Robust Image Population Based Stain Color Normalization: How Many Reference Slides Are Enough?

Histopathologic evaluation of Hematoxylin & Eosin (H&E) stained slides is essential for disease diagnosis, revealing tissue morphology, structure, and cellular composition. Variations in staining protocols and equipment result in images with color nonconformity. Although pathologists compensate for color variations, these disparities introduce inaccuracies in computational whole slide image (WSI) analysis, accentuating data domain shift and degrading generalization. Current state-of-the-art normalization methods employ a single WSI as reference, but selecting a single WSI representative of a complete WSI-cohort is infeasible, inadvertently introducing normalization bias. We seek the optimal number of slides to construct a more representative reference based on composite/aggregate of multiple H&E density histograms and stain-vectors, obtained from a randomly selected WSI population (WSI-Cohort-Subset). We utilized 1,864 IvyGAP WSIs as a WSI-cohort, and built 200 WSI-Cohort-Subsets varying in size (from 1 to 200 WSI-pairs) using randomly selected WSIs. The WSI-pairs' mean Wasserstein Distances and WSI-Cohort-Subsets' standard deviations were calculated. The Pareto Principle defined the optimal WSI-Cohort-Subset size. The WSI-cohort underwent structure-preserving color normalization using the optimal WSI-Cohort-Subset histogram and stain-vector aggregates. Numerous normalization permutations support WSI-Cohort-Subset aggregates as representative of a WSI-cohort through WSI-cohort CIELAB color space swift convergence, as a result of the law of large numbers and shown as a power law distribution. We show normalization at the optimal (Pareto Principle) WSI-Cohort-Subset size and corresponding CIELAB convergence: a) Quantitatively, using 500 WSI-cohorts; b) Quantitatively, using 8,100 WSI-regions; c) Qualitatively, using 30 cellular tumor normalization permutations. Aggregate-based stain normalization may contribute in increasing computational pathology robustness, reproducibility, and integrity.

A retrospective cohort study comparing a novel, spherical, resorbable particle against five established embolic agents for uterine fibroid embolisation.

AIM: To evaluate the effectiveness of a novel, resorbable, spherical embolic agent compared with other established agents, by studying percentage fibroid infarction (the best indicator of long-term symptom improvement) in patients undergoing uterine fibroid embolisation (UFE). MATERIALS AND METHODS: This retrospective cohort study examined six different embolic agents used for fibroid embolisation, including a new gelatin-based, fully resorbable, spherical agent. The primary effectiveness outcomes were magnetic resonance imaging (MRI)-determined dominant fibroid infarct percentage (DF%) and all fibroid percentage infarct (AF%) at 3 months post-embolisation. MRI-determined uterine artery patency rate was the secondary outcome. Chi-squared test (χ2), relative risk (RR) calculation (primary outcomes), and analysis of variance (ANOVA) (secondary outcome) were the statistical tests employed. RESULTS: One hundred and twenty patients were treated with six embolic agents (20 consecutive patients per group, overall mean age 44.8±6.4, initial uterine volume 570±472 ml, dominant fibroid volume 249±324 ml). Fibroid infarctrates were similar between the cohorts with no significant difference between the new gelatin-based resorbable particle and other embolics in either DF% (χ2=3.92, p=0.56) or AF% (χ2=2.83, p=0.73). Complete DF% RR=1.07 (0.90-1.27) and AF% RR=1.09 (0.85-1.41) suggest non-inferiority of the resorbable particle (d=0.67, p<0.05). A favourable uterine artery patency rate was demonstrated for the resorbable particle compared with gelatin slurry (82.5% versus 27.5%, p<0.001 after Bonferroni adjustment). CONCLUSIONS: This new gelatin-based, fully resorbable particle is an effective embolic agent for fibroid embolisation and achieves an infarct rate non-inferior to established embolics.

Factors Predicting a Good Symptomatic Outcome After Prostate Artery Embolisation (PAE).

