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S Lehmann

Publications and source records attributed to S Lehmann.

At least 19 recordsLinked to original sources
PubMed2006

Predictors for response to rehabilitation in patients with hip or knee osteoarthritis: a comparison of logistic regression models with three different definitions of responder.

OBJECTIVE: To identify pre-treatment predictors of who will benefit from a 3-4-week comprehensive rehabilitation intervention in patients with osteoarthritis (OA) of the knee or hip. METHODS: A prospective cohort study with assessments at admission to the clinic and after 6 months was conducted. Two hundred and fifty patients from the rehabilitation clinic Rehaclinic Zurzach, Switzerland, were included. Three different measures of response to a 3-4-week comprehensive rehabilitation intervention were used: one indirect measure (minimal clinically important difference (MCID) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score=18% improvement), one direct measure (transition question) and a combination of both criteria. Responders were predicted by a sequential logistic regression analysis with nine personal variables, five lifestyle risk factors, seven psychological status variables and the WOMAC global baseline score. RESULTS: The set of statistically significant predictors was dependent on the definition of response. The comparison of predictors that were statistically significant in any of the prediction models showed similar odds ratios (ORs) for the majority of predictors across three regression models with the different response definitions as dependent variable. Female gender, absence of depressive symptoms (dep), history of complementary medicine (cm) and low comorbidity (com) were the most stable predictors and had ORs above 2.0 (female) and above 1.5 (dep, cm, com) across the three regression models with different response definitions. CONCLUSION: A set of predictors for the outcome of rehabilitation in patients with OA was identified. If these predictors could be confirmed in future research, this knowledge might help to adopt and individualize the treatment of patients who are, at present, less likely to respond.

Aged↗
PubMed2006

Stentless mitral valve implantation in comparison to conventional mitral valve repair or replacement at five years.

OBJECTIVE: A chordally supported stentless mitral valve (SMV) may be a suitable prosthesis for patients with severe degenerative mitral valve disease. We analyzed the five-year results and compared them with results after conventional mitral valve repair or replacement. METHODS: 155 patients, operated on since August 1997, were evaluated. 53 patients (ages, 68 +/- 8 years, 37 female, valve repair not feasible) received a SMV (Quattro), 51 patients (69 +/- 9 years, 32 female) had mitral valve repair (MVR) and 51 patients (66 +/- 9 years, 32 female) had a conventional mitral valve replacement (MVP). There were no significant differences with respect to preoperative NYHA functional class, left ventricular ejection fraction, cardiac index and surgical risk, according to the EuroSCORE. Mean follow-up is 64 +/- 18 (21-89) months. RESULTS: Surgery was performed using a median sternotomy (32 [SMV]/20 [MVR]/34 [MVP]) or a lateral mini-thoracotomy 21/31/17 approach. The SMV was safely attached to the papillary muscles. In-hospital mortality was 1, 2 and 4 respectively; re-operation was required in 6, 2 and 3 patients. Five-year survival rate was 80.6 +/- 4.4 % (SMV), 80.2 +/- 5.6 % (CMV) and 82.6 +/- 5.6 % (MVP), p = n.s. After hospital discharge, there was no significant difference in mortality in comparison to an age-matched control population. Echocardiography revealed acceptable SMV hemodynamics with preservation of left ventricular function. CONCLUSION: Midterm results after SMV implantation are comparable to conventional approaches. Complete preservation of the annulo-ventricular continuity is advantageous and close to physiologic hemodynamics can be achieved. Long term follow-up is required.

Aged↗
PubMed2006

PRIMA-1 induces apoptosis in acute myeloid leukaemia cells with p53 gene deletion.

