Search PubMed⌕ Search

Biomedical subjects

G Thiel

Publications and source records attributed to G Thiel.

At least 217 records · Page 12Linked to original sources
PubMed1986

Effect of cyclosporine A on ischemic renal failure in the rat.

The influence of cyclosporine A on renal function was investigated in unilaterally nephrectomized rats subjected to 30 or 45 min of ischemia. Acute i.v. administration of high dose CyA equivalent to 1000 mg/kg/d, did not produce a decrease in glomerular filtration or renal blood flow within 2 hours and its influence on proximal tubular pressure could be attributed to the cremophor vehicle. Chronic oral administration of 20 mg/kg/d CyA after ischemia produced no alteration in renal function after 2 or 9 days, but 40 mg/kg/d CyA lowered renal function demonstrably by 9 days. When pair-fed to eliminate CyA-induced weight loss as a cause of depressed renal function, the loss of renal function after 9 days was smaller but still evident. At this time renal cortical prostaglandin E2 and thromboxane B2 production were also reduced, but plasma renin remained unaltered because of the exclusion of volume depletion through weight loss. These kidneys showed no signs of delayed regeneration from ischemic renal injury but did show signs of tubulotoxicity, which seemed to be more apparent after longer periods of ischemia.

Acute Kidney Injury↗
PubMed1986

Morphology of cyclosporine nephrotoxicity in the rat.

Cyclosporine (CSA) nephrotoxicity was investigated in the rat. Morphologically, CSA nephrotoxicity is characterized by the following features: (a) Tubular inclusion bodies (TIB) corresponding to autolysosomes and giant mitochondria; (b) tubular vacuolization (TV) due to dilatation of the endoplasmatic reticulum; (c) tubular microcalcification (TM); and (d) tubular regeneration (TR). The morphologic features are limited to (a and b) or predominate (c and d) in the proximal tubule. CSA tubulopathy as defined above is dose dependent, independent of the route of a drug administration, develops quickly (within a week), is reversible after CSA withdrawal, is more pronounced in male than in female rats and shows no clear cut differences in various rat strains. Body weight shows a dose dependent reduction. The functional changes are usually slight. No significant correlation exists between functional changes and morphologic lesions. The type of CSA nephrotoxicity in the rat is very similar to CSA-tubulopathy in man but associated with less severe functional changes.

Animals↗
PubMed1986

Acutely impaired renal function during intravenous administration of cyclosporine A: a cremophore side-effect.

The parenteral application of a cyclosporine A (CyA)-containing solution in high doses, 0.7 mg/kg/min, was associated with an acute reduction in renal blood-flow and a depression in creatinine clearance to approximately one half of control values. Exactly the same effect can be produced by the intravenous administration of the vehicle, cremophore, a polyoxyethylated castor-oil derivative. Although these observations are not of great clinical importance, since the doses of CyA used in man are much lower and the drug is generally taken orally, they are of considerable importance when studying the effects of CyA under experimental conditions. For the purpose of examining the influence of CyA on renal function, cremophore-containing solutions should be avoided.

Animals↗
PubMed1986

The potassium content of heart muscle following cyclosporine.

The potassium content of cardiac muscle was examined after 9 or 22 days of cyclosporine A administration in normal rats and rats exposed to either renovascular, Goldblatt hypertension or renal ischemia. Cyclosporine A did not result in any alteration in cardiac muscle potassium compared to untreated rats in either group, even though the animals which had been subjected to renal ischemia and cyclosporine A plasma potassium was raised compared to animals subjected just to renal ischemia. The potassium content of cardiac muscle, however, was found to be raised in the hypertrophic hearts of the Goldblatt, renovascular hypertensive animals, both with and without cyclosporine.

Animals↗
PubMed1985

Regulation of protein kinases in exocrine secretory cells during agonist-induced exocytosis.

