Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 19 recordsLinked to original sources

PubMed2006

Unexpected higher-order effects in charged particle impact ionization at high energies.

Most of the experimental and theoretical studies of electron-impact ionization of atoms, referred to as (e, 2e), have concentrated on the scattering plane. The assumption has been that all the important physical effects will be observable in the scattering plane. However, very recently it has been shown that, for C6+-helium ionization, experiment and theory are in nice agreement in the scattering plane and in very bad agreement out of the scattering plane. This lack of agreement between experiment and theory has been explained in terms of higher-order scattering effects between the projectile and target ion. We have examined electron-impact ionization of magnesium and have observed similar higher-order effects. The results of the electron-impact ionization of magnesium indicate the possible deficiencies in the calculation of fully differential cross sections in previous heavy particle ionization work.

Journal Article↗

PubMed2006

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

Adenocarcinoma↗

PubMed2006

Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines.

Interactions between neoplastic and stromal cells contribute to tumor progression. Wnt genes, involved in cell migration and often deregulated in cancers, are attractive candidates to regulate these effects. We have recently shown that coculture of breast cancer cells with macrophages enhances invasiveness via matrix metalloproteases and TNF-alpha. Here we demonstrate that coculture of MCF-7 cells and macrophages leads to up-regulation of Wnt 5a in the latter. This was accompanied by activation of AP-1/c-Jun in MCF-7. Recombinant Wnt 5a mimicked the coculture effect. Wnt 5a was also detectable in tumor-associated macrophages in primary breast cancers. Experiments with agonists and antagonists of Wnt signaling revealed that a functional canonical pathway in the tumor cells was a necessary prerequisite; however, noncanonical signaling via Wnt 5a and the Jun-N-terminal kinase pathway was critical for invasiveness. It was also responsible for induction of matrix metalloprotease-7, known to release TNF-alpha. All these effects could be antagonized by dickkopf-1. Our results indicate that Wnt 5a is essential for macrophage-induced invasiveness, because it regulates tumor cell migration as well as proteolytic activity of the macrophages. The function of Wnt 5a as either a suppressor or promoter of malignant progression seems to be modulated by intercellular interactions. Wnt 5a detection in tumor-associated macrophages in breast cancer biopsies supports the assumption that similar events play a role in vivo.

Breast Neoplasms↗

PubMed2006

Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVE: Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Serum levels of testosterone (T), androstenedione (Delta4), dehydroepiandrosterone sulphate (DHEAS), estrone (E1), estradiol (E2) and SHBG were measured by direct immunoassays. Free T (fT) and free E2 (fE2) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires. RESULTS: Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Delta4 and about 40% higher E1, concentrations compared to women who were non-consumers. E2, fE2 and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Delta4, and E1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E2 or fE2 were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers. CONCLUSION: This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood.

Adult↗

PubMed2006

Spots, blots, peaks and chips: proteomic approaches in autoimmune diseases.

During the past five years, investigations employing a variety of proteomic technologies have yielded a wealth of information on a number of autoimmune disorders. Animal models of autoimmune disease have been examined and have provided clues that can be useful in elucidating molecular pathways and mechanisms that play a role in autoimmune disorders. Human sera and body fluids have been analyzed and have resulted in the identification of autoantibodies that can be used as diagnostic markers in specific autoimmune diseases, and proteomic fingerprints of tissues and body fluids have resulted in the identification of individual proteins or patterns of protein expression that are deregulated in autoimmune diseases. The information provided by these proteomic studies are of diagnostic and therapeutic potential. This review provides an overview of the approaches used in the proteomic analyses of autoimmune disease.

Animals↗

PubMed2006

Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study.

