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Biomedical subjects

C Aufricht

Publications and source records attributed to C Aufricht.

At least 19 recordsLinked to original sources

Diuretic potential of energy drinks.

Recent literature suggests that both caffeine and taurine can induce diuresis and natriuresis in rat and man. Although they act via different cellular mechanisms, their diuretic actions might be additive. This is of considerable interest, as several commercially available energy drinks contain both substances. In this study we examined the possible diuretic effects of caffeine and taurine in a cross-over-design in which 12 healthy male volunteers received each of 4 different test drinks (750 ml of energy drink containing 240 mg caffeine and 3 g taurine, the three other test drinks either lacked caffeine, taurine or both) after restraining from fluids for 12 h. Mixed model analyses demonstrated that urinary output and natriuresis were significantly increased by caffeine (mean differences 243 ml and 27 mmol; both p < 0.001) and that there were no such effects of taurine (mean differences 59 ml and -4 mmol). Additionally, urinary osmolarity at baseline was significantly related to the urinary output (p < 0.001). Urine osmolarity values at baseline and in the 6 h urine collection did not differ significantly between treatments. Taken together, our study demonstrates that diuretic and natriuretic effects of the tested energy drink were largely mediated by caffeine. Taurine played no significant role in the fluid balance in moderately dehydrated healthy young consumers. Consequently, the diuretic potential of energy drinks will not differ significantly from other caffeine containing beverages.

Adolescent↗

MRI in the diagnosis of a peritoneal leak in continuous ambulatory peritoneal dialysis.

Mechanical problems in continuous ambulatory peritoneal dialysis (CAPD) can result in ultrafiltration failure and disruption of CAPD therapy. The recently described tool of CT peritoneography with water-soluble contrast medium has the disadvantage of radiation and instillation of nephrotoxic substances. We report a child with a peritoneal leak diagnosed by MRI after instillation of a gadodiamide-dialysate mixture. This method provided good anatomical detail without radiation or nephrotoxic agents.

Child↗

Low serial serum neopterin does not predict low risk for chronic renal graft rejection.

Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P = 0.63, NS, r = 0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy.

Child↗

Reduction of delayed renal allograft function using sequential immunosuppression.

Previous data suggested that outcome in small children with cadaveric renal transplantation might be improved with sequential therapy. This protocol combines augmented immunosuppression [by including antibody induction (ATG)] with avoidance of nephrotoxic medication in the immediate postoperative phase (by delayed start of cyclosporin therapy). In this report, we describe effects of this approach in 12 consecutively transplanted small children of less than 5 years of age (mean 3.2 years) who received a cadaveric renal graft at our institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone, azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone, azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for immunosuppression. Five children had delayed graft function (45.4%), all of whom were treated with triple therapy including cyclosporin from the very beginning, whereas children treated by the sequential protocol gained immediate graft function (P<0.05). There was no statistical difference between the two protocols concerning frequency or severity of rejections (67% vs. 60%, all steroid responsive), difference in the incidence of either bacterial or viral infections, or between the incidence of hypertension. Although not reaching statistical significance, 1-year graft survival rates also increased from 60% for triple therapy to 80% for sequential therapy. In conclusion, our findings confirm previous studies showing that outcome in small children undergoing renal transplantation may be improved by specially tailored treatment protocols such as sequential therapy.

Antibodies↗

Plasmapheresis-induced remission in otherwise therapy-resistant FSGS.

We report an 8-year-old Caucasian boy who presented with steroid-resistant nephrotic syndrome. Renal biopsy showed the cellular variant of focal segmental glomerulosclerosis (FSGS). Within 1 year he received a series of therapies that have induced remission in other patients with this disease, all to no avail (conventional-dose cyclosporin A, methylprednisolone pulse therapy, high-dose cyclosporin A, and therapy with mycophenolate mofetil). He achieved remission after five sessions of plasma exchange. This case argues for aggressive therapy of resistant nephrotic syndrome in the native kidney. Plasma exchange should be considered as a possible rescue therapy arm in future study protocols.

Child↗

Peritoneal dialysate fluid composition determines heat shock protein expression patterns in human mesothelial cells.

