[Diagnostic errors in nephrology].
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Adult↗
Biomedical subjects
A Schwarz
Publications and source records attributed to A Schwarz.
Protocol biopsy program after renal transplantation: structure and first results.
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Biopsy, Needle↗
Apoptosis induced by disruption of the actin cytoskeleton is mediated via activation of CD95 (Fas/APO-1).
Activation of the death receptor CD95 by its ligand or by UV radiation is associated with receptor clustering. The mechanism underlying this clustering is mostly unclear. Here we show that although disruption of the actin cytoskeleton by cytochalasin B (CyB) itself induces moderate apoptosis, it enhances apoptosis in HeLa cells induced either by UV radiation or an agonistic anti-CD95 antibody. CyB augments UV-induced apoptosis independently of UV-mediated DNA damage, since induction of DNA repair by exogenous DNA repair enzymes did not alter its enhancing effect. Inhibition of caspase-8, the most upstream caspase in CD95 signaling, blocked the apoptotic effect of CyB and the enhancing effect on UV- and CD95-induced apoptosis. Confocal laser scanning microscopy revealed that (i) CyB induces CD95 clustering, (ii) enhances UV-induced CD95 clustering, and (iii) CD95 clusters colocalize with disrupted actin filaments, suggesting a link between receptor clustering and actin rearrangement. Disruption of CD95 signaling by a dominant negative mutant of the signaling protein FADD protected from CyB-induced apoptosis and prevented the UV-enhancing effect. Accordingly, both the apoptotic and the enhancing effect of CyB was reduced in epidermal cells obtained from CD95 deficient mice (lpr) when compared to wild-type mice. These data suggest that disruption of the cytoskeleton causes apoptosis via activation of CD95 and enhances UV-induced apoptosis, possibly via aiding receptor clustering.
Actins↗
Autonomic auras: left hemispheric predominance of epileptic generators of cold shivers and goose bumps?
PURPOSE: Autonomic seizures in temporal lobe epilepsies associated with "cold shivers and goose bumps" as a principal ictal sign or aura have only rarely been studied. METHODS: Sixteen patients with autonomic auras [cold shivers or cold sweats (n=11), goose bumps (n=4), one patient showed both ictal signs] were analyzed. RESULTS: Lesions were detected in 12 patients. The etiology was heterogeneous [cryptogenic, arteriovenous (AV)-malformation cyst, trauma, hippocampal sclerosis]. Eight patients underwent epilepsy surgery. The localization and lateralization of the focal epileptic activity in the temporal lobes was determined either by magnetic resonance imaging lesions, EEG, ictal signs, or single-photon emission computed tomography imaging. CONCLUSIONS: The patients with temporal lobe epilepsies associated with "cold shivers and/or goose bumps" showed a left hemispheric predominance of the focal abnormality in the temporal lobe.
Adult↗
Bite forces in patients after treatment of mandibular angle fractures with miniplate osteosynthesis according to Champy.
Maximal biting forces were evaluated in 22 patients with mandibular angle fractures treated with miniplate osteosynthesis according to Champy. An electric test procedure for evaluating the load resistance between the incisors, canines and molars was carried out 1 to 6 weeks following the treatment and additionally in 15 controls, too. This revealed that after surgical fracture treatment 1 week postoperatively only 31%, of the maximal vertical loading found in controls was registered. These values increased to 58% at the 6th week postoperatively.
Adolescent↗
High-flux hemodialysis--an effective alternative to hemoperfusion in the treatment of carbamazepine intoxication.
Carbamazepine intoxication is associated with seizures, coma, arrhythmias and death. In acute intoxication, charcoal hemoperfusion is employed for removal of the drug. This can be associated with thrombocytopenia, coagulopathy, hypothermia and hypocalcemia. Alternatively, we used high-efficiency hemodialysis with a batch dialysis system (Genius), lowering not only serum levels of carbamazepine but removing a considerable amount of the drug as measured in the dialysate. This treatment regimen was compared to treatment by hemoperfusion. A 3.5-hour high-flux hemodialysis was as effective as a 2-hour hemoperfusion. We conclude that high-efficiency hemodialysis is a safe and effective alternative for treating life-threatening carbamazepine intoxication.
