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Biomedical subjects

S Beer

Publications and source records attributed to S Beer.

At least 19 recordsLinked to original sources

[Disability in lupus erythematosus].

Morbidity and co-morbidities in patients with lupus erythematosus (LE) result in an impairment, limiting activities of daily living. We compared the handicap, appraised by the German welfare system in patients with LE and their diagnosis, morbidities and co-morbidities, therapy, functional capacity, psychological status and general health. The data were obtained in an anonymous self-administered questionnaire conducted by the lupus patient association. 892 data sets were available for the trial. The mean age was 46.9y, disease duration was 10.3y. The patients had 3.8 concomitant diseases on average. 39.7% were still working and 35.4% drew a pension. 59.2% made an application for disability, which wasn't assigned in only 2.5% of cases. 82.6% had an average grade of disability of more than 50%. It demonstrated a good correlation to age, disease duration, type of LE and therapy. Predictors for a worse assessment were disease duration, osteoarthritis, cerebral insults and functional capacity. In conclusion the data demonstrate a fair appraisal of disability by the German welfare system in patients with LE. Self-administered questionaires can yield credible results.

Disability Evaluation↗

[Gestational diabetes: what follow-up after delivery?].

Women with gestational diabetes have a high risk for dysglycemia and metabolic syndrome. The post-partum screening evaluation allows to establish the "metabolic profile". The components of the SM must be recognized and treated. The life-style modifications are the priority. A follow-up by the general practitioner, assisted by a dietitian when it is indicated must be set up and the objectives regularly evaluated. The difficulty perceiving the long-term benefits and the changes of priority when the child is born represent specific barriers for the preventive interventions and must be identified. Specific preventive strategies to this population at high risk must be created and evaluated.

Continuity of Patient Care↗

[Preventing type 2 diabetes complications: from evidence-based recommendations to patient-based reality].

The vascular complications of type 2 diabetes count for the principal causes of morbidity, hospitalisation and mortality in this population. Therefore, preventing these complications is the cornerstone of the management of these patients. This prevention is through multifactorial interventions aiming at controlling the parameters of the metabolic syndrome in order to prevent or slow down these vascular complications. This prevention is also through a regular and exhaustive screening performed early enough in the disease. Above all, the management of these patients implies involving them as the main actors of their disease and treatments. This necessitates to take into account the beliefs and to actively seek the obstacles to therapeutic adherence.

Continuity of Patient Care↗

[Accelerated atherosclerosis in rheumatic systemic diseases as an example of systemic lupus erythematosus--what is the consequence?].

Large increases in mortality related to premature atherosclerosis with coronary artery disease and stroke have been reported during the last few years in patients with systemic lupus erythematosus (SLE). Studies found relative risks of 5 to 7 for myocardial infarction in SLE patients. The traditional risk factors fail to fully account for accelerated atherosclerosis in SLE and APS, in addition prolonged glucocorticoid therapy and long duration of SLE seem to be of importance. The disease SLE per se is an independent risk factor. The current pathogenic hypothesis for atherosclerosis involves an inflammatory response, autoantibodies, immune complexes (containing antibodies to phospholipids, to oxidized LDLs, and to endothelial cells), CD40/CD40 ligand interactions, and bacterial or viral infections responsible for an immune response. The determination of classic and new risk factors, together with specific autoantibody titers and the use of Doppler carotid ultrasound, are useful methods to detect early atherosclerosis. Therapeutic strategies, including early risk factor intervention and effective control of inflammation, are essential to reduce morbidity and mortality and should be incorporated into the management of connective tissue disease with the goal of protecting patients against atherosclerosis.

Arteriosclerosis↗

Increased plasma levels of N-terminal brain natriuretic peptide (NT-proBNP) in type 2 diabetic patients with vascular complications.

