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Biomedical subjects

E Roman

Publications and source records attributed to E Roman.

At least 37 records · Page 2Linked to original sources
PubMed2002

The importance of full participation: lessons from a national case-control study.

Differential participation between cases and controls can lead to biased estimates of risk. However, the effects of participation are often ignored. We report a detailed analysis of locations of residence for participants and non-participants in a large, national case-control study of childhood cancer in Great Britain, using the 1991 census. The initial selection of 7669 controls, taken from lists of those registered with a General Practitioner, was representative of the British population in respect to an areal-based index of material deprivation. However, parents of controls agreeing to participate were living in more affluent areas than initially selected controls and their matched 3838 cases. The three components of the deprivation index, persons unemployed, households not owning a car or their home were similarly associated with participation. Other census characteristics, such as proportion of flat dwellers and centrally heated households were also associated with control participation. Population density of the local area was not different between participating controls and their matched cases. However, initially selected controls lived in more urban areas than their cases. Such differences are not unique to this study, as they are an inevitable consequence of incomplete participation. The implications of these differences are discussed, in relation to the difficulty this imposes in the interpretation of studies of disease aetiology.

Adolescent↗
PubMed2002

Vitamin K and childhood cancer: analysis of individual patient data from six case-control studies.

To investigate the hypothesis that neonates who receive intramuscular vitamin K are at an increased risk of developing cancer, particularly leukaemia, a pooled analysis of individual patient data from six case-control studies conducted in Great Britain and Germany has been undertaken. Subjects comprised 2431 case children diagnosed with cancer before 15 years of age and 6338 control children. The retrospective assessment of whether or not an individual baby received vitamin K is not straightforward. In many cases no record was found in stored medical notes and two types of analysis were therefore conducted; in the first it was assumed that where no written record of vitamin K was found it had not been given, and in the second, where no written record of administration was found, information on hospital policy and perinatal morbidity was used to 'impute' whether or not vitamin K had been given. In the first analysis, no association was found between neonatal administration of intramuscular. vitamin K and childhood cancer: odds ratios adjusted for mode of delivery, admission to special care baby unit and low birth weight were 1.09 (95% confidence interval 0.92-1.28) for leukaemia and 1.05 (0.92-1.20) for other cancers. In the second analysis, the adjusted odds ratios increased to 1.21 (1.02-1.44) for leukaemia and 1.10 (0.95-1.26) for other cancers. This shift did not occur in all studies, and when data from the hypothesis generating Bristol study were excluded, the adjusted odds ratios for leukaemia became 1.06 (0.89-1.25) in the first analysis and 1.16 (0.97-1.39) when data on prophylaxis imputed from hospital policy and perinatal morbidity were used. We conclude that whilst the broad nature of the diagnostic groups and the poor quality of some of the vitamin K data mean that small effects cannot be entirely ruled out, our analysis provides no convincing evidence that intramuscular vitamin K is associated with childhood leukaemia.

Adolescent↗
PubMed2002

Smoking and the risk of acute myeloid leukaemia in cytogenetic subgroups.

Cytogenetically-defined subgroups of acute myeloid leukaemia have distinct biologies, clinical features and outcomes. Evidence from therapy-related leukaemia suggests that chromosomal abnormalities are also markers of exposure. Our results suggest that the smoking-associated risk for acute myeloid leukaemia is restricted to the t(8;21)(q22;q22) subgroup. This supports the hypothesis that distinct cytogenetic subgroups of acute myeloid leukaemia have separate aetiologies.

Chromosome Aberrations↗
PubMed2002

Molecular detection of human calicivirus among Spanish children with acute gastroenteritis.

A survey was conducted among Spanish children with gastroenteritis treated in an emergency room. Reverse transcription-PCR with specimens negative for other enteric pathogens was used. The minimum incidence of human calicivirus infection was 7.7%, with Lordsdale as the predominant genotype. The clinical features and severity of calicivirus and rotavirus were similar.