Adult↗
[Pathophysiology of gastric pouch surgery].
Reservoir function of a jejunum pouch is better than a simple Roux-en-Y limb. Postoperative processes of adaptation take at least 6 months. Pouch volume increases substantially after the operation and reaches about 200% of its initial volume. Morphological structure changes with muscular wall hypertrophy, plump deformation and widening of the villi, and a reduction of the mucosal surface. There is a change of motility pattern with a reduction of the propagation velocity. Randomized studies demonstrate a better reservoir function, less reflux, less heart burn, a slower passage time and fewer dumping symptoms after pouch reconstruction.
Anastomosis, Roux-en-Y↗
Genetic association analysis of behavioral inhibition using candidate loci from mouse models.
Genes influence the development of anxiety disorders, but the specific loci involved are not known. Genetic association studies of anxiety disorders are complicated by the complexity of the phenotypes and the difficulty in identifying appropriate candidate loci. We have begun to examine the genetics of behavioral inhibition to the unfamiliar (BI), a heritable temperamental predisposition that is a developmental and familial risk factor for panic and phobic disorders. Specific loci associated with homologous phenotypes in mouse models provide compelling candidate genes for human BI. We conducted family-based association analyses of BI using four genes derived from genetic studies of mouse models with features of behavioral inhibition. The sample included families of 72 children classified as inhibited by structured behavioral assessments. We observed modest evidence of association (P = 0.05) between BI and the glutamic acid decarboxylase gene (65 kDA isoform), which encodes an enzyme involved in GABA synthesis. No significant evidence of association was observed for the genes encoding the adenosine A(1A) receptor, the adenosine A(2A) receptor, or preproenkephalin. This study illustrates the potential utility of using candidate genes derived from mouse models to dissect the genetic basis of BI, a possible intermediate phenotype for panic and phobic disorders.
Animals↗
Impaired sodium excretion, decreased glomerular filtration rate and elevated blood pressure in endothelin receptor type B deficient rats.
The renal endothelin (ET) system, particularly the ET type B receptor, has been implicated in the regulation of sodium excretion and glomerular filtration rate (GFR). We analyzed kidney morphology and function in a rat strain characterized by complete absence of a functional ETB receptor. Due to Hirschsprung's disease limiting lifetime in these rats, studies were performed in 23-day-old rats. Kidney size and morphology (glomerular and interstitial matrix content, glomerular size and cell density and intrarenal vascular morphology) were normal in ETB-deficient rats. There were also no evidence of altered kidney cell cycle regulation in these rats. GFR was significantly lower, by 72% (P<0.001), in homozygous ETB-deficient rats than in wild-type rats. Fractional sodium excretion was likewise markedly reduced by 84% in homozygous ETB-deficient rats (P<0.001 versus wild-type rats). Treatment with the specific epithelial sodium channel blocker amiloride led to a much higher increase in fractional sodium excretion in ETB-deficient rats (934.2+/-73% in ETB-deficient rats versus 297+/-20% in wild-type rats, expressed as percentage of corresponding placebo treated control; P<0.001). Mean arterial blood pressure was elevated by 7.9 mmHg in homozygous ETB-deficient rats (P<0.05 versus wild-type rats). Our study demonstrates that ETB-deficiency causes early onset kidney dysfunction characterized by a markedly reduced sodium excretion, decreased GFR, and slightly elevated blood pressure. The complete absence of the ETB receptor causes in the kidney--in contrast to the colon--a functional rather than a developmental, neural crest cell dependent disease, since kidney morphology was normal in ETB-deficient rats. The much higher increase in the fractional sodium excretion in ETB-deficient rats after pharmacological blockade of the epithelial sodium channel indicates that the decreased fractional sodium excretion in ETB-deficient rats is most probably due to a lack of the inhibitory property of the ETB receptor on the epithelial sodium channel activity.
