Biomedical subjects

Gunter Laux

Publications and source records attributed to Gunter Laux.

11 recordsLinked to original sources

PubMed2006

No improvement of patient or graft survival in transplant recipients treated with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers: a collaborative transplant study report.

It was reported recently that treatment of kidney transplant recipients with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) is associated with strikingly improved long-term graft and patient survival. This finding has important implications for future posttransplantation therapy recommendations. In an analysis of 17,209 kidney and 1744 heart transplant recipients, an association of treatment with ACEI/ARB with improved transplant outcome could not be confirmed. It is concluded that recommendations for a widespread use of ACEI/ARB treatment in transplant recipients are unwarranted.

Aged↗

PubMed2006

Use of a patient information leaflet to influence patient decisions regarding mode of administration of NSAID medications in case of acute low back pain.

Despite dissuasive recommendations, intramuscular (i.m.) injections of NSAIDS are still a widespread treatment of acute pain in General Practice as well as among orthopaedic physicians. Most physicians argue that patients who are used to receive NSAIDS i.m. would insist on this application mode while being convinced of its therapeutic superiority for pain relief. Therefore, the aim of the study was to find out if patients' decision can be influenced towards an oral application by receiving a simple information leaflet. An information leaflet, providing information about the risks of NSAIDS particularly in case of i.m. application was provided to 161 patients with acute low back pain. Decision in favour or against i.m. application of NSAIDS was documented. Severity of disease was assessed by the Roland Morrison pain questionnaire and visual analogue scale (VAS) at the first visit and again 3-5 days later. From May to December 2004, 161 patients, visiting their GP (13 practices) with acute pain and demanding an injection were included in the study. After reading the information leaflet, 139 of the 161 (86.3%) patients decided for an oral application instead of receiving an injection of NSAIDS as in the past. This effect was statistically significant (P</=0.01). Of the initial 161 patients, 156 could be re-evaluated and no significant differences in the VAS and the Roland Morris Score between the patients with oral and i.m. application mode could be found. Only 2 patients of the 139 who decided for oral application indicated that they would opt for an i.m. injection next time. Our study demonstrates that patients' decision can be influenced even in case of severe pain by providing adequate information on a short information leaflet. The results should help to reduce physicians' fear of losing patients when not following their demand for i.m. injections and therefore enable a safer pain treatment.

Acute Disease↗

PubMed2006

Comparison of AIMS2-SF, WOMAC, x-ray and a global physician assessment in order to approach quality of life in patients suffering from osteoarthritis.

BACKGROUND: Chronic diseases like osteoarthritis (OA) substantially affect different dimensions of quality of life (QoL). The aim of the study was to reveal possible factors which mainly influence general practitioners (GPs) assessment of patients' QoL. METHODS: 220 primary care patients with OA of the knee or the hip treated by their general practitioner for at least one year were included. All GPs were asked to assess patients' QoL based on the patients' history, actual examination and existing x-rays by means of a visual analog scale (VAS scale), resulting in values ranging from 0 to 10. Patients were asked to complete the McMaster Universities Osteoarthritis Index (WOMAC) and the Arthritis Impact Measurement Scale2 Short Form (AIMS2-SF) questionnaire. RESULTS: Significant correlations were revealed between "GP assessment" and the AIMS2-SF scales "physical" (rho = 0.495) and "symptom" (rho = 0.598) as well as to the "pain" scale of the WOMAC (rho = 0.557). A multivariate ordinal regression analysis revealed only the AIMS2-SF "symptom" scale (coefficient beta = 0.2588; p = 0.0267) and the x-ray grading according to Kellgren and Lawrence as significant influence variables (beta = 0.6395; p = 0.0004). CONCLUSION: The results of the present study suggest that physicians' assessment of patients' QoL is mainly dominated by physical factors, namely pain and severity of x-ray findings. Our results suggest that socioeconomic and psychosocial factors, which are known to have substantial impact on QoL, are underestimated or missed. Moreover, the overestimation of x-ray findings, which are known to be less correlated to QoL, may cause over-treatment while important and promising targets to increase patients' QoL are missed.

Adult↗

PubMed2006

Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era.

Despite the introduction of new immunosuppressive agents, a steady decline of functioning renal allografts after living donation is observed. Thus nonpharmacological strategies to prevent graft loss have to be reconsidered, including donor-specific transfusions (DST). We introduced a cyclosporine-based DST protocol for renal allograft recipients from living-related/unrelated donation. From 1993 to 2003, 200 ml of whole blood, or the respective mononuclear cells from the potential living donor were administered twice to all of our 61 recipient candidates. The transplanted subjects were compared with three groups of patients without DST from the Collaborative Transplant Study (Heidelberg, Germany) during a 6-year period. Six patients were sensitized without delay for a subsequent cadaveric kidney. DST patients had less often treatment for rejection and graft survival was superior compared with subjects from the other Swiss transplant centers (n = 513) or from Western Europe (n = 7024). To diminish the probability that superior results reflect patient selection rather than effects of DST, a 'matched-pair' analysis controlling for relevant factors of transplant outcome was performed. Again, this analysis indicated that recipients with DST had better outcome. Thus, our observation suggests that DST improve the outcome of living kidney transplants even when modern immunosuppressive drugs are prescribed.

