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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 55 records · Page 3Linked to original sources
PubMed2002

Reliability of causes of death in persons with Type I diabetes.

AIMS/HYPOTHESIS: To compare causes of death assessed by a clinical review committee, the information given on death certificates, and ICD-codes provided by the State Documentation Office in deceased persons with Type 1 (insulin-dependent) diabetes mellitus. METHODS: A cohort of 3674 patients were monitored for 10+/-3 (mean +/- SD) years. Vital status and end-stage diabetic complications were documented for 97%; 251 patients had died. Causes of death were assessed by a clinical review committee and compared to the information provided by death certificates and ICD-9 codes. RESULTS: The review committee defined a leading cause of death in 94% of cases, whereas death certificates were available for 73% and ICD-codes for 79% of patients; 10% of death certificates could not be evaluated due to insufficient information. Diabetes was mentioned on 71% of death certificates, and renal disease in 75% of cases with renal replacement therapy. There was acceptable agreement between the committee, death certificates and ICD-codes only for deaths due to neoplasma, and between the committee and death certificates for deaths due to acute myocardial infarction, cerebrovascular events and accidents. In only one out of four deaths due to hypoglycaemia and in four of seven deaths due to ketoacidosis was this diagnosis mentioned on the death certificate. No death due to hypoglycaemia or ketoacidosis and 41% due to suicide were identifiable by ICD-codes. CONCLUSION/INTERPRETATION: Reliance on death certificates or ICD-codes as the only sources of information on the cause of specific mortality does not provide data of sufficient reliability for evaluation of clinical outcome in Type I diabetes.

Adult↗
PubMed2002

Slowing of human arm movements during weightlessness: the role of vision.

The human motor system responds to weightlessness by the slowing of movement. It has been suggested that deficits in visuo-motor co-ordination cause this effect. We studied the mechanisms of the slowing of movement in three long-term missions to the Russian space station Mir. In particular, the role of vision in the control of movement in microgravity has been studied in these experiments on seven cosmonauts, pre-, in-, and post-flight. The cosmonauts made arm movements to visual targets under the following conditions of visual control: no visual control, interrupted visual control, and undisturbed visual control. The results showed that the slowing of movement during weightlessness was manifested by decreases of peak velocity and peak acceleration, was not associated with a prolongation of the movement phase of deceleration, and was not affected by manipulation of the conditions of visual control. The slowing of movement tended to subside after the months of the flight and completely disappeared within days after the landing. Accuracy of the movements strictly depended on the constraints imposed on the vision and remained unaffected in-flight. The data presented demonstrate that the slowing of movement in microgravity is not directly related to deficits in sensori-motor co-ordination and is not associated with a reduction of the accuracy of movement. The strategy for motor control in microgravity seems to be directed towards the generation of smooth movements and the maintenance of their accuracy.

Acceleration↗
PubMed2002

IL-4 receptors on human medulloblastoma tumours serve as a sensitive target for a circular permuted IL-4-Pseudomonas exotoxin fusion protein.

Cytotoxins directed to interleukin-4 receptors have shown to mediate relatively selective cytotoxicity against a variety of human cancer cells in vitro and in vivo. In an ongoing Phase I clinical trial, a recombinant protein comprised of circularly permuted IL-4 fused to a mutated form of Pseudomonas exotoxin (the fusion protein termed IL-4(38-37)-PE38KDEL or cpIL4-PE) has shown antitumour activity against malignant glioma. Human medulloblastomas are neuroectodermal tumours that occur in children and have a poor prognosis. The goal of this study was to determine whether human medulloblastoma derived cell lines express interleukin-4 receptor and whether interleukin-4 receptor expression is accompanied by sensitivity to cpIL4-PE. Medulloblastoma cell lines express interleukin-4 receptor at the protein and mRNA levels as determined by binding, indirect immunofluorescence and RT--PCR studies. These cells expressed IL-4Ralpha (also known as IL-4Rbeta) and IL-13Ralpha1 (also known as IL-13Ralpha') chains, however common gamma(c), a component of the interleukin-4 receptor system in immune cells was not detected. Consistent with the expression of IL-4R, cpIL4-PE was found to be highly and specifically cytotoxic to four of five medulloblastoma cell lines. Susceptibility of medulloblastoma cell lines to cpIL4-PE seemed to correlate closely to the functional IL-4 binding sites in general as demonstrated by 125I-IL-4 binding, but did not seem to correlate with mRNA or cell surface immunoreactive receptor protein expression. The sensitivity of medulloblastoma cells to cpIL4-PE could be eliminated by concurrent incubation with IL-4 or IL-13, but not with IL-2. None of these cell lines showed any change in proliferation upon treatment with exogenous IL-4. These studies establish the interleukin-4 receptor as a medulloblastoma-associated target for possible tumour-directed cancer therapy. Further studies are warranted to investigate interleukin-4 receptor expression in primary medulloblastoma tumours and sensitivity to cpIL-4PE in vitro and in vivo.

