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R Schindler

Publications and source records attributed to R Schindler.

At least 19 recordsLinked to original sources
PubMed2006

3-year study of donepezil therapy in Alzheimer's disease: effects of early and continuous therapy.

Delays in the diagnosis of Alzheimer's disease, and, therefore, delays in treatment, may have a detrimental effect on a patient's long-term well-being. This study assessed the effects of postponing donepezil treatment for 1 year by comparing patients treated continuously for 3 years with those who received placebo for 1 year followed by open-label donepezil for 2 years. Patients (n = 286) with possible or probable Alzheimer's disease (according to DSM-IV, NINCDS-ADRDA, and Mini-Mental State Examination criteria; see text) were randomized to receive donepezil (5 mg/day for 4 weeks, 10 mg/day thereafter) or placebo (delayed-start group) for 1 year. Of the 192 completers, 157 began a 2-year, open-label phase of donepezil treatment. Outcome measures were the Gottfries-Bråne-Steen scale, the Mini-Mental State Examination, the Global Deterioration Scale, the Progressive Deterioration Scale, the Neuropsychiatric Inventory, and safety (adverse events). Mixed regression analysis was used to compare changes between the groups over 3 years on the efficacy measures. There was a trend for patients receiving continuous therapy to have less global deterioration (Gottfries-Bråne-Steen scale) than those who had delayed treatment (p = 0.056). Small but statistically significant differences between the groups were observed for the secondary measures of cognitive function (Mini-Mental State Examination; p = 0.004) and cognitive and functional abilities (Global Deterioration Scale; p = 0.0231) in favor of continuous donepezil therapy. Over 90% of the patients in both cohorts experienced one treatment-emergent adverse event; most were considered mild or moderate. In conclusion, patients in whom the start of treatment is delayed may demonstrate slightly reduced benefits as compared with those seen in patients starting donepezil therapy early in the course of Alzheimer's disease. These data support the long-term efficacy and safety of donepezil.

Aged↗
PubMed2006

Living kidney donation: anemia and inflammation in the early postoperative period.

Studies on living donor kidney transplantation primarily address the recipients; few publications focus on kidney donors. The aim of the present study was to detect changes in and compensations of defined parameters of anemia and inflammation in the immediate postnephrectomy period. We included six living kidney donors who underwent an open anterior-extraperitoneal nephrectomy. We excluded donors with complications, such as significant blood loss or infection. Blood samples were taken before nephrectomy as well as on postoperative days 1, 3, 5, and 7, and at discharge for measurements of hemoglobin (Hb), serum erythropoietin (Epo), reticulocytes (Reti), pentraxin 3 (PTX3), and C-reactive protein (CRP). There was a significant decrease in Hb (>3 g/dL), reaching a maximum on day 3 followed by a significant threefold increase in Epo levels on day 5 and a nonsignificant elevation of Reti count. CRP increased approximately 80-fold on day 3. PTX3 showed a similar course, peaking on day 3 with an approximate 70-fold increase. After living donor nephrectomy, there was an unexpectedly pronounced inflammatory reaction in the absence of any signs of bacterial infection simultaneous with a significant decrease in Hb. These parameters improved during the hospital stay, in some cases they achieved the prenephrectomy level at discharge. These data may assist in interpreting laboratory results after nephrectomy among living kidney donors.

Aged↗
PubMed2006

Amelioration of anemia after kidney transplantation in severe secondary oxalosis.

INTRODUCTION: In small bowel disease such as M. Crohn, the intestinal absorption of oxalate is increased. Severe calcium oxalate deposition in multiple organs as consequence of enteric hyperoxaluria may lead to severe organ dysfunction and chronic renal failure. The management of hemodialyzed patients with short bowel syndrome may be associated with vascular access problems and oxalate infiltration of the bone marrow leading to pancytopenia. Although the risk of recurrence of the disease is very high after renal transplantation, it may be the ultimate therapeutic alternative in secondary hyperoxaluria. CASE: Here, we report a patient with enteric oxalosis due to Crohn's disease. He developed end-stage renal disease, erythropoietin-resistant anemia, oxalate infiltration of the bone marrow and severe vascular access problems. Following high-urgency kidney transplantation, daily hemodiafiltration of 3 hours was performed for 2 weeks to increase oxalate clearance. Despite tubular and interstitial deposition of oxalate in the renal transplant, the patient did not require further hemodialysis and the hematocrit levels normalized. DISCUSSION: Early treatment of hyperoxaluria due to short bowel syndrome is essential to prevent renal impairment. Declining renal function leads to a further increase in oxalate accumulation and consecutive oxalate deposition in the bone marrow or in the vascular wall. If alternative treatments such as special diet or daily hemodialysis are insufficient, kidney transplantation may be a therapeutic alternative in severe cases of enteric oxalosis despite a possible recurrence of the disease.

