Does research into sensitive areas do harm? Experiences of research participation after a child's diagnosis with Ewing's sarcoma

Objective: To investigate family members' experiences of involvement in a previous study (conducted August 1995 to June 1997) following their child's diagnosis with Ewing's sarcoma. Design: Retrospective survey, conducted between 1 November and 30 November 1997, using a postal questionnaire. Participants: Eighty-one of 97 families who had previously completed an in-depth interview as part of a national case-control study of Ewing's sarcoma. Main outcome measures: Participants' views on how participation in the previous study had affected them and what motivated them to participate. Results: Most study participants indicated that taking part in the previous study had been a positive experience. Most (n = 79 [97.5%]) believed their involvement would benefit others and were glad to have participated, despite expecting and finding some parts of the interview to be painful. Parents whose child was still alive at the time of the interview recalled participation as more painful than those whose child had died before the interview. Parents who had completed the interview less than a year before our study recalled it as being more painful than those who had completed it more than a year before. Conclusions: That people suffering bereavement are generally eager to participate in research and may indeed find it a positive experience is useful information for members of ethics review boards and other gatekeepers, who frequently need to determine whether studies into sensitive areas should be approved. Such information may also help members of the community to make an informed decision regarding participation in such research.

Minor physical anomalies and quantitative measures of the head and face in patients with psychosis

Background: The aim of this study was to examine minor physical anomalies and quantitative measures of the head and face in patients with psychosis vs healthy controls. Methods: Based on a comprehensive prevalence study of psychosis, we recruited 310 individuals with psychosis and 303 controls. From this sample, we matched 180 case-control pairs for age and sex. Individual minor physical anomalies and quantitative measures related to head size and facial height and depth were compared within the matched pairs. Based on all subjects, we examined the specificity of the findings by comparing craniofacial summary scores in patients with nonaffective or affective psychosis and controls. Results: The odds of having a psychotic disorder were increased in those with wider skull bases (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.02-1.17), smaller lower-facial heights (glabella to subnasal) (OR, 0.57; 95% CI, 0.44-0.75), protruding ears (OR, 1.72; 95% CI, 1.05-2.82), and shorter (OR, 2.29; 95% CI, 1.37-3.82) and wider (OR, 2.28; 95% CI, 1.43-3.65) palates. Compared with controls, those with psychotic disorder had skulls that were more brachycephalic. These differences were found to distinguish patients with nonaffective and affective psychoses from controls. Conclusions: Several of the features that differentiate patients from controls relate to the development of the neuro-basicranial complex and the adjacent temporal and frontal lobes. Future research should examine both the temporal lobe and the middle cranial fossa to reconcile our anthropomorphic findings and the literature showing smaller temporal lobes in patients with schizophrenia. Closer attention to the skull base may provide clues to the nature and timing of altered brain development in patients with psychosis.

A study of five cervicocephalic relocation tests in three different subject groups

Objective: To compare head relocation accuracy in traumatic ( whiplash), insidious onset neck pain patients and asymptomatic subjects when targeting a natural head posture (NHP) and complex predetermined positions. Design: A case-control study. Setting: University-based musculoskeletal research clinic. Participants: Sixty-three volunteers divided into three groups of similar gender and age: Group 1 (n=21) an asymptomatic group; group 2 (n=20) insidious onset neck pain; group 3 (n=22) a history of whiplash injury. Intervention: Five randomly ordered tests designed to detect relocation accuracy of the head. Outcome measures: A 3-Space Fastrak system measured the mean absolute relocation error of three trials of each relocation test. Results: A significant difference was found between groups in one of the tests targeting the NHP (p=0.001). Post-hoc pairwise comparisons revealed a significant difference (pless than or equal to0.05) between the asymptomatic group and each symptomatic group. The difference between the symptomatic groups just failed to reach significance (p=0.07). None of the other four tests revealed significant differences. Conclusion: The test of targeting the NHP indicates that relocation inaccuracy exists in patients with neck pain with a trend to suggest that the deficit may be greater in whiplash patients. Tests employing unfamiliar postures or more complex movement were not successful in differentiating subject groups.

Dietary influences on survival after ovarian cancer

We evaluated the effects of various food groups and micronutrients in the diet on survival among women who originally participated in a population-based case-control study of ovarian cancer conducted across 3 Australian states between 1990 and 1993. This analysis included 609 women with invasive epithelial ovarian cancer, primarily because there was negligible mortality in women with borderline tumors. The women's usual diet was assessed using a validated food frequency questionnaire. Deaths in the cohort were identified using state-based cancer registries and the Australian National Death Index (NDI). Crude 5-year survival probabilities were estimated using the Kaplan-Meier technique, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression models. After adjusting for important confounding factors, a survival advantage was observed for those who reported higher intake of vegetables in general (HR = 0.75, 95% CI = 0.57-0.99, p-value trend 0.01 for the highest third, compared to the lowest third), and cruciferous vegetables in particular (HR = 0.75, 95% CI = 0.57-0.98, p-value trend 0.03), and among women in the upper third of intake of vitamin E (HR = 0.76, 95% CI = 0.58-1.01, p-value trend 0.04). Inverse associations were also seen with protein (p-value trend 0.09), red meat (p-value trend 0.06) and white meat (p-value trend 0.07), and modest positive trends (maximum 30% excess) with lactose (p-value trend 0.04), calcium and dairy products. Although much remains to be learned about the influence of nutritional factors after a diagnosis of ovarian cancer, our study suggests the possibility that a diet high in vegetable intake may help improve survival. (C) 2003 Wiley-Liss, Inc.

