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Biomedical subjects

N T Richards

Publications and source records attributed to N T Richards.

17 recordsLinked to original sources

Pigeons and peritonitis?

We report an outbreak of fungal peritonitis due to Candida parapsilosis in 12 patients undergoing chronic ambulatory peritoneal dialysis (CAPD). All 12 patients were treated by removal of the CAPD catheter together with systemic antifungal therapy. There were no peritonitis-related deaths. Four patients were successfully returned to CAPD at a later date. Microbiological investigation during the outbreak demonstrated colonization of various areas of the CAPD Unit and medical ward with the organism. C. parapsilosis was also isolated from pigeon guano obtained from window-sills. The number of cases of peritonitis due to this organism decreased markedly after bird-proof netting was installed. We believe that this is the first report of an outbreak of CAPD peritonitis due to faecal carriage of C. parapsilosis by pigeons.

Adult

Increased prevalence of renal biopsy findings other than diabetic glomerulopathy in type II diabetes mellitus.

It is a widely held view that when a patient with type I diabetes mellitus and diabetic retinopathy or neuropathy develops renal impairment the renal lesion will be diabetic glomerulonephropathy. This has been extrapolated to apply to type II diabetes. We have performed a retrospective study of the clinical data of patients with diabetes mellitus who have had a renal biopsy between November 1980 and December 1990. Seventy-one patients were biopsied, data were available on 68. Nineteen of 22 type I diabetics had diabetic glomerulopathy, two had diabetic glomerulopathy in addition to another lesion only one patient did not have diabetic glomerulopathy. Twenty-three of 46 type II diabetics had diabetic glomerulopathy alone 22 having an alternative diagnosis. Eight further patients were identified who were not known to be diabetic at the time of renal biopsy, but whose biopsies revealed diabetic glomerulopathy. These data suggest that patients with type II diabetes and renal impairment should have a renal biopsy as part of their investigation.

Adult

Low-concentration ouabain does not inhibit noradrenaline-induced contraction of human resistance arteries.

1. Using a Mulvany-Halpern myograph to measure changes in isometric tension, we have investigated the effect of ouabain on noradrenaline-induced contraction of human subcutaneous resistance arteries. 2. Low concentrations of ouabain (10 nmol/l or less) were shown not to alter vascular smooth muscle contractility or sensitivity to noradrenaline. 3. In contrast, higher concentrations of ouabain (100 nmol/l or more) were found to depress vascular smooth muscle contractility and to reduce the sensitivity of the noradrenaline concentration-response relationship. 4. These findings may have implications regarding the presence of an endogenous inhibitor of the sodium pump in essential hypertension and in pregnancy-associated hypertension.

Arteries

Acute haemodialysis during the Armenian earthquake disaster.

On the 7 December 1988 an earthquake struck a densely populated region in northern Armenia. Up to 50,000 people were killed and many thousands were seriously injured. At least 385 of these casualties developed acute renal failure secondary to crush syndrome and required dialysis. The Armenian renal unit at Yerevan, in common with units elsewhere, was already overstretched to cope with the dialysis requirements of their patients with chronic renal failure before the earthquake. Most of the patients requiring dialysis were transferred to other hospitals in the USSR but 120 patients remained in Yerevan, the majority at the regional renal unit, overwhelming the resources. We assisted by taking a team of dialysis personnel, equipped with portable haemodialysis machines, to Yerevan. We performed 57 haemodialysis sessions and treated 15 patients, 13 of whom ultimately survived. Valuable lessons were learnt about the medical management of disasters abroad.

Acute Kidney Injury

Immunoglobulin heavy chain switch region gene polymorphisms in glomerulonephritis.

