Tissue kallikreins of the guinea-pig.
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Biomedical subjects
Publications and source records attributed to G Mayer.
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The ability to distinguish relevance from irrelevance has been attributed to an attention-related mechanism and may be supposed to be disturbed in aging. The reaction to low electrical stimuli which causes neither pain nor escape behavior was investigated by means of a newly developed test in adult and aged rats. The animals' reaction was classified into two different responses depending on the intensity of the electrical stimuli. The first reaction related to sensitivity, the second reaction contained two components, an orienting response and a cognition-controlled type of discriminative behavior. There was no significant difference between the amperage values of the two reactions in adult rats. With respect to aged rats, the amperage values of both reactions are significantly increased as compared with the adult rats. The sensitivity reaction and the attention-related behaviors diverged considerably. These findings show very precisely that certain behavioral reactions may decline differently or even independently with age indicating different age-related changes in the underlying neuroanatomical systems of attention. The results demonstrate the sensitivity of the test used as a model for studying some types of attention-related mechanisms in the aging process. The use of a relatively simple test of animals' reactivity to sensory stimuli may reveal changes that are critical to understanding not only of the aging brain, but of different types of brain lesions and disorders, as well as of drug treatments.
Bacteriological investigations and endotoxin (ET) determinations were performed during a routine haemodialysis session for six patients. The glucose free dialysate was prepared with untreated tap water. All patients were dialysed for 5 h. Pseudomonas aeruginosa was regularly isolated in numbers up to 10(7) cfu ml-1 from samples of the dialysate inflow, the dialysate site and the dialysate outflow. ET levels in the plasma of the patients increased continuously during haemodialysis and were always higher in the blood outflow line of the dialyzer than in the blood inflow. Despite the high bacterial counts in the dialysate and the increasing ET levels in the patients plasma neither bacteraemia nor fever was observed. The former is due to the impermeability of the dialyzer membrane for bacteria, the latter is explained by low pyrogenicity of P. aeruginosa endotoxin. Inspection of the dialyzer machines revealed that air-traps and heater-unit for the incoming (untreated) tap water before mixing with the dialysate concentrate were the only sites where high bacterial release was feasible, as this part of the machine escaped disinfection due to the construction of these devices. We recommend the regular disinfection of all parts of a dialyzer machine, including heating units, air traps and valves.
1. In order to evaluate the influence of varying degrees of anaemia on exercise capacity and haemodynamic parameters, 13 patients on chronic intermittent haemodialysis with haemoglobin levels between 5.1 and 12.2 g/100 ml were subjected to an exhaustive exercise test. Measurements during bicycle ergometry consisted of O2 uptake at the anaerobic threshold and of maximum O2 uptake. Resting haemodynamic parameters such as cardiac index, heart rate, stroke volume index and blood pressure were assessed non-invasively in the 13 patients undergoing exercise and in an additional three patients. 2. O2 uptake at the anaerobic threshold as well as maximum peripheral O2 uptake were severely impaired and were positively correlated with haemoglobin concentration. The strongest correlation was found between the impairment of O2 uptake at maximum workload, as assessed by maximum O2 uptake/predicted maximum O2 uptake, and haemoglobin concentration. Haemodynamic alterations in the resting state consisted of a cardiac index in the upper normal range and did not correlate with the haemoglobin concentration. 3. We conclude from our study that exercise capacity in patients on chronic intermittent haemodialysis is severely impaired and that the impairment of aerobic and anaerobic capacity is significantly correlated with the severity of renal anaemia.
In earlier studies we have shown that partial correction of anemia by recombinant human erythropoietin (r-HuEPO) already after 12 weeks results in a significant increase of exercise capacity in patients on chronic hemodialysis. As causative effect increased oxygen availability with improved oxygen delivery to the tissues was assumed. To elucidate the long-term effects of a partial correction of anemia with r-HuEPO on exercise capacity, oxygen uptake at maximum exercise and at the anaerobic threshold was measured by repetitive spiroergometry. Measurements were done before, 3 months and 6 months after initiation of r-HuEPO therapy. The results are summarized below: (table; see text) Our results show that a long-term improvement of peripheral oxygen availability leads to a further increase of anaerobic threshold in patients on chronic hemodialysis even without a further increase of hemoglobin levels and without exercise training. It appears that elimination of the chronic hypoxic condition results in a restoration of previously diminished mitochondrial enzymes in muscle, particularly for aerobic glycolysis. Besides acute improvement of aerobic and anaerobic exercise capacity, the long-term administration of r-HuEPO with its increased anaerobic threshold enhances the patients' everyday life working capacity.