INTRODUCTION: As prostate artery embolisation (PAE) becomes an established treatment for benign prostatic obstruction, factors predicting good symptomatic outcome remain unclear. Pre-embolisation prostate size as a predictor is controversial with a handful of papers coming to conflicting conclusions. We aimed to investigate if an association existed in our patient cohort between prostate size and clinical benefit, in addition to evaluating percentage volume reduction as a predictor of symptomatic outcome following PAE. MATERIALS OR METHODS: Prospective follow-up of 86 PAE patients at a single institution between June 2012 and January 2016 was conducted (mean age 64.9 years, range 54-80 years). Multiple linear regression analysis was performed to assess strength of association between clinical improvement (change in IPSS) and other variables, of any statistical correlation, through Pearson's bivariate analysis. RESULTS: No major procedural complications were identified and clinical success was achieved in 72.1% (n = 62) at 12 months. Initial prostate size and percentage reduction were found to have a significant association with clinical improvement. Multiple linear regression analysis (r2 = 0.48) demonstrated that percentage volume reduction at 3 months (r = 0.68, p < 0.001) had the strongest correlation with good symptomatic improvement at 12 months after adjusting for confounding factors. CONCLUSION: Both the initial prostate size and percentage volume reduction at 3 months predict good symptomatic outcome at 12 months. These findings therefore aid patient selection and counselling to achieve optimal outcomes for men undergoing prostate artery embolisation.

Improving trauma imaging in Wales through Kotter's theory of change.

AIM: To improve the practice of trauma computed tomography (CT) within Wales using recognised leadership techniques for change. MATERIALS AND METHODS: Royal College of Radiologists' (RCR) guidance, in addition to other key recent evidence, were used to form an aspirational standard. All centres across Wales with a major emergency department were included. Kotter's theory of change was utilised to facilitate an improvement in practice across the region, with larger units prioritised initially. RESULTS: Of the 13 major emergency units in Wales, eight centres had no formal trauma CT protocol. Only one centre utilised the Bastion protocol (in comparison to 75% of major trauma centres). After the campaign to improve trauma imaging, seven centres now offer the Bastion protocol, with currently only three peripheral centres still without a procedure for whole-body CT. The two largest centres have implemented an emergency department pro forma. CONCLUSION: Trauma CT within Wales has significantly improved as a result of this project. Kotter's theory is demonstrated as an effective tool for facilitating a change in practice on a regional/national scale.

Is the follow-up of small renal angiomyolipomas a necessary precaution?

AIM: To investigate the natural history and rationalize follow-up of renal angiomyolipomas (AMLs). MATERIALS AND METHODS: A prospectively gathered radiology database was scrutinized to identify patients with renal AMLs over a 3 year period (January 2006 to December 2008). Radiological investigations were examined to identify those AMLs exhibiting change during surveillance. RESULTS: A total of 135 patients were identified. Mean age at first detection was 49.6 years and patients were followed up for a median 21.8 months (6-85.3 months). Small AMLs (≤20 mm) were less likely to grow than their larger counterparts [odds ratio 13.3, confidence interval (95% CI) 1.4-123.9, p = 0.02] and exhibited a slower growth rate (0.7 versus 9.2 mm/year). Patients with AMLs that increased in size were significantly younger (median age 43 versus 52 years, p < 0.001). Multiple AMLs or those associated with genetic conditions grew at a significantly greater rate (3 versus 0.1 mm/year, p < 0.001). AMLs with a large extra-renal component are less reliably measured on ultrasound (median error 7 versus 1 mm, p < 0.001). CONCLUSION: This is the first study with the primary purpose to investigate growth of small AMLs (≤20 mm). Small, solitary AMLs (≤20 mm) do not require follow-up due to their low probability of growth. Patients with multiple AMLs and younger patients require closer monitoring due to their comparatively greater AML growth rate. Ultrasound-detected AMLs with an extra-renal component may require computed tomography (CT) to confirm their size.

