The Relationship Between Homocysteine and Genes of Folate-Related Enzymes in Migraine Patients

(Headache 2010;50:99‐168) Background.— It has been suggested that homocysteine (Hcy) and the 5′‐10′‐methylenetetrahydrofolate reductase (MTHFR) C677T variant are implicated in the pathogenesis of migraine. Homocysteine has the potential to damage endothelium and accelerate atherosclerosis. Genetic factors such as the MTHFR C677T polymorphism, and other polymorphisms in folate‐related genes associated with high homocysteine levels, may contribute to increasing this vascular risk. Results.— We recruited 427 migraine patients (199 without aura [MO]; 228 with aura [MA]), and 310 controls in a neurologic clinic. Hcy levels and 6 polymorphisms corresponding to 6 folate‐related genes, including the MTHFR C677T variant, were determined in all migraine participants and in a subset of 155 controls. We found higher sex‐adjusted Hcy levels in MA (mean: 11.02 µM) than MO patients (9.86 µM; P = .005 for the difference). Hcy levels higher than 12.0 µM doubled the risk for MA (OR = 2.145; 95% confidence intervals [CI] = 1.3‐3.4; P = .001), and those higher than 15.0 µM incurred a 6‐fold increase (OR = 5.95; 95% CI = 2.1‐20.0, P < .001). The number of MTHFR 677T alleles was the best genetic predictor of Hcy levels (r² = 0.06; P = 6.2e‐6; corrected for genetic variants analyzed) and this effect remained significant after correction for other confounding factors. Using multi‐dimensionality reduction approaches, we observed significant epigenetic interaction among some of the folate‐related genetic variants to predict higher Hcy levels, and also among higher Hcy levels and folate‐related genetic variants to predict the end‐diagnosis of MA only among migraineurs. In controls, Hcy levels and the number of MTHFR 677T alleles were found to be intermediate between those observed in MA and MO patients. Conclusion.— Our results suggest that MA patients have higher Hcy levels. We also observed complex epigenetic interaction among folate‐related enzymes, sex, and Hcy levels predicting MA phenotype. Nevertheless, genetic factors explained only a minor proportion of the variance for both Hcy plasma levels and for predicting MA phenotype. Determination of MTHFR C677T polymorphisms and Hcy levels may be useful to identify patients with a high risk of suffering from MA.     

Severe acute respiratory syndrome: quantitative assessment from chest radiographs with clinical and prognostic correlation

OBJECTIVE: This study examined findings of severe acute respiratory syndrome (SARS) on chest radiographs and presented a classification scheme using quantitative radiographic data supported by clinical parameters. MATERIALS AND METHODS: Three radiologists who were blinded to the identity, diagnosis, treatment protocol, and outcome of each patient independently evaluated serial chest radiographs from 67 patients with confirmed SARS. In addition to the chest radiographic abnormalities and percentage of involvement, several quantitative improvement parameters, including the peak to 50% improvement time (PIT(50)), were collected. Correlation between PIT(50) and clinical parameters (duration of fever, cough, dyspnea, oxygen supplementation, intubation, and death) were evaluated using Wilcoxon's rank sum testing and Spearman's correlation. RESULTS: The most common initial findings were unifocal air-space disease in the periphery of the lower lungs occurring a mean of 3.6 +/-2.4 (SD) days from symptoms onset. Peak abnormalities were seen at 10.4 +/- 2.9 days. PIT(50) was dependent on disease severity, showing a strong linear correlation with the clinical parameter duration of oxygen supplementation (r = 0.44, p = 0.0015). Three patterns of disease were recognized: pattern A (severe, 29.9%) with PIT(50) of more than 10 days, pattern B (typical, 44.8%) with PIT(50) of 10 or fewer days, and pattern C (mild, 25.4%) with minimal findings throughout the course of the disease. This classification was supported by collaborative clinical parameters. CONCLUSION: The quantitative radiographic parameter PIT(50) has strong clinical correlation and can be used to differentiate severity of disease into severe, typical, and mild types.     

Hospital preparedness and SARS

On May 23, 2003, Toronto experienced the second phase of a severe acute respiratory syndrome (SARS) outbreak. Ninety cases were confirmed, and >620 potential cases were managed. More than 9,000 persons had contact with confirmed or potential case-patients; many required quarantine. The main hospital involved during the second outbreak was North York General Hospital. We review this hospital's response to, and management of, this outbreak, including such factors as building preparation and engineering, personnel, departmental workload, policies and documentation, infection control, personal protective equipment, training and education, public health, management and administration, follow-up of SARS patients, and psychological and psychosocial management and research. We also make recommendations for other institutions to prepare for future outbreaks, regardless of their origin.     

Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area

Context  Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in China in November 2002 and has subsequently spread worldwide. Objectives  To describe the clinical characteristics and short-term outcomes of SARS in the first large group of patients in North America; to describe how these patients were treated and the variables associated with poor outcome. Design, Setting, and Patients  Retrospective case series involving 144 adult patients admitted to 10 academic and community hospitals in the greater Toronto, Ontario, area between March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS. Patients were included if they had fever, a known exposure to SARS, and respiratory symptoms or infiltrates observed on chest radiograph. Patients were excluded if an alternative diagnosis was determined. Main Outcome Measures  Location of exposure to SARS; features of the history, physical examination, and laboratory tests at admission to the hospital; and 21-day outcomes such as death or intensive care unit (ICU) admission with or without mechanical ventilation. Results  Of the 144 patients, 111 (77%) were exposed to SARS in the hospital setting. Features of the clinical examination most commonly found in these patients at admission were self-reported fever (99%), documented elevated temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%). Common laboratory features included elevated lactate dehydrogenase (87%), hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea. A total of 126 patients (88%) were treated with ribavirin, although its use was associated with significant toxicity, including hemolysis (in 76%) and decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were admitted to the ICU with or without mechanical ventilation, and 8 patients died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95% CI, 1.4-7.2; P = .01) or other comorbid conditions (RR, 2.5; 95% CI, 1.1-5.8; P = .03) were independently associated with poor outcome (death, ICU admission, or mechanical ventilation). Conclusions  The majority of cases in the SARS outbreak in the greater Toronto area were related to hospital exposure. In the event that contact history becomes unreliable, several features of the clinical presentation will be useful in raising the suspicion of SARS. Although SARS is associated with significant morbidity and mortality, especially in patients with diabetes or other comorbid conditions, the vast majority (93.5%) of patients in our cohort survived.      

Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging

To enable a more quantitative diagnosis of senile dementia of the Alzheimer type (SDAT), the authors developed and tested a semiautomated method to define regions of interest (ROIs) to be used in quantitating results from single photon emission computed tomography (SPECT) of regional cerebral blood flow performed with N-isopropyl iodine-123-iodoamphetamine. SPECT/IMP imaging was performed in ten patients with probable SDAT and seven healthy subjects. Multiple ROIs were manually and semiautomatically generated, and uptake was quantitated for each ROI. Mean cortical activity was estimated as the average of the mean activity in 24 semiautomatically generated ROIs; mean cerebellar activity was determined from the mean activity in separate ROIs. A ratio of parietal to cerebellar activity less than 0.60 and a ratio of parietal to mean cortical activity less than 0.90 allowed correct categorization of nine of ten and eight of ten patients, respectively, with SDAT and all control subjects. The degree of diminished mental status observed in patients with SDAT correlated with both global and regional changes in IMP uptake.