Febrile convulsions in a national cohort followed up from birth. II--Medical history and intellectual ability at 5 years of age.

Three hundred and three children with febrile convulsions were identified in a national birth cohort of 13 135 children followed up from birth to the age of 5 years. Breech delivery (p less than 0.05) was the only significantly associated prenatal or perinatal factor. There were no associations with socioeconomic factors. Excluding the 13 known to be neurologically abnormal before their first febrile convulsion, children who had had a febrile convulsion did not differ at age 5 from their peers who had not had febrile convulsions in their behaviour, height, head circumference, or performance in simple intellectual tests.     

Complications of ileal conduit diversion in adults with cancer followed up for at least five years.

A total of 111 adults with malignant disease of the bladder were studied to determine the long term complications of ileal conduit diversion. Each patient had survived at least five years (mean 10 years) after cystectomy. At final follow up the radiological appearance of one or both kidneys had deteriorated in 50 (47%) of 107 patients: deterioration worsened significantly (p less than 0.01) with increasing duration of follow up. Eighteen patients (16%) developed biochemical evidence of impaired renal function, of whom four died of complications of renal failure. Bilateral upper tract dilatation was noted in 30 patients (28%), and in 21 its cause was obscure. Ten patients formed renal stones, and an additional 12 required further operations on the conduit or stoma. Despite the age of patients with bladder cancer and the poor prognosis of those with invasive tumours clinically important side effects were observed in a significant proportion of the long term survivors. Further efforts to determine the aetiology of upper tract dilatation in patients with an ileal conduit diversion are justified.     

Proximity relationships within a birth cohort of immature Japanese monkeys (Macaca fuscata) in a free-ranging group during the first four years of life

This study was designed to characterize the proximity relationships among 20 immature Japanese monkeys (Macaca fuscata) of the same age in a free-ranging group during the first 4 years of life. Most male and female immature monkeys showed a consistent preference for proximity within their cohort to certain same-sex individuals whose dominance ranks were immediately adjacent to their own throughout the first 4 years. Such prolonged proximity relationships between peers of the same sex were largely a reflection of those between their mothers. Therefore, the proximity relationships between peers seem to be formed under the influence of social relationships between the mothers. © 1996 Wiley-Liss, Inc.     

Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life

Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5′UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3′UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.     

Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life

Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5′UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3′UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.     

The first five seconds in the life of a clathrin-coated pit

Coated pits assemble by growth of a clathrin lattice, which is linked by adaptors to the underlying membrane. How does this process start? We used live-cell TIRF imaging with single-molecule EGFP sensitivity and high temporal resolution to detect arrival of the clathrin triskelions and AP2 adaptors that initiate coat assembly. Unbiased object identification and trajectory tracking, together with?a statistical model, yield the arrival times and numbers of individual proteins, as well as experimentally confirmed estimates of the extent of substitution of endogenous by expressed, fluorescently tagged proteins. Pits initiate by coordinated arrival of clathrin and AP2, which is usually detected as two sequential steps, each of one triskelion with two adaptors. PI-4,5-P(2) is essential for initiation. The accessory proteins FCHo1/2 are not; instead, they are required for sustained growth. This objective picture of coated pit initiation also shows that methods outlined here will be broadly useful for studies of dynamic assemblies in living cells.     

Progression of HIV disease in a haemophilic cohort followed for 11 years and the effect of treatment.

