Perspectives on emerging zoonotic disease research and capacity building in Canada.

Zoonoses are fundamental determinants of community health. Preventing, identifying and managing these infections must be a central public health focus. Most current zoonoses research focuses on the interface of the pathogen and the clinically ill person, emphasizing microbial detection, mechanisms of pathogenicity and clinical intervention strategies, rather than examining the causes of emergence, persistence and spread of new zoonoses. There are gaps in the understanding of the animal determinants of emergence and the capacity to train highly qualified individuals; these are major obstacles to preventing new disease threats. The ability to predict the emergence of zoonoses and their resulting public health and societal impacts are hindered when insufficient effort is devoted to understanding zoonotic disease epidemiology, and when zoonoses are not examined in a manner that yields fundamental insight into their origin and spread.EMERGING INFECTIOUS DISEASE RESEARCH SHOULD REST ON FOUR PILLARS: enhanced communications across disciplinary and agency boundaries; the assessment and development of surveillance and disease detection tools; the examination of linkages between animal health determinants of human health outcomes; and finally, cross-disciplinary training and research. A national strategy to predict, prevent and manage emerging diseases must have a prominent and explicit role for veterinary and biological researchers. An integrated health approach would provide decision makers with a firmer foundation from which to build evidence-based disease prevention and control plans that involve complex human/animal/environmental systems, and would serve as the foundation to train and support the new cadre of individuals ultimately needed to maintain and apply research capacity in this area.     

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease

OBJECTIVE: Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects approximately 40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation-AAU-of a multisystem, inflammatory, genetically complex disease, AS. METHODS: Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. RESULTS: As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. CONCLUSION: This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.     

Physical and pH properties of gastroesophagopharyngeal refluxate: a 24-hour simultaneous ambulatory impedance and pH monitoring study

OBJECTIVES: Frequency occurrence of nonacidic and nonliquid reflux events in the pharynx has not been systematically studied. The aim of the present study was to characterize the physical (liquid, gas, and mixed gas/liquid) and pH properties of the gastroesophagopharyngeal refluxate. METHODS: We performed a total of 31 24-h simultaneous ambulatory pharyngoesophageal impedance and pH recordings in 11 GERD patients, 10 patients with reflux-attributed laryngitis, and 10 healthy controls. RESULTS: On average, the total number of reflux events (all kinds) in the pharynx was less than half of that in the proximal esophagus (18 +/- 4 vs 50 +/- 4, p < 0.01). Most of the pharyngeal reflux events were gas events and were observed in all three studied groups. Prevalence of these gas reflux events ranged between 0 and 74. The number of gas reflux events accompanied by a minor pH drop in laryngitis patients (1 (0-36)) was significantly higher than those in GERD and controls (0 (0-2) and 0 (0-1), respectively, p < 0.05). There was no significant difference in the number of nonacidic gas reflux events among the three groups (GERD: 10 (2-57), laryngitis: 11.5 (0-51), controls: 10.5 (0-27)). Impedance recording identified a total number of 566 events in the pharynx. Of these, a total of 563 events were compatible with gas reflux events, 101 events were accompanied by minor drops in intrapharyngeal pH, whereas 460 events were not accompanied by any pharyngeal pH change. CONCLUSIONS: Concurrent impedance and pH recordings detect significantly more events qualifying as reflux in the pharynx than pH recordings alone. A substantial majority of these events are gaseous refluxes both with and without minor pH drops. Gas reflux events with weak acidity appear to be more common among patients with reflux-attributed laryngeal lesions compared to GERD patients and controls.     

