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Biomedical subjects

E Roman

Publications and source records attributed to E Roman.

At least 19 recordsLinked to original sources

First detection of group C rotavirus in children with acute diarrhea in Spain.

Group C rotavirus causes sporadic cases and outbreaks of acute diarrhea in children and adults in many countries, but has never been detected among children in Spain. In a recently conducted surveillance study to screen fecal specimens for bacteria and viruses from a cohort of 822 young children who were treated for acute diarrhea in Madrid, no pathogens were detected in fecal specimens from 238 (29%) children. In this study, we examined 147 of those specimens for group C rotavirus by EIA and PCR and found 22 (15%) were positive. Our findings demonstrate that group C rotavirus is an important cause of childhood diarrhea in Spain.

Child↗

Viruses causing gastroenteritis.

Acute gastroenteritis is one of the most common diseases in humans worldwide. Viruses are recognized as important causes of this disease, particularly in children. Since the Norwalk virus was identified as a cause of gastroenteritis, the number of viral agents associated with diarrheal disease in humans has steadily increased. Rotavirus is the most common cause of severe diarrhea in children under 5 years of age. Astrovirus, calicivirus and enteric adenovirus are also important etiologic agents of acute gastroenteritis. Other viruses, such as toroviruses, coronaviruses, picobirnaviruses and pestiviruses, are increasingly being identified as causative agents of diarrhea. In recent years, the availability of diagnostic tests, mainly immunoassays or molecular biology techniques, has increased our understanding of this group of viruses. The future development of a safe and highly effective vaccine against rotavirus could prevent, at least, cases of severe diarrhea and reduce mortality from this disease.

Acute Disease↗

Occupational exposure to electromagnetic fields and acute leukaemia: analysis of a case-control study.

AIMS: To investigate whether the risk of acute leukaemia among adults is associated with occupational exposure to electromagnetic fields. METHODS: Probable occupational exposure to electromagnetic fields at higher than typical residential levels was investigated among 764 patients diagnosed with acute leukaemia during 1991-96 and 1510 sex and age matched controls. A job exposure matrix was applied to the self reported employment histories to determine whether or not a subject was exposed to electromagnetic fields. Risks were assessed using conditional logistic regression for a matched analysis. RESULTS: Study subjects considered probably ever exposed to electromagnetic fields at work were not at increased risk of acute leukaemia compared to those considered never exposed. Generally, no associations were observed on stratification by sex, leukaemia subtype, number of years since exposure stopped, or occupation; there was no evidence of a dose-response effect using increasing number of years exposed. However, relative to women considered never exposed, a significant excess of acute lymphoblastic leukaemia was observed among women probably exposed to electromagnetic fields at work that remained increased irrespective of time prior to diagnosis or job ever held. CONCLUSION: This large population based case-control study found little evidence to support an association between occupational exposure to electromagnetic fields and acute leukaemia. While an excess of acute lymphoblastic leukaemia among women was observed, it is unlikely that occupational exposure to electromagnetic fields was responsible, given that increased risks remained during periods when exposure above background levels was improbable.

Adolescent↗

Exposure to power frequency electric fields and the risk of childhood cancer in the UK.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.

Adolescent↗

Age-specific incidence rates for cytogenetically-defined subtypes of acute myeloid leukaemia.

It is generally considered that most cancers arise following the accumulation of several genetic events and that as a consequence its incidence increases with age. We report a cytogenetic subgroup of acute myeloid leukaemia whose incidence is independent of age. This observation indicates that acute myeloid leukaemia can develop via multiple pathways, and underlines the importance of cytogenetics in understanding this disease.

Acute Disease↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