ADP Ribose Transferases↗
PubMed2002

[Comorbidity of depressive disorders and cardiovascular diseases. Implications for diagnosis, pharmaco- and psychotherapy].

Controlled studies and meta-analyses show not only that depression and cardiovascular disease often occur together, but that depressive illnesses are an independent risk factor in the development and the progression of coronary heart disease. It can be difficult to distinguish between reactive mood disturbance after myocardial infarction and depressive episodes that may have preceded the infarction and which require treatment. Due to this difficulty, depressive disorders are rarely diagnosed, and only a minority of patients receive adequate treatment. However, owing to the introduction of new antidepressants in recent years, the number of treatment options has increased. Specifically, selective serotonin reuptake inhibitors (SSRI) offer a valuable alternative to tricyclic antidepressants, which are problematic in heart disease. The authors describe on the one hand controlled studies of SSRIs and discuss differential therapeutic consequences. On the other hand, studies of psychotherapeutic interventions in comorbid patients with depression and coronary heart disease are reported. Finally, the authors discuss which psychotherapeutic interventions may be suitable.

Antidepressive Agents↗
PubMed2002

[Psychopharmacotherapy of bipolar affective diseases].

The broadening of the classification systems for manic-depressive illness towards a spectrum of bipolar disorders implicates a more differentiated use of pharmacotherapies. However, many questions still remain open. This implies that all consensus guidelines and recommendations have to be considered as preliminary. On the other hand, research in the last decade has developed many new treatment alternatives, both for mood stabilizers and antidepressants as well as antipsychotics. These recommendations, which have been developed in the process of two consensus meetings, try to consider the broadening of the concept of bipolar disorder by differentiating between subgroups according to acute symptomatology and characteristics of the long-term course, e.g., rapid cycling. In particular, the emerging role and new indications of mood stabilizing antiepileptic drugs, atypical antipsychotics, and new antidepressants will be discussed.

Antidepressive Agents↗
PubMed2002

Role of different medium and growth factors on placental blood stem cell expansion: an in vitro and in vivo study.

Expansion of haemopoietic stem cells from placental blood has been obtained with a combination of flt3 ligand (FL), thrombopoietin (TPO), kit-ligand (KL) with or without interleukin-6 (IL6) in serum-replete medium. For clinical use, cell expansion in the absence of serum is a clear advantage. Therefore, stem cell expansion in serum-free (SF) medium with a combination of three (FL, TPO, KL) or four (FL, TPO, KL, IL6) growth factors was compared with the results obtained using fetal calf serum (FCS) or human serum (HS). Human CD34(+) placental blood cells were cultured in the presence of FL, TPO, KL +/- IL6 with SF medium, HS and FCS for up to 8 weeks. CD34(+), CFC, LTC-IC content was measured at intervals. To determine the in vivo repopulating capacity of expanded cells, CD34(+) expanded cells were transplanted in sublethally irradiated NOD/SCID mice. With the three growth factor combination the CD34(+) cell number increased steadily up to the 8 weeks of culture. CD34(+) cells were expanded 67.5-fold with SF, 11.7 with HS and 49.2 with FCS. However, when CFCs and LTC-ICs were considered, a continuous expansion was observed only with HS and FCS, whereas in SF medium after 6 weeks their number started to decline. The addition of IL-6 did not change the expansion significantly. Cells grown ex vivo for 14 days were transplanted into NOD/SCID mice. The engraftment of human cells in mice was higher for serum-replete than for SF expanded cells. Nevertheless, SF cultured cells were also able to engraft both marrow and spleen in all animals. In addition, engrafted human cells still maintained clonogenic ability. With KL, FL, TPO +/- IL6 it is possible to expand haemopoietic progenitor cells in a SF medium. Compared with serum-replete cultures, the absolute number of clonogenic cells and in vivo repopulating cells is lower. Although the degree of expansion remains significant, a clinical trial still needs to be carried out to address the question of whether this expansion might be useful in reducing post-transplant aplasia.