Amiloride↗
Radio-frequency probe for 1H decoupled 31P MRS of the head and neck region.
For optimal performance of 31P MRS at 1.5 Tesla, the use of a double resonant probe is essential to enable the application of 1H decoupling and Nuclear Overhauser Enhancement. This note describes the design, evaluation and safety validation of a versatile and compact probe optimized for 1H decoupled 31P MRS studies of tumors close to the surface of the body, in particular the head and neck region.
Equipment Design↗
[Comparison of Hannover Functional Ability Questionnaire (FFbH) and the SF-36 subscale "Physical Functioning"].
Pretesting of a questionnaire for evaluating day-patient rehabilitation, which included comparison of the "Hannover Functional Ability Questionnaire" (FFbH) and the SF-36 subscale "physical functioning" (SF-36 PF), gave rise to more extensive validity testing of the two instruments. In the framework of an expanded pretest, a questionnaire including FFbH and SF-36 PF was sent out to 520 adult former patients who had undergone inpatient orthopaedic rehabilitation following total hip or knee replacement an average 16 months ago. Return rate was 76%. Checks on plausibility showed no complaints about the Hannover Functional Ability Questionnaire while, on the SF-36 subscale, it was found that 16 of 374 patients (4.3%) had confused positive and negative ratings. Moreover, problems were found concerning the wording of several items (understanding, multidimensionality). In contrast to the FFbH, the SF-36 subscale shows weaknesses in the formulation of its items and particularly its ratings.
Adult↗
Plasmapheresis in streptococcal toxic shock syndrome.
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Adult↗
Epidermal growth factor induces cyclin D1 in human pancreatic carcinoma: evidence for a cyclin D1-dependent cell cycle progression.
INTRODUCTION: We recently showed that cyclin D1 is overexpressed in human pancreatic carcinoma cells, and that this overexpression correlates significantly with a poor prognosis. AIMS: To assess the interrelations of epidermal growth factor (EGF), EGF receptor (EGFR), and cyclin D1 in human pancreatic carcinoma. METHODOLOGY AND RESULTS: In pancreatic carcinoma cell lines (BxPC-3, AsPC-1), cell cycle analysis revealed an increase in cells in the S/G1 phase between 18 and 30 hours after stimulation with 50 ng/mL EGF. Cyclin D1 mRNA increased after 2 hours, corresponding to an increase in cyclin D1 protein, with the maximum level between 7.5 and 10 hours after stimulation, as demonstrated by Western blot analysis. We performed immunohistochemical analysis on 61 adenocarcinoma tissues for the expression of EGF, EGFR, and cyclin D1 and demonstrated an overexpression in the tumor cells in 51%, 54%, and 62.3%, respectively, whereas normal human pancreas stained negative for all of the three factors. Interestingly, EGF and EGFR expression correlated significantly with the cyclin D1 expression in human pancreatic tumor cells (p < 0.001 and p < 0.01, respectively). CONCLUSION: These results demonstrate that cyclin D1 overexpression in the tumor cells of pancreatic carcinoma tissue is at least partly dependent on the mitogenic effects of EGF signaling through the EGFR.
Blotting, Western↗
Effects of endothelin receptor antagonists on the progression of diabetic nephropathy.
BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease in European countries and is associated with an enhanced renal synthesis of endothelin (ET)-1. ETs are - beside their potent vasoconstrictor properties - very potent profibrotic acting paracrine hormones especially in the kidney. METHODS: We analyzed in rats with streptozotocin-induced diabetes the effects of an ETA-type (ETA) receptor antagonist (LU 135252) in comparison to a combined ETA/ETB receptor antagonist (LU 224332) on the expression of interstitial and glomerular collagen type I, III and IV as well as on fibronectin and laminin by quantitative immunohistochemistry using a computer-aided image analysis system. Global glomerular matrix deposition was analyzed after PAS staining. In addition to the morphometric examination of the kidneys, we also investigated GFR, urinary albumin and total protein excretion. The diabetic rats were treated for 36 weeks. RESULTS: Treatment with either LU 135252 or LU 224332 normalized the amount of PAS-positive material within the glomeruli. The expression of glomerular fibronectin and type IV collagen was increased 36 weeks after induction of diabetes. The overexpression of these two matrix proteins within the glomeruli of diabetic rats was completely abolished by both ET receptor antagonists, whereas protein excretion was only reduced by about 50% as compared to diabetic rats without treatment. CONCLUSION: The present study indicates that ETA receptor antagonists as well as combined ETA/ETB receptor antagonists reduce proteinuria and completely normalize the renal matrix protein expression in hyperglycemic rats with streptozotocin-induced diabetes. The antifibrotic effect seems to be mediated via the ETA receptor. ET receptor antagonists might be a new approach in the treatment of diabetic nephropathy.