Genotoxicity biomarkers micronucleus, nucleoplasmic bridges and nuclear buds

The increase of mortality from cancer brought urgency in identification and validation of predictive markers of risk and therefore early diagnosis. There is evidence that cytogenetic biomarkers are positively correlated with risk of cancer, and this is validated by studies of cohort and case-control. Cytokinesis-blocked micronucleus (CBMN) assay is used extensively in molecular epidemiology, and can be considered as a “cytome” assay covering cell proliferation, apoptosis, necrosis and chromosomal changes. The chromosomal alterations most reported and studied by the CBMN are: micronucleus (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUDS). The use of the MN assay in biomonitoring studies had a large increase in the last 15 years and international projects such as the HUMN have helped to increase the applicability and reliability of these tests.

Susceptibility of asthmatic children to respiratory infection

OBJECTIVE: A case-control study of patients with pneumonia was conducted to investigate whether wheezing diseases could be a risk factor. METHODS: A random sample was taken from a general university hospital in S. Paulo City between March and August 1994 comprising 51 cases of pneumonia paired by age and sex to 51 non-respiratory controls and 51 healthy controls. Data collection was carried out by two senior paediatricians. Diagnoses of pneumonia and presence of wheezing disease were independently established by each paediatrician for both cases and controls. Pneumonia was radiologically confirmed and repeatability of information on wheezing diseases was measured. Logistic regression analysis was used to identify risk factors. RESULTS: Wheezing diseases, interpreted as proxies of asthma, were found to be an important risk factor for pneumonia with an odds ratio of 7.07 (95%CI= 2.34-21.36), when the effects of bedroom crowding (odds ratio = 1.49 per person, 95%CI= 0.95-2.32) and of low family income (odds ratio = 5.59 against high family income, 95%CI= 1.38-22.63) were controlled. The risk of pneumonia attributable to wheezing diseases is tentatively calculated at 51.42%. CONCLUSION: It is concluded that at practice level asthmatics should deserve proper surveillance for infection and that at public health level pneumonia incidence could be reduced if current World Health Organisation's guidelines were reviewed as to include comprehensive care for this illness.

Reproductive outcomes in an area adjacent to a petrochemical plant in southern Brazil

OBJECTIVE: To evaluate possible adverse reproductive outcomes in an area adjacent to a petrochemical plant in southern Brazil. METHODS: A review of 17,113 birth records of the main hospital of the municipality of Montenegro, southern Brazil, from 1983 to 1998 was carried out. Three groups of cases were selected: (1) newborns with major congenital malformations; (2) newborns with low birth weight (<2,500 g); and (3) stillborns (>500 g). A control was assigned to each case. Controls were the first newborns weighing > or = 2,500 g without malformations and of case-matching sex. Mother's residence during pregnancy was used as an exposure parameter. Statistical analyses were performed using Chi-square test or Fisher test, odds ratio, 0.05 significance level, and 95% confidence interval. RESULTS: For unadjusted analysis, it was found a correlation between low birth weight and geographical proximity of mother's residence to the petrochemical plant (OR = 1.66; 95% CI = 1.01--2.72) or residence on the way of preferential wind direction (OR = 1.62; 95% CI = 1.03--2.56). When other covariates were added in the conditional logistic regression (maternal smoking habits, chronic disease and age), there was no association. CONCLUSIONS: Despite final results were negative, low birth weight could be a good parameter of environmental contamination and should be closely monitored in the studied area.

Microcytic anemia factor no estudo das anemias microcíticas

A anemia ferropénica e a β-Talassemia menor são as anemias microcíticas mais frequentes na prática laboratorial, sendo o seu diagnóstico de extrema importância clínica. O objectivo deste estudo consistiu na análise do poder discriminatório do MAF na caracterização destas anamias. Foi desenvolvido um estudo caso-controlo, tendo sido analisados os hemogramas de um grupo de 47 indivíduos com anemia ferropénica e 37 com β-talassemia, e de um grupo controlo constituído por 58 indivíduos saudáveis. Na diferenciação dos grupos patológicos, apenas a Hemoglobina, o VGM e o RDW apresentaram diferenças significativas. O MAF não demonstrou poder discriminatório relativamente às anemias microcíticas.

Modern cancer epidemiological research: genetic polymorphisms and environment

Individual cancer susceptibility seems to be related to factors such as changes in oncogenes and tumor suppressor genes expression, and differences in the action of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and cancer have revealed low relative risks. Research considering genetic polymorphisms prevalence jointly with environmental exposures could be relevant for a better understanding of cancer etiology and the mechanisms of carcinogenesis and also for new insights on cancer prognosis. This study reviews the approaches of molecular epidemiology in cancer research, stressing case-control and cohort designs involving genetic polymorphisms, and factors that could introduce bias and confounding in these studies. Similarly to classical epidemiological research, genetic polymorphisms requires considering aspects of precision and accuracy in the study design.

