Aortenisthmusstenose mit offenem Ductus Botalli als Ursache einer schweren Herzinsuffizienz bei einer 36-j?hrigen Patientin –Fallbericht über eine erfolgreiche operative Behandlung Fallbericht über eine erfolgreiche operative Behandlung

Wir beschreiben den Krankheitsverlauf einer 36-j?hrigen Frau mit unbehandelter Aortenisthmusstenose und offenem Ductus Botalli, die aufgrund einer ausgepr?gten linksventrikul?ren Dysfunktion eine therapierefrakt?re Herzinsuffizienz entwickelte. Nach operativer Korrektur der Aortenisthmusstenose und Ductusresektion normalisierte sich die linksventrikul?re Pumpfunktion, sodass davon ausgegangen werden kann, dass auch schwere linksventrikul?re Dysfunktionen auf dem Boden langj?hriger Druck- und Volumenbelastung durch angeborene Herzfehler nach operativer Korrektur reversibel sein k?nnen.     

G protein beta3 subunit 825T genotype is not associated with differing outcome in pediatric renal transplant recipients

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. The donor GNB3 825TT genotype was associated with reduced kidney allograft survival in adults. We examined (in 100 Caucasian pediatric renal transplant recipients) whether the GNB3 (C825T) polymorphism was associated with disease progression and outcome after renal transplantation. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal transplantation, and the population was divided into two groups of equal size, before and after transplantation, according to the slope. The observed frequencies were 57 for the CC, 33 for the CT, and 10 for the TT haplotype. For comparison, 738 consecutive newborn babies with the same ethnic background were typed in the same hospital. Allele frequencies were statistically not significantly different (chi-square test, p = 0.1327). When dividing the pediatric renal transplant recipients into two groups with regard to the slope of 1/creatinine, both before and after renal transplantation, the observed proportions were CC 26, CT 17, and TT 7 in the group with the poorer slope and CC 31, CT 16, and TT 3 in the group with the better slope before renal transplantation (not significant [NS], chi-square test, p = 0.1777). The observed proportions after renal transplantation were CC 26, CT 16, and TT 8 in the group with the poorer slope and CC 31, CT 15, and TT 4 in the group with the better slope, respectively (NS, chi-square test, p = 0.167). Allograft survival was not associated with the T allele. In conclusion, in a sizeable number of pediatric renal transplant recipients the GNB3 C825T polymorphism was found not to be a genetic risk factor for end-stage kidney disease. In addition, kidney graft function and survival was also found not to be associated with a recipient GNB3 C825T polymorphism.     

L-arginine supplementation accelerates renal fibrosis and shortens life span in experimental lupus nephritis

BACKGROUND: Inducible, high-output nitric oxide (NO) production has been identified as a central mediator of cell injury in immune-mediated renal disease. In acute anti-thy-1 glomerulonephritis prefeeding with the NO precursor L-arginine increases mesangial cell injury and the subsequent fibrosis. The present study tested the hypothesis that L-arginine supplementation may also be detrimental in chronic, NO-mediated murine lupus nephritis. METHODS: Groups (N = 18) of female MRL/lpr mice with lupus nephritis were fed the following diets: (1) normal protein (22% casein); (2) normal protein and 1.0% L-arginine in the drinking water; (3) low protein (6% casein); (4) low protein + 0.4%l-arginine; and (5) low protein + 1.0% L-arginine. After 40 days mouse survival, albuminuria, matrix accumulation, inflammatory cell infiltration, immunoglobulin G (IgG) deposition, expression of transforming growth factor-beta 1 (TGF-beta 1), fibronectin and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein, anti-DNA antibody titer, inducible nitric oxide synthase (iNOS) mRNA expression, blood amino acid levels, blood urea nitrogen (BUN) concentrations and blood and urinary NOx (nitrite + nitrate) levels were assessed. RESULTS: L-Arginine supplementation increased mortality significantly (P < 0.02). The death rate increased from 0% in the lowest to 50% in the highest L-arginine intake group (normal protein + 1.0% L-arginine). L-Arginine administration increased albuminuria, renal matrix accumulation, TGF-beta 1, fibronectin, PAI-1, blood L-arginine, L-citrulline, BUN and blood and urine NOx levels, while protein restriction reduced these parameters. Renal cell infiltration and iNOS mRNA expression were decreased in the low protein group only. Anti-ds DNA-IgG and renal IgG deposition were comparable in all groups CONCLUSIONS: Increasing L-arginine intake increases the severity of renal fibrosis and the likelihood of death in MRL/lpr mice. The results appear to be at least in part mediated through enhanced cytotoxic NO generation via iNOS. The data suggest that L-arginine restriction should be considered in human immune-mediated renal diseases.     

