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F Saudek

Publications and source records attributed to F Saudek.

At least 55 records · Page 3Linked to original sources
PubMed1995

The effect of combination therapy with cyclosporine A and hydrocortisone on glucose metabolism in diabetic rats following pancreatic islet transplantation.

Glucose tolerance, insulin secretion and in vitro insulin action were examined in streptozotocin-induced diabetic rats following pancreatic islet allotransplantation treated with combination of oral cyclosporine A (10 mg/kg) and hydrocortisone (1.5 mg/kg) intramuscularly. 1400 pure islets from multiple donors were implanted either into the portal vein (n = 10) or under the renal capsule (n = 11). Ten sham-operated non-diabetic animals receiving the same immunosuppressive therapy, 8 healthy animals without any treatment and 10 diabetic animals without immunosuppression following islet transplantation were used as controls. In all transplanted animals blood glucose was normalized by day 3 after transplantation with lower levels in those transplanted intraportally (p < 0.05). Non-immunosuppressed animals rejected the graft after 6.5 +/- 1.2 days after transplantation, immunosuppressed animals in both groups remained normoglycaemic till the end of the experiment on day 28. Oral glucose tolerance tests and insulin levels on days 10 and 28 improved dramatically. No differences in glucose and insulin levels between intraportal and subcapsular groups were found. Post-load glucose levels in immunosuppressed non-transplanted animals were higher on day 28 than before treatment and were also higher than in the healthy non-treated group (p < 0.05). In vitro insulin action determined by the incorporation of labelled glucose into adipose tissue was impaired only in animals in which islets were transplanted into the liver (p < 0.05 vs other groups). In conclusion, therapy with cyclosporine A and hydrocortisone prevents allogeneic islet rejection in rats during a short-term experiment. Although glucose tolerance is not completely normalized following transplantation, slight impairment is also demonstrable in healthy animals on the same drug therapy.

Animals↗
PubMed1994

[Insulin resistance and insulin secretion in type II non-obese diabetics].

BACKGROUND: Glucose tolerance depends essentially on insulin secretion and its action in target tissues. Diabetes mellitus type II (insulin-nondependent diabetes) is a disease conditioned by a dysbalance between insulin secretion and effect; it has not been decided whether the cause is insulin resistance or impaired insulin secretion, although a defect of insulin secretion for the manifestation of the disease is generally accepted. The purpose of the submitted study was to assess to what extent insulin secretion and its effect after an oral glucose load and a hyperglycaemic clamp is affected in different groups of non-obese patients with diabetes type II. METHODS AND RESULTS: The authors examined 21 men with diabetes type II (age 41 +/- 2.6 years, BMI 26.2 +/- 3.2, HbA1,c 9.4 +/- 2.9%) in the course of one year after detection of the disease, treated by diet alone. The second group was formed by 20 patients with diabetes type II (age 46.1 +/- 3.6 years, BMI 26.0 +/- 2.1, HbA1,c 6.94 +/- 1.6%) who suffered from diabetes for 5-10 years and who were treated by diet alone. The third group was formed by 32 diabetics type II (age 51.8 +/- 6.1 years, BMI 26.7 +/- 2.2, HbA1,c 8.7 1.2% +/-) who suffered from diabetes for 5-10 years and were treated with oral antidiabetics. The control group was formed by 42 healthy men matched for body weight and age (age 39.9 years, BMI 25.3, blood sugar level 4.8 mmol/l). Although the diabetic groups did not differ in the fasting blood sugar level (8.0-8.29-8.2 mmol/l), the glycosylated haemoglobin HbA1,c level is lowest in the group of diabetics treated by diet alone, similarly as the rise of the blood sugar level 120 mins, following oral administration of 75 g of glucose (10.3 mmol/l, as compared with 16.2 mmol/l and 15.5 mmol/l in the other groups). The authors found in all groups of diabetic patients, as compared with controls, a comparable drop of the insulin effect evaluated as the metabolic glucose clearance during an hyperinsulinaemic euglycaemic (5 mmol/l) or isoglycaemic (fasting blood sugar level) clamp, the insulin level being 75 microU/ml (controls 10.9 +/- 3.3 ml/kg.min., first group 5.35 +/- 2.7 ml/kg.min., second group 5.47 +/- 2.35 ml/kg.min., third group 5.38 +/- 2.1 ml/kg.min. The differences, as compared with controls, were significant in all groups, p < 0.01). At an insulin level of 1500 microU/ml the results are similar (controls 17.4 +/- 3.8 ml/kg.min., as compared with 13.3 +/- 3.3 in the first group, 13.3 +/- 3.0 in the second group and 12.5 +/- 3.0 ml/kg.min. in the third group: statistical significance in all three groups, as compared with controls, is p < 0.05). The authors did not reveal any differences in the specific insulin bond to insulin receptors of erythrocytes. The total glucose consumption during an isoglycaemic clamp in diabetics and a euglycaemic clamp in controls did not differ. In all diabetic groups, as compared with controls, higher C peptide values and insulin values (IRI) were found on fasting and a slower rise and longer persistence of higher levels after oral glucose administration, although an inadequate secretory response during the hyperglycaemic clamp in diabetics is apparent. Hyperinsulinism was significantly higher in the second group. The number of insulin receptors on erythrocytes, the affinity for insulin, regardless whether the receptors were free or occupied, did not differ significantly between groups. CONCLUSIONS: All investigated groups of type II diabetics had a comparable degree of insulin resistance which did not depend on the duration of diabetes, its compensation or the type of treatment. Although impaired insulin action was proved, the total glucose utilization in relation to hyperglycaemia is not reduced. The differences in the degree of glucose intolerance in the investigated groups of diabetics type II depend on the degree of impairment of insulin secretion.

