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Biomedical subjects

R J Winney

Publications and source records attributed to R J Winney.

At least 37 records · Page 2Linked to original sources
PubMed1991

The disposition of paracetamol and the accumulation of its glucuronide and sulphate conjugates during multiple dosing in patients with chronic renal failure.

We have compared the disposition of oral paracetamol (1.0 g t.d.s. for 10 days) in 6 healthy volunteers and 6 conservatively-managed patients with chronic renal failure (mean plasma creatinine 451 mumol.l-1). Blood was sampled daily for 10 days before the morning dose of paracetamol. Each day the pretreatment plasma concentrations of paracetamol were higher in the renal failure patients than in the volunteers, with mean values over the 10 days of 3.1 and 1.1 mg.l-1 respectively. The mean daily plasma concentrations of the sulphate and glucuronide conjugates of paracetamol were markedly higher in the renal failure group and apparent steady-state concentrations of about 25 and 85 mg.l-1 were reached on the 2nd and 6th days respectively. The mean steady-state plasma concentrations of the glucuronide conjugate on the 7th to 10th days of treatment were positively correlated with the plasma creatinine concentration (r = 0.97), but this relationship did not hold for the sulphate conjugate. Cysteine and mercapturate conjugates could only be detected in one patient. Predictions of steady-state concentrations based on previous studies with single doses of paracetamol in renal failure patients were remarkably accurate for the glucuronide but not for the sulphate conjugate. These results are consistent with some extra-renal elimination of retained paracetamol conjugates in patients with chronic renal failure, with limited regeneration of the parent compound. The sulphate metabolite did not accumulate as predicted, possibly because of depletion of inorganic sulphate.

Acetaminophen↗
PubMed1991

Heart rate variability and cardiac arrhythmias in patients with chronic renal failure.

Heart rate variability was measured from 24-h electrocardiograms in 61 patients with end stage chronic renal failure. The method used counts the number of times successive RR intervals differ by more than 50 ms over the 24-h period, and is a reliable indicator of cardiac parasympathetic activity. Also analysed were the frequency and type of ectopic beats and other arrhythmias. Twenty-one subjects (34%) had varying numbers of ventricular ectopic beats, and twelve (20%) had frequent supraventricular ectopics. Total 24-h count values were abnormal in 30 (76%) of the 41 subjects whose tapes were technically suitable for this analysis. There were no sex differences, but those patients maintained on haemodialysis had significantly lower counts than those on continuous ambulatory peritoneal dialysis. We conclude that about three-quarters of patients with chronic renal failure have abnormal cardiac parasympathetic activity. This may increase susceptibility to cardiac arrhythmias and sudden death and contribute to the high mortality of patients with chronic renal failure.

Adolescent↗
PubMed1991

Multiple forms of alkaline phosphatase in plasma of hemodialysis patients.

We used quantitative assays to measure the activity of the bone, liver, and intestinal forms of alkaline phosphatase in plasma in 75 patients with endstage chronic renal failure undergoing hemodialysis. The results were correlated with radiological and other biochemical indices of bone disease and with biochemical indices of liver disease. The total activity of alkaline phosphatase in plasma increased in 28 patients. In 10 of these patients, nine of whom had increased activity of gamma-glutamyltransferase in plasma, the increase in total activity of alkaline phosphatase was from the liver isoenzyme alone (nine patients) or from the liver and bone isoenzymes together (one patient). Intestinal alkaline phosphatase in plasma, although greater than 23 U/L in eight patients, was solely responsible for the increase in total alkaline phosphatase in one patient (who had normal gamma-glutamyltransferase). Bone alkaline phosphatase in plasma was increased in 25 patients, seven of whom had normal total alkaline phosphatase, and was closely correlated (r = 0.78) with osteocalcin concentration in plasma, which was increased in a much greater proportion of patients (99%). Both total and bone alkaline phosphatase were correlated with parathyrin in plasma (r = 0.46 and 0.50, respectively) and with osteocalcin (r = 0.60 and 0.78, respectively). Osteocalcin and bone alkaline phosphatase, but not parathyrin, decreased with age, implying that the skeletal response to parathyrin may be age dependent. In patients with increased total alkaline phosphatase undergoing hemodialysis, the concurrent measurement of gamma-glutamyltransferase may help identify whether the enzyme increase originates from the liver or bone, but this approach wrongly identified the source of the increase in three of 28 patients. Therefore, we recommend a separate measurement of the bone isoenzyme of alkaline phosphatase.

