Presenting stage and risk group in men dying of prostate cancer.

Introduction: Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. Methods: The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan-Meier method. Results: A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. Conclusions: This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

Exposure to maternal depressive symptoms in childhood and adolescent suicide-related thoughts and attempts: mediation by child psychiatric symptoms.

AIMS: The nature of the association between child psychiatric symptoms and adolescent suicide-related thoughts (SRT) and attempts (SA) remains unclear. Our objective was to assess whether child psychiatric symptoms from 6 to 10 years of age mediate the association between exposure to maternal depressive symptoms in childhood and offspring SRT and SA in adolescence. METHODS: A population-based cohort study was constructed by linking all eight cycles from the National Longitudinal Survey of Children and Youth (NLSCY), a nationally representative Canadian panel survey conducted from 1994 to 2009. Self-reported maternal depressive symptoms were measured when offspring were between 0 and 5 years. Maternal-reported child psychiatric symptoms and psychiatric comorbid symptoms were measured from 6 to 10 years, and offspring self-reported SRT and SA were measured between 11 and 19 years. Indirect effects, the effect proportion mediated and their corresponding bootstrapped 95% confidence intervals (CI) were estimated. RESULTS: Hyperactivity and inattention significantly mediated the association between maternal depressive symptoms in childhood and risk of both SRT and SA from 11 to 19 years, where approximately 60% (SRT 95% CI 23-94%; SA 95% CI 27-95%) of this association was explained by hyperactivity and inattention. Psychiatric comorbid symptoms also significantly mediated this relationship and accounted for 50% (95% CI 18-81%) of this association with SA. CONCLUSIONS: Targeting hyperactivity and inattention, and co-occurring psychiatric symptoms in offspring of depressed mothers could reduce risk of SRT, eventual SA and halt progression towards suicide. However, further understanding of comorbid psychiatric symptoms in childhood that most strongly predict adolescent SA is needed.

Exposure to parental psychopathology and offspring's risk of suicide-related thoughts and behaviours: a systematic review.

AIMS: The primary objective of this systematic review was to identify and synthesise analytic studies examining the association between exposure to parental psychopathology in childhood and the nature of subsequent suicide-related thoughts (SRT) and suicide-related behaviour (SRB) (severity of ideation, planned/unplanned attempts/lethality) and to describe the direction, and magnitude of associations. The secondary objective was to determine if the associations from the primary objective differ by the type(s) and timing of parental psychopathology, sex/gender of the parent and child and is mediated by child psychiatric symptoms and family functioning. METHODS: A systematic review was conducted using guidelines from the PRISMA statement. MEDLINE, CINAHL, EMBASE, psycINFO, Web of Science and grey literature sources were searched by two reviewers to March, 2017. Studies were included if they examined any parental psychopathology (Diagnostic and Statistical Manual of Mental Disorders criteria or equivalent) or SRT or SRB and offspring SRT or SRB occurring from birth <25 years of age. RESULTS: Out of 10 231 studies identified, 54 were included for review. Studies were clinically and methodologically heterogeneous with none at low risk of bias (ROB). Nine studies with moderate ROB indicated a significantly increased risk of offspring SRT, suicide attempts (SA) and suicide among those exposed to maternal SA and suicide in childhood or adolescence. In the remaining 45 studies with higher ROB this association persisted. Several studies (67%) did not confirm that the exposure occurred in the offspring's childhood or adolescence. Findings were suggestive of a mediating effect of offspring psychiatric symptoms, however, few studies examined mediation and effect modification of contextual variables. CONCLUSIONS: Offspring exposed to maternal SA are at an increased risk of these same behaviours early in life. Prospective attention to the types and timing of maternal and paternal psychopathology and the intermediate pathways to offspring SRT and SRB onset is needed and could have implications for informing modifiable targets for early intervention and prevention.

Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels of GFAP and of caspases-3 and -8.

