A Study of the Effectiveness of Workplace Health and Safety Programmes in a University Setting in Canada.

Introduction: Nearly a quarter-million people work in universities in Canada, making it one of the fastest-growing sectors. Although each university provides occupational health and safety services and training programmes to their employees, there have been no studies conducted on the impact of such programmes on employees' knowledge, attitude and behaviour. The aim of this study was to evaluate the effectiveness of dissemination of information of workplace health and safety programmes to workers at a Canadian university. Methods: The study compared two cross-sectional online surveys of employees of a Canadian university regarding workplace health and safety with a previously conducted cross-sectional study and thematic analysis of key informant interviews to address the issues raised in the surveys. Results: Participation in health and safety presentations could enhance understanding and practices of safety. Age, employment status and duration of employment were associated with the levels of knowledge, attitudes and behaviour of employees and graduate students. The key informant interviews highlighted some new initiatives such as the establishment of workplace health and safety committees in all university buildings; the development of a safety app and health and safety management system; routine annual inspections of all university building offices and laboratories; new orientation for undergraduate students where general safety rules are described. Discussion: University should have regular presentations on the available health and safety programmes and should increase the number of safety training programmes and keep track of the employees that have not received any training, particularly for those working in hazardous environments.

A Quality Improvement Emergency Department Surge Management Platform (SurgeCon): Protocol for a Stepped Wedge Cluster Randomized Trial.

BACKGROUND: Despite many efforts, long wait times and overcrowding in emergency departments (EDs) have remained a significant health service issue in Canada. For several years, Canada has had one of the longest wait times among the Organisation for Economic Co-operation and Development countries. From a patient's perspective, this challenge has been described as "patients wait in pain or discomfort for hours before being seen at EDs." To overcome the challenge of increased wait times, we developed an innovative ED management platform called SurgeCon that was designed based on continuous quality improvement principles to maintain patient flow and mitigate the impact of patient surge on ED efficiency. The SurgeCon quality improvement intervention includes a protocol-driven software platform, restructures ED organization and workflow, and aims to establish a more patient-centric environment. We piloted SurgeCon at an ED in Carbonear, Newfoundland and Labrador, and found that there was a 32% reduction in ED wait times. OBJECTIVE: The primary objective of this trial is to determine the effects of SurgeCon on ED performance by assessing its impact on length of stay, the time to a physician's initial assessment, and the number of patients leaving the ED without being seen by a physician. The secondary objectives of this study are to evaluate SurgeCon's effects on patient satisfaction and patient-reported experiences with ED wait times and its ability to create better-value care by reducing the per-patient cost of delivering ED services. METHODS: The implementation of the intervention will be assessed using a comparative effectiveness-implementation hybrid design. This type of hybrid design is known to shorten the amount of time associated with transitioning interventions from being the focus of research to being used for practice and health care services. All EDs with 24/7 on-site physician support (category A hospitals) will be enrolled in a 31-month, pragmatic, stepped wedge cluster randomized trial. All clusters (hospitals) will start with a baseline period of usual care and will be randomized to determine the order and timing of transitioning to intervention care until all hospitals are using the intervention to manage and operationalize their EDs. RESULTS: Data collection for this study is continuing. As of February 2022, a total of 570 randomly selected patients have participated in telephone interviews concerning patient-reported experiences and patient satisfaction with ED wait times. The first of the 4 EDs was randomly selected, and it is currently using SurgeCon's eHealth platform and applying efficiency principles that have been learned through training since September 2021. The second randomly selected site will begin intervention implementation in winter 2022. CONCLUSIONS: By assessing the impact of SurgeCon on ED services, we hope to be able to improve wait times and create better-value ED care in this health care context. TRIAL REGISTRATION: ClinicalTrials.gov NCT04789902; https://clinicaltrials.gov/ct2/show/NCT04789902. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30454.

Rationale and protocol for a randomized waitlist controlled trial of videoconference delivered cognitive behaviour therapy for insomnia (CBT-I) to improve perceived cognitive impairment (PCI) among cancer survivors.

