Occupation and Breast Cancer: a Canadian Case-Control Study

A local collaborative process was launched in Windsor, Ontario, Canada to explore the role of occupation as a risk factor for cancer. An initial hypothesis-generating study found an increased risk for breast cancer among women aged 55 years or younger who had ever worked in farming. On the basis of this result, a 2-year case–control study was undertaken to evaluate the lifetime occupational histories of women with breast cancer. The results indicate that women with breast cancer were nearly three times more likely to have worked in agriculture when compared to the controls (OR = 2.80 [95% CI, 1.6–4.8]). The risk for those who worked in agriculture and subsequently worked in automotive-related manufacturing was further elevated (OR = 4.0 [95% CI, 1.7–9.9]). The risk for those employed in agriculture and subsequently employed in health care was also elevated (OR = 2.3 [95% CI, 1.1–4.6]). Farming tended to be among the earlier jobs worked, often during adolescence. While this article has limitations including the small sample size and the lack of information regarding specific exposures, it does provide evidence of a possible association between farming and breast cancer. The findings indicate the need for further study to determine which aspects of farming may be of biological importance and to better understand the significance of timing of exposure in terms of cancer risk.

The Economic Costs of Health Service Treatments for Asbestos-Related Mesothelioma Deaths

This article explores the complex and neglected picture of occupational and environmental disease healthcare costs specifically relating to asbestos. Diagnosed mesothelioma cases in Scotland in one calendar year were used to investigate the subject in greater depth. Data from UK sources on asbestos disease types recorded in 2000 and their disease treatment costs were obtained. Acute care economic costs of these diseases are estimated. One hundred and twenty diagnosed, recorded, and treated cases of asbestos-related diseases occurred in 2000 in Scotland. Mesothelioma accounted for 100 cases and directly cost Scottish National Health Service hospitals an estimated 942,038 pounds. The estimated UK figure in 2000 was at least 16,014,646 pounds because official figures for diagnosed and recorded deaths from mesothelioma are running at over 1700 a year with rises predicted for 2010 of 2000 deaths. By 2003, 50,000 people in the UK had died from diagnosed and recorded mesothelioma since records began. Earlier disease treatment costs would have been significantly lower than those in 2000 but, at 2000 prices, cost to the UK was roughly 471,019,000 pounds in acute hospital expenditure. Figures for primary care costs, including caregiver costs, are incomplete or unknown. These disease costs are substantial and have some international generalizability. Treatment patterns and costs vary greatly. Many lung cancer cases due to asbestos exposure occur globally for each mesothelioma case. Hence figures provided in this article are certain to be gross underestimates of the total health service and personal economic costs of asbestos illness and treatment in Scotland.

Work-family characteristics as determinants of sickness absence: A large-scale cohort study of three occupational grades

This study examined the previously unexplored occupational grade-specific relationships of domestic responsibilities, the age of children, and work-family spillover, with registered sickness absence (>3 days' sick leave episodes, a mean follow-up of 17 months; n = 18,366 municipal employees; 76% women). The results showed that negative spillover from work into family life predicted a heightened rate of sickness absence spells among both women and men in all occupational categories (except upper white-collar men), but especially among blue-collar and lower white-collar employees. Furthermore, among all white-collar employees (except upper white-collar men), having young children (

Efficacy and safety of adjunctive mitomycin C during Ahmed Glaucoma Valve implantation:A prospective randomized clinical trial

