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Biomedical subjects

G G Duggin

Publications and source records attributed to G G Duggin.

At least 91 records · Page 5Linked to original sources
PubMed1979

Labetalol and bendrofluazide: comparison of their antihypertensive effects.

A randomized double-blind crossover trial of labetalol, bendrofluazide and placebo was carried out in 18 patients with mild to moderate hypertension. The reduction in blood pressure observed with labetalol and bendrofluazide was similar. The plasma levels of labetalol showed a significant correlation with changes in blood pressure (r = 0.07; P less than 0.021); and plasma level determinations of this drug may be of value in the management of patients who receive antihypertensive agents.

Adult↗
PubMed1978

Trimethoprim/sulfamethoxazole and renal function in transplant patients.

Twenty-two patients with functioning renal allografts took part in a double-blind crossover trial during which placebo, sulfamethoxazole, and trimethoprim/sulfamethoxazole were given for periods of 14 days. The patients were divided into 2 groups. The first group consisting of 12 patients had serum creatinine levels less than 0.18 mmol/L and the second group of 10 patients had serum creatinine levels between 0.18 mmol/L and 0.35 mmol/L. Renal function at the end of each period was assessed by clearance of inulin (CIn), p-aminohippurate (CPAH) and endogenous creatinine (CCr). The second group also had a pitressin concentration test as a measure of distal tubule function. There was no change in inulin or creatinine clearance or in maximum concentration after pitressin in any of the patients in any of the phases. In the first group there was an increase in PAH clearance during the sulfonamide and trimethroprim/sulfamethoxazole phases. This change was not seen in the second group of patients with significantly impaired renal function.

Adult↗
PubMed1978

Aspirin, protein transacetylation and inhibition of prostaglandin synthetase in the kidney.

1 The effect of aspirin on the kidney has been investigated in mice and rabbits. [Acetyl-(14)C]-aspirin was administered intraperitoneally in doses ranging from subtherapeutic to toxic. The degree of acetylation of protein was determined by the radioactivity remaining on protein precipitates of renal cortex and medulla after sequential washing designed to remove non-covalently bound material. Controls were established, by the use of [carboxyl-(14)C]-aspirin.2 The acetyl-(14)C residue was bound to renal proteins in a linear manner in increasing amounts with increasing dosage up to 100 mg/kg. The [carboxyl-(14)C]-aspirin was not bound and thus the salicylate portion of the molecule was not bound covalently to the renal protein. The time course of the acetylation was rapid, consistent with the rate of aspirin absorption. The disappearance of acetylated protein was slow, with a T(1/2) of 112.5 h in the renal cortex, and 129.5 h in the renal medulla.3 Differential centrifugation, Sephadex chromatography and gel electrophoresis were carried out on tissue homogenates to determine the site of acetylation. The acetylation was greatest in the microsomal fraction, although all protein fractions showed some degree of acetylation.4 The prostaglandin synthetase activity of a particulate preparation from rabbit kidney was determined by a spectrophotometric assay of malondialdehyde formation. Aspirin (10 mg/kg, i.v.) significantly inhibited prostaglandin synthetase in the renal cortex and medulla.5 Aspirin and renal proteins undergo a transacetylation reaction resulting in stable acetylated protein, with acetylation being greatest in the microsomal fraction. Aspirin has been shown to inhibit prostaglandin synthetase and this could lead to functional impairment of the tissue.

Acetylation↗
PubMed1978

Covalent binding of metabolites of acetaminophen to kidney protein and depletion of renal glutathione.

Experiments in CD-1 mice and Sprague-Dawley rats were carried out to determine the extent to which biochemical changes described previously for acute acetaminophen-induced hepatotoxicity might be applicable to the kidney. After intraperitoneal injection of acetaminophen, tissue glutathione and covalent binding of tritiated metabolites of acetaminophen to tissue protein were measured for liver, kidney cortex and kidney papilla. Glutathione was reduced more in mice than in rats, and more in liver than in kidney, without appearance of oxidized glutathione in either tissue. Covalent binding was likewise greater in mice than in rats and greater in liver than in kidney. The determination of covalent binding was extremely sensitive to the trace radiochemical impurities of the labeled drug. With prior administration of 3-methyl-cholanthrene, the induced changes were far greater in liver than in kidney, suggesting that the formation of a reactive metabolite from acetaminophen occurred in each organ by slightly different mechanisms. At doses less than those associated with demonstrable acute toxicity, the duration of covalent binding to protein was longer for renal papilla than for renal cortex or for liver. The results may be applicable to the pathogenesis of both acute and chronic nephrotoxicity.