Acute Disease↗
PubMed2001

Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia.

Glutathione S-transferases (GSTs) detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Functional polymorphisms exist in at least three genes that encode GSTs, including GSTM1, GSTT1, and GSTP1. We hypothesize, therefore, that polymorphisms in genes that encode GSTs alter susceptibility to chemotherapy-induced carcinogenesis, specifically to therapy-related acute myeloid leukemia (t-AML), a devastating complication of long-term cancer survival. Elucidation of genetic determinants may help to identify individuals at increased risk of developing t-AML. To this end, we have examined 89 cases of t-AML, 420 cases of de novo AML, and 1,022 controls for polymorphisms in GSTM1, GSTT1, and GSTP1. Gene deletion of GSTM1 or GSTT1 was not specifically associated with susceptibility to t-AML. Individuals with at least one GSTP1 codon 105 Val allele were significantly over-represented in t-AML cases compared with de novo AML cases [odds ratio (OR), 1.81; 95% confidence interval (CI), 1.11-2.94]. Moreover, relative to de novo AML, the GSTP1 codon 105 Val allele occurred more often among t-AML patients with prior exposure to chemotherapy (OR, 2.66; 95% CI, 1.39-5.09), particularly among those with prior exposure to known GSTP1 substrates (OR, 4.34; 95% CI, 1.43-13.20), and not among those t-AML patients with prior exposure to radiotherapy alone (OR,1.01; 95% CI, 0.50-2.07). These data suggest that inheritance of at least one Val allele at GSTP1 codon 105 confers a significantly increased risk of developing t-AML after cytotoxic chemotherapy, but not after radiotherapy.

Chromosome Aberrations↗
PubMed2001

Sex ratio of nuclear industry employees' children.

Does preconceptional exposure to ionising radiation before conception affect the health of offspring? Some studies have suggested that radiation exposure might influence the sex ratio at birth, potentially indicating genetic damage. We examined the sex ratio of over 46000 children born to UK nuclear industry workers, using information on exposure from the workers' individual employment and dosimetry records. We found no statistically significant alterations of the sex ratio, and no evidence that exposure to low-level ionising radiation at work influences the sex ratio of children conceived after exposure.

Air Pollution, Radioactive↗
PubMed2001

Vitamin K policies and midwifery practice: questionnaire survey.

OBJECTIVES: To investigate policies on neonatal vitamin K and their implementation. DESIGN: Two phase postal survey. SETTING: United Kingdom. PARTICIPANTS: A 10% random sample of midwives registered with the United Kingdom Central Council for nursing, midwifery, and health visiting. Of 3191 midwives in the sample, 2515 (79%) responded to phase one and 2294 (72%) completed questionnaires on their current jobs (November 1998 to May 1999). In phase two, 853 (62%) of 1383 eligible midwives gave details on 2179 of their earliest jobs (start dates before 1990). RESULTS: All the midwives in clinical practice at the time of the survey (2271, 99%) reported that they were working in areas with official policies on neonatal vitamin K. Seven distinct policies were described: intramuscular vitamin K for all babies (1159, 51.0%); intramuscular vitamin K for babies at "high risk," oral for others (470, 20.7%); oral vitamin K for all babies (323, 14.2%); parental choice for all (124, 5.5%); parental choice for all except babies at high risk, (119, 5.2%); intramuscular vitamin K for babies at high risk only (33, 1.5%); oral vitamin K for babies at high risk only (17, 0.7%); and a disparate group of policies including intravenous vitamin K for some babies (26, 1.1%). Previous policies were (and some may still be) open to individual interpretation and were not always followed. CONCLUSIONS: Hospital policy is not necessarily a good guide to individual practice. The primary purpose of clinical records is to document patient care, and recording practices reflect this. There is considerable variation in vitamin K policies and midwifery practice in the United Kingdom, and there is no clear consensus on which babies should receive vitamin K intramuscularly.