Patients on chronic hemodialysis with hyperlipidemia were found to respond either with decreased levels (responders) or with a further increase of the plasma triglyceride levels (nonresponders) to a carnitine substitution therapy. The aim of the present study was to find possible predictors to distinguish between responders and nonresponders prior to the initiation of therapy. Since it is suggested that erythrocytes are involved in carnitine transport to tissues, it was of interest to determine plasma and erythrocyte carnitine concentrations in the hemodialyzed patients before and during carnitine substitution therapy and to compare the results with those of healthy controls. Before therapy, comparatively lower plasma levels of both free and total carnitine, but higher portions of short-chain acylcarnitine on total carnitine were found in all patients. In erythrocytes, the nonresponders showed significantly higher total carnitine levels, compared to responders and controls. After the start of carnitine substitution, the increase of total plasma carnitine during the substitution period corresponded with the carnitine dose administered in responders, in nonresponders the highest carnitine values were found in the second week when the lower carnitine dose was administered. The changes of the plasma short-chain acylcarnitine levels with time were very similar to those of plasma triglycerides. All patients showed a time-delayed accumulation of carnitine in erythrocytes and, interestingly, markedly higher concentrations in the second week when the lower carnitine dose was administered. The results of the present study demonstrate that the erythrocyte carnitine content is a reliable predictor to distinguish between responders and nonresponders prior to the start of a carnitine substitution therapy.
Percutaneous transluminal angioplasty (PTA), a method combining diagnostic and therapeutic procedures, was studied prospectively in 40 patients with clinically failing a-v fistulae. Forty-seven procedures were performed in 40 patients with a variety of a-v fistulae (26 Cimino, five saphenous loops, five goretex grafts, and four upper-arm fistulae). In 43 cases the procedure was initially successful. The mean time of fistula patency after first PTA was 10.06 +/- 2.10 months. Primary failures were due either to technical inability to pass the stenosis (two patients) or to vessel perforation during the attempt (two patients). Surgical intervention had to follow both perforations. Restenosis at the dilatation site occurred in six patients, and in one a new stenosis at a different site occurred; the mean time of fistula patency in these patients was 5.8 months. Our results suggest that PTA is a highly effective therapy for the majority of cases of shunt stenosis. The success rate of the method is excellent and the complication rate low. The combination of this interventional approach with the mandatory angiographic procedure if stenosis of a fistula is suspected makes PTA a favourable first-line treatment and appears to save a considerable number of surgical interventions.
In order to evaluate the differences in morbidity and mortality of diabetics on haemodialysis (HD), data on 12 patients with diabetic nephropathy and 14 non-diabetic patients have been analyzed retrospectively since 1982. The groups were matched for sex, age and duration of HD. We analyzed the differences in survival rate, the number of hospitalization days and the causes of death. Values of BUN, creatinine, calcium, phosphate, cholesterol and triglycerides, alkaline phosphatase, erythrocyte count and haemoglobin were compared throughout the dialysis period. No significant differences occurred between the two groups as regards blood chemistry values (except for creatinine) throughout the observation period. The number of hospitalization days per month of dialysis was significantly different: 1.8 days in diabetic versus 0.9 days in non-diabetic patients (p less than 0.005). This difference is due to a higher rate of vascular access complications and infections. The 3-year survival rate on HD was 73% in type I diabetics (controls 93%), while none of the type II diabetics survived for more than 24 months on HD. The most common causes of death in the diabetic patients were cardiovascular (44%) and septic (44%) complications, followed by cerebrovascular problems (12%). We conclude from our study that the reason for the poor prognosis of diabetic patients on HD is not lack of efficiency of the procedure, but progression of the multisystemic diabetic condition.
This paper reports on experience in various methods of reconstructive and palliative surgery in 50 patients and discusses the problems of establishing a diagnosis. The clinical symptoms are decisive; the conclusive indication for surgery is the detection of a hemarthrosis. Persistent cartilaginous defects in chondral or osteochrondral fractures will lead to the development of secondary arthrosis of the knee joint. Therefore, we emphasize immediate surgical revision of the injured joint. The results obtained in this way are good, especially in younger patients.