Body Weight↗
PubMed1994

[Therapy in kidney transplant rejection using murine monoclonal IgG2a A1CD3 (Cedetrin)].

BACKGROUND: One of the substances used in recent years to suppress immune reactions after organ and tissue transplantations is mouse IgG2a globulin which acts selectively on CD3 lymphocytes; it is known under the name of Orthoclone (Ortho Co.) An analogous preparation was developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, although the idiotype is different. The authors submit a report on the experience with treatment of rejection of transplanted kidneys. METHODS RESULTS: Monoclonal mouse globulin IgG2a (Cedetrin) was administered to 20 patients after renal transplantation on account of a rejection episode or progressing rejection; the mean interval after transplantation was 16.1 (range 0.25-96) months; the rejection episode or progressing rejection responded little in the majority of patients to 6-alpha-methyl prednisolone (Urbason, Hoechst, Solu-Medrol, Upjohn). For prophylactic immunosuppression the following combinations were used: cyclosporin + azathioprine + prednisone (17x) or azathioprine + prednisone (3x). Cedetrin was administered by the i.v. route in two to 11 doses a 3 mg substance. Of 20 patients in 6 Cedetrin administration had to be discontinued (allergy, infection, leucopenia, hyperhydration). In 14 the tolerance was satisfactory, the type and frequency of side-effects was similar as after Orthoclone; the antibody formation was less frequent. The specificity of Cedetrin as regards its action on T lymphocytes was confirmed. The effect was good to very good in 6 of 8 patients where the rejection filtrate was histologically active. In 9 patients treated during the first year after renal transplantation the cumulative survival of the graft at the end of the 12th, 24th and 36th month following transplantation was 89%, 67% and 56% resp. Because the therapeutic effect depended on histologically proved rejection activity, the authors consider biopsy of the graft before Cedetrin treatment essential. CONCLUSIONS: The therapeutic administration of monoclonal mouse globulin IgG2a A1CD3 (Cedetrin), developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, produced by Exbio Co., CR) has a favourable effect on rejection episodes or progressing rejection of transplanted kidneys. Treatment is indicated in confirmed histologically active rejection.

Adult↗
PubMed1991

Insulin action and insulin binding following pancreas transplantation.