BACKGROUND: Low biocompatibility of peritoneal dialysis fluids (PDF) contributes to mesothelial injury. We investigated whether the heat shock proteins (HSP)-27, HSP-72, and HSP-90 are differentially induced upon exposure of mesothelial cells to PDF and whether this was affected by selective modulation of the physicochemical properties of PDF. METHODS: Human mesothelial cells (Met5A and primary human mesothelial cells) were exposed to acidic lactate and glucose-monomer based PDF (CAPD2 and CAPD3), to control culture media, or to a neutral lactate and glucose-monomer-based PDF with reduced levels of glucose degradation products (BALANCE). Expression of HSP-27, HSP-72, and HSP-90 and cellular distribution of HSP-72 were assessed by Western blotting and immunocytochemistry. RESULTS: Mesothelial cells exhibited strong constitutive expression of HSP-27 and to a lesser extent HSP-72 and HSP-90. Exposure of the cells to CAPD2 and CAPD3 resulted in strong up-regulation of HSP-72. HSP-27 levels were slightly increased, but HSP-90 levels were unchanged upon exposure to CAPD2 or CAPD3. In contrast, exposure of the cells to BALANCE did not affect HSP-27 or HSP-72 expression. The acidic pH and glucose degradation products were found to be principal in mediating increased HSP-72 expression upon exposure to PDF. CONCLUSIONS: Analysis of HSP expression represents a novel tool to assess biocompatibility of PDF. Among the HSP investigated, HSP-72 is the most predictive and accurate parameter to assess mesothelial cell injury in the early phase of exposure to PDF.

Cells, Cultured↗

Reproducible erythroid aplasia caused by mycophenolate mofetil.

Anemia secondary to mycophenolate mofetil (MMF) was recently described in experimental animals. A clinical association between MMF and anemia has been observed, but there are no proven reports. We describe a girl with chronic graft failure who developed erythroid aplasia under immunosuppression with MMF. She showed prompt resolution when MMF was discontinued and a recurrence of this clinical course when MMF was restarted. As re-challenge with a medication is the most definitive approach for showing a direct relationship between the drug and the side effect, this case clearly demonstrates that MMF can cause erythroid aplasia.

Adolescent↗

Heat shock protein-70 repairs proximal tubule structure after renal ischemia.

BACKGROUND: Recent studies have suggested a role of heat shock protein (HSP)-70 in cytoskeletal repair during cellular recovery from renal ischemia. The aim of this study was to test the hypothesis that HSP-70 interacts in vitro with cytoskeletal elements obtained from rat renal cortex during early reflow after renal ischemia. METHODS: Cellular proteins were fractionated into cytoskeletal pellets and noncytoskeletal supernatants by Triton X-100 extraction of rat renal cortex obtained after 15 minutes or 18 hours of reflow after 45 minutes of renal ischemia, or from controls. Aliquots of isolated pellets were coincubated with aliquots of isolated supernatants in different combinations. A repeat Triton extraction was performed, and differential distribution of Na, K-ATPase or HSP-70 was assessed by Western blots and densitometric analysis. RESULTS: Coincubation of cytoskeletal pellets obtained during early reflow after renal ischemia (exhibiting severe injury of the cytoskeletal anchorage of Na,K-ATPase) and noncytoskeletal supernatant obtained during later reflow (showing high HSP expression) resulted in specific translocation of HSP-70 from the supernatant into the pellet, functionally associated with dose-dependent stabilization of Na,K-ATPase within this cytoskeletal fraction. These effects could be reproduced by incubation with purified HSP-70 and were abolished by the addition of anti-HSP-70 antibodies. CONCLUSION: These data support the hypothesis that HSP-70 interacts with cytoskeletal elements during the restoration of proximal tubule cell structure and polarity after renal ischemia. This experimental approach represents a new in vitro assay to study further the role of HSP in cellular repair.

Animals↗

First in vitro and in vivo experiences with Stay-Safe Balance, a pH-neutral solution in a dual-chambered bag.