OBJECTIVE--To describe the progression of HIV disease in a haemophilic cohort and to show the influence of treatment. DESIGN--11 year longitudinal clinical and laboratory study. SETTING--A haemophilia centre. PATIENTS--111 patients infected with HIV during October 1979 to July 1985. MAIN OUTCOME MEASURES--Symptoms of HIV infection, AIDs, and death. INTERVENTIONS--26 asymptomatic patients started taking zidovudine or placebo (1000 mg/day) during November 1988 to February 1990; 10 patients with CD4+ counts of 0.2 x 10(9)/l started zidovudine 500 mg/day during January to November 1990. 35 patients used pentamidine for primary or secondary prophylaxis. RESULTS--At 11 years from seroconversion the estimated rate of progression to AIDS was 42% (95% confidence interval 27% to 57%); to symptoms 85% (75% to 95%); and to death 41% (25% to 57%). Progression to AIDS was significantly faster in patients aged 25 and over than in those aged less than 25 (relative risk 5.0 (2.4 to 10.4); p less than 0.00001) and in those with previous cytomegalovirus infection than in those not infected (relative risk 3.0 (1.4 to 6.8); p = 0.006). 16 of 27 (59%) patients with p24 antigenaemia developed AIDS compared with 17 of 84 (20%) patients without p24 antigen (p less than 0.001). The risk of progression to AIDS before 30 November 1988 in patients with CD4+ counts less than or equal to 0.2 x 10(9)/l was higher than after November 1988 (relative risk 1.9 (0.85 to 4.43); p = 0.1). For 1989 and 1990 the observed cumulative numbers of AIDS cases (among 81 patients with sufficient CD4+ counts) were 22 and 25 compared with 29 and 37 predicted from the rate of fall of CD4+ counts up to the end of 1988 (p = 0.03). CONCLUSION--Treatment seems to be reducing the progression of HIV disease in this haemophilic cohort.     

Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study.

OBJECTIVE--To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN--Population based birth cohort study. SETTING--The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS--Information available for 14,676 children. OUTCOME MEASURES--Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS--19 children had lengthy febrile convulsions and 18 had status epilepticus. Two children with status epilepticus died (one at 5 years old); neither death was directly due to the status epilepticus. Four of the 19 (21%) developed afebrile seizures after lengthy febrile convulsions compared with 14 of the 17 (82%) survivors after status epilepticus. Measures of intellectual performance were available for 33 of the 35 survivors: 23 were normal and 10 were not normal but eight of them had preceding developmental delay or neurological abnormality. CONCLUSION--The outcome in children after lengthy febrile convulsions and status epilepticus is better than reported from studies of selected groups and seems determined more by the underlying cause than by the seizures themselves.     

Predictors of the desire/decision to quit smoking in a cohort of Croatian adult smokers followed for five years: the crohort study

This study provides an overview of the incidence of smoking, the socio-demographic characteristics of Croatian smokers during a five-year period and an assessment of predictors of the desire/decision to quit smoking. Analyses were performed separately for 2003 and 2008. A total of 3,229 subjects were included in the survey. There is a significant trend of a decreasing number of smokers in all age groups in 2008, compared to 2003. Almost half of the smokers included in the study expressed desire to quit smoking. Factors contributing significantly to decision to quit smoking were different in 2003 and 2008, except one. Concern about the harmful effects of tobacco smoking on health was a significant predictor in both models. Very worried respondents were more likely to decide to quit smoking (OR 17.6, 95% CI 9.41 to 33.17 vs. OR 12.54; 95% CI 6.0 to 26.2) than those who were not worried at all.     

The epidemiology of soil-transmitted helminth infections in children up to 8 years of age: Findings from an Ecuadorian birth cohort

BackgroundThere are few prospective longitudinal studies of soil-transmitted helminth (STH) infections during early childhood. We studied the epidemiology of and risk factors for soil-transmitted helminth infections from birth to 8 years of age in tropical Ecuador.Methods2,404 newborns were followed to 8 years of age with periodic stool sample collections. Stool samples were collected also from household members at the time of the child’s birth and examined by microscopy. Data on social, environmental, and demographic characteristics were collected by maternal questionnaire. Associations between potential risk factors and STH infections were estimated using generalized estimated equations applied to longitudinal binary outcomes for presence or absence of infections at collection times.ResultsOf 2,404 children, 1,120 (46.6%) were infected with at least one STH infection during the first 8 years of life. The risk of A. lumbricoides (16.2%) was greatest at 3 years, while risks of any STH (25.1%) and T. trichiura (16.5%) peaked at 5 years. Factors significantly associated with any STH infection in multivariable analyses included age, day-care (OR 1.34, 95% CI 1.03–1.73), maternal Afro-Ecuadorian ethnicity (non-Afro vs. Afro, OR 0.55, 95% CI 0.43–0.70) and lower educational level (secondary vs. illiterate, OR 0.31, 95% CI 0.22–0.45)), household overcrowding (OR 1.53, 95% CI 1.21–1.94)), having a latrine rather than a water closet (WC vs. latrine, OR 0.77, 95% CI 0.62–0.95)), and STH infections among household members (OR 2.03, 95% CI 1.59–2.58)). T. trichiura was more associated with poverty (high vs. low socioeconomic status, OR, 0.63, 95% CI 0.40–0.99)] and presence of infected siblings in the household (OR 3.42, 95% CI 2.24–5.22).ConclusionSTH infections, principally with A. lumbricoides and T. trichiura, peaked between 3 and 5 years in this cohort of children in tropical Ecuador. STH infections among household members were an important determinant of infection risk and could be targeted for control and elimination strategies.     

