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G G Duggin

Publications and source records attributed to G G Duggin.

At least 73 records · Page 4Linked to original sources
PubMed1984

Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response.

Whether the expression of DR antigens is altered in cadaver renal transplants was examined by the use of monoclonal antibodies to the non-polymorphic region of the DR molecule and an indirect immunoperoxidase stain. Expression of DR antigens increased considerably on renal tubular cells in all 25 biopsy specimens which showed severe cellular rejection, but in only 4 of 14 biopsy specimens with no or minimum evidence of rejection. 2 of these 4 specimens were from patients recently treated for severe rejection and the other 2 subsequently lost their grafts from chronic rejection. DR antigens were also expressed on the cell surface of isolated tubular cells aspirated from transplanted kidneys with acute cellular rejection but not on tubular cells in normal kidneys or aspirates from kidneys without rejection. Biopsy specimens with increased DR expression in tubules usually had an interstitial T cell infiltrate. Expression of DR antigens on tubular cells was not related to HLA-DR incompatibility between donor and host, or to the type of immunosuppressive therapy given. The expression of DR antigens on renal tubular cells may be induced by the infiltrating activated T cells or be a consequence of tubular regeneration following rejection or ischaemic damage. The increased expression of DR antigens on renal tubular cells during rejection makes these cells potential targets for delayed type hypersensitivity responses, which are only effective against DR antigen bearing cells.

Adult↗
PubMed1984

Differential distribution of glutathione and glutathione-related enzymes in rabbit kidney. Possible implications in analgesic nephropathy.

Whole tissue reduced glutathione (GSH) concentration was found to be lowest in rabbit renal inner medulla and progressively higher in outer medulla and cortex. Activities of cytosolic glutathione reductase in inner medulla and outer medulla were similar, and each was only approximately 50% of that of cortex. Whole tissue and microsomal gamma-glutamyl transpeptidase activities were high in cortex and outer medulla but were low in inner medulla. Cytosolic activity of selenium-dependent glutathione peroxidase ( GPx -I) was similar in both outer medulla and inner medulla but was only 50% of that of cortex. Activity of cytosolic selenium-independent glutathione peroxidase ( GPx -II) was highest in cortex and lowest in inner medulla (approximately 15% of cortex and approximately 50% of outer medulla). Cytosolic glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene as substrate was high in all three regions of kidney. With 1,2-dichloro-4-nitrobenzene and 1,2-epoxy-(4-nitrophenoxy)propane as substrates, cytosolic glutathione S-transferase activities were very low in cortex, outer medulla, and inner medulla. Microsomal activities of glutathione reductase, GPx -I, GPx -II and glutathione S-transferases were much lower than activities of corresponding cytosolic enzymes. Activities of the glutathione peroxidases in renal inner medulla would hence be expected to cause little interference to prostaglandin endoperoxide synthetase mediated cooxidative activation of paracetamol. It has been demonstrated that the paracetamol metabolite can react rapidly with GSH, forming not only glutathione conjugate but also paracetamol itself and oxidized glutathione. Low GSH concentrations, as well as low activities of glutathione reductase, GPx -I, GPx -II, and gamma-glutamyl transpeptidase, may therefore render the inner medullary region of kidney particularly vulnerable to paracetamol-related analgesic nephropathy.

Acetaminophen↗
PubMed1984

Renal function and lithium treatment: initial and follow-up tests in manic-depressive patients.

Assessment of renal function was carried out in an unselected sample of patients with bipolar manic-depressive disorder receiving lithium for an average period of 4.5 years. Overall, glomerular filtration rate (GFR) fell within the established normal range based on sex and age, whereas measures of urinary concentrating ability were generally impaired. There was no relationship between duration of lithium treatment and either GFR or impairment of urinary concentrating ability. Moreover, there was no evidence of a progressive impairment of glomerular or tubular function in patients re-tested after 2 years. The results of this study confirm the safety of lithium administration in the majority of patients and emphasize the importance of careful clinical monitoring to avoid lithium intoxication.

Adult↗
PubMed1984

Identification of the cellular subpopulations infiltrating rejecting cadaver renal allografts. Preponderance of the T4 subset of T cells.

In the rejection response against renal allografts, the relative importance of helper/inducer T cells mediating a delayed-type hypersensitivity response and of T cells with direct cytotoxicity has not been defined. These subpopulations were identified with commercially available monoclonal antibodies and an indirect immunoperoxidase technique in 31 renal biopsies from patients undergoing acute rejection episodes and in 9 rejected nephrectomy specimens. T lymphocytes were the predominant cell population in all biopsies and in 8 of 9 nephrectomies. The T4 helper/inducer subset was equal to, or greater than, the T8 cytotoxic/suppressor subset in 28 of the 31 biopsies and in the 8 nephrectomy specimens that had histological evidence of cellular rejection. T4 lymphocytes were found predominantly in large areas of cellular infiltrate. T8 lymphocytes had a more diffuse interstitial distribution and were a minority of the cells in the large areas of cellular infiltration. These results show that helper/inducer T lymphocytes are often more frequent than cytotoxic/suppressor cells in acute renal allograft rejection in humans and they suggest that helper/inducer T cells may play an important role in the mediation of graft destruction.