INTRODUCTION: Mucoactive substances such as ambroxol, available in several countries as over-the-counter (OTC) medicines, are used for the treatment of acute and chronic bronchitis. OBJECTIVE: This study was designed to evaluate the "real life" behavior of consumers with non-prescription access to an ambroxol cough syrup with special focus on tolerability and the pattern of product usage. METHODS: Customers who bought the ambroxol syrup were recruited in 300 community pharmacies in Germany. Baseline data were collected from the participants in the pharmacy. Completing a self-administered questionnaire, participants provided information on tolerability, self-perceived effectiveness and usage pattern. RESULTS: 2,707 participants were recruited in 266 pharmacies. 2,664 questionnaires were evaluable. At baseline, the respondents reported a complex pattern of symptoms. Productive cough, congested airways, dry cough, cough irritation in the throat and soreness in the throat were the most common ones. 67 patients (2.5%) reported a total of 81 adverse events (AE) which were usually mild in nature and mostly affecting the gastrointestinal tract (n = 53) followed by skin and subcutaneous tissue disorders (n = 9). No serious or unknown AE were reported. In general, 97% of the participants assessed the safety as "very good" (51%) or "good" (46%). Overall, the respondents complied with the indications for use and the recommended dosages, with only 0.7% of the participants using the maximum daily dose. 92% of the patients assessed the self-perceived effectiveness as "very good" (29%) or "good" (63%) and 89% were willing to purchase this ambroxol cough syrup again. CONCLUSIONS: This study confirms that ambroxol is used according to the advice given in the patients' leaflet and supports the already established safety and efficacy of this product in acute bronchitis. It also demonstrates that the use of an OTC cough medication can be successfully monitored in a pharmacy-based cohort study.

Adolescent↗

PubMed2006

Prescribing of COX-2 inhibitors in Germany after safety warnings and market withdrawals.

The emergence of safety concerns associated with the use of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) led to market withdrawals of rofecoxib in September 2004 and valdecoxib in April 2005. These events were accompanied by safety alerts from drug authorities and recommendations from professional medical associations. This study analysed the temporal influence of these measures on drug use in Germany, with the objective to assess overall appropriateness of prescribing and to evaluate the potential for pharmaceutical interventions. Drug prescriptions for patients within the statutory health insurance system (GKV) were analysed based on the total amount of DDDs of single drug substances dispensed every month in German pharmacies. The market withdrawal of rofecoxib in September 2004 resulted initially in increased prescribing of other coxibs. New safety warnings on coxibs later in 2004 and the withdrawal of valdecoxib in April 2005 led to pronounced reductions in coxib prescribing. Comparing the third quarter of 2005 with 2004, coxib prescriptions dropped from 47.5 to 10.4 million DDDs. Conversely, in the same time frame, NSAID prescriptions increased by 19.0 million DDDs. This is mostly due to increased prescribing of ibuprofen, diclofenac and, to a lesser degree, meloxicam, acemetacin, piroxicam, and naproxen. However, total prescribing of inhibitors of cyclooxygenases decreased by about 8.4%, indicating a relative reluctance to prescribe these drugs after cardiovascular safety warnings have been issued by drug authorities. Unexpectedly, also prescribing of metamizol (dipyrone) increased by 2.8 million DDDs (20%), despite recommendations to limit its use by medical associations. Furthermore, increased prescribing of proton pump inhibitors of 12.6 million DDDs could be observed. NSAIDs and coxibs are to a larger extent prescribed by a broad range of medical specialist groups including orthopaedists and surgeons, whereas drugs used in gastrointestinal or cardiovascular disorders are mainly prescribed by general practitioners and internal specialists, respectively. Therefore, the individual physician may not always be aware of the risk profiles of their patients. Pharmacists can close this gap by providing comprehensive medication records and information on self medication used by the patient to prescribing practitioners, thereby contributing to improved patient safety.

Anti-Ulcer Agents↗

PubMed2005

Long-term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC).

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40,429 premenopausal and 57,923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrollment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend < or = 0.0002). Compared to women with a stable weight (+/-2 kg), the relative risk for women who gained 15-20 kg was 1.50 (95% confidence interval (CI) 1.06-2.13). The pooled RR per weight gain increment of 5 kg was 1.08 (95% CI 1.04-1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones.

Adult↗

PubMed2005

Bacteria induce expression of apoptosis in human spermatozoa.

An increased number of sperm undergoing apoptosis has been observed during inflammatory processes in the male genital tract, which might be associated with elevated reactive oxygen species (ROS) levels. However, another factor to stimulate apoptosis could be the direct contact with bacteria or its products, even in the absence of ROS. The aim of this study was to investigate whether bacteria can directly initiate apoptosis in human spermatozoa. Human spermatozoa selected by density gradient centrifugation were incubated with polymorphonuclear granulocytes (PMN) isolated from blood and/or E. faecalis, E. coli or S. aureus. As ROS inductor in PMN, phorbol-12-myristate-13-acetate was used. After incubating the cells for 60 min at 37 degrees C, ROS were determined by chemiluminescence and phosphatidyl serine (PS) externalization was analyzed by flow cytometry with Annexin V-FITC and propidium iodide (PI). The increase in the percentage of spermatozoa Annexin V-FITC-positive/ PI-negative (early event of late apoptosis) was significant after the incubation with PMN plus PMA, PMN plus E. coli and E. coli alone. The percentage of spermatozoa Annexin V-FITC-positive/ PI-positive (apoptosis/necrosis) increased significantly in sperm incubated with E. coli and S. aureus (20.3% +/- 3 and 13.6% +/- 3.2 compared to sperm alone, 6% +/- 0.5). Sperm incubated with PMN-PMA activated showed only a relative increase in apoptosis/necrosis (8.4% +/- 1). Our results show that bacteria directly increase the PS externalisation in ejaculated human sperm. This way of inducing apoptosis does not require external ROS and may result from anyone of the molecular mechanisms that account for changes in motility, vitality and DNA integrity, that are characteristics of spermatozoa in male genital tract infection.

