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Biomedical subjects

C R Tomson

Publications and source records attributed to C R Tomson.

At least 19 recordsLinked to original sources

Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines.

BACKGROUND: Chronic renal failure (CRF) is associated with an increased risk of ischaemic heart disease (IHD), but the mechanisms responsible are controversial. We investigated the relationship of two sets of candidate mechanisms-indices of LDL oxidation and markers of inflammatory activity-with vascular endothelial dysfunction (VED). METHODS: We carried out cross-sectional analysis of 23 dialysed and 16 non-dialysed CRF patients, 28 healthy controls, and 20 patients with stable angina and normal renal function. The following were determined: (i) LDL oxidation by Cu(2+) and ultraviolet light, serum autoantibodies to oxidized LDL (oxLDL); (ii) forearm flow-mediated vasodilatation, plasma concentrations of adhesion molecules, and von Willebrand factor (vWF); and (iii) circulating levels of TNF-alpha and IL-6, C-reactive protein (CRP), and fibrinogen. RESULTS: Endothelium-dependent vasodilatation (EDV) was lower in angina, pre-dialysis, and dialysis CRF patients than in controls (all P<0.005). Compared with controls, vWf (P<0.005) and adhesion molecules (vCAM-1, P<0.005; iCAM-1, P=0.01; E-selectin, P=0.05) were raised in dialysis, and vCAM-1 (P=0.01) in pre-dialysis CRF patients. Dialysed patients had lower HDL cholesterol (P=0.01) and higher triglyceride (P=0.05) than controls, but LDL-oxidation was similar in all groups. Autoantibodies to oxLDL were raised in angina (P<0.005) and pre-dialysis (P=0.006), but were absent in most dialysed patients. Concentrations of IL-6, TNF-alpha, CRP and fibrinogen were elevated in CRF compared with control and angina patients (P<0.005). In the whole population, IL-6 and TNF-alpha correlated negatively with EDV, HDL cholesterol, and positively with triglyceride, blood pressure, vWf, iCAM-1, vCAM-1 and E-selectin (r=-0.43 to +0.70, all P<0.05). CONCLUSIONS: Endothelial dysfunction is unrelated to LDL oxidation, suggesting that LDL oxidation might not be a major cause of VED in CRF. In contrast VED was more severe in CRF than in angina patients and is associated with increased acute-phase proteins and plasma cytokines, demonstrating a chronic inflammatory state. These observations may explain the VED and increased IHD risk of patients with CRF.

Adult↗

Renal complications of jejuno-ileal bypass for obesity.

Jejuno-ileal bypass has until recently been an accepted treatment for refractory morbid obesity. Although hyperoxaluria causing renal tract calculi is a well-recognized complication, we describe eight patients who developed significant renal failure attributable to hyperoxaluria resulting from this procedure, three requiring renal replacement therapy. We review the literature, describing 18 other cases with renal failure, the mechanisms of hyperoxaluria and its treatment. Because reversal of the bypass may result in stabilization or partial improvement of renal function, these patients require long-term follow-up of renal function.

Adult↗

Can the use of low-dose dopamine for treatment of acute renal failure be justified?

The use of dopamine for the prevention and treatment of acute renal failure is widespread. Its use is based on physiology suggesting selective renal vasodilation when it is infused at low dose. This article reviews the available data on the clinical use of dopamine. When used to prevent acute renal failure in high-risk treatments there is no evidence of benefit of dopamine but, given the low incidence of significant renal failure, the studies are underpowered. In treatment of acute renal failure, the quality of the data is poor. Only in one small randomised trial of moderate acute renal failure in patients with malaria was a clinically significant benefit of dopamine shown. The rest of the data, in the form of case series, showed either no benefit of dopamine or small benefits of little clinical significance. Again, these studies are of insufficient power for conclusions to be drawn as to the overall benefits and risks. We conclude that benefits of dopamine use cannot be ruled out by currently available data but its use cannot be advised until trials examining clinically important endpoints in large numbers of patients have been performed.

Acute Kidney Injury↗

Calcified plaque is common in the carotid and femoral arteries of dialysis patients without clinical vascular disease.

BACKGROUND: Cardiac and vascular mortality are common in end-stage renal disease (ERSD) and are often attributed to accelerated atherosclerosis. SUBJECTS AND METHODS: We studied 24 non-diabetic ESRD patients without cardiac or vascular disease (M = 12, F = 12) and 24 age-, sex- and race-matched healthy controls. All underwent B-mode ultrasound for carotid and femoral intima media thickness (IMT) and plaque (% stenosis) together with blood pressure (BP), and echocardiograms to determine left ventricular mass. RESULTS: Both BP and mean IMT were similar in patients and controls. However, discrete plaque was present in 71% (17/24) of patients compared with 21% (5/24) of controls (P = 0.001), and % stenosis was greater in patients (carotid 12.2 +/- 11% vs 2.3 +/- 5.9%, P < 0.0004; femoral 16.4 +/- 19.1% vs 3.1 +/- 6.4%, P < 0.003). Plaque was soft/atheromatous in 3 of the 5 controls, but not in any of the 17 patients (P = 0.007), all of whom had calcified lesions. BP and cholesterol were not correlated with IMT or plaque in patients, but in control subjects carotid IMT was correlated with systolic BP (r = 0.66, P < 0.0005) and diastolic BP (r = 0.45, P < 0.03). In patients, the only independent variables related to vascular morphology were serum albumin which was inversely related to IMT (P < 0.03) and to plaque (carotid P < 0.05, femoral P < 0.02) and age, which was related to femoral plaque only (P < 0.04). Left ventricular end-diastolic internal dimension, not LVMI, correlated positively with carotid IMT (P < 0.04). CONCLUSION: Our results show that calcified plaque is common in ESRD patients and hypoalbuminaemia may be an associated factor.

