Biomedical subjects

W Klein

Publications and source records attributed to W Klein.

At least 19 recordsLinked to original sources

PubMed2006

[Causal illness attributions and healthcare utilization in fibromyalgia syndrome].

INTRODUCTION: High utilization of medical services has been described for patients with fibromyalgia syndrome (FMS). There are no studies available that assess whether the patients' subjective illness beliefs influence their behavior in utilizing healthcare. METHODS: Examinations were performed by taking the history of pain treatment in 100 FMS patients evaluated by experts for the social court and 25 patients attending an outpatient pain center. The subjective illness theories were drawn from the patients' responses to the German Pain Questionnaire (GPQ). The statements made on the GPQ regarding utilization of healthcare services were compared with the records and the answers given in the interview on pain therapy. RESULTS: Of the patients, 44% specified a somatic, 2% a psychogenic, 9% none, and 45% a psychosomatic illness belief. The patients were classified as high utilizers of specialized medical services in 25% of the cases and of psychiatric-psychotherapeutic services in 14%. No significant correlations between the type of subjective illness theory and utilization of specialized medical or psychiatric-psychotherapeutic services were observed. CONCLUSION: From the psychosomatic viewpoint, only part of the FMS patients exhibited an inordinately one-sided somatic illness belief. The utilization of healthcare services cannot be explained by the subjective perception of the illness.

Attitude to Health↗

PubMed2006

Mutations in the calcium-sensing receptor: a new genetic risk factor for chronic pancreatitis?

OBJECTIVE: In 2003 we identified a family with familial hypocalciuric hypercalcemia (FHH) (heterozygous CASR gene mutation L173P) and a mutation in the pancreatic secretory trypsin inhibitor gene (SPINK1) (N34S). While family members with an isolated calcium-sensing receptor gene (CASR) mutation remained healthy, a combination of the CASR and SPINK1 gene mutation caused chronic pancreatitis (CP). We thus speculate that the combination of two genetic defects affecting calcium homeostasis and pancreatic enzyme activation might represent a novel approach in chronic inherited pancreatic disease. We therefore sought to explore whether CASR gene mutations were prevalent in a cohort of patients with CP and confirmed SPINK1 mutations. MATERIAL AND METHODS: A cohort of 19 families (n=170) with a history of idiopathic CP (ICP) was screened for mutations within the CASR gene; 104 members of that cohort had a mutation (N34S) within the SPINK1 gene and 66 of those were suffering from CP. The entire CASR gene was screened for single strand conformation polymorphism under varying polyacrylamide gel conditions and subjected to direct dideoxy nucleotide sequencing of amplified cDNA. RESULTS: Single-strand conformation polymorphisms were observed in 59 samples, clustering of exons 3, 4 and 7. DNA sequence analysis revealed a yet unreported missense mutation in exon 7 (R896H) and two conservative mutations in exon 4 (F391F) and exon 7 (E790E). Furthermore, an intronic polymorphism in nucleotide position 493-19 G>A was detected in 19 out of 170 members of that cohort. CONCLUSIONS: We identified three novel calcium-sensing receptor gene mutations (1 missense mutation, 2 silent mutations and 1 intronic polymorphism) in a cohort of 19 families with ICP. In particular, the kindred with the R896H mutation presenting with a similar pedigree to the family described above may indicate a role for CASR gene mutations in SPINK1-related CP. Again, only the patient with the combination of both CASR and N34S SPINK1 gene mutation developed pancreatitis, whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected. We suggest that the CASR gene is a novel yet undetected co-factor in a multifactorial genetic setting of SPINK1-related pancreatitis that alters the susceptibility for pancreatitis in these patients.

Calcium Signaling↗

PubMed2005

Simulation of the Burridge-Knopoff model of earthquakes with variable range stress transfer.

Simple models of earthquake faults are important for understanding the mechanisms for their observed behavior, such as Gutenberg-Richter scaling and the relation between large and small events, which is the basis for various forecasting methods. Although cellular automaton models have been studied extensively in the long-range stress transfer limit, this limit has not been studied for the Burridge-Knopoff model, which includes more realistic friction forces and inertia. We find that the latter model with long-range stress transfer exhibits qualitatively different behavior than both the long-range cellular automaton models and the usual Burridge-Knopoff model with nearest-neighbor springs, depending on the nature of the velocity-weakening friction force. These results have important implications for our understanding of earthquakes and other driven dissipative systems.

Algorithms↗

PubMed2005

Posttraumatic anterior-inferior instability of the shoulder: arthroscopic findings and clinical correlations.