Adolescent↗
PubMed1989

Paracetamol disposition and metabolite kinetics in patients with chronic renal failure.

The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life of paracetamol from 2 to 8 h was similar in the 3 groups (2.1 to 2.3 h) but from 8 to 24 h it disappeared much more slowly in the renal failure patients (half-life 11.7 compared with 4.9 h in the healthy volunteers). Plasma concentrations of paracetamol glucuronide and sulphate conjugates were greatly increased in the patients with moderate renal failure and the mean plasma half-lives were 30.5 and 21.8 h respectively compared with about 3 h in the healthy volunteers. Plasma concentrations of these metabolites were even higher in the dialysis patients and there was no significant fall over 24 h. The cysteine and mercapturic acid conjugates of paracetamol could only be measured in plasma in the patients with renal failure and concentrations were very low. The fractional urinary recovery of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates was similar in healthy volunteers and patients with moderate renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1989

Leptospira icterohaemorrhagiae infection presenting as acute renal failure.

The features of leptospiral infection should be sought in all cases of acute renal failure since management depends on the recognition of the clinical syndrome and serological confirmation is usually delayed. Hepatic and renal involvement is usual but renal failure without significant derangement of liver function is described.

Acute Kidney Injury↗
PubMed1989

Can low-dosage aluminium hydroxide control the plasma phosphate without bone toxicity?

Sixteen patients treated exclusively by haemodialysis using reverse osmosis water treatment for up to 7 years (mean 49.3 +/- 17 months) were assessed for evidence of bone aluminium accumulation and toxicity. All patients were treated with aluminium hydroxide phosphate binders for the duration of dialysis but the dosage was restricted to a maximum of 2.85 g daily (mean daily dose 2.6 +/- 0.8 g). The mean plasma phosphate over the 12 months prior to the study was 1.68 +/- 0.42 mmol/l and in only three patients was adequate control of the plasma phosphate not achieved. No patient had evidence of fracturing bone disease. Bone aluminium staining was present in only two patients but was seen at the calcification front in only one of these. Three patients had histological evidence of osteomalacia, but in none was aluminium staining present. Mean bone aluminium was moderately high at 36.67 +/- 31 micrograms/g and in only three patients exceeded 40 micrograms/g. This study indicates that adequate control of the plasma phosphate can be achieved with low dosage of aluminium hydroxide, and in the medium term is not associated with evidence of bone aluminium toxicity.

Aged↗
PubMed1988

Altered lung vascular permeability during intermittent haemodialysis.

Hypoxia is known to develop during intermittent haemodialysis. To investigate if increased pulmonary capillary permeability to protein contributes to this phenomenon, a dual-isotope technique using Indium-labelled transferrin and Technetium-labelled red blood cells was used. Lung vascular permeability was measured in eight patients with dialysis-dependent chronic renal failure immediately before and during intermittent haemodialysis with cuprophane membranes. As a group there was a significant increase in lung vascular permeability during the early stages of haemodialysis, compared to predialysis values (P less than 0.05) and this increase occurred during the period when the patients were leucopenic and maximally hypoxic. During the haemodialysis period, but not the predialysis period, the permeability index was also significantly increased compared to a group of eight controls (P less than 0.05). These results suggest that increased vascular permeability may contribute to dialysis-induced hypoxia and that this may relate to neutrophil activation within the pulmonary vascular bed.

Adolescent↗
PubMed1988

Mefenamic acid nephropathy: an interstitial and mesangial lesion.

