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1.  Prevalence of Hyperthyroidism Following Exposure During Childhood or Adolescence to Radioiodines from the Chornobyl Nuclear Accident: Dose-Response Results from the Ukrainian-American Cohort Study 
Radiation research  2010;174(6):763-772.
Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of < 0.3 mIU/L, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 (I-131) (mean and median doses = 0.6 Gray (Gy) and 0.2 Gy). We investigated the relationship of I-131 and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12–14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n=5,767) and males (23 cases, n=6,086) separately, but found no convincing evidence of a dose response relationship between I-131 and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR=1.86, P=0.06), but the statistical significance level was reduced (P=0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose response relationship between individual I-131 thyroid doses and prevalent hyperthyroidism.
PMCID: PMC3927725  PMID: 21128800
2.  Extensive cervical spine and foregut anomaly in ‘serpentine syndrome’ 
We report an extremely rare and challenging combination of congenital anomalies. Only five similar cases have been described in the English language medical literature to date.
A male infant was born at 30+5 weeks gestation by emergency caesarian section. Cervical spine rachischisis, shortened oesophagus, intrathoracic stomach, atretic duodenum and absent spleen were noted, in addition to respiratory insufficiency. Gastrointestinal re-anastomosis, particularly oesophageal lengthening, was not feasible at the initial thoracotomy. Surgical stabilization of the cervical spine was unlikely to be successful until two years of age. Asplenia predisposed the infant to sepsis from encapsulated organisms, and recurrent respiratory infections occurred.
A close relationship exists between the upper gastrointestinal tract and cervical spine during embryonic development. An embryonic aberration at this level could account for all the deformities present in this infant. Tethering of the embryonic cervical oesophagus to the somites in the first trimester, preventing foregut elongation, and producing ischaemia at the coeliac axis, is suggested as the aetiology.
This case presented a challenge to the multi-disciplinary team involved in his management and prompted extensive consultation with international experts. After considerable counseling of the parents, care was directed towards palliation.
PMCID: PMC3731719  PMID: 23567544
Thoracic stomach; Short oesophagus; Asplenia; Congenital anomalies; Rachischisis; Cervical spine
3.  Thyroid cancer risk in Belarus among children and adolescents exposed to radioiodine after the Chornobyl accident 
British Journal of Cancer  2010;104(1):181-187.
Previous studies showed an increased risk of thyroid cancer among children and adolescents exposed to radioactive iodines released after the Chornobyl (Chernobyl) accident, but the effects of screening, iodine deficiency, age at exposure and other factors on the dose–response are poorly understood.
We screened 11 970 individuals in Belarus aged 18 years or younger at the time of the accident who had estimated 131I thyroid doses based on individual thyroid activity measurements and dosimetric data from questionnaires. The excess odds ratio per gray (EOR/Gy) was modelled using linear and linear–exponential functions.
For thyroid doses <5 Gy, the dose–response was linear (n=85; EOR/Gy=2.15, 95% confidence interval: 0.81–5.47), but at higher doses the excess risk fell. The EOR/Gy was significantly increased among those with prior or screening-detected diffuse goiter, and larger for men than women, and for persons exposed before age 5 than those exposed between 5 and 18 years, although not statistically significant. A somewhat higher EOR/Gy was estimated for validated pre-screening cases.
10–15 years after the Chornobyl accident, thyroid cancer risk was significantly increased among individuals exposed to fallout as children or adolescents, but the risk appeared to be lower than in other Chornobyl studies and studies of childhood external irradiation.
PMCID: PMC3039791  PMID: 21102590
thyroid neoplasms; iodine radioisotopes; Chernobyl nuclear accident; risk; iodine deficiency
4.  Muscular strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides 
Methods: This study concerns the third of a series of three examinations of hand strength and vibration thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men. The first two examinations were performed at hospital discharge and seven weeks after poisoning, and the present examination two years later. Twenty eight cattle ranchers and fishermen who had never experienced pesticide poisoning were examined as controls, also three times over the two year period. The poisonings were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each subdivided in moderate and severe poisonings.
Results: Men poisoned with OP insecticides had persistent reduced hand strength. We previously reported weakness at hospital discharge for OP poisoned in all categories that worsened seven weeks later for those severely poisoned with neuropathic OPs. Strength improved over time, but the poisoned were still weaker than controls two years after the poisoning, most noticeably among the subjects most severely poisoned with neuropathic OPs. Also, index finger and toe vibration thresholds were slightly increased at the end of the two year period, among men with OP poisonings in all categories, but patterns of onset and evolvement of impairment of vibration sensitivity were less clear than with grip and pinch strength.
