Search PubMed⌕ Search

Biomedical subjects

I Roberts

Publications and source records attributed to I Roberts.

At least 181 records · Page 10Linked to original sources

Does home visiting prevent childhood injury? A systematic review of randomised controlled trials.

OBJECTIVE: To quantify the effectiveness of home visiting programmes in the prevention of child injury and child abuse. DESIGN: Systematic review of 11 randomised controlled trials of home visiting programmes. Pooled odds ratios were estimated as an inverse variance weighted average of the study specific odds ratios. SETTING: Randomised trials that were available by April 1995. SUBJECTS: The trials comprised 3433 participants. RESULTS: Eight trials examined the effectiveness of home visiting in the prevention of childhood injury. The pooled odds ratio for the eight trials was 0.74 (95% confidence interval 0.60 to 0.92). Four studies examined the effect of home visiting on injury in the first year of life. The pooled odds ratio was 0.98 (0.62 to 1.53). Nine trials examined the effect of home visiting on the occurrence of suspected abuse, reported abuse, or out of home placement for child abuse. Because of the potential for bias in outcome reporting in these studies, pooled effect estimates were not calculated. CONCLUSIONS: Home visiting programmes have the potential to reduce significantly the rates of childhood injury. The problem of differential surveillance for child abuse between intervention and control groups precludes the use of reported abuse as a valid outcome measure in controlled trials of home visiting.

Child↗

Novel mutations and polymorphisms in the Fanconi anemia group C gene.

Fanconi anemia (FA) is an autosomal recessive disorder associated with hypersensitivity to DNA cross-linking agents and bone marrow failure. At least four complementation groups have been defined, and the FA group C gene (FAC) has been cloned. We have screened 76 unrelated FA patients of diverse ethnic and geographic origins and from unknown complementation groups for mutations in the FAC gene either by chemical cleavage mismatch analysis or by single-strand conformational polymorphism (SSCP). Five mutations were detected in four patients (5.3%), including two novel mutations (W22X and L496R). Nine polymorphisms were detected, seven of which have not been described previously (663A-->G, L190F, IVS6 + 30C-->T, I312V, V449M, Q465R, and 1974G-->A). Six of the nine polymorphisms occurred in patients or controls from the Tswana or Sotho chiefdoms of South Africa and were not found in 50 unrelated European controls. Restriction site assays were established for all 8 pathogenic mutations identified in the FAC gene to date and used to screen a total of 94 unrelated FA patients. This identified only one other group C patient, who was homozygons for the mutation IVS4 + 4A-->T. This study indicates that the proportion of FA patients from complementation group C is generally likely to be less than 10%. Guidelines for the selection of FA patients for FAC mutation screening are proposed.

Cell Cycle Proteins↗

Effect of profound ischaemia on human muscle: MRI, phosphorus MRS and near-infrared studies.

A pressure cuff was applied to the legs of two human volunteers in order to stop any blood supply for a period of about 30 min. The affected muscle was monitored using proton magnetic resonance imaging (MRI), phosphorus magnetic resonance spectroscopy (MRS) and near infrared (NIR) spectroscopy before, during and after this procedure. The internal temperature of the tissue was also measured. The phase of water protons in muscle showed changes that were not accounted for by the measured temperature, but which correlated with the large increase in deoxyhaemoglobin and deoxymyoglobin observed with NIR as well as the decrease in PCr and increase in Pi observed with MRS. Little or no change was found in proton density or T2*. These results show that in vivo measurements of temperature using the chemical shift method may be confounded by changes in tissue oxygenation. They also show that T2* is an insensitive measure of changes in tissue oxygenation.

Constriction↗

Idiopathic myelofibrosis in children.

Childhood myelofibrosis (Mf) is rare with variable outcome reported in the literature. We present clinical and investigate details of three children who presented with idiopathic Mf in early childhood. Two of these children were identical twins and have been haematologically stable over the past 7 years since their diagnosis. The third patient underwent an allogeneic bone marrow transplant (BMT) procedure as her clinical status was deteriorating. She remains engrafted at 13 months post BMT. None of the children had hepatosplenomegaly although extramedullary haemopoiesis was demonstrated on 52Fe studies in two patients. Circulating progenitors in these patients were increased in the face of reduced marrow precursors. The aetiology of childhood Mf is unclear and its natural history seems different from the adult disease. Allogeneic BMT can be an option for definitive treatment.