The p53 tumour suppressor gene located on chromosome 17p13 is the most frequently mutated gene in human tumours. About 5-8% of cases with acute myeloid leukaemia (AML) carry the p53 mutation. Recently, the compound p53-dependent reactivation and induction of massive apoptosis (PRIMA-1) has been shown to induce cytotoxic effects and apoptosis in human tumour cells by restoration of the transcriptional activity of mutated p53. This is believed to be mediated by a change in the conformation of mutated p53 protein, restoring DNA binding and activation of p53 target genes. We studied the effects of PRIMA-1 and commonly used antileukaemic drugs on AML cells from 62 patients. Cells were obtained from peripheral blood or bone marrow and were exposed to PRIMA-1, cytarabine, daunorubicin, chlorodeoxyadenosine and fludarabine. This study showed that PRIMA-1 had cytotoxic effects on AML cells. Conventional AML drugs were less effective in cells with hemizygous p53 deletion. Interestingly, our data indicated that PRIMA-1 was more effective in this subgroup of patients compared with patients with normal chromosome 17. Our data suggest that the concept of restoration of p53 protein by PRIMA-1 or a PRIMA-1-based new drug may increase the efficacy of AML treatment in patients with p53 mutations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Autopsy findings in patients on postcardiotomy extracorporeal membrane oxygenation (ECMO).

OBJECTIVES: To assess the clinical sensitivity of causes of death, concomitant diseases and postoperative complications including thromboembolic events in ECMO patients. METHODS: Between January 2000 and December 2004 154/202 patients (76.2%) died after postcardiotomy ECMO circulatory support. Autopsy was performed in 78 (50.6%) consecutive patients. Clinical and post-mortem data were prospectively recorded and compared concerning causes of death and postoperative complications including venous and arterial thromboembolisms and significant comorbidities. RESULTS: Mean age was 62.1+/-11.3 years, ejection fraction was 43.4+/-17.3%. 39.7% were emergency operations including acute coronary syndrome in 25.6% and preoperative cardiogenic shock in 28.2%. Successful ECMO weaning rate was 43.6%. Mean postoperative survival was 11.3 days. Premortem unknown concomitant diseases were found in 63 patients (80.8%) with clinical relevance in 9 patients (11.5%). Clinically unrecognized postoperative complications were found in 59 patients (75.6%) including acute cerebral infarction (n=7), acute bowel ischemia (1), intestinal perforation (3), pneumonia (4), venous thrombus formation (25) and systemic thromboembolic events (24). Clinically based causes of death were cardiac in 62.8%, multi-organ failure in 10.3%, cerebral in 5.1%, respiratory in 10.3%, fatal pulmonary embolism in 2.6%, technical in 5.1%, and others in 3.8%. Unexpected causes of death were found by autopsy in 22 patients (28.2%) including myocardial infarction (n=5), acute heart failure (4), fatal pulmonary embolism (2), pneumonia (2), ARDS (1), lung bleeding (1), fatal cerebrovascular event (4) and multiorgan failure (3). CONCLUSIONS: In ECMO patients major discrepancies between clinical and post-mortem examination were found. The true incidence of thromboembolic events is highly underestimated by clinical evaluation.

Aged↗
PubMed2004

[Progressive symmetric erythrokeratodermia of Darier-Gottron].

A 5 1/2-year-old boy revealed symmetric erythematous plaques on both arms and legs as well as in the face. Additionally, contractions of several digital joints were noted. We diagnosed a progressive symmetric erythrokeratoderma and initiated a topical therapy with tretinoin. Here we discuss the etiology, differential diagnoses, and therapeutic options of this rare disorder of keratinization.

Administration, Topical↗
PubMed2004

[Incontinentia pigmenti in a five-week-old girl].

Shortly after birth, a five-week-old female infant developed small blisters and erythema that followed the lines of Blaschko on the upper and lower extremities as well as the abdomen. Histological examination confirmed the clinical presumptive diagnosis of incontinentia pigmenti. We discuss the dinical features, diagnosis, and the molecular genetic basis of this rare inherited skin disorder.

Biopsy↗
PubMed2004

[Identification of geophilic and zoophilic dermatophytes in siblings with tinea capitis. A pathogenic factor or contamination?].