Tanshinone IIA (TSA) is a lipid soluble agent derived from the root of Salvia miltiorrhiza (Danshen). This plant is a traditional Chinese herb, which has been used widely in China especially for enhancing circulation. However mechanisms underlying its efficacy remain poorly understood. The present study was designed to illuminate events that may underlie the apparently neuroprotective effects of TSA following ischemic insult. Adult Sprague-Dawley rats were subjected to transient focal cerebral ischemia by use of a middle cerebral artery occlusion model. They were then randomly divided into a sham-operated control group, and cerebral ischemia/reperfusion groups receiving a two-hour occlusion. Further subsets of groups received the same durations of occlusion or were sham-operated but then received daily i.p. injections of high or low doses of TSA, for seven or 15days. Hematoxylin and eosin staining revealed lesions in the entorhinal cortex of both rats subject to ischemia and to a lesser extent to those receiving TSA after surgery. Levels of glial fibrillary acidic protein (GFAP), caspase-3 and caspase-8, were quantified by both immunohistochemistry and Western blotting. TSA treatment after middle cerebral artery occlusion, markedly reduced infarct size, and reduced the expression of caspase-3 and caspase-8. These changes were considered protective and were generally proportional to the dose of TSA used. These results suggest that TSA may effect neuroprotection by way of reduction of the extent of cell inflammation and death within affected regions.

Dietary melatonin attenuates age-related changes in morphology and in levels of key proteins in globus pallidus of mouse brain.

The ability of melatonin treatment of aged animals to partially restore the pattern of gene expression characterizing the younger animal has been frequently reported. The current study examines the effect of melatonin upon age-related changes of some key proteins relevant to the aging process. Male B6C3F1 mice, aged 5.5 months and 23.4 months were used as a model for aging and half of each group received a diet supplemented with 40-ppm (w/w) melatonin for 9.3 weeks. Protein components of the globus pallidus were studied including glial fibrillary acidic protein (GFAP), NF-κB, protein disulfide isomerase (PDI), and Nissl staining. Some age-related changes were in an upward direction (GFAP and NF-κB), while others were depressed with age (PDI and intensity of Nissl staining). However, in either case, melatonin treatment of aged mice generally altered these parameters so that they came to more closely resemble the levels found in younger animals. The extent of this reversal to a more youthful profile, ranged from complete (for NF-κB) to very minor (for Nissl staining and PDI). Overall, these findings are in accord with prior data on the effect of melatonin on cortical gene expression and confirm the value of melatonin as a means of retarding events associated with senescence.

Air quality, mortality, and economic benefits of a smoke - free workplace law for non-smoking Ontario bar workers.

We estimated the impact of a smoke-free workplace bylaw on non-smoking bar workers' health in Ontario, Canada. We measured bar workers' urine cotinine before (n = 99) and after (n = 91) a 2004 smoke-free workplace bylaw. Using pharmacokinetic and epidemiological models, we estimated workers' fine-particle (PM2.5 ) air pollution exposure and mortality risks from workplace secondhand smoke (SHS). workers' pre-law geometric mean cotinine was 10.3 ng/ml; post-law dose declined 70% to 3.10 ng/ml and reported work hours of exposure by 90%. Pre-law, 97% of workers' doses exceeded the 90th percentile for Canadians of working age. Pre-law-estimated 8-h average workplace PM2.5 exposure from SHS was 419 µg/m(3) or 'Very Poor' air quality, while outdoor PM2.5 levels averaged 7 µg/m(3) , 'Very Good' air quality by Canadian Air Quality Standards. We estimated that the bar workers' annual mortality rate from workplace SHS exposure was 102 deaths per 100000 persons. This was 2.4 times the occupational disease fatality rate for all Ontario workers. We estimated that half to two-thirds of the 10620 Ontario bar workers were non-smokers. Accordingly, Ontario's smoke-free law saved an estimated 5-7 non-smoking bar workers' lives annually, valued at CA $50 million to $68 million (US $49 million to $66 million).

A systematic review and meta-analysis of the prevalence of chlamydia, gonorrhoea and syphilis in incarcerated persons.