Animals↗
PubMed2002

Amputations and diabetes: a case-control study.

AIMS: Data concerning the relative risk of amputations in diabetic patients compared with the general population are scarce. Therefore, we carried out a case control study to quantify the relationship between diabetes and amputations. METHODS: In 20 hospitals in seven German cities and counties we obtained complete lists of non-traumatic lower limb amputations performed in 1990 and 1991. CONTROLS were selected from patients of the same surgical departments operated on in the same years. We drew a random sample of patients with procedures not likely to be associated with diabetes. Diabetic status was determined from patients' records in both cases and controls. We calculated age- and sex-specific and, using logistic regression, adjusted odds ratios (OR) and attributable risks. RESULTS: N = 2400, mean age 61.7 (SD 16.3) years. CASES: n = 729; 486 (66.7%) of them had diabetes. CONTROLS: n = 1671; 127 (7.6%) of them had diabetes. Adjusted OR: 18.2 (confidence interval (CI) 14.2-23.6). Adjusted attributable risk among exposed (ARE): 0.95 (CI 0.93-0.96). Adjusted population attributable risk (PAR): 0.62 (CI 0.57-0.66). CONCLUSIONS: This study has demonstrated a strong association between the risk of amputation and diabetes. The odds ratios and attributable risks for diabetic individuals are higher in the younger than in the older age groups. Population attributable risks are great. We conclude that the reduction of amputations in the general population will be achieved by improving foot care in people with diabetes.

Age Factors↗
PubMed2002

Less severe hypoglycaemia, better metabolic control, and improved quality of life in Type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII) therapy; an observational study of 100 consecutive patients followed for a mean of 2 years.

AIMS: To compare glycaemic control, occurrence of acute complications, and diabetes-specific quality of life in Type 1 diabetic patients (on intensified conventional insulin treatment (ICT)) before and after initiation of CSII. METHODS: One hundred and three patients (58 women) started CSII between October 1995 and April 1999 in our department. The indication for CSII was optimization of metabolic control and improvement of flexibility of life style (OF group) in 60 patients (58%), and prevention of severe hypoglycaemia (HY group) in 43 patients. Mean age at initiation of CSII was 33 +/- 11 years (OF 33 +/- 10, HY 33 +/- 11 (mean +/- sd)), diabetes duration 18 +/- 9 years (OF 16 +/- 9, HY 20 +/- 9). Three patients stopped CSII, mean duration of CSII of the remaining 100 patients was 1.8 +/- 1.2 years. The occurrence of hypoglycaemia, ketoacidosis and skin abscesses was assessed retrospectively for the 12 months before starting CSII, and recorded continuously during CSII. Quality of life was assessed with a validated, diabetes-specific questionnaire before and after CSII in 50 patients. RESULTS: The incidence of serious hypoglycaemia (any external help) was reduced from 1.23 (OF 0.0; HY 2.93) during ICT to 0.29 cases/patient per year (OF 0.09; HY 0.55) during CSII. The incidence of severe hypoglycaemia (SH) (treated with i.v. glucose or glucagon injection) fell from 0.70 (OF 0.0; SH 1.67) during ICT to 0.06 cases/patient per year (OF 0.02; HY 0.12) during CSII. HbA1c improved from 7.7 +/- 1.1% to 7.2 +/- 1.0% (P < 0.001) (OF 7.8% vs. 7.2%; HY 7.6% vs. 7.2%). During CSII the incidence of abscesses was 0.11 and of ketoacidosis 0.01 cases/patient per year. Quality of life assessments showed significant improvement in all parameters during CSII. CONCLUSIONS: In our cohort of Type 1 diabetic patients, we observed a substantial decrease of hypoglycaemia along with a significant fall of HbA1c. Quality of life on CSII was improved when compared with ICT.

Administration, Cutaneous↗
PubMed2002

Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study.