Six cases of acute renal failure associated with mefenamic acid therapy are described. Five patients were non-oliguric and five patients had clinical features of salt and water depletion. In these patients the presenting symptoms were abdominal pain, diarrhoea and vomiting. Renal biopsy in five patients showed interstitial nephritis and mesangial proliferation. All patients recovered without specific therapy after withdrawal of the drug, but in four patients mild renal impairment persisted. These findings indicate that both interstitial and mesangial changes are common features of acute renal failure due to mefenamic acid therapy.

Adult↗
PubMed1987

Aluminium-related osteomalacia: response to reverse osmosis water treatment.

It is generally accepted that aluminium induces osteomalacia in chronic hemodialysis patients by binding to the calcification front, thereby inhibiting mineralization of osteoid. Because this form of osteomalacia is vitamin D resistant, the condition has often been assumed to be irreversible, although promising results have been achieved recently by using a chelating agent for removal of aluminium from the skeleton. In this paper we present four chronic hemodialysis patients with aluminium toxicity and histologic osteomalacia in whom the mineralization defect greatly regressed after the use of reverse osmosis treated-water for dialysis, but without further treatment. In three other patients, also with aluminium toxicity and histologic osteomalacia, similarly treated, the histological severity of the osteomalacia remained static. Those patients in whom bone mineralization status improved developed hyperparathyroidism after reverse osmosis water-treatment, whereas the static patients remained euparathyroid. The results suggest that resolution of aluminium related osteomalacia may occur with reduction in dialysis fluid aluminium, and that parathyroid hormone plays a role in the healing of aluminium related osteomalacia. The therapeutic implications are twofold: attempts to remove all traces of hyperparathyroidism may be detrimental to the bone mineralization status; and stimulation of the parathyroid glands by means of a mild reduction in dialysis fluid calcium may be of value in the management of those cases with persistent osteomalacia and low bone turnover.

Adult↗
PubMed1986

Chronic renal failure and cardiovascular autonomic function.

Autonomic function was assessed in 67 patients with chronic renal failure using a standardized battery of five cardiovascular reflex tests. The results showed that 38 (65%) had early or definite parasympathetic abnormalities, while 14 (24%) had additional sympathetic damage. There were no significant differences between those treated conservatively (n = 19), those on continuous ambulatory peritoneal dialysis (n = 8) and those on intermittent haemodialysis (n = 40). Cardiovascular autonomic damage is widespread among patients with chronic renal failure, however treated, and may have a number of clinical sequelae.

Adolescent↗
PubMed1986

Effect of a blood transfusion protocol and low dose steroid regime on renal transplant survival.

The effects of introduction of a low steroid regime and pre-transplant blood transfusion were evaluated. The kidney and patient survival rates for the period before such a policy was adopted were compared with the period after this policy. There has been a highly significant rise in patient survival rates to the present level of 95 per cent at three years. There was a similar rise in three year graft survival rates from less than 40 per cent to 66 per cent.

Actuarial Analysis↗
PubMed1986

Acquired cystic disease of the kidney in patients with end-stage chronic renal failure: a study of prevalence and aetiology.

Renal ultrasound scanning was performed in 100 patients with end-stage renal failure treated by both haemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Each kidney was assessed for the presence of acquired cystic disease and solid lesions. The appearances were divided into five grades from grade 0 (no cysts detected) to grade 4 (greater than 15 cysts per kidney). Other intra-abdominal organs were also scanned for the presence of cysts. The findings were then correlated with possible aetiological factors, including the type of dialysis used. Sixty-three percent of all the patients had acquired cystic disease of the kidney (ACDK). No solid lesions were found and no cysts were detectable in other organs. The presence and grade of ACDK did not correlate with the age or sex of the patient, the nature of the underlying renal disease, or the duration of chronic renal failure. There was a significant correlation between the grade of ACDK and the duration of both haemodialysis (P less than 0.001) and CAPD (P less than 0.01). The presence of residual renal function did not influence the development of cysts. ACDK had no effect on haemoglobin or other laboratory parameters measured.

Adult↗