Purpose To evaluate the efficacy and safety of intraoperative mitomycin C (MMC) in eyes undergoing Ahmed Glaucoma Valve implantation. Design Randomized controlled clinical trial. Participants Sixty patients with refractory glaucoma. Intervention Sixty eyes of 60 patients with refractory glaucoma were randomized to receive intraoperative MMC (0.5 mg/ml for 5 minutes) (n = 34) or balanced salt solution (n = 26) during Ahmed Glaucoma Valve implantation. Main outcome measures Surgical success was defined according to 2 different criteria: (1) postoperative intraocular pressure (IOP) between 6 and 21 mmHg, with or without antiglaucoma medications, and (2) IOP reduction of at least 30% relative to preoperative values. Eyes requiring additional glaucoma surgery, developing phthisis, or showing loss of light perception were classified as failures. Success rates in both groups were compared using Kaplan-Meier survival curves and the log rank test. Other outcome measures were mean IOP, number of glaucoma medications, and complications. Results After a mean follow-up of 12.3 months, Kaplan-Meier survival analysis showed a probability of success of 59% at 18 months for the MMC group and 61% for the control group when the first criterion for success was used (IOP between 6 and 21 mmHg). When an IOP reduction of at least 30% was used as the criterion to define success, the Kaplan-Meier survival analysis demonstrated a probability of success at 18 months of 62% for the MMC group and 67% for the control group. There were no significant differences in survival rates between the 2 groups with either criterion (P = 0.75 and P = 0.37, respectively). After 15 days postoperatively, the mean IOP did not significantly differ for both MMC and control eyes. Mean numbers of postoperative antiglaucoma medications were similar in MMC-treated eyes and controls. There was no significant difference between the incidences of postoperative complications in both groups. Conclusion Mitomycin C did not increase the short- or intermediate-term success rates of Ahmed Glaucoma Valve implantation. © 2004 by the American Academy of Ophthalmology.

Characterization of metabolites of sweroside in rat urine using ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry and NMR spectroscopy

Sweroside, a major active iridoid in Swertia pseudochinensis Hara, is recognized as an effective agent in the treatment of liver injury. Based on previous reports, the relatively short half-life (64 min) and poor bioavailability (approximately 0.31%) in rats suggested that not only sweroside itself but also its metabolites could be responsible for the observed hepato-protective effect. However, few studies have been carried out on the metabolism of sweroside. Therefore, the present study aimed at identifying the metabolites of sweroside in rat urine after a single oral dose (100 mg/kg). With ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS), the metabolic profile revealed 11 metabolites in rat urine, including phase I, phase II and aglycone-related products. The chemical structures of metabolites were proposed based on accurate mass measurements of protonated or deprotonated molecules and their fragmentation patterns. Our findings showed that the aglycone of sweroside (M05) and its glucuronide conjugate (M06) were principal circulating metabolites in rats. While several other metabolic transformations, occurring via reduction, N-heterocyclization and N-acetylation after deglycosylation, were also observed. Two metabolites (M05 and M06) were isolated from the rat urine for structural elucidation and identifcation of reaction sites. Both M05 and M06 were characterized by 1H, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. UHPLC/Q-TOF-MS analysis has provided an important analytical platform to gather metabolic profile of sweroside.

Opções de utilização sequencial de anti-retrovíricos em doentes com falência terapêutica em Angola

