Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air

BACKGROUND: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries. OBJECTIVE: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross-sectional study of a cohort of 670 children, aged 10-13 years. METHODS: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR. RESULTS: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 +/- 0.48] compared to those in rural [31.9% (52/163), 9.84 +/- 0.83] and coastal [33.3% (67/201), 7.17 +/- 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P < 0.007]. Schoolchildren with atopy had lower PC20 than those without atopy (5.98 +/- 0.60 vs 8.15 +/- 0.45, P < 0.001). Positive allergy skin tests and living in a polluted area were risk factors in multivariate analyses adjusted for sex, parents' smoking habits, age, body mass index, nose symptoms and lung symptoms (odds ratio for location = 2.4875, confidence interval 1.6542-3.7406, P < 0.000; odds ratio for allergy skin test = 1.5782, confidence interval 1.1130-2.2379, P < 0.0104). CONCLUSION: Our findings demonstrate that more children living in polluted areas have airway hyperresponsiveness than do those living in less polluted areas.     

Endometrial cancer in HNPCC syndrome

The Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) has initially been described as a predisposition to colorectal cancers (CRC). Subsequently, other cancers, such as endometrial cancers (EC), have been added. The objective of this review was to update data on endometrial cancers of HNPCC syndrome. Endometrial cancers of the HNPCC syndrome are characterized by a younger age at diagnosis (46-48 year old), and a higher cumulative risk along life (30% at 70 years). Complex atypical hyperplasia seems to occur before the cancer, but the transition between precursors and cancer seems to be short. Histology of endometrial cancers of the HNPCC syndrome appears quite similar to that of sporadic cases, except for non-endometrioid lesions which seem more frequent and could occur in younger women. Screening of endometrial cancer in predisposed women should associate annual clinical examination, transvaginal sonography and endometrial sampling. Unfortunately, available data on screening by sonography show that this test seems poorly accurate, with no asymptomatic cancer or hyperplasia recognized and interval cancers between screenings. Endometrial biopsy appears as the most interesting method, since 11 asymptomatic cancers and 14 hyperplasia have been diagnosed in 175 mutation carriers. Diagnostic hysteroscopy seems also interesting, but requires further evaluation. Prophylactic hysterectomy confers a complete protection against endometrial cancer. However, perioperative morbidity (especially in women with history of colorectal surgery) and long-term effects of ovarian suppression should also be considered. Screening of endometrial cancer remains the main objective of the management of those patients. Endometrial biopsy should have a larger place.     

Consistency and inconsistency in testing biomarkers in breast cancer. A GRELL study in cut-off variability in the Romance language countries

PurposeBiological markers are crucial factors in order to differentiate female breast cancers and to determine the right therapy. This study aims at evaluating whether testing for biomarkers for female breast cancer has similar frequency and characteristics across and within countries.MethodsPopulation-based cancer registries of the Association for cancer registration and epidemiology in Romance language countries (GRELL) were asked to complete a questionnaire on biomarkers testing. The data collected referred to invasive female breast cancer cases diagnosed between 2004 and 2009. The investigation focused on 1) the overexpression and amplification of the human epidermal growth factor receptor 2 oncogene (HER2); 2) the expression of oestrogen (ER) and progesterone (PgR) receptors; and 3) the proliferation index (PI). Weighted percentages, the heterogeneity among and within countries, and the correlation between responses and calendar years were evaluated. The study was based on 19,644 breast cancers.ResultsOverall, 85.9% of the cases were tested for HER2, 91.8% for both ER and PgR, and 74.1% for proliferative markers. For HER2 and ER–PgR, the frequency of testing increased from 2004 to 2009. Testing varied among countries (HER2 from 82.0% to 95.9%, ER–PgR from 89.3% to 98.9%, PI from 10% to 92%) and also within the same country (e.g. HER2 in Italy from 51% to 99%) as well as within single cancer registries. The most relevant differences were in the scores for positive/negative/not clearly defined HER2 (e.g. HER2 was defined positive if IHC 3+ in 21/33 registries), and in the cut-off of positive cells for ER/PgR (from >0% to >30%) and PI positivity (from >0% to >20%).ConclusionsBiological markers are widely tested in the Romance language countries; however, the parameters defining their positivity may vary, raising concerns about homogeneity in breast cancer classification and treatment.     