In recent years, sedating antidepressants have been increasingly used to treat primary insomnia. Up to now, only one open pilot study with trimipramine and one double-blind placebo-controlled study with doxepin have provided scientific support for this approach in treating primary insomnia. In order to test the hypothesis that sedating antidepressants are useful in the treatment of primary insomnia, the effect of trimipramine on objectively and subjectively measured parameters of sleep was investigated in a double-blind placebo- and lormetazepam-controlled study in a sample of 55 patients with primary insomnia attending outpatient sleep-disorder clinics. Trimipramine was selected since it has shown positive effects on sleep continuity with a lack of REM sleep suppression in studies on depressed patients and in one pilot study on patients with primary insomnia. Trimipramine at an average dose of 100 mg over a period of 4 weeks significantly enhanced sleep efficiency, but not total sleep time (which had been the primary target variable) compared to placebo as measured by polysomnography. Changes in objective sleep parameters were paralleled by changes in subjective sleep parameters. Trimipramine did not suppress REM sleep. Lormetazepam decreased wake time and sleep stage 3 and increased REM sleep compared to placebo. After switching trimipramine to placebo, sleep parameters returned to baseline. There was no evidence of any rebound effect from trimipramine. Side effects from trimipramine were only marginal. This first double-blind placebo-controlled study with trimipramine suggests its efficacy in the treatment of primary insomnia. However, due to the large intra- and interindividual variance in the parameters of interest before and during treatment a larger sample size would have been necessary to strengthen the validity of our findings.

Adult↗
PubMed2001

S(+)-4-(1-Phenylethylamino)quinazolines as inhibitors of human immunoglobulin E synthesis: potency is dictated by stereochemistry and atomic point charges at N-1.

Since the pathogenesis of allergic diseases is associated with elevated levels of immunoglobulin E (IgE), we developed a high throughput reporter gene assay in a human B-cell line to screen for low molecular weight IgE inhibitory compounds. Monitoring the IL-4 driven IgE-germline promoter activity (IgE-GLP), we discovered 4-(1-phenylethylamino)qinazolines as potent inhibitors of IgE-germline gene expression. Testing of the individual enantiomers (1, 2) revealed that only the S(+) enantiomer 1 was active. A cell viability assay done in the same cell line in parallel discriminated the dose-dependent inhibition from a general antiproliferative effect. The observed correlation of the inhibitory potencies found in the reporter gene assay with those measured by IgE-ELISA in primary human splenocytes provided evidence that the blockade of IgE synthesis is the direct consequence of IgE-germline gene inhibition, thereby validating the reporter gene assay. Parallel synthesis in solution rapidly provided a series of analogues of compound 1 with modifications in the phenethylamine side chain and the quinazoline core for SAR studies. Increasing the lipophilicity of the arylalkylamine moiety yielded S(+)-4-(1-(2-naphthyl)ethylamino)quinazoline (6) as the most potent inhibitor (IC(50) of 14 nM) while the R(-) enantiomer was again found to be inactive. Within the set of S enantiomers, quantum mechanical calculations revealed that the IgE inhibitory activity can be quantitatively described by the charge at N-1 of the heterocyclic core and to a lesser extent by the molar refractivity. These results demonstrate the importance of electron-deficient fused 4-aminopyrimidines and lipophilic side chains for biological activity. The strong preference for the S configuration of the phenethylamine side chain is remarkable insofar as biological activity for fused 4-(1-phenylethylamino)pyrimidines has been published for the R enantiomers only (EGFR tyrosine kinase inhibition).

Animals↗
PubMed2001

Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.

Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

Bacterial Proteins↗
PubMed2001

[Sleep disorders. Differential diagnosis and therapy in general practice].

Sleep Disorders are one of the most common complaints of patients seen by general practitioners. Prevalences vary considerably--depending on the kind of research and the definition of sleep disorders--between 4 and 40%. In 2000 the first grand nationwide survey was carried out in primary care settings [1]. 12.3% of the 17,928 questioned stated sleep disorders as the main reason for their consultation, the prevalence of all kinds of sleep disorders being 29%. Like seen in other studies sleep complaints increased with age and predominated significantly in women. In one-third of the sample the differential diagnosis was primary or non-organic insomnia [1] while treatment was mainly conducted by the general practitioner. In two-thirds of the patients sleep disorders existed for more than 12 months while 41%--by their own account--took sleep agents at least once a week. This article gives an overview of the causes and treatment of sleep disorders, particularly therapy of non-organic insomnia.

Central Nervous System Agents↗
PubMed2001

Insight into patient dissatisfaction with asthma treatment.