Administration, Oral↗
PubMed2001

Karyotype and age in acute myeloid leukemia. Are they linked?

A novel hierarchical cytogenetic classification for acute myeloid leukemia (AML) has been developed. Patients with successful cytogenetics and a diagnosis of AML were categorized into four mutually exclusive karyotype groups: normal, translocation, deletion and trisomy. Patients with more than one chromosomal abnormality were classified using the hierarchy: established translocation>established deletion>established trisomy>non-established translocation>non-established deletion>non-established trisomy. A total of 593 AML patients from a large population-based case-control study of acute leukemia were classified according to their diagnostic karyotype. The four karyotype groups showed different age distributions. Overall the frequency of patients increased with age as did the frequency of patients with a deletion, trisomy or normal karyotype. Although the increase of patients with age was much sharper for patients with a deletion. In contrast, the distribution of patients with a translocation was roughly constant with age. We concluded that there was a link between karyotype and the age of the patient at diagnosis. Furthermore, two karyotype groups, translocations and deletions, may define disease entities with different etiologies. This novel cytogenetic classification will allow other studies to examine whether AML cases with very different types of chromosomal abnormality have the same etiology.

Acute Disease↗
PubMed2001

Low NAD(P)H:quinone oxidoreductase 1 activity is associated with increased risk of acute leukemia in adults.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme that detoxifies quinones and reduces oxidative stress. A cysteine-to-threonine (C --> T) substitution polymorphism at nucleotide 609 of the NQO1 complementary DNA (NQO1 C609T) results in a lowering of NQO1 activity. Individuals homozygous for this mutation have no NQO1 activity, and heterozygotes have low to intermediate activity compared with people with wild type. DNA samples from 493 adult de novo acute leukemia patients and 838 matched controls were genotyped for NQO1 C609T. The majority of cases were diagnosed as acute myeloid leukemia (AML) (n = 420); 67 as acute lymphoblastic leukemia (ALL); and 6 as other forms of acute leukemia. The frequency of cases with low or null NQO1 activity (heterozygote + homozygous mutant) was significantly higher among total acute leukemia case subjects compared with their matched controls (odds ratio [OR] = 1.49; 95% confidence interval [CI], 1.17-1.89). Both ALL (OR = 1.93; 95% CI, 0.96-3.87) and AML case subjects (OR = 1.47; 95% CI, 1.13-1.90) exhibited a higher frequency of low or null NQO1 genotypes than controls. For de novo AML, the most significant effect of low or null NQO1 activity was observed among the 88 cases harboring translocations and inversions (OR = 2.39; 95% CI, 1.34-4.27) and was especially high for those harboring inv(16) (OR = 8.13; 95% CI, 1.43-46.42). These findings were confirmed in a second group of 217 de novo AML cases with known cytogenetics. Thus, inheritance of NQO1 C609T confers an increased risk of de novo acute leukemia in adults, implicating quinones and related compounds that generate oxidative stress in producing acute leukemia.

Acute Disease↗
PubMed2001

New immunochromatographic method for rapid detection of rotaviruses in stool samples compared with standard enzyme immunoassay and latex agglutination techniques.

Three different commercial immunologic tests for rapid detection of group A rotavirus (an immunochromatographic method, latex agglutination, and enzyme immunoassay) were used to evaluate 228 faecal specimens obtained from Spanish children with acute gastroenteritis. After resolution of 30 (13.2%) discordant results by reverse transcription-polymerase chain reaction for rotavirus, the statistical values of the enzyme immunoassay, latex agglutination, and immunochromatographic method were respectively 96%, 68%, and 99% for sensitivity; 99%, 99%, and 96% for specificity; 98%, 96%, and 92% for positive predictive value; and 98%, 88%, and 99% for negative predictive value. The immunochromatographic technique showed high sensitivity and specificity and was rapid and easy to perform in the routine clinical laboratory.