Communicable diseases are common in people who are incarcerated. We aimed to define the prevalence of chlamydia, gonorrhoea and syphilis in people who are incarcerated and to identify subgroups with the highest risk of infection. We searched for prevalence studies of chlamydia, gonorrhoea or syphilis in incarcerated populations. Pooled estimates were generated, and meta-regression was conducted. Random effects models yielded pooled prevalence estimates of 5.75% (95% confidence interval [CI] 5.01, 6.48) and 12.31% (95% CI 10.61, 14.01) for chlamydia in men and women, 1.4% (95% CI 1.09, 1.70) and 5.73% (4.76, 6.69) for gonorrhoea in men and women, and 2.45% (95% CI 2.08, 2.82) and 6.10% (95% CI 4.75, 7.46) for syphilis in men and women, respectively. Each infection was associated with female gender in meta-regression models. Chlamydia, gonorrhoea and syphilis are highly prevalent in these populations. Primary and secondary prevention efforts could improve individual and population health.

Assessing the reach of nicotine replacement therapy as a preventive public health measure.

INTRODUCTION: Access to Nicotine Replacement Therapy (NRT) is a key public health intervention to reduce smoking. We assessed prevalence and correlates of use of NRT in Ontario, where NRT is available without prescription. METHODS: Participants were a representative sample of 2262 adult smokers in the Ontario Tobacco Survey cohort. Prospectively measured use of NRT over a 6-month period was reported in relation to smoking behaviour and history, attempts to quit, receipt of other supports for cessation supports and attitudes toward NRT. RESULTS: Overall, 11% of smokers used NRT over the six-month follow-up period. Prevalence was 25% among the 27% of smokers matching clinical guidelines that recommend NRT as a therapeutic option, and low among smokers not trying to quit. CONCLUSION: With increasing accessibility of NRT, further surveillance and research are warranted to determine the impact of the reach and benefits of NRT, considering both the general and targeted smoking populations.

The role of drinking water in the transmission of antimicrobial-resistant E. coli.

To determine whether drinking water contaminated with antimicrobial-resistant E. coli is associated with the carriage of resistant E. coli, selected households sending water samples to Ontario and Alberta laboratories in 2005-2006 were asked to participate in a cross-sectional study. Household members aged ≥12 years were asked to complete a questionnaire and to submit a rectal swab. In 878 individuals, 41% carried a resistant strain of E. coli and 28% carried a multidrug-resistant strain. The risk of carriage of resistant E. coli was 1·26 times higher for users of water contaminated with resistant E. coli. Other risk factors included international travel [prevalence ratio (PR) 1·33], having a child in nappies (PR 1·33), being male (PR 1·33), and frequent handling of raw red meats (PR 1·10). Protecting private water sources (e.g. by improving systems to test and treat them) may help slow the emergence of antimicrobial resistance in E. coli.

Red wine but not ethanol at low doses can protect against the toxicity of methamphetamine.

The goal of this study was twofold: (a) to search for possible interactive effects between two common drugs of abuse, ethanol and methamphetamine. b) To inquire whether any effects of ethanol could be replicated using an equivalent amount of ethanol in the form of red wine. Adult male C57/6N mice received 2% ethanol for 8 weeks in drinking water or red wine diluted to yield the same ethanol content. On the 9th week animals received multiple injections of methamphetamine (4 x 10 mg/kg, ip, every 2 h). They were then sacrificed 72 h after treatment. Methamphetamine produced a significant depletion of dopamine and DOPAC in the striatum. Treatment with both ethanol and methamphetamine led to a reduction of striatal dopamine and DOPAC that were both non-significantly greater than that observed with methamphetamine alone. Alcohol alone produced no changes in the striatal content of dopamine or its metabolite, DOPAC. These data suggest that low doses of alcohol potentiate methamphetamine-induced neurotoxicity in mice and that this combination may be especially detrimental to the brain. However, an equivalent dose of ethanol in the form of red wine actually partially protected against methamphetamine-induced depletion of dopamine and DOPAC in red wine treated mice. This implies the presence of other agents in red wine, which may mitigate the toxicity of methamphetamine.

Predictive validity and measurement issues in documenting quit intentions in population surveillance studies.

