Search PubMed⌕ Search

Biomedical subjects

Martin Haas

Publications and source records attributed to Martin Haas.

At least 19 recordsLinked to original sources
PubMed2006

The association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use during postischemic acute transplant failure and renal allograft survival.

BACKGROUND: Postischemic acute renal transplant failure occurs in approximately one fourth of all dead donor transplantations. Uncertainty exists regarding the putative association between the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) and kidney transplant graft survival in patients with delayed allograft function. METHODS: We conducted an open cohort study of all 436 patients who experienced an acute renal transplant failure out of all 2,031 subjects who received their first kidney transplant at the Medical University of Vienna between 1990 and 2003. Actual and functional graft survival was compared between users and nonusers of ACEI/ARB using exposure propensity score models and time-dependent Cox regression models. RESULTS: Ten-year actual graft survival averaged 44% in the ACEI/ARB group, but only 32% in patients without ACEI/ARB (P=0.002). The hazard ratio of actual graft failure was 0.58 (95% confidence interval: 0.35-0.80, P=0.002) for ACEI/ARB users compared with nonconsumers. Seventy-one percent of subjects with ACEI/ARB had a functional graft at 10 years versus 64% of ACEI/ARB nonusers (P=0.027). The hazard ratio of functional graft loss was 0.48 (95% confidence interval: 0.24-0.91, P=0.025). CONCLUSIONS: Use of ACEI/ARB in patients experiencing delayed allograft function was associated with longer actual and functional transplant survival.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Complete renal tubular acidosis late after kidney transplantation.

BACKGROUND: Neither the prevalence nor the associated risk factors of late post-transplant renal tubular acidosis (RTA) are known. METHODS: We conducted a cross-sectional study with 576 patients for more than 12 months after kidney transplantation, and a glomerular filtration rate (GFR) >40 ml/min. RTA was diagnosed by measurement of the urine anionic gap, urine pH and plasma potassium during acidosis, and fractional bicarbonate excretion after bicarbonate loading. Uni- and multi-variable analysis were used to isolate factors associated with post-transplant RTA, and with the different RTA subtypes. RESULTS: All patients (n = 76) had distal post-transplant RTA. A significant association with the presence of RTA was found for the intake of tacrolimus or renin-angiotensin-aldosterone blockers, the Parathyroid hormone level and the GFR. Type Ia (classic, distal), type Ib (hyperkalaemic, voltage-dependent), rate-limited and type IV RTA were present in 37, 14, 21 and 28% of the patients. Acute transplant rejection was the only significant different parameter between the RTA subtypes and more often present in patients with type Ia or Ib RTA. CONCLUSIONS: We conclude that a significant fraction of stable long-term renal transplant recipients with adequate graft function develop post-transplant RTA, with a preponderance for type Ia and type IV, and absence of type II. In addition, acute transplant rejection seems to have an influence on the subtype of RTA present post-transplantation.

Acidosis, Renal Tubular↗
PubMed2006

Effects of bisphosphonates on bone loss in the first year after renal transplantation--a meta-analysis of randomized controlled trials.

BACKGROUND: Bone loss remains a serious problem after kidney transplantation and is most pronounced during the first months after engraftment. Bisphosphonates are frequently used to treat post-transplant osteodystrophy, but data of large randomized controlled trials (RCTs) are missing. METHODS: We, therefore, conducted this systematic review of the literature, searching electronic databases, reference lists and abstracts from scientific meetings to identify RCTs in all languages. The primary outcome assessed was the change in bone mineral density (BMD) during the early post-transplantation period. Based on the mean BMD change presented in the identified publications, the authors were asked for the individual BMD results of all randomized patients, determined at lumbar spine and femoral neck before and after bisphosphonate therapy. Data were pooled for summary estimates by using weighted mean differences of absolute change in BMD. An analysis of covariance was performed, adjusted for individual baseline values, treatment arm and individual trial. RESULTS: Five studies involving 180 participants were included in our meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing post-transplant osteodystrophy. BMD decline at the lumbar spine within 6-12 months after transplantation was significantly reduced by 0.06 g/cm(2) in patients treated with bisphosphonates (95% CI 0.05-0.08 g/cm(2)). At the femoral neck, the loss of BMD was reduced by 0.05 g/cm(2) during this period (95% CI 0.0-0.11 g/cm(2)), reaching just non-statistical significance. This benefit of bone loss prevention could be reached without major side effects. CONCLUSION: Bisphosphonates are effective in preventing bone loss in the early post-transplant period.

