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Biomedical subjects

R Oberbauer

Publications and source records attributed to R Oberbauer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects.

AIMS: The prevalence of hyperuricaemia and gout increases with age as does the incidence of adverse effects to allopurinol, the major uric acid lowering drug. The present study was performed to compare the disposition and effects of allopurinol and its active metabolite oxipurinol in elderly and young subjects without major health problems. METHODS: Ten elderly (age range 71-93 years) and nine young subjects (24-35 years) received an oral dose of 200 mg allopurinol in an open, single dose, cross sectional design. Four of these individuals were additionally dosed with 200 mg allopurinol intravenously. Plasma and urine concentrations of allopurinol, oxipurinol, hypoxanthine, xanthine, and uric acid were measured by h. p.l.c. RESULTS: Total clearance of allopurinol was not different in elderly (15.7+/-3.8 ml min-1 kg-1, mean+/-s.e. mean) and young subjects (15.7+/-2.1), whereas total clearance of oxipurinol was significantly reduced in the aged (0.24+/-0.03) compared with young controls (0.37+/-0.05) as was the distribution volume of oxipurinol (0.60+/-0.09 and 0.84+/-0.07 l kg-1, respectively). Oxipurinol was eliminated primarily by the kidneys, allopurinol by metabolism. Fractional peroral bioavailability of allopurinol was 0.81+/-0.16 (n=4, two elderly and two young subjects). Although maximal plasma concentrations of oxipurinol were significantly higher in elderly (5. 63+/-0.83 microgram ml-1 ) than in young persons (3.75+/-0.25) as was the area under the oxipurinol plasma concentration-time curve, AUC (260+/-46 and 166+/-23 microgram ml-1 h, respectively), the pharmacodynamic effect of oxipurinol was smaller in elderly than young subjects (time-dependent decrease of plasma uric acid 83+/-30 microgram ml-1 h in elderly compared with 176+/-21 in young controls). Oxipurinol increased the renal clearance of xanthine, suggesting inhibition of tubular xanthine reabsorption by oxipurinol. CONCLUSIONS: Although allopurinol elimination is not reduced in the aged, that of its active metabolite oxipurinol is because of an age-dependent decline in renal function. Xanthine oxidase inhibition by oxipurinol appears to be reduced in old age. In addition to its uricostatic action, oxipurinol has a xanthinuric effect which is also diminished in the elderly.

Adult↗
PubMed1999

Effect of anticoagulation on blood membrane interactions during hemodialysis.

BACKGROUND: Adequate anticoagulation is a precondition to prevent extracorporeal blood clotting and to improve biocompatibility during hemodialysis. In this study, we performed a morphologic analysis by using scanning electron microscopy to compare three modes of anticoagulation-conventional unfractionated heparin (UFH), low molecular weight heparin (LMWH; dalteparin sodium), or sodium citrate during hemodialysis-on membrane-associated coagulation activation. METHODS: Fifteen patients on regular hemodialysis therapy were investigated. Five patients received UFH, five patients LMWH, and five patients sodium citrate as an anticoagulant during a standardized hemodialysis protocol using a single-use polysulfone capillary dialyzer. Membrane-associated clotting was evaluated using a scanning electron microscope. A dialyzer clotting score was used for quantitative description of coagulation activation on membrane segments. RESULTS: Using UFH as an anticoagulant revealed the most pronounced cell adhesion and thrombus formation and the highest dialyzer clotting score (11.5 +/- 1.3 of a maximal 20 points). LMWH had a lower dialyzer clotting score than UFH (10.4 +/- 1.2 of 20 points). During the use of sodium citrate, a negligible thrombus formation and the lowest dialyzer clotting score (1.6 +/- 0.6 of 20 points, P < 0.05) were observed. CONCLUSION: The results of this investigation indicate that using sodium citrate as an anticoagulant during hemodialysis induces a lower activation of coagulation than both conventional and fractionated heparin, which might contribute to an improvement of biocompatibility of hemodialysis extracorporeal circulation.

Adult↗
PubMed1999

Bacterial and fungal infections after kidney transplantation.

Infectious diseases in renal transplant recipients are a major issue both from the medical and from the economical point of view. The major risk factor is the immunosuppressive therapy. Infections observed during the first weeks after transplantation are not different from those observed in nonimmunosuppressed patients after surgery. Infections with opportunistic pathogens, however, emerge at the beginning of the second month and are mainly determined by the allograft function.

Bacterial Infections↗
PubMed1999

Apoptosis of tubular epithelial cells in donor kidney biopsies predicts early renal allograft function.