Much evidence suggests that primary IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN) are immune complex mediated diseases. Moreover, genetic factors may play an important role in their pathogenesis. Recently, restriction fragment length polymorphisms (RFLPs) of the immunoglobulin heavy chain genes have been described which appear to associate with glomerulonephritis. We have studied RFLPs of the switch region of the IgM (S mu) and IgA1 (S alpha 1) heavy chain in MN and IgAN. DNA obtained from British Caucasoids with IgAN (N = 75), MN (N = 43), and normal controls (N = 73), was digested with the restriction enzyme Sac1, and studied using Southern blot techniques and hybridization with a 32P labelled DNA probe homologous to S mu. This probe detects RFLPs at the S mu and S alpha 1 loci. The genotypic and allelic frequencies of the S mu and S alpha 1 alleles in IgAN and MN was similar to normal controls. Caucasoid subjects with IgAN from Northern and Southern Europe (Finland and Italy, respectively) were also studied to determine whether an ethnic variation in genetic susceptibility to IgAN exists. The frequency of the S mu and S alpha 1 alleles was similar between the patient groups and their respective local healthy controls. These results do not support the recent findings of an association with RFLPs of the S mu and S alpha 1 loci in IgAN and MN, and suggest that the immunoglobulin heavy chain switch region genes are not important in conferring disease susceptibility to IgAN or MN.

Blotting, Southern

HLA DQ region gene polymorphism associated with primary IgA nephropathy.

IgA nephropathy (IgAN) has been associated with HLA-DR4. We have recently described two non-allelic Taq I DQ beta gene-associated fragments sized 2.0 kb (T2) and 6.0 kb (T6), which strongly associate with DR4. T2 represents a polymorphism of the DQ beta gene and has been redesignated DQw8 (10th International HLA Workshop). The origin of the T6 fragment has not been determined, but probably represents a polymorphism of either the DQ beta or DX beta gene. When present together T2 and T6 define a subgroup of DR4 subjects at high risk of developing autoimmune disease. We have, therefore, studied DQ beta gene polymorphisms in IgAN. The DR antigen distribution was similar in IgAN and normal controls. The T2+/T6+ phenotype was present in 49% patients with IgAN compared to 15% of controls [P less than 0.0001, chi 2 = 32.8, Cramer's V = 0.41; relative risk = 5.5 (range, 2.8-11.0)]. Seventy-two percent of DR4+ IgAN patients and 29% of DR4+ controls were T2+/T6+ (P = 0.007, chi 2 = 17.0). These findings confirm the hypothesis that disease susceptibility genes are important in IgAN, and suggest that the putative gene(s) are located within or near to the DQ subregion. Moreover, similar DQ beta gene associations have been found in IDDM and pemphigus vulgaris, pointing to a common immunogenetic mechanism predisposing to several autoimmune diseases.

Blotting, Southern

Cyclosporin A inhibits endothelium-dependent, prostanoid-induced relaxation in human subcutaneous resistance vessels.

The effect of cyclosporin on endothelium-dependent relaxation of human subcutaneous resistance vessels was investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Acetylcholine-induced relaxation was shown to consist of at least two components, one mediated through vasodilatory prostanoids, the other through endothelium-derived relaxing factor (EDRF). Incubation with cyclosporin inhibited endothelium-dependent relaxation, as assessed by the response to acetylcholine. The inhibitory effect of cyclosporin on the acetylcholine response was most marked in the presence of methylene blue, which is an inhibitor of EDRF. This suggests that the inhibition of endothelium-dependent relaxation by cyclosporin is mediated by an effect on vasodilatory prostanoids.

Acetylcholine

Cyclosporine A inhibits relaxation but does not induce vasoconstriction in human subcutaneous resistance vessels.

The effects of cyclosporine on the functional characteristics of human subcutaneous resistance vessels were investigated. Resistance vessels were obtained from normal subjects undergoing routine surgery. Incubation with cyclosporine did not alter the resting tone of the vessels, but decreased the maximum contractile response and the sensitivity of the vessels to stimulation with exogenous noradrenaline and potassium. Cyclosporine decreased the rate of spontaneous relaxation and inhibited endothelium-dependent relaxation as assessed by the response to acetylcholine. Paradoxically, endothelium-independent relaxation as assessed by the response to sodium nitroprusside was augmented. Hypertension induced by cyclosporine may, in part, be explained by a reduction in relaxation of peripheral resistance vessels.

