Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

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.

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.

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.

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.

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.

Acute renal failure and gout as presenting features of acute lymphoblastic leukaemia.

A leukaemic child is described who presented with renal failure and gout attributable to hyperuricaemia before the leukaemia could be diagnosed.

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.

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.

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.

Galactosaemia: estimated live birth incidence in New Zealand.

194 cord blood samples were studied in both a fluorimetric assay and an electrophoresis method for Gal-1-PUT. From this the expected live birth incidence was 1:37000. The New Zealand neonatal screening programme has detected 5 cases in 223326 live births--an apparent incidence of 1:44600. The Beutler testing of dried blood spots collected on filter paper cards is a satisfactory method of detecting galactosaemia in the neonate.

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.

Genetics of classic Alport's syndrome.

41 families with classic Alport's syndrome (hereditary nephritis with sensorineural deafness) were studied. All their pedigrees were compatible with X-linked inheritance. DNA probes were used to investigate genetic linkage in these families. Linkage to probe S21 (DXS17) was confirmed (LOD score = 4.72 at 0 = 0.06), localising the gene for Alport's syndrome to the middle of Xq; thus the disorder is X-chromosomal in nature.