Adult↗

PubMed2005

Analysis of KIR ligand incompatibility in human renal transplantation.

Natural killer cells express killer immunoglobulin-like receptors (KIR) that bind to MHC class I antigens. Lack of self-MHC on the target cell can cause NK-cell mediated killing. Here, we analyzed the effect of KIR ligand incompatiblity on renal allograft survival in humans. Kidney recipient/donor pairs were separated according to their HLA-Cw alleles and HLA-Bw4 specificity which are considered epitopes for KIR. A total of 2,757 renal transplants were examined. Graft survival rates were computed according to the Kaplan-Meier method. No effect of KIR ligand matching on graft survival was observed in cadaver kidney transplants. Our results indicate that KIR ligand matching cannot be recommended as a strategy for improving renal allograft survival.

Graft Survival↗

PubMed2005

Long-term prospective study of steroid withdrawal in kidney and heart transplant recipients.

A large prospective study of steroid withdrawal was performed within the framework of the Collaborative Transplant Study to analyze long-term graft and patient outcome in renal and heart transplant recipients. Steroids were withdrawn no earlier than 6 months posttransplantation. A comparison of 7-year outcomes in renal transplant recipients (94% receiving cyclosporine; 97% Caucasian) showed a benefit of steroid withdrawal versus steroid continuation in retrospectively matched controls, for graft survival (81.9% +/- 1.8% vs. 75.3% +/- 1.2%, p = 0.0001), patient survival (88.8% +/- 1.5% vs. 84.3 +/- 1.0%; p = 0.0016) and death-censored graft survival (91.8% +/- 1.3% vs. 87.9%+/- 1.0%: p = 0.0091). Steroid withdrawal was associated with improved graft survival in heart recipients also (76.2% +/- 2.4% vs. 66.9% +/- 1.7%, p = 0.0008). A total of 58.6% of renal recipients and 44.3% of heart recipients never required steroids during follow up. Rates of acute rejection and renal dysfunction did not differ between steroid-free and steroid-continuation groups. Steroid withdrawal was associated with significantly improved cardiovascular risk factors compared with steroid continuation. Rates of the development of osteoporosis and cataracts did not differ in the entire patient cohort, but were strikingly lower in patients taken off steroids during the first posttransplant year.

Adrenal Cortex Hormones↗

PubMed2005

The CONTENT project: a problem-oriented, episode-based electronic patient record in primary care.

In order to obtain a proper knowledge base in primary care, a form of electronic patient record is needed that takes into account the specific characteristics of the doctor-patient encounter, the patient population, the presentation of diseases and the associated prevalences. However, in real life this has not happened for several reasons. For the most part, existing patient records are determined by invoicing requirements rather than by endeavours to meet the intrinsic needs of primary care. CONTENT (CONTinuous morbidity registration Epidemiologic NeTwork) is an ambitious scientific project in Germany to establish a system for adequate record keeping and analysis in primary care. Based on a classification system designed for the special situation of primary care, a scientific network is being established consisting of participating surgeries, general practitioners, computer scientists and statisticians. The project is supported by the German Federal Ministry of Education and Research. The aims are strictly scientific and the underlying hypothesis is that the knowledge-gaining process can be accelerated by combining the experience of many, especially with respect to complex interactions of factors and the analysis of rare events. Aside from maintaining a morbidity registry, within the CONTENT framework various prospective and retrospective studies on particular epidemiological and health economic research topics will be conducted.

Episode of Care↗

PubMed2004

Immunological relevance of CREG matching in cadaver kidney transplantation.

BACKGROUND: On the basis of cross-reactive antibodies that react with different human leukocyte antigens (HLA) with shared epitopes, HLA-A and -B antigens can be assigned to cross-reactive groups (CREG). In the context of renal transplantation, it has been reported that matching for CREG results in improved graft outcome and reduces the requirement for rejection treatment. Because CREG matching also improves the equity of kidney distribution to ethnic minorities, a CREG-based cadaver kidney allocation policy was introduced in the United States a few years ago. METHODS: The authors reexamined the immunologic relevance of matching according to CREG using the data of the international Collaborative Transplant Study. A total of 91,917 patients who received a first cadaver kidney transplant between 1991 and 2002 formed the basis of this analysis. RESULTS: The authors found that the underlying impact of matching for HLA antigens accounts entirely for the observed positive effect of CREG matching. For patients with a particular HLA antigen match grade, matching for CREG had no advantageous effect on graft outcome or rejection treatment. An immunologic basis for CREG matching could thus not be found in this large analysis of cadaver kidney transplants. CONCLUSIONS: The findings indicate that CREG matching for kidney allocation is conceptually flawed from an immunologic viewpoint.