In addition to low pH and high osmolarity, glucose degradation products (GDPs) are considered to play a major role in the bioincompatibility of peritoneal dialysis fluids (PDFs). The formation of GDPs can be reduced by separating the glucose component of the solution (kept at very low pH) from the lactate component of the solution (kept at alkaline pH) during sterilization and storage. This development has been achieved by the use of a dual-chambered bag. Immediately before infusion, the seam between the two chambers is opened, and the contents are mixed. The result is a fluid with a more physiologic pH in the range 6.8 - 7.4. Concentrations of 3-deoxyglucosone (3-DG), methylglyoxal (MG), acetaldehyde (AA), and formaldehyde (FA) in Stay-Safe Balance (Fresenius Medical Care, Bad Homburg, Germany) were remarkably reduced when compared to conventional PD solution [conventional PDF (1.5% glucose): 172 micromol/L, 6 microLmol/L, 152 micromol/L, and 7 micromol/L respectively; Stay-Safe Balance (1.5% glucose): 42 micromolL, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively; conventional PDF (4.25% glucose): 324 micromol/L, 10 micromol/L, 182 micromol/L, and 13 micromol/L respectively; Stay-Safe Balance (4.25% glucose): 60 micromol/L, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively). Human peritoneal mesothelial cells (HPMCs) were exposed to a control solution, a conventional PDF [CAPD 2, 1.5% glucose (Fresenius Medical Care, Bad Homburg, Germany)], and Stay-Safe Balance, either in a co-incubation model (24-hour PDF exposure) or in a pre-incubation model (30-min PDF exposure), followed by 24-hour recovery in culture medium. Interleukin-1beta (IL-1beta)-stimulated (1 ng/mL) IL-6 secretion from HPMCs was assessed by ELISA. Exposure of HPMCs to conventional PDF resulted in a significant reduction in IL-6 release, which was fully restored following exposure to Stay-Safe Balance. In addition to the short-term investigations, long-term in vitro studies were also carried out. All fluids had near-neutral pH and were changed every second day. After 1, 3, 5, 7, 10, and 13 days of exposure, cell viability was assessed. Whereas exposure to conventional PDF resulted in a significant reduction in HPMC viability after just 3 - 5 days, no significant toxicity of filter-sterilized or dual-chambered fluid was observed for up to 13 days. An observational study with 9 patients suggested that the efficacy of Stay-Safe Balance is equivalent to that of conventional solution. However, even short-term treatment (8+/-1 weeks) with this more biocompatible solution seems to improve mesothelial cell mass as indicated by a rise in cancer antigen 125 (CA125) from a baseline of 47+/-37 U/min to 172+/-90 U/min. Our data indicate that Stay-Safe Balance may help to better preserve peritoneal membrane cell function. An ongoing European multicenter study is expected to confirm these results.

Cells, Cultured↗

Subcutaneous recombinant human erythropoietin in chronic renal allograft dysfunction.

We investigated the efficacy and safety of subcutaneous recombinant human erythropoietin (rHuEpo) in 25 children with chronic renal allograft dysfunction (13 girls, 12 boys, mean age 15.8 +/- 4.2 years) for a treatment period of 9-162 (median 43) weeks. rHuEpo was started once weekly at a dose of 105 +/- 25 U/kg per week in 16 children, twice weekly at a dose of 175 +/- 70 U/kg per week in 6 children, and three times weekly at a dose of 270 +/- 28 U/kg per week in 3 children. The hematocrit increased in 21 children from 23.2% +/- 3.1% to 33% +/- 3.1% within 7.2 +/- 4.9 weeks at a mean rate of 1.98%/week. The hematocrit increase and rHuEpo starting dose were linearly related (delta hematocrit/week = 0.8+0.08 U/kg per week, r = 0.44, P < 0.05). The maintenance dose was 74 +/- 23 (43-114) U/kg per week. Four children failed to reach the target hematocrit, most likely due to noncompliance. Seventeen recurrences of anemia ("anemic episodes") during rHuEpo therapy were identified in 12 children, mostly associated with acute or insidious deteriorations in graft function. There was no acceleration of progression of graft dysfunction with rHuEpo treatment. We conclude that subcutaneous rHuEpo at a single weekly dose of 100 IU/kg per week is highly effective in children with chronic graft dysfunction. Children who appear to be rHuEpo resistant or experience rHuEpo-resistant episodes should be assessed for noncompliance, changes in graft function since the last dosage adjustment, and blood loss, such as seen in dysfunctional uterine bleeding in adolescent girls.

Adolescent↗

Heat-shock protein 25 induction and redistribution during actin reorganization after renal ischemia.