Perceived cognitive impairment (PCI) and sleep disturbances (such as insomnia) are commonly reported barriers preventing cancer survivors from resuming normal functioning. Cognitive-behaviour therapy for insomnia (CBT-I) is the treatment of choice for insomnia among cancer survivors. Literature suggests that treatment with CBT-I may lead to an improvement in PCI, but this needs to be tested in a sample of patients with PCI at study entry with cognitive impairments as the primary study outcome. Here we describe the design of a clinical trial to evaluate the efficacy of videoconference-delivered CBT-I for the improvement of PCI among cancer survivors. This project is a randomized waitlist-controlled trial with a recruitment target of 124 adult cancer survivors (solid tumors and hematological malignancies) who have completed primary treatment at least 6 months prior, report PCI and meet criteria for insomnia disorder. Participants will complete assessments at baseline, 4 weeks (mid-treatment), 8 weeks (post treatment), and 3 and 6 months post-treatment. The primary outcome is the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog). Treatment of PCI in cancer patients is a priority for clinicians, researchers, and patients. This research will increase our understanding of the mechanisms of cognitive impairment associated with cancer, and potentially expand currently available treatment options.

Relationship Between Psychosocial Factors and Glucose Control in Adults With Type 2 Diabetes.

OBJECTIVES: Despite significant advances in medical therapy and unrestricted access to health care, >50% patients with type 2 diabetes (T2D) cannot maintain their blood glucose target levels. This cross-sectional study investigated the association between psychosocial behaviour and diabetes management in Newfoundland and Labrador, where the prevalence of T2D is the highest in Canada. METHODS: Data were collected from 165 adult T2D patients. Four sets of self-administered standardized questionnaires, a study-specific data form and electronic health records were utilized to obtain psychosocial information, patient characteristics and glycated hemoglobin (A1C) levels. RESULTS: The group of participants with emotional burnout due to diabetes-related stress showed poor glycemic control (89.4%) compared to the group with low stress (55.6%). The group with higher stress appraised T2D negatively (correlation coefficient r=0.719, and p<0.01), and had a tendency to use emotion-oriented coping (r=0.542, p<0.01) and had a poor perception of autonomous supportiveness (r=-0.300, p<0.01). A path model showed that stress, appraisal and coping explained 7.4% of the variance in A1C. Appraisal plays the role of mediator and explained 5.8% of the variance in A1C. CONCLUSIONS: A high prevalence of poor glycemic control was found in participants with a body mass index of ≥35. Participants with higher stress had a negative appraisal of T2D. The highly stressed group tended to use emotion-oriented coping and have a poor perception of autonomous supportiveness.

A randomized controlled trial of the effect of an intensive 1-year care management program on measures of health status in independent, community-living old elderly: the Eldercare project.

BACKGROUND: Primary care practitioners are familiar with the frail elderly and commonly have to deal with their multi-morbidity and their functional decline, both physically and mentally. However, there are well elderly with high quality of life and very few co-morbidities who seldom seek medical care. OBJECTIVE: To determine if a nurse-based program of home-delivered care, linked directly with the primary care practitioner or primary care team, would improve quality of life, symptoms, satisfaction with care and utilization of community and medical services, in independent community living old elderly. DESIGN: Randomized controlled trial. SETTING: St. John's, Newfoundland, Canada. PARTICIPANTS: Two hundred and thirty-six independent, community-dwelling, cognitively functioning, people aged 80 years and older. INTERVENTION: A nurse-based program of care, carried out in the patients home, that involved a detailed assessment of needs, the development of a plan to meet the needs, and up to eight visits to the patients home during a 1-year period to facilitate the meeting of those needs. CONTROL GROUP: Usual care MAIN OUTCOME MEASUREMENTS: Quality of Life measured using the SF-36 and the CASP-19 scales; symptomology using the Comorbidity Symptom Scale; patient satisfaction using the PSQ-18; and assessment of health care services (community services, emergency room visits, hospitalizations, use of diagnostic services and family doctor visits) through patient recall, family physician chart review and assessment of hospitalization records. RESULTS: There were no statistical or meaningful differences between the intervention and control groups in any of the outcomes measured. CONCLUSION: The intensive, home-delivered, program of care for the well old elderly did not have an impact on the outcomes measured.

