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Biomedical subjects

V Parsons

Publications and source records attributed to V Parsons.

At least 37 records · Page 2Linked to original sources

Reactivity of monoclonal antibody P1 with glomerular basement membrane in thin-membrane nephropathy.

A monoclonal antibody, P1, possessing antiglomerular basement membrane specificity similar to that of naturally-occurring Goodpasture antibody, was used to study renal biopsy material from patients with thin-membrane nephropathy. Immunofluorescence and immunoperoxidase techniques were employed to detect tissue localisation after sections had been incubated with P1. Staining of glomerular and tubular basement membranes in the 14 patients with thin-membrane nephropathy was similar to that in 10 subjects with various other renal diseases, whereas three patients with Alport's syndrome all gave diminished or absent staining, as has been reported previously. These observations confirm that Goodpasture antigen is present in the basement membranes in thin-membrane nephropathy and that it reacts normally with P1 antibody. They also add to the evidence that the lesions of thin-membrane nephropathy and Alport's syndrome are fundamentally different. The staining method may be used as a differential diagnostic test.

Adult↗

Chronic dialysis in patients with multiple myeloma and renal failure: a worthwhile treatment.

Severe renal failure is a life-threatening complication of multiple myeloma. Aggressive treatment can reverse acute renal failure in many cases but the prognosis for those who require chronic renal replacement therapy is not clear. We have reviewed the treatment of these patients in the Brighton, Dulwich and Guy's Hospitals renal units. Twenty-three patients were treated for a total of 385 months. Over half presented with end-stage renal failure and required dialysis immediately. Fifteen patients died during the study period and actuarial survival was 45 per cent at one year; six have survived for longer than two years. No prognostic features at presentation were identified but those who responded to chemotherapy survived significantly longer than those who did not. Haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) appeared to be equally effective treatments. Complications from dialysis were more common than in patients with renal failure from other causes. Infection in those treated by CAPD was a serious problem and may be exacerbated by aggressive chemotherapy. Maintenance dialysis offers some patients with multiple myeloma long-term survival and should be offered to all patients who are considered to warrant continuing treatment for their underlying disease.

Actuarial Analysis↗

Non-insulin-dependent diabetes and renal replacement therapy.

Reports of renal replacement therapy in diabetes usually refer to patients with insulin-dependent diabetes mellitus (IDDM) only, and little is known about renal failure in non-insulin-dependent diabetics (NIDDM). A high proportion, 46/141 (32%), of the diabetics treated at our unit since 1974 had NIDDM. They were older at treatment (56 +/- 9 years, mean +/- SD) compared to the IDDM patients (39 +/- 10 years, p less than 0.001), and had a shorter duration of diabetes (13 +/- 8 years versus 23 +/- 8 years, p less than 0.001). Asians and Afro-Caribbeans accounted for 48% of the NIDDM patients (22/46) compared to only 7% of those having IDDM (6/95, p less than 0.0001). Non-diabetic renal disease accounted for the renal failure in 32% (15/46) of the NIDDM patients but only in 10.5% (10/95) of the IDDMs (p less than 0.001). Despite these differences the prevalence of other diabetic complications (retinopathy, neuropathy, and cardiovascular disease) was similar. Patient survival after transplantation was poorer in NIDDM than IDDM (23% and 57%, respectively, at 2 years). Survival on dialysis was equally poor in NIDDM and IDDM. Thus, NIDDM patients treated for renal failure are more commonly non-European and more often have non-diabetic renal disease. Yet other diabetic complications occur to the same extent in both IDDM and NIDDM patients with diabetic nephropathy.

Adult↗

Kidney pathology in liver allograft recipients after long-term treatment with cyclosporin A.

Organ transplant recipients given immunosuppressive treatment with cyclosporin A are at risk of injury due to nephrotoxicity. Eight liver allografted patients whose renal function became impaired during therapy with cyclosporin A for up to 4.5 years were investigated by renal biopsy. Ischemic changes in glomeruli were found to be greater than in controls, and there was focal tubular atrophy, but an excess of lesions in small arteries could not be demonstrated. In one patient there were glomerular changes suggestive of thrombotic microangiopathy. Interstitial fibrosis and cellular infiltration were slight. The pathogenesis of the ischemia remains to be elucidated, but reasons are advanced for favoring the view that the mechanism of cyclosporin A nephrotoxicity is primarily vasomotor, causing a reduction of renal blood flow and glomerular filtration rate without permanent organic arterial narrowing; nephrons become damaged irreversibly nevertheless.

Adult↗

The effects of zero magnesium dialysate and magnesium supplements on ionised calcium concentration in patients on regular dialysis treatment.

The effect of oral magnesium carbonate or aluminium hydroxide on serum ionised calcium, total calcium, aluminium and magnesium, was assessed in 31 patients with chronic renal failure, during and after one haemodialysis. The behaviour of ionised calcium and total calcium was the same in both groups. Each showed a slight fall during dialysis, which was not significant. Serum total calcium was 0.2-0.3 mmol/l (0.8-1.2 mg/dl) greater throughout the period of dialysis in the group taking aluminium hydroxide. Serum magnesium and aluminium were both lower in the group treated with magnesium carbonate. In the group taking magnesium carbonate, serum magnesium concentrations fell markedly during dialysis, but otherwise were maintained within the reference range by the use of a magnesium-free dialysate. These results show the effectiveness of magnesium carbonate oral phosphate-binding agents and zero magnesium dialysate in reducing serum aluminium without affecting the behaviour of serum calcium fractions during dialysis.