Bone Density↗
PubMed2006

Changes of coronary calcification after kidney transplantation.

BACKGROUND: Coronary artery calcification (CAC) in patients with end-stage renal disease is driven by uremia and increased serum calcium and phosphate levels. Improvement in calcium-phosphate homeostasis and uremia by kidney transplantation therefore might favorably influence CAC. METHODS: We measured the extent of CAC by using multidetector computed tomography in 31 patients immediately after transplantation and at 6 and 12 months' follow-up. Baseline and follow-up measurements were compared, and the effect of atherogenic factors on CAC progression was determined by means of multivariate regression analysis. RESULTS: Mean total Agatston score increased significantly from baseline to 6 months (716 +/- 980 [SD] versus 916 +/- 1,307; P < 0.001), but remained unchanged at 12 months' follow-up (890 +/- 1,263; P = not significant). Progression of calcification was present only in patients with a baseline total Agatston score higher than 10. In these patients, the score increased from 964 +/- 1,028 to 1,234 +/- 1,385 (P < 0.001) at 6 months and remained stable thereafter (1,199 +/- 1,338; P = not significant). Duration of pretransplantation dialysis treatment and smoking were identified as independent predictors of posttransplantation CAC progression. Conversely, changes in calcium and phosphate levels were not associated with calcification. CONCLUSION: This study shows that CAC progresses during the early posttransplantation course, but slows between 6 and 12 months after transplantation. The extent of early calcification is influenced mainly by dialysis treatment duration and smoking.

Adult↗
PubMed2005

[Therapeutic implications of ACE-gene polymorphism].

The serum concentration of the angiotensin converting enzyme (ACE) depends on the individual genotype. Thus, ACE levels might be higher (DD-genotype), intermediate (ID) or low (II). Pre-therapeutic determination of the genotype might therefore optimize therapy with ACE-inhibitors or angiotensin II blockers. However, although numerous interventional studies have been performed they are hampered by a low number of included patients and have often yielded differing results. Thus, in order to overcome current controversies larger multicenter studies are warranted before recommending a general testing for genotype prior to initiation of therapy which interferes with the rennin-angiotensin-aldosterone system.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

The effect of oral anticoagulation on clotting during hemodialysis.

BACKGROUND: Between 5% and 10% of hemodialysis patients are treated with oral anticoagulants. It is currently unknown whether additional anticoagulation with heparin or low-molecular-weight heparin (LMWH) is needed to prevent clotting during hemodialysis. METHODS: In this prospective, randomized, cross-over study 10 patients treated with oral anticoagulants (phenprocoumon) received either no additional anticoagulation or low dose dalteparin (bolus of 40 IU/kg body weight) before dialysis. Efficacy of hemodialysis was measured by normalized weekly Kt/V and urea reduction rate (URR). Thrombus formation was evaluated by measurement of D-dimer and inspection of air traps and dialyser. RESULTS: The median international normalized ratio (INR) did not differ between both observation periods (phenprocoumon 2.2(2 to 3) vs. dalteparin 2.1(2 to 2.9). The anti-Xa level in dalteparin patients was 0.33 (0.27 to 0.38) IU/mL after 2 hours and 0.16 (0.03 to 0.23) IU/mL after 4 hours of hemodialysis. The median increase of D-dimer was significantly higher in patients without additional dalteparin therapy during hemodialysis (DeltaD-dimer 0.23 microg/mL vs. 0.03 mug/mL) (P= 0.0004). Complete thrombosis of the dialyser membrane occurred in one patient in the phenprocoumon group but in none with combined treatment. The extent of thrombosis in the arterial and venous air trap and dialyser was significantly less in patients with additional dalteparin therapy (P= 0.0014, P= 0.0002, and P= 0.0005, respectively). Weekly Kt/V and URR was similar in both groups. CONCLUSION: Standard oral anticoagulation with an INR between 2 and 3 is insufficient to prevent clotting during hemodialysis. Additional low dose anticoagulation with a LMWH or heparin is necessary to facilitate treatment.