The healthy aged: Descriptive analysis by sex of cognitively functioning elderly patients 80 years and older living independently in the community.

OBJECTIVE: To describe a population of cognitively functioning seniors aged 80 years and older who are livingin dependently in the community. DESIGN: Descriptive cross-sectional study based on the enrolment cohort of a randomized controlled trial. SETTING: St John's, Nfld. PARTICIPANTS: A total of 236 cognitively functioning seniors aged 80 years and older living independently in the community. MAIN OUTCOME MEASURES: Demographic characteristics including age, sex, marital status, and education; health status and quality of life measured by the Short Form-36 and the CASP-19 (control, autonomy, self-realization,and pleasure); use of formal and informal community services;satisfaction with family physician care as measured by the Patient Satisfaction Questionnaire-18; and use of health care resources (family physician visits, emergency department visits,hospitalizations, and laboratory and diagnostic imaging tests). RESULTS: Overall, 66.5% of those in the group were women and the average age was 85.5 years. A quarter had postsecondary diplomas or degrees; 54.7% were widowed (69.4% of women and 25.3% of men). The cohort scored well in terms of health status and quality of life, with a range of scores on the Short Form­36 from 57.5 to 93.5 out of 100, and a score of 44 out of 57 on the CASP-19; they were satisfied with the care received from family physicians, with scores between 3.8 and 4.3 out of 5 on the Patient Satisfaction Questionnaire-18; and use of health services was low-70% had no emergency department visits in the previous year and 80% had not used any laboratory or diagnostic services. CONCLUSION: Seniors aged 80 years and older living in dependently are involved in the social fabric of society. They are generally well educated, slightly more than half are widowed,and two-thirds are female. They score well on scales that measure well-being and quality of life, and they use few health services. They are the healthy aged. TRIAL REGISTRATION NUMBER: NCT00452465 (ClinicalTrials.gov).

Adverse drug reactions in elderly hospitalized patients: a 12-year population-based retrospective cohort study.

BACKGROUND: Although research has identified some risk factors for first-time adverse drug reactions (ADRs), little is known about the risks associated with the number of ADRs. Modeling ADR counts is relatively complex because of the rarity of the events, requiring careful consideration of appropriate models that best present the observed data. OBJECTIVE: To determine the incidence of ADRs among elderly hospitalized patients, assess patient-related risk factors for the number of ADRs, and review drug classes commonly responsible for ADRs. METHODS: This retrospective cohort study used a population-based large administrative database on hospital separations from all acute care hospitals in the Canadian province of Newfoundland and Labrador. Patients aged 65 years or older with at least 1 hospital admission from April 1, 1995, to March 31, 2007, were included. Comorbidities, Charlson Comorbidity Index (CCI), and sociodemographic factors were assessed as predictors of ADR counts. A zero-inflated negative binomial regression model was used for analysis. RESULTS: The study cohort contained 64,446 patients. The incidence of ADRs was 15.2 per 1000 person-years (95% CI 14.8 to 15.7). Of those having an ADR, 15.4% had recurrent ADRs. The most common drug category implicated in ADRs was cardiovascular agents (17.7%). A dose-response relationship was found between CCI and ADR counts (rate ratio [RR] 1.67, 95% CI 1.41 to 1.98 for CCI 2-3; RR 2.38, 95% CI 1.98 to 2.87 for CCI 4-5; and RR 3.83, 95% CI 3.21-4.57 for CCI ≥6). Comorbid conditions including congestive heart failure (RR 1.58, 95% CI 1.33 to 1.89), diabetes (RR 2.42, 95% CI 1.64 to 3.56), and cancer (RR 3.12, 95% CI 2.58 to 3.76) were strong predictors. Rural areas (RR 1.22, 95% CI 1.01 to 1.46) were associated with increased risk for ADRs, whereas age and sex had no effect. CONCLUSIONS: Comorbidity from chronic diseases and severity of illness, rather than individual characteristics (advancing age and sex), increased the likelihood of ADRs. Changes in the delivery of care focusing on the monitoring of prescribed drugs in elderly patients with comorbidities could mitigate ADRs.

