Biomedical subjects
Publications and source records attributed to M H Winterborn.
Two infants with meningitis who were treated with phenobarbitone and high-dose chloramphenicol showed progressive falls in the peak blood levels of chloramphenicol. A standard chloramphenicol dose of 50 mg/kg daily would have produced subtherapeutic blood levels after only a few days. The importance of measuring serial blood chloramphenicol concentrations is stressed.
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All the survivors of a series of 88 patients with Henoch-Schönlein nephritis were examined after a follow-up of six and a half to 21 years (mean 9-9). Sixty-one patients had no demonstrable abnormality; six had minor urinary abnormalities; five had hypertension without urinary abnormally or renal dysfunction; four had heavy proteinuria; eight were in chronic renal failure, three of whom were on regular dialysis; and four patients had died within 25 months of onset. Neither corticosteroids nor immunosuppressive drugs alone or in combination appeared to influence the outcome. A clinical presentation with a combination of acute nephritis and a nephrotic syndrome and a high proportion of crescents in renal biopsy specimens was associated with a poor outcome. Neither the clinical presentation nor the renal morphology were, however, precise determinants of outcome. Outcome was not related to age, associated streptococcal infection, or recurrences of the rash. The clinical state two years after presentation was compared with the state six and a half years or more after presentation in 76 patients. The clinical state had changed in 32 patients, in 17 of whom it had deteriorated. It was not possible to identify with any certainty the patients who would deteriorate (or improve). Patients who have had Henoch-Schönlein nephritis should be followed up for at least five years.
Urinary tract infection is a common disorder of childhood which frequently causes no symptoms. Bacteriological proof should always be obtained because symptoms may be misleading. The diagnosis of a first infection should lead to radiological investigation. Routine tests to localize the site of infection are not yet available but their use in the future in conjunction with increased awareness of the factors leading to pyelonephritis should help to identify children at risk from renal damage. Two thirds of children with urinary infections have normal lower urinary tracts or only minor abnormalities and may be treated for symptomatic infections with intermittent antibiotics. The risk of renal damage from infection is virtually confined to the remainder: children with obstructive uropathy, preschool children with severe vesicoureteric reflux, and those with pre-existing chronic renal failure. It remains to be shown by controlled therapeutic trials whether renal scarring can be prevented by long-term chemoprophylaxis or surgical correction of reflux. Until the results of current trails are known, children with reflux or impaired renal function should be treated medically in the first instance and screening of healthy children for covert bacteriuria should probably be confined to the preschool age-group.
The plasma disappearance rate, or slope clearance, after a single intravenous injection of 51Cr-EDTA was compared with simultaneously determined standard (UV/P) clearances of inulin, creatinine and 51Cr-EDTA in 4 healthy adults and 18 children with renal disease but no reflux. Slope clearance correlated well with standard inulin (r=0.99) and 51Cr-EDTA (r=0.97) clearances and was more accurate than creatinine clearance. Slope clearance x0.82 estimated standard 51Cr-EDTA clearance with +/- 12% accuracy in these subjects. In 18 children with vesico-ureteric reflux the correlations of the standard clearance methods with slope clearance were significantly reduced. Slope clearance may be measured with only two plasma samples and is recommended as the method of choice for determining glomerular filtration rate in children with gross reflux or impaired ability to empty their bladders.
The treatment of five children with the haemolytic-uraemic syndrome using streptokinase is described to illustrate the difficulties and limitations of thrombolytic therapy in this disease. This experience is germane to the design of multicentre clinical trials.A multivariate analysis relating clinical outcome to the data obtained at the time of admission was also carried out for 31 children with the disease treated in four centres. The results suggest that this technique may help to identify those patients likely to have a fatal outcome. An expanded form of this type of analysis should be incorporated in future clinical trials.
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Quantitative bone histology, serum biochemistry and skeletal survey were studied in 21 children aged 6-18 years with moderate renal impairment (glomerular filtration rate (GFR) 20-50 ml/min/1.73 m2) but no previous history of bone disease to try and identify early markers of the disease simpler and less invasive than histomorphometry. Ninety percent of the 20 biopsies studied exhibited abnormal quantitative bone histology. Predominant hyperparathyroidism was noted in 30%; osteomalacia in 5%, mixed picture in 55%. Parathyroid hormone (PTH) levels were elevated in all the patients. Alkaline phosphatase bone isoenzyme was elevated in 95% of the patients. X-ray was relatively insensitive showing mild changes of hyperparathyroidism in only 3 patients (14.3%), all of whom had GFR less than 30 ml/min/1.73 m2. We feel that the elevated PTH levels denote a true state of hyperparathyroidism which probably precedes histological derangement in chronic renal failure, and may justify prophylactic treatment of renal osteodystrophy in children with moderate renal impairment.
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