Stimulation of exocytosis in exocrine glands is associated with an increased phosphorylation of several particulate proteins. Irrespective of the type of secretagogue (cAMP-dependent agonists, calcium-dependent agonists, calcium ionophores, phorbol esters) exocytosis is always accompanied by an enhanced phosphorylation of the ribosomal protein S6. It is shown by an analysis of the phosphopeptide pattern of the in vivo and the in vitro phosphorylated S6 protein that the protein kinase responsible for phosphorylation of the S6 protein during enhanced exocytosis is protein kinase C. This is so irrespective of whether the agonist uses cAMP or calcium as second messenger. Experiments with isolated guinea pig parotid gland lobules reveal that not only the acetylcholine analog carbamoylcholine, but also the beta-agonist isoproterenol lead within seconds to an increased formation of diacylglycerol. As diacylglycerol increases the affinity of protein kinase C for calcium this finding would explain why the phosphorylation pattern of the S6 protein reflects activation of protein kinase C also under conditions where (as in the case of stimulation with beta-agonists) cAMP is the primary second messenger. It would further explain why the changes of the phosphorylation of individual histones observed during agonist-induced exocytosis in the parotid gland are quite similar for isoproterenol on one hand and carbamoylcholine on the other. A 22 K protein which becomes phosphorylated only when cAMP serves as second messenger is located in the membrane of the endoplasmic reticulum. A possible relationship of this protein with the calcium transport ATPase of the endoplasmic reticulum is under investigation.

Animals↗
PubMed1985

Renal mercury content in HgCl2-induced acute renal failure in furosemide/saline-protected and nonprotected rats.

Renal mercury content, urinary mercury excretion and renal function were studied in rats with acute renal failure (ARF) induced by subcutaneous injection of 2, 3, 6, or 10 mg/kg HgCl2. Similarly poisoned rats were protected against ARF by continuous intravenous infusion of furosemide and saline. Excellent protection was obtained in rats receiving 2,3, and 6 mg/kg HgCl2, whilst some animals developed moderate azotemia after 10 mg/kg HgCl2. Renal mercury content 48 h after HgCl2 injection did not differ appreciably between protected and nonprotected groups of rats and showed no relation to the dose of HgCl2 injected or to the degree of renal failure. Urinary Hg excretion was variable during the first 24 h after HgCl2 injection and tended to be higher with higher dosage unless the animals became anuric early on. Hg excretion during the second 24 h was independent of dosage, but was comparatively high in functionally well protected rats and low in oliguric animals with severe renal failure. Attempts at detoxication with the potent chelating agent complexon I after 6 mg/kg HgCl2 failed completely: Renal mercury content was similar to that in the other groups of rats and every single rat so treated developed severe anuric renal failure. Although dose-dependent functional injury after HgCl2 may be related to the amount of Hg reaching the kidney during the initial phase, we have to conclude that HgCl2 toxicity is unrelated to the amount of Hg found in renal tissue at 48 h. Furthermore, furosemide/saline protection does not act through increasing urinary Hg excretion or decreasing the amount of toxin accumulating in renal tissue.

Acute Kidney Injury↗
PubMed1984

[Tumors and kidney transplantation].

Incidence and type of de novo tumours were studied retrospectively in 187 consecutive patients who had received kidney transplants between 1967 and 1981 and undergone immunosuppressive therapy for 2 months or longer. Up to the end of June 1983, 18 patients (9.6%) had developed 22 malignancies and 7 of them had died from the tumour. The risk of developing a malignancy appeared to increase with prolonged immunosuppression. No significant difference was noted between patients with and without tumours regarding primary renal disease, duration of pretransplant dialysis, and type or total dose of immunosuppressive drugs. The risk of developing any malignancy appeared to be some 20 times that in the general population. The practical management of patients with de novo tumours is described in the light of our own patient material and the recent literature. Finally, two further oncological problems are discussed: first, the incidental grafting of malignant cells with the transplant, and second, how to proceed in a transplant candidate with a previous malignancy.

Adult↗
PubMed1984

[Criteria for hemostasis in kidney transplant patients. Comparison of patients undergoing immunosuppression with cyclosporin and azathioprine steroids].

Studies on one-year function conducted by the European Multicenter Trial showed that, after renal allograft transplantation, bleeding complications were only found in patients treated with cyclosporin as compared with those treated with azathioprin/steroids. To investigate a possible relationship between the bleeding tendency and the cyclosporin treatment, 18 parameters of hemostasis were studied in 11 patients, 6 of whom received cyclosporin A and the other 5 conventional treatment with azathioprin/steroids. Bleeding tendency could not be related to any specific coagulation parameter. Of interest is that clot retraction was significantly lower in the cyclosporin group (88 +/- 9% vs. 125 +/- 10%). Considering the fact that the skin bleeding time according to Ivy was normal in all patients, the clinical significance of the lower levels of the clot retraction appears to be minor. Discriminant analysis showed that these significantly lower clot retraction values could not be related to the lower platelet count levels in platelet rich plasma (205 000 +/- 85 000/mm3 vs. 280 000 +/- 67 000/mm3) but were associated with cyclosporin A treatment. All factor-VIII related activities were elevated in both groups. The main difference between the cyclosporin group and the conventionally treated group was significantly elevated levels of factor VIII procoagulant antigen (VIII: CAg) (cyclosporin A treated group: VIII: CAg 435 +/- 145%, conventionally treated group: VIII: CAg 215 +/- 99%). These results suggest hypercoagulability rather than bleeding tendency under cyclosporin treatment.

Adult↗
PubMed1984

Cyclosporine alone or in combination with prednisone in cadaveric renal transplantation.

One hundred recipients of first cadaveric kidney transplants were treated with three different immunosuppressive regimens: (1) conventional immunosuppression, (2) CsA alone, and (3) low-dose CsA in combination with low-dose prednisone, with rapid adjustment to give CsA whole blood trough levels of 300 to 800 ng/mL. One-year graft survival in the aza + pred group was 76%, and in the CsA alone group 75%. Graft survival at two and six months in the CsA-pred group was 94%. The dose of CsA in the CsA-pred group in the first two months posttransplant was only about half that given to the CsA-alone group. Surprisingly, the reduction in the CsA dose also reduced the number of methylprednisolone pulses given for treating rejection by greater than 50%. The incidence of nephrotoxicity and extrarenal side effects also fell considerably. Withdrawal of prednisone in the CsA-pred group after five months led to reversible rejection in two cases. In conclusion, (1) the rapid reduction in the CsA dosage is beneficial and has no drawbacks, and (2) our guidelines for withdrawing prednisone (timing of withdrawal, rate of reduction in dosage) still need further refinement.

Adult↗
PubMed1983

Cyclosporin A used alone or in combination with low-dose steroids in cadaveric renal transplantation.

The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15-28 months posttransplant, mean serum creatinine levels have remained stable at 175 mumol/l in the CyA group. The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p less than 0.001). The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300-800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0 +/- 0.5 mg/kg/d compared with an average daily dose of 11.4 +/- 0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174 +/- 14 as compared with 289 +/- 31 mumol/l) (p less than 0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month. We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.

Azathioprine↗
PubMed1983

Chronic interstitial nephritis in Whipple's disease.

Report is given on a 68-year-old man who suffered primarily from progressive weight loss and repeated episodes of fever and arthralgia. Later, liver dysfunction and renal insufficiency developed. Liver and kidney biopsies disclosed granulomatous hepatitis and nephritis. Because of the morphologic and clinical findings, the diagnosis of Boeck's disease was made. Shortly before death, diarrhea developed. Autopsy revealed a massive systemic involvement in Whipple's disease proven by light and electron microscopy and immunofluorescence. Tuberculoid and epitheloid cell granulomas and isolated giant cells were found in addition to the biopsy findings in skeleton muscles, the small intestine, lymphnodes and bronchi. At autopsy, the kidney showed chronic interstitial nephritis. The literature of kidney involvement in Whipple's disease is reviewed. This is the first case with granulomatous interstitial nephritis and chronic renal insufficiency in an inadequately treated Whipple's disease.

Aged↗