Insulin action and insulin specific binding to erythrocytes were examined in ten recipients of a pancreatic segment and renal graft (Group 1), in nine non-diabetic kidney recipients (Group 2) and in ten age- and weight-matched healthy control subjects (Group 3). All transplant recipients were normoglycaemic without need of insulin, received the same immunosuppression and had good renal graft function at 11-18 months post-transplantation, when the investigation was performed. Using the insulin clamp technique, insulin action was expressed as the metabolic clearance rate of glucose at insulin infusion rates of 1.0 (MCRsubmax) and 10.0 (MCRmax) mU.kg-1.min-1. In comparison with the healthy control subjects, fasting free insulin and C-peptide levels were significantly higher in Groups 1 and 2, but no differences between Groups 1 and 2 were found (p greater than 0.05). Mean values +/- SEM of MCRsubmax in Groups 1, 2 and 3 were 6.30 +/- 0.55, 6.09 +/- 0.69 and 10.52 +/- 1.10 ml.kg-1.min-1 respectively, and of MCRmax 12.65 +/- 0.78, 13.14 +/- 0.92 and 19.28 +/- 1.42 ml.kg-1.min-1 respectively. Insulin action was significantly decreased in Groups 1 and 2 at the low as well as the high insulin infusion rates but there was no difference between the two groups of recipients (p greater than 0.05). No differences in binding data (specific binding, number of binding sites per cell) were found. It is concluded that insulin resistance is common to all immunosuppressed organ recipient and is not related to the pancreas graft. The decrease maximal response to insulin and normal insulin binding to erythrocytes tend to suggest a post-receptor defect in insulin action.

Adult↗
PubMed1991

Arteriolosclerosis of the human renal allograft: morphology, origin, life history and relationship to cyclosporine therapy.

In the decade 1979-1988, 658 biopsies were collected from 568 cadaveric renal allografts. In 118 grafts a non-proliferative insudative vasculopathy (IVA) was found in afferent vessels. Immunosuppression was based on azathioprine (AZA) or on cyclosporin A (CsA), from 1983. The prevalence and extent of IVA has increased significantly since 1984. Light microscopy showed fibrinoid and hyaline masses of varying extent; transmural insudative "knobs", intimal oedema with metachromasia, and microthrombosis were also seen with CsA. The ultrastructure of the insudates was unremarkable but CsA grafts displayed early oedema and hypergranulation of endothelial cells with a disarray of smooth muscle cell (SMC) microfibrils, and pronounced degenerative changes of SMC. Rebiopsy showed stationary IVA in AZA grafts and progression in one-half of CsA-treated patients. Nephrectomy specimens revealed, however, a marked predominance of late rejection endarteritis; in only 3 cases was IVA and/or microthrombosis the possible cause of nephrectomy. The mean donor age was higher in severe IVA in CsA grafts and the mean post-transplantation interval at the time of diagnosis of IVA was significantly shorter in CsA-treated patients. No important differences in cumulative graft survival were seen between grafts with absent, moderate or severe IVA. Unused cadaveric donors' kidneys of comparable age exhibited normal arterioles or a slight focal insudative or hyaline lesion.

Arteries↗
PubMed1990

[The effect of a combined transplantation of the pancreas and kidney on the course of peripheral diabetic neuropathy].

Sixteen type I diabetics were followed up from the neurological aspect and by electromyography for 6 to 42 months following successful combined transplantation of the pancreas and kidney. Before transplantation all patients suffered from medium severe to severe peripheral polyneuropathy, grade 3-5 according to the commonly used quantitative classification. All patients reported after transplantation subjective improvement, e.g. of the muscular strength or steadiness of gait. In six patients the clinical and in eight patients the electromyographic finding improved by one grade, in four patients at least the conductivity in the nerves of the upper extremities improved. In four patients the neurological and electromyographic finding did not change; none of the patients after successful transplantation deteriorated. The authors discuss the favourable effect not only of elimination of the uraemic syndrome, but also the effect of the improved carbohydrate metabolism on regenerating processes in the peripheral nervous system.

Adult↗
PubMed1990

[Effectiveness of replacement of renal function in diabetics].