Two siblings of African origin presented with multiple scaling patches and alopecia on the scalp four weeks after returning from a vacation in Eritrea. Direct KOH examination revealed fungal elements; Trichophyton mentagrophytes and Trichophyton terrestre were identified in the fungal culture. We discuss the putative pathogenic role of both microorganisms in causing disease. Although infection with Microsporum canis currently accounts for almost fifty percent of all cases of tinea capitis in Germany, other fungi have gained importance due to tourism and increasing migration.

Alopecia↗
PubMed2004

Detection of prion after decontamination procedures: comparative study of standard Western blot, filter retention and scrapie-cell assay.

Prion diseases such as Creutzfeldt-Jakob disease represent a unique infection control problem because the infectious agent exhibits an unusual resistance to conventional chemical and physical decontamination methods. We investigated the reliability and sensitivity of a filter retention assay and standard Western blot to detect the scrapie form of cellular prion protein (PrPSc), the most commonly used surrogate prion disease marker, on tissue infected samples, treated with five commercially available decontamination solutions currently used in hospitals. Major discrepancies were observed between the two immunoblot methods. By using Western blot, we observed that three decontamination solutions have a strong ability to reduce PrPSc levels, whereas in the filter assay, none have this effect and two even enhanced the detection of PrPSc. We used an original and rapid ex vivo approach called the scrapie-cell assay to analyse the persistence of infectivity on scrapie-treated tissues. We observed that tissues remained infectious after treatment with the decontaminant in concordance with in vivo data. This study suggests that conventional PrPSc detection methods are not adapted for the rapid study of a large number of prion decontaminants tested on infectious tissues, and that the scrapie-cell assay could be proposed as a relevant alternative method.

Animals↗
PubMed2004

Effects of PRIMA-1 on chronic lymphocytic leukaemia cells with and without hemizygous p53 deletion.

The tumour suppressor gene p53 is the most commonly mutated gene in solid tumours. Although less common in haematological malignancies, 10-15% of B-cell chronic lymphocytic leukaemia (B-CLL) cases carry a p53 mutation. Recently, the compound P53-dependent reactivation and induction of massive apoptosis (PRIMA-1) has been shown to induce cytotoxic effects and apoptosis in human tumour cells by restoration of the transcriptional activity of mutated p53. This is believed to be mediated by a change in the conformation of mutated p53 protein, restoring DNA binding and activation of p53 target genes. We studied the effects of PRIMA-1 and commonly used anti-leukaemic drugs on B-CLL cells from 14 patients with and without hemizygous p53 deletion. Cells obtained from peripheral blood or bone marrow were exposed to PRIMA-1 and fludarabine alone or in combination. PRIMA-1 showed cytotoxic effects on B-CLL cells from samples with and without hemizygous p53 deletion. Furthermore, conventional B-CLL drugs were less effective in cell samples with hemizygous p53 deletion and the response depended on the size of the p53 deleted clone. Finally, we found evidence for synergistic and additive effects of PRIMA-1 in combination with fludarabine.

Antineoplastic Agents↗
PubMed2004

Inpatient rehabilitation for hip or knee osteoarthritis: 2 year follow up study.

OBJECTIVE: To examine the course of pain, physical function, and other health dimensions after a comprehensive inpatient rehabilitation intervention in patients with osteoarthritis (OA) of the hip or knee. METHODS: An observational, prospective cohort study with assessments at baseline (entry into clinic), 1 (discharge from inpatient rehabilitation), 3, 6, 9, 12, and 24 months after baseline. Consecutively referred patients to an inpatient rehabilitation centre fulfilling the inclusion criteria were studied. 3-4 week comprehensive rehabilitation intervention, including strengthening exercise, flexibility training, endurance training, relaxation strategies, and consultations for preventive measures, was carried out. Individual home rehabilitation programmes were taught. Generic health status was measured using the SF-36, condition specific health was measured with the WOMAC questionnaire. Effects were analysed with sensitivity statistics (effect size, ES) and non-parametric tests. RESULTS: Data from 128 patients with complete follow up data were analysed. Both pain and physical function improved moderately (WOMAC pain: ES = 0.56, WOMAC function ES = 0.44) until discharge. Although the effect in pain reduction remained significant by month 24 (WOMAC: ES = 0.26), physical function deteriorated close to baseline values after 12 months. CONCLUSIONS: Comprehensive inpatient rehabilitation of patients with OA of the hip or knee may improve pain and physical function in the mid-term, and pain in the long term.

