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Biomedical subjects

M H Winterborn

Publications and source records attributed to M H Winterborn.

At least 19 recordsLinked to original sources

Hypercalciuria and ultrasound abnormalities in children with cystinosis.

We noted microscopic haematuria in children with cystinosis. To investigate this we studied urinary calcium excretion and undertook renal ultrasound scans. Most patients had elevated urinary calcium excretion and all had abnormal appearances on ultrasound scan, ranging from increased cortical echogenicity only to those with increased cortical and medullary echogenicity. The ultrasound scan appearance was graded and correlated with laboratory parameters. It remains unclear as to the aetiology of the ultrasound findings and whether they are a consequence of treatment or a hitherto unrecognised feature of the disease.

Calcium Metabolism Disorders↗

Assessment of retinol-binding protein excretion in normal children.

Retinol-binding protein (RBP) is a low molecular weight protein freely filtered at the glomerulus. The fractional tubular reabsorption of RBP is 99.97% and increased excretion is therefore a sensitive marker of tubular dysfunction. We obtained early-morning urine specimens from 151 well children, from newborn to 16 years of age. RBP was measured using an enzyme-linked immunosorbent assay, albumin by a radioimmunoassay and creatinine by a modified Jaffé reaction. Protein excretion was assessed by calculating the protein:creatinine ratio for early-morning urine samples. We found a fall in both RBP and albumin excretion with increasing age, particularly in the 1st year of life, with a much wider variation in values from the infants studied. The mean excretion of RBP for children aged 0-6 months [51.4 (0.6-4,719) micrograms/mmol] was significantly higher (P < 0.001) than the mean for children aged 6 months to 16-years [15.0 (3.8-60) micrograms/mmol]. It has been shown that measurement of tubular proteinuria using the RBP: creatinine ratio is useful in the assessment of children with renal disease and we propose a value two standard deviations above the geometric mean for the age of the patient as an upper limit of normal.

Adolescent↗

Cerebral blood flow in acute mountain sickness.

Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS.

Acetazolamide↗

Effect of carbon dioxide in acute mountain sickness: a rediscovery.

The effect of adding CO2 to inhaled air in six subjects with acute mountain sickness was investigated during a medical expedition to 5400 m.3% CO2 in ambient air increased ventilation and resulted in a rise in PaO2 of between 24% and 40%. There was a 9-28% increase in PaCO2 and a reduction of the respiratory alkalosis normally seen at high altitude. Symptoms of acute mountain sickness were rapidly relieved. In three subjects cerebral blood flow increased by 17-39%, so that oxygen delivery to the brain would have been considerably improved. This study confirms earlier suggestions of the beneficial effect of CO2 inhalation at high altitude.

Administration, Inhalation↗

Oral mannitol in control of fluid balance.

Oral mannitol 40 g/m2 was given as 5.5% and 20% solutions to six dialysed children. Both solutions caused diarrhoea. Body weight showed no significant change after the 5.5% solution, which may be used as 'free drink', but fell by 19.8 g/g mannitol after the 20% solution.

Administration, Oral↗

The origin of proteinuria at high altitude.

Urinary protein excretion was measured before and after the intravenous infusion of lysine in 14 normal subjects after 4-6 days' acclimatization at 4846 m. Urinary albumin excretion before lysine was elevated in 11 subjects but alpha 1-microglobulin was detected in only four. After lysine a large increase in albumin excretion occurred in all subjects. Together with the absence of alpha 1-microglobulin before lysine this implies that increased glomerular capillary permeability is the major cause of proteinuria after acclimatization to high altitude. The estimated minimum glomerular fluid albumin concentration was increased two to three fold above the published values in normal controls.

Acclimatization↗

Haemolytic-uraemic syndrome: clinical experience of an outbreak in the West Midlands.

In 1982-3, 35 children from the West Midlands developed the haemolytic-uraemic syndrome. This was a higher incidence than expected and included an epidemic localised to the Wolverhampton area in July 1983 which comprised 11 cases in two weeks. Twenty three children were treated with dialysis, of whom three died. Six patients developed chronic renal failure, four of them from Wolverhampton. Extrarenal manifestations included neurological sequelae in four, two of whom also developed insulin dependent diabetes mellitus and chronic renal failure. Cardiomyopathy occurred in one child, who also had chronic renal failure. The outcome of these 35 patients was not predictable from prognostic criteria derived from previous experience in Britain. This, together with the high prevalence of extrarenal disease and the geographical localisation of the 1983 outbreak, suggested an aetiological agent new to the region. Faeces from 10 patients were examined for verotoxin producing Escherichia coli, and positive strains of serotype O157.H7 were found in three patients during the Wolverhampton outbreak.

Child↗

The role of prostaglandins in Bartter's syndrome.

In two children with Bartter's syndrome, treatment with indomethacin halved the urinary excretion of prostaglandins E and F within 24 hours and subsequently maintained it within the normal range during follow-up for more than 5 years. Growth rate was improved and plasma renin and aldosterone and the urinary excretions of sodium and calcium fell to normal. Both children continued to lose excessive quantities of potassium in the urine. The results provide further evidence that over-production of prostaglandins is not the primary cause of Bartter's syndrome.

Aldosterone↗

Effect of low dose 1 alpha-hydroxycholecalciferol on glomerular filtration rate in moderate renal failure.

Serial measurements of 51Cr edetic acid clearance were made over a period of one year in two groups of 8 children, in a double blind trial of 1 alpha-hydroxycholecalciferol (10 ng/kg/day) and calciferol (670 ng/kg/day). Glomerular filtration rate (GFR) at the beginning of the trial was 20-50 ml/min/1.73 m2; it rose in the children given 1 alpha-hydroxycholecalciferol (group A) after 6 months but was not appreciably different from the pretreatment value after 12 months. The GFR in the children given calciferol (group B) showed no significant difference at 6 or 12 months. Parathyroid hormone values fell markedly in group A after 6 months but not in group B. Quantitative bone histology improved considerably in group A but not in group B at 12 months. Low dose 1 alpha-hydroxycholecalciferol may be used effectively for renal osteodystrophy in children with moderate but stable renal failure without jeopardising renal function.

Adolescent↗

Plasma renin activity in children after surgical relief of hydronephrosis.

Blood pressure and supine plasma renin were measured in fourteen children aged seven to eighteen years whose hydronephrosis had been relieved surgically two to eleven years previously. Values did not differ significantly from age matched controls. It has been suggested that renal ischemia may persist after relief of hydronephrosis but our results show that hyperreninemia rarely occurs within two to eleven years of effective surgery. Further studies of blood pressure and renin after this period of time remain to be done.

Adolescent↗

Hypocomplementaemia due to a genetic deficiency of beta 1H globulin.

An 8-month-old Asian boy who presented with the haemolytic uraemic syndrome was found to have a low haemolytic complement, and in particular a very low C3 level, with a normal C4 level. These abnormalities persisted after recovery and were not associated with the presence of circulating C3 nephritic factor. A clinically healthy 3-year-old brother was found to have an identical complement profile, which indicated increased alternative pathway activation. Both brothers had normal levels of the C3b inactivator, but very low levels of beta 1H globulin (less than 10% of a reference standard serum). The parents, who were first cousins, had half-normal levels of beta 1H globulin, and low levels were found in other members of the family, indicating that the defect was inherited.

Child, Preschool↗