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Biomedical subjects

R Wilkinson

Publications and source records attributed to R Wilkinson.

At least 361 records · Page 20Linked to original sources

Renal biopsy appearances in rheumatoid disease.

The renal biopsies of 30 patients with rheumatoid arthritis and clinical evidence of renal disease were reviewed; only patients in whom the intravenous pyelogram was normal were subjected to biopsy, thus excluding those with papillary necrosis and chronic pyelonephritis. Tissue was studied by light, electron and immunofluorescence microscopy. There were 13 cases of mesangial change, 9 of membranous glomerulonephritis, 4 of tubulointerstitial change, 2 cases of focal segmental glomerulosclerosis, 1 case of amyloid and 1 of diffuse proliferative glomerulonephritis with crescents. All 9 patients with membranous glomerulonephritis but only 6 of 13 with mesangial change had received gold or penicillamine. We found no evidence of "glomerulitis" or of a rheumatoid vasculitis.

Adult↗

Osteomalacia in patients with chronic renal failure before dialysis or transplantation.

The case records of 327 patients who underwent bone biopsy in late or terminal renal failure, before any form of dialysis or transplantation, were examined for clues to the aetiology of renal osteomalacia and its manifestations. Fifty four per cent of the biopsies showed pure osteitis fibrosa, 34 per cent osteomalacia with osteitis fibrosa and 12 per cent showed neither abnormality. Osteomalacia was strongly associated with chronic pyelonephritis and obstructive uropathy as primary renal disease. In two matched groups of 100 each, and within the major primary diseases, it was associated with acidosis, hypocalcaemia and normophosphataemia (as opposed to hyperphosphataemia). There was no association with known length or uraemia and only a weak and inconsistent relationship with severity of uraemia. In the few patients studied, there was no relationship between osteomalacia and serum 25-hydroxycholecalciferol level. In contrast to the state of patients treated by haemodialysis, osteomalacia in this undialysed group was manifested by a higher level of serum alkaline phosphatase than pure osteitis fibrosa, serum iPTH did not differ between the groups, there was no predominance of symptoms in one group, other than proximal myopathy which had a weak association with osteomalacia, and Looser zones were more common than complete fractures. Our study shows that osteomalacia has different manifestations, and probably different causes, before and after the start of haemodialysis. These two stages of renal failure should be clearly distinguished in reports of renal bone disease.

Acidosis↗

Superiority of B locus matching over other HLA matching in renal graft survival.

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.

Adult↗

The effects of cimetidine on serum calcium and parathyroid hormone levels in primary hyperparathyroidism.

1 Cimetidine has been reported to reduce serum calcium and parathyroid hormone (PTH) levels in primary hyperparathyroidism, but some studies have reported negative findings. 2 A double-blind, controlled trial of cimetidine in this condition was, therefore, conducted. Eight patients were given cimetidine and placebo for 2 months each, in random order. Only one patient showed a significant fall in serum calcium on cimetidine and no patient showed a fall in PTH levels. 3 In addition, eight patients were studied during a 48 h continuous intravenous infusion of cimetidine. The first five patients exhibited no effect of the drug on either calcium of PTH levels, but in the sixth there appeared to be a dose-dependent suppression of PTH. The seventh and eighth patients were, therefore, given a higher dose of the drug but it failed to suppress calcium or PTH values. 4 It is concluded that cimetidine is not of value in primary hyperparathyroidism.

Administration, Oral↗

Computed tomographic studies of the head in a teaching hospital and a community hospital: a comparison.

This investigation compared the use of computed tomography (CT) of the head at a large primary medical-school-affiliated hospital and at a large community hospital. There were two aims: first, to study the intrinsic characteristics of the patients in an attempt to determine the potential for developing accurate discrimination algorithms; and second, to study the patterns of neurodiagnostic tests used at these facilities. The results indicated that separability of patients into normal and abnormal categories at both institutions was extremely small. In addition, there was no significant difference in the numbers of types of ancillary tests used at both institutions. Overall, these data once more confirm the difficulty of altering CT usage patterns in primary or secondary hospitals without significantly affecting the number of abnormal patients identified.