Acetaminophen↗
PubMed1976

Calcium metabolism after renal transplantation.

Calcium metabolism was studied in four patients who had undergone renal transplantation from eight to 19 months previously. The studies included conventional biochemical and radiological parameters, undecalcified bone histology and metabolic balances. The only abnormality found was biochemical and histologic evidence of mild hyperparathyroidism. All patients were in approximate calcium balance, and there was no evidence of osteoporosis, osteomalacia or osteitis fibrosa. It is suggested that transplantation patients with stable, well functioning grafts and normal biochemical and radiologic parameters are unlikely to have or to be at risk of developing metabolic bone disease.

Adult↗
PubMed1976

Phenacetin: renal tubular transport and intrarenal distribution in the dog.

In a total of 22 studies in the anesthetized dog, the renal clearnace of phenacetin was measured over a range of plasma concentrations and at different urinary pH and rates of urine flow. Phenacetin is reabsorbed by passive diffusion. The urine/plasma ratio is essentially unity under all conditions. As measured by ultraviolet-spectrophotometric and colorometric methods and by high-pressure liquid chromatography, a labile metabolite appears in urine and renal papilla which upon hydrolysis gives rise to falsely high values for phenacetin. Renal cortical and papillary concentrations were determined in six dogs during hydropenia or diuresis. All tissue/plasma concentration ratios for phenacetin were essentially unity. The results indicate that the papillary localization of the earliest lesions of analgesic nephropathy cannot be attributed to high phenacetin concentrations within the papilla. This is in contrast to acetaminophen, the major metabolite of phenacetin.

Animals↗
PubMed1976

Analgesic nephropathy: renal distribution of acetaminophen and its conjugates.

Acetaminophen (APAP) and its conjugates (APAP-conj) are the major metabolites of phenacetin. To study their significance in the pathogenesis of analgesic nephropathy, their concentrations in the renal parenchyma were determined in conjunction with clearance measurements in 15 dogs with inulin as a reference marker. Particular attention was given to interpretation of the mechanisms responsible for the concentrations generated within the papilla. For APAP, APAP-conj and inulin there is a significant corticomedullary gradient which is inversely related to the rate of urine flow. For inulin and APAP-conj, this gradient may be explained by their concentrations within the tubular fluid of the distal nephron. With concentration in the urine as a reference, the apparent volume of distribution of inulin within the papilla is not fixed, but varies with the rate of urine flow. Using several different types of comparison with inulin, we found that the results with APAP are consistent with its penetration by diffusion into the cellular compartment of the papilla. Dehydration leads to maximal concentrations of APAP in the urine as well as in the tubular fluid and the cells of the distal nephron. This is consistent with the kinetics of diffusion.

Acetaminophen↗
PubMed1975

Low dose heparin and early kidney transplant function.

A prospective randomised double blind trial was carried out to assess the effect of subanticoagulant doses of subcutaneous heparin (Calciparine) compared to placebo on early renal allograft function. Thirty-six patients were entered into the trial, 18 received placebo and 18 heparin. There was no significant difference between the patients in either group in respect to early graft function, the number of rejection episodes or the response of graft function to treatment of rejection. There were four patients with haemorrhagic complications who had received heparin, whereas no patients in the placebo group had bleeding combinations. It is concluded that subanticoagulant doses of heparin have no demonstrable effect on early graft function and may cause haemorrhagic complications.

Adolescent↗
PubMed1975

Renal tubular transport of paracetamol and its conjugates in the dog.

1 The renal tubular transport of paracetamol and its conjugates was investigated with renal clearance and stop flow studies in the dog. Paracetamol is sparingly bound to plasma proteins and therefore undergoes glomerular filtration. It is reabosrbed in the renal tubules by simple diffusion. 2 The conjugates of paracetamol, the sulphate and the glucuronide, both undergo glomerular filtration being weakly protein bound. At low concentrations in plasma both compounds are secreted by an active transport process. At higher concentrations both compounds are reabsorbed. Clearances are not dependent on urinary pH or flow rate. It is concluded that reabsorption is not a passive process but that there is an active bidirectional transport of the conjugates. 3 Net tubular secretion of the sulphate, but not the glucuronide, conjugate was inhibited by the administration of probenecid.

Acetaminophen↗