Postharvest Disease Development on Southern Highbush Blueberry Fruit in Relation to Berry Flesh Type and Harvest Method.

Postharvest decay, incited by various fungal pathogens, is a major concern in most blueberry production areas of the United States. Because the risk of infection is increased by fruit bruising, which in turn is increased by machine-harvesting, it has been difficult to harvest fruit from the early-maturing but soft-textured southern highbush blueberries (SHB) mechanically for the fresh market. This could change fundamentally with the recent development of SHB genotypes with crisp-textured ("crispy") berries, i.e., fruit with qualitatively firmer flesh and/or more resistant skin. Four replicate row sections of two or three SHB genotypes having crispy fruit and three with conventional fruit were either hand- or machine-harvested at a commercial blueberry farm in northern Florida in April 2009 and May 2010. Harvested fruit were sorted, packed, and placed in cold storage (2°C) for up to 3 weeks. Average counts of aerobic bacteria, total yeasts and molds, coliforms, and Escherichia coli on fruit samples before the cold storage period were below commercial tolerance levels in most cases. In both years, natural disease incidence after cold storage was lowest for hand-harvested crispy fruit and highest for machine-harvested conventional fruit. Interestingly, machine-harvested crispy fruit had the same or lower disease incidence as hand-harvested conventional fruit. Across all treatments, natural postharvest disease incidence was inversely related to fruit firmness, with firmness values >220 g/mm associated with low disease. In separate experiments, samples from the 0-day cold storage period were inoculated at the stem end with Alternaria alternata, Botrytis cinerea, or Colletotrichum acutatum, and disease incidence was assessed after 7 days in a cold room followed by 60 to 72 h at room temperature. In response to artificial inoculation, less disease developed on crispy berries. No significant effect of harvest method was observed, except for A. alternata inoculation in 2009, when hand-harvested fruit developed a lower level of disease than machine-harvested fruit. Taken together, this study suggests that mechanical harvesting of SHB cultivars with crisp-textured berries is feasible from a postharvest pathology perspective.

Therapeutic hypothermia for out-of-hospital cardiac arrest: An analysis comparing cooled and not cooled groups at a Canadian center.

BACKGROUND: Out of hospital cardiac arrest is a devastating event and is associated with poor outcomes; however, therapeutic hypothermia (TH) is a novel treatment which may improve neurological outcome and decrease mortality. Despite this, TH is not uniformly implemented across Coronary Care and Intensive Care Units in Canada. OBJECTIVE: The purpose of this study was to compare cerebral recovery and mortality rates between patients in our Coronary Care Unit who received TH with a historical control group. MATERIALS AND METHODS: A retrospective chart review was performed of patients admitted to a tertiary care center with out-of-hospital cardiac arrest. Twenty patients who were admitted and cooled after December 2006 were compared with 29 noncooled patients admitted in the 5 years prior as a historical control group. The primary outcomes of interest were in-hospital mortality and neurological outcome. RESULTS: Eleven of 20 (11/20, 55%) patients who were cooled as per protocol survived to hospital discharge, all having a good neurological outcome. Eleven of 29 (11/29, 38%) noncooled patients survived to hospital discharge (Odds Ratio: 0.50, 95% CI: 0.16- 1.60, P=0.26). Eleven of 20 patients who were cooled had a good neurological outcome (CPS I-II, 11/20, 55%), versus 7 of 29 (7/29, 24%) of noncooled patients (Odds ratio: 3.84, 95% CI: 1.13- 13.1, P=0.03). One hundred percent (11/11) of survivors in the cooled group had a good neurological outcome. CONCLUSION: In our center, the use of TH in out-of-hospital cardiac arrest survivors was associated with improved neurological outcome.

Colobronchial fistula presenting with persistent pneumonia in a patient with Crohn's disease: a case report.

