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Biomedical subjects

T M Barratt

Publications and source records attributed to T M Barratt.

At least 73 records · Page 4Linked to original sources

Early markers of the renal complications of insulin dependent diabetes mellitus.

We investigated the associations between albuminuria, metabolic control, glomerular filtration, blood pressure, and platelet function in children with insulin dependent diabetes mellitus. The geometric mean (95% tolerance levels) albumin excretion (expressed as the geometric mean albumin to creatinine ratio on two overnight urine collections (UA/UC], in 60 diabetic children was 0.72 (0.80-6.9) mg/mmol, significantly greater than in 45 normal children (geometric mean 0.41 (0.14-1.17]. Mean (SD) glomerular filtration rate, measured by 51Cr edetic acid clearance during constant infusion, was significantly greater in diabetic children (129 (20) ml/min/1.73 m2) compared with normal controls (109 (13]. Mean (SD) renal length for height standard deviation score was +0.25 (1.1); systolic blood pressure standard deviation score was 0.15 (0.65), and diastolic blood pressure was 0.51 (0.82). Spontaneous platelet aggregation, expressed as percentage fall in platelet count in stirred whole blood after 2 minutes was 17.8 (9.2)% in the diabetic compared with 12.3 (7.9)% in normal children. UA/UC correlated with renal length and of the children with UA/UC above the normal range, 70% also had a glomerular filtration rate above the normal range. There was a weak correlation between UA/UC and glycated haemoglobin (HbA1c). All children with spontaneous platelet aggregation above normal had had diabetes for more than seven years. These cross sectional data define some of the early markers and inter-relationships that may be important in the development of nephropathy.

Adolescent↗

Hemolytic uremic syndrome.

HUS has now emerged as a common clinical and pathologic syndrome that may result from a variety of disease processes. On the basis of clinical and epidemiologic criteria, several distinct subgroups of the disorder have been distinguished, the most common of which are the result of infectious processes, whereas the rarer forms may be genetically determined or acquired defects in vascular homeostasis. A related group of bacterial toxins, verotoxins, and Shiga toxin, produced by a variety of species of enteric pathogens, have been implicated in the pathogenesis of typical childhood HUS. In the few years since verotoxin-producing organisms were first incriminated as the possible etiologic agents of HUS, there has been a remarkable growth in knowledge of the biology of verotoxin and its role, not only in HUS but in hemorrhagic colitis and childhood diarrhea. The availability of purified toxin and new tools for detection of verotoxin and verotoxin-producing organisms, such as monoclonal antibodies and probes for DNA hybridization, should enable definitive studies of the epidemiology and pathogenesis of verotoxin-associated HUS to be undertaken. The growing understanding of HUS should eventually lead to improved treatment and ultimately to prevention of this serious childhood disorder.

Child↗

Investigation of the dilated urinary tract.

Dilatation of the urinary tract does not necessarily imply obstruction, and other factors may be operative: maldevelopment, infection, reflux, and polyuria. Obstruction of the urinary tract in intra-uterine life is associated with renal dysplasia: the original obstructive lesion may be transient but the consequent dysplasia and dilatation may be permanent. Routine antenatal ultrasound identifies a new population of infants with urinary tract dilatation, many of whom remain asymptomatic and would not otherwise have come to medical attention: the natural history and appropriate schedules of investigation and management of this group are still being evaluated. Anatomical imaging by ultrasound establishes the presence and extent of dilatation. Micturating cystourethrography, intravenous urography and antegrade pyelography establish the site but not the functional significance of an obstructive lesion. Isotope renal scanning with 99mTc-DTPA may identify an acutely obstructed kidney with a decrease renal uptake, prolonged parenchymal transit time, and delayed clearance of the isotope from the renal pelvis after furosemide. However, such analyses often give equivocal results in infants with poor renal function and markedly dilated urinary tracts. Obstructive uropathy should be seen as a disturbance of the normal pressure-flow relationships in the urinary tract, and be defined and investigated as such. Antegrade perfusion with renal pelvic pressure measurements has technical pitfalls, but is the definitive method of establishing upper tract obstruction. Videocystourethrography is the established method of investigating the lower urinary tract in older children but needs further development to be applicable to infants.

Child↗

Intravascular platelet activation in the hemolytic uremic syndrome.

We studied intravascular platelet activation in patients with typical (epidemic) and atypical (sporadic) HUS and found defective aggregation, decreased platelet and increased plasma serotonin in both groups. The findings were present not only on admission during the thrombocytopenic stage of the disease, but persisted for several weeks after recovery of the platelet count. Reduced endothelial PGI2 production was significantly more common in plasma from atypical than typical cases. Plasma from both typical and atypical HUS patients induced aggregation of normal platelets, but this phenomenon was unrelated to both the presence of thrombocytopenia or the stage of the disease. Serum platelet aggregating activity was higher in the atypical HUS patients, and was not associated with immune complexes detectable by polyethylene glycol precipitation. The data indicate that intravascular platelet activation is a feature of both forms of HUS, and may be initiated by different mechanisms in the two subgroups. While abnormal PGI2 synthesis appears to be important in the atypical cases, neither defective PGI2 production nor platelet aggregation by plasma factors adequately accounts for platelet activation in the majority of typical cases.

Adolescent↗

Long-term outcome of boys with posterior urethral valves.