Aptima HPV E6/E7 mRNA test is as sensitive as Hybrid Capture 2 Assay but more specific at detecting cervical precancer and cancer.

Detection of human papillomavirus (HPV) E6/E7 oncogene expression may be more predictive of cervical cancer risk than testing for HPV DNA. The Aptima HPV test (Gen-Probe) detects E6/E7 mRNA of 14 oncogenic types. Its clinical performance was compared with that of the Hybrid Capture 2 DNA test (HC2; Qiagen) in women referred for colposcopy and those routinely screened. Aptima was also compared with the PreTect HPV-Proofer E6/E7 mRNA assay (Proofer; Norchip) in the referral population. Cervical specimens collected in PreservCyt (Hologic Inc.) were processed for HPV detection and genotyping with the Linear Array (LA) method (Roche Molecular Diagnostics, Laval, Quebec, Canada). Histology-confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN 2+) served as the disease endpoint. On the basis of 1,418 referral cases (CIN 2+, n = 401), the sensitivity of Aptima was 96.3% (95% confidence interval [CI], 94.4, 98.2), whereas it was 94.3% (95% CI, 92.0, 96.6) for HC2. The specificities were 43.2% (95% CI, 40.2, 46.2) and 38.7% (95% CI, 35.7, 41.7), respectively (P < 0.05). In 1,373 women undergoing routine screening (CIN 2+, n = 7), both Aptima and HC2 showed 100% sensitivity, and the specificities were 88.3% (95% CI, 86.6, 90.0) and 85.3% (95% CI, 83.5, 87.3), respectively (P < 0.05); for women ≥ 30 years of age (n = 845), the specificities were 93.9% (95% CI, 92.3, 95.5) and 92.1% (95% CI, 90.3, 93.9), respectively (P < 0.05). On the basis of 818 referral cases (CIN 2+, n = 235), the sensitivity of Aptima was 94.9% (95% CI, 92.1, 97.7) and that of Proofer was 79.1% (95% CI, 73.9, 84.3), and the specificities were 45.8% (95% CI, 41.8, 49.8) and 75.1% (95% CI, 71.6, 78.6), respectively (P < 0.05). Both Aptima and Proofer showed a higher degree of agreement with LA genotyping than HC2. In conclusion, the Aptima test is as sensitive as HC2 but more specific for detecting CIN 2+ and can serve as a reliable test for both primary cervical cancer screening and the triage of borderline cytological abnormalities.

Clinical performance of the PreTect HPV-Proofer E6/E7 mRNA assay in comparison with that of the Hybrid Capture 2 test for identification of women at risk of cervical cancer.

Human papillomavirus (HPV) DNA testing has a higher clinical sensitivity than cytology for the detection of high-grade cervical intraepithelial neoplasia or worse (CIN 2+). However, an improvement in specificity would be desirable. As malignant transformation is induced by HPV E6/E7 oncogenes, detection of E6/E7 oncogene activity may improve specificity and be more predictive of cervical cancer risk. The PreTect HPV-Proofer assay (Proofer; Norchip) detects E6/E7 mRNA transcripts from HPV types 16, 18, 31, 33, and 45 with simultaneous genotype-specific identification. The clinical performance of this assay was assessed in a cross-sectional study of women referred for colposcopy in comparison with the Hybrid Capture 2 (HC2; Qiagen) test, which detects DNA of 13 high-risk oncogenic HPV types collectively. Cervical specimens were collected in PreservCyt, and cytology was performed using the ThinPrep method (Hologic). The samples were processed for HPV detection with Proofer and HC2 and genotyping with the Linear Array method (Roche Molecular Systems). Histology-confirmed CIN 2+ served as the disease endpoint to assess the clinical performance of the tests. A total of 1,551 women were studied, and of these, 402 (25.9%) were diagnosed with CIN 2+ on histology. The Proofer assay showed a sensitivity of 78.1% (95% confidence interval [CI], 74.1 to 82.1) versus 95.8% (95% CI, 93.8 to 97.8) for HC2 (P < 0.05) and a specificity of 75.5% (95% CI, 73.0 to 78.0) versus 39.6% (95% CI, 36.8 to 42.4), respectively (P < 0.05). The lower sensitivity and higher specificity of Proofer for detection of CIN 2+ can be attributed to the fact that this test detects the expression of E6/E7 genes beyond a threshold from a limited number of oncogenic HPV types. In conclusion, Proofer is more specific than HC2 in identifying women with CIN 2+ but has a lower sensitivity.

