Particulate air pollution, social confounders, and mortality in small areas of an industrial city

Scientists and policymakers have shown growing interest in the health effects of chronic air pollution exposure. In this study, we use geostatistical techniques in combination with small-area data to address a central research question: "Does chronic exposure to particulate air pollution significantly associate with mortality when the effects of other social, demographic, and lifestyle confounders are taken into account?" Our analysis relies on age-standardized mortality ratios for census tracts (CTs) of Hamilton (average population of 3419 persons), social and demographic data from the 1991 Census of Canada, smoking variables extracted from secondary surveys, and total suspended particulate (TSP) data from 23 monitoring stations operated by the Ministry of the Environment. Air pollution data are interpolated with a geostatistical procedure known as "kriging". This method translates fixed-site pollution monitoring observations into a continuous surface, which was overlaid onto the population-weighted centroids of the CTs. Our results show substantively large and statistically significant health effects for women and men. Evaluated over the inter-quartile range of the data, we found the relative risk of premature mortality for TSP exposure to be 1.19 (95% CI: 1.13-1.26) for women and 1.30 (95% CI: 1.24-1.37) for men. We also tested associations with cardio-respiratory and cancer mortality. We found positive, significant associations between particulate exposure and these causes of death in most models. Inclusion of socioeconomic, demographic, and lifestyle reduced but did not eliminate the health effects of exposure to particulate air pollution. Overall our results suggest that intra-urban variations in particulate air pollution significantly associate with premature, all-cause, cardio-respiratory, and cancer mortality in small areas of Hamilton.     

Fulminant hepatic failure from primary hepatic lymphoma: successful treatment with orthotopic liver transplantation and chemotherapy

Systemic lymphomas may involve the liver but rarely cause fulminant hepatic failure (FHF). Acute liver failure from primary hepatic lymphoma (PHL) is even less common with most patients succumbing to the sequelae of FHF before the correct diagnosis is made. We report a patient who underwent successful orthotopic liver transplant (OLT) and chemotherapy for FHF secondary to PHL. This previously-well male developed profound coagulopathy and encephalopathy 6 weeks after the onset of jaundice and fatigue. Workup failed to reveal the underlying cause of his liver failure and the patient soon required urgent OLT. Pathologic evaluation of his explanted liver revealed a malignant T-cell rich, large B-cell non-Hodgkin's lymphoma with widespread hepatocellular necrosis. The patient made an excellent clinical recovery and is undergoing CHOP-Rituxan chemotherapy. This scenario demonstrates that lymphoma should be considered in the differential diagnosis of FHF without clear etiology because of the potential for intervention with transplant and chemotherapy.     

Time from dosing to sexual intercourse attempts in men taking tadalafil in clinical trials

OBJECTIVE: To determine whether patients with erectile dysfunction (ED) and treated with tadalafil use the 36-h duration of effect of the drug, and to discern if the timing of intercourse attempts is influenced by patient age, baseline severity of ED, or previous experience with sildenafil citrate. PATIENTS AND METHODS: In 11 multicentre, double-blind, placebo-controlled studies, 2102 patients with ED were randomized to a maximum of one dose per day of tadalafil 10 or 20 mg (1464 men), or placebo (638 men) with no time restrictions before attempting sexual activity after the dose. A post hoc analysis was used to determine the proportion of men with ED who attempted sexual intercourse during various intervals (>0 to < or = 1, >1 to < or = 4, and >4 to < or = 36, including >12 to < or = 36 h) after dosing with tadalafil or placebo over a 12-week period. Patients were stratified by age, baseline severity of ED, and previous history of sildenafil use. RESULTS: Of patients in different age groups and various ED severity, > or = 79% and > or = 53% chose to attempt sexual intercourse at least once during the 12-week treatment period at 4-36 and 12-36 h, respectively, after taking tadalafil. Regardless of previous experience with sildenafil, about a third of patients using tadalafil attempted intercourse a mean of at least once per week at 4-36 h after the dose over 12 weeks. Furthermore, 58% of patients attempted intercourse at least once during two intervals (>1 to < or = 4 h and >12 to < or = 36 h) after separate doses of tadalafil. CONCLUSION: Regardless of age, ED severity, or previous experience with sildenafil, most patients attempted sexual intercourse at least once at 12-36 h after one dose of tadalafil over a 12-week treatment period. Furthermore, by engaging in sexual intercourse at both earlier and later intervals after separate doses, most patients on treatment did not adhere to a fixed schedule of intimacy and thus took advantage of the 36-h duration.     

Mycotic Common Iliac Artery Aneurysm Complicating Methicillin-Resistant Staphylococcus aureus Bacteremia: An Unusual Cause of Ureteric Obstruction

A 60-year-old man presented with ureteric obstruction secondary to a mycotic right common iliac artery aneurysm complicating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The diagnosis of MRSA was not known at the time of surgery, and in situ replacement of the aneurysm using a rifampicin-bonded prosthesis was performed. The patient made a full recovery, and to date there is no evidence of residual or recurrent infection. To our knowledge, this is the first reported case of mycotic iliac aneurysm infected with MRSA in the literature. We discuss the consequences and the considerable diagnostic and therapeutic problems that arise. Presented at the Fifty-third International Congress of the European Society for Cardiovascular Surgery, Ljubljana, Slovenia, June 2-5, 2004.     

Reliability of traditional and fractal dimension measures of quiet stance center of pressure in young, healthy people

OBJECTIVES: To assess reliability of traditional and fractal dimension measures of quiet stance center of pressure (COP). DESIGN: Cross-sectional study. SETTING: University laboratory. PARTICIPANTS: Thirty young healthy men (n=20) and women (n=10) (mean age, 23 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: COP was recorded for 3 trials across 4 conditions: eyes open and eyes closed standing on firm and foam surfaces. Traditional COP variables--peak sway velocity and range of sway, both in the anteroