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Biomedical subjects

G Thiel

Publications and source records attributed to G Thiel.

At least 235 records · Page 13Linked to original sources
PubMed1983

Intravenous cyclosporine kinetics in renal failure.

Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA] up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t 1/2 alpha 0.10 +/- 0.03 hr), followed by a biphasic elimination phase with corresponding t 1/2s of 1.08 +/- 0.25 hr (t 1/2 beta) and 15.8 +/- 8.4 hr (t 1/2 gamma). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 +/- 0.48 l/kg (volume of the central compartment) and 3.49 +/- 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 +/- 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross-reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required.

Chromatography, High Pressure Liquid↗
PubMed1983

Withdrawal of azathioprine in renal transplant patients with chronic active hepatitis: is it wise or not?

Withdrawal of azathioprine in renal transplant recipients with chronic active hepatitis and persisting HBs antigenemia was recommended for its beneficial effect on the course of liver disease. We report here three cases in which azathioprine treatment was stopped for this reason. One of these patients lost his graft due to irreversible vascular rejection 6 years after successful transplantation. Decrease of graft function paralleled azathioprine withdrawal in a second patient. Data from other reports indicate that cessation of azathioprine treatment may be followed by decreased graft function or even graft loss. We conclude that the risk of altered graft function is substantial and this is too high a price to pay for a procedure that may not prevent chronic active hepatitis from progressing cirrhosis.

Azathioprine↗
PubMed1983

The role of tubuloglomerular feedback in acute impairment of renal function in obstructive jaundice.

Acute renal functional impairment not infrequently accompanies liver dysfunction and, particularly with bile duct obstruction, may be extremely severe. Recent studies suggest that tubuloglomerular feedback (TGF) activated by circulating non-electrolyte factors which occur during liver dysfunction may contribute to the intense renal vasoconstriction thought to be central to the functional renal impairment. In this study, serum from two patients with obstructive jaundice (OJ) and renal impairment, and from rats with OJ due to bile duct ligation were either dialysed or treated with furosemide, known to block electrolyte-mediated TGF. These sera, when perfused into loops of Henle in rat nephrons, induced a significant fall of 28% in stop-flow pressure, an indirect measure of glomerular capillary pressure thus implying arteriolar vasoconstriction. These findings are consistent with the hypothesis that circulating, non-electrolyte factors, which stimulate TGF, occur in cases of obstructive jaundice and that these may contribute to the renal impairment.

Acute Kidney Injury↗
PubMed1982

[Clinical relevance of N-acetylglucosaminidase determination in urine of kidney transplant recipients with and without cyclosporin A].

From January to September 1981 urinary gamma-N-acetyl-glucosaminidase (NAG) excretion was measured in 23 cadaver kidney recipients up to 90 days posttransplant. Conventional immunosuppression with azathioprine and prednisone was used in 12 patients, and cyclosporin A (CyA) in 11 patients. The purpose of this study was to assess the clinical value of NAG determinations in the diagnosis of acute rejection episodes and CyA-induced nephrotoxicity. A total of 26 acute rejection episodes were observed. 14 (54%) of these were associated with a significant increase in NAG excretion. The other 46 episodes of increased NAG excretion (77% of a total of 60 episodes) were unrelated to acute rejection reactions. No obvious reason was apparent in 39 instances (63%). Nine out of 11 patients treated with CyA showed one or more increases in NAG excretion, but the number of such episodes did not differ between patients with CyA serum concentrations below 500 ng/ml and those with levels above 500 ng/ml. Histological signs of CyA toxicity in graft biopsies correlated well with increased NAG excretion. It is concluded that increases in NAG excretion are not sensitive and specific enough to be of definite help in the diagnosis of acute rejection and/or CyA-induced nephrotoxicity.

Acetylglucosaminidase↗
PubMed1982

[Phenacetin abuse. VII: Urinary tract tumors in dialysis patients and patients with kidney grafts].

From 1965 to 1981, 9 out of 346 patients treated by chronic hemodialysis or kidney transplants had tumours of the lower urinary tract. All the tumour patients belonged to the analgesic abusers group (n = 87). The frequency of urinary tract tumours in this analgesic abusers group does not differ from the frequency in analgesic abusers in general (about 10%). In the 9 analgesic abusers a total of 18 urothelial tumours were recorded: 4 tumours of the renal pelvis, 3 of the ureter and 8 tumours of the urinary bladder. One female patient had a tumour of the urethra. Diagnostic and therapeutic problems are discussed on the basis of two case histories. Our experience in recent years is summarized in a program for tumour-screening, diagnosis and therapy for analgesic abusers treated by dialysis and kidney transplantation.

Carcinoma, Squamous Cell↗
PubMed1982

[Netilmicin in refractory urinary tract infections. Good therapeutic effect in spite of long dosage intervals].

Aminoglycoside antibiotics are useful--despite potential toxicity--for treating urinary tract infection when other antibacterial agents have failed to eradicate bacteriuria. That this is true of the recently introduced aminoglycoside netilmicin was shown by 16 cases of tenacious and frequently recurring urinary tract infection. In contrast to previous recommendations, but relying on well known pharmacokinetic data which show prolonged urinary excretion of aminoglycosides, netilmicin was administered according to the following dosage schedule: Intramuscular injections of 3 mg/kg in cases where renal function was unimpaired, and of 2 mg/kg where it was reduced, were administered at dosage intervals of 1 to 4 days. Peak serum levels of netilmicin measured 1 hour after intramuscular injection were within the expected range of 8-14 micrograms/ml (3 mg/kg) and 6-10 micrograms/ml (2 mg/kg). As a result of the long dosage intervals the serum trough levels were usually far below 1 microgram/ml except in patients with moderate renal failure. Urinary concentrations of netilmicin, however, remained for the most part above the limit of antibacterial activity throughout the dosage intervals of 1 to 4 days. One week after the usual three weeks treatment course, urinary concentrations were still between 1 and 5 mcg/ml, and slowly decreasing amounts of the drug could be detected at least in traces up to 3 months beyond the last dose. Considering the type of urinary tract infections selected to receive netilmicin, the response to treatment was satisfactory and seemed unaffected by the long dosage intervals. Bacteriological cure was achieved in 5 of 11 infections associated with chronic pyelonephritis or analgesic nephropathy and in 4 of 5 urinary infections in patients with renal transplants. Treatment failures could be accounted for by obstructive lesions, stones, and in one transplanted patient by infection localized to her own shrunken kidneys. No instance of ototoxicity or nephrotoxicity due to netilmicin could be detected. Netilmicin administered according to the dosage schedule described can be recommended for ambulatory treatment of tenacious, recurring urinary tract infections due to gram-negative bacteria and refractory to cure by the usual oral antibiotic therapy.

Drug Administration Schedule↗
PubMed1982

Morphology of the renal medulla in ischemic acute renal failure in the rat.

In the initial phase of ischemic acute renal failure in the rat the outer medulla is characterized by widening of peritubular capillaries in the inner stripe and by accumulation of cytoplasmic blebs in dilated proximal straight tubules in the outer stripe. Both findings contribute to tubular obstruction. In the maintenance phase, outer and inner stripes show tubular necrosis mainly of proximal straight tubules and thick ascending loops of Henle. In both phases the papilla is apparently spared from damage. Protective measures act at least partly by prevention of peritubular capillary widening in the inner stripe of outer medulla.

Acute Kidney Injury↗
PubMed1982

Superficial nephron obstruction and medullary congestion after ischemic injury: effect of protective treatments.

90 min of renal artery occlusion in previously unilaterally nephrectomized rats produce acute renal failure (ARF) (plasma creatinine at 48 h after ischemia: 636 +/- 44 vs. 133 +/- 9 mumol/l in controls). Between 1 and 48 h after releasing the occlusion, two populations of superficial nephrons could be observed, one with dilated tubules and elevated proximal tubular pressures (PTP: 39 +/- 1 vs. 12 +/- 1 mm Hg in controls) and the other with collapsed tubules and decreased PTP (9 +/- 1 mm Hg). Proximal tubular passage time (PPT) could not be determined with the Lissamine green technique. Seven methods of pretreatment were tested, 5 of which provided partial functional protection (DOCA/NaCl/NaCl, furosemide infusion, inosine bolus, mannitol bolus and the combination of the last two). Neither renal renin levels nor urinary NaCl excretion were consistently correlated with protection. Functionally protected rats consistently showed no PTP increase and normal PPT in the tubules at the kidney surface. However, plasma creatinine at 48 h differed markedly within the 5 protected groups, ranging from 168 +/- 18 to 398 +/- 35 mumol/l. Extensive medullary congestion was seen at 1-6 h after ischemia only in those rats with obstructed, high pressure nephrons at the kidney surface. To conclude: (1) Functional protection from ischemic ARF, both with and without an accompanying increase in solute excretion, was achieved by the abolition of tubular obstruction. (2) Despite similar degrees of restoration of superficial nephron function, the persisting impairment of whole kidney function differed markedly between the protected groups. (3) Impairment of deeper nephron function must therefore play a major role, perhaps through persisting obstruction in the long loops of Henle. (4) High pressure nephrons may compromise medullary venous outflow in the outer zone of the outer medulla.

Animals↗
PubMed1982

Femoral nerve lesion subsequent to renal transplantation.

Severe femoral neuropathy subsequent to renal transplantation is described in a patient who died in the 5th postoperative week. Postmortem examination revealed a compression of the femoral nerve by an older hematoma of the iliac muscle, ipsilateral to the transplantation, and severe Wallerian degeneration of the nerve beginning at the site of the hematoma. It is postulated that the hematoma resulted from surgical trauma on the iliac muscle and was facilitated by previous anticoagulation and hypertensive vasculopathy. We suggest that every patient with similar symptoms occurring after renal transplantation should be investigated for a retroperitoneal hematoma. If such a hematoma is diagnosed, immediate decompression neurolysis should be performed in order to prevent prolonged recovery time or permanent disability.

Femoral Nerve↗
PubMed1982

Focal necrotizing brain stem encephalopathy and cranial radiculopathy in a kidney transplant recipient.

A 48-year-old female patient developed sensory and motor palsy of the V-Xth cranial nerves immediately after kidney transplantation due to terminal uremia. A second exacerbation followed about 4 weeks later. After 46 days post transplantation she died from bronchopneumonia. Autopsy showed multiple acute and subacute necrotic foci in proximal portions of the cranial nerves as well as a discontinuous necrotizing encephalopathy localized mainly in the subpial zone of the brain stem. The mechanism by which lesions of the nervous system were produced remains speculative. A possible neurotoxic role was attributed to the drugs administered after transplantation. Herpes virus hominis antigen could be demonstrated in the cells of the pons and of the trigeminal ganglion, but its presence was thought to be coincidental and probably not causally related to the described lesions.

Brain↗
PubMed1982

Hgcl2-induced acute renal failure in the rat. Effect of water diuresis, saline loading, and diuretic drugs.

A variety of pretreatment-treatment protocols were applied to rats with ARF induced by the subcutaneous injection of 6 mg of HgCl2 per kilogram body weight. Renin depletion induced by DOCA-saline pretreatment was associated with protection against HgCl2-induced ARF only when the saline diuresis was maintained by drinking 1% NaCl after injury. Twenty-four dehydration followed by free access to tap water annihilated the protective effect of DOCA-saline pretreatment despite maintained depletion of renal renin. Continuous intravenous loading with saline and furosemide, although increasing renal renin levels, afforded as much protection as saline loading alone. Ethacrynic acid, which did not increase salt excretion in our rats, as well as water diuresis, failed to be protective. A loose correlation was found between he amount of histological damage to the convoluted parts of the proximal tubules and the degree of renal functional impairment. Thus protection against HgCl2-induced ARF was independent of the renal renin level but closely related to urinary NaCl excretion after the injury. Saline diuresis could act by relieving or preventing tubular obstruction.

Acute Kidney Injury↗
PubMed1981

[Endotoxin effect on intravascular volume and kidney function in an acute experiment in the rat].

The effect of intravenous endotoxin (Sal. abortus equi) in a semilethal dose in rats was very individual. Animals showing a drop in creatinine clearance were termed sensitive (E II), and animals without effect on the creatinine clearance non sensitive (E I). In the sensitive animals a reduction of intravascular space by albumin loss into the extravascular space, a decrease of renal blood flow and an average fall in creatinine clearance of 40% were found. The non sensitive animals (E I), on the other hand, showed no significant change in albumin space but, in contrast to E II, their hematocrit fell, a fact interpreted as vasodilatation and inflow of fluid. In these animals (E I) no change in creatinine clearance was measured. Orthograde tubular perfusion of endotoxin through the loop of Henle elicited no tubular glomerular feedback response. In these sensitive animals (E II), the absence of tubular glomerular feedback vasoconstriction, hypovolemia and a fall in blood pressure suggest a prerenal cause for this type of acute renal failure. Additional factors responsible for acute renal failure are discussed.

Animals↗