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Biomedical subjects

J F Mahony

Publications and source records attributed to J F Mahony.

At least 55 records · Page 3Linked to original sources

Is phenacetin responsible for analgesic nephropathy in New South Wales?

A lifetime history of analgesic consumption was recorded at interview from 91 patients (11 men, 80 women) with a secure diagnosis of renal papillary necrosis, 38 patients (5 men, 33 women) with probable renal papillary necrosis and 223 control subjects from two sources. Consumption of phenacetin-containing analgesics increased the risk of renal papillary necrosis in women some seventeen times over that for non-consumers, but analgesics containing no phenacetin did not confer an increased risk of renal papillary necrosis; in both calculations the confounding effect of taking the other type of analgesic was controlled.

Adult↗

Impaired lipoprotein lipase activation by uraemic and post-transplant sera.

1. Lipoprotein lipase was separated from normal human post-heparin plasma by affinity chromatography and assayed with a 14C-labelled triolein emulsion. No enzyme activity was detected unless whole serum was included in the assay as a source of cofactor, apolipoprotein C-II. 2. After a 10 h fast, serum obtained from 46 normal subjects, eight patients with hypertriglyceridaemia but normal renal function, patients with chronic renal failure (24 undialysed, 20 haemodialysed) and 14 recipients of renal allografts, was added to incubation medium for the assay of lipoprotein lipase to determine the maximum activation of the enzyme. 3. When serum was obtained from normal subjects, maximum activation of the enzyme correlated positively with the concentration of triacylglycerol in the sample. Neither sex nor age had a significant effect on the maximum activation achieved by serum from control subjects. 4. The maximum lipoprotein lipase-activating capacity of serum from uraemic and transplant patients was significantly reduced when compared with serum from healthy controls or from the non-uraemic hypertriglyceridaemic patients. 5. Maximum enzyme activation correlated positively with high-density lipoprotein cholesterol in serum from undialysed patients, but did not correlate positively with total serum triacylglycerols in any of the patient groups. Only in transplant recipients was there a significant inverse relationship between serum creatinine concentrations and maximum enzyme activation. 6. Although lipoprotein lipase activation was impaired in uraemic subjects and renal transplant recipients, this appeared to be due more to the presence of an inhibitor than to cofactor deficiency.

Apolipoprotein C-II↗

Impaired plasma triglyceride clearance as a feature of both uremic and posttransplant triglyceridemia.

After accurate plasma volume calculation, endogenous plasma very-low-density-lipoprotein (VLDL)-triglyceride turnover rates were measured in 20 undialyzed patients with chronic renal failure (CRF) and in 16 renal transplant recipients with stable graft function. When kinetic criteria were based on a group of healthy subjects (Vmax = 36.7 mumoles/hr/kg), it was clear that, on the whole, CRF patients had a reduced capacity for VLDL-triglyceride removal (Vmax = 14.0 mumoles/hr/kg), as did graft recipients (Vmax = 19.5 mumoles/hr/kg). In transplant recipients with impaired graft function, however, extremes of both under removal and over production of VLDL-triglycerides were observed. In CRF, defective clearance was accompanied by a reduction in postheparin lipoprotein and hepatic lipase activities, although there was no statistical relationship. Enzyme activities were not reduced, however, after transplantation, and the metabolic factors responsible for defective clearance were not clearly identified.

Adolescent↗

"Satellite" haemodialysis.

Thirty of the 39 patients treated at the Blacktown Dialysis Centre, the first "satellite" dialysis centre in the greater metropolitan Sydney, had been referred from four Sydney renal units for long-term dialysis therapy. The move save approximately 150 kilometres in travelling and eight hours time each week for each of these patients. The cost of running the unit was approximately $10,000 per patient per year in the first year--no greater than that of home dialysis, and less than that of dialysis in a teaching hospital. The advantages of establishing satellite dialysis centre, the method of operation, and the results of the first year of operation of the Blacktown Dialysis Centre are described.

Adult↗

The relevance of 25-hydroxycalciferol measurements in sera of patients with renal failure.

Iliac crest biopsies and serum specimens were obtained from 36 non-dialyzed uraemic patients. The mean serum 25-hydroxycalciferol concentration of the patients was lower than that of normal subjects and a significant correlation was found between 25-hydroxycalciferol values and the severity of osteomalacia. Parathyroid osteopathy was significantly correlated with serum immunoreactive parathyroid hormone but not with serum 25-hydroxycalciferol values. While normal serum 25-hydroxycalciferol concentrations in uraemic patients do not exclude the presence of osteomalacia, a low concentration is virtually diagnostic of this disorder.

Antigens↗

High density and low density lipoproteins in chronic renal failure before and after renal transplantation.

The hyperlipoproteinaemia accompanying chronic renal failure and renal transplantation has been re-examined in terms of the apoprotein (apo A and apo B) moieties of the high density (HDL) and low density (LDL) lipoproteins. Hypertriglyceridaemia is prevalent in chronic uraemia and is not corrected by haemodialysis or renal transplantation. Hypercholesterolaemia is characteristic only of renal allograft recipients. Apo A levels are reduced in undialyzed uraemic and remain low during haemodialysis, as well as in patients with renal allografts of less than six months duration. In renal transplant recipients of greater than one year duration, apo A levels are normalized. The normalization of apo A level is related to the stability of graft function, as determined by sequential analysis of 15 renal transplant recipients. Apo B levels are normal transplant recipients. Apo B levels are normal in uraemic and dialyzed patients, but are elevated in long term transplant recipients. Unlike apo A levels, this alteration does not appear to reflect the restoration of kidney function.