Adult↗
PubMed2005

"Periodic fever" without fever: two cases of non-febrile TRAPS with mutations in the TNFRSF1A gene presenting with episodes of inflammation or monosymptomatic amyloidosis.

BACKGROUND: Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS) is caused by dominant mutations in the TNFRSF1A gene. In typical cases TRAPS begins early in childhood and is characterised by high and remittent fever over a period of 1-4 weeks or longer, accompanied by systemic and local inflammation. CASE REPORTS: Patient 1 presented with recurrent episodes of weakness, migrating myalgias, arthralgias, exanthema, and chest pain lasting for 1-4 weeks, but without any fever over an initial period of 4 years at least. Diagnosis of TRAPS was confirmed by the heterozygous mutation Y20H in TNFRSF1A. Patient 2, a 23 year old woman never had any symptoms indicative of TRAPS. Genetic evaluation of all members of her family with a TRAPS index patient disclosed the T50M mutation in TNFRSF1A. A medical check up showed proteinuria, and renal biopsy disclosed AA amyloidosis. CONCLUSIONS: TRAPS associated mutations can induce considerable inflammation that is not necessarily accompanied by fever. Even monosymptomatic severe amyloidosis can occur in these patients. Genetic counselling and appropriate management to prevent or mitigate amyloidosis may be necessary.

Adult↗
PubMed2005

Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia.

BACKGROUND: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. PATIENTS AND METHODS: Sixty otherwise healthy subjects with total cholesterol > or = 5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. RESULTS: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area undercurve: 5.29 +/- 1.62 to 4.99 +/- 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 +/- 1.88 to 5.18 +/- 1.78, p > 0. 1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. CONCLUSIONS: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

Adult↗
PubMed2004

First non-mosaic case of isopseudodicentric chromosome 18 (psu idic(18)(pter --> q22.1::q22.1 --> pter) is associated with multiple congenital anomalies reminiscent of trisomy 18 and 18q- syndrome.

Isopseudodicentric chromosome 18 is very rare and results in a combination of partial trisomy and partial monosomy of chromosome 18. We report here a hypotrophic newborn with a lateral cleft lip and palate and multiple craniofacial dysmorphisms, a combined heart defect, unilateral hypoplasia of the kidney, bilateral aplasia of thumbs, and generalized contractures. Cytogenetic analysis revealed an isopseudodicentric chromosome 18 with breakpoint in 18q (46,XX,psu idic(18)(pter --> q22.1::q22.1 --> pter)). The isopseudodicentric chromosome 18 was observed in 100% of blood lymphocytes and umbilical cord fibroblasts, thus indicating a non-mosaic finding of the isopseudodicentric chromosome in the child. An elongated derivative chromosome 18 had also been found prenatally in amniotic cells. In contrast, a terminal deletion (18q-) was detected in placental cell cultures. The breakpoint was mapped to a 0.9 Mb region on 18q22.1 (located 64.8-65.7 Mb from the telomere of the p-arm) by a novel quantitative PCR approach with SYBR green detection. The results indicate an identical breakpoint of the isopseudodicentric chromosome 18 in the child and the 18q- chromosome in the placenta. To our knowledge this is the first report that a fetus carrying an isopseudodicentric chromosome 18 with breakpoint in 18q (46,XX,psu idic(18)(pter --> q22.1::q22.1 --> pter)) in non-mosaic form can be viable, but is associated with severe congenital malformations of the child.

Abnormalities, Multiple↗
PubMed2004

Bilirubin-adsorption in 23 critically ill patients with liver failure.