Conclusions: Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.
PMCID: PMC1757809  PMID: 14691285
6.  The ACE I allele is associated with increased risk for ruptured intracranial aneurysms 
Journal of Medical Genetics  2000;37(7):498-500.
Genetic and environmental factors play roles in the aetiology of ruptured intracranial aneurysms. Hypertension has been reported as a risk factor for intracranial aneurysm haemorrhage. We have tested if genotypes at the angiotensin converting enzyme (ACE) gene locus are associated with ruptured intracranial aneurysms. The insertion/deletion polymorphism in the ACE gene was genotyped in 258 subjects presenting in East Anglia with ruptured intracranial aneurysms (confirmed at surgery or angiographically) and 299 controls from the same region. ACE allele frequencies were significantly different in the cases and the controls (alleles χ21=4.67, p=0.03). The I allele was associated with aneurysm risk (odds ratio for I allele v D allele = 1.3 (95% CI=1.02-1-65); odds ratio for II v DD genotype = 1.67 (95% CI=1.04-2.66)). The I allele at the ACE locus is over-represented in subjects with ruptured intracranial aneurysms. These data are supported by non-significant trends in the same direction in two previous smaller studies. Thus, this allele may be associated with risk for ruptured intracranial aneurysms.

Keywords: ACE I allele; ruptured intracranial aneurysms
PMCID: PMC1734634  PMID: 10882751
7.  Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function 
Thorax  2000;55(4):271-276.
BACKGROUND—Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development.
METHODS—A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993.Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics.
RESULTS—In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF75) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV1). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0.4) and FEF75 (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF75 associated with all measurements of ETS were substantially reduced and were not statistically significant.
CONCLUSIONS—In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.

PMCID: PMC1745733  PMID: 10722765
10.  Air pollution and bronchitic symptoms in Southern California children with asthma. 
Environmental Health Perspectives  1999;107(9):757-760.
The association of air pollution with the prevalence of chronic lower respiratory tract symptoms among children with a history of asthma or related symptoms was examined in a cross-sectional study. Parents of a total of 3,676 fourth, seventh, and tenth graders from classrooms in 12 communities in Southern California completed questionnaires that characterized the children's histories of respiratory illness and associated risk factors. The prevalences of bronchitis, chronic phlegm, and chronic cough were investigated among children with a history of asthma, wheeze without diagnosed asthma, and neither wheeze nor asthma. Average ambient annual exposure to ozone, particulate matter (PM(10) and PM(2.5); [less than/equal to] 10 microm and < 2.5 microm in aerodynamic diameter, respectively), acid vapor, and nitrogen dioxide (NO(2)) was estimated from monitoring stations in each community. Positive associations between air pollution and bronchitis and phlegm were observed only among children with asthma. As PM(10) increased across communities, there was a corresponding increase in the risk per interquartile range of bronchitis [odds ratio (OR) 1.4/19 microg/m(3); 95% confidence interval (CI), 1.1-1.8). Increased prevalence of phlegm was significantly associated with increasing exposure to all ambient pollutants except ozone. The strongest association was for NO(2), based on relative risk per interquartile range in the 12 communities (OR 2.7/24 ppb; CI, 1.4-5.3). The results suggest that children with a prior diagnosis of asthma are more likely to develop persistent lower respiratory tract symptoms when exposed to air pollution in Southern California.
PMCID: PMC1566453  PMID: 10464077
11.  A theoretical basis for investigating ambient air pollution and children's respiratory health. 
Environmental Health Perspectives  1999;107(Suppl 3):403-407.
Acute respiratory health effects in children from exposure at current ambient levels of ozone are well documented; however, evidence for acute effects from other criteria pollutants such as nitrogen dioxide and respirable particles is inconsistent. Whether chronic effects result from long-term exposure to any of these pollutants during childhood is an important unresolved question. Establishing whether acute or chronic effects result from childhood exposure and identifying sensitive subgroups may require integration of biologic mechanisms of lung defenses, injury, and response into the study design and statistical models used in analyses. This review explores the theoretical basis for explaining such adverse effects in light of our contemporary understanding of mechanisms of lung injury and response at the cellular and molecular levels. The rapidly evolving understanding of the effects of air pollution on cellular and molecular levels presents an opportunity to develop and refine innovative biologically based hypotheses about the effects of childhood exposure. We hypothesize that children with low fruit and vegetable intake, low antioxidant levels, high polyunsaturated fat intake, or who have inherited certain alleles for genes involved in lung defenses and immune response regulation may be at increased risk for adverse effects. Because responses to air pollutants of interest are complex and involve a number of pathophysiologic processes, the magnitude of main effects of dietary factors, genes, and gene-environment interactions may be modest for individuals; however, each may make an important contribution to the population burden of preventable respiratory diseases.
