine whether combining IDDM1/HLA and IDDM2/ insulin( INS) 5' variable number of tandem repeat locus (VNTR) genotypes improves T1D risk assessment. METHODS: Patients with T1D (n=488), control subjects (n=846), and offspring of parents with T1D (n=1122) were IDDM1 and IDDM2 genotyped. Offspring were followed for islet autoantibodies and T1D from birth until the age of 2 to 12 years. RESULTS: Compared to the I/I INS VNTR genotype, the I/III and III/III genotypes reduced T1D risk conferred by IDDM1/HLA in all HLA genotype categories of the case-control cohort by 1.6-fold to three-fold. The highest T1D risk was associated with INS VNTR class I/I plus HLA DR3/DR4-DQ8 (20.4% in patients, 0.6% in control subjects) or HLA DR4-DQ8/DR4-DQ8 (6.3% in patients, 0.2% in control subjects). In the offspring, HLA DR3/DR4-DQ8 and DR4-DQ8/DR4-DQ8 conferred increased risk for early development of islet autoantibodies (14.6% and 12.9% by age 2 years). Offspring with these high risk IDDM1 genotypes plus the INS VNTR class I/I genotype (n=71; 6.3%) had the highest risk of developing islet autoantibodies (21.8% by age 2 years vs 8.9% in offspring with high risk IDDM1 plus INS VNTR class I/III or III/III genotypes, p<0.05) and T1D (8.5% by age 6 years vs 4.3%). Offspring who developed autoantibodies to multiple antigens had increased frequencies of both high risk IDDM1 and IDDM2 genotypes (p<0.0001), whereas offspring who developed autoantibodies to GAD only had increased frequencies of high risk IDDM1 and protective IDDM2 genotypes, suggesting that IDDM2 influences the autoimmune target specificity. CONCLUSION/INTERPRETATION: Combining IDDM1 and IDDM2 genotyping identifies a minority of children with an increased T1D risk.
Living donor liver transplantation (LDLT) is becoming an established method for treatment of terminal liver disease in adults. After resection of the right hepatic lobe, postoperative complications can arise in healthy donors, and even individual cases of death have been recorded. There remains, however, little research on the psychosocial aspects in living donors before and after LDLT. Using the WHOQOL questionnaire, this prospective study investigates the quality of life (QoL) in a sample of 28 living donors, including the relationship between postoperative complications and QoL before and 6 months after donation. Before LDLT, the donor QoL is high, above that of the general healthy population. After LDLT, a significant reduction in the QoL appears in the areas of "physical health" and "living conditions." Nevertheless, the QoL remains above the level of the general population. Only two donors showed general QoL values below those of the general population. The postoperative complications had no significant influence on the QoL after transplantation. The high QoL of donors following LDLT indicates a positive psychosocial outcome for the majority of donors, irrespective of donation-related complications. Additional psychosocial studies will be necessary to disclose predictors for an unfavorable psychosocial outcome following LDLT.
The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to energy demand and supply by directly phosphorylating rate-limiting enzymes in metabolic pathways as well as controlling gene expression.
AIM: To determine whether a thoracoscopic lobectomy used for treatment of primary non-small cell lung cancer shows a higher or lower morbidity in comparison to the conventional resection (thoracotomy) postoperatively. METHODOLOGY: 42 patients with the presumption diagnosis of a lung cancer received a thoracoscopic lobectomy (n=28) or a conventional lobectomy (n=14). Postoperative complication rate (30 days) was analysed prospectively. There were no differences between the groups referring to age, co-morbidity, localisation of the tumor and stage. RESULTS: Patients with a conventional operation revealed a significant higher morbidity in comparison to the patients of the thoracoscopic group (50 % vs. 14.2 %, p=0.03). CONCLUSION: The thoracoscopic lobectomy represents a safe operation method and an alternative to the conventional operation (thoracotomy).
The current study deals with the results of the examination of 685 patients, who were treated in the department of traumatology in the KKH Garmisch-Partenkirchen during the winter season 99/00 and 00/01. The study included 259 injured carvers (120 female, 139 male) with an average age of 33.9 years and 426 injured conventional skiers (212 female, 214 male) with an average age of 33.2 years. The aim of the investigation was to compare both ski groups concerning injuries, the pathomechanism and the skiing experience. The results of the investigation showed that the knee injuries of carvers were more severe than in the conventional skiers. The difference was significant (p < 0.05).