Acute renal failure (ARF) is a serious complication in the early postoperative period after kidney transplantation. In an effort to identify subjects at risk, several donor-, recipient-, and procedure-related factors have been studied. Because no morphologic parameter predictive of delayed graft function has been identified to date, this study was conducted to determine whether the number of apoptotic cells in donor biopsies obtained before engraftment is predictive of the development of posttransplant ARF. Donor biopsies of patients with "biopsy-proven" acute tubular damage but no signs of rejection (n = 23) showed significantly higher counts of apoptotic tubular epithelial cells when compared to patients with immediate transplant function (n = 44) or early rejection (n = 22). In all groups, a significantly higher percentage of apoptotic cells was found in the distal compared to the proximal tubule. The expression of bcl-2 and proliferating cell nuclear antigen was not different among the groups. Late allograft function was not affected by early ARF as serum creatinine values were similar in all three groups after 6 mo. These data suggest that the number of apoptotic renal tubular epithelial cells in donor biopsies before engraftment is predictive of the early postoperative course in patients undergoing kidney transplantation.

Acute Kidney Injury↗
PubMed1998

Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults.

The prognosis of patients with incompletely resected malignant brain tumors is almost fatal. In an attempt to improve the outcome of children and young adults with unfavorable brain tumors an intensive multimodal therapeutic strategy was developed combining simultaneous (hyper)fractionated external beam irradiation and conventional adjuvant chemotherapy after initial surgery. 17 patients aged between 2.10 and 25.11 years were entered into the study. 16/17 patients were treated according to the German/Austrian Pediatric Brain Tumor Study Group multicenter trial HIT '91. They are not protocol patients of this HIT '91 trial. Induction chemotherapy consisted of 2 courses of ifosfamide (3 g/m2/d) on days 1-3, etoposide (150 mg/m2/d) on days 4-6, methotrexate (5 g/m2) on days 15 and 22, cisplatin (40 mg/m2/d) and cytarabine (400 mg/m2/d) on days 29-31. Three weeks after the last dose of cisplatin/cytarabine the second course of chemotherapy was started. The last patient entered into the study received a modified therapy containing ifosfamide, cisplatin and etoposide. Synchronously at a median of 12 days after initiation of chemotherapy 12/17 patients received local radiotherapy (6000-7040 cGy) to the brain and 5/17 patients craniospinal irradiation (3520 cGy with a tumor boost of 1400-2000 cGy). 4-6 weeks after completion of the second course of chemotherapy maintenance therapy was started with carmustine (CCNU) (75 mg/m2) and carboplatin (400 mg/m2) each on day 1 and vincristine (1.5 mg/m2) on day 1, 8, 15. This course was repeated eight times every six weeks. 9/17 patients are alive at a median follow-up of 25 months (range 5-50) with 4 complete remissions, 2 partial remissions and 1 stable disease lasting 42+ months. Two patients, who initially had stable disease, progressed, but are still alive at 31+ and 41+ months after diagnosis. Median progression-free survival and median overall survival is 19 and 36 months, respectively. Hematologic and methotrexate-induced toxicity were severe and resulted in one therapy-related death. However, radiotherapy concomitant to chemotherapy appears to be an effective method of treatment for brain tumors with poor prognosis, though toxicity is severe in some cases.

Adolescent↗
PubMed1998

Natriuretic effect of adenosine A1-receptor blockade in rats.

BACKGROUND: Many effects of adenosine on renal function have been identified. The development of adenosine receptor blockers has made it possible to identify which of these effects are exerted by endogenous adenosine. At least four adenosine receptor subtypes, denoted A1, A2a, A2b, and A3 are currently known. In the present study the selective A1 receptor blocker 1,3-dipropyl-8[2-(5,6-epoxy) norbanyl] xanthine (CVT-117) was used to assess the effect of A1 activation by endogenous adenosine on renal function in rats. METHODS: Clearance studies were performed before and after administration of 0.1 mg/kg and 0.8 mg/kg of CVT-117 in separate groups of rats and before and after administration of vehicle in time-control rats. Measurements of heart rate before and after administration of exogenous adenosine confirmed effective A1 receptor blockade. RESULTS: At both the lower and higher doses, A1 receptor blockade with CVT-117 increased fractional sodium excretion and urine flow rate without altering GFR. The increase in sodium excretion following A1 blockade was not accompanied by increases in the excretion of phosphate or potassium. CONCLUSION: These results show that endogenous adenosine promotes sodium retention by activation of A1 receptors.

Animals↗
PubMed1998

Plasma immunadsorption treatment in patients with primary focal and segmental glomerulosclerosis.