Apoptosis↗

PubMed2005

Associations of short-term weight changes and weight cycling with incidence of essential hypertension in the EPIC-Potsdam Study.

The aim of this study was to examine the relationships of short-term weight gain, weight loss, and weight cycling on the odds of developing hypertension. Normotensive middle-aged German men and women (n=12,362) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study were assigned to categories of 2-year short-term weight changes that were self-reported to have occurred prior to recruitment into the study (gain only, loss only, weight cycling, stable). After 2 years of follow-up after recruitment, 180 cases of incident essential hypertension were identified. In logistic regression models, odds ratios were estimated for the associations between short-term weight changes and risk of developing hypertension. Obesity status (BMI>or=30 or BMI<30 kg/m2) modified the associations between short-term weight change and incidence of diagnosed hypertension. Among obese individuals, short-term weight gain occurring during the 2 years prior to recruitment (OR=2.79, 95% CI 1.19-6.56), weight loss (OR=6.74, 95% CI 2.58-17.6) and weight cycling (OR=4.29, 95% CI 1.55-11.9) were strongly positively associated with incident hypertension, adjusted for age and gender, compared to obese individuals with short-term stable weight. No significant associations between short-term weight changes and risk of diagnosed hypertension were detected among non-obese individuals. Short-term weight changes appeared to present strong risk factors for developing hypertension among obese individuals. The effect seen for weight cycling supports the hypothesis that weight cycling increases the risk of hypertension. The finding for short-term weight loss may be explained by subsequent weight regain and needs further investigation.

Adult↗

PubMed2005

[Early results of proximal interphalangeal joint replacement with pyrolytic carbon prosthesis (Ascension) in idiopathic and post-traumatic arthritis].

Surgical treatment of painful idiopathic and post-traumatic arthritis with joint replacement of the proximal interphalangeal joint has become increasingly important. Due to shortcomings of former constrained and partially constrained prostheses with regard to abrasion and durability we have been using an unconstrained prosthesis since April 2002. This model is an almost abrasion free, biocompatible 2-component prosthesis. The surface is shaped like the condyles and the position is secured in a press-fit technique. During October 2004 we reviewed the results of 20 out of 29 patients with idiopathic or post-traumatic arthritis who had been treated with a pyrolytic carbon proximal interphalangeal joint prosthesis from April 2002 to April 2004 retrospectively. Clinical, subjective and radiological parameters were studied. On follow-up after 0.5 to 2.5 years the patients were satisfied with the pain relief. The range of motion varied. However, with an average ROM of 50 degree it was equivalent to the results in literature. Signs of periprosthetic cysts, osteophytes and loosening of the proximal as well as of the distal component could be seen in the radiograms of some patients. There was no correlation between these radiological observations and range of motion, pain or grip strength. In three cases the joint prosthesis had to be converted to an arthrodesis of the proximal interphalangeal joint. Bearing in mind the correct indications (intact collateral ligaments, stable bone stock and sufficient extensor and flexor tendons), pyrocarbon prosthesis are a treatment option for idiopathic and posttraumatic arthritis preserving motion and reducing pain. Radiological results seem to indicate an absence of osteointegration and tension forces at the prosthesis/bone interface. Further investigation will be necessary to improve surface and design to increase radiological results in long-term follow-up. Additional surveys are required to improve indications, surgical approach and intraoperative control of correct component positioning.

Adult↗

PubMed2005

Counselling quality in community pharmacies: implementation of the pseudo customer methodology in Germany.