AIMS: The plasma levels of either brain natriuretic peptide (BNP) or the N-terminal fragment of the prohormone (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction. Patients with type 2 diabetes are at high risk of developing cardiovascular complications. This study was aimed to assess whether plasma NT-proBNP levels are at similar levels in type 2 diabetics with or without overt cardiovascular diseases. METHODS: We assayed plasma NT-proBNP in 54 type 2 diabetics, 27 of whom had no overt macro- and/or microvascular complications, while the remaining ones had either or both. The same assay was carried out in 38 healthy control subjects age and sex matched as a group with the diabetics. RESULTS: Plasma NT-proBNP was higher in diabetics (median 121 pg/ml, interquartile range 50-240 pg/ml, ) than in those without complications (37 pg/ml, 21-54 pg/ml, P<0.01). Compared with the controls (55 pg/ml, 40-79 pg/ml), only diabetics with vascular complications had significantly increased plasma NT-proBNP levels (P<0.001). In the diabetics, coronary heart disease and nephropathy (defined according to urinary excretion of albumin) were each independently associated with elevated values of plasma NT-proBNP. CONCLUSIONS: In type 2 diabetes mellitus, patients with macro- and/or micro-vascular complications exhibit an elevation of plasma NT-proBNP levels compared to corresponding patients with no evidence of vascular disease. The excessive secretion of this peptide is independently associated with coronary artery disease and overt nephropathy. The measurement of circulating NT-proBNP concentration may therefore be useful to screen for the presence of macro- and/or microvascular disease.

Blood Pressure↗

Barrett's esophagus: a discrepancy between macroscopic and histological diagnosis.

BACKGROUND AND STUDY AIMS: The diagnosis of Barrett's esophagus at present requires endoscopic and histological confirmation of specialized intestinal metaplasia. This study prospectively analyzed the endoscopic and histological prevalence of Barrett's esophagus and the risk factors for the presence of Barrett's esophagus among patients being treated in an endoscopy unit. PATIENTS AND METHODS: A total of 474 unselected patients (58% men; mean age 52 y) were included in the study. Two biopsy specimens each were taken from below and above the squamocolumnar junction and from the antrum and gastric body. Four-quadrant biopsies were taken every 1-2 cm to confirm a macroscopic suspicion of Barrett's esophagus. RESULTS: Barrett's esophagus was suspected at endoscopy in 109 patients (23%). Of the 109 patients with endoscopically suspected Barrett's esophagus, only 46 (42%) had the finding confirmed histologically. The sensitivity and specificity for the endoscopic diagnosis of Barrett's esophagus were 62% and 84%, respectively. A multivariate logistic regression analysis identified age (P = 0.0001; odds ratio per life-year 1.087; 95% CI, 1.046-1.139), male sex (P = 0.0020; OR 6.346; 95% CI, 2.094-22.314), and the number of biopsies (P = 0.0025; OR 1.661; 95% CI, 1.247-2.392) as factors associated with evidence of intestinal metaplasia on biopsy. CONCLUSION: The striking discrepancy between the endoscopic findings and the histological diagnosis may be due to the focal distribution of intestinal metaplasia. This emphasizes the importance of an adequate biopsy protocol. In addition, better methods of detecting focal islands of intestinal metaplasia that are not visible at conventional endoscopy are needed.

Adolescent↗

[School nutrition and nutrition lessons].

Nutrition behavior usually becomes manifest during childhood and once learned food patterns and eating habits are often maintained for the rest of life. Therefore, imparting knowledge early about food composition, food habits, nutritional physiology, and connections between health and nutrition as well as instilling competence in dealing with food are of particular importance. In the EiS project, it was recently shown that fewer students than ever obtain less and less nutrition education in German schools. Promoting healthy eating is not only a matter of nutritional knowledge. It is also very much about creating a healthy environment and providing proper food, drinks, and meal service in schools. Therefore, both aspects will be discussed in the following article.

Adolescent↗

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↗

Quantification of Uhthoff's phenomenon in multiple sclerosis: a magnetic stimulation study.

OBJECTIVE: To quantify temperature induced changes (=Uhthoff phenomenon) in central motor conduction and their relation to clinical motor deficits in 20 multiple sclerosis (MS) patients. METHODS: Self-assessment of vulnerability to temperature and clinical examination were performed. We used motor evoked potentials to measure central motor conduction time (CMCT) and applied the triple stimulation technique (TST) to assess conduction failure. The TST allows an accurate quantification of the proportion of conducting central motor neurons, expressed by the TST amplitude ratio (TST-AR). RESULTS: Temperature induced changes of TST-AR were significantly more marked in patients with prolonged CMCT (P=0.037). There was a significant linear correlation between changes of TST-AR and walking velocity (P=0.0002). Relationships were found between pronounced subjective vulnerability to temperature and (i) abnormal CMCT (P=0.02), (ii) temperature induced changes in TST-AR (P=0.04) and (iii) temperature induced changes in walking velocity (P=0.04). CMCT remained virtually unchanged by temperature modification. CONCLUSIONS: Uhthoff phenomena in the motor system are due to varying degrees of conduction block and associated with prolonged CMCT. In contrast to conduction block, CMCT is not importantly affected by temperature. SIGNIFICANCE: This is the first study quantifying the Uhthoff phenomenon in the pyramidal tract of MS patients. The results suggest that patients with central conduction slowing are particularly vulnerable to develop temperature-dependent central motor conduction blocks.

