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Biomedical subjects

R Schindler

Publications and source records attributed to R Schindler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of the hemodialysis membrane on the inflammatory reaction in vivo.

BACKGROUND: Increased levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with myocardial infarction, stroke and the development of peripheral arterial disease. Hemodialysis patients show signs of an inflammatory reaction indicated by elevated plasma levels of CRP and by increased plasma levels of interleukins. PATIENTS AND METHODS: To investigate the effect of the dialysis membrane on the inflammatory reaction, we conducted a randomized study in 18 hemodialysis patients. Patients were subsequently treated with dialyzers containing polyamide, polycarbonate or cuprophan for 8 weeks on each dialyzer in a crossover design. During each treatment period, CRP plasma levels were measured 6 times at weekly intervals. The total content and the spontaneous and lipopolysaccharide- (LPS) stimulated production of interleukin-1beta (IL-1beta), IL-6 and IL-1 receptor antagonist (IL-1Ra) were determined in whole blood samples. RESULTS: CRP plasma levels were significantly higher in hemodialysis patients (all patients, 1.63 +/- 0.23 mg/dl) compared to normals (0.14 +/- 0.02 mg/dl, p < 0.0001). CRP levels were lower when patients were dialyzed with polyamide (1.19 +/- 0.18 mg/dl) compared to the levels when the same patients were dialyzed with cuprophan (1.77 +/- 0.37 mg/dl, p = 0.02) or with polycarbonate (1.34 +/- 0.2 mg/dl, n.s). The whole blood content of IL-1Ra in non-incubated samples was significantly lower in normal subjects (512 +/- 60 pg/ml) compared to hemodialysis patients (980 +/- 80 pg/ml, p < 0.01). The whole blood content of IL-1Ra was higher when patients were dialyzed with cuprophan (1,062 +/- 119 pg/ml) compared to the same patients on polyamide (906 +/- 78 pg/ml, p < 0.05) or on polycarbonate (973 +/- 80 pg/ml, n.s.). Spontaneous and LPS-induced production of IL-1beta and IL-6 was similar for all dialyzers. CONCLUSION: We conclude that the inflammatory reaction in hemodialysis patients is affected by the choice of the dialyzer.

Biocompatible Materials↗
PubMed1999

New aminocarboxamides with class III anti-arrhythmic activity.

In the search for new anti-arrhythmic substances we discovered the class III activity of aminocarboxamides. These compounds show a prolongation of the effective refractory period. With some of them the prolongation is more pronounced after faster than after slower stimulation of the guinea pig papillary muscle. They should therefore be of interest in the treatment of cardiac arrhythmias after myocardial infarction and atrial fibrillation. The chemical synthesis, the structure-activity relationships of the new derivatives, their efficacy on the action potential duration (APD) and the effective refractory period (ERP) in vitro of isolated guinea pig papillary muscles are described and discussed in this paper. Since AWD 160-275 (13) and AWD 23-111 (14) exerted a pronounced APD90 and ERP prolongation at faster stimulation, they were selected for further electrophysiological characterization in vitro and in vivo. Anti-arrhythmic and pro-arrhythmic effects were determined in several animal models in comparison with dofetilide, sematilide, and sotalol. 13 was found to be effective in preventing programmed electrical stimulation-induced arrhythmias in anaesthetized dogs and may therefore contribute to the therapy of dysrhythmias after myocardial infarction. The pro-arrhythmic effect of 14, investigated in a model of triggered activity in chloralose-anaesthetized rabbits under methoxamine infusion, is low in comparison with other class III anti-arrhythmics.

Action Potentials↗
PubMed1999

Bilateral emphysematous pyelonephritis caused by Candida infection.

Emphysematous pyelonephritis is a rare, often severe infection of one or both kidneys that is most often caused by bacterial infection. Surgical intervention is often necessary. We describe a case of a diabetic patient with bilateral emphysematous pyelonephritis caused by Candida infection that was treated conservatively. Renal function recovered almost completely in spite of giving a potential nephrotoxic drug for 6 weeks.

Aged↗
PubMed1999

Prognostic value of cardiac troponin T and I elevations in renal disease patients without acute coronary syndromes: a 9-month outcome analysis.