PURPOSE: Previous studies suggest that high levels of bilirubin exert cytotoxic, neurotoxic and encephalopathic effects that themselves may lead to further deterioration of liver function and multiorgan failure. Although extracorporeal BA is not a causal therapy, there are case reports of clinical benefits of BA. The present retrospective study investigated the clinical utility and effectiveness of BA in 23 patients with liver failure. METHODS: Twenty-three patients (61+/-11 years) with excessive hyperbilirubinemia (>25 mg/dL) after liver transplantation (n=7), partial liver resection (n=12) and others (n=4) were treated with BA (3.6 liters plasma per BA, BR350, Asahi) and followed for 45+/-8 days. RESULTS: A mean of 6.6 treatments (3-16) were performed per patient. On average, a single BA treatment reduced bilirubin-levels from 31+/-12 to 23.7+/-9 mg/dL (p<0.001). Levels of bile acid were reduced from 41.8+/-6 to 33.5+/-5 mg/dL. The 30-day mortality was 50%. BA was able to halt and stabilize the progressive increase in bilirubin levels in all patients. In contrast to survivors, non-survivors were characterized by a repeated rapid rise in bilirubin levels after cessation of BA treatment. CONCLUSIONS: BA is able to stabilize or decrease bilirubin levels in patients with liver failure. Our experience suggests that BA is a safe and promising short-term treatment option for patients with acute deterioration of hepatic function.

Adsorption↗
PubMed2003

Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens.

AIMS: The increasing use of high-flux membranes for hemodialysis has raised concerns that patients dialyzed with these membranes may be at higher risk of being exposed to cytokine-inducing bacterial substances in the dialysate than patients dialyzed with low-flux membranes. We investigated the permeability of various high-flux membranes for both purified E. coli lipopolysaccharide (LPS) as well as for LPS derived from Stenotrophomonas (Sten.) maltophilia. MATERIALS AND METHODS: An in vitro dialysis circuit with saline in the blood compartment of 3 dialyzers containing different membranes (polysulfone, helixone and Diapes) was employed. The dialysate was challenged with increasing doses of sterile filtrates derived from Sten. maltophilia cultures or with purified LPS from E. coli. Samples from the blood compartment were tested for cytokine induction (IL-1beta, IL-6 and TNF) in mononuclear cells as well as for LPS by limulus amebocyte lysate test (LAL). RESULTS: IL-6 induction above sterile controls (< 0.02 ng/ml IL-6) was observed by samples from the blood side of DIAPES dialyzers (1.2 +/- 0.7 ng/ml IL-6) after challenging the dialysate with 4.1 +/- 3.6 U/ml E. coli LPS (9.9 +/- 4.5 ng/ml IL-6). In contrast, at the same challenge dose no significant IL-6 induction above sterile controls was observed by blood side samples of polysulfone (0.15 +/- 0.07 ng/ml) and helixone (0.09 +/- 0.05 ng/ml) dialyzers. Increasing the amount of E. coli LPS in the dialysate further augmented IL-6 induction by blood side samples of Diapes but not of polysulfone and helixone dialyzers. Similar results were obtained for IL-1beta and TNF. After challenging the dialysate with E. coli LPS as well as with cultures of Sten. maltophilia, significantly more LAL reactivity was observed in the blood compartment of Diapes compared to polysulfone and helixone. CONCLUSIONS: There are considerable differences between high-flux membranes regarding their permeability for cytokine-inducing substances from E. coli as well as for LPS derived from E. coli and Sten. maltophilia. Dialyzers that leak CIS under aqueous conditions in vivo should not be used unless the dialysate has passed through an ultrafilter.

Escherichia coli Proteins↗
PubMed2001

Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents.

Identification of inhibitors of retinyl ester hydrolase (REH) would help to elucidate its role in vitamin A metabolism in vivo. By using standard incubation conditions, the effects of 215 drugs as potential inhibitors of purified pig and human liver REH when acting on micellar substrate retinyl palmitate were evaluated at 16.7, 167, and 1670 microM. Out of the compounds tested, 103 were inhibitors of the pig liver enzyme. The most potent compounds, in order of decreasing activity, were chloral hydrate, lovastatin, phytomenadione, alimemazine, physostigmine, thioridazine, phenoxybenzamine, probucol, cinnarizine, cyclandelate, amiodarone, flupenthixol, and naftidrofuryl; this order is roughly similar to that of their inhibition of human liver REH. Of the 10 tricyclic ring-containing drugs tested, alimemazine was the most potent enzyme inhibitor. The concentrations necessary for 50% enzyme inhibition ranged from <2.6 up to >540 microM. Moreover, inhibitory kinetic studies showed that at least two pharmaceuticals, chloral hydrate and amiodarone, are potent REH inhibitors at therapeutically achievable serum concentrations. First-pass metabolites were inactive as REH inhibitors compared to that of the parent compounds, in the cases of chloral hydrate, lovastatin, and cyclandelate.

Animals↗
PubMed2001

Removal of contrast media by different extracorporeal treatments.