Colobronchial fistula is an uncommon complication of Crohn's Disease. It is also rarely diagnosed on first presentation. We describe a case of colobronchial fistula and recurrent pneumonia in a patient with Crohn's Disease.A 52-year-old gentleman with a history of Crohn's Disease presented with cavitating left lower lobe pneumonia that did not resolve despite a one month course of antibiotics. A computed tomography of the thorax confirmed the presence of a cavitating left lower lobe pneumonia. A subsequent abdominal computed tomography revealed a fistulous communication between the colon at the splenic flexure and the left bronchial space. The patient underwent surgery and a fibrous tract was visualized from the splenic flexure to the left lung. Medical treatment was continued with a six week course of antibiotics and the patient was doing well 12 weeks after surgery.There have been few case reports of colobronchial fistula with a clinical picture similar to this case.

Transmission of syphilis by solid organ transplantation.

Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.

Oxidative stress and nitric oxide synthase in skeletal muscles of rats with post-infarction, compensated chronic heart failure.

AIM: Involvement of oxidative stress and nitric oxide synthase (NOS) isoforms in skeletal muscle cellular adaptations to chronic heart failure (CHF) is controversial, and possible muscle fibre-type heterogeneity in the oxidative stress and NOS responses to CHF have not been examined. Consequently, we hypothesized that the changes in determinants of elevated oxidative and nitrosylative stress associated with CHF would occur in skeletal muscle and would be similar in predominantly type I slow twitch muscle (soleus) and type II fast twitch muscle (plantaris) of rats. METHODS: The purpose of this study was to measure NOS isoforms (endothelial, inducible and neuronal NOS) and antioxidant enzymes (SOD-1, SOD-2, catalase) by protein immunoblot as well as markers of oxidative stress by biochemical assays in soleus and plantaris muscle sections of the rat hind limb. This was performed for control and post-infarction, compensated CHF rats. RESULTS: Twelve weeks after coronary artery ligation-induced moderate CHF, soleus exhibited decreased SOD-1, SOD-2 and eNOS, but increased iNOS and nNOS isoforms assessed by immunoblot. This was associated with elevated lipid and DNA oxidative damage assessed by biochemical assays. In contrast, plantaris muscle exhibited no changes in antioxidant enzymes or NOS isoforms, and had lower lipid and DNA oxidative damage. CONCLUSION: These observations suggest a heretofore unreported muscle fibre-type-specific response of oxidative stress and NOS isoforms to CHF is of importance in understanding the cellular mechanisms of skeletal muscle dysfunction in CHF.

Phase I clinical and pharmacological study of intraperitoneal cis-bis-neodecanoato( trans- R, R-1, 2-diaminocyclohexane)-platinum II entrapped in multilamellar liposome vesicles.

PURPOSE: To perform a phase I study of intraperitoneal cis-bis-neodecanoato ( trans- R, R-1, 2-diaminocyclohexane)-platinum II entrapped in multilamellar vesicles (L-NDDP) for peritoneal carcinomatosis or sarcomatosis. METHODS: Eligible patients had normal renal, hematologic, and liver functions. Laparoscopy was performed on the first two courses for evaluation, adhesiolysis, and chemotherapy administration. Afterwards, chemotherapy was administered through a peritoneal catheter. Up to six courses were allowed. Peritoneal imaging with technetium-labeled sulfur colloid was used to determine adequate distribution prior to each course. Volunteering patients underwent pharmacokinetics studies during the second course. RESULTS: Fifteen of 16 registered patients, seven women and eight men (median age 53 years (range 26-76) and median performance status of 1) were assessable. Diagnoses were: malignant mesothelioma (six patients), signet ring cell (three), colon adenocarcinoma, pseudomyxoma peritonei, gastrointestinal stromal tumor (two each), and ovarian carcinoma (one). Median number of courses was two (range, one to six) Dose-limiting toxicity symptoms were fatigue and abdominal pain. Hematologic toxicities were minimal. Peri-operative complications included one colonic perforation requiring primary closure, a peritoneal catheter malfunction, a port site hematoma, and an ascites leak requiring re-suture. Five patients survived at least 3 years. Pharmacokinetics studies indicated a rapid but low absorption of drug into the systemic circulation, with a prolonged retention of platinum in the plasma compartment. Peritoneal L-NDDP exposure was 17 to 49-times greater than in the plasma compartment. CONCLUSIONS: Peritoneal cavity exposure to L-NDDP is prolonged, and systemic absorption is limited, yielding a high peritoneal/plasmatic ratio. The recommended dose for phase II studies is 400 mg/m2 every 28 days.