Adolescent↗

Positive diepoxybutane test in only one of two brothers found to be compound heterozygotes for Fanconi's anaemia complementation group C mutations.

Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by diverse congenital abnormalities, the development of progressive bone marrow failure, and an increased predisposition to malignancy, particularly acute leukaemia. The FA phenotype is so variable that diagnosis on the basis of clinical manifestations alone can be difficult. The modern diagnosis of FA no longer rests entirely on the constellation of clinical and haematological abnormalities first described by Fanconi, but depends on finding elevated chromosomal breakage after incubation of peripheral blood lymphocytes with the chemical clastogens diepoxybutane (DEB) or mitomycin-C (MMC). The cloning of the gene for FA complementation group C [FAC] provides an opportunity to test the validity of the "DEB test' which in recent times has become the main arbiter as to whether a patient is classified as FA or non-FA. We report on two brothers with similar clinical and haematological features who have both been identified as compound heterozygotes for the FAC mutations L554P and delta G322, but only one of the brothers has a positive DEB test. On the basis of the DEB test one would be classified as FA and the other as non-FA. The time has come to re-evaluate the diagnostic criteria of "Fanconi's anaemia'.

Adolescent↗

Out-of-home day care and health.

Evidence from randomised trials indicates that out-of-home day care has important effects in domains that are integral to the health of mothers and children. The evidence that day care results in cognitive gains is compelling. These effects and the long term effects in reducing crime and violence should suffice to put the question of day care provision high on the paediatric agenda. However, some important questions remain to be answered. Evidence from a randomised trial suggests that the effect of infant day care on infectious disease morbidity is not as great as would be expected on the basis of results from observational studies. However, the trial in question had some important methodological weaknesses. No trials to date have examined the effect of day care on otitis media. Data from observational studies on the effect of day care on injury occurrence are confliciting. Finally, studies in the US point to an important effect of out-of-home day care on maternal employment. The effect of day care on maternal employment and income inequality in Britain has yet to be examined.

Child Day Care Centers↗

Injuries and the risk of disability in teenagers and young adults.

OBJECTIVE: To examine the risk of disability from unintentional injury in teenagers and young adults. METHODS: Analyses of data from the National Child Development Study, a follow up study of 98% of all children born in England, Scotland, and Wales in one week in March, 1958. In 1981, 12,537 study participants, 76% of the original cohort, were asked about unintentional injuries since age 16 years requiring hospital treatment, and whether these injuries resulted in permanent disability. RESULTS: 62% of men and 26% of women reported at least one accident since age 16 resulting in injury that required hospital treatment. Of these accidents, 3.2% caused permanent disability. The risk of disability increased with accident frequency. Injuries requiring hospital admission carried the highest risk of disability (9.7%). However, 54% of permanent disability reported by men and 74% reported by women resulted from injuries treated as outpatients. Road traffic accidents caused 42% of admissions and 31% of disability. Fractures constituted 21% of all injuries but were responsible for 32% of permanent disabilities. Of the permanent disabilities resulting from work related accidents, 82% involved the hand. Of the permanent disabilities resulting from accidents in the home, 32% involved the hand. CONCLUSIONS: The targeting of prevention strategies towards the major causes of injury mortality may have a smaller impact on population levels of injury related disability. Non-life threatening injuries, in particular injuries to the hand and limb fractures, resulting from accidents in the workplace, the home, and during sports, make a significant contribution to the prevalence of permanent injury related disability in young adults.

Accidents↗

Limited role for nitric oxide in mediating cerebrovascular control of newborn piglets.

AIMS: To investigate the effects of the nitric oxide (NO) synthase inhibitor L-nitro-arginine methyl ester (L-NAME) on cerebral blood flow, and its response to alterations in arterial carbon dioxide tension (CBF-CO2 reactivity). METHODS: Cerebral blood flow was measured six times at varying arterial carbon dioxide tension (PaCO2) using the intravenous 133Xenon clearance technique in eight mechanically ventilated piglets of less than 24 hours postnatal age. After the third measurement L-NAME was administered as a bolus (20 mg/kg) and subsequently infused (10 mg/kg/hour). RESULTS: PaCO2 ranged between 2.7-8.9 kPa. Cerebral blood flow decreased by 14.0% (95% confidence interval 1.9-27.4) after L-NAME. CBF-CO2 reactivity was 18.4% per kPa (95% CI 14.1-22.2) before L-NAME and 15.2%/kPa (95% CI 11.1-19.3) afterwards; the difference between the CBF-CO2 reactivities was 3.2%/kPa (95% CI -0.4-6.8): these were not significantly different. CONCLUSIONS: Inhibition of nitric oxide synthesis reduces cerebral blood flow no more than a 0.5-1.0 kPa fall in PaCO2. Nitric oxide is not an important mediator of CBF-CO2 reactivity.