Aged↗
PubMed2003

Citation networks in high energy physics.

The citation network constituted by the SPIRES database is investigated empirically. The probability that a given paper in the SPIRES database has k citations is well described by simple power laws, P(k) proportional to k(-alpha), with alpha approximately 1.2 for k less than 50 citations and alpha approximately 2.3 for 50 or more citations. A consideration of citation distribution by subfield shows that the citation patterns of high energy physics form a remarkably homogeneous network. Further, we utilize the knowledge of the citation distributions to demonstrate the extreme improbability that the citation records of selected individuals and institutions have been obtained by a random draw on the resulting distribution.

Journal Article↗
PubMed2003

Prion-like protein Doppel expression is not modified in scrapie-infected cells and in the brains of patients with Creutzfeldt-Jakob disease.

Doppel protein has been discovered in prnp knock-out mouse lines, with overproduction of this protein in the brain causing ataxia and neurodegeneration. We investigated whether Doppel expression (i) affected or was affected by the course of prion propagation in neuroblastoma cells, or (ii) modulated Creutzfeldt-Jakob disease pathogenesis. No change in Doppel production was detected in N2a cells, before or after infection. Transient murine Doppel gene expression had no effect on N2a viability or PrP(Sc) production. A sensitive immunometric assay revealed low levels of Doppel in human brain, reflecting weak transcription of the corresponding gene. No difference in brain Doppel levels was observed between Creutzfeldt-Jakob disease patients and controls, adding further evidence that Doppel is unlikely to be involved in prion disease pathogenesis.

Animals↗
PubMed2002

The expression of cellular retinoid binding proteins in non-APL leukemic cells and its association with retinoid sensitivity.

Retinoic acid (RA) has important effects on cell differentiation and cell growth and on normal embryonic development. Intracellular retinoid signaling induced by endogenous or exogenous RA is regulated by retinoid binding proteins such as CRBPI, CRABPI and CRABPII and there are data suggesting that the expression of these proteins can influence the sensitivity to the growth inhibitory effects of ATRA. In this study, we investigated the basal and ATRA-induced expression of CRBPI and CRABPI and II in leukemic cell lines and in cells from patients with acute myeloid leukemia (AML). CRBPI as well as CRABPI and II were expressed in all tested cell lines and in leukemic cells from all 18 AML-patients. CRABPII mRNA expression was more abundant than CRBPI and CRABPI in both the cell lines and the patient cells but the levels compared the house keeping gene was lower in the patient cells. In all cell lines and in 69% of the patient samples, ATRA did upregulate CRABPII whereas CRBPI exhibited a varying response and CRABPI was more commonly downregulated. The sensitivity to the growth inhibitory effects of ATRA did not correlate with the basal expression of any of these proteins. However, ATRA-induced upregulation of CRABPII did significantly correlate with the ATRA sensitivity (p < 0.005) as well as with ATRA-induced upregulation of the retinoid receptor RARbeta (p < 0.05). We conclude that the retinoid binding proteins CRBPI and CRABPI and II are expressed in myeloid leukemic cells of non-M3 type but that the level of expression does not affect ATRA sensitivity.

Gene Expression↗
PubMed2001

Cell culture models of transmissible spongiform encephalopathies.

