Dose-dependent repression of T-cell and natural killer cell genes by PU.1 enforces myeloid and B-cell identity.

The Ets transcription factor PU.1, encoded by the gene Sfpi1, functions in a concentration-dependent manner to promote myeloid and B-cell development and has been implicated in myeloid and lymphoid leukemias. To determine the consequences of reducing PU.1 concentration during hematopoiesis, we analyzed mice with two distinct hypomorphic alleles of Sfpi1 that produce PU.1 at approximately 20% (BN) or approximately 2% (Blac) of wild-type levels. Myeloid development was impaired in these mice, but less severely than in Sfpi1 null mice. To identify the downstream target genes that respond to changes in PU.1 concentration, we analyzed ex vivo interleukin-3 dependent myeloid cell lines established from Sfpi1(BN/BN), Sfpi1(Blac/Blac) and Sfpi1(-/-) fetal liver cells. Unexpectedly, many T-cell and natural killer cell genes were expressed in Sfpi1(-/-) cells and repressed in a dose-dependent manner in Sfpi1(Blac/Blac) and Sfpi1(BN/BN) cells. This pattern of dose-dependent T/NK-cell gene repression also occurred in ex vivo interleukin-7 dependent progenitor B cell lines. These results suggest that PU.1 functions in a concentration-dependent manner to repress T-cell and natural killer cell fates while promoting myeloid and B-cell fates.

The changing pattern of children's dialysis and transplantation over 20 years.

The changing treatment and outcome for children with chronic renal failure (CRF) requiring renal replacement therapy (RRT) was assessed in children referred to the only paediatric unit in the North West Region of England between 1968 and 1988. There were 108 children. Referrals in consecutive 5-year time periods increased from 9 to 41 over the 20 years with the overall incidence of new referrals less than 15 years old reaching 8.5 per million childhood population in 1983-87, whilst the proportion of children under 5-years increased from 0% to 22%. The survival rate was better in those commencing RRT in the later years: 5-year survival 56% for the 1968-72 cohort vs 88% for 1978-82. The increasing number of referrals particularly among young children, coupled with improved survival rates have considerable implications when determining the provision of care for children with ESRD.

Home collection of urine specimens--boric acid bottles or Dipslides?

Sterile mid stream specimens of urine (MSSU) were obtained from 84 children in a hospital outpatient department. All 84 children collected urine at home by one of two Dipslide methods and by collection into boric acid within 24 hours of the hospital collected MSSU. The samples collected at home were posted to the hospital. Thirty six of the Dipslides (43%) and nine of the boric acid samples (10%) were not sterile but none had a pure growth of a single organism of greater than 10(5) organisms/ml. In addition, 17 of the Dipslides (20%) were returned with one or both media detached and therefore could not be relied upon to exclude urinary tract infection. In a second part to the study, 95 urines which showed a significant growth in primary culture were also cultured after storage in boric acid. Inhibition was noted in nine samples after storage in boric acid, seven of which were in underfilled bottles. Transport of specimens in boric acid produced less contamination than Dipslides but may inhibit growth in a small number of specimens. Technical failures with Dipslides were disappointingly high.

Access for peritoneal dialysis in neonates and infants.

A new catheter for peritoneal dialysis in neonates and infants was used on 28 occasions in 17 patients. Advantages over other catheters included easy safe introduction over a guide wire, absence of early leakage of dialysate, and the ability to change the catheter without creating a second abdominal wound.

Nephrotic syndrome: from toddlers to twenties.

63 patients with steroid-sensitive, biopsy-proven minimal-change nephrotic syndrome were followed for between 10 and 21 years. 2 died. All the survivors had normal renal function and blood pressure, and only 2 had a single attack. Frequent relapse was more common with young age of onset and in boys. The frequency of relapse fell rapidly over the first 4 years after diagnosis and then plateaued. Relapses continued into adult life. No definite endpoint to the disease could be defined although there was a linear relation between length of remission and risk of subsequent relapse.

Transient neonatal tyrosinaemia.

Children who had presented with transient neonatal tyrosinaemia (TNT) were compared with a group of unaffected controls at 7-9 years of age. A comprehensive psychometric assessment revealed significant differences between the groups in adaptive behaviour, psycholinguistic abilities, and speed of learning. In nearly all components of the tests used, higher levels of TNT were associated with lower levels of performance. This study demonstrates that TNT, a condition commonly regarded as benign in the short term, has long-term effects which may be detrimental to the child in school.

Long term prognosis of recurrent haematuria.