Adult↗

Control of varicella-zoster infection on renal and other specialist units.

The introduction of chickenpox onto our renal unit recently raised several issues surrounding the management of patient and staff contracts. This paper describes the action taken and makes various recommendations for future management of similar cases. Guidelines are proposed for the management of patients and staff as well as the role of the infection control team in handling a chickenpox problem. Future developments, including the use of VZ vaccine for patient and staff, are also discussed.

Chickenpox↗

The pharmacokinetics of once-daily oral 400 mg ofloxacin in patients with peritonitis complicating continuous ambulatory peritoneal dialysis.

Seven patients with end-stage renal disease requiring support by continuous ambulatory peritoneal dialysis received once-daily 400 mg oral ofloxacin for 7 days for the treatment of bacterial peritonitis. Serum and peritoneal dialysis fluid (PDF) were collected for assay throughout the course of the study and for 5 days thereafter. Ofloxacin, desmethyl ofloxacin and ofloxacin-N-oxide accumulated over the course of therapy and could still be detected in serum and PDF 5 days after the end of therapy. The mean elimination half-life of ofloxacin in serum was 32 +/- 7 h, desmethyl ofloxacin 45 +/- 26 h and for ofloxacin-N-oxide 44 +/- 15 h. The total mean recovery of ofloxacin and its metabolites from the PDF was 15.4%. This regimen results in serum and PDF concentrations likely to be effective for the treatment of infection for at least 10 days.

Aged↗

Interdialytic weight gain and 48-h blood pressure in haemodialysis patients.

BACKGROUND: Hypertension, which is often associated with hypervolaemia, is common in haemodialysis patients and is a known determinant of target organ damage. Interdialytic weight gain due to volume overload has also been associated with mortality in haemodialysis patients. METHODS: We therefore studied 27 chronic haemodialysis patients who underwent 48-h ambulatory blood pressure monitoring between two midweek dialysis sessions, and 2D and M-mode echocardiography for determination of left ventricular mass index. RESULTS: Left ventricular hypertrophy (left ventricular mass index in men > 131 g/m2, women > 100 g/m2) was present in 70% (19/27) patients despite a mean 48-h blood pressure of 132 +/- 19/81 +/- 15 mmHg. Mean interdialytic weight gain was 1.6 +/- 0.8 kg and was not related to left ventricular mass index. Two patterns of interdialytic blood pressure change were apparent: in group 1 (16 patients) 48-h blood pressure increased (+19 +/- 12/13 +/- 9 mmHg), whereas in group 2 (11 patients) blood pressure fell (-10 +/- 13/-8 +/- 10 mmHg P < 0.0001). In both groups the number of hypertensive patients (group 1, 10/16; group 2, 6/11), the 48-h blood pressure (132 +/- 20/80 +/- 15 vs 132 +/- 18/82 +/- 15 mmHg) and interdialytic weight gain (+1.9 +/- 0.7 vs +1.3 +/- 0.7 kg) were similar. There was also no correlation between interdialytic blood pressure change and weight gain in either group. CONCLUSIONS: We conclude that interdialytic blood pressure changes cannot be directly related to interdialytic fluid gain, even in apparent volume-dependent hypertension, emphasizing the importance of additional factors in the control of blood pressure in end-stage renal disease.

Adult↗

A randomized controlled study of iron supplementation in patients treated with erythropoietin.

In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin (EPO), a prospective randomized controlled study was designed to investigate this issue. All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were randomized into three groups with different iron supplementation: Group 1, i.v. iron dextran 5 ml every 2 weeks; Group 2, oral ferrous sulphate 200 mg tds; Group 3, no iron. All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously. The hemoglobin concentration, reticulocyte count, serum ferritin, transferrin saturation, and EPO dose were monitored every two weeks for the first four months. Thirty-seven patients entered the study (12 i.v., 13 oral, 12 no iron). The three groups were equivalent with regard to age, sex, and other demographic details. Even allowing for dosage adjustments, the hemoglobin response in the group receiving i.v. iron (7.3 +/- 0.8 to 11.9 +/- 1.2 g/dl) was significantly greater than that for the other two groups (7.2 +/- 1.1 to 10.2 +/- 1.4 g/dl and 7.3 +/- 0.8 to 9.9 +/- 1.6 g/dl for Groups 2 and 3, respectively; P < 0.005 for both groups vs. Group 1 at 16 weeks). There was no difference between the groups supplemented with oral iron and no iron. Serum ferritin levels remained constant in those receiving i.v. iron (345 +/- 273 to 359 +/- 140 micrograms/liter), in contrast to the other two groups in which ferritin levels fell significantly (309 +/- 218 to 116 +/- 87 micrograms/liter and 458 +/- 206 to 131 +/- 121 micrograms/liter for Groups 2 and 3, respectively; P < 0.0005 for Group 1 vs. Group 2, and P < 0.005 for Group 1 vs. Group 3 at 16 weeks). Dosage requirements of EPO were less in Group 1 (1202 +/- 229 U/kg/16 weeks) than in Group 2 (1294 +/- 314 U/kg/16 weeks) or Group 3 (1475 +/- 311 U/kg/16 weeks; P < 0.05 vs. Group 1). The results of this study suggest that, even in iron-replete patients, those supplemented with i.v. iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO, compared with those patients receiving oral iron and no iron supplementation.

Cost-Benefit Analysis↗