BACKGROUND: Moderate elevations of cardiac troponin (Tn) T, up to levels presumably diagnostic for minor myocardial damage, are suspected to be false positive in nearly 0.3 of end-stage renal disease (ESRD) patients undergoing haemodialysis (HD). It is not clear whether cardiac TnI is superior to TnT in those patients, if differences between ESRD and pre-ESRD occur, and what the prognostic meaning of these troponin elevations might be. SUBJECTS AND METHODS: We examined 40 chronic renaldisease patients [56.4 SD 13.9 years; 22 male, 18 female) without evidence of an acute coronary syndrome (ACS) for at least 28 days prior to the investigation. Cardiac status was determined by history, physical examination, ECG and echocardiography. Patients were divided into subgroups with HD (n = 20) and without HD (n = 20). Patients without HD had a mean creatinine clearance (CC) of 13.45 ml/min. Tn were measured by immunoassay techniques. TnT was compared to two different TnI tests (TnID, TnIB), CK/CKMB activity and myoglobin (MYO) concentrations. In all patients, a 9-month follow-up for acute myocardial infarction, re-hospitalization, and death was completed. RESULTS: None of the troponins significantly predicted patient outcome. Tn did not correlate with CC (r<0.6). Applying the lowest reported threshold values for all tests in the HD group, 0.3 patients were positive for TnT, 0.55 patients were positive for TnID, and 0.15 for TnIB. In the group without HD, 0.2 patients were positive for TnT and TnID and 0.1 for TnIB. CONCLUSIONS: Moderate elevations of cardiac troponins are common in clinically stable patients with renal disease and are neither diagnostic for an acute coronary syndrome nor predictive of outcome. It is concluded that increased troponins in asymptomatic renal patients are of questionable value for risk stratification, most probably due to unspecific elevations.

Adult↗
PubMed1999

Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells.

Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte beta-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-alpha (TNF-alpha). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-alpha-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-alpha-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under "normoxic" (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of L-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2 to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-L-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.

Cells, Cultured↗
PubMed1999

Empowering the aged--a postmodern approach.

With the growth of the elderly population, the theme of empowerment and its actual negotiation will emerge as an issue of great importance. The aged are vulnerable in many ways and occupy still relatively limited social roles with restricted access to social goods. They are often undermined in their desire for self-determination. It is suggested that by introducing a postmodern approach in helping this group, the basic principles of social work can be enriched. Empowerment that includes opportunities for growth, mastery, significance, and meaning can be substantially increased. This article outlines the rationale for this approach and discusses the process of collaboration, the therapeutic relationship, and intervention strategies. While this article is limited to the elderly, the appreciation of the postmodern approach has implications for people in need for other populations as well.

Aged↗
PubMed1998

Purification and characterization of retinyl ester hydrolase as a member of the non-specific carboxylesterase supergene family.

Hepatic retinyl ester hydrolase (REH) activity was isolated from porcine and human liver and characterized, and some of its properties were compared with those of other retinyl-ester-splitting enzymes. Sequence analysis revealed that the REH proteins are structurally similar to non-specific carboxylesterases and distinct from bile salt-activated lipases and cholesterol esterases. Pig REH, a 64-kDa protein, hydrolyzed retinyl palmitate at a rate of 595 nmol x h(-1) x mg(-1) protein in the presence of 100 mM Chaps with an apparent Km value for retinyl palmitate of 27.5 microM. The pH optimum was 7.0-9.2. Its human counterpart has a molecular mass of 65 kDa and a pH optimum near 6.5. In the presence of Chaps, pig REH activity was stimulated up to 1.7-fold by various non-ionic detergents. The ranking order of retinyl palmitate cleavage initiated by the stimuli was n-dodecylglucoside > octanoyl-N-methylglucamide > n-octyglucoside > n-dodecylmaltoside > Triton X-114 > Triton X-100. Porcine REH was effectively inhibited by alpha-tocopherol and bis-(4-nitrophenyl) phosphate [(Np)2P]. The structural, immunological and catalytic features, pH dependence, and the effect of (Np)2P on enzyme activity of pig REH are similar to those reported for the non-specific carboxylesterase ES-4. However, ES-4 differed from REH in molecular mass and the requirement of Chaps or Chaps-like detergents as cofactor. Judging from these results, pig REH may be a non-specific carboxylesterase isoform.