Animals↗
Pregnancy and renal failure: the case for application of dosage guidelines.
Pregnancies in women with renal disease, undergoing dialysis treatment or with kidney transplants are increasingly observed. Serious problems with drug dose adjustment may arise in pregnant women with renal impairment. This review gives a practical overview on the risks of drug use during gestation, the recommended drugs of choice (e.g. methyldopa, cyclosporin), and provides some proposals for dosage adjustments in pregnant women with renal impairment. In normal pregnancy, the glomerular filtration rate and plasma volume increase, whereas plasma protein binding and liver function may be impaired. An increase in dosage is needed for cyclosporin and for methadone because of increased hepatic clearance. The dosage of erythropoetin must be increased because of lower potency in pregnant women. Little more is known on the impact of gestation on drug dose, since pharmacokinetic studies are rarely done in pregnant women. The dosages of magnesium, lithium and morphine must be reduced in renal impairment. Dose adjustment to renal function is critical and is essential for anti-infective agents (e.g. ceftazidime, ganciclovir). Basing drug dose on estimated creatinine clearance might be the most practical solution in pregnant women with renal impairment.
Dose-Response Relationship, Drug↗
New aspects of the treatment of nephrotic syndrome.
The nephrotic syndrome, caused by glomerulonephritis, diabetes mellitus, or amyloidosis, is still a therapeutic challenge. Newer therapeutic approaches may be sought in the fields of immunosuppression, nonspecific supportive measures, heparinoid administration, and removal of a supposed glomerular basement membrane toxic factor. In immunosuppression, the newer drugs now used in organ transplantation (cyclosporine, tacrolimus, and mycophenolate mofetil) can also be used in the treatment of glomerulonephritis. In nonspecific supportive treatment, angiotensin II receptor antagonists are now used in addition to angiotensin-converting enzyme inhibitors. Positive effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on the nephrotic syndrome have not yet been proven. Cyclooxygenase II inhibitors must be tested but probably have too many renal side effects, similar to those of nonsteroidal anti-inflammatory drugs. Heparinoids or glycosaminoglycans serve as polyanions and thus have protective effects on the negative charge of the glomerular basement membrane. They can now be administered as oral medications. The removal of a supposed glomerular basement membrane toxic factor that induces proteinuria has been attempted for 20 yr and now is usually performed using immunoadsorption. Especially in cases of recurrent nephrotic syndrome after renal transplantation for patients with glomerulonephritis, this approach has been successful in decreasing proteinuria, although in most cases its effect is not lasting but must be continuously renewed.
Animals↗
Nephrotoxicity of selective COX-2 inhibitors.
We describe 2 male patients, a 49-year-old with psoriatic arthritis and impaired renal function and a 43-year-old renal transplant recipient, who both sustained a marked decline in glomerular filtration rate in conjunction with a selective inhibitor of cyclooxygenase-2 (COX-2), rofecoxib. In the second patient, acute renal failure necessitated hemodialysis. Both patients made an uneventful recovery. Our report lends further support to the assumption that COX-2 inhibitors, as a class, can be as nephrotoxic as their nonselective predecessors. Therefore, COX-2 inhibitors should be used with caution in renal transplant recipients and in patients with salt depletion and renal insufficiency.
Acute Kidney Injury↗