Child, Preschool↗
PubMed2001

Malignant neoplasms of the brain during childhood: the role of prenatal and neonatal factors (United Kingdom).

OBJECTIVES: To evaluate whether factors in pregnancy and around birth influence the risk of childhood malignant neoplasms of the brain or other parts of the nervous system. METHODS: The distribution of certain characteristics of pregnancy and birth among 83 cases of malignant neoplasms of the brain and other parts of the nervous system (diagnosed between 0 and 14 years of age) and 166 controls (individually matched on date of birth, sex, and hospital of birth) were compared. Odds ratios (OR), 95% confidence intervals (95% CI) and two-sided p-values were calculated using conditional logistic regression for matched sets. RESULTS: Children whose mothers had documented evidence of a clinically diagnosed viral infection during pregnancy had an approximately 11-fold increase in risk of developing a malignant neoplasm of the brain or other part of the nervous system (OR = 10.6, 95% CI = 1.1-503.2). In addition, non-statistically significant increased risks were observed among children who had a non-cephalic presentation (OR = 3.3, 95% CI = 0.8-13.9) or a low 1-minute apgar score (OR = 2.7, 95% CI = 1.0-7.4). No other aspects of the index pregnancy, delivery, or maternal characteristics were associated with an increased risk of childhood brain tumors. CONCLUSIONS: The results reported here provide limited evidence for the role of prenatal and neonatal factors in the etiology of childhood malignant neoplasms of the brain. The finding for maternal viral infection during pregnancy warrants further investigation.

Adolescent↗
PubMed2001

CD4(+) T cell effectors can become memory cells with high efficiency and without further division.

Whether memory T lymphocytes are derived directly from effector T cells or via a separately controlled pathway has long been debated. Here we present evidence that, after adoptive transfer, a large fraction of in vitro--derived effector CD4(+) T cells have the potential to become memory T cells and that this transition can occur without further division. This data supports a linear pathway from effector to memory cells and suggests that most properties of memory cells are predetermined during effector generation. We suggest, therefore, that evaluation of vaccine efficacy in the induction of memory CD4(+) T cells should focus on the effector stage.

Animals↗
PubMed2001

Large tables.

The traditional exploration of large contingency tables leads to multiple comparisons with the inherent generation of chance associations. To allow for this, a simple empirical Bayesian approach is used here to derive estimates of association 'shrunk' towards a global mean. Estimates are displayed on ordered normal plots, to allow visual detection of outliers, with the addition of 'guide rails', derived from simulation, to facilitate their detection. The methods, and the interpretation of results, are illustrated using a large table of occupations for cancer registrations in England and Wales for 1971-90.

Journal Article↗
PubMed2001

Primary infertility in nuclear industry employees: report from the nuclear industry family study.

OBJECTIVE: To determine whether men and women who are occupationally exposed to ionising radiation are at increased risk of primary infertility. METHODS: A cross sectional analysis of reproductive outcome was reported in an occupational cohort of nuclear industry workers from the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels in the United Kingdom. Data on employment and radiation monitoring supplied by employers were linked to data obtained from self administered questionnaires sent to all current employees and a sample of past workers. A total of 5353 men and 603 women aged 40 years or more at the time of survey whose first pregnancy, or attempt at pregnancy, had occurred after first employment in the nuclear industry were recruited to the study. Primary infertility was defined as consultation with a doctor about the failure to achieve at least one viable (24 weeks gestational age or more) pregnancy. RESULTS: 2.6% Of men and 3.7% of women reported primary infertility. For men, this proportion did not differ by amount of radiation monitored or by dose received. The prevalence of infertility was higher among monitored women than non-monitored women, but not significantly so and the numbers were too small to draw any firm conclusions. CONCLUSIONS: No support was found for a hypothesis linking exposure to low level ionising radiation among men with primary infertility. There was weak evidence of an association in women, but the relatively few monitored women prevented detailed examination of these data.