Treating type 2 diabetes in renal insufficiency: the role of pioglitazone

The advent of new antidiabetic drugs is of special importance for diabetic patients with already impaired renal function since renal insufficiency is a relative or absolute contraindication for several of the established hypoglycemic drugs. Pioglitazone is a novel oral hypoglycemic agent that increases insulin responsiveness in target tissues. Pioglitazone and its active metabolites are excreted mainly via the liver. Drug exposure remains almost constant across a wide range of renal function since there is no accumulation of the drug or its active metabolites during repeated dosing in renal insufficiency. The pharmacokinetic properties of pioglitazone are ideally suited for patients with renal insufficiency. Although there are possible side effects (mainly fluid retention and weight gain and--very rarely--hepatotoxicity). Pioglitazone has a good safety profile in diabetic patients with impaired renal function.     

Different impact of biomarkers as mortality predictors among diabetic and nondiabetic patients undergoing hemodialysis

Diabetic patients undergoing hemodialysis demonstrate much worse survival rates than do nondiabetic patients undergoing hemodialysis. To search for risk predictors, a prospective cohort study was performed with 245 hemodialysis patients, including 84 with diabetes mellitus, for 2 yr. C-reactive protein, troponin T (TnT), total, HDL, LDL, and lipoprotein(a) cholesterol, apoA2, apoB, triglyceride, fibrinogen, D-dimer, albumin, and creatinine levels and clinical characteristics at the time of entry were recorded. Survival rates were compared with Kaplan-Meier and Cox regression analyses. Forty-three diabetic patients and 30 nondiabetic patients died. Among diabetic patients, oliguria (<200 ml/d) (relative risk, 3.24; 95% confidence interval, 1.63 to 6.41; P = 0.001), elevated C-reactive protein levels (relative risk, 2.57; 95% confidence interval, 1.06 to 6.18; P = 0.035), and elevated D-dimer levels (relative risk, 2.36; 95% confidence interval, 1.11 to 5.01; P = 0.025) predicted all-cause mortality rates. Oliguria was by far the most important predictor, particularly for infectious disease-related death (relative risk, 23.35; 95% confidence interval, 2.60 to 209.97; P = 0.005). Among nondiabetic patients, elevated TnT levels (relative risk, 4.00; 95% confidence interval, 1.58 to 10.10; P = 0.003), elevated D-dimer levels (relative risk, 3.45; 95% confidence interval, 1.27 to 9.33; P = 0.015), and low cholesterol levels (relative risk, 3.61; 95% confidence interval, 1.34 to 9.71; P = 0.011) predicted all-cause mortality rates. Subdivision of the causes of death among nondiabetic patients revealed that TnT levels predicted cardiovascular mortality rates (relative risk, 5.38; 95% confidence interval, 1.11 to 26.10; P = 0.037) and infectious disease-related mortality rates (relative risk, 12.02; 95% confidence interval, 1.42 to 191.96; P = 0.023). In conclusion, mortality predictors among patients undergoing hemodialysis differed substantially between diabetic and nondiabetic patients. Strategies to reduce mortality rates should consider these differences.     

Entry-into-human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients

AIMS: To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). METHODS: This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. RESULTS: All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. CONCLUSIONS: SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.     

Intraabdominal hematoma following orchiectomy: a potential pitfall in using CT for staging of testicular cancer

Internal bleeding in patients undergoing orchiectomy for a malignant testicular tumor can cause a dissecting hematoma in the retroperitoneum. This mass may have the clinical appearance of an iliac fossa mass and may simulate metastasis on computed tomography (CT). This condition was seen in four of 486 orchiectomy patients who underwent postoperative staging with CT. One patient is described in detail.