BACKGROUND: In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be obtained by treatment. In some patients a permeability factor, responsible for damaging the glomerular epithelial cell and detectable by an in vitro test (GVV-test), seems to be present in the serum. METHOD: We determined the effects of an immunadsorption treatment (IAT) on proteinuria and glomerular permselectivity (using a neutral dextran and dextransulfate-sieving technique to assess glomerular size and charge selectivity) in five patients with FSGS in the native kidneys and three patients with recurrence of FSGS after kidney transplantation. Furthermore, we performed the GVV-test using sera obtained from the patients before and after therapy. RESULTS: IAT reduced proteinuria by more than 50% in four patients, all of whom had an improvement in glomerular-size selectivity. Charge selectivity was better preserved after therapy in three out of these four subjects. The GVV-test prior to IAT was positive in two patients who also responded clinically to therapy. After IAT the GVV-test was negative in all patients, indicating an elimination of the proteinuric factor in the two previously positive patients. CONCLUSION: We conclude that a positive GVV-test before treatment makes a favourable response of IAT on proteinuria likely in patients with FSGS. If a reduction of proteinuria can be obtained by IAT this is due to an improvement in glomerular size and/or charge selectivity.

Adolescent↗
PubMed1998

Urinary apolipoprotein (a) excretion in patients with proteinuria.

Increased plasma lipoprotein (a) (Lp(a)) levels are strongly associated with premature cardiovascular disease and stroke. Recently we, as well as other groups, found that apolipoprotein (a) (apo(a)) fragments appear in the urine of healthy individuals, and that renal transplant patients with impaired renal function excrete fewer apo(a) fragments into their urine compared with controls. As the excretion mode of apo(a) is presently unknown, we determined plasma Lp(a) levels and urinary apo(a) excretion in relation to kidney function in 58 proteinuric patients and 58 healthy controls. For the first time, urinary apo(a) excretion was related to apo(a) isoforms. Plasma Lp(a) values were higher in the proteinuric patients compared with the controls, independent of their renal function. The patients with low-molecular-weight apo(a) isoforms had higher Lp(a) plasma levels, whereas the patients with high-molecular-weight apo(a) isoforms had lower Lp(a) plasma levels. Urinary apo(a) showed a very similar pattern to that of plasma Lp(a), being significantly higher in patients with low-molecular-weight isoforms as compared with patients with high-molecular-weight isoforms. Urinary apo(a) excretion was significantly decreased in the patient group when compared with healthy controls. There was a close correlation (P < 0.001) between the plasma Lp(a) and urinary apo(a) excretion in both the patient group and the control group. Urinary apo(a) excretion did not correlate with protein excretion, creatinine clearance or plasma creatinine levels. We conclude that urinary apo(a) excretion correlates with plasma Lp(a) and Lp(a) isoforms, and that proteinuric patients excrete significantly less apo(a) into their urine than healthy controls, a factor that might contribute to increased plasma Lp(a) levels in these patients.

Adult↗
PubMed1997

Not nonsense but antisense--applications of antisense oligonucleotides in different fields of medicine.

This brief overview will give the reader an idea what antisense oligonucleotides are, how they act, what one can do with them, and what future perspectives might emerge. The idea behind this new therapeutic strategy is the selective blockage of a specific gene in vivo, which is responsible for a certain disease. Anti-sense oligonucleotides are short, traditionally 15 to 25 bases long, single stranded DNA fragments, which are targeted against a specific mRNA. This is the classical antisense mechanism. These DNA fragments can also be targeted against a specific genomic DNA sequence which is known as antigene therapy. The oligonucleotides have to be modified in order to increase their stability in vivo. Three mechanisms of action have been reported for the oligonucleotides: 1. Oligonucleotides are designed in a complementary (antisense) orientation to their target (sense) mRNA to which they hybridize in a strictly base pair specific manner (Watson-Crick base pairing) and thus block translation. 2. They can bind to the genomic DNA in the nucleus and thus block transcription (Hoogsten-type base triplets). A third, unspecific mechanism of action is the binding of the oligonucleotide to a target protein in what has been referred to as aptamer-binding. In addition, other nonspecific effects of cytokine and neutrophil activation were observed. The antisense strategy is a useful research tool for the identification of specific gene-protein functions. The first in vivo animal studies and clinical experiences have been carried out in the fields of cardiovascular medicine, oncology and virology yielding promising results. Currently, the first clinical trials using antisense oligonucleotides for the inhibition of gene expression are being performed; the results will be available in the next years.

Animals↗
PubMed1997

Urinary excretion of apo(a) fragments in NIDDM patients.

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.

Aged↗
PubMed1997

Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients.

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Urinary excretion of apo(a) in patients after kidney transplantation.