The authors compared the survival of four groups of patients and of renal grafts: 1. diabetics after renal transplantation (24 subjects), 2. diabetics after transplantation of the kidney and pancreas (35 subjects), 3. diabetics where transplantation was indicated but who were treated only by dialysis and 4. non-diabetics after transplantation of the kidney (170 subjects). The two-year cumulative survival of the entire group of diabetics regardless of the type of treatment was 59%. The two-year survival of diabetics after transplantation of the kidney alone was 95%, after transplantation of the kidney and pancreas 70% and in non-diabetics after transplantation of the kidney 90%. In diabetics treated by dialysis it was 33%. The two-year survival of the function of renal grafts in the entire group of diabetics treated by transplantation of the kidney was 61%, in non-diabetics 68% and the three-year survival was in both groups 61%. As compared with the EDTA register, the results of transplantation treatment are favourable, the results of dialyzation treatment are poor. From the results the authors draw conclusions for indication of different ways of replacement of renal function in diabetics in relation to the general health status of the patients.

Adult↗
PubMed1990

Transplantation of the kidneys in diabetics.

Diabetic nephropathy affects half the type 1 diabetics and is the most frequent cause of death there. While in some countries diabetics account for 25-30% of all patients newly admitted in dialysis and transplantation programmes, in Czechoslovakia the number of diabetics treated by dialysis or transplantation is small. From August 1985 to June 1988, 15 isolated kidney transplant operations were performed on 13 diabetics with serious late complications of diabetes. By the time of writing, all recipients had been surviving (for 1 up to 35 months), and only two were receiving artificial kidney treatment. Progressive vascular complications were in two cases the cause of gangrene of the lower extremity, one patient had a central cerebrovascular attack. Despite this, successful transplantation resulted in a marked improvement of the patients' general condition and quality of life. Due to intensified insulin therapy, diabetes, too, was satisfactorily compensated in the majority of the recipients. As experience so far indicates, if the patient is prepared in good time, which includes diabetological, nephrological and ophthalmological treatment, the results of transplantation in diabetics can be comparable to those achieved in non-diabetic patients. Renal transplantation in diabetics should be developed in all transplantation centres in Czechoslovakia, and uraemic diabetics should not be eliminated from the dialysis-transplantation programme except in cases of serious contraindication.

Adult↗
PubMed1989

[Kidney transplantation in diabetics].

Diabetic nephropathy affects half the type I diabetics and is their most frequent cause of death. While in some countries diabetics account for 25-30% of all newly admitted patients in dialyzation-transplantation programmes, in the CSSR the number of diabetic patients treated by dialyzation or transplantation is small. From August 1985 to June 1988 in the Institute of Clinical and Experimental Medicine a total of 15 isolated transplantations of the kidneys were made in 13 diabetics with serious late complications of diabetes. At present all recipients survive (1-35 months) and only two are treated by an artificial kidney. Progressing vascular complications were in two instances the cause of gangrene of the lower extremity, one recipient had a central cerebrovascular attack. Despite this, successful transplantation caused a marked improvement of the general condition and quality of life. The compensation of diabetes was also, due to intensified insulin therapy, satisfactory in the majority of recipients. Hitherto assembled experience indicates that when the patient is prepared in time, which includes diabetological, nephrological and opthalmological treatment, the results of transplantation treatment in diabetic patients can be comparable with results in should be developed in all transplantation centres in the CSSR and uraemic diabetics should be eliminated from the dialyzation transplantation programme only in case of fundamental contraindications.

Adult↗
PubMed1989

Insulin-pump treatment of pancreas-graft rejection.

Continuous subcutaneous insulin infusion (CSII) was combined with antirejection therapy in four diabetic recipients of pancreas and kidney grafts with persisting hyperglycemia due to pancreas rejection. In three of the patients, full function of the pancreas was restored after as many as 40, 86, and 139 days of CSII. In another patient, the dose of insulin was halved, and his graft function was classified as partial. Pancreas rejection treated without CSII was reversible only in one of four other recipients. We conclude that restoration of the function of a pancreas graft damaged by rejection can be achieved even after a long period with the help of CSII therapy.

Adult↗
PubMed1989

[Is the prognosis of pars plana vitrectomy in diabetic retinopathy dependent on the general status of the diabetic?].