Antibodies, Monoclonal↗
PubMed1984

Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer.

A comparative study of reduced glutathione (GSH) concentrations and activities of GSH related-enzymes in urinary bladder transitional epithelium (UBTE), urinary bladder nontransitional tissue (UBNT), and liver of the rabbit, was carried out to investigate the reasons for the susceptibility of UBTE towards peroxidase-mediated chemical carcinogenesis. Cooxidative activation of chemical carcinogens by prostaglandin H synthase occurs at high levels in UBTE and minimally in UBNT. Other peroxidases are also likely to activate carcinogenic xenobiotics in the urinary bladder. GSH concentrations in UBTE and UBNT were low compared to that in the liver. gamma-Glutamyl transpeptidase activities were much lower in UBTE and in UBNT than those in the liver. Activities of selenium-dependent and selenium-independent glutathione peroxidases were very low in UBTE and UBNT. Cytosolic glutathione S-transferase activity towards 1,2-epoxy-(4-nitrophenoxy)propane was very low in UBTE. Microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene was much lower in UBTE than in the liver. We propose that the low GSH concentration and diminished activities of glutathione peroxidases, gamma-glutamyl transpeptidase, and certain isozymes of glutathione S-transferase could be responsible for the vulnerability of UBTE towards chemical carcinogenesis.

Animals↗
PubMed1984

DT-diaphorase: differential distribution in rabbit kidney and possible protection against quinone toxicity in the inner medulla.

DT-diaphorase, presently regarded as a protective enzyme against quinone toxicity, was found to increase in activity from cortex to inner medulla within the rabbit kidney. The high activity of DT-diaphorase in renal inner medulla would therefore provide effective protection in that region of kidney against toxicity and carcinogenicity of xenobiotics which are either quinones or converted to quinones via prostaglandin H synthase.

Animals↗
PubMed1984

Renal biopsy morphology in renal transplantation. A comparative study of the light-microscopic appearances of biopsies from patients treated with cyclosporin A or azathioprine prednisone and antilymphocyte globulin.

Nephrotoxicity is a major side effect of cyclosporin A (CSA) when used in renal transplantation, and the distinction between nephrotoxicity and rejection is important in patient management. One hundred twenty-five renal biopsies were examined from 56 patients entered into a controlled clinical trial aimed at comparing the efficacy of CSA therapy alone to a combination of prednisone, azathioprine, and antilymphocyte globulin (AZA). In order to define the histopathology of rejection and nephrotoxicity, all the biopsies were evaluated in a semiquantitative manner by an observer unaware of the clinical state of the patient. Comparison of the morphological appearances of 32 biopsies from patients on CSA, and 22 biopsies from AZA-treated patients performed during clinically apparent rejection episodes showed that the histological patterns of rejection were the same in both treatment groups. Comparison of the morphological features of 34 biopsies from patients receiving CSA and 13 from patients receiving AZA, performed during prolonged periods of post-transplant renal failure, who eventually recovered on continuation of original therapy, showed that there were no morphological features specific to the CSA-treated group. Five patients on CSA had oliguria which was prolonged by CSA nephrotoxicity. Thirteen biopsies from all five patients showed a diffuse interstitial fibrosis that was peculiar to this group of patients.

Antilymphocyte Serum↗
PubMed1984

Stimulation of renin release from rat renal cortical slices by cyclosporin A.

Cyclosporin A is known to produce increases in plasma and kidney renin in vivo. In this study, Cyclosporin A was shown to stimulate renin release in vitro in rat renal cortical slices. At the optimal concentration of 8 x 10(-6) M Cyclosporin A, renin release was stimulated by up to 43% during a 2 hr incubation at 37 degrees. This observation strengthens the hypothesis that the intra renal renin-angiotensin system may participate in the mechanism of Cyclosporin A nephrotoxicity.

Animals↗
PubMed1984

Cyclosporin A and renal prostaglandin biosynthesis.

The effect of cyclosporin A (CyA) treatment of rats on prostaglandin synthesis in the renal cortex was studied. Renal cortical slices were prepared from control and CyA-treated rats and the release of prostaglandins into the medium during incubation at 37 degrees was measured. Rats killed 4 hours after receiving 100 mg/kg CyA orally showed no changes in renal slice release of PGE2, PGF2 alpha, 6-keto-PGF1 alpha or thromboxane B2. The slice release of 6-keto-PGF1 alpha was tested after 5 days of CyA treatment and again there was no difference from control rats. The effect of CyA added to slice incubations in vitro was examined: CyA had no effect on PGE2 or 6-keto-PGF1 alpha release in the presence or absence of angiotensin II. Under all of these experimental conditions there was evidence of CyA-induced stimulation of the renin-angiotensin system. Indomethacin treatment did not inhibit CyA-mediated accumulation of renin in the renal cortex. The results suggest that renal prostaglandins do not play a role in CyA-stimulated renin storage or release, or in CyA nephrotoxicity.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

High risk hypertensive pregnancies: maternal and foetal outcome.