BACUP--the first two years: evaluation of a national cancer information service.

The cancer information service of the British Association of Cancer United Patients (BACUP) was launched in October 1985 as a national service to patients and their relatives, the public, and health professionals. Information is provided by telephone and letter by seven nurses trained in oncology. In the first two years over 30,000 inquiries were received: 23,527 (80%) were from women; 9445 (32%) were from cancer patients 11,574 (39%) from relatives of patients, and 2869 (10%) from health professionals. Inquiries came from all over the United Kingdom and from all sections of society but users were predominantly middle class, aged between 30 and 49, and living in south east England. Information about specific cancer sites, treatment, and how to cope was most commonly sought. Nearly a third of all inquiries were related to breast cancer. Though the service is used more by particular groups focusing on particular diseases, clearly there is a need for a cancer information service in the UK.     

Blood pressure in first 10 years of life: the Brompton study.

OBJECTIVES--To determine the normal range of blood pressure and its pattern of change in the first 10 years of life. To estimate at what age (if any) children consistently appear in one part of the blood pressure distribution and at what age familial correlations in blood pressure become significant. DESIGN--Longitudinal cohort study. SETTING--South east England. SUBJECTS--2088 children of both sexes born consecutively in Farnborough Hospital, Kent, and their parents. MAIN OUTCOME MEASURE--Blood pressure measured by Doppler ultrasonography and sphygmomanometry. RESULTS--Systolic blood pressure rose from a mean of 88.5 mm Hg at age 6 months to 96.2 mm Hg at 8 years measured with a 8 cm cuff and from 89.1 mm Hg at age 5 years to 94.3 mm Hg at age 10 years measured with a 12 cm cuff. The larger cuff gave blood pressure readings about 6 mm Hg lower. This effect was independent of body weight and arm circumference. Diastolic blood pressure rose from 57.8 mm Hg at 5 years to 61.8 mm Hg at 10 years (12 cm cuff). There was only about 1 mm Hg difference between sexes. Blood pressure was correlated with weight, weight adjusted for height, height, and arm circumference at all ages studied. The correlation coefficient of repeated yearly measurements increased steadily with age from 0.28 at 2 years to 0.59 at 10 years. The correlation coefficients between child''s blood pressure and mother''s average blood pressure increased from 0.1 at age 1 year to 0.23 at age 10. CONCLUSIONS--Blood pressure changes relatively little between the ages of 6 months and 10 years. Yet because of the increasing strength of between occasion and family correlations, children are more consistently occupying a specific part of the blood pressure distribution as they grow older. Studies in children should help determine why some adults have hypertension and others do not.     

Life-history theory, chronic childhood illness and the timing of first reproduction in a British birth cohort

Life-history theoretical models show that a typical evolutionarily optimal response of a juvenile organism to high mortality risk is to reach reproductive maturity earlier. Experimental studies in a range of species suggest the existence of adaptive flexibility in reproductive scheduling to maximize fitness just as life-history theory predicts. In humans, supportive evidence has come from studies comparing neighbourhoods with different mortality rates, historical and cross-cultural data. Here, the prediction is tested in a novel way in a large (n = 9099), longitudinal sample using data comparing age at first reproduction in individuals with and without life-expectancy-reducing chronic disease diagnosed during childhood. Diseases selected for inclusion as chronic illnesses were those unlikely to be significantly affected by shifting allocation of effort away from reproduction towards survival; those which have comparatively large effects on mortality and life expectancy; and those which are not profoundly disabling. The results confirmed the prediction that chronic disease would associate with early age at first reproduction: individuals growing up with a serious chronic disease were 1.6 times more likely to have had a first child by age 30. Analysis of control variables also confirmed past research findings on links between being raised father-absent and early pubertal development and reproduction.