In this review, we describe the generation and use of cell culture models of transmissible spongiform encephalopathies, also known as prion diseases. These models include chronically prion-infected cell lines, as well as cultures expressing variable amounts of wild-type, mutated, or chimeric prion proteins. These cell lines have been widely used to investigate the biology of both the normal and the pathological isoform of the prion protein. They have also contributed to the comprehension of the pathogenic processes occurring in transmissible spongiform encephalopathies and in the development of new therapeutic approaches of these diseases.

Animals↗
PubMed2001

Ex vivo propagation of infectious sheep scrapie agent in heterologous epithelial cells expressing ovine prion protein.

Transmissible spongiform encephalopathies, or prion diseases, are fatal degenerative disorders of the central nervous system that affect humans and animals. Prions are nonconventional infectious agents whose replication depends on the host prion protein (PrP). Transmission of prions to cultured cells has proved to be a particularly difficult task, and with a few exceptions, their experimental propagation relies on inoculation to laboratory animals. Here, we report on the development of a permanent cell line supporting propagation of natural sheep scrapie. This model was obtained by stable expression of a tetracycline-regulatable ovine PrP gene in a rabbit epithelial cell line. After exposure to scrapie agent, cultures were repeatedly found to accumulate high levels of abnormal PrP (PrPres). Cell extracts induced a scrapie-like disease in transgenic mice overexpressing ovine PrP. These cultures remained healthy and stably infected upon subpassaging. Such data show that (i) cultivated cells from a nonneuronal origin can efficiently replicate prions; and (ii) species barrier can be crossed ex vivo through the expression of a relevant PrP gene. This approach led to the ex vivo propagation of a natural transmissible spongiform encephalopathy agent (i.e., without previous experimental adaptation to rodents) and might be applied to human or bovine prions.

Animals↗
PubMed2001

Automated 5' nuclease assay for detection of virulence factors in porcine Escherichia coli.

This paper describes the development of a 5' nuclease assay for detection of virulence factor genes responsible for colonization factors and toxins in Escherichia coli isolated from pigs. Colonization factors were F4, F5, F6, F18, F41 and the outer membrane protein intimin. Toxins were heat stable (STa, STb, EAST1) and heat labile (LT) enterotoxins and the verocytotoxin variant 2e (VT2e). To correctly identify false negative results, an endogenous internal control targeting the E. coli 16 S rRNA gene was incorporated in each test tube. The assay was evaluated using a collection of E. coli reference strains which have previously been examined with phenotypical assays or DNA hybridization. Furthermore, the assay was evaluated by testing porcine E. coli field strains, previously characterized. The 5' nuclease assay correctly detected the presence of virulence genes in all reference strains. When testing field strains there was generally excellent agreement with results obtained by laboratories in Belgium and Germany. In conclusion, the 5' nuclease assay developed is a fast and specific tool for detection of E. coli virulence genes in the veterinary diagnostic laboratory.

5'-Nucleotidase↗
PubMed2001

Landscape metrics for assessment of landscape destruction and rehabilitation.

This investigation tested the usefulness of geometry-based landscape metrics for monitoring landscapes in a heavily disturbed environment. Research was carried out in a 75 sq km study area in Saxony, eastern Germany, where the landscape has been affected by surface mining and agricultural intensification. Landscape metrics were calculated from digital maps (1912, 1944, 1973, 1989) for the entire study area and for subregions (river valleys, plains), which were defined using the original geology and topography of the region. Correlation and factor analyses were used to select a set of landscape metrics suitable for landscape monitoring. Little land-use change occurred in the first half of the century, but political decisions and technological developments led to considerable change later. Metrics showed a similar pattern with almost no change between 1912 and 1944, but dramatic changes after 1944. Nonparametric statistical methods were used to test whether metrics differed between river valleys and plains. Significant differences in the metrics for these regions were found in the early maps (1912, 1944), but these differences were not significant in 1973 or 1989. These findings indicate that anthropogenic influences created a more home geneous landscape.

Animals↗