Boston↗

Beta-blockers and renal function.

alpha-, beta 1- and beta 2-adrenergic receptors in the kidney mediate vasoconstriction, renin secretion and vasodilatation, respectively. Blockade of beta-receptors may therefore be expected to influence renal blood flow and possibly glomerular filtration rate by intrarenal effects as well as by reducing cardiac output and blood pressure. Since the various beta-adrenergic blocking drugs available differ in the degree to which they block beta 2-receptors (cardioselectivity) and also in their intrinsic sympathomimetic activity, they would be expected to have different effects on renal function. The acute administration of beta-blockers usually results in a reduction in effective renal plasma flow and glomerular filtration rate, whether or not the drug is cardioselective or has intrinsic sympathomimetic activity, with the exceptions of nadolol, which has actually increased effective renal plasma flow in some studies and of tolamolol. With chronic oral administration, the non-cardioselective beta-blockers reduced glomerular filtration rate and effective renal plasma flow. The cardioselective drugs do not usually produce significant reductions in glomerular filtration rate or effective renal plasma flow, although small increases in serum urea during treatment do occur. Interestingly, in contrast to findings with intravenous administration, orally administered nadolol produced a slight reduction in glomerular filtration rate in 1 study, so the effect of this agent on renal function under clinical conditions remains uncertain. It seems likely that beta-blockers reduce renal function predominantly by blocking beta 2-receptors in the kidney. To keep area of discussion in perspective, it is important to realise that although there have been isolated reports of serious deterioration in renal function coinciding with beta-blocker treatment, the great majority of reports are of reduction in glomerular filtration rate which are not of clinical significance, even in patients with pre-existing impairment of renal function. The beta-blockers with low lipid solubility-i.e. atenolol, nadolol and sotalol-are not metabolised, and their dose must be reduced in renal failure. Propranolol has active metabolites and its dose must also be reduced slightly in uraemia.

Adrenergic beta-Antagonists↗

Management skills: where to get them.

To discover the prevalence of physicians seeking health care management skills, The Hospital Medical Staff polled 28 U.S. graduate schools and several professional organizations. The results of this survey are reported here, along with a geographically arranged directory of where to write for more information.

Data Collection↗

The natural history of chronic pyelonephritis in the adult.

One hundred and thirty patients with primary chronic pyelonephritis diagnosed radiologically or by nephrectomy, 84 with unilateral and 46 with bilateral disease, have been followed for six to 240 months. The clinical and radiological features of the disease at presentation, together with its influence on pregnancy, have been analysed. Serial observations of bacteriuria, blood pressure and renal function have been made during follow up and the intravenous urogram (IVU) has been repeated after five years in most patients. Although the disease probably starts in early childhood it often presents to the nephrologist in young adults, mainly women, as symptomatic urinary tract infection, hypertension, renal insufficiency or a combination of these features. Though associated with increased morbidity in pregnancy it does not usually interfere with fertility and in this series it did not cause increased fetal loss. Repeated urinary tract infections and hypertension are common events. Proteinuria is usually minimal and when present is associated with hypertension. The disease in most patients with unilateral disease runs a benign course; a poorer prognosis is associated with bilateral disease, hypertension and proteinuria. Since we found no association between frequent urinary infections and declining renal function we suggest that only symptomatic urinary infection should be treated in adults with chronic pyelonephritis.

Adolescent↗

The combination of melphalan with prednisolone. Anti-tumor effect and normal tissue toxicity in laboratory systems.

The effect of prednisolone upon the therapeutic index of melphalan has been studied in a variety of laboratory systems. The anti-tumour action of melphalan was assessed for a human melanoma xenograft growing in immune-deprived mice, clonogenic cell survival and tumour growth delay being used as end-points. Normal tissue toxicity was assessed for human bone marrow colony-forming units, murine bone marrow colony-forming units, murine gastrointestinal crypt microcolony-forming cells, and mouse survival. Prednisolone had no anti-tumour effect when given alone, but increased the anti-tumour effect of melphalan significantly. No increase in the toxicity of melphalan to marrow or gut colony-forming cells could be demonstrated. However, mouse survival was significantly lower after treatment with the combination than with melphalan alone. This study supports the view that steroids may enhance the anti-tumour effect of some alkylating agents, but this may be at the expense of increased normal tissue toxicity in some circumstances.

Animals↗

Vasopressin function in hypercalcaemia.