BACKGROUND: Although the capability of extracorporeal treatments after administration of contrast media to prevent radiocontrast-induced nephropathy is controversial, haemodialysis is performed in many institutions after radiographic procedures. There are conflicting reports on the efficacy of different dialysers and treatment modalities to remove contrast media. METHODS: We compared the contrast medium-removing ability of different extracorporeal treatments in a randomized trial. Thirty-nine patients on chronic renal-replacement therapy or with chronic renal failure were randomized to receive low-flux haemodialysis (Low-HD, n=10), high-flux haemodialysis (High-HD, n=10), online haemodiafiltration (HDF, 10 litre substitution, n=10) and online haemofiltration (HF, 18 litre substitution, n=9) after administration of contrast medium during routine radiological procedures. Plasma concentrations of contrast medium (iopromide or iomeprol) were measured by energy-dispersive X-ray fluorescence analysis. RESULTS: The extraction ratio for contrast media was 0.64+/-0.1 for Low HD (P<0.05 vs. High-HD and vs. HDF), 0.74+/-0.1 for High-HD (P<0.05 vs. HF), 0.81+/-0.1 for HDF (P<0.05 vs HF), and 0.62+/-0.1 for HF. Mean extracorporeal plasma clearances were 82+/-2 for Low-HD (P<0.05 vs. High-HD and vs HDF), 100+/-2 for High-HD, 115+/-4 for HDF (P<0.05 vs. HF), and 86+/-5 ml/min for HF. CONCLUSIONS: We conclude that HDF and High-HD remove contrast media more effectively than Low-HD and HF during the time of each treatment session. However, whether this is also true for the overall elimination of contrast media by these different procedures needs to be addressed in future studies, by a precise assessment of the drug time course after the session.

Angiography↗
PubMed2001

Blood components influence cytokine induction by bacterial substances.

While some studies clearly demonstrated transfer of cytokine-inducing substances (CIS) through dialysis membranes, other authors were unable to reproduce such a transfer. This inconsistency may have been caused by marked differences in experimental design. We performed a systematic evaluation of cytokine induction in whole blood and from separated peripheral blood mononuclear cells (PBMC) using either purified lipopolysaccharide (LPS) or culture supernatants from various bacterial strains. An in vitro hemodialysis circuit with whole blood in the blood compartment was employed; the dialysate was contaminated with sterile filtrates from Pseudomonas aeruginosa cultures. Addition of plasma samples from the blood side to PBMC readily induced interleukin (IL)-1beta and IL-6 after contamination of the dialysate, while the same samples failed to induce cytokine production in whole blood. In experiments using direct incubation, purified P. aeruginosa LPS induced more IL-1beta and IL-6 in whole blood compared to PBMC. In contrast, bacterial filtrates from Escherichia coli, Enterobacter cloacae and especially P. aeruginosa induced significantly less cytokines in whole blood compared to PBMC. Addition of erythrocytes but not granulocytes decreased cytokine induction by bacterial filtrates as well as by LPS, probably by adsorption of these substances. The addition of 30% plasma increased cytokine induction by LPS but decreased cytokine induction by P. aeruginosas filtrates. Our results suggest that cellular and plasmatic components of whole blood interact with bacterial CIS altering their pyrogenic activity. The detection of CIS depends on the test system used; whole blood cultures are not as sensitive for the detection of CIS from bacterial filtrates as PBMC cultures.

Antigens, Bacterial↗
PubMed2001

Aldolase-localization in cultured cells: cell-type and substrate-specific regulation of cytoskeletal associations.

The role of aldolase as a true F- and G-actin binding protein, including modulating actin polymerization, initiating bundling, and giving rise to supramolecular structures that emanate from actin fibrils, has been established using indirect immunofluorescence, permeabilization of XTH-2 cells and keratocytes, and microinjection of fluorescence-labeled aldolase. In addition, binding to intermediate filaments, vimentin, and cytokeratins has been demonstrated. In permeabilized cells in the presence of fructose-1,6-bisphosphate (20-2000 microM) aldolase shifts from association with actin fibres to intermediate filaments. Plenty of free binding sites on microtubules have been revealed by addition of fluorochromed aldolase derived from rabbit skeletal muscle. However, endogenous aldolase was never found associated with microtubules. Differences in actin polymerization in the presence of aldolase as revealed by pyrene-labeled actin fluorimetry and viscosimetry were explained by electron microscopy showing the formation of rod-like structures (10 nm wide, 20-60 nm in length) by association of aldolase with G-actin, which prevents further polymerization. Upon the addition of fructose-1,6-bisphosphate, G-actin-aldolase mixture polymerizes to a higher viscosity and forms stiffer filaments than pure actin of the same concentration.