Cadaver↗

PubMed2004

Critical evaluation of the amino acid triplet-epitope matching concept in cadaver kidney transplantation.

BACKGROUND: A computer-based approach for determining human leukocyte antigen (HLA) compatibility between kidney donors and recipients on the basis of differences of amino acid sequences as motifs for immunogenic epitopes was proposed by Duquesnoy et al. The HLAMatchmaker algorithm focuses on HLA class I polymorphisms of serologically defined antigens encoded by the HLA-A and -B loci. HLA phenotypic mismatches that represent only a few mismatches at the amino acid triplet level are held to be not or only mildly immunogenic. This approach was proposed as being especially suitable for the allocation of donor kidneys to highly sensitized patients. METHODS: We reexamined this attractive concept using the data of the Collaborative Transplant Study. Intra- and interlocus comparisons for HLA-A and -B were performed according to the original HLAMatchmaker algorithm. To exclude the influence of HLA-DR, only transplants with no HLA-DR mismatch were considered. Patients who had one HLA-A and one HLA-B antigen mismatch were separated into subgroups, depending on the number of triplet mismatches as calculated by the HLAMatchmaker software. Separate analyses were performed for first transplants, retransplants, and patients with a panel-reactive antibody activity of 50% or more. A total of 16,997 white patients matched for HLA-DR who received a cadaver kidney transplant between 1991 and 2001 formed the basis of this analysis. RESULTS: Application of the HLAMatchmaker method could not be shown to result in any statistically significant effect on graft survival. CONCLUSIONS: The HLAMatchmaker concept is theoretically attractive; however, it could not be shown to yield useful results in this analysis. Serologic HLA typing appears to provide an insufficient basis for applying epitope matching in clinical kidney transplantation.

Algorithms↗

PubMed2004

Relevance of IL10, TGFbeta1, TNFalpha, and IL4Ralpha gene polymorphisms in kidney transplantation: a collaborative transplant study report.

Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to influence cytokine plasma levels. Cytokines are important mediators during organ graft rejection. It was reported that certain cytokine genotypes are associated with improved kidney graft survival. In the present study, SNPs within the IL10 promoter gene, the first exon of the TGFbeta1 gene, the TNFalpha promoter gene, and the IL4Ralpha gene were analyzed in 2298 first and 1901 repeat cadaver kidney recipients. We found no significant effect on the survival rate of first grafts. Among retransplants, we observed that recipients who were homozygous for the high TNFalpha producer genotype -308 A had a significantly lower graft survival rate than patients who were carriers of the low producer genotype -308 G (at 3 years: 63.0% vs. 79.5%; pcorrected = 0.0116). The results of this large-scale study suggest that IL10, TGFbeta1, TNFalpha, and IL4Ralpha cytokine genotypes do not affect the survival of primary kidney grafts. The outcome of retransplants appears to be affected by TNFalpha genotypes only.

Cadaver↗

PubMed2003

A new epitope-based HLA-DPB matching approach for cadaver kidney retransplants.

BACKGROUND: Several years ago a significant impact of matching for HLA-DPB1 alleles on the survival of cadaver kidney retransplants was shown. Here we report the results of a new approach, based on matching for HLA-DPB1 epitopes. METHODS: The analysis is based on 1,478 patients who received a cadaver kidney retransplant between 1988 and 1998. DNA methodology (polymerase chain reaction, sequence-specific oligonucleotides) was used to perform HLA-DPB1 typing. Epitope matching was facilitated with the aid of sequence databases and computer calculations. RESULTS: Matching for the HLA-DP epitopes A, B, E, and F, corresponding to the homonymous hypervariable regions of the second exon of the DPB1 gene, seems to have a greater influence on graft survival than matching for the epitopes C and D. Within a group of 529 retransplants with exactly one allelic HLA-DPB1 mismatch, a significantly better graft outcome was observed when less than two epitope mismatches were found, compared with the group with more than three epitope mismatches (at 2 years: 77.8% vs. 65.8%, P=0.0112). Importantly, patients with two DPB1 allele mismatches who had less than or equal to two epitope mismatches exhibited a significantly better graft outcome than recipients who had one HLA-DPB1 allelic mismatch but more than three epitope mismatches (at 2 years: 77.1% vs. 65.8%, P=0.0488). CONCLUSIONS: The findings indicate that the impact of HLA-DPB1 matching on the outcome of kidney retransplants is a result of the predominant immunogenicity of certain epitopes of the HLA-DP molecule. Matching for immunogenic HLA-DPB1 epitopes seems to be functionally more relevant than classical matching at the allelic level.

Cadaver↗