To investigate the effect of partial correction of anemia in patients maintained by chronic intermittent hemodialysis on aerobic and anaerobic working capacity, eight patients underwent a bicycle spiro-ergometry before and after treatment with recombinant human erythropoietin (r-HuEPO). the initial mean (+/- SD) hemoglobin value was 5.9 mg/dl +/- 0.61 and increased during treatment to 10.9 +/- 0.59 mg/dl, P less than 0.0001). This partial correction of anemia resulted in a significant increase of both oxygen uptake at the anaerobic threshold and peak peripheral oxygen uptake at subjective exhaustion (P less than 0.01 and P less than 0.0002, respectively). The increase in oxygen uptake corresponded to significant increases in Watts, both at the anaerobic threshold and at maximum workload (P less than 0.02 and P less than 0.0004). These data show that partial correction of renal anemia results in a significant increase of both exercise capacity and maximum work.
The incidence and clinical relevance of cytomegalovirus (CMV) infection has been investigated in 120 consecutive renal allograft recipients receiving cyclosporin A and low-dose steroid (CsA/LDS) immunosuppression. Forty patients (33.3%) showed serological evidence of recent CMV infection; 21 patients (17%) developed clinically symptomatic infection. A seronegative recipient status and an aggressive additional immunosuppressive therapy were significant risk factors for the development of serological infection. There was, however, no difference with regard to these or any other relevant parameters (HLA matching; pretransplant history) between the symptomatic and asymptomatic group. Furthermore there was no influence of CMV infection, whether symptomatic or not, on graft outcome. During the study CMV infection prophylaxis consisted of single-shot CMV hyperimmunoglobulin in 72 patients immediately before grafting, recombinant interferon alpha 2 in 28 patients, and placebo in 20 patients. There was no beneficial effect of either interferon or hyperimmunoglobulin on the incidence and severity of CMV infection. However, steroid-resistant vascular rejections were much more common in the interferon group. We conclude that the incidence of CMV infection after kidney transplantation using CsA/LDS immunosuppression is lower when compared to kidney grafting with conventional immunosuppression. Prophylactic treatment with single-shot hyperimmunoglobulin is not effective, and recombinant interferon alpha 2 prophylaxis may even exert deleterious effects on graft survival by inducing steroid-resistant vascular rejection.
Since infections with Herpetoviridae after kidney transplantation still remain a major clinical problem, we conducted a double-blind, placebo-controlled trial using low-dose recombinant interferon-alpha-2C (rIFNa2C) prophylaxis in 50 renal graft recipients immunosuppressed with cyclosporine and methylprednisolone. Ten patients were excluded from further analysis because of graft loss due to surgical complications, side effects of rIFNa2C, and because of lack of compliance. There was a significant difference in graft loss due to irreversible rejections between the verum and the placebo group (6 vs. 0; P less than 0.05), whereas no difference was observed with regard to the occurrence of viral infections. We conclude, that low-dose rIFNa2C prophylaxis is harmful in renal allograft recipients treated with cyclosporine in view of the high incidence of irreversible transplant rejections without beneficial effects on the occurrence of viral infections.
beta 2-Microglobulin (beta 2m) has been identified as the major constituent of dialysis-related amyloid. Although there is no clear correlation between absolute beta 2m levels and amyloidosis-related symptoms, elevated serum levels are thought to be the basis for tissue deposition of beta 2m. Besides diminished renal excretion and insufficient removal during hemodialysis, a dialysis-related induction of beta 2m production is discussed as the major cause of elevated serum beta 2m levels. In order to evaluate the influence of hemodialysis membranes and the hemodialysis procedure on beta 2m levels we determined serum beta 2m levels in patients on chronic intermittent hemodialysis. Polymethylmethacrylate 2.0 m2, cuprophane and cellulose acetate dialyzers led to increasing beta 2m levels during dialysis, which was in excess of what could be accounted for by hemoconcentration. The polymethylmethacrylate 1.6 m2 dialyzer did not result in a significant rise of beta 2m levels during dialysis. This indicates that production of beta 2m is not only dependent on the membrane material but also on the surface area of the dialyzer. The use of polysulfone and hemophane low-flux dialyzers did not induce an increase in beta 2m levels during dialysis but a significant clearance of beta 2m was not demonstrable either. Volume-controlled dialysis with high-flux membranes (polysulfone 0.65 m2 and polysulfone 1.25 m2) lowered beta 2m; clearance values, however, were significantly higher when these dialyzers were used in a hemodiafiltration procedure. We conclude from our study that some dialysis membranes appear to induce beta 2m production, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS)
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