Administration, Oral↗

Substitution of aluminium salts by magnesium salts in control of dialysis hyperphosphataemia.

For two years all 28 patients undergoing hospital haemodialysis were switched from a dialysate magnesium (Mg) of 0.85 mmol/l to one containing none. Oral aluminium hydroxide was discontinued, and magnesium carbonate was substituted as a phosphate binder. After 24 months on this regimen predialysis aluminium concentration had fallen significantly. There was no significant change in predialysis phosphate, which remained above the normal range; nor was there evidence of increased secondary hyperparathyroidism as judged by parathyroid hormone immunoassay and biochemical or clinical criteria. Predialysis Mg concentrations tended to fall towards the normal range. Aluminium-containing phosphate binders seem to be unnecessary for the control of dialysis hyperphosphataemia. Magnesium carbonate may be an alternative and less toxic compound.

Administration, Oral↗

Evidence for extrarenal metabolism of 25-hydroxyvitamin D3 in man.

Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40 000 i.u. of cholecalciferol. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.

Adult↗

Diabetic pregnancy following renal transplantation.

Renal transplantation for diabetic nephropathy prolongs survival and the return of fertility makes pregnancy possible. We describe a successful pregnancy in a 38-year-old diabetic renal transplant recipient despite blindness, gangrenous toes, cardiac impairment, and both sensory and autonomic neuropathy. Renal function remained stable throughout the pregnancy which was complicated by supine hypertension, postural hypotension and increasing proteinuria. Fetal distress and increasing proteinuria precipitated delivery by Caesarean section at 29 weeks of a female infant weighting 1.1 kg. Following delivery, hypertension improved, gangrene resolved, proteinuria decreased, and renal function remained stable. Pregnancy in long-standing diabetic patients with renal transplants, although hazardous, may be successful yet the maternal morbidity and mortality makes them inadvisable.

Adult↗

Metabolic activity of erosions in rheumatoid arthritis.

The hands of 10 patients with rheumatoid arthritis were investigated with diphosphonate scanning and radiology. Increased uptake of isotope can be associated with some erosions but not all and also reflects other processes more linked to acute inflammatory areas unassociated with the development of erosions. If the latter are the hallmark of active rheumatoid arthritis then bone scans are not.

Adult↗

Fish oil modifies lipids and reduces platelet aggregability in haemodialysis patients.

Haemodialysis patients have an exceptionally high incidence of death from cardiovascular causes, related in part to abnormalities of lipids and platelets. Eskimos, however, have a low incidence of myocardial infarction and have a high dietary intake of fish, rich in omega-3 polyunsaturated fatty acids. We have, therefore, studied the effect of a fish oil MaxEPA, containing 3.6 g of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid on lipids and platelet function in haemodialysis patients. Following 8 weeks of therapy there was a 35% fall in triglycerides, a 10% rise of high-density lipoprotein (HDL) cholesterol, a 36% rise of HDL2 cholesterol fraction and a 54% rise of the HDL2:HDL3 cholesterol ratio. The platelet aggregation to adenosine diphosphate and collagen was significantly reduced. The activated whole-blood clotting time was prolonged from 141 to 153 s, and 69% of patients showed a reduction of factor VIII related antigen which is usually elevated in haemodialysis patients and is thought to be a marker of endothelial damage. The blood pressure fell from 147/82 to 124/74. We have thus shown that a dietary supplement of eicosapentaenoic acid produces potentially beneficial effects on lipids, platelets, and blood pressure and may help to protect against atheroma and thus cardiovascular mortality in high-risk haemodialysis patients.

Adolescent↗

Natural progesterone and antihypertensive action.

In a placebo controlled, double blind crossover study natural progesterone was given by mouth, in increasing doses, to six men and four postmenopausal women with mild to moderate hypertension who were not receiving any other antihypertensive drugs. When compared with values recorded before treatment and during administration of placebo progesterone caused a significant reduction in blood pressure, suggesting that progesterone has an antihypertensive action rather than a hypertensive one as has been previously thought. This possible protective effect of progesterone should be investigated further.

Adult↗

Bone metabolism in acute parathyroid crisis.

Studies on bone metabolism described in a fatal case of acute parathyroid crisis, occurring in a 48-year-old woman in whom serum immunoreactive parathyroid hormone levels were very high, and a 5 g parathyroid adenoma was found at operation. The histological and biochemical findings suggested a massive and acute increase in bone resorption. There was, however, no evidence of any compensatory increase in bone formation, indicating that acute parathyroid crisis is characterized by a marked dissociation between bone resorption and formation. It is suggested that a sudden fall in oestrogen levels may contribute to the pathogenesis of this disorder.

Acute Disease↗

Progressive, predominantly motor, uraemic neuropathy.

A severe rapidly progressive neuropathy is described in 4 young male adults with end-stage renal failure, 3 of whom had accelerated hypertension. The onset of symptoms developed after regular haemodialysis had been started and in all 4 patients was closely associated with a septicaemic illness. In 2 patients, renal transplantation led to considerable clinical improvement, and in a third patient charcoal haemoperfusion halted further clinical progression of the neuropathy. This improvement was not reflected by the nerve conduction studies which remained grossly impaired. A possible ischaemic aetiology related to accelerated hypertension and septicaemia is suggested for this unusual variant of uraemic neuropathy.

Adolescent↗