Administration, Oral↗
PubMed2004

c-Myb protein interacts with Rcd-1, a component of the CCR4 transcription mediator complex.

Transcriptional initiation of eukaryotic genes depends on the cooperative interaction of various transcription factors. Using the yeast two-hybrid assay, we have identified the murine Rcd-1 protein as a cofactor of the c-myb proto-oncogene product. Rcd-1 is evolutionarily conserved among many species, and moreover the yeast homologue CAF40 is part of the carbon catabolite repressor protein transcriptional mediator thought to be involved in the negative regulation of genes transcribed by RNA polymerase II. Rcd-1 is located mainly in the nucleus, and it interacts with c-Myb both in vitro and in vivo. The activation of the myeloid c-myb-specific mim-1 promoter is repressed by Rcd-1. Interestingly, rcd-1 is an erythropoietin regulated gene, which also represses the action of the AP-1 transcription factor on its target genes.

Amino Acid Sequence↗
PubMed2004

Renal osteodystrophy.

Patients with chronic renal failure suffer from four different kinds of typical bone lesions which are summarized as renal osteodystrophy (ROD). These changes can occur early during renal disease and are dependent on several factors, such as the calcium-phosphorus homeostasis, the type of renal disease or the frequency and dose of potentially harmful drugs administered. ROD usually gets worse as renal failure progresses, and during hemodialysis, and culminates, in the case of kidney transplantation, in the early post-transplant phase. Although the decrease of parathyroid hormone (PTH) and the dose of immunosuppression administered subsequently permit a certain restitution of bone stability, ROD persists lifelong in the majority of cases and is associated with a high rate of bone fractures. However, the abnormalities of mineral metabolism that lead to ROD are not only confined to bone morphology but also predispose to vascular or soft tissue calcification. This might lead to severe tissue or coronary artery calcification. It is therefore not surprising that life expectancy on hemodialysis is correlated to the expression and form of ROD. The awareness and early diagnosis of renal osteodystrophy are therefore of great importance, in particular since a number of new treatment options have recently evolved. Previously-used phosphate binders, which contain either aluminium or calcium, might be replaced by non-absorbable drugs which bind phosphate through ion exchange. In addition, PTH production can be reduced efficiently by administration of recently developed calcimimetic agents that increase the sensitivity of calcium-sensing receptors in the parathyroid gland. In patients with high-turnover bone disease or after transplantation, bisphosphonates might prevent or restore bone loss.

Biopsy↗
PubMed2004

The effect of ACE inhibitor and angiotensin II blocker therapy on early posttransplant kidney graft function.

BACKGROUND: It is unknown whether continuation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II (ATII) blocker therapy after kidney transplantation has an influence on early kidney graft function. METHODS: We compared early postoperative graft function between 260 cadaveric kidney transplant recipients, either with or without peritransplantation ACE inhibitor/ATII blocker therapy. Regression analysis was used to show the influence of variables interfering with posttransplantation serum creatinine levels. The effect of different variables on the occurrence of delayed graft function (DGF) was analyzed by means of stepwise logistic regression. Improvement in kidney function during the first week after transplantation was compared between groups by means of Kaplan-Meier survival analysis. RESULTS: Intake of an ACE inhibitor or ATII blocker did not influence immediate posttransplantation graft function or the occurrence of DGF. Conversely, serum creatinine levels decreased significantly faster in patients administered an ACE inhibitor/ATII blocker than in those without therapy (P < 0.01). The only variables delaying graft function were number of previous transplantations, cold ischemia time, and male sex. Among patients with DGF, those with ACE inhibitor/ATII blocker therapy had significantly faster graft recovery (P < 0.001). CONCLUSION: Our results suggest that intake of an ACE inhibitor or ATII blocker during the immediate posttransplantation course is safe and does not impair graft function. Additionally, patients with DGF might profit from blockade of the renin-angiotensin-aldosterone system, which possibly shortens the time to graft recovery.