Cyclosporins

Endothelin-induced contraction of human peripheral resistance vessels is partly dependent on stimulation of sodium-hydrogen exchange.

The role of Na-H exchange in endothelin-induced contraction of human peripheral resistance vessels was investigated. Endothelin produced a dose-dependent contraction which was greatly attenuated in the presence of a low extracellular sodium concentration. Inhibition of Na-H exchange by the amiloride analogue 5-(N,N-hexamethylene) amiloride (5-NNHA) resulted in a greater than 65% relaxation of a maximal endothelin-induced contraction in the presence of normal extracellular sodium. However, in the presence of a low extracellular sodium concentration, inhibition of Na-H exchange only resulted in a 25% relaxation. These data suggest that endothelin-induced vasoconstriction of human peripheral resistance vessels is mediated in part by stimulation of Na-H exchange.

Amiloride

Changes in the impedance cardiogram occurring with change in posture in patients with heart disease.

The response of the heart to changes in posture from supine through sitting to standing was recorded by impedance cardiography. The study comprised 22 normal subjects and 74 patients with a variety of heart diseases. The results demonstrate that in normal subjects acceleration of blood in systole decreased on sitting and standing. In subjects with impaired cardiac function this acceleration increased on sitting and standing from the supine position. This clear-cut difference in response provides a subtle method of detecting impaired function and in addition, provides a method of monitoring the effects of vasodilator or other treatment.

Cardiography, Impedance

Long term follow-up of patients with Cushing's disease treated by interstitial irradiation.

The first 86 patients with Cushing's disease treated with interstitial irradiation (by needle implantation) as the sole therapy were reviewed. In the 82 patients who were reassessed 1 yr after treatment 63 (77%) achieved remission. This study comprises the outcome and complications in the 54 patients who had a remission and whom we were able to follow. The follow-up period ranged from 3-26 yr (mean, 10.5) from the time of remission. No instance of clinical or radiological relapse has occurred. Of these 54 patients, yttrium-90 alone was used in 32, of whom 12 (37%) required corticosteroid or T4 replacement therapy in a mean time of 3.5 months; in 7 of these 12 we elected to give an ablative dose. Gold-198 alone was used in 15 patients, of whom 7 (47%) developed hypopituitarism in a mean time of 76 months. Both isotopes were used in 7 patients. A diurnal serum cortisol rhythm was found in 28 of the 31 patients who were not receiving corticosteroid therapy. In 5 of the 7 patients with an initially abnormal pituitary fossa, serial radiological studies revealed remodelling in 3. There have been no complications in the last 17 years. Pituitary implantation with yttrium-90 is an effective alternative to transsphenoidal hypophysectomy, with a high remission rate, no recurrence (as yet), no operative complications, and avoidance of hormone replacement in the majority.

Adolescent

Developments in dialysis for acute renal failure.

Although the complication of acute renal failure may occur in all types of medical and surgical patients, many clinicians still treat it using the conservative methods of management first described over 30 years ago. Active management, with early dialysis and adequate nutrition, keeps the patient in the best possible condition so that sufficient time for recovery of renal function is allowed. Many refinements in dialysis technique have occurred and some of these are described below.

Acetates

Impaired growth hormone response to human pancreatic growth hormone releasing factor [GRF(1-44)] in type 2 (non-insulin-dependent) diabetes.

Human pancreatic growth hormone releasing factor [GRF(1-44)] is the largest molecule of several peptides recently isolated from pancreatic tumours associated with acromegaly. It has been shown to stimulate the release of growth hormone in normal subjects and provides a safe and reliable tool for examining growth hormone release. A study was conducted to examine the release of growth hormone in patients with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes. GRF(1-44) stimulated the release of growth hormone in normal subjects and produced no side effects. A response of similar magnitude occurred in Type 1 diabetic patients despite their concomitant hyperglycaemia. In contrast, the response in Type 2 diabetes was significantly impaired compared with normal volunteers (p less than 0.05) and Type 1 diabetic patients (p less than 0.02). These findings may well indicate that there is a defect in central hormonal control in Type 2 diabetes.

Adolescent