Adult↗

Withdrawal of cerivastatin induces monocyte chemoattractant protein 1 and tissue factor expression in cultured vascular smooth muscle cells.

OBJECTIVE: The withdrawal of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase inhibitors (statins) deteriorates endothelial function. We determined in vascular smooth muscle cells whether statin withdrawal leads to the expression of proinflammatory genes involved in the development and progression of arteriosclerosis. METHODS AND RESULTS: The withdrawal of cerivastatin from pretreated vascular smooth muscle cells induced an increase in monocyte chemoattractant protein 1 (MCP-1) and tissue factor (TF) mRNA expression and enhanced MCP-1 secretion as well as cell surface TF activity. In the presence of cerivastatin, this effect was mimicked by geranylgeranyl pyrophosphate or mevalonate. Withdrawal-induced MCP-1 expression was sensitive to PD98059, SB203580, and diphenylene iodonium, suggesting an involvement of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and the NADPH oxidase. Withdrawal increased the activity of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase and enhanced radical generation. Because the latter effect may result from an Rac-mediated activation of the NADPH oxidase, the effect of withdrawal on Rac translocation was studied. Statin treatment induced an increase in Rac-1 content in the cytoplasm. On withdrawal, however, an "overshoot" translocation of Rac to the plasma membrane occurred. CONCLUSIONS: These observations suggest that statin withdrawal results in the activation of Rac and enhanced oxidative stress. The subsequent activation of redox-activated signal-transduction cascades results in the expression of MCP-1 and TF.

Animals↗

Testosterone undecanoate: a useful tool for testosterone administration in rats.

A major obstacle of testosterone (T) treatment in experimental animals is the difficulty of maintaining long-term physiologic/anabolic steady serum levels after exogenous T administration. In two complementary studies we investigated the pharmacokinetic properties of different T formulations in male rats. Study I. Mature male Wistar rats (> 380 g, n = 4 - 7/group) were divided into four treatment groups: (1) sham-operated non orchiectomised (non-ORX) and placebo; (2) orchiectomised (ORX) and subcutaneous testosterone pellets (TP) (15, 25, 75 mg/60 days release or placebo pellets); (3) ORX and a single injection of testosterone undecanoate (TUD) (31, 62.5 or 125 mg/kg body weight subcutaneously (s.c.) or vehicle; (4) ORX and testosterone propionate (Tprop) (10, 20, 40 mg/month) or vehicle as a single injection s.c. Serum T was measured at baseline and in weekly intervals for 4 weeks. Study II. Mature male Wistar rats (180 - 200 g) were randomly assigned to one of 5 experimental groups (n = 5 - 6/group): (1) normal untreated rats (controls); (2) ORX untreated rats, and non-ORX rats receiving one of three treatment options; (3) 250 mg/kg body weight TUD i.m. (TUD 250); (4) 500 mg/kg body weight TUD i.m. (TUD 500); (5) 100-mg testosterone pellet/90 days release s.c. (TP 100). Serum T was measured at baseline and in intervals for 6 weeks after T administration. In both studies, the kinetic profile of TUD showed favourable continuous steady state levels over several weeks. In contrast, testosterone release by subcutaneous pellets resulted in a shorter than expected duration of elevated serum T levels with high inter-individual variability. Tprop administration led to only a short-lasting serum T increase with low serum T levels already 14 days after injection. In conclusion, a single injection of TUD (100 mg/kg body weight s.c.) is effective in inducing physiological testosterone levels in ORX rats for a minimum of four weeks. High dose TUD (500 mg/kg body weight i.m.) given as a single injection results in supraphysiological anabolic testosterone concentrations for up to six weeks in non-ORX rats. TUD was superior to other T release preparations and represents a convenient and effective tool for T administration in experimental animals.

Anabolic Agents↗

Molecular cloning and characterization of a novel SH3 protein (SLY) preferentially expressed in lymphoid cells.