PMCID: PMC1566227  PMID: 10346989
13.  Lead exposure in Latin America and the Caribbean. Lead Research Group of the Pan-American Health Organization. 
Environmental Health Perspectives  1997;105(4):398-405.
As a result of the rapid industrialization of Latin America and the Caribbean during the second half of this century, exposure to lead has become an increasingly important problem. To obtain an estimate of the magnitude of lead exposure in the region, we carried out a survey and a literature search on potential sources of lead exposure and on blood lead concentrations. Sixteen out of 18 Latin American and 2 out of 10 Caribbean countries responded to the survey. Lead in gasoline remains a major problem, although the lead content has decreased in many countries in the last few years. The impact of leaded fuel is more important in urban settings, given their high vehicular density. Seventy-five percent of the population of the region lives in urban areas, and children younger than 15 years of age, the most susceptible group, comprise 30% of the population. Other sources of lead exposure identified in the region included industrial emissions, battery recycling, paint and varnishes, and contaminated food and water. Lead is recognized as a priority problem by national authorities in 72% of the countries that responded to the survey, and in 50% of the countries some legislation exists to regulate the lead content in certain products. However, compliance is low. There is an urgent need for a broad-based coalition between policy makers, industry, workers, unions, health care providers, and the community to take actions to reduce environmental and occupational lead exposures in all the Latin American and Caribbean countries.
PMCID: PMC1469970  PMID: 9189704
15.  Angiosarcoma, porphyria cutanea tarda, and probable chloracne in a worker exposed to waste oil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. 
A worker developed angiosarcoma, porphyria cutanea tarda, and skin lesions characteristic of mild chloracne. About 10 years earlier he had been employed at a truck terminal in Saint Louis, Missouri, at a time when it was sprayed with waste oil contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The occurrence of these three rare conditions in a single exposed worker supports the aetiological relation between environmental exposure to TCDD and the subsequent development of soft tissue sarcoma and porphyria cutanea tarda.
PMCID: PMC1012172  PMID: 8104464
16.  Hazards of closed pesticide mixing and loading systems: the paradox of protective technology in the Third World. 
In studies in developing countries, closed systems for mechanically mixing and loading hazardous pesticides have been shown to reduce exposure to workers. To evaluate the efficacy of closed systems in preventing worker exposure in the developing world, a cross sectional study was conducted at rural crop dusting airports in the cotton growing region of Nicaragua. Worker exposure was evaluated by measuring the activity of erythrocyte cholinesterase in the field with a new design battery operated colorimeter. The 10 mixer loaders at four airstrips with closed systems were compared with the 16 mixer loaders at four airstrips where pesticides were hand poured. Paradoxically, cholinesterase activity was 1.1 IU/ml blood (95% Cl 0.49-1.8) lower (inhibited) among workers in airstrips with closed systems than among workers hand pouring insecticides, after adjusting for weight of organophosphates sprayed in the past 14 days, and for prior training in safe use of pesticides. Mixer loaders with prior training had cholinesterase activity 0.83 IU (95% Cl 0.30-1.4) higher than untrained workers, and the weight of organophosphates sprayed was also a statistically significant predictor in the model. Unfortunately, management viewed the closed systems primarily as a production tool, rather than as a way to protect workers. Airstrips with closed systems were able to apply an average of 3250 lb organophosphates per worker in the 14 days before the survey compared with 849 lb per worker in airstrips without closed systems. Only three of 10 mixer-loaders at airstrips with closed systems had received formal training in safer use of pesticides. Because of shortage of personnel and transport, it was difficult for the responsible government agencies to train workers adequately and to enforce pesticide health and safety standards at multiple dispersed worksites.