Comparative analysis of nutrition data from national, household, and individual levels: results from a WHO-CINDI collaborative project in Canada, Finland, Poland, and Spain.

STUDY OBJECTIVE: This project determined to what extent data on diet and nutrition, which were collected in a non-uniform manner, could be harmonised and pooled for international and national comparison. DESIGN: Direct comparisons of dietary data between studies were made using food balance sheets (FBS), household budget surveys (HBS), and individual dietary data (IDS); comparisons were also made within countries. Differences in study design and methodological approaches were taken into consideration. Data from research projects from the following four World Health Organisation (WHO) Countrywide Integrated Noncommunicable Disease Intervention (CINDI) countries were included-Canada, Finland, Poland, and Spain. MAIN RESULTS: FBS overestimated food consumption and nutrient intake compared to IDS. Results between HBS and IDS were quite similar, except for fish, meat, pulses and vegetables, which were underestimated by HBS, and sugar and honey and cereals, which were overestimated. Percentages of energy from fat, carbohydrates and proteins were higher when estimated from FBS, HBS, and IDS respectively. CONCLUSIONS: Results suggest that estimations from these three sources of dietary data are difficult to compare because they are measuring different levels of dietary information. The understanding of their relations may be important in formulating and evaluating a nutrition policy.

Wireless capsule endoscopic detection of Meckel's diverticulum after nondiagnostic surgery.

A patient aged 26 was investigated for recurrent severe gastrointestinal bleeding. Over a 4-year period, he was transfused more than 400 units of blood. Multiple investigations included three negative Meckel's scans. A right hemicolectomy for supposed angiodysplasia failed to control his bleeding. Wireless capsule endoscopy demonstrated the presence of a Meckel's diverticulum. At a repeat laparotomy, the ulcerated Meckel's diverticulum was identified and resected. The patient had no further bleeding and had a normal haemoglobin level on repeat blood tests up to 12 months after surgical excision of the diverticulum.

Inheritance and mapping of 11 avirulence genes in Phytophthora sojae.

Two new crosses involving four races (races 7, 16, 17, and 25) of the soybean root and stem rot pathogen Phytophthora sojae were established (7/16 cross; 17/25 cross). An F2 population derived from each cross was used to determine the genetic basis of avirulence towards 11 different resistance genes in soybean. Avirulence was found to be dominant and determined by a single locus for Avr1b, 1d, 1k, 3b, 4, and 6, as expected for a simple gene-for-gene model. We also observed several cases of segregation, inconsistent with a single dominant gene being solely responsible for avirulence, which suggests that the genetic background of the different crosses can affect avirulence. Avr4 and 6 cosegregated in both the 7/16 and 17/25 crosses and, in the 7/16 cross, Avr1b and 1k were closely linked. Information from segregating RAPD, RFLP, and AFLP markers screened on F2 progeny from the two new crosses and two crosses described previously (a total of 212 F2 individuals, 53 from each cross) were used to construct an integrated genetic linkage map of P. sojae. This revised genetic linkage map consists of 386 markers comprising 35 RFLP, 236 RAPD, and 105 AFLP markers, as well as 10 avirulence genes. The map is composed of 21 major linkage groups and seven minor linkage groups covering a total map distance of 1640.4cM.

Depressive symptoms predict medical care utilization in a population-based sample.