OBJECTIVES: To investigate a new method for evaluating counselling performance of staff in community pharmacies and to assess the quality of patient counselling. METHOD: Trained pseudo customers, instructed to play their role according to two different self-medication scenarios, visited voluntarily participating community pharmacies in Berlin. After documenting the counselling process, immediately after each visit, outside the pharmacy on an assessment form, the pseudo customer re-entered the pharmacy and gave detailed performance feedback to the counsellor and the pharmacist in charge in order to provide support for improving counselling skills and practice behaviour, when appropriate. This was followed with a written summary of the general performance of all participating pharmacies and additional individual feedback and suggestions for improvement. Educational needs were identified for subsequent performance-based educational strategies such as group-workshops, team-training and on-site team-coaching. RESULTS: Forty-nine community pharmacies in Berlin volunteered to participate in this pilot study. Ninety-eight per cent of the participating pharmacies offered advice. However, in 36% of the cases, advice was only given on request. The different types of scenarios--presentation of a symptom or request for a specific product--made a great difference to the spontaneity of questions and advice. At least one question to check on accuracy of self-diagnosis was asked in 95% of the cases of symptom presentation but in only 47% of the cases of specific product request. Information on appropriate self-medication was provided on at least one item in 74% of pseudo customer visits, but most of the time the information was not sufficient. Communication skills (nonverbal elements, comprehensibility etc.) were very good or good in 54% of the visits. Potential for improvement was mainly in relation to the use of open-ended questions to gain more information and on counselling about appropriate self-medication. Direct feedback was given in 96% of the pharmacies (one person refused to accept feedback and one feedback had to be postponed because of time shortage). All of the participants regarded counselling as an important subject in pharmacy practice. CONCLUSION: The pseudo customer method was successfully used in this study of German community pharmacies. It was shown that pseudo customer visits and performance feedback following the counselling process, were feasible in daily practice and well accepted by the participants. A training program, focussing on areas in most need of improvement, has been developed. The promising results have led to the Federal Chamber of Pharmacists in Germany adopting this method as part of a continuous quality improvement program in community pharmacies.

Community Pharmacy Services↗

PubMed2004

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

PubMed2004

Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients.

Relaxin (RLX) is known to induce remodeling of benign stromal tissues through upregulation of matrix metalloproteases (MMPs). Recently, we could show that RLX also induces MMPs in breast cancer cells and enhances in vitro invasiveness. To investigate its potential role for progression of breast cancer in vivo, RLX serum concentrations were determined in 160 breast cancer patients during post-surgical follow-up. RLX concentrations in cancer patients were significantly higher than in a control population of healthy blood donors and patients with various other diseases (0.47 versus 0.29 ng/ml, p < 0.0001). There was a significant difference between patients with metastases (0.62 ng/ml) and those without (0.38 ng/ml, p < 0.0001). Overall survival was shorter in RLX-positive ( > 0.4 ng/ml) than in RLX-negative patients (p = 0.016). Cox regression analysis showed that RLX was not an independent variable, in contrast to metastatic disease and primary lymph node involvement. Taken together, the detection of elevated RLX concentrations especially in patients with metastases supports the assumption that there is a role for RLX in tissue remodeling during breast cancer progression.

Adult↗

PubMed2004

[Smoking habits of employees and patients in the psychiatric department of a general hospital].

OBJECTIVE: Health promotion is becoming an increasingly more meaning in hospitals within their health promotion, primary and secondary prevention programmes. With reference to the preventive measures regarding nicotine dependence, it was first of all the objective of this study to determine the smoking habits of employees and patients in a psychiatric clinic. The question was also which implications for clinical practice could be drawn from this. METHODOLOGY: Apart from the Fagerstroem Test for nicotine dependence, a new questionnaire was developed, supported by the questionnaire "Smoke free in hospital", developed by the Federal Agency for Health Education, and implemented. 382 Patients and 484 employees were questioned. The statistical analysis was done using SPSS, and in addition thereto, the T-Test and the chi (2)-Test were used. RESULTS: Definite gender differences pertaining to smoking habits could be demonstrated. Women smoked less often (p < 0.001) and less (p < 0.01) than men and were less dependent on nicotine (p < 0.007). With increasing age, the number of smokers declined. In questioning the employees, it was clear, that there were no significant differences between doctors and nurses regarding their smoking habits. However, employees in the clinic working shifts were consuming more cigarettes daily (p < 0.044) and had a higher degree of dependence (p < 0.01). On questioning the patients, it was demonstrated that the number of smokers (92%) consuming cigarettes, dependence were significantly higher on the wards for dependence diseases. Overall it was clear that there were definite qualitative and quantitative differences in the smoking habits of both patients and employees. Patients smoke more often (p < 0.001) and are more dependent (p < 0.001) than employees. There were no differences between the two groups regarding the motivation to stop smoking (smokers willing to stop: 36%). However, more patients (38.5%) than employees (23.8%) expressed the opinion, that it is the task of the Hospital employees to regularly point out the risks of smoking. DISCUSSION: In the psychiatric clinic in question, the results demonstrated that cigarette consumption and nicotine dependency, for both patients and employees, are serious problems that can be transferred into comparable clinics and departments. Patients are more affected than employees. Other studies proved that psychiatric patients smoke twice as much as people without psychiatric diseases. CONCLUSION: Against the background, that health promotion and prevention should increasingly become the task of every hospital, further studies will be necessary to establish health promotive activities influencing smoking patients and employees. Specific treatment modalities regarding the motivation to change are still not available. Added to that, it must be tested within the German Health System, whether a clinically supervised smoking cessation programme complementing the treatment of the main diagnosis (a psychiatric disease) is demanded by the affected person, whether the clinic can finance it, and whether it can be successfully implemented.