INTRODUCTION: The main purpose of our study was to evaluate intra-articular lesions in glenohumeral-instability with arthroscopy and correlate them with clinical findings as well as history of instability. MATERIAL AND METHODS: In this prospective multi-centre study, we evaluated arthroscopic findings in 303 patients with posttraumatic anterior-inferior instability of the shoulder. The study cohort was divided into 2 groups: patients with a history of one dislocation (Group 1, n=61, 20.1%) and patients with a history of more than one dislocation (Group 2, n=242, 79.9%). RESULTS: In Group 1, 37 patients had an IGHL-lesion, 31 a MGHL-lesion and 41 a Hill-Sachs lesion. In Group 2, 182 patients had an IGHL-lesion, 172 a MGHL-lesion and 203 a Hill-Sachs lesion. The percentage of lesions in Group 2 (IGHL-75.2%, MGHL-71.1%, Hill-Sachs-83.9%) was significantly higher than in Group 1 (IGHL-60.7%, MGHL-50.8%, Hill-Sachs-67.2%, P=0.0233, P=0.0026, and P=0.0033, respectively). Within Group 2 we found significantly more Hill-Sachs-lesions with a history of an increasing number of recurrences (P=0.0436). We also found an increase of IGHL- and MGHL-lesions with an increasing number of recurrences, but this difference was not significant. The distribution of lesion types of the anterior labrum-ligament complex showed no significant difference between the two groups, apart from a higher incidence of ALPSA-lesions within Group 2 (34.7% versus 18.0% in Group 1). The results of this study show that recurrences after primary posttraumatic anterior-inferior shoulder dislocation cause increasing ligamental damage as well as increasing Hill-Sachs lesions within the gleno-humeral joint. CONCLUSION: Thus we conclude that early surgical stabilization after posttraumatic anterior-inferior shoulder dislocation is necessary to prevent increasing damage within the shoulder joint.

Adolescent↗

PubMed2005

A simulation-based approach to forecasting the next great San Francisco earthquake.

In 1906 the great San Francisco earthquake and fire destroyed much of the city. As we approach the 100-year anniversary of that event, a critical concern is the hazard posed by another such earthquake. In this article, we examine the assumptions presently used to compute the probability of occurrence of these earthquakes. We also present the results of a numerical simulation of interacting faults on the San Andreas system. Called Virtual California, this simulation can be used to compute the times, locations, and magnitudes of simulated earthquakes on the San Andreas fault in the vicinity of San Francisco. Of particular importance are results for the statistical distribution of recurrence times between great earthquakes, results that are difficult or impossible to obtain from a purely field-based approach.

Disasters↗

PubMed2005

Simulations of spinodal nucleation in systems with elastic interactions.

Systems with long-range interactions quenched into a metastable state near the pseudospinodal exhibit nucleation that is qualitatively different from classical nucleation near the coexistence curve. We observe nucleation droplets in Langevin simulations of a two-dimensional model of martensitic transformations and determine that the structure of the nucleating droplet differs from the stable martensite structure. Our results, together with experimental measurements of the phonon dispersion curve, allow us to predict the nature of the droplet. The results have implications for nucleation in many solid-solid transitions and the structure of the final state.

Journal Article↗

PubMed2005

Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease.

BACKGROUND AND AIMS: Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions. PATIENTS AND METHODS: The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD15/NOD2 mutations was analysed. RESULTS: No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non-fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery. CONCLUSION: Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.

Adolescent↗

PubMed2005

Association between the promoter polymorphism T/C at position -159 of the CD14 gene and anti-inflammatory therapy in patients with inflammatory bowel disease.

Immune response to intestinal bacteria and genetic predisposition seem to play a crucial role in the pathogenesis of inflammatory bowel disease. A single nucleotide polymorphism in the promoter of the lipopolysaccharide-receptor CD14 gene (T/C at position -159) has recently been described. To evaluate the role of the CD14 gene in anti-inflammatory therapy, the functionally relevant T(-159)-->C promoter polymorphism has been genotyped in 72 patients with inflammatory bowel disease and associated with the cumulative steroid dose. Cumulative corticosteroid dose was significantly higher in ulcerative colitis patients with the TT genotype (2447.7 +/- 927.0 mg/yr) compared with the CT genotype (142.3 +/- 142.3 mg/yr, p=0.016) and the CC genotype (391.7 +/- 272.7 mg/yr, p=0.047). In contrast, in patients with Crohn's disease there was no significant difference of the cumulative corticosteroid doses between the various T(-159)-->C promoter CD14 genotypes. An altered immune response to lipopolysaccharides with influence on the anti-inflammatory therapy seems to play a role in the genetic predisposition to ulcerative colitis. Genetic stratification will lead to the development of individualized therapies in inflammatory bowel disease.

Adrenal Cortex Hormones↗

PubMed2005

Pulmonary oxygen diffusing capacity of the South American lungfish Lepidosiren paradoxa: physiological values by the Bohr method.