BACKGROUND: Increased plasma Lipoprotein (a) (Lp(a)) levels are strongly associated with premature cardiovascular disease and stroke. The kidney is purported to play an important role in apo(a) catabolism. Therefore we investigated plasma Lp(a) levels in relation to kidney function and urinary apo(a) excretion. METHODS: One hundred and sixteen kidney transplant patients with normal or impaired renal function and 109 age- and sex-matched healthy controls were investigated. Plasma Lp(a) and urinary apo(a) levels were determined immunochemically and all other parameters were determined by routine laboratory methods. RESULTS: Transplant recipients were found to have significantly elevated total cholesterol and LDL-C values, but equal HDL-C values compared to controls. Plasma Lp(a) values were higher and urinary apo(a) excretion was lower in transplant recipients compared to controls, independent of renal function. When the patient group was subdivided into 'normal' and 'impaired creatinine clearance', only the latter group secreted less apo(a) than normal controls. CONCLUSION: These data suggest that urinary apo(a) excretion is reduced in transplant recipients with impaired excretory graft function, which may contribute to the elevation of plasma Lp(a) levels in these patients.

Aged↗
PubMed1996

Serum tumor markers after renal transplantation.

The overall incidence of malignancy in renal transplant recipients is 100-fold higher compared with age matched controls. Routine clinical evaluation therefore often includes the determination of serum tumor markers AFP, CA19-9, CEA, CA125, CA15-3, PSA, and calcitonin. We evaluated the specificity and the sensitivity of these markers in 575 renal allograft recipients. Specificity varied between 0.69 (CA 125) and 0.96 (PSA) in 532 patients without cancer. Cyclosporine therapy and excretory allograft function did not affect marker concentration; impaired liver function was associated with significantly elevated AFP, CA19-9, CA125, and CA15-3 levels. In 43 patients with malignancies the sensitivity of the markers ranged between 0.2 (CEA) and 1 (CA 125, CA 15-3). We therefore conclude that routine screening of the transplant population with serum tumor markers is not useful because of the low sensitivity and specificity of these tests.

Adult↗
PubMed1996

In vivo suppression of the renal Na+/Pi cotransporter by antisense oligonucleotides.

A 20-mer phosphorothioate oligonucleotide (AS1) was designed to hybridize to the message for the rat kidney sodium phosphate cotransporter NaPi-2 close to the translation initiation site. Single intravenous doses of this oligonucleotide were given to rats maintained on a low phosphorus diet to increase NaPi-2 expression. At 3 days after oligonucleotide infusion, rats receiving 2.5 micromol of AS1 exhibited a reduction in renal NaPi-2 to cyclophilin mRNA ratio by 40% +/- 17%, and rats receiving 7.5 micromol of AS1 exhibited a reduction in NaPi-2 to cyclophilin mRNA ratio by 46% +/- 21%. Reversed-sequence AS1 was without effect. The higher dose of 7.5 micromol of AS1 also reduced the rate of phosphate uptake into renal brush border membrane vesicles and the expression of NaPi-2 protein detected by Western blotting in these vesicles. Reversed sequence AS1 was again without effect on these parameters. These results suggest that systemically infused oligonucleotides can exert antisense effects in the renal proximal tubule.

Animals↗
PubMed1996

Atubular glomeruli in patients with chronic allograft rejection.

Morphometric studies were performed in 15 patients with chronic renal allograft rejection. Biopsy cores were serially sectioned so that atubular glomeruli could be identified and volumes of individual glomeruli could be measured. Control tissue was obtained from 9 cadaver donors and 8 living donors. Serial sectioning revealed that atubular glomeruli were as common as sclerotic glomeruli in chronic rejection. The prevalence of atubular glomeruli averaged 18 +/- 15% (mean +/- SD) in recipients with chronic rejection, 2 +/- 2% in cadaver donors, and 1 +/- 3% in living donors (P<0.05, recipients vs. donor groups). In comparison, the prevalence of sclerotic glomeruli averaged 19 +/- 13%, 4 +/- 7%, and 7 +/- 10% in the three groups (P<0.05 recipients vs. donor groups). Atubular glomeruli exhibited reduced mean volume (3.1 +/- 0.9 x 10(6)micron(3) vs. 4.5 +/- 1.5 x lO(6)micron(3), atubular vs. open glomeruli in recipients, P < 0.05) but could not be distinguished from open glomeruli by their appearance on single sections. Recipients with chronic rejection exhibited tubular atrophy and interstitial fibrosis with an increase in the interstitial volume fraction to 51 +/- 14% as compared with 29 +/- 6% in cadaver donors and 17 +/- 2% in living donors (P<0.05 recipients vs. donor groups). Similar interstitial expansion was observed in recipients with a high prevalence of atubular glomeruli, recipients with a high prevalence of sclerotic glomeruli, and also in four recipients in whom the predominant form of glomerular injury was transplant glomerulopathy. These results suggest that mechanisms responsible for development of atubular glomeruli are among the processes that contribute to loss of graft function in patients with chronic rejection.

Adult↗