Adverse drug events in adult patients leading to emergency department visits.

BACKGROUND: Adverse drug events (ADEs) occurring in the community and treated in emergency departments (EDs) have not been well studied. OBJECTIVE: To determine the prevalence, severity, and preventability of ADEs in patients presenting at EDs in 2 university-affiliated tertiary care hospitals in the Canadian province of Newfoundland and Labrador. METHODS: A retrospective chart review was conducted on a stratified random sample (n = 1458) of adults (> or =18 y) who presented to EDs from January 1 to December 31, 2005. Prior to the chart review, the sample frame was developed by first eliminating visits that were clearly not the result of an ADE. The ED summary of each patient was initially reviewed by 2 trained reviewers in order to identify probable ADEs. All eligible charts were subsequently reviewed by a clinical team, consisting of 2 pharmacists and 2 ED physicians, to identify ADEs and determine their severity and preventability. RESULTS: Of the 1458 patients presenting to the 2 EDs, 55 were determined to have an ADE or a possible ADE (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found to be 2.4%. Prevalence increased with age (0.7%, 18-44 y; 1.9%, 45-64 y; 7.8%, > or =65 y) and the mean age for patients with ADEs was higher than for those with no ADEs (69.9 vs 63.8 y; p < 0.01). A higher number of comorbidities and medications was associated with drug-related visits. Approximately 29% of the ADEs/PADEs identified were considered to be preventable, with 42% requiring hospitalization. Cardiovascular agents (37.4%) were the most common drug class associated with ADEs/PADEs. CONCLUSIONS: Adult ADE-related ED visits are frequent in Newfoundland and Labrador, and in many cases are preventable. Further efforts are needed to reduce the occurrence of preventable ADEs leading to ED visits.

Fructose and moderately high dietary salt-induced hypertension: prevention by a combination of N-acetylcysteine and L-arginine.

Diets containing 8% salt or 4% fructose (FR) cause insulin resistance and increase tissue methylglyoxal and advanced glycation end products (AGEs), platelet cytosolic-free calcium, and systolic blood pressure (SBP) in rats. In WKY rats, we have shown that moderately high salt, 4% NaCl (MHS) alone in diet does not cause hypertension, and when given along with 4% FR it does not have an additive effect. N-acetylcysteine (NAC) or L-arginine (ARG), treatment alone does not prevent hypertension in this model. The objectives of this study were to investigate the effect of NAC plus ARG in diet on SBP, platelet cytosolic-free calcium in a MHS + FR model, and to measure the plasma levels of methylglyoxal and the AGE, methylglyoxal-derived hydroimidazolone (MGH). At 7 weeks of age, WKY rats were divided into three groups: control group was given regular rat chow (0.7% NaCl) and water; MHS + FR group, diet containing 4% NaCl and 4% FR in drinking water; and MHS + FR + NAC + ARG group, MHS diet supplemented with 1.5% N-acetylcysteine (NAC) and 1.5% L-arginine (ARG), and 4% FR in drinking water, and followed for 6 weeks. NAC + ARG prevented the increase in platelet cytosolic-free calcium and SBP in MHS + FR treated rats. There was no difference in mean values of plasma methylglyoxal and MGH among the groups. In conclusion, NAC + ARG treatment is effective in preventing hypertension in a moderately high salt + FR-induced animal model. Plasma methylglyoxal and MGH may not represent tissue modification or, alternatively, other tissue AGEs, derived from methylglyoxal or other aldehydes, may be involved in hypertension in this model.

Cervical cancer screening among Asian Canadian immigrant and nonimmigrant women.