Angiotensin II↗
PubMed2004

Maintenance and self-renewal of long-term reconstituting hematopoietic stem cells supported by amniotic fluid.

The maintenance and self-renewal of hematopoietic stem cells (HSC) in culture is a central focus of hematopoietic stem cell research. In vivo, the balance between HSC differentiation, apoptosis, and self-renewal is regulated at the endosteal surface niche in the bone marrow (BM). In feeder-free cultures, the fate of HSC is affected by growth factors/interleukins and serum, which affect the balance between self-renewal, differentiation, and apoptosis and lead to the rapid loss of multipotent HSC. We report that substituting human amniotic fluid (AF) for serum in HSC cultures provides a growth milieu in which HSC differentiation and apoptosis are down-regulated and multipotent HSC are maintained. Murine BM cells were cultured in serum-free medium containing 25% amniotic fluid and stem cell factor (SCF) only, "AF/SCF" cultures. Compared with serum and multiple growth factor-containing medium, cells cultured for 4 weeks in AF/SCF medium displayed downregulation of differentiation markers while maintaining a high fraction of cells expressing Sca1 (51.8%) and c-kit (10.2%). Reconstitution of lethally irradiated C57BL/6 (Ly5.2) mice with cultured Ly5.1 BM cells resulted in high levels of (cultured) donor cells in primary (78 +/- 19.4% and 94.32 +/- 2.5%, 10(5) and 10(6) cells injected, respectively) and secondary (96.5%) recipients at 8 and 11 months post-transplantation. Hence, long-term repopulation with AF/SCF cultured BM cells was maintained. Addition to the cultures of 10% serum, interleukin (IL)-3, IL-6, granulocyte colony stimulating factor (G-CSF), or granulocyte-macrophage colony stimulating factor (GM-CSF), singly or in combination, resulted in rapid differentiation and apoptosis, leading to the total loss of HSC.

Amniotic Fluid↗
PubMed2004

Nonsustained effect of short-term bisphosphonate therapy on bone turnover three years after renal transplantation.

BACKGROUND: We recently showed that two doses of 4 mg of zoledronic acid (ZOL) ameliorated the bone loss and improved bone histology within the first six months after kidney transplantation. The aim of the present study was to evaluate whether this early short-term intervention exhibited a sustained bone-sparing effect. METHODS: A homogenous group of 20 de novo renal transplant recipients were equally randomized to two infusions of 4 mg of ZOL or placebo at two weeks and three months after engraftment. Patients were followed up for three years by sequential determination of bone densitometry and specific biochemical markers. RESULTS: From month six to three years after transplantation, both treatment groups exhibited an improvement of bone mineralization. Femoral neck bone mineral density z-scores increased statistically significantly from -1.3 (2.6) to -0.2 (3.6) in the placebo group and from -1.6 (2.9) to -1.2 (1.9) in the ZOL group (median, range). Biochemical parameters of osteoblast activity such as osteocalcin and bone-specific alkaline phosphatase did not increase significantly in both groups. Osteoprotegerin, a marker of osteoclast inhibition, was significantly elevated over the first six months in the ZOL group, but decreased to similar levels, as in the placebo group, over the next two and a half years. Other markers of osteoclast activity such as c-telopeptide of type 1 collagen, calcitonin, and intact parathyroid hormone were not different between six months and three years in either group. CONCLUSION: The early bone-sparing effect of short-term ZOL therapy confers no sustained benefit versus placebo at three year post-transplantation.

Acute Disease↗
PubMed2003

Lamb shift of laser-dressed atomic states.

We discuss radiative corrections to an atomic two-level system subject to an intense driving laser field. It is shown that the Lamb shift of the laser-dressed states, which are the natural state basis of the combined atom-laser system, cannot be explained in terms of the Lamb shift received by the atomic bare states which is usually observed in spectroscopic experiments. In the final part, we propose an experimental scheme to measure these corrections based on the incoherent resonance fluorescence spectrum of the driven atom.