Positive troponin in diabetic ketoacidosis without evident acute coronary syndrome predicts adverse cardiac events

BACKGROUND: Elevated troponin I has been associated with increased mortality in critically ill patients without acute coronary syndrome (ACS). However, the prognostic significance of troponin elevation in patients with diabetic ketoacidosis (DKA) without evident ACS has not been studied. METHODS: Retrospective study of all patients admitted to a U.S. tertiary center between 01/98 and 12/00 with DKA and had troponin I level measured. Patients with evidence of ACS or who met the American College of Cardiology/European Society of Cardiology (ACC/ESC) definition for myocardial infarction were excluded. Baseline characteristics, cardiac evaluation and 2 year major adverse coronary event (MACE) rate were compared between patients with positive and negative troponin. RESULTS: Ninety-six patients fulfilled the inclusion criteria of this study, 26 had positive troponin. There were no differences in baseline characteristics between the two groups. After a 2 year follow-up, there was significantly increased mortality in patients with elevated troponin (50.0% versus 27.1%, hazard-ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.8, p = 0.02). Patients with elevated troponin also had significantly increased MACE rate at 2 years (50.0% versus 28.6%, HR 2.6, 95% CI 1.3-5.3, p = 0.007) driven primarily by mortality. Using Cox Proportional Hazard Analysis, elevated troponin was a predictor of increased MACE after adjusting for confounding variables. (Adjusted HR 2.3, 95% CI 1.1-4.6, p = 0.02) CONCLUSIONS: Elevated troponin I in diabetic patients admitted with DKA identifies a group at very high risk for future cardiac events and mortality. Whether cardiac risk stratification of these patients will improve long term outcome remains to be studied.     

Temporal analysis of acute myocardial infarction in Ontario, Canada

BACKGROUND: Acute myocardial infarction (AMI) is a substantial cause of morbidity and mortality in Canada. Evidence suggests that the incidence and mortality of AMI increase in the winter. Determining the strength and nature of seasonality patterns in relation to age and sex may be helpful in health care planning. OBJECTIVES: To examine the seasonal patterns of AMI hospital admissions by age and sex, to assess the strength of the seasonal patterns and to examine the overall trends in admissions. METHODS: A retrospective population-based study was conducted to assess temporal patterns in 14 years of hospital admissions for AMI (from April 1, 1988, to March 31, 2002) in Ontario. Seasonality was assessed using the autoregression coefficient (R2Autoreg), and Fisher's Kappa and Bartlett's Kolmogorov-Smirnov tests. RESULTS: There were 271,321 people in the cohort, of whom 63% (n = 171,546) were male and 37% (n = 99,775) were female. There was an increase in AMI admissions since 1988 that reached a plateau in 1992, which was attributable mostly to the increased rate in the oldest age groups (70 years and older), where admission rates more than doubled. An association between seasonality and AMI admissions was found in most age and sex groups, with men consistently exhibiting a stronger seasonality pattern. The greatest difference in the cohort, 2.5 per 100,000 per month (134 admissions), occurred between December and September (13.64 per 100,000 in September versus 16.14 per 100,000 in December). CONCLUSIONS: AMI admissions show seasonality patterns, which are more pronounced in men. Although statistically significant, the seasonal differences are small in terms of absolute numbers, and are likely irrelevant in health care planning.     

VE1 immunohistochemistry is an adjunct tool for detection of BRAF V600E mutation: Validation in thyroid cancer patients

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy among other endocrine tumors, and BRAF ^V600E is a frequent genetic mutation occurring in the disease. Although different molecular techniques, most importantly sequencing has been widely recognized as a gold standard but molecular diagnosis remains an expensive, laborious, and time‐intensive process. Recently, immunohistochemistry (IHC) with anti‐BRAF V600E (VE1) antibody has increased practical utility and implemented clinically for the detection of BRAF ^V600E mutation. Therefore, the study aimed to evaluate diagnostic accuracy of VE1 IHC for detecting the BRAF ^V600E mutation frequency and clinical implementation in diagnostic laboratories. In this study, 72 formalin fixed paraffin‐embedded tissues (FFPE) were used to determine the BRAF ^V600E mutation status using IHC and Sanger sequencing. The mutation was found in 29% and 28% cases using IHC and Sanger sequencing, respectively. Furthermore, the results showed 100% sensitivity, 98.07% specificity, 95.2% positive predictive value, and 100% negative predictive value. Notably, significant associations were found between BRAF ^V600E status and tumor stage, tumor focality, and extrathyroidal extensions, respectively. VE1 IHC was found to be a highly sensitive, specific, and diagnostically accurate method in this cohort. Therefore, BRAF ^V600E detection through IHC has been considered as the best tailored technique for routine pathology laboratories.