Apolipoproteins↗

Circulating thyroid hormone levels and adequacy of dialysis.

In vitro thyroid function tests were performed in three groups of patients with chronic renal failure who were receiving, on average, 15, 18 and 27 hours of maintenance hemodialysis per week. Total thyroxine levels were low and total triiodothyronine levels low to normal in those receiving the least dialysis (15 hours), and were significantly higher in those receiving longer dialysis. Free thyroxine levels, as measured by the effective thyroxine ratio, were normal and similar in all three groups, as were serum thyrotrophin levels. All patients were clinically euthyroid. As total hormone levels showed a significant inverse relationship to both urea and creatinine, this study suggests that there is a dialyzable metabolite retained in uremia which competes with thyroid hormones for protein-binding sites.

Adult↗

Analgesic abuse, renal parenchymal disease and carcinoma of the kidney or ureter.

In a consecutive series of 88 cases of carcinoma of the kidney and upper urinary tract seen at one hospital, 31 had malignant urothelial tumours of the renal pelvis or ureter. Forty-two per cent of these transitional-cell carcinomas occurred in patients with renal papillary necrosis following upon prolonged and heavy analgesic ingestion. Other possible aetiological factors were heavy cigarette smoking (61% of cases), long standing urinary obstruction or infection (23%) and possible occupational exposure (6%); in only four cases (13%) was there no identifiable aetiological factor. Those cases with analgesic nephropathy were characterised by renal functional impairment, hypertension and interstitial nephritis, but there was no difference in the clinical behaviour or pathological appearances of the tumours in the two groups. The clinical and experimental evidence that certain metabolites of phenacetin are carcinogenic is reviewed.

Adult↗

Hemodialyzer performance: an assessment of currently available units.

The performance characteristics of nine currently available disposable parallel-flow dialyzers were assessed, both before and immediately following dialysis, by measuring: (i) in vitro clearances of C14 labeled urea, creatinine, and sucrose and H3 labeled vitamin B12 at standard conditions, (ii) ultrafiltration rates in saline at 37C, and (iii) loss in the mass transfer coefficient-membrane area product (hoA), following a single dialysis. Parallel-plate dialyzers underwent considerable membrane stretching during dialysis and exhibited greater variability, particularly regarding vitamin B12 clearance and ultrafiltration ability, than did capillary dialyzers. The variability in plate units was greater for large-area dialyzers where there were 25 to 26 blood channels. However, despite considerable differences in performance characteristics, all dialyzers were judged to be clinically acceptable in terms of both solute clearance and ultrafiltration characteristics.

Creatinine↗

Occlusive arterial disease in uraemic and haemodialysis patients and renal transplant recipients. A study of the incidence of arterial disease and of the prevalence of risk factors implicated in the pathogenesis of arteriosclerosis.

The prevalence of clinical and sub-clinical occlusive arterial disease and of risk factors implicated in the pathogenesis of arteriosclerosis was assessed in 21 patients with chronic renal failure, 27 on maintenance haemodialysis and 51 renal allograft recipients. Clinical occlusive arterial disease was present in 27 patients, and sub-clinical arterial disease in 34. Myocardial infarction, cerebral thrombosis and lower limb arterial thrombosis had occurred only in the transplant recipients; these patients had, however, been followed for a longer period of time than the other two groups. In the allograft recipients, the cumulative incidence of any occlusive arterial disease was 416 per 1000, and that of coronary heart disease was 267 per 1000 at six years. Hypertension was present in 76 per cent of patients prior to renal replacement therapy. Following institution of definitive therapy, hypertension was of shorter duration and less common in haemodialysis patients than in renal transplant recipients. Uraemic and haemodialysis patients with occlusive arterial disease had required antihypertensive medication for significantly longer than those free of arterial disease. Transplant recipients with hypertension had a greater mean serum creatinine, were receiving a larger maintenance dosage of corticosteroids and less frequently had undergone prior bilateral nephrectomy than those transplant patients without hypertension. Serum lipid levels were elevated in 62 per cent of patients. In the uraemic and haemodialysis patients hypertriglyceridaemia was the predominant abnormality while in the transplant recipients combined hypertriglyceridaemia/hypercholesterolaemia was more frequent. Despite regular aluminium hydroxide therapy 81 per cent of uraemic and haemodialysis patients had a calcium X phosphate product higher than normal. Arterial and/or soft tissue calcification as demonstrable in 20-38 per cent of patients within each group, but could not be related to the calcium X phosphate product of radiographic evidence of hyperparathyroidism. Glucose intolerance was present in 71 per cent of the uraemic and haemodialysis patients and 33 per cent of the transplant recipients. Hyperuricaemia, cigarette smoking, obesity and a sedentary existence were also prevalent. The majority of patients had several risk factors implicated in the pathogenesis of arteriosclerosis. Occlusive arterial disease is a major problem in patients with end stage renal disease, being no less common after transplantation than with long-term maintenance dialysis. The aetiology is multifactorial.

Adult↗

Hypophosphataemic osteomalacia in patients receiving haemodialysis.

Four patients had symptomless osteomalacia at the time of starting regular haemodialysis. After 21-40 months they became hypophosphataemic and developed disabling skeletal symptoms. In each case an exacerbation of histological osteomalacia was shown. Symptoms improved after measures designed to raise serum inorganic phosphate concentrations or vitamin D administration, or both. Patients undergoing maintenance haemodialysis should have their serum phosphate and alkaline phosphatase levels monitored every month. Predialysis phosphate levels below 1 mmol/1 (3 mg/100 ml) and rising serum alkaline phosphatase concentrations are danger signals. If the diagnosis is confirmed early aggressive treatment should be started.

Adolescent↗