A infecção pelo VIH/SIDA constitui um dos principais problemas de saúde no Mundo e em África. A África Sub-sahariana detém actualmente 67% das infecções a nível global. Angola, localizada na sub-região central de África (OMS) tem uma prevalência actual média estimada em 2.4%, estando rodeada a Sul e Leste por países de prevalências mais elevadas. Em Angola, predomina o VIH-1. Os dados publicados sobre a epidemiologia molecular do VIH em Angola mostram uma grande diversidade de subtipos e formas recombinantes circulantes (CRF), recombinantes circulantes únicas (URF) e amostras não tipificadas. A motivação para o estudo presente foi o conhecimento ainda limitado sobre a infeção por VIH em Angola, desde a epidemiologia molecular às características clínicas, imunológicas, virológicas, resposta à terapêutica anti-retrovírica combinada (TARVc) e perfil de resistência do VIH à TARVc. Foi estudado um coorte de 300 doentes adultos, com infecção por VIH, de 15 de Junho de 2006 a 15 de Junho de 2010. Predomina o género feminino, 65% (194/300) e o grupo etário dos 25 aos 39 anos, 62% (186/300). A mediana de idades é 33 anos, residem em Luanda 98% (295/300), 94% são angolanos, sendo os estrangeiros de S. Tomé e RDC. A Classificação CDC de 1993 na linha de base mostrou um predomínio de doentes da categoria clínica C, 53% (160/300), com uma ou duas doenças definidoras; 34% (101/300) dos doentes eram da Categoria C3 do CDC e 49% (147/300) tinham linfócitos T CD4+ abaixo das 200 cel/l. A doença definidora mais frequente foi a Tuberculose, em 39% dos doentes (117/300). A mediana de linfócitos T CD4+ na linha de base foi de 195 cel/μl [1-1076]. Apenas 12,2% dos doentes (37/302) tinha T CD4+ de base superior a 500 células/l. Determinou-se a carga vírica na linha de base, em 213 dos doentes (71%), verificando-se que 46% destes doentes (97/213) tinham cargas virícas superiores a 100.000 cp/ml, 32% (69/213) entre 10001 e 100000, 21% (45/213) entre 400 e 10000, 0,9% (2/213) abaixo de 400 cp/ml. Iniciaram terapêutica anti-retrovírica no período de estudo 206 doentes (69%) com esquemas terapêuticos baseados em NNRTI, sendo 131 (64%) medicados com a associação d4t+3TC+ NVP. Ao fim de 4 anos, em Junho de 2010, havia 126 doentes monitorizados com contagem de linfócitos T CD4+ e CV, estando 62% dos doentes com CV indetectável (79/126). Os doentes em falência virológica corresponderam a 16% (20/126), 9% (11/126) tinham resultados discordantes (boa resposta imunológica mas carga viral detectável) e 13% (16/126) foram inconclusivos. Foi mudada a terapêutica para esquema de 2ª linha em 5 doentes, 4 dos 5 doentes com critérios de falência virológica e 1 sem critérios de falência virológica, por toxicidade ao EFV. Os doentes com critérios de falência imunológica ou virológica segundo a OMS e os doentes com dados inconclusivos foram seleccionados para testes genotípicos de resistência aos anti-retrovíricos (TR). Foram realizados TR e subtipagem em 37 doentes. Nos doentes que realizaram TR sob TARVc, as mutações de resistência mais frequentemente encontradas foram a M184V, em 16 doentes, a K103N em 12 doentes e a Y181C em 7 doentes. O subtipo C, foi o subtipo predominante em 30% (11/37) dos casos. Para avaliar a adesão à TARVc, foram estudados 63 doentes, faltosos a consultas ou demonstrado sinais de falência clínica, imunológica ou virológica. O método realizado foi o auto-relato por entrevista. Verificou-se uma adesão à TARVc de 100% em 33% (21/63), adesão entre 100% e 90% em 7% (4/63), de 50 a 90% em 7% (4/63) e inferior a 50% em 54% (34/63). Como factores de não-adesão, predominavam a mobilidade no emprego Opções de utilização sequencial de anti-retrovíricos em doentes com falência terapêutica em Angola X e factores familiares e sociais, apontados como razão para a falta às consultas que davam acesso aos medicamentos ARV. Fazendo corresponder os resultados dos testes de resistência realizados à adesão de todos os doentes entrevistados, verifica-se que o grupo de 34 doentes com menos de 50% de adesão, 19 realizaram TR e desses, 13 mostraram mutações de resistência, sendo 10 resistentes a 2 classes de ARV, NITR e NNITR, 2 a NNITR e 1 a NITR. Os restantes 6 doentes deste grupo eram aparentemente susceptíveis às 3 classes de ARV. Actualmente, estão em seguimento 58% dos doentes (176/300), 26 % (77/300) perderam-se no seguimento e 16% (47/300) faleceram. O estudo realizado salienta a fase tardia da chegada aos cuidados médicos; mostra a tuberculose como doença indicadora mais frequente e mostra que a maioria dos doentes foi medicada com D4T+3TC+NVP. Os critérios de sucesso terapêutico descem ao longo do estudo de 71% para 62%. Indica a necessidade de acções urgentes para acesso mais precoce aos cuidados de saúde e intervenção social para ultrapassar as limitações à adesão à TARVc e tornar esta mais eficaz. As opções de segunda linha já disponíveis são muito reduzidas (tenofovir, lopinavir potenciado com ritonavir e saquinavir), havendo necessidade de continuar estes estudos para uma avaliação mais profunda da eficácia destas terapêuticas.

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

PURPOSE: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS). METHODS: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered. KEY FINDINGS: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS. SIGNIFICANCE: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.

Stem cell transplantation in brain tumors: a new field for molecular imaging?

Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.

L'Écho de Paris

1887/02/24 (Numéro 1076).