Results of pars plana vitrectomy (PPV) were compared in two groups of patients. The first group was formed from 105 eyes of 87 diabetics without clinical signs of the diabetic nephropathy or nephropathy without decrease of renal functions. The other group was formed from 64 eyes of 50 diabetics suffering from diabetic nephropathy in the stage of the renal insufficiency. In the first group PPV was successful during the mean observatory period of 26 months, in 59 from 105 eyes (56%) and the mean visual acuity was 0.12. In the second group PPV was successful, during the mean observatory period of 18 months, in 34 from 64 eyes (53%) and the mean visual acuity was 0.09. Number of the successfully treated PPV was steadily decreasing according to the prolonged period of the further observations, in both mentioned groups: from 85 (81%) after 3 months on 62 (41%) after the interval of 3 years. The mean visual acuity in both followed groups was, with respect to the length of observation, moderately increased. Diabetic nephropathy in the stage of the renal insufficiency was without negative effect on the prognosis of PPV in complicated diabetic retinopathy. The more advanced organ complications of diabetes were not evaluated as contraindications of PPV and the operation may significantly improve the quality of the life of an otherwise heavily ill diabetic patient.

Adult↗
PubMed1989

Cefoperazone pharmacokinetics in patients with liver cirrhosis: a predictive value of the ujoviridin test.

Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers and in 11 patients with liver cirrhosis. In the same persons, we also examined the clearance of ujoviridin--a preparation of indocyanine green. Within 12 h, 31.8 (+/- 7.6)% of the 2 g dose of cefoperazone was eliminated in the urine of healthy persons and 74.3 (+/- 7.9)% (mean +/- SD) was eliminated in the urine of cirrhotics. The biological half-life (beta-phase) of cefoperazone in healthy volunteers and in cirrhotics was 1.77 (+/- 0.25) and 4.29 (+/- 1.16) h, total clearance 1.009 (+/- 0.187) and 0.583 (+/- 0.169) ml/s and hepatic clearance 0.694 (+/- 0.174) and 0.152 (+/- 0.079) ml/s, respectively. The differences are statistically significant (p less than 0.001). We also found good correlation between total clearance of cefoperazone and clearance of ujoviridin (r = 0.842) and even better between hepatic clearance of cefoperazone and ujoviridin clearance (r = 0.957), both statistically significant. The findings suggest that the dosage of cefoperazone should be reduced in patients with liver cirrhosis and that the ujoviridin clearance test is a good indicator of impaired cefoperazone elimination.

Adult↗
PubMed1987

Preparation and implementation of pancreas transplantation programme in diabetic patients.

Having reviewed the state-of-the art trends in pancreas transplantation over the world, the authors describe their own experimental studies preceding elaboration of the technique of pancreatic segment transplantation with duct obliteration. In their technique, the splenic artery is interposed in the course of the iliac arteries of the recipient. The procedure of the selection of diabetic patients suitable for a combined pancreas and kidney transplantation is presented. The results in 13 recipients with insulin-dependent diabetes and progressed organ complications are evaluated. In these patients a combined pancreas and kidney transplantation is of a better prognosis compared with the conventional treatment methods.

Adult↗
PubMed1986

Pharmacokinetics of cefoperazone in healthy volunteers.

Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers following 15 min intravenous infusion of 2 g. Cefoperazone levels in the blood serum and in the urine were determined microbiologically. At the end of the infusion, mean serum concentrations of the antibiotic were 340.4 (+/- 81.5) mg/l, at the 4th hour after the infusion 38.4 (+/- 10.3) mg/l, and 12 hours after the infusion all subjects had detectable concentrations with the mean value 2.2 (+/- 0.7) mg/l. Within 12 hours, 33.3 (+/- 6.1) % of the total dose of cefoperazone had been eliminated in the urine. The fitting of the individual serum concentration curves and the determination of pharmacokinetic constants were done according to a two-compartment model with the aid of nonlinear least-squares regression analysis on a programmable calculator TI 59. The mean value of the biological half-life (beta phase) of cefoperazone was 1.77 (+/- 0.25) h, mean serum clearance was 61.7 (+/- 12.1) ml/min and the mean distribution volume (Vd area) was 9.44 (+/- 2.2) 1. Our data are in agreement with those previously reported in the literature. The only exception is the distribution volume, which we found to be smaller.

Adolescent↗