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Biomedical subjects

T M Barratt

Publications and source records attributed to T M Barratt.

At least 91 records · Page 5Linked to original sources

Platelet-derived growth factors as possible mediators of vascular proliferation in the sporadic haemolytic uraemic syndrome.

Mitogenic activity was measured in matched plasma and serum samples from 17 children with typical epidemic haemolytic uraemic syndrome (HUS), 13 with atypical sporadic HUS, 7 with other renal diseases, and 8 normal children. The serum mitogenic activity of the normal children (median 18.35, range 15-35 U/ml) greatly exceeded that of plasma (median 5.4, range 1.04-11.9 U/ml). Patients with atypical sporadic HUS had raised plasma mitogenic activity (median 9.35, range 0-35 U/ml, p less than 0.01). Both plasma and serum from children with the typical epidemic form of HUS had low or undetectable mitogenic activity (median for plasma 1.0, range 0-5.9 U/ml, p less than 0.001; median for serum 1.85, range 0-23.8 U/ml, p less than 0.005). These low concentrations in typical epidemic HUS were associated with the presence of an inhibitor of cell growth. The results suggest that there is intravascular release of platelet mitogens in atypical sporadic HUS and that these mitogens may therefore be mediators of the vascular proliferative lesions.

Adolescent↗

Use of a monoclonal antibody in differential diagnosis of children with haematuria and hereditary nephritis.

In a retrospective, double-blind study, paraffin-embedded renal biopsy sections from 44 children with haematuria were examined to see whether a mouse monoclonal antibody (MCA-P1) against glomerular basement membrane (GBM) could identify a subgroup of patients with hereditary glomerulonephritis (Alport's syndrome) in whom the Goodpasture antigen was abnormal. There was strong linear binding of MCA-P1 to GBM in all of 29 patients with no evidence of hereditary nephritis and in 2 patients in whom the diagnosis of hereditary nephritis was thought possible but not definite on available clinicopathological evidence. In contrast, 12 of 13 patients with strong evidence of hereditary nephritis showed no binding (9) or greatly reduced binding (3). These findings suggest that a major subgroup of patients with hereditary glomerulonephritis have biochemical abnormalities of the GBM involving Goodpasture antigen and that MCA-P1 is useful in the differential diagnosis of children with haematuria.

Adolescent↗

Steroid-responsive nephrotic syndrome: a generalised disorder of membrane negative charge.

A simple chemical test, based on the binding of the cationic dye alcian-blue 8GX (AB), has been devised to measure negative charge on cell membranes. The test has demonstrated that AB binding to red blood cells and platelets is significantly less in children with steroid-responsive nephrotic syndrome (SRNS) or nephrotic syndrome associated with focal segmental glomerulosclerosis than in normal controls. However, the sialic acid content of the nephrotic cell membrane is normal. This suggests that a generalised loss of membrane negative charge occurs in SRNS and that this is due to neutralisation rather than absence of anionic groups.

Adolescent↗

Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis.

The role of platelets in the pathogenesis of vasculitis and the formation of coronary artery aneurysms was studied in 19 children with Kawasaki disease and five with polyarteritis. All patients with Kawasaki disease developed thrombocytosis in the third week of illness. The peak platelet count was significantly correlated (p less than 0.005) with the subsequent development of coronary artery aneurysms. The rise in platelet count was associated with the appearance in the circulation of a factor that induced aggregation and serotonin release in normal platelets. This factor was shown to be of high molecular weight, and its activity was lost at low pH--features suggestive of an immune complex. Immune complexes, detected by precipitation with polyethylene glycol, also appeared in the circulation as the platelet count increased. These complexes induced platelet aggregation, and there was a significant correlation (p less than 0.001) between the concentrations of IgG and IgA in the polyethylene glycol precipitated material and the platelet aggregating activity. Similar platelet aggregating activity was also detected in patients with polyarteritis but followed a different time course, persisting in the circulation for several months in association with continued disease activity. These findings imply that different mechanisms have a role in distinct phases of Kawasaki disease. The initial feverish phase (probably infective) is probably followed by an immune complex vasculitis that occurs when antibodies to the initiating agent appear in the circulation. The immune complexes aggregate platelets and induce release of serotonin. Platelet derived vasoactive mediators may increase vascular permeability and facilitate further deposition of complexes in the tissues.

Aneurysm↗

Physiological variations of normal transit time in children.

Quantitation of the 99mTc-diethylenetriaminepentaacetic Acid (DTPA) scan yields by uptake analysis an estimate of individual kidney glomerular filtration rate (IKGFR) and by deconvolutional analysis an estimate of the mean transit time (MTT) of the non-reabsorbable tracer through the kidney. The whole kidney MTT is compounded of the renal parenchymal MTT and the rate of pelvic clearance; both functions are influenced by prevailing rates of salt and water excretion. The present study was undertaken to investigate the effect of physiological variations on the normal DTPA scan. The contralateral normal kidney in 11 children with suspected unilateral urinary tract obstruction were studied twice, first with an early morning scan (EMS) and second, 24 h later, following hypotonic volume expansion (HVE). A strong correlation was shown between urine osmolality and MTT. IKGFR was independent of the state of hydration, but in comparison to mild hydration, HVE shortened significantly (P less than 0.001) the normal whole kidney MTT, with less effect on parenchymal MTT (P less than 0.01) and therefore has its predominant effect on pelvic clearance. We advise caution in the interpretation of whole kidney transit time analysis without standardization of salt and water excretion rates. Parenchymal transit time offers a potentially useful clinical index.

Adolescent↗

Renal toxicity of cisplatin in children.