Lungfish (Dipnoi) may represent the sister group to all land vertebrates and are therefore important for reconstructing the conquest of land by tetrapods. We determined venous and arterial blood gases, pulmonary O(2) uptake, and the form of the hemoglobin-O(2) dissociation curves in the South American lungfish Lepidosiren paradoxa. Measurements were performed at 25 degrees and 35 degrees C. Based on this information, we calculated its pulmonary O(2) diffusing capacity (D(L)O(2)), using the Bohr integration procedure. D(L)O(2) increased with temperature to reach about 0.04 mL stpd kg(-1) min(-1) mmHg(-1) at 35 degrees C. This value represents about 40% of the morphometric diffusing capacity and is similar to physiological values in some amphibians and reptiles.

Analysis of Variance↗

PubMed2005

Baseline characteristics of patients recruited into the CARE-HF study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising new treatment for patients with heart failure and cardiac dyssynchrony. The CARE-HF study is a morbidity/mortality trial designed to provide conclusive evidence of the effects of CRT in patients with moderate to severe heart failure. METHODS: A description of the baseline characteristics of patients randomised in the CARE-HF trial. RESULTS: 813 Patients with predominantly NYHA class III (94%) heart failure were randomised in 82 centres. Their mean age was 65 (interquartile range [IQR] 59 to 72) years, 34% were aged >70 years and 27% were women. Thirty-eight percent of the patients had ischaemic heart disease. Mean heart rate was adequately controlled at 70 (IQR 60 to 78) bpm consistent with the use of beta-blockers. Supine systolic blood pressure was low at 117 (IQR 105 to 130) mm Hg. Eighty-eight percent of patients had a QRS > or =150 ms. Mean LV ejection fraction was 26% (IQR 22 to 29) and end-diastolic dimension was 7.2 (IQR 6.4 to 7.8) cm. Ninety-four percent of patients were receiving loop diuretics, 95% an ACE inhibitor or angiotensin receptor blocker (ARB), 72% a beta-blocker and 56% were taking spironolactone. CONCLUSIONS: The patients enrolled in CARE-HF had moderately severe heart failure and cardiac dysfunction with evidence of cardiac dyssynchrony. The population appears at high risk of events despite pharmacological therapy and therefore appropriate for a trial of CRT.

Aged↗

PubMed2005

Association of interleukin-8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma.

Chronic obstructive pulmonary disease (COPD) and asthma are common complex diseases characterized by airflow obstruction and inflammatory processes in the small airways. lnterleukin 8 (IL-8) is a potent proinflammatory cytokine which interacts with the IL-8 receptor alpha (IL8RA, CXCR1) and beta (IL8RB, CXCR2), leading to activation and migration of leukocytes. In order to evaluate the role of the IL8RA gene in the pathogenesis of COPD and asthma, we screened the coding region of IL8RA for mutations by means of single-strand conformation polymorphism analysis in 50 COPD patients and identified three exchanges (M31R, S276T and R335C). These three polymorphisms were subsequently genotyped in 182 adult patients with COPD, 68 adult patients and 130 children with asthma as well as 454 healthy controls. The frequencies of the IL8RA 31R and 335C alleles were significantly increased in patients with COPD and in children with asthma compared to healthy controls (P=0.0073 and 0.023, respectively). Thus, these polymorphisms may play a role in the pathogenesis of COPD and asthma.

Amino Acid Substitution↗

PubMed2005

Identification of a novel calcium-sensing receptor gene mutation causing familial hypocalciuric hypercalcemia by single-strand conformation polymorphism analysis.

Calcium-sensing receptor gene (CASR) mutations that alter the function of the G protein coupled Ca (2+)-sensing receptor are reported in patients with familial hypocalciuric hypercalcemia (FHH), autosomal dominant hypocalcemia (ADH), and neonatal severe hyperparathyroidism (NSHPT). In search for novel disease causing mutations in the CASR gene, we screened exons 2 - 7 of the CASR gene of a family with FHH using single-strand conformation polymorphism analysis. We identified a novel CASR mutation (c.518 T > C; L173 P) in exon 4 encoding for the extracellular domain of the Ca (2+)-sensing receptor. This region seems to represent a hot spot within the CASR gene with at least 13 reported disease causing mutations thus far.

Adult↗

PubMed2005

Association study of Wegener granulomatosis and the functionally relevant A645G polymorphism in the bactericidal/permeability increasing protein (BPI) gene.

In antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV), bactericidal/permeability increasing protein (BPI) ANCAs are detected. Recent observations suggest that BPI-ANCAs can potentially contribute to a proinflammatory setting in the absence of proteinase 3 (PRTN3) ANCAs during the development of a pulmonary relapse by impeding the elimination of Gram-negative bacteria (GNB). However, it is as yet not clear whether the genetic background contributes to the generation of BPI-ANCAs in Wegener granulomatosis (WG) or if BPI polymorphisms are associated with WG. In this study we genotyped the functionally relevant single nucleotide polymorphism (SNP) A645 (Glu216Lys) of the BPI gene in 201 WG patients and 608 healthy controls. To investigate whether further SNPs might be associated with WG, we also examined an intragenic microsatellite marker. No significant differences were found between patients and controls. Thus BPI polymorphisms do not appear to contribute to genetic predisposition to WG. Moreover, our data do not suggest a genetic background for the generation of BPI-ANCAs in WG.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2005

A case-control study of tyrosine phosphatase (PTPN22) confirms the lack of association with Crohn's disease.

In Crohn's disease (CD), the whole gastrointestinal tract can be affected by discontinuous and transmural inflammation. The terminal ileum and colon are especially prone to inflammation that comprises granulomata and later intestinal and perianal fistulas. Genome-wide linkage and epidemiological studies established genetic predisposition factors to CD. Recently, a variation of the intracellular protein tyrosine phosphatase nonreceptor-type 22 (PTPN22) was associated with several autoimmune diseases. Here, we analysed the functionally relevant polymorphism R620W (rs 2476601) of the PTPN22 gene in 146 patients suffering from CD using restriction fragment length polymorphism (RFLP) analyses. This study revealed evidence that PTPN22 variation may have no influence in the genetic predisposition to CD, at least not in another well-characterized Caucasian cohort.

Amino Acid Substitution↗

PubMed2004

The G2964A polymorphism of the STAT6 gene in inflammatory bowel disease.

BACKGROUND AND AIMS: Linkage of inflammatory bowel diseases to chromosome 12p13.2-q24.1 (IBD2) has been confirmed in several genome wide screens. The STAT6 gene is located within this chromosomal region. The transcription factor STAT6 is involved in the regulation of the TH1/TH2 immune response. Increased production of TH1 cytokines is crucial in the pathogenesis of Crohn's disease. PATIENTS AND METHODS: Therefore, we genotyped a single nucleotide polymorphism in the 3' untranslated region of the STAT6 gene (G2964A) in 243 patients with Crohn's disease, 100 patients with ulcerative colitis and 548 healthy controls. RESULTS: In comparison to controls, the G allele and the GG genotype frequencies were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene (p<0.03 and p<0.02, respectively). CONCLUSIONS: Alterations in the STAT6 pathway may play a crucial role in the pathogenesis of distinct subgroups of patients with Crohn's disease.

Adult↗

PubMed2004

Zeros of the partition function and pseudospinodals in long-range Ising models.

The relation between the zeros of the partition function and spinodal critical points in Ising models with long-range interactions is investigated. We find that the spinodal is associated with the zeros of the partition function in four-dimensional complex temperature/magnetic field space. The zeros approach the real temperature/magnetic field plane as the range of interaction increases.

Journal Article↗

PubMed2003

Ergodic dynamics in a natural threshold system.

Numerical simulations suggest that certain driven, dissipative mean-field threshold systems, including earthquake models, can be characterized by statistical properties often associated with ergodic dynamics, in the same sense as stochastic Brownian motion. We applied a fluctuation metric proposed by Thirumalai and Mountain [Phys. Rev. E 47, 479 (1993)]] for statistically stationary systems and find that the natural earthquake fault system in California demonstrates similar ergodic dynamics.

Computer Simulation↗

PubMed2003

[Periodic surveillance of nosocomial infections in two neurology intensive care units. A valuable tool for quality management in intensive care].

BACKGROUND AND OBJECTIVE: Nosocomial infections are a common problem in intensive care therapy and have relevant influence on morbidity, mortality and associated costs. The aim of this study was to assess data on the epidemiology of nosocomial infections and related risk factors in neurological intensive care patients and to use them for internal quality management. METHODS: Prospective periodic surveillance was performed in the first quarter of the years 1999 and 2000 in two neurology intensive care units. RESULTS: Within the surveillance period, 340 patients with 2443 patient days and a mean length of stay 7,6 days were enrolled. A total of 63 nosocomial infections were identified in 51 patients. In comparison with national reference data, device utilisation rates as well as device-associated nosocomial infection rates were on a higher level. By timely and interpretative feedback of the surveillance data, for the first time the unit-specific nosocomial infection situation was made clear for the ward staff. As a result, different quality management activities like establishment of evidence-based infection control guidelines, continuous surveillance for pneumonia and optimisation of empirical antibiotic therapy were initiated in both units. CONCLUSION: The establishment of periodic surveillance proved to be a valuable tool for the promotion of quality management activities in both intensive care units.

Anti-Bacterial Agents↗