Parental SCN1A mutation mosaicism in familial Dravet syndrome

Different SCN1A mutations are known to cause a variety of phenotypes, such as generalized epilepsy with febrile seizures plus (GEFS+), Dravet syndrome and familial hemiplegic migraine (FHM). In Dravet syndrome, most mutations are de novo and familial cases are rare. In this study, Dravet syndrome is observed in two maternal half sisters. They have healthy fathers and their common mother has never experienced seizures, but has a lifelong history of migraine. Direct sequencing of DNA extracted from blood revealed a heterozygous SCN1A nonsense mutation c.3985C>T in the sisters, but not in the mother. The mutation induces a premature stop codon and probably leads to a non-functional protein. Further examination of the mother's DNA showed that she has a mosaicism of the mutation. This report of parental SCN1A nonsense mutation mosaicism in familial Dravet syndrome suggests that mosaicism might be more common than previously suspected and emphasizes the importance of taking mosaicism into account in genetic counselling of Dravet syndrome and SCN1A mutations. Furthermore, whether the migraine of the mother could be influenced by her SCN1A mutation mosaicism is not known, but increased awareness of migraine in future studies of SCN1A related epilepsies could clarify this intriguing link between migraine and epilepsy.     

A new coding mutation in the Tnf-alpha leader sequence in tuberculosis-sensitive I/St mice causes higher secretion levels of soluble TNF-alpha

I/St and A/Sn mice are polar extremes in terms of several parameters defining sensitivity to Mycobacterium tuberculosis. TNF-alpha, mainly produced by activated macrophages, can mediate both physiological and pathophysiological processes. Adequate TNF-alpha levels are essential for a forceful protective response to M. tuberculosis. We have functionally characterized a nonsynonymous substitution, Arg8 His, in the highly conserved cytoplasmic domain of the pro-TNF-alpha leader peptide from extremely M. tuberculosis-sensitive I/St mice. This was compared to the common pro-TNF-alpha variant found in A/Sn mice. Using cDNA constructs, both variants were constitutively expressed in HEK293A cells. A significantly higher secretion level of Arg8 His TNF-alpha was shown using flow cytometry and ELISA analysis (P=0.0063), while intracellular levels were similar for both protein variants. An even TNF-alpha distribution throughout the cells was seen using confocal microscopy. This suggests that the Arg8 His substitution affects pro-TNF-alpha processing. The I/St mouse may serve as a model to further explore the function of the well-conserved cytoplasmic region of TNF-alpha. However, other identified substitutions in the I/St promoter, introns and 3'UTR of Tnf-alpha, as well as the cellular environment in vivo may affect the balance between soluble and intracellular Arg8 His TNF-alpha before and during M. tuberculosis infection.     

Validity of the BVAQ: a study in eating disorder patients and controls

Alexithymia core features are the difficulties in identifying and describing feelings; the difficulties in distinguishing feelings from the bodily sensations of emotional arousal; an impaired symbolization, as evidenced by a paucity of fantasies and other imaginative activity; and a tendency to focus on external events rather than inner experience. Several measures of alexithymia have been developed, including interviewer-rated questionnaires and self-report questionnaires. Among the self-report questionnaires, the 20-item Toronto Alexithymia scale (TAS-20) is the most commonly used, but it fails to measure all the core features of alexithymia. A recently developed instrument, the Bermond-Vorst Alexithymia Questionnaire (BVAQ), allows the measurement of the alexithymia core features, as well as an additional one. It appeared to present good psychometric properties, notably the abbreviated BVAQ-form B. The results of recent studies comparing the psychometric properties of the TAS-20 and the BVAQ have recommended the BVAQ over the TAS-20. However, this questionnaire needed further validation. OBJECTIVES: Thus, the aim of the present study was to determine the convergent, discriminant and concurrent validity of the Bermond-Vorst Alexithymia Questionnaire -- form B (BVAQ-B) in a clinical sample of 59 eating disorder patients, as well as in 191 controls. The TAS-20 constituted the gold standard for the assessment of the BVAQ-B' convergent validity. To compare the concurrent validity of the BVAQ-B and the TAS-20, participants also completed several self-reports investigating different dimensions of emotion regulation capacities: the 13-item Beck Depression Inventory (BDI), the Spielberger State and Trait Anxiety Inventory (STAI-form Y), as well as the Chapman and Chapman Physical and Social Anhedonia Scales (PAS and SAS). One way analyses of variance were used for mean scores comparisons. Convergent validity was determined using Pearson coefficients of correlation. RESULTS: Results of the analyses suggested the BVAQ-B has a satisfying convergent and discriminant validity. This was observed in both the clinical and control samples. Moreover, the comparison of the convergent validity of the BVAQ-B and the TAS-20 revealed several differences between these two alexithymia self-report questionnaires. The BVAQ-B appeared less sensitive to the subjective emotional state of the participants than the TAS-20. Whereas it was argued the TAS-20 overlaps with other emotional state scores, the BVAQ-B would allow to measure alexithymia more specifically. In addition, the present results allowed to further determine the relations between alexithymia and other dimensions of emotion regulation capacities. The analyses confirmed that alexithymia is linked to other emotion regulation dimensions such as depression and anxiety. Moreover, alexithymia was associated with physical and social anhedonia, two dimensions that received less interest in the alexithymia literature to date. This study also showed that control and clinical sample have different emotion regulation capacities. Eating disorder patients were not only more alexithymic and more depressed, but also more anxious and more anhedonic than the controls. Finally, this study revealed that alexithymia differs whether the alexithymic individuals are patients or controls. Healthy alexithymic individuals (ie, individuals categorized as alexithymic in the control group) seemed characterised by a selective deficit of emotional cognition, with sparing of emotional experience (Bermond's type II alexithymia). Alexithymics individuals of the eating -disorder group seemed particularly unabled to experience affect. This pattern could correspond to Bermond's type I alexithymia, which is characterised by the absence of emotional experience and, consequently, by the absence of the cognition accompanying the emotion. In summary, results of the present study add to the literature debating on whether alexithymia is similar in different types of population.     