Animals↗

Smoke alarm use: prevalence and household predictors.

OBJECTIVE: To determine the prevalence of smoke alarm use among families with children and to identify household factors that predict the absence of a smoke alarm. DESIGN: Cross sectional analysis of data collected in the September and November 1995 Omnibus Survey, conducted by the Office of Population Censuses and Surveys in the UK. SUBJECTS: A random sample of British households. Interviews were completed with 4,043 householders. The response rate was 78%. RESULTS: 29% of British households do not have a smoke alarm and smoke alarms were absent in 20% of households with children under 15 years. A smoke alarm was absent in 41% of privately rented homes compared with 17% of owner occupied homes. Living in private rental accommodation was the strongest household predictor of the absence of a smoke alarm (odds ratio = 3.25, 95% confidence interval 1.94 to 5.42). Householders who had heard of National Fire Safety Week or the TV smoke alarm advertising campaign were significantly more likely to have a smoke alarm. The apparent effect of these campaigns was greatest in families with children. CONCLUSIONS: Smoke alarm use has continued to increase but a substantial proportion of British homes still do not have smoke alarms. Homes at greatest risk of residential fire are the least likely to have an alarm. Health professionals may be able to increase smoke alarm use among families with children, by counselling families about the benefits of smoke alarms. They may also be effective in this regard by lobbying local councils, houseing associations, or private landlords to install alarms in all properties and by advocating for national legislation.

Adolescent↗

Child pedestrian injury rates: the importance of "exposure to risk" relating to socioeconomic and ethnic differences, in Auckland, New Zealand.

STUDY OBJECTIVE: To examine how child pedestrian exposure to risk, as measured by the mean number of streets crossed, varies according to indices of material disadvantage and ethnic group. DESIGN: A questionnaire on pedestrian exposure to risk was distributed to children for completion by parents and return to school. Children from 40 schools were selected using a probability cluster design. SETTING: The Auckland region of New Zealand. SUBJECTS: Questionnaires were distributed to 3388 pupils of whom 2873 (85%) completed and returned the questionnaire. RESULTS: The mean number of streets crossed was 2.19 (95% confidence interval 1.82, 2.56) at age 6 years and 2.80 (2.42, 3.17) at age 9 years. The mean number of streets crossed for boys (2.57 (2.15, 2.98)) was similar to that for girls (2.38 (2.05, 2.72)). The mean number of streets crossed by Pacific Island children was 4.87 (4.01, 5.73), more than twice the number crossed by children of predominantly European origin (1.90 (1.65, 2.15)). Children from families without a car crossed an average of 5.34 (4.35, 6.34) streets, compared with 2.90 (2.50, 3.31) streets for children from families with one car, and 1.97 (1.65, 2.29) streets for children from families with two or more cars. CONCLUSION: There are large differences in pedistrian exposure to risk in relation to ethnic group and levels of car ownership. These differences may explain ethnic and socioeconomic differentials in child pedestrian injury rates.

Accidents, Traffic↗

Delayed vasodilation and altered oxygenation after cerebral ischemia in fetal sheep.