Amino Acid Sequence↗
PubMed1998

1,5-Disubstituted indazol-3-ols with anti-inflammatory activity.

A series of new indazol-3-ol derivatives was synthesized. Some of these compounds exhibit interesting anti-inflammatory activities in various models of inflammation. 5-Methoxy-1-[quinoline-2-yl-methoxy)-benzyl]-1H-indazol-3-ol (27) strongly inhibits the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid catalyzed by 5-lipoxygenase (IC50 = 44 nM). 27 also inhibits the contraction of sensitized guinea pig tracheal segments (IC50 = 2.9 microM). In guinea pigs treated with 27 (1 mg/kg i.p.) 2 h before antigen provocation, there was a marked inhibition (47%) of the antigen-induced airway eosinophilia. After topical application of 1 microgram/ear 27 inhibits the arachidonic acid induced mouse ear edema (41%).

Animals↗
PubMed1998

No predictive value of the micronucleus assay for patients with severe acute reaction of normal tissue after radiotherapy.

In approximately 5% of cancer patients undergoing radiotherapy, this treatment has to be interrupted because of an acute reaction of normal tissues. To test the possibility of predicting this type of reaction, the micronucleus assay was used to determine radiosensitivities of peripheral blood lymphocytes of 15 patients with severe acute reaction of normal tissue, 15 patients without this reaction and 15 healthy donors. Whole-blood cultures were irradiated with X-rays (4 Gy, 1.08 Gy/min) and treated with cytochalasin B. The micronuclei scores observed in irradiated cells were corrected for the scores in unirradiated cells. Intra-individual and interindividual variations in micronuclei scores were analysed in samples from healthy donors, and highly significant interindividual differences were found (P < 0.001). Scores of cells not irradiated in vitro were higher for cancer patients before radiotherapy than for healthy donors (P < 0.001), and those for cancer patients after radiotherapy were higher than for patients before radiotherapy (P < 0.001). Average micronuclei scores induced by in vitro irradiation were significantly higher in samples from cancer patients compared with those from healthy donors (P < 0.01). Moreover, all subgroups of cancer patients included individuals with very high levels of micronuclei after in vitro irradiation. There was, however, no relationship between the micronuclei scores and the occurrence of severe acute reactions in normal tissues.

Acute-Phase Reaction↗
PubMed1998

Peritoneal mononuclear cell differentiation and cytokine production in intermittent and continuous automated peritoneal dialysis.

The long period without dialysate exchanges in nightly intermittent peritoneal dialysis (NIPD; no peritoneal filling during the day) and continuous cyclic peritoneal dialysis (CCPD; peritoneal filling during the day) might lead to an improved repopulation and functional regeneration of peritoneal macrophages (PMOs). We investigated this issue in seven stable, noninfected CCPD patients and seven stable, noninfected NIPD patients. PMO differentiation and cytokine production were measured after automated peritoneal dialysis and after a 12- to 14-hour period without dialysate exchanges. PMO maturation was evaluated by antibody staining. The proportion of "young" monocytes (positive for 27E10 and RM3/1) was decreased, whereas the proportion of mature macrophages (positive for 25F9) was significantly increased after the exchange-free interval. No differences between NIPD and CCPD were observed. The cytokine response to lipopolysaccharide was significantly increased after the exchange-free interval in both NIPD and CCPD. The interleukin-1 receptor antagonist (IL-1Ra) content of PMO lysates significantly increased after the exchange-free interval in both groups, but no changes were found in dialysate and serum IL-1Ra. We conclude that the long daytime interval without dialysate exchanges allows for additional PMO differentiation. Furthermore, the potential for cytokine release, which is inhibited (possibly by dialysate effects) after automated peritoneal dialysis, is restored after a 12- to 14-hour interval without peritoneal dialysis exchanges. The "dry" day in NIPD seems to have no important additional positive effect compared with CCPD.