A comparative study in Stockholm,Sweden of labour outcome and women's perceptions of being referred in labour

OBJECTIVE: to study the outcome of labour and women's perceptions of being referred after onset of labour. DESIGN: a comparative study carried out between October 1998 and April 1999. SETTING: prospective parents in Stockholm, Sweden are offered a choice of which of the five hospitals in which they want to give birth. In reality, there is a lack of maternity beds in Stockholm to implement this policy and therefore nearly 10% of labouring women are being referred during labour. PARTICIPANTS: the study population was selected from one of the five hospitals. Included in the study were 266 labouring women, with a 37-42 weeks uncomplicated pregnancy, fetus presenting by the vertex and spontaneous onset of labour. During pregnancy, all the women had chosen the same labour ward where they planned to deliver. However, at the onset of labour half of the women, case group I (n = 133) were referred to another maternity unit due to lack of space in the labour ward. For every referred woman a control woman matched for age, parity and date of delivery was selected, with the same inclusion criteria, except being referred, control group II (n = 133). METHODS: a questionnaire with closed and open questions was posted to the women after birth and used to collect quantitative and qualitative data on the outcome of labour and the women's perceptions of referral during labour. FINDINGS: routines such as epidural analgesia (EDA) (p<0.002), episiotomies (p<0.015) and morphine/pethidine during labour (p<0.023) were more common in the referred group. The women in the referred group considered to a higher extent that referral during labour had affected their emotional state (p<0.001). Women in both groups had been worried during pregnancy by the thought of having to be referred when labour had started and the referral had caused practical problems, stress and a feeling of not being welcome in the referral labour ward. KEY CONCLUSION AND IMPLICATIONS FOR PRACTICE: referral during established normal labour may affect labour outcome, and the possibility that they may be referred worries women during pregnancy. Maternity policies and practices should be organised so that caring goals, such as continuity of care and women's' participation in birth planning, can be met.     

Evaluation of measles, mumps and rubella vaccine coverage in 3 year old children in twelve French counties. Time-trends and related factors

BACKGROUND: The aims of our study were to estimate the measle-mumps-rubella (MMR) vaccine coverage in 3 years old children in 12 French countees, to document the evolution between 1997 and 1999 in two groups of 6 countees (pilot group and control group) before and after the implementation of promotion programmes in the pilot group, and to identify factors related to measle-mumps-rubella vaccination. METHODS: Two telephone surveys were carried out in 1997 and 1999 among children randomly selected in the birth rolls of 12 French countees. Parents of 3 years old children were interviewed on measle-mumps-rubella vaccination, knowledge and opinions on vaccinations, utilisation of health care and socio-demographic characteristics. RESULTS: The participation rate was 97% in both surveys. Among the 7382 respondent parents, 98% had immediate access to the child's medical file and could document the vaccine status. The vaccine coverage did not increase significantly between 1997 and 1999 (86.7% versus 87.2%), both in control (89.3% vs. 90.2%) and pilot groups (84.3% vs. 84.3%). A logistic regression model showed that several factors were independently and significantly related to measle-mumps-rubella vaccination (utilisation of homeopathic medicines, mother's age, number of children, physician speciality (general practitioner or pediatrician) and opinion on vaccinations). CONCLUSION: Our study shows that there is a stagnation of vaccine coverage in several French countees, which makes unlikely the national objective of viruses eradication. This epidemiological situation makes very likely outbreaks of measles, mumps and rubella in these countees. National and local pilot programmes did not succeed to promote vaccination in countees with a low measle-mumps-rubella vaccine coverage. Our study identified sub-groups of parents who should be targeted by promotion programmes.