INTRODUCTION: Discrete classification of smokers by intention to quit is desirable in many public health and clinical settings. METHODS: Two methodological studies examine measurement properties of measures of discrete-time intention to quit smoking used in population-based tobacco surveillance surveys: an ecological comparison of rates of positive intention in relation to the form of measure used and a prospective analysis examining predictive validity of self-reported quit intentions using multiple possible points of dichotomization of an ordinal measure of intention to quit. The prospective analysis used a repeated measures design and follow-up to 1 year for 2,047 smokers in the Ontario Tobacco Survey cohort. RESULTS: The estimated percent of smokers intending to quit was significantly higher using the Stages of Change intention measure, relative to another single question measure. Significant dose-response effects were found. The sooner one intended to quit the more likely one was to make an attempt or achieve at least 30 days abstinence in the next 6 months. Intending to quit in a month or later was not associated with cessation during follow-up among respondents without prior attempts. Examination of cutpoints revealed no value, which maximized both positive and negative prediction. Regardless of quit attempt history, greatest predictive validity was found where respondents stated that they had no intention at all. DISCUSSION: Measures of intentions quit smoking in specific time periods and expressed as dichotomies have limited psychometric properties but utility in applied research. Our findings suggest a possible measurement effect warranting caution in comparisons across studies.

Origin and use of the 100 cigarette criterion in tobacco surveys.

Truly global standards and definitions will likely never exist for tobacco control surveillance. One difference across definitions of smoking status is whether or not a lifetime consumption of 100 cigarettes is a necessary criterion for ever and current smoking. Frequently asked questions about this measure demonstrate a need for information on its development and appropriateness in different settings. This commentary attempts to assemble information on the origin and adoption of this measure and provide some critical commentary on its usefulness. The question has been traced to Canadian and American mortality cohort studies from the mid-1950s. From there it has spread to inconsistent use in many settings. To our knowledge, it was not originally (or since) empirically defined as a threshold of exposure related to health consequences or future smoking risk when used in youth. Anecdotal evidence over several decades, however, shows the question has pragmatic utility in self-report data collection. It is a useful, if somewhat arbitrary, screener for "never regular" tobacco use among adults, where never smoking needs to be defined in data collection. Use of the criterion may lower prevalence estimates somewhat. Definitions must always be considered when creating time-trends or international comparisons. There are also circumstances where it is inappropriate to exclude individuals who do not meet this criterion from further data collection, or reports. For research in youth, the criterion typically should be used only with more detailed information about experimentation, but it may be a useful additional indicator of established smoking.

Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways.

In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS effects in apolipoprotein E knockout (ApoE-/-) mice exposed to two levels of concentrated ultrafine particulate matter in central Los Angeles. Mice were euthanized 24h after the last exposure and brain, liver, heart, lung and spleen tissues were collected and frozen for subsequent bioassays. There was clear evidence of aberrant immune activation in the brains of exposed animals as judged by a dose-related increase in nuclear translocation of two key transcription factors, NF-kappaB and AP-1. These factors are involved in the promotion of inflammation. Increased levels of glial fibrillary acidic protein (GFAP) were also found consequent to particulate inhalation suggesting that glial activation was taking place. In order to determine the mechanism by which these events occurred, levels of several MAP kinases involved in activation of these transcription factors were assayed by Western blotting. There were no significant changes in the proportion of active (phosphorylated) forms of ERK-1, IkB and p38. However, the fraction of JNK in the active form was significantly increased in animals receiving the lower concentration of concentrated ambient particles (CAPs). This suggests that the signaling pathway by which these transcription factors are activated involves the activation of JNK.

Examining the relationships between job control and health status: a path analysis approach.

OBJECTIVE: To examine the pathways through which job control affects health status; to examine if the effects of job control on health status are attenuated by including other measures associated with lower socioeconomic status, and to examine if the relationship between job control and health status is consistent across socioeconomic status groups. DESIGN: A prospective observational cohort study over eight years (1994-2002). PARTICIPANTS: 4886 Respondents aged 25-60 years, who were non-self-employed labour force participants, working more than 20 hours per week, without physical or mental limitations restricting the type or amount of work they could do at baseline. After longitudinal attrition, the remaining study sample was 3411 (87% of the original study sample who did not die or become pregnant during the survey period). MAIN RESULTS: Low job control in 1994 was associated with worse than expected self-rated health in 2002, both directly and indirectly via a lower physical activity level in 1996. Adjustment for other factors associated with low socioeconomic status did not attenuate these relationships to a large extent. No differences were found in the effects of job control on physical activity or health status between socioeconomic groups (high and low education and high and low household income). CONCLUSIONS: The inclusion of other factors associated with lower socioeconomic status did not attenuate the direct and indirect effects of job control on health status. The finding that low job control is associated with lower physical activity levels deserves further investigation, given the increasing concern about rising levels of obesity in the developed world.