Adult↗
PubMed2000

Fetal death and congenital malformation in babies born to nuclear industry employees: report from the nuclear industry family study.

BACKGROUND: There is some concern about the genetic effects of exposure to low-level ionising radiation, but the evidence is sparse and conflicting. Most work has concentrated on cancer in offspring and little has been done on adverse reproductive outcome. We aimed to assess whether the offspring of men and women who are occupationally exposed to ionising radiation are at increased risk of fetal death and congenital malformation. METHODS: We analysed pregnancies reported by an occupational cohort of nuclear industry workers in the UK, employed at establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. Employment and radiation monitoring data supplied by employers was linked to each pregnancy. FINDINGS: 11,697 men and 1903 women reported one or more singleton pregnancy conceived after first employment within the nuclear industry, the men reporting a total of 23,676 singleton pregnancies and the women 3585. The risks of fetal death and congenital malformation were not related to whether the father had been monitored before conception or to the dose of radiation received. Among pregnancies reported by women, the risk of early (<13 weeks of gestation) miscarriage was higher if the mother had been monitored before conception (odds ratio [OR] 1.3, 95% CI 1.0-1.6), but there was no trend with dose. The risk of stillbirth was also higher if the mother had been monitored before conception (OR 2.2, 95% CI 1.0-4.6), but the finding was based on only 29 cases (13 exposed). The risk of any major malformation, or of specific groups of malformations, was not associated with maternal monitoring, or dose received, before conception. INTERPRETATION: We found no evidence of a link between exposure to low-level ionising radiation before conception and increased risk of adverse reproductive outcome in men working in the nuclear industry. Similarly for women there was no evidence of an association between monitoring before conception and malformation in offspring. The findings relating maternal preconceptual monitoring to increased risk of fetal death are equivocal and require further investigation.

Abnormalities, Radiation-Induced↗
PubMed2000

Basal levels and alcohol-induced changes in nociceptin/orphanin FQ, dynorphin, and enkephalin levels in C57BL/6J mice.

In order to investigate the involvement of the opioid and nociceptin/orphanin FQ (N/OFQ) system in alcohol drinking behaviour, N/OFQ and the opioid peptides dynorphin B (DYNB) and Met-enkephalin-Arg(6) Phe(7) (MEAP) were examined in the alcohol-preferring C57BL/6J mice. Basal peptide levels were compared in the brain and the pituitary gland with basal levels in the alcohol-avoiding DBA/2J mice. Furthermore, the effects of chronic alcohol self-administration on peptides were studied in the C57BL/6J mice. Compared to the DBA/2J mice, C57BL/6J mice had low immunoreactive (ir) levels of DYNB and MEAP in the nucleus accumbens, the hippocampus, and the substantia nigra, low ir-DYNB levels in the striatum and low ir-MEAP levels in the frontal cortex. Higher ir-DYNB levels in the pituitary gland and in the periaqueductal gray (PAG) and higher ir-N/OFQ levels in the frontal cortex and in the hippocampus were detected in C57BL/6J mice compared to the DBA/2J mice. After 4 weeks of voluntary alcohol consumption, only minor changes in steady-state peptide levels were identified. However, 5 days after the alcohol-drinking period, lower levels of all peptides were detected in the ventral tegmental area and ir-DYNB levels were also lower in the amygdala and in the substantia nigra. Twenty-one days after cessation of alcohol self-administration, the opioid peptides in alcohol-consuming C57BL/6J mice were lower in the PAG, the N/OFQ was lower in the frontal cortex and DYNB was higher in the amygdala and substantia nigra as compared to control C57BL/6J mice. This study demonstrates strain differences between C57BL/6J mice and DBA/2J mice that could contribute to divergent drug-taking behaviour, and it also demonstrates time- and structure-specific changes in neuropeptide levels after alcohol self-administration in the C57BL/6J mice.

Alcohol Drinking↗