Journal Article↗
PubMed2003

Zoledronic acid to prevent bone loss in the first 6 months after renal transplantation.

BACKGROUND: Bisphosphonates can prevent bone mineral density loss after renal transplantation, but their effect on trabecular mineralization and bone morphology, two key factors of bone stability, remains unknown. METHODS: In a 6-month, randomized, placebo-controlled study, 20 kidney transplant recipients received either 4 mg zoledronic acid or placebo twice within 3 months after engraftment. At transplantation and after 6 months, mean trabecular calcium concentration and trabecular morphometry were measured in bone biopsies. Bone mineral density (BMD) of the femoral neck and the lumbar spine were evaluated by dual-energy x-ray absorptiometry, and serum biochemical markers of bone metabolism were determined monthly. RESULTS: Trabecular calcium content increased significantly in the zoledronic acid group, but remained unchanged in the placebo group. BMD at femoral neck showed no change in the zoledronic acid group, but decreased in the placebo group. BMD of the lumbar spine was increased in the zoledronic acid group without change in the placebo group. High-turnover bone disease resolved similarly in both groups, as evidenced by a significant decrease of eroded bone surface, osteoclast and osteoblast surface. Serologic markers of bone formation and resorption were significantly lower in zoledronic acid-treated patients throughout the study. Kidney transplant function was stable after zoledronic acid therapy. CONCLUSIONS: Our results show that administration of zoledronic acid improves the calcium content of cancellous bone after kidney transplantation. The beneficial effect of bisphosphonate therapy is further evidenced by an increase of lumbar spine BMD, and stabilization of femur BMD.

Biomarkers↗
PubMed2002

Influence of plasma immunoglobulin level on antibody synthesis.

In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with immunoadsorption (IA) therapy. Specific and bulk immunoglobulin levels were obtained simultaneously. The mean serum flc concentration increased to the preapheresis value within 1 day and remained unchanged thereafter. Total immunoglobulin G (IgG) and specific antibody concentrations increased to pretreatment values in 88% and 43% of the patients, respectively, and remained below the original values in the others. In conclusion, the lack of increased flc synthesis after IA confirms the absence of a feedback mechanism regulating antibody synthesis. The restoration of serum IgG levels after IA, therefore, does not result from increased antibody synthesis but is probably related to changes of catabolism and immunoglobulin backflow.

Adult↗
PubMed2002

Antioxidant treatment of therapy-resistant idiopathic membranous nephropathy with probucol: a pilot study.

BACKGROUND: Proteinuria in Heymann's nephritis, an experimental rat model disease corresponding to membranous nephropathy, has been shown to be due to lipid peroxidation. Since the pathophysiology might be similar to idiopathic membranous nephropathy in humans, we performed a prospective multicenter trial to investigate the efficacy of the lipid peroxidation scavenger, probucol. METHODS: Fifteen patients with biopsy-proven idiopathic membranous nephropathy resistant to conventional immunosuppressive therapy (n = 7) and/or ACEI treatment (n = 12) were recruited. Probucol (1 g/d orally) was administered for three months, followed by a washout period of four weeks, whereon lovastatin (10-20 mg/d orally) was administered for additional three months. RESULTS: A significant reduction in proteinuria was seen during the probucol treatment (median (range): 6.4 (3.8-9.1) g/d vs. 4.7 (1.3-16) g/d; P < 0.05), with partial remission achieved in four patients. Three of these patients had previously been resistant to immunosuppressive therapy. Median protein excretion increased to pretreatment values during the washout period (6.2 (1.9-15) g/d; P < 0.05) and was not significantly different after the intake of lovastatin (4.9 (1.8-19) g/d; P = NS). None of the patients achieved partial remission during lovastatin therapy (P < 0.05 vs. probucol). CONCLUSION: The present study led us to conclude that proteinuria can be reduced by probucol in some patients with idiopathic membranous nephropathy. A randomized multicenter study to further elucidate the influence of lipid peroxidation scavengers on membranous nephropathy is warranted.

Adult↗