A long term follow up study of 100 children referred with recurrent haematuria for at least one year to two regional paediatric nephrology units is described. The mean duration of follow up was 8.2 years. An adequate renal biopsy was obtained in 96 and eight cases of Alport's syndrome and 10 of IgA nephropathy were diagnosed (20% and 26% respectively of the biopsies examined by electron microscopy and immunofluorescence). Five patients developed end stage renal failure and six hypertension requiring treatment, with the occurrence of these complications increasing progressively with increasing duration of follow up (1% at five years compared with 12% at 10 years). Adverse prognostic features were persistence of microscopic haematuria, proteinuria at presentation, and appreciable changes on renal biopsy. Eighty four patients had first degree relatives tested for haematuria; 30% of these families had another affected member. With long term follow up recurrent haematuria is associated with considerable morbidity and potential mortality.

Objective structured clinical examination compared with other forms of student assessment.

Two hundred and twenty nine final year medical students were assessed in paediatrics using an objective structured clinical examination (OSCE) and a traditional viva voce examination, and the results were compared with other assessments of the students made during and at the end of the undergraduate course. Results of the OSCE correlated positively with other forms of assessment and more strongly than the viva voce examination. There was little correlation between the OSCE and viva results. Eighty per cent of students felt the OSCE to be a fairer system than other examinations and all external examiners commented favourably on it. An OSCE is an acceptable alternative to traditional means of examination in paediatrics and may be superior in certain aspects.

Modulation of cellular immune function by cyclophosphamide in children with minimal-change nephropathy.

Cyclophosphamide is widely used to induce a remission of minimal-change nephropathy, but concerns have been raised about whether its effects on cellular immunity persist after treatment is discontinued. We studied functional and numerical measures of cellular immunity in children who had minimal-change nephropathy with frequent steroid-responsive relapses and were receiving cyclophosphamide (2.5 mg per kilogram of body weight per day for eight weeks). Sequential studies during such treatment showed that cyclophosphamide caused lymphopenia, particularly among T helper cells, resulting in a significant fall in the immunoregulatory (helper/suppressor) cell ratio. This change persisted 1 to 3 months after cyclophosphamide was discontinued, but measures of immune function reverted to normal after 6 to 12 months. Children with minimal-change nephropathy in long-term remission had no difference in T-cell subpopulations, lymphocyte responses to mitogens, or suppressor-cell function that could be attributed to the disease itself or to the previous use of cyclophosphamide.

Zinc supplementation and its effect on taste acuity in children with chronic renal failure.

Diminished taste acuity (hypogeusia) and zinc deficiency have been reported in children on maintenance haemodialysis and with varying degrees of chronic renal failure. We have studied the effect of 6 weeks' zinc supplementation in 20 children with chronic renal impairment using a double-blind crossover trial. Although we achieved significant increases in serum zinc levels no significant improvement in taste acuity could be demonstrated. These studies provide no support for the belief that routine zine supplements are necessary in children with chronic renal failure.

Evaluation of an objective structured clinical examination.

An objective structured clinical examination (OSCE) was introduced at the end of the fourth year undergraduate paediatric training. We have compared the results obtained with those of our traditional method of assessment. We feel that the OSCE is a valid and reliable assessment; it provided good feedback and was well received by the students.

Postural deformities in congenital nephrotic syndrome.

Six successive cases of congenital nephrotic syndrome are described. Each one showed flexion deformities of the knees and hips, widely open anterior and posterior fontanelles, and wide separation of the skull sutures. These abnormalities were present not only in cases in which the renal histology was of the microcystic Finnish type of congenital nephrotic syndrome, but also in those in which the histological picture was one of the variants associated with congenital nephrotic syndrome. It is suggested that such abnormalities are postural deformities, possibly produced by the large placenta.

Bone disease in children with chronic renal failure: therapy with 1alpha-hydroxyvitamin D3.

Results of 1alpha-hydroxyvitamin D3 therapy in twelve children with renal bone disease are described. Nine of the twelve children showed a good response to 0.05--0.08 microgram/kg/day. Hypercalcaemia was the only side effect and proved easy to manage because of the short half-life of 1alpha-OHD3.

Symptomatic urinary infection in childhood: presentation during a four-year study in general practice and significance and outcome at seven years.

Thirty-eight children (12 boys and 26 girls) with symptomatic urinary infection have been studied in general practice. Patients were collected over a four-year period and we report an incidence of urinary infection according to Kass's criterion of 7.7 per 1,000 girls at risk per year and 3.8 per 1,000 boys at risk per year. Eighty-four per cent of the children had symptoms which suggested an origin in the genitourinary tract. Proteus infection was found in five of the boys and only one of the girls. At the end of the four-year study period follow-up had taken place over a mean period of 25 months and recurrent infection had been demonstrated in four boys and 12 girls. All the children had an excretion urogram and two children, both girls, were found to have pyelonephritic scarring. Twelve children with recurrent infection were investigated for vesicoureteric reflux, which was found only in the two children with scarring. At seven years 31 of the children remained in the practice and, with a mean follow-up of 42 months, no significant alteration in the figures for recurrent infection was demonstrated. Guidelines are suggested for the management of childhood urinary infection in general practice.