Actins↗
PubMed2000

Mid-infrared quantum cascade lasers for flow injection analysis

A Fabry-Perot quantum cascade laser (QCL) was used as a powerful light source for mid infrared (MIR) detection in flow injection analysis. The QCL lased at several wavelengths close to each other within a few wavenumbers (990-1010 cm-1), hence fitting well to the broad absorption bands of molecules in liquid phase. As compared with that of a state-of-the-art Fourier transform spectrometer, the signal-to-noise ratio could be improved by a factor of 50. Additionally, by using a QCL as the light source, optical path lengths of more than 100 microns could be used even in aqueous matrixes which reduced the danger of cell clogging. In the example shown here phosphate was determined in Diet Coke samples. The flow injection system used allowed the measurement of the sample at two pH values (5 and 13) at which the analyte was present as H2PO4- and PO4(3-), respectively. As the analytical readout the difference in IR absorption of H2PO4- and PO4(3-) at the laser wavelengths was taken. The FIA-QCL measurements were corroborated by ion chromatography which was used as a reference method.

Journal Article↗
PubMed2000

Plasma levels of endothelin-1 in patients with the hepatorenal syndrome after successful liver transplantation.

The hepatorenal syndrome (HRS) is characterized by renal vasoconstriction leading to deterioration of renal function in patients with liver disease. A possible role of endothelin-1 (ET-1) in the pathogenesis of HRS has been suggested, but a correlation between ET-1 plasma levels and the development of HRS as well as the recovery from HRS following OLT has not been shown yet. We performed longitudinal measurements of ET-1 plasma levels in four groups of patients, 5 patients with HRS before and after orthotopic liver transplantation (OLT), 10 patients without HRS undergoing OLT, 20 patients with chronic renal failure but without liver disease, and 12 healthy controls. Before OLT, plasma levels of ET-1 were higher in patients with HRS (19.5 +/- 8.6 ng/l, P < 0.001; n = 5) compared to patients without HRS (4.9 +/- 1.1 ng/l; n = 10), normals (1.2 +/- 0.18 ng/l; n = 12), and patients with chronic renal failure (2.4 +/- 0.4 ng/l; n = 20). Patients with HRS compared to patients without HRS had higher levels for creatinine (2.42 +/- 0.6 vs. 0.89 +/- 0.05 mg/dl, P < 0.05), creatinine clearance (107 +/- 9 ml/min vs. 44.6 +/- 5.5 ml/ min, P < 0.001), and bilirubin (11.4 +/- 3.8 vs. 3.7 +/- 1 mg/dl, P < 0.05) before OLT. Within one week after OLT, there was a rapid decrease in ET-1 levels in patients with HRS while creatinine and bilirubin levels decreased slower. Regression analysis revealed a weak correlation between serum creatinine and ET-1 (r = 0.192, P = 0.04) and a significant correlation between serum bilirubin and ET-1 (r = 0.395, P < 0.001). The means of the ET-1 levels decreases rapidly with improvement of liver function after OLT. Levels of ET-1 correlate with excretory liver function assessed by bilirubin. The fall in ET-1 levels preceding improvement of renal function further strengthens the concept of ET-1 being a causative factor in HRS.

Acute Kidney Injury↗
PubMed2000

Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets.

Low oxygen (O(2)) is the key stimulus for expression of vascular endothelial growth factor (VEGF) in several adherent cells. Whether hypoxia also directs the release of VEGF protein from neutrophils (polymorphonuclear neutrophils; PMN) and platelets has not been investigated. We therefore compared VEGF release of platelets, PMN, and human vascular smooth muscle cells (HSMC) in response to hypoxia with that to activators of cellular degranulation. In contrast to HSMC, VEGF release from PMN and platelets or VEGF mRNA expression in PMN was not stimulated under hypoxic conditions (1% O(2)). Hypo- or hyperthermia and acidosis, other conditions potentially associated with ischemic and inflammatory tissue injury, also did not stimulate VEGF secretion from PMN. However, stimulation of platelets with thrombin and of PMN with phorbol 12-myristate 13-acetate induced a time-dependent release of VEGF, peaking after 30 and 60 min, respectively. This was blocked by the degranulation inhibitor pentoxifylline but not by the protein-synthesis inhibitor cycloheximide. We conclude that rapid release of VEGF from platelets and PMN may occur independently of oxygenation during inflammation and hemostasis.

Adult↗