Prevalence of screening in patients newly diagnosed with colorectal cancer in Ontario.

OBJECTIVES: The primary objective was to determine the proportion of individuals with a new diagnosis of colorectal cancer (CRC) in Ontario in whom the cancer was screen detected. The secondary objectives were to determine the cancer stage at diagnosis and the indications for the procedure in patients who received their first colonoscopy. PATIENTS AND METHODS: Individuals admitted to a hospital with a new diagnosis of CRC were randomly selected after stratifying by hospital type (teaching or community). The Canadian Institute for Health Information's Discharge Abstract Database was used to identify individuals with a first diagnosis of CRC during calendar year (CY) 2000, and Ontario Health Insurance Plan data were used to identify people 50 to 74 years of age who had their first colonoscopy during CY 2000. Up to 20 individuals were selected for each group (CRC or colonoscopy) in each of seven randomly selected community hospitals and three randomly selected teaching hospitals. Data were abstracted from the hospital charts. RESULTS: The hospital charts of 152 patients with a new diagnosis of CRC were examined. Of the 133 patients in whom screening status could be determined, eight had screen-detected cancers (6.0%). Of the 99 patients (65% of the sample) in whom stage could be determined, 43 (43.4%) had advanced disease (tumour-node-metastasis stage III or IV) at diagnosis. The hospital charts of 184 patients who underwent their first colonoscopy were examined. Of the 175 patients in whom the indication for colonoscopy could be determined, 45 underwent the procedure for screening purposes, 10 were for diagnostic workup of anemia and 120 for evaluation of symptoms. CONCLUSIONS: The low proportion (6%) of screen-detected CRC and the high proportion of patients (43.4%) with advanced disease at diagnosis reflect the lack of an organized screening program.

A tale of two time periods: ovarian cancer trends in Ontario.

We assessed population-based trends in incidence and survival rates for epithelial ovarian cancer in Ontario in two time periods. Our population-based study cohort included all women with epithelial ovarian cancer treated initially with abdominal surgery in Ontario for January 1996 through December 2001. Incident surgical cases were documented by hospital contact data and the Ontario Cancer Registry. Patient characteristics (age, for example) were obtained from electronic administrative data records. Regression analyses were used to assess the influence of time period on survival while controlling for age, comorbidity, and other factors associated with this outcome.A total of 3825 women met the inclusion criteria. We found that the age-standardized incidence of ovarian cancer remained stable during 1996-2001. A shift to a younger age at diagnosis was found between the two time periods being compared. The univariate analysis revealed a clear difference in death rate, to which age at diagnosis, Charlson comorbidity score, and treatment period contributed. Earlier time period (p < 0.0001), advancing age (p < 0.0001), higher Charlson score (p < 0.0001), and lower income quartile score (p = 0.03) were significantly associated with poorer survival in the univariate analysis. Younger age, lower Charlson score, and more recent time period of diagnosis and treatment (p < 0.0001) were associated with improved survival in the proportional hazards model.We conclude that age-standardized incidence and mortality rates for ovarian cancer in Ontario have remained stable. For women initially treated with surgery, advances in management have led to an improvement in survival.

Duration and distance of exposure are important predictors of transmission among community contacts of Ontario SARS cases.

We report attack rates and contact-related predictors among community contacts of severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area outbreak. Community contact data was extracted from public health records for single, well-defined exposures to a SARS case. In total, 8662 community-acquired exposures resulted in 61 probable cases; a crude attack rate of 0.70% [95% confidence interval (CI) 0.54-0.90]. Persons aged 55-69 years were at higher risk of acquiring SARS (1.14%) than those either younger (0.60%) or older (0.70%). In multivariable analysis exposures for at least 30 min at a distance of

Melatonin treatment in old mice enables a more youthful response to LPS in the brain.