OBJECTIVES: To examine whether Pap smear screening and determinants of screening for Asian immigrants are different from those for nonimmigrants in Canada. METHODS: Data from the Canadian Community Health Survey Cycle 2.1 (2003) were used. Explanatory and multivariate logistic regression analyses were performed to compare rates and determinants of Pap smear screening between Asian immigrants and nonimmigrants. RESULTS: In this study, 64,604 women were included. Asian immigrants had significantly lower rates of Pap smear screening (52%) compared to nonimmigrants (72%). Lack of necessity and time are important barriers. CONCLUSION: Pap smear screening should be promoted, particularly in recent Asian immigrants.

Adverse drug events among children presenting to a hospital emergency department in Newfoundland and Labrador, Canada.

OBJECTIVES: The aim of this study was to examine epidemiologic characteristics of Adverse Drug Events (ADEs) among children and adolescents presenting to an Emergency Department (ED) in Newfoundland and Labrador (NL), Canada. MATERIALS AND METHODS: This study was conducted in three phases and included an ED chart review of visits to the Janeway Hospital in St. John's, NL, between 27th April 2006 and 26th April 2007. The first phase narrowed the sampling frame by excluding visits highly unlikely to be drug-related. In the second phase, a random sample of ED charts was selected for review by two research nurses using a Trigger Assessment Tool that classified ED visits according to their likelihood of being drug related ('high', 'moderate', 'low', 'very low', or 'no' probability). The third phase included a full chart review of all 'high', 'moderate', 'low', and 'very low' probability ADE charts, carried out independently by two ED pediatricians and two clinical pharmacists. Each ADE was also scored for severity and preventability, and consensus was reached among all four reviewers during meetings held at the end of this phase. RESULTS: In this study, 69 patients presented to the ED either due to an ADE or a possible ADE (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found to be 2.1%. The number of co-morbidities was inversely associated with medication-related visits. There was no significant difference found between patients with and without medication related visits with respect to mean age of the patient and the mean number of current medications being taken. Of the 69 confirmed ADE/PADEs, none were fatal, six (8.7%) were serious/life-threatening, and 63 (91.3%) were considered significant. Antimicrobial agents (45.0%) were the most common drug classes associated with ADEs/PADEs. Approximately 20% of the 69 ADEs/PADEs identified were considered preventable. CONCLUSIONS: In St. John's NL, emergency department visits as a result of ADEs are common among the pediatric population and in many cases preventable. Age and number of current medications do not appear to be associated with ED visits related with ADE. Antimicrobial agents were found to be to the cause of most ADEs/PADEs.

Relationship between serum magnesium values, lipids and anthropometric risk factors.

UNLABELLED: Serum magnesium (SMg) has been reported to negatively correlate with an atherogenic lipid profile in individuals with diabetes mellitus (DM) and metabolic syndrome. This study examines whether the relationships between SMg levels and biochemical and anthropometric risk factors for these conditions are also present in the general adult population. DESIGN AND METHODS: Biochemical parameters and anthropometric variables were assessed in 1318 healthy adult subjects recruited from the Newfoundland population. RESULTS: SMg positively correlated with age, and serum phosphate, calcium, albumin, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels. SMg negatively correlated with HOMA-beta and percent body fat measured by DEXA. On sub-grouping subjects according to sex, menopausal status or after excluding subjects with DM, only a significant correlation of SMg with albumin, calcium, phosphate, and total cholesterol was common to all. Stepwise linear regression analysis revealed albumin, phosphate, age, total cholesterol, glucose, and body mass index as independent predictors of SMg levels. CONCLUSIONS: These results indicate that SMg levels positively correlate with total cholesterol and possibly all lipoproteins in a large adult study population which suggests that variation of SMg with serum lipid levels may be different in healthy individuals compared with those with DM. We speculate on a possible binding interaction.

Effect of moderately high dietary salt and lipoic acid on blood pressure in Wistar-Kyoto rats.