Adult↗
PubMed1998

Evaluation of expanded polytetrafluoroethylene as a soft-tissue filling substance: an analysis of design-related implant behavior using the porcine skin model.

Soft-tissue augmentation using the synthetic nonfluid biomaterial expanded polytetrafluoroethylene (ePTFE) has been supported by number of recent reports citing the favorable characteristics of biocompatibility, soft and natural feel, ease of use, and permanent augmentation. Concern has been expressed about this application for ePTFE material because of the proximity of the implants to the skin surface and potential problems with infection and extrusion. We evaluated the behavior of a series of specific ePTFE implant designs using a long-term subcutaneous augmentation model. By using a porcine model, 466 implants of ePTFE in the form of strips, rolls, or tubes were placed using a percutaneous insertion device subcutaneously over the dorsum and face. The animals were divided into three study groups by length of implantation (3 weeks, control; 6 months, intermediate term; and 12 months, long-term) and en-bloc tissue specimens, including skin, implants, and underlying soft tissue, were harvested for gross and histologic examination. Implants were removed at the earliest sign of infection, exposure, or extrusion and the difficulty of removal was ascertained and recorded. These data reveal that ePTFE material elicits acceptable levels of tissue activity with low extrusion rates over the short and long term supporting its use for soft-tissue augmentation. The data show a clear difference, however, in the host response and behavior of the implants for this application based on shape or design. A statistically significant difference in the low, but measurable, extrusion rates was observed amongst these implant designs. ePTFE tubes showed greater stability and predictable augmentation over other implant designs for soft-tissue augmentation and seem to represent a substantial improvement for this application.

Animals↗
PubMed1998

Peritonitis associated with vancomycin-resistant Lactobacillus rhamnosus in a continuous ambulatory peritoneal dialysis patient: organism identification, antibiotic therapy, and case report.

A case of Lactobacillus rhamnosus-associated peritonitis in a patient undergoing continuous ambulatory peritoneal dialysis is reported. The patient was treated with vancomycin after isolation of glycopeptide-susceptible coagulase-negative staphylococci. After a skin rash developed, vancomycin was discontinued and replaced with teicoplanin. Seven weeks after the glycopeptide therapy was discontinued, a Lactobacillus strain was isolated in pure cultures. The isolate was identified first incorrectly as L. acidophilus but later correctly as L. rhamnosus. Antibiotic susceptibility testing showed that the isolate was resistant to glycopeptides but susceptible to several other antibiotics. The antibiotic treatment was then switched to imipenem and was successful.

Anti-Bacterial Agents↗
PubMed1998

The role of magnesium in the generation and therapy of benign muscle cramps. Combined in-vivo/in-vitro studies on rat phrenic nerve-diaphragm preparations.

Rats received during 3 weeks a Mg-deficient or a Mg-rich diet; Mg-deficient animals revealed hypomagnesemia, cellular K-depletion and Ca-loading. Phrenic nerve-diaphragm preparations were studied; the physiological Tyrode solution contained low or high-Mg concentrations and 0 or 12 mmol lactate/L. Electric stimulation (indirect via the nerve or direct) produced tetanic contractions and increased force at increasing stimulation frequencies. Significantly lower frequencies were needed to elicit these effects when intra- and extracellular Mg levels were low, in comparison to plentiful Mg supply. Comparing unstimulated and stimulated diaphragmatic tissue electrolyte concentrations revealed tissue losses of Mg, K Ca from stimulated tissues which were less pronounced when Mg supply was optimal. These data support the empiric finding that relief from muscle cramps is promptly offered by Mg supplements.

Animals↗
PubMed1997

Unanticipated separations and normative re-attachments in later life: a personal account.

Unanticipated separations can have profound reverberations upon individual and family development. When these separations are at a young age the consequences tend to exert a long and lasting effect. This article presents a personal account of the abrupt separation from the author's parents, the trauma the family faced in Europe on the brink of war and how this impacted his family intergenerationally. It is suggested that loyalties and caregiving are dynamics which enable adult children to emotionally reconnect with their adult parents in later life. These renewed levels of attachments are normative in nature, enriching the family as a whole.

Acculturation↗