One hundred and fourteen boys with posterior urethral valves were treated between 1966 and 1975. Four died during the first hospital admission, 6 died from renal failure during childhood, 1 died from other causes and 15 were lost to follow-up. Eighty-eight were reviewed 11 to 22 years after diagnosis and the renal outcome of 98 patients is therefore known. Approximately one-third of patients presented under 1 month of age, between 1 month and 1 year, and over 1 year respectively. Bilateral vesicoureteric reflux was observed in one-quarter of the boys, more frequently in those presenting in the first month of life. Half of the patients were treated by primary valve ablation and half underwent temporary upper tract diversion: the outcome was worse for the diverted group. One-third of the boys had a long-term bad outcome for renal function. This outcome was associated with early presentation, bilateral vesicoureteric reflux and day-time urinary incontinence after the age of 5 years. The association of bad outcome with incontinence points to continuing bladder dysfunction as a major determinant of long-term outcome for renal function.

Follow-Up Studies↗

Antineutrophil cytoplasm antibody in crescentic glomerulonephritis.

Antineutrophil cytoplasm antibody (ANCA) has been reported in the sera of adults with Wegener's granulomatosis and microscopic polyarteritis, but this phenomenon has not so far been described in children. We report three children with crescentic glomerulonephritis in whom ANCA concentrations were raised at presentation. Two cases were idiopathic, and the other later developed features of Wegener's granulomatosis. In all three, plasma exchange and immunosuppression removed ANCA, but in only one case was there clinical improvement. This child later developed classical nasal lesions of Wegener's granulomatosis associated with a decline in renal function and a rise in ANCA. Plasma exchange and immunosuppression again produced a good clinical response and removed ANCA. This suggests that ANCA is either a marker of disease activity, or is involved in the pathogenesis of disease.

Autoantibodies↗

Imaging the kidneys and urinary tract in the neonate with acute renal failure.

Transitional nephrology seriously affects the manner in which radiological investigations and other forms of imaging are undertaken in the neonate. When this is complicated by acute renal failure then caution must be exerted in taking care of the neonate. The use of ultrasound and micturating cystourethrography are well described and form the baseline for all imaging of the renal tract. The physiological handling of TC99m DTPA and the contrasts used for IVU are described as well as the normal appearances of these techniques in the neonate. TC99m DMSA is also included, as are other modalities of imaging.

Acute Kidney Injury↗

Decreased sensitivity to heparin in vitro in steroid-responsive nephrotic syndrome.

The in vitro heparin sensitivity of 18 nephrotic children was compared with that of 10 normal children and 13 children with other renal diseases. The influence of age on the heparin sensitivity of 52 normal subjects (aged 12 to 85 years) was also studied. The heparin sensitivity was calculated from the dose-response curve obtained when increasing amounts of heparin were added to plasma and the kaolin partial thromboplastin time (KPTT) was measured. There was a significantly-reduced heparin sensitivity in nephrotic children compared to the control children and a progressive decline in heparin sensitivity with age. In the nephrotic syndrome heparin-sensitivity correlated with albumin and triglyceride concentrations but not with antithrombin III, platelet factor 4, cholesterol, fibrinogen, heparin cofactor II or histidine-rich glycoprotein. Addition of exogenous albumin did not restore the heparin sensitivity of nephrotic plasma. Four patients with Type II hyperlipidemia had a normal sensitivity to heparin. The decreased sensitivity to heparin thus does not appear to be a consequence of the nephrotic state, and may be a reflection of an underlying disturbance of charged macromolecules in steroid-responsive nephrotic syndrome.

Adolescent↗

Five year prospective study of plasma renin activity and blood pressure in patients with longstanding reflux nephropathy.

Eight of 100 normotensive children who had pyelonephritic scarring secondary to urinary infection and vesicoureteric reflux were found in an earlier study to have increased plasma renin activity (PRA). Because the risk of these patients becoming hypertensive is between 10% and 20% and because renin activity may play a part in the pathogenesis of the hypertension, PRA and blood pressure were studied in 98 of the original group after five years of follow up. Two patients could not be traced, and other factors that might influence blood pressure or PRA led us to exclude 13 others, 10 of whom were girls taking oral hormonal contraceptives. Increased PRA was found in 11 of the remaining 85 patients but not in five of the eight patients with increased PRA in the first study. Of eight children identified as hypertensive in the follow up study, only three had had increased PRA five years previously. In normal children PRA decreases with age. In the initial study this tendency was less pronounced in children with renal scars, and in the follow up study it was reversed. This was also confirmed by PRA standard deviation scores, which showed a significant increase in PRA during the five years. PRA tends to rise in patients with pyelonephritic scars as they grow older. There was no direct correlation between blood pressure and PRA, plasma creatinine concentration, or degree of scarring. Analysis of blood pressure standard deviation scores, however, suggested an excessive rise in blood pressure during the five years.

Adolescent↗

Inhibition of lipoprotein lipase by plasma from children with the steroid responsive nephrotic syndrome.

The study was designed to investigate the hyperlipidaemia associated with the steroid responsive nephrotic syndrome in children and in particular to examine the mechanism for the delayed clearance of the circulating triglyceride-rich lipoproteins. The possibility that plasma from patients with steroid responsive nephrotic syndrome may contain an inhibitor of lipoprotein lipase activity was studied by examining the effect of the addition of plasma from patients, on normal postheparin lipoprotein lipase activity. Plasma from children with steroid responsive nephrotic syndrome significantly inhibited lipoprotein lipase activity (p less than 0.001), whereas that from patients with familial hypercholesterolaemia and normal children had no significant effect. The inhibition of lipoprotein lipase activity by plasma from patients with steroid responsive nephrotic syndrome correlated significantly with their increased plasma cholesterol and reduced plasma albumin concentrations (p less than 0.001 and less than 0.02, respectively), but there was no significant correlation with plasma triglyceride concentrations. Thus, the degree of inhibition probably reflected the severity of the condition at the time of study. Neither the cholesterol, albumin nor triglyceride concentrations appeared to directly influence the lipoprotein lipase activity of postheparin plasma.

Adolescent↗