The small heat-shock proteins appear to have a regulatory role in actin dynamics. Since cytoskeletal disruption is integral to ischemic renal injury, we evaluated expression and intracellular distribution of heat-shock protein 25 (HSP-25) in rat renal cortex after 45 min of renal ischemia. HSP-25 was constitutively expressed and induced by ischemia with peak levels reached by 6 h reflow. Ischemia caused a shift of HSP-25 from the detergent-soluble into the insoluble cytoskeletal fraction. By 2 h reflow, the majority of HSP-25 had redistributed into the soluble fraction. HSP-25 was predominantly localized in a subapical distribution in control proximal tubules, a pattern intermediate between deoxyribonuclease (DNase)-reactive and filamentous actin. After ischemia, HSP-25 dispersed through the cytoplasm with small punctate accumulations similar to DNase-reactive actin. During later reflow, all three proteins were found in coarse intracytoplasmic accumulations; however, HSP-25 and DNase-reactive actin were in separate accumulations. HSP-25 and microfilamentous actin staining returned to the subapical domain. Thus the temporal and spatial patterns of HSP-25 induction and distribution suggest specific interactions between HSP-25 and actin during the early postischemic reorganization of the cytoskeleton. HSP-25 may have additional roles distinct from actin dynamics later in the course of postischemic recovery.

Actins↗

ATP releases HSP-72 from protein aggregates after renal ischemia.

The pattern of 72-kDa heat-shock protein (HSP-72) induction after renal ischemia suggests a role in restoring cell structure. HSP-72 activity in the repair and release from denatured and aggregated proteins requires ATP. Protein aggregates were purified from normal and ischemic rat renal cortex. The addition of ATP to cortical homogenates reduced HSP-72, Na(+)-K(+)-ATPase, and actin in aggregates subsequently isolated, suggesting that their interaction is ATP dependent. Altering ATP hydrolysis in the purified aggregates, however, had different effects. ATP released HSP-72 during reflow and preserved Na(+)-K(+)-ATPase association with aggregates at 2 h but had no effect in controls or at 6 h reflow and caused no change in actin. These results indicate that HSP-72 complexes with aggregated cellular proteins in an ATP-dependent manner and suggests that enhancing HSP-72 function after ischemic renal injury assists refolding and stabilization of Na(+)-K(+)-ATPase or aggregated elements of the cytoskeleton, allowing reassembly into a more organized state.

Actins↗

[Chronic peritoneal dialysis as home therapy in childhood--risks and complications].

BACKGROUND: The aim of our study was to ascertain the complications of chronic peritoneal home dialysis in childhood. PATIENTS: 17 children were treated by ambulatory peritoneal home dialysis between 1984 and 1994 at the paediatric dialysis unit of the University Children's Hospital in Vienna, Austria. Their average age was 6.5 years (1 week to 12 years); 7 (41.2%) children were below school age (< 6 years). RESULTS: In our observation period of 369 dialysis months (DM), the average duration of dialysis was 21.7 months (4.0-74.3). In relation to total DM the incidence of peritonitis was 1:23.1 of exit site infection 1:14.8 and of catheter related complications 1:41.0. 5 children developed hernias. 5 children were switched to haemodialysis and 8 children received kidney transplants. 2 children died from non-dialysis-associated causes. CONCLUSION: Peritoneal dialysis, in contrast to haemodialysis, is a home treatment modality applicable even to infants. The most common complication is infection. Our data and the European and North American literature show that by close ambulatory monitoring and special hygenic procedures peritonitis frequency can be markedly reduced.

Austria↗

Intratracheal furosemide in infants after cardiac surgery: its effects on lung mechanics and urinary output, and its levels in plasma and tracheal aspirate.

OBJECTIVE: Recent studies have suggested direct pulmonary effects of furosemide in asthmatics and infants with bronchopulmonary dysplasia. We tested the hypothesis that intratracheally administered furosemide also increases respiratory compliance in children after cardiac surgery, and investigated whether furosemide has a topical and/or systemic action. STUDY DESIGN: Prospective study with intra-individual control. In twelve infants and toddlers (age: 10 +/- 8 months, weight: 6.9 +/- 3 kg) mechanically ventilated for compromised lung mechanics after cardiac surgery, 0.5 mg/kg furosemide was intratracheally administered to the lungs. Lung mechanics were serially assessed using a computerised system (Sensormedics 2600) during a 2 h control and 2 h intervention period. Urine output was measured by an indwelling bladder catheter and levels of furosemide were determined in blood and tracheal aspirates. RESULTS: Static compliance improved within 30 min in all patients, reached a maximum of 44 (20-85)% above baseline and remained improved throughout the study (p < 0.05). An immediate, short and significant diuretic effect of intratracheally applied furosemide was observed. Furosemide levels 1 h after intervention were 795 ng/ml in the blood and 431 micrograms/ml (i.e. 1000-fold higher) in the tracheal aspirate. Changes in compliance were correlated only to urine output values over the 2 h (r = 0.82, p = 0.044, n = 9) after furosemide administration. CONCLUSION: We conclude that intratracheally applied furosemide improves static compliance in infants and toddlers with compromised lung mechanics after cardiac surgery. We demonstrated that furosemide is absorbed from the lung and has a systemic effect within 15 min after its intratracheal instillation.