BACKGROUND: Measures of patient satisfaction or dissatisfaction with treatment are increasingly being used as indicators of quality of care. As these measures become more widely used, it is important to know if patient dissatisfaction is associated with important processes or outcomes of medical care. METHODS: Survey of patient-reported asthma management issues using the Asthma Therapy Assessment Questionnaire in a large health maintenance organization in the Pacific Northwest. Associations between patient dissatisfaction with asthma treatment and patient-reported measures of asthma control, patient-provider communication, and belief in asthma medications (self-efficacy) were examined. RESULTS: Of the 5181 adult members with asthma enrolled in the health maintenance organization, 30% indicated dissatisfaction with current treatment. Dissatisfaction was higher among patients with a higher number of asthma control problems, patient-provider communication problems, or belief in medication problems (eg, failure to believe their medications are useful and inability to take asthma medications as directed). The odds of dissatisfaction with treatment were 2.8 (95% confidence interval [CI], 2.4-3.3; P<.001) for asthma control problems, 2.0 (95% CI, 1.6-2.6; P<.001) for communication problems, and 8.0 (95% CI, 6.7-9.5; P<.001) for belief in medication problems compared with patients without these perceived problems. CONCLUSION: Patient dissatisfaction with treatment may be related to important asthma disease management issues.

Adult↗
PubMed2001

Physiological functions and hormonal regulation of mouse vas deferens protein (AKR1B7) in steroidogenic tissues.

The MVDP (mouse vas deferens protein) gene encodes an aldose reductase-like protein (AKR1B7) highly expressed in vas deferens epithelium and zona fasciculata of the adrenal cortex. Recombinant MVDP showed kinetic properties distinct from those of aldose reductase, including its spectrum of substrates, cofactor preference and sensitivity to inhibitors. We demonstrate that in adrenocortical cells, MVDP, rather than aldose reductase, is the principal reductase for isocaproaldehyde (a product of side-chain cleavage of cholesterol) and 4-hydroxynonenal (a lipid peroxidation product). In steroidogenic tissues MVDP expression is regulated by pituitary trophic hormones, namely ACTH in adrenals, FSH in ovaries, and LH in testicular Leydig cells.

Adrenal Cortex↗
PubMed2001

[Prescribing of sildenafil by national insurance program physicians. What basic sexual medicine qualification is required?].

The role of sildenafil in the treatment of erectile dysfunction is discussed. Especially in primary care there is a necessity to weigh the individual cost-benefit-ratio. Functional analysis of erectile dysfunction, exclusion of psychiatric and organic comorbidity, identification of sexual deviance and couple counseling about the advantages and disadvantages of sildenafil prescription are the core prerequisites of sildenafil application in primary care. The counseling model of PLIS-SIT is proposed as a guideline for counseling process. Current approaches of education for general practitioners are reviewed and the integration in a recently developed training for management of psychiatry and psychosomatic illness in general medical settings is proposed. Finally open questions for research and quality management are discussed.

Cost-Benefit Analysis↗
PubMed2001

Changes in the brain protein levels following administration of kainic acid.

Kainic acid (KA), a potent neurotoxin and excitatory amino acid, leads to derangements and modulation of brain proteins. No global brain protein expression pattern induced by KA-treatment has been reported yet. We therefore studied the effect of systemic KA administration on the levels of brain proteins. Rats were injected placebo or KA intraperitoneally and brain was taken after one week. The mitochondrial and cytosolic fractions of the brain proteins were analyzed by proteomics technologies and the levels of selected proteins were quantified using specific software. Heat shock protein HSP 27 was exclusively detected in brains of animals treated with KA, whereas the glucose regulated protein GRP 78 was downregulated. The levels of neurofilaments and alpha-internexin were significantly decreased and a fragment of tubulin alpha-1 chain was manifold increased in KA-brains. The mitochondrial enzymes dihydrolipoamide dehydrogenase, ATP synthase beta chain and isocitrate dehydrogenase were reduced and pyruvate kinase M1 was increased following KA treatment. We conclude that the concomitant determination of the brain proteins indicates altered regulation of heat shock proteins, neuronal death, cytoskeletal disruption, and mitochondrial derangement by systemic KA administration. This report confirms and extends previous studies on the effect of KA on the expression of brain proteins and suggests that our analytical system can serve as a model for neurotoxicological, neurobiological, and neuropathological proteome studies.

Animals↗