The study investigated the hypothesis that delayed cerebral injury after transient cerebral ischemia is associated with vasoconstriction and decreased cerebral oxygenation. Eight chronically instrumented, late gestation fetal sheep were subjected to 30 min of cerebral ischemia in utero. Cortical impedance (CI) and electrocorticogram (ECoG) were recorded to determine the time course of cellular dysfunction. Histologic outcome was assessed 4 d postischemia. Changes in cerebral vascular tone and oxygenation were observed during and for 4 d after the insult using near infrared spectroscopy to measure changes in total cerebral Hb ([tHb]), oxyhemoglobin ([Hbo2]), and oxidized cytochrome aa3 ([Cyto2]). Results are expressed as mean +/- SEM. CI increased transiently during ischemia; then a delayed increase commenced 17.5 +/- 2.3 h postischemia and peaked at 42.3 +/- 2.4 h. ECoG was depressed during and after the insult. Seizures started 13.6 +/- 3.0 h postinsult and persisted for 25.4 +/- 3.2 h. Increases in [tHb] indicated two periods of cerebral vasodilation: immediately after early reperfusion, lasting 2.3 +/- 0.4 h and peaking to 20 +/- 2.0 mumol.L-1; and a later phase, commencing 12.8 +/- 2.0 h postischemia, peaking to 43 +/- 4.0 mumol.L-1 and lasting 43.1 +/- 5.2 h. [Hbo2] was relatively elevated (18 +/- 3.0 mumol.L-1) during d 4 postischemia, demonstrating a delayed increase in mean cerebral oxygen saturation. [Cyto2] fell during the insult (-0.7 +/- 0.2 mumol.L-1); and, commencing at 28-30 h postischemia, fell progressively to reach a minimum of -5.0 +/- 2.8 mumol.L-1 at 78-80 h postischemia. A greater fall in [Cyto2] was related to worse cerebral injury (p < 0.05). Delayed cerebral injury is accompanied by vasodilation and increased mean cerebral oxygen saturation, although a progressive fall in [Cyto2] might indicate a fall in mitochondrial oxygenation, cell loss, or changes in tissue optical characteristics.

Animals↗

Nitric oxide synthase inhibition attenuates delayed vasodilation and increases injury after cerebral ischemia in fetal sheep.

Transient cerebral ischemia in fetal sheep is followed by a period of delayed cerebral injury associated with cerebral vasodilation. As nitric oxide (NO) can mediate both vasodilation and neuronal death, this study investigated whether inhibition of NO synthesis would attenuate the vasodilation and decrease cerebral injury. Eleven late gestation (range 122-133 d) fetal sheep were subjected to 30 min of transient cerebral ischemia in utero. Two hours later, treatment group (n = 5) received a continuous infusion of NG-nitro-L-arginine (L-NNA) at a dose of 50 mg.h-1 for 4 h followed by 20 mg.h-1 for the subsequent study period, a competitive inhibitor of NO synthase (NOS), whereas a control group (n = 6) received PBS. Inhibition of NOS activity was confirmed in the treatment group by 1) suppression of the fall in mean arterial blood pressure (MAP) associated with acetylcholine (p < 0.01), and 2) persistent increase in MAP after commencement of L-NNA (p < 0.05). Changes in cerebral blood volume (CBV) were observed for 3 d by measuring changes in concentration of total cerebral Hb ([tHb]) using near infrared spectroscopy. The delayed increase in CBV commenced at 13.1 +/- 1.0 h postischemia in the control and 12.7 +/- 2.3 h in the treatment group. Maximum increase at 30-36 h was 0.5 +/- 0.1 mL.100 g-1 in the treatment group and 1.2 +/- 0.2 mL.100 g-1 in the control (p < 0.05). Final CBV was depressed below preischemic baseline in the treatment (-0.7 +/- 0.2 mL.100 g-1) but not the control group (-0.1 +/- 0.3 mL.100 g-1) (p < 0.05). Neuronal loss, quantified histologically 3 d postischemia, indicated that cerebral injury was increased in the treatment group (p < 0.05). The results indicate that after transient cerebral ischemia in fetal sheep, NOS inhibition attenuates the delayed rise in CBV but does not decrease the extent of cerebral injury.

Animals↗

Mutant ras promotes haemopoietic cell proliferation or differentiation in a cell-specific manner.

The ras gene products play a fundamental role in signal transduction in haemopoiesis. In this study, we have examined the effects of ras upon haemopoietic cell proliferation and differentiation, using two human cell lines which represent different stages of haemopoietic cell maturation. When a mutant H12-ras gene (codon 12: gly-->asp) was expressed in the monoblastic cell line, U937, marked inhibition of growth was seen together with morphological, functional and immunophenotypic evidence of monocytic maturation. Infection of U937 cells with a c-myc retrovirus produced similar changes strongly suggesting that Myc plays an important role in this action of Ras. By contrast, expression of H12-ras promoted factor-independent growth of the multipotent cell line, TF-1. Furthermore, mutant ras dramatically enhanced the growth of TF-1 cells in the presence of added GM-CSF or erythropoietin, but did not influence the state of differentiation of these cells. These data clearly indicate that in haemopoietic cells, Ras may promote either proliferation or differentiation depending upon cell type and/or state of maturation.

Base Sequence↗