Risk-factors for antepartum fetal deaths in the city of São Paulo, Brazil

OBJECTIVE: To assess risk factors for antepartum fetal deaths. METHODS: A population-based case-control study was carried out in the city of São Paulo from August 2000 to January 2001. Subjects were selected from a birth cohort from a linked birth and death certificate database. Cases were 164 antepartum fetal deaths and controls were drawn from a random sample of 313 births surviving at least 28 days. Information was collected from birth and death certificates, hospital records and home interviews. A hierarchical conceptual framework guided the logistic regression analysis. RESULTS: Statistically significant factors associated with antepartum fetal death were: mother without or recent marital union; mother's education under four years; mothers with previous low birth weight infant; mothers with hypertension, diabetes, bleeding during pregnancy; no or inadequate prenatal care; congenital malformation and intrauterine growth restriction. The highest population attributable fractions were for inadequacy of prenatal care (40%), hypertension (27%), intrauterine growth restriction (30%) and absence of a long-standing union (26%). CONCLUSIONS: Proximal biological risk factors are most important in antepartum fetal deaths. However, distal factors - mother's low education and marital status - are also significant. Improving access to and quality of prenatal care could have a large impact on fetal mortality.

Risk factors for metabolic bone disease in Crohn's disease patients

Background: The aim was to evaluate the presence of metabolic bone disease (MBD) in patients with Crohn’s disease (CD) and to identify potential etiologic factors. Methods: The case–control study included 99 patients with CD and 56 controls with a similar age and gender distribution. Both groups had dual-energy x-ray absorptionmetry and a nutritional evaluation. Single nucleotide polymorphisms at the IL1, TNF-a, LTa, and IL-6 genes were analyzed in patients only. Statistical analysis was performed using SPSS software. Results: The prevalence of MBD was significantly higher in patients (P ¼ 0.006). CD patients with osteoporosis were older (P < 0.005), small bowel involvement and surgical resections were more frequent (P < 0.005), they more often exhibited a penetrating or stricturing phenotype (P < 0.05), duration of disease over 15 years (P < 0.005), and body mass index (BMI) under 18.5 kg/m2 (P < 0.01) were more often found. No association was found with steroid use. Patients with a Z-score < 2.0 more frequently had chronic active disease (P < 0.05). With regard to diet, low vitamin K intake was more frequent (P ¼ 0.03) and intake of total, monounsaturated, and polyunsaturated fat was higher in patients with Z-score < 2.0 (P < 0.05). With respect to genetics, carriage of the polymorphic allele for LTa252 A/G was associated with a higher risk of osteoporosis (P ¼ 0.02). Regression analysis showed that age over 40 years, chronic active disease, and previous colonic resections were independently associated with the risk of developing MBD. Conclusions: The prevalence of MBD was significantly higher in CD patients. Besides the usual risk factors, we observed that factors related to chronic active and long-lasting disease increased the risk of MBD.

Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity

Background & aims: Crohn’s disease (CD) is a multifactorial disease where resistance to apoptosis is one major defect. Also, dietary fat intake has been shown to modulate disease activity. We aimed to explore the interaction between four single nucleotide polymorphisms (SNPs) in apoptotic genes and dietary fat intake in modulating disease activity in CD patients. Methods: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques were used to analyze Caspase9þ93C/T, FasLigand-843C/T, Peroxisome Proliferator-Activated Receptor gammaþ161C/T and Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNPs in 99 patients with CD and 116 healthy controls. Interactions between SNPs and fat intake in modulating disease activity were analyzed using regression analysis. Results: None of the polymorphisms analyzed influenced disease susceptibility and/or activity, but a high intake of total, saturated and monounsaturated fats and a higher ratio of n-6/n-3 polyunsaturated fatty acids (PUFA), was associated with a more active phenotype (p < 0.05). We observed that the detrimental effect of a high intake of total and trans fat was more marked in wild type carriers of the Caspase9þ93C/T polymorphism [O.R (95%CI) 4.64 (1.27e16.89) and O.R (95%CI) 4.84 (1.34e17.50)]. In the Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNP, we also observed that a high intake of saturated and monounsaturated fat was associated to a more active disease in wild type carriers [OR (95%CI) 4.21 (1.33e13.26) and 4.37 (1.52e12.51)]. Finally, a high intake of n-6 PUFA was associated with a more active disease in wild type carriers for the FasLigand-843C/T polymorphism [O.R (95%CI) 5.15 (1.07e24.74)]. Conclusions: To our knowledge, this is the first study to disclose a synergism between fat intake and SNPs in apoptotic genes in modulating disease activity in CD patients.

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients

Background: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC). Objective: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk. Design: Patients withCRC(n 196) and healthy controls (n 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms. Results: Except for folate intake, which was significantly lower in patients (P 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate ( 406.7 g/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677TMTHFRvariant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk ofCRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms. Conclusion: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.

eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.