PMCID: PMC1039305  PMID: 1390266
17.  Fading teacher prompts from peer-initiation interventions for young children with disabilities. 
This study examined a system for fading teacher prompts to children who served as peers in peer-initiation interventions for young children with disabilities. A teacher taught peers to direct social initiations to children with disabilities, provided verbal prompts for those initiations, and introduced a system that provided peers with visual feedback about the social interactions of the children with disabilities. She then systematically withdrew the verbal prompts to peers, and subsequently faded the visual feedback system. Peer initiations increased when the intervention began and resulted in increases in social interaction for the children with disabilities. As the teacher systematically faded the prompts and visual feedback to the peers, social interaction continued at the levels found during intervention and was maintained during a short maintenance period.
PMCID: PMC1279712  PMID: 1386069
18.  Treadmill protocols for determination of maximum oxygen uptake in runners. 
Four testing protocols were completed by each of 10 runners using a common speed for protocols 1 and 2 (P1 and P2), each runner's training pace for protocol 3 (P3) and a speed selected manually by the runner for protocol 4 (P4). Stages were increased by 2.5% grade every 2 min for each protocol except for P1, which had 1 min stages. There were no significant differences in maximum oxygen uptake (VO2 max) between protocols (P1, 65.0 +/- 5.6 min-1; P2, 64.5 +/- 5.3 min-1; P3, 66.2 +/- 3.9 min-1; P4, 64.7 +/- 5.8 min-1). Treadmill time was significantly less for P1 than for the other protocols. The rate of perceived exertion obtained at maximal exercise during P1 was less than that obtained during the other three protocols. Heart rate was significantly lower (P less than 0.05) at any level of submaximal VO2 during P3 than during the other protocols. We recommend a testing protocol using speeds approximating the runner's training pace and 1 min stages. This may result in lower perception of difficulty and HR throughout the test and shorter testing times.
PMCID: PMC1478508  PMID: 3370399
19.  Pseudopolycythaemia and coeliac disease. 
Gut  1987;28(8):1041-1042.
We report two patients in whom introduction of a gluten free diet for coeliac disease was associated with the development of pseudopolycythaemia.
PMCID: PMC1433153  PMID: 3666556
20.  Changing patterns of coeliac disease frequency: an analysis of Coeliac Society membership records. 
Gut  1985;26(2):175-178.
Examination of Coeliac Society records from eight areas of England has shown that the number of members rose with birth dates from 1900 to 1972, apart from a decline between 1941 to 1962, and then fell steeply. The steep decline in the number of members with birth dates after 1972 is unexplained, and is unlikely to be accounted for by change in diagnostic practice or registration and may reflect a true fall in disease incidence; but the fall in numbers of members with birth dates from 1941 to 1962 is explainable by a tendency for the disease to remit in adolescence or early adult life.
PMCID: PMC1432428  PMID: 3967836
21.  HLA-DR typing in coeliac disease: evidence for genetic heterogeneity. 
Sixty nine propositi from a family study of coeliac disease were typed for HLA-DR antigens. Sixty three (91%) were found to carry the antigen DR3, which was a significantly greater proportion (p = 9.6 X 10(-24] than among the 168 controls (26%). Concurrently 42 children with the disease were DR typed. Not only was the frequency of DR3 significantly increased in these patients (86% versus 26% in controls; p = 3.1 X 10(-12] but so also was the frequency of DR7 (patients 60%, controls 29%; p = 5.8 X 10(-4]. When those propositi whose coeliac disease presented before the age of 20 were combined with the childhood coeliac group and a comparison made between these patients and the remainder of the propositi, all of whom presented when they were older than 20, the childhood onset group had a significant excess of DR7 (p = 2.2 X 10(-3] and a significant deficiency of DR2 (p = 3.5 X 10(-3]. These findings indicate that childhood coeliac disease and adult coeliac disease are genetically heterogeneous.
PMCID: PMC1443876  PMID: 6439322
24.  Identification of cellular immunoglobulins in chronic lymphocytic leukaemia by immunoperoxidase staining. 
Journal of Clinical Pathology  1983;36(12):1391-1396.
An indirect immunoperoxidase technique has been used for visualisation of cellular immunoglobulins in chronic lymphocytic leukaemia. Baker's formol calcium was used as fixative. Monoclonal light and heavy chain patterns were demonstrated in 24 out of 27 cases. Only one case did not have any demonstrable immunoglobulins. The presence of alpha or gamma heavy chain immunoglobulin isotypes in leukaemic lymphocytes was found to be related to low mouse rosetting capacity (p less than 0.05).
PMCID: PMC498575  PMID: 6418770

Results 1-25 (72)