We measured renal function in 22 children receiving cisplatin as initial treatment for neuroblastoma or malignant germ cell tumors. Glomerular filtration rates were estimated from the plasma clearance of 51Cr-EDTA and were compared with measurements of plasma creatinine concentration and creatinine clearance. The degree of cisplatin-induced renal damage varied widely, and plasma creatinine measurements and creatinine clearances were not reliable guides to glomerular filtration rate. Renal function in children receiving cisplatin should be monitored by measurement of glomerular filtration rate with an isotope clearance technique.

Albuminuria↗

Tubular proteinuria in children without other defects of renal function.

3 patients are described in whom proteinuria was detected on routine urine analysis and subsequently shown to be predominantly tubular in origin. Renal biopsies showed only minor changes. Hypercalciuria was also noted in 1 of the 3 patients but no other tubular abnormalities were demonstrated. The precise diagnosis remains uncertain, but an unusual presentation of idiopathic hypercalciuria or of the adult Fanconi syndrome must be considered. These patients may alternatively have a previously undescribed disorder.

Calcium↗

Renal parenchymal determination and analysis during dynamic 99Tcm-DTPA scans in children.

Twenty-six children underwent a total of 75 99TCm-DTPA scans. Two experienced operators, using different techniques were able to identify parenchyme in 77 of 111 kidneys. Parenchymal regions of interest were drawn by an entirely operator dependent and a relatively operator-independent technique. Transit time analysis, using a matrix algorithm, through the parenchyme of both normal and abnormal kidneys showed a high degree of correlation (tau = 0.595, P less than 0.001). The technique concurred in the studies for which the analysis could not be applied, generally due to poor technical factors or gross hydronephrosis with insufficient parenchyme to generate a time activity curve. Either technique may be used in clinical practice to identify renal parenchyme for further analysis.

Adolescent↗

Haemolytic-uraemic syndrome: an analysis of prognostic features.

Seventy-two children with the haemolytic-uraemic syndrome were seen between 1969 and 1980 at The Hospital for Sick Children and Guy's Hospital, London. They probably constitute the majority of such cases in south-east England during that period. Boys and girls were affected equally, the mean age at presentation was 3.5 years, and a peak incidence of the disorder in summer months was observed. In 52 (72%) there was a history of diarrhoea at onset. Fifty-seven (78%) were managed by dialysis. Fifty (70%) of the 72 children had a favourable outcome with complete recovery, 3 (4%) died in the acute phase of the illness, 8 (11%) had residual hypertension or chronic renal failure, and 11 (16%) never recovered renal function. The probability of complete recovery of renal function was analysed by logistic regression which indicated that younger age, presentation in the summer months, diarrhoea at onset and, in those patients who were dialysed, a short prodromal illness were associated with a good outcome. Further analysis of the interaction among these variables in the patient group as a whole indicated that diarrhoea favoured a good outcome among boys but not girls.

Acute Kidney Injury↗

Goodpasture's syndrome: treatment with plasmapheresis, immunosuppression, and anticoagulation.

We report 3 children with Goodpasture's syndrome. In 2 children the diagnosis was delayed, treatment began late, and they did not recover renal function. In the third child early diagnosis and intensive treatment with plasmapheresis, immunosuppression, and anticoagulation resulted in an initial return of renal function after a prolonged period of anuria. In this child, however, although there was no evidence of disease activity, further deterioration of renal function subsequently occurred.

Anti-Glomerular Basement Membrane Disease↗

Inhibitor of prostacyclin production in sporadic haemolytic uraemic syndrome.

Prostacyclin (PGI2) production was diminished when rat aortic rings were incubated with plasma from 5 of 6 patients with the sporadic form of haemolytic uraemic syndrome but was normal in the presence of plasma from 7 patients with the epidemic form of haemolytic uraemic syndrome or from patients with other renal diseases. The reduced PGI2 production was caused by an unstable inhibitor, extractable into polar lipid solvents, in sporadic haemolytic uraemic plasma. These results suggest that there may be at least 2 different pathogenetic mechanisms in epidemic and sporadic haemolytic uraemic syndrome and that the reduced PGI2 production observed in the sporadic type is due to an inhibitor of PGI2 production rather than a deficiency of stimulating factors.

Adolescent↗

Renal function following cardiopulmonary bypass surgery in children: a randomized comparison of the effects of gentamicin and cloxacillin with cephalothin.

Renal function was studied in 36 children who were randomly allocated to receive either gentamicin and cloxacillin or cephalothin as prophylactic antibiotic cover for complex cardiopulmonary bypass surgery. Both groups of children developed a similar degree of impairment of glomerular function with significant elevations in plasma creatinine concentrations and urine albumin excretion compared to preoperative levels which tended to resolve by the 5th postoperative day. The urine excretion of N-acetyl-glucosaminidase increased in both groups postoperatively but remained significantly elevated only in those children who had received gentamicin. These findings suggest that whilst gentamicin exerts a demonstrable nephrotoxic effect on the proximal renal tubules it does not contribute significantly to either the incidence or severity of postoperative renal glomerular impairment.

Acute Kidney Injury↗

Renal failure due to 2,8-dihydroxyadenine urolithiasis.

A four-year-old girl presented in renal failure due to dihydroxyadenine urolithiasis. Prior to this she had been fed a high purine macrobiotic diet, rich in pulses and grain. She was comatose, anuric, requiring peritoneal dialysis, and bilateral radiolucent renal calculi were revealed by ultrasonography and retrograde pyelography. 2,8-dihydroxyadenine stones were found at pyelolithotomy, renal biopsy revealed interstitial birefringent crystals, and a complete lack of adenine phosphoribosyl transferase (APRT) was found subsequently in erythrocyte lysates. APRT levels were initially falsely raised due to a blood transfusion on admission. The mother was shown to have heterozygote levels. The child was treated successfully with allopurinol, and a reduction in dietary purine but with only partial return of renal function.

Adenine↗