BACKGROUND: Approximately one-half of hypertensive individuals are salt sensitive, and animal models of human hypertension also exhibit increased blood pressure when exposed to high-salt diets. Salt sensitivity is associated with insulin resistance, which results in altered glucose metabolism, increasing aldehydes. Previously, the authors have shown that a high-salt diet (8% NaCl) caused an increase in blood pressure, tissue aldehyde conjugates and cytosolic free calcium, with resulting adverse renal vascular changes, in Wistar-Kyoto rats. Treatment with lipoic acid (LA) prevented an increase in blood pressure and attenuated biochemical and histopathological changes. OBJECTIVES: The objective of the present study was to investigate the effect of a moderately high-salt (MHS) diet (4% NaCl) on these same parameters, and the modulating effect of LA in Wistar-Kyoto rats. METHODS: At seven weeks of age, animals were divided into three groups. The normal-salt group was given a diet containing 0.7% NaCl; the MHS group was given a diet containing 4% NaCl; and the MHS+LA group was given a diet containing 4% NaCl plus LA (500 mg/kg diet) for 10 weeks. RESULTS: At the end of the study, animals in the MHS group did not show any increase in systolic blood pressure, platelet cytosolic free calcium and tissue aldehyde conjugates. Furthermore, there were no adverse effects in renal vascular morphology compared with the normal salt group. In the MHS+LA group, LA did not lower blood pressure or affect other biochemical and histopathological parameters. CONCLUSION: The present study suggests that moderately high sodium intake, over a short period, may not have any adverse effect and that LA does not lower blood pressure in normotensive rats.

Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients.

Studies aimed at elucidating the immunological and prognostic significance of HLA-DR expression on breast carcinoma cells have yielded contradictory results. To expand on previous studies, we have investigated the associations of tumor cell expression of HLA-DR and its related co-chaperones, invariant chain (Ii) and HLA-DM, with infiltrating inflammatory cells, in situ cytokine mRNA levels and prognosis and outcome in 112 breast carcinoma patients with a median follow-up of 59 months. While the majority of HLA-DR+ tumors co-express Ii, only a minority express HLA-DM. Tumor cell expression of HLA-DR and co-chaperones positively associated with both infiltrating CD4+ and CD8+ T-cell subsets (P < 0.01). Expression of HLA-DR and Ii associated with decreased estrogen receptor alpha levels and younger age at diagnosis, suggesting a role for hormones in the control of HLA class II expression in breast carcinoma. Patients with DR+Ii+DM- tumors had markedly decreased recurrence-free and disease-specific survival as compared with patients with DR+Ii+DM+ tumors (P < 0.05) and HLA-DR/co-chaperone expression was an independent predictor of survival by multivariate Cox regression analysis, controlling for standard prognostic indicators. Tumors that co-express HLA-DR, Ii and HLA-DM have increased levels of IFN-gamma, IL-2 and IL-12 mRNA, suggesting improved survival of patients with DR+Ii+DM+ tumors may be attributable to Th1-dominated immunity. We conclude that expression of determinants of the immune response by tumor cells may influence breast tumor progression and patient outcome.

Low ethanol intake prevents salt-induced hypertension in WKY rats.

Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue aldehyde conjugates and hypertension in salt-induced hypertensive Wistar-Kyoto (WKY) rats. This study investigated the antihypertensive effect of chronic low alcohol consumption in high salt-treated WKY rats and its effect on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i, and renal vascular changes. Animals, aged 7 weeks, were divided into three groups of six animals each. The control group was given normal salt diet (0.7% NaCl) and regular drinking water; the high salt group was given a high salt diet (8% NaCl) and regular drinking water; the high salt + ethanol group was given a high salt diet and 0.25% ethanol in drinking water. After 10 weeks, SBP, platelet [Ca2+]i, and tissue aldehyde conjugates were significantly higher in rats in the high salt group as compared with controls. Animals on high salt diets also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidney. Ethanol supplementation prevented the increase in SBP and platelet [Ca2+]i and aldehyde conjugates in liver and aorta. Kidney aldehyde conjugates and renal vascular changes were attenuated. These results suggest that chronic low ethanol intake prevents salt-induced hypertension and attenuates renal vascular changes in WKY rats by preventing an increase in tissue aldehyde conjugates and cytosolic [Ca2+]i.