Vasopressin function and thirst were studied in fourteen hypercalcaemic patients (ten hyperparathyroid and four disseminated malignant disease). Ten patients had decreased renal concentrating ability which reversed within a few days in the majority of patients whose hypercalcaemia was corrected by parathyroidectomy. Although eight patients complained of thirst, none showed a lowered threshold of thirst appreciation during hypertonic saline infusion. Osmoregulation of vasopressin secretion was not reduced in any patient, but the hyperparathyroid group had an exaggerated vasopressin response to osmotic stimulation. We conclude that a partial, reversible nephrogenic diabetes insipidus occurs in at least 70% of hypercalcaemic patients irrespective of cause, which accounts for the polyuria induced by hypercalcaemia.

Adult↗

Sodium status and the renin-angiotensin-aldosterone system in compensated liver disease.

Exchangeable sodium, plasma renin activity, plasma angiotensin II and plasma aldosterone were measured in forty-six control subjects, nineteen patients with chronic non-cirrhotic liver disease and twenty patients with compensated cirrhosis (i.e. without ascites or oedema). In the three groups respectively, mean exchangeable sodium (mmol/kg lean body mass) was 53 (SD = 3), 50 (SD = 5) and 52 (SD = 8). Mean plasma renin activity (pmol l(-1) min(-1)) was 3.2, 3.1 and 3.0 supine and 6.2, 6.2 and 5.1 erect. Mean plasma angiotensin II (pmol l(-1) was 7.3, 5.8 and 6.6 supine and 10.6, 7.9 and 9.0 erect. Mean plasma aldosterone (pmol l(-1)) was 82, 64 and 77 supine and 188, 133 and 121 erect. There were no significant differences among the mean values of any of these variables. These findings indicate that, on the basis of exchangeable sodium measurements, sodium retention is not present in compensated liver disease and that the renin--angiotensin--aldosterone system is essentially normal.

Adult↗

Studies on the mechanism of action of LS 1727, a nitrosocarbamate of 19-nortestosterone.

LS 1727, a nitrosocarbamate of 19-nortestosterone, was active against lymphoid, antimetabolite-sensitive, cell lines in vitro especially L1210 and Ehrlich ascites tumour lines. It was less effective against alkylating agent-sensitive lines such as the Walker 256 carcinosarcoma. These results suggested a possible antimetabolite mode of action but LS 1727 had no effect on deoxy-or ribonucleotide pool sizes in L1210 cells. Studies on macromolecular synthesis showed an early inhibition of DNA synthesis whilst RNA and protein synthesis continued for 24-48 hours. This was reminiscent of a classic alkylating agent-like effect. In vivo studies with specific alkylating agent-sensitive, or antimetabolite-sensitive tumours showed no antitumour activity although significant inhibition of Ehrlich ascites tumour cell growth was observed at high doses. In vitro cytotoxicity studies showed LS 1727 to be inactivated in the presence of mouse, rat and dog liver supernatants. This would explain the poor antitumour effects in vivo compared with the in vitro observations. Because LS 1727 is a nitrosocarbamate its possible mutagenic activity was investigated. LS 1727 was highly mutagenic but this property was also lost in the presence of a rat liver microsomal fraction. Although an effective cytotoxic agent in vitro LS 1727 is only effective in vivo at toxic doses.

Alkylating Agents↗

Serum calcium levels in rheumatoid arthritis.

Total and corrected (for albumin) serum calcium levels were investigated in a cross-sectional study of 394 patients with rheumatoid arthritis, 4490 healthy subjects, and 2609 inpatients at a district general hospital. Patients with rheumatoid arthritis had lower mean calcium levels than the healthy subject (p less than 0.001), but had similar levels to inpatients at the district general hospital. Thirty-eight inpatients with rheumatoid arthritis at a hospital for rheumatic diseases had lower mean corrected and total calcium levels than all other groups (p less than 0.01). Corrected or total calcium levels higher than 2.60 mmol/l or corrected calcium levels lower than 2.20 mmol/l were uncommon in the patients with rheumatoid arthritis. A longitudinal study of serum calcium levels in 17 patients with rheumatoid arthritis over 6-48 months showed considerable temporal variation in total and corrected calcium levels. Transient hypercalcaemia and hypocalcaemia occurred occasionally, but for most of the time calcium levels were normal. Changes in calcium levels were not related to changes in clinical, haematological, or immunological parameters of disease activity. Mean serum calcium levels are lower in disease than health; this occurs in RA as well as other diseases.

Adrenal Cortex Hormones↗