Melatonin modulates the expression of a number of genes related to inflammation and immunity. Declining levels of melatonin with age may thus relate to some of the changes in immune function that occur with age. mRNA expression levels in murine CNS were measured using oligonucleotide microarrays in order to determine whether a dietary melatonin supplement may modify age-related changes in the response to an inflammatory challenge. CB6F1 male mice were fed 40-ppm melatonin for 9 weeks prior to sacrifice at 26.5 months of age, and compared with age-matched untreated controls and 4.5-month-old controls. A subset of both young and old animals was injected i.p. with lipopolysaccharide (LPS). After 3 h, total RNA was extracted from whole brain (excluding brain stem and cerebellum), and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. Data were analyzed in Dchip and GeneSpring. Melatonin treatment markedly altered the response in gene expression of older animals subjected to an LPS challenge. These changes in general, caused the response to more closely resemble that of young animals subjected to the same LPS challenge. Thus melatonin treatment effects a major shift in the response of the CNS to an inflammatory challenge, causing a transition to a more youthful mRNA expression profile.

Chronic exposure to low levels of aluminum alters cerebral cell signaling in response to acute MPTP administration.

Two-month-old male B/6C3F1 mice were treated for 10 weeks with 100 microM aluminum lactate (Al) in drinking water. This dose of Al did not alter body weight, and there was no evidence of systemic toxicity. The degree of phosphorylation of several kinases which lead to transcription factor activation (reflecting the extent of their activation) was studied. The proportion of extracellular signal-regulated kinase (ERK) that was activated was depressed in cortex but not in the hippocampus following treatment but c-Jun N-terminal kinase (JNK), p38, IkappaB phosphorylation was unaltered in either tissue. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) alone produced no significant changes in the degree of activation of any transcription factor studied. When MPTP dosing had been preceded by extended exposure to low levels of Al in drinking water, ERK activation was profoundly depressed in cortex and hippocampus, whereas JNK in hippocampus and IkappaB in cortex were greatly elevated. These changes consequent to exposure to both Al and MPTP were accompanied by an increase in NF-kappaB in both regions, whereas AP-1 was elevated in the hippocampus alone. Neither agent alone modulated AP-1 or NF-kappaB. Thus a synergistic interaction occurred between the toxicants. This interaction tended to promote the functioning of a kinase largely associated with inflammation and to depress that of ERK, which is associated with maintenance of cell survival. It is concluded that exposure to levels of Al with no evident toxicity can worsen the response to an acute challenge with MPTP. Al treatment alone was able to increase striatal 3,4-dihydroxyphenylacetic acid levels, suggesting an elevation of the rate of dopamine turnover in the striatum. However, no interaction in alteration of monoamine levels was found between Al and MPTP.

Prognostic factors for women with Stage 1 ovarian cancer with or without adhesions.

OBJECTIVE: To identify those prognostic factors in women with Stage 1 epithelial ovarian cancer that predict survival. METHODS: A population-based cohort study was conducted which included all newly diagnosed ovarian cancer patients treated initially with surgery from 1996-1998 in Ontario, Canada (N = 1,341). We abstracted charts from hospitals and cancer centres and used hospital and billing claims databases. Cox survival analysis was used to model the association between prognostic factors (including patient characteristics, surgical findings, pathologic findings and subsequent treatment) and survival for those with Stage 1 ovarian cancer. RESULTS: 327 women had Stage 1 or 2 ovarian cancer (where Stage 2 was based on adhesions alone). Prognostic factors that had significant, unadjusted, association with survival were patient age, presence or absence of adhesions, grade, and surface involvement. The multivariable model that best described survival included premenopausal age group (HR 0.32, 95% CI, 0.18-0.55), poor differentiation (HR 2.17, 95% CI, 1.33-3.51), and surface capsule involvement (HR 2.97, 95% CI, 1.59-5.55). A lack of influence of treatment modality stands in contrast to the literature. CONCLUSIONS: Our dataset confirmed that poor grade and surface capsule involvement are poor prognostic factors. Adjuvant therapy did not confer an improved outcome; however, it was likely used in only those patients with poor prognostic indicators and so improved their survival to that of women with good prognostic factors who received surgery alone.