BACKGROUND: Several examinations have detected a relation between depressive symptoms and medical utilization. However, selection biases have been involved in most previous examinations. We sought to test the association between depressive symptoms and prospective, increased medical care utilization, in a population-based Canadian sample, while controlling for utilization due to medical illness and controlling for selection bias. METHODS: Data from the Nova Scotia Health Survey 1995, an age- and sex-stratified random sampling of 3227 Nova Scotian adults, included the Center for Epidemiological Studies-Depression scale and items assessing chronic medical conditions and current limitations in daily activities resulting from medical illness. We linked survey data with medical care utilization measures for the year following the survey, including out-patient visits, reimbursement for out-patient services, hospitalizations, and hospitalization days. RESULTS: After controlling for age, sex, count of medical diagnoses and current medical severity, those with a greater level of depressive symptoms were at greater risk of having increased medical care utilization in the following year. These results remained after removing mental health care utilization costs. CONCLUSIONS: In a population-based sample, depressive symptoms predicted greater medical care utilization, independent of a number of medical severity measures. Whether depressive symptoms are a risk marker or a causal risk factor for increased medical utilization remains to be explored.

The exercise metaboreflex is maintained in the absence of muscle acidosis: insights from muscle microdialysis in humans with McArdle's disease.

1. In McArdle's disease, muscle glycogenolysis is blocked, which results in absent lactate and enhanced ammonia production in working muscle. Using McArdle patients as an experimental model, we studied whether lactate and ammonia could be mediators of the exercise pressor reflex. 2. Changes in muscle interstitial ammonia and lactate were compared with changes in blood pressure and muscle sympathetic nerve activity (MSNA) during static arm flexor exercise at 30% of maximal contraction force. Muscle interstitial changes in lactate and ammonia were assessed by microdialysis of the biceps muscle, and MSNA by peroneal nerve microneurography, in six McArdle patients and 11 healthy, matched controls. One McArdle patient also had myoadenylate deaminase deficiency, a condition associated with abolished ammonia production in exercise. 3. Exercise-induced increases were higher in McArdle patients vs. controls for MSNA (change of 164 +/- 71 vs. 59 +/- 19%) and blood pressure (change of 47 +/- 7 vs. 38 +/- 4 mmHg). Interstitial lactate increased in controls (peak change 1.3 +/- 0.2 mmol x l(-1)) and decreased in McArdle patients (peak change -0.5 +/- 0.1 mmol x l(-1)) during and after exercise. Interstitial ammonia did not change during exercise in either group, but was higher post-exercise in McArdle patients, except in the patient with myoadenylate deaminase deficiency who had a flat ammonia response. This patient had an increase in MSNA and blood pressure comparable to other patients. MSNA and blood pressure responses were maintained during post-exercise ischaemia in both groups, indicating that sympathetic activation was caused, at least partly, by a metaboreflex. 4. In conclusion, changes in muscle interstitial lactate and ammonia concentrations during and after exercise are temporally dissociated from changes in MSNA and blood pressure in both patients with McArdle's disease and healthy control subjects. This suggests that muscle acidification and changes in interstitial ammonia concentration are not mediators of sympathetic activation during exercise.

Distribution of blood pressure and hypertension in Canada and the United States.