Adolescent↗

PubMed2004

Novel ligands: fine tuning the transcriptional activity of the glucocorticoid receptor.

Glucocorticoids are the first line medication used in the therapy of many severe inflammatory disorders. They exert their activity through binding to the glucocorticoid receptor, a ligand-dependent transcription factor, and result in either activation or repression of a large set of glucocorticoid responsive genes. The desired immunosuppressive effect is apparently due largely to the down-regulation of a variety of pro-inflammatory factors, whereas adverse reactions such as corticoid-induced diabetes and osteoporosis could be connected to the inappropriate activation of genes involved in the control of metabolic processes. The discovery of improved glucocorticoids, which maintain beneficial therapeutic activity together with a diminished risk of side effects, focuses on ligands that lead to repression rather than activation of genes targeted by the glucocorticoid receptor. Current drug-screening programs have yielded a number of molecules including steroidal as well as non-steroidal compounds, which preferentially induce receptor-mediated repression. The characterization of these novel glucocorticoids in several in vitro and in vivo models for their immune modulating activity marks an important step towards the development of a new class of safer glucocorticoid preparations.

Animals↗

PubMed2003

Probing scattering wave functions close to the nucleus.

Recently, three-dimensional imaging of the ejected electrons following 100 MeV/amu C6+ single ionization of helium led to the observation of a new structure not predicted by theory [Nature (London) 422, 48 (2003)]]. Instead of the usual "recoil lobe" centered on the momentum-transfer axis, a ring-shaped structure centered on the beam axis was observed. New measurements at 2 MeV/amu exhibit a similar structure, which is now predicted by theory. We argue that the same theory failed at 100 MeV/amu because the faster projectiles probe distances much closer to the nucleus, where our multiple-scattering model is expected to break down.

Journal Article↗

PubMed2003

[Disease management program (DMP) diabetes mellitus: simulation of therapeutic results of different guidelines. A new diabetes mellitus model (DMM)].

BACKGROUND AND OBJECTIVE: In conjunction with the introduction of disease management programmes in Germany there is an ongoing scientific debate on the desirable goals for HbA1c in the management of patients with type 2 diabetes mellitus. PATIENTS AND METHODS: In this study, a novel computer-based simulation model (diabetes mellitus model = DMM) was used to estimate the consequences of different levels of metabolic control as assessed by HbA1c for the development of short- and long-term complications of this disease. RESULTS: At a mean difference of 1 % the rate of severe hypoglycaemic events over 10 years was by 32-84 % higher in those with a lower HbA1c. In contrast, the incidence of microvascular complications (proliferative retinopathy, end-stage kidney disease, clinical neuropathy) was by 20-33 % lower in the group with the lower as compared to the higher HbA1c level according to the scenario applied. The rates of myocardial infarction and stroke were reduced by 15-20 % under these conditions. CONCLUSIONS: This model calculation suggests that a more strict metabolic control in patients with type 2 diabetes mellitus results in a greater reduction of microvascular complications than of macrovascular complications, but is associated with a higher rate of hypoglycaemic episodes. The diabetes mellitus model is a non-expensive alternative to simulate clinically relevant questions on the management of type 2 diabetes and to provide rapid and realistic answers.

Aged↗