Two hundred and thirty-six pregnant women were referred for assessment and management of hypertension and/or renal disease. A Unit consisting of a physician, an obstetrician and a perinatologist jointly assessed each patient and advised on management. All patients were hospitalized and at bed rest. Drug therapy was clonidine hydrochloride or methyl dopa and in some patients a vasodilator was added. The decision to deliver was dictated by foetal maturity and wellbeing, in conjunction with maternal condition. There was no maternal mortality and the overall perinatal survival was 97%. The outcome of these pregnancies compares favourably with studies previously reported and reflect a successful approach to management of high risk hypertensive pregnancies.

Adult↗
PubMed1982

Comparative nephrotoxicity of two aminoglycosides: gentamicin and tobramycin.

A prospective comparative study was undertaken to assess the relative nephrotoxicity of tobramycin and gentamicin. Patients receiving these drugs in the medical and surgical wards of the Royal Prince Alfred Hospital, Sydney, over a six-week period were included in the study. There was 33 patients treated with gentamicin and 19 treated with tobramycin (mean age, 52.6 years and 42.9 years respectively). Nine patients (27%) treated with gentamicin and two (10%) treated with tobramycin developed abnormally elevated plasma creatinine levels (greater than 110 mumol/L). Of patients with normal plasma creatinine level at the beginning of therapy, no significant change in the plasma level of creatinine was noted in the group treated with tobramycin, whereas those treated with gentamicin showed a significant increase in plasma creatinine level with time. It was concluded that tobramycin was significantly less nephrotoxic than gentamicin when used in typical clinical setting. With both drugs, monitoring of renal function is essential during therapy, particularly if other drugs excreted by the kidney are administered.

Adult↗
PubMed1982

Cyclosporin A-induced increases in renin storage and release.

The effect of Cyclosporin A (CyA) on renin storage and release in rats was investigated. Renin release from incubated renal cortical slices was increased in rats treated with 25 or 50 mg/kg/day of CyA for 3 to 7 days. This was associated with an increase in renal cortical renin content, which was also increased over the same time period. Plasma renin activity was similarly elevated in these rats. It is possible that these increases in renin are related to the nephrotoxicity of CyA.

Animals↗
PubMed1982

The detection of renovascular hypertension: a study of 490 patients by renal angiography.

Four hundred and ninety patients with hypertension were studied to determine those clinical characteristics or simple investigations that predict the presence of operable renal artery stenosis on renal angiography. One hundred and fifty two of the 490 patients were below the age of 40, had a good response to treatment, a normal physical examination, normal renal function, and normal intravenous pyelogram. Only one of the 152 patients had an operable renal artery lesion. Of the remaining 338 patients, 168 had a normal angiograms, 50 had surgically correctable renal artery stenosis, 75 had renal artery narrowing of less than 70 per cent and 45 patients had significant parenchymal renal disease. Abnormal renal angiograms were found significantly (p less than 0.05) more often in patients with poor control of blood pressure, impaired renal function or a history of antipyretic analgesic abuse. Our experience in hypertensive patients suggests that renal arteriography is unlikely to provide useful information in patients under 40 years old, but may well demonstrate a remediable abnormality in older patients with poor control of hypertension associated with a history of antipyretic analgesic abuse and/or impaired renal function.

Adolescent↗
PubMed1981

A disarmed world.

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Acetaminophen↗
PubMed1981

Regional differences in peroxidatic activation of paracetamol (acetaminophen) mediated by cytochrome P450 and prostaglandin endoperoxide synthetase in rabbit kidney.

Microsomes from renal cortex, outer medulla, and inner medulla of rabbit kidneys were found to catalyze the metabolic activation of paracetamol (acetaminophen), leading to covalent binding to protein when incubated with cumene hydroperoxide and T-butyl hydroperoxide. Differential distribution of cytochrome P450 and prostaglandin endoperoxide synthetase and each enzyme's preference for either cumene hydroperoxide or T-butyl hydroperoxide enabled the present investigation to distinguish their respective contributions in the cooxidative activation of paracetamol. Addition of methemoglobin caused enhancement of prostaglandin endoperoxide synthetase mediated activation of paracetamol when initiated by both arachidonic acid and the hydroperoxides. Aspirin and indomethacin inhibited the protein covalent binding of the reactive metabolite of paracetamol only when its formation was initiated by arachidonic acid. This study demonstrates the differences in the peroxidation metabolic activation of paracetamol mediated by cytochrome P450 (cortex greater than outer medulla greater than inner medulla) and prostaglandin endoperoxide synthetase (inner medulla greater than outer medulla greater than cortex) in rabbit kidney.

Acetaminophen↗