Administration, Topical↗

Oral metronidazole does not improve cyclosporine A-induced gingival hyperplasia.

Recently, resolution of cyclosporine A (CSA)-induced gingival hyperplasia was reported with antibiotic treatment. We therefore assessed the oral status of 45 children on CSA after renal transplantation and evaluated the effects of metronidazole treatment in children with high-grade gingival hyperplasia. Gingival hyperplasia was absent in 19 (42%), mild in 5 (11%), moderate in 13 (29%), and severe in 8 (18%) children. There was no significantly different incidence in high-grade gingival hyperplasia (moderate and severe) between children with (16 of 30) or without (5 of 15) concomitant treatment with calcium channel blockers. The mean trough level of CSA was not different between children with varying severities of gingival hyperplasia. We treated 13 children with high-grade CSA-induced gingival hyperplasia (9 boys, 4 girls, mean age 14.2 +/- 3.4 years) with 750 mg metronidazole in three divided doses (10-25 mg/kg) for a total of 7 days. All 13 children were concomitantly treated with calcium channel blockers for hypertension; their mean monoclonal CSA trough level was 246 +/- 34 ng/ml. Oral examination and photographic documentation were performed by the same examiner on all patients before and 1 and 3 months after metronidazole treatment. We found no changes in gingival hyperplasia; gingival inflammation improved in 5 children (P = ns). We conclude that synergistic effects of calcium channel blockers and high concentrations of CSA in our population may outweigh beneficial effects of metronidazole treatment of CSA-induced gingival hyperplasia after renal transplantation.

Adolescent↗

Clinical impact of peritoneal equilibration testing in treatment of congenital lactic acidosis by acute peritoneal dialysis.

Although peritoneal equilibration testing (PET) is increasingly used in chronic peritoneal dialysis, there is little knowledge about the clinical impact of PET in the acute setting. We report about more than threefold increases in lactate removal by adjusting the dialysis prescription according to the results of PET in an infant with severe congenital lactic acidosis.

Acidosis, Lactic↗

Arginine reduces kidney collagen accumulation, cross-linking, lipid peroxidation, glycoxidation, kidney weight and albuminuria in the diabetic kk mouse.

In diabetic nephropathy a major current concept for pathogenesis is increased collagen accumulation in the glomerulus by increased collagen synthesis and decreased degradation. In the present study, we tested the hypothesis whether arginine is able to influence kidney lipid peroxidation, glycoxidation, collagen accumulation, glucose-mediated cross-linking, hydroxy radical attack, protein oxidation, nitric oxide formation and albuminuria in the diabetic kk mouse. Ten diabetic kk mice were given arginine 50 mg/kg body weight, 10 diabetic kk mice were not treated and used as negative controls and 10 kk mice were kept as healthy controls. Our results show that oral administration of low-dose arginine reduces kidney collagen accumulation as reflected by kidney hydroxyproline, cross-linking as reflected by pentosidine, lipid peroxidation, glycoxidation as reflected by carboxymethyl lysine, kidney weight and albuminuria in the diabetic kk mouse. Albuminuria in untreated animals was closely correlated with lipid peroxidation. Our results in the spontaneously diabetic kk mouse representing type 2 diabetes mellitus therefore confirm and extend recent findings of collagen reduction by arginine in a different animal model. The mechanism of reducing proteinuria can be assigned to the blocking of lipid peroxidation products by L-arginine.

Albuminuria↗

Use of prostaglandin I2 in three small children at high risk of early renal graft thrombosis.

We report the use of prostaglandin I.2. (PGI2) in three small children weighing less than 15 kg at high risk of graft thrombosis after cadaveric renal transplantation complicated by acute tubular necrosis. PGI2 was started at a dose of 5 ng/kg per min within the first 6 h after transplantation, and was continued for 12-15 days. Before and during PGI2 infusion, color-coded and pulsed Doppler sonography was performed. We found immediate restoration of diastolic flow, consistent with a decrease in vascular resistance. During the subsequent days, the sonographically assessed flow pattern and clinical graft function improved gradually. None of the three consecutively treated children developed graft thrombosis or lost his graft; no clinically relevant bleeding or adverse hemodynamic or pulmonary effects were seen.

Child, Preschool↗