BACKGROUND: Two North American population based surveys, the Third National Health and Nutrition Examination Survey (NHANES III) and the Canadian Heart Health Surveys (CHHS) have similar time frames and methods that allow comparisons between these countries in terms of the distribution of systolic (SBP) and diastolic (DBP) blood pressure and the levels of hypertension awareness, treatment, and control. METHODS: Cross-sectional population surveys using similar methods conducted home interviews and clinic visits (CHHS), and medical examinations (NHANES III). The CHHS included the ten Canadian provinces (1986-1992) and NHANES III, a representative sample of the United States population (1988-1994). Blood pressure measurements were available for 23,111 Canadians (age 18-74 years), and restricted to the 15,326 US participants in the same age range (age 18-74 years) with both systolic and diastolic mean values. Standardized techniques were used for BP measurements. Mean of all available measurements was used from four measurements for the CHHS and six measurements for NHANES III. A mean SBP/DBP of 140/90 mm Hg or treated with medication defined hypertension. All measures were weighted to represent population values. RESULTS: Both surveys showed similar trends in mean BP by age, with slightly higher levels in the CHHS. Hypertension prevalence using the same definitions and the same age range (18-74 years) was NHANES III: 20.1%, CHHS: 21.1%. Although the prevalence of isolated systolic hypertension (ISH) was similar in both studies, around 8% to 9%, the CHHS had higher ISH prevalence than NHANES III in the younger age groups and lower prevalence in the older age groups. Elevated SBP dominated the prevalence figures after the 1950s in both studies. Compared to NHANES III, the CHHS showed a lower proportion (43% v 50%) of individuals with optimal BP (< 120/80 mm Hg) and a very low proportion of hypertensives under control (13% v 25%). About half of diabetic participants were hypertensive (using 140/90 mm Hg) in both countries with a very low level of control in Canada (9%) v the US (36%) for ages 18 to 74 years. CONCLUSIONS: The results of these two surveys highlight the importance of SBP, in the later decades of life, an overall low control of hypertension in both countries, and a better overall awareness, treatment, and control of hypertension in the US than in Canada for that period. Dissemination of hypertension guidelines and a more aggressive focus on SBP are urgently needed in Canada, with special attention to diabetics.

Capacity building for health promotion and chronic disease prevention--Nova Scotia's experience.

The purpose of this paper is to report on the capacity building efforts that took place during the dissemination research phase of Heart Health Nova Scotia (HHNS). HHNS, a health promotion research team, is funded by Health Canada and the Nova Scotia Department of Health. It is located in Halifax, Nova Scotia, a province of 937,000 people situated on the east coast of Canada. It has been a member of the Canadian Heart Health Initiative since its inception in 1989. The first phase of the program, Demonstration, was successfully completed in December 1995 (Heart Health Nova Scotia, 1995). In 1996, HHNS entered its second phase, Dissemination Research, which was conducted between April 1996 and March 2001 in the Western Health Region of Nova Scotia. This was completed in collaboration with organizations, community groups, and government agencies who joined HHNS to form the Heart Health Partnership (HHP) (Heart Health Nova Scotia, 2001). The main aim of this phase of the initiative was to build and research organizational capacity for health promotion and chronic disease prevention.

Differential effects of E and droloxifene on C-reactive protein and other markers of inflammation in healthy postmenopausal women.

Although increased levels of C-reactive protein have been linked to E therapy, the significance of this finding and whether it occurs with the selective ER modulators are unknown. Thirty-five healthy postmenopausal women were enrolled in a placebo-controlled, two-period cross-over design trial to evaluate the effects of 0.625 mg oral conjugated E and 60 mg droloxifene, a structural analog of tamoxifen, on serum levels of C-reactive protein, IL-6, and endothelial cell adhesion molecules. E treatment resulted in 65.8% higher levels of C-reactive protein (P = 0.0002) and 48.1% higher levels of IL-6 (P < 0.001), but also resulted in a 10.9% reduction in soluble E-selectin (P = 0.002) and borderline reductions in vascular cell adhesion molecule-1. In contrast, droloxifene had no effect on C-reactive protein and IL-6, but did produce a significant 11% reduction in E-selectin (P < 0.00001). However, droloxifene also resulted in an 11.6% increase in vascular cell adhesion molecule-1 (P < 0.007). These data provide additional evidence of a proinflammatory effect of E that may have adverse cardiovascular consequences. However, these changes were also accompanied by a reduction in E-selectin, suggesting an antiinflammatory effect at the level of the endothelium. The net clinical impact of these changes is not yet well established. In contrast, droloxifene had little or no proinflammatory effects on C-reactive protein and IL-6 and had mixed effects on endothelial adhesion molecules. This observation provides additional rationale for continuing to evaluate the potential cardiovascular benefits of selective ER modulators.