A novel full-length cDNA was isolated from a murine T-cell lymphoma library that has an open reading frame encoding 381 amino acids. The predicted protein (termed SLY) contains a Src homology 3 domain and a sterile alpha motif, suggesting that it functions as a signaling adaptor protein in lymphocytes. Northern blot and in situ hybridization analysis showed a preferential expression in lymphoid tissues. The sly gene is located on the X-chromosome in close proximity to genes involved in various immune disorders. This is consistent with an additional role of SLY in immune pathology.

Animals↗

[Anterior interosseous nerve syndrome as differential diagnosis of closed isolated flexor tendon lesion].

Lesions of the anterior interosseus nerve can result in a variety of clinical manifestations, depending on location and degree of axonal damage. Clinical presentation with an isolated palsy of the flexor pollicis longus muscle is difficult to distinguish from a closed tendon rupture, especially when a trauma occurred. We would like to present five of our cases and discuss the diagnostic and therapeutic modalities.

Adult↗

Impact of neurorehabilitation on disability in patients with acutely and chronically disabling diseases of the nervous system measured by the Extended Barthel Index.

To study the impact of rehabilitation on disability in an unselected patient group with acutely and chronically disabling neurologic diseases, the Extended Barthel Index (EBI) was determined at the beginning and at the end of the rehabilitation stay in all patients admitted to our Neurorehabilitation Centre in Valens, Switzerland. Patients who reached the highest possible EBI score at entry ("ceiling effect"), with a short stay (<1 week), or with a deterioration due to other medical complications were excluded. Finally EBI data of 743 patients could be analyzed. The mean EBI at entry was 45 and 51 at discharge. The mean increase of the EBI score per week was 1.1 (SD, 1.7). The change of the EBI score was analyzed independently in patients with acute neurologic diseases admitted in the postacute phase (acute group) and patients with chronically disabling neurologic diseases (chronic group). As expected, the increase of the EBI score was higher in the acute group than in the chronic group; 80.8% of the acute group patients and 42.5% of the chronic group patients showed an increase of the EBI score at discharge. Both groups showed a significant EBI gain with a marked shift to higher EBI scores at discharge. The mean gain per week was 1.6 in the acute group and 0.5 in the chronic group, respectively. Analysis of EBI changes considering the different underlying diseases showed the highest increase in patients with stroke and traumatic brain injury.

Activities of Daily Living↗

Quantitative real-time PCR assay for determining transgene copy number in transformed plants.

The development of transgenic events can be limited by many factors. These include expression levels, insert stability and inheritance, and the identification of simple insertion events. All of the factors can be related to the copy number of the transgene. Traditionally, copy number has been determined by laborious blotting techniques. We have developed an alternative approach that utilizes the fluorogenic 5' nuclease (TaqMan) assay to quantitatively determine transgene copy level in plants. Using this assay, hundreds of samples can be analyzed per day in contrast to the low throughput encountered with traditional methods. To develop the TaqMan copy number assay, we chose to utilize our highly efficient Agrobacterium-mediated transformation system of maize. This transformation procedure generates predominantly low copy number insertion events, which simplified assay development. We have also successful applied this assay to other crops and transformation systems.

Computer Systems↗

Thrombin-induced MCP-1 expression involves activation of the p22phox-containing NADPH oxidase in human vascular smooth muscle cells.

UNLABELLED: Activation of vascular smooth muscle cells (VMSC) by thrombin induces the expression of the chemokine, monocyte chemoattractant protein-1 (MCP-1). We investigated in cultured human and rat VSMC whether reactive oxygen species (ROS) derived from the vascular NADPH oxidase contribute to this effect. Exposure of cultured VSMC to thrombin rapidly increased ROS formation, phosphorylation of p38 MAP kinase as well as the expression of MCP-1. Specific inhibition of the p22phox subunit of the vascular NADPH oxidase using either p22phox neutralizing antibody or p22phox antisense oligonucleotides attenuated thrombin-induced ROS generation. Furthermore, thrombin-induced p38 MAP kinase activation as well as MCP-1 expression were impaired by antioxidants as well as by p22phox antisense oligonucleotides. Inhibition of p38 MAP kinase diminished the thrombin-induced expression of MCP-1. CONCLUSION: Thrombin, by activating a p22phox-containing NADPH oxidase, elicits ROS generation and activation of p38 MAP kinase in VSMC. The subsequent induction of MCP-1 expression highligts the crucial role of the p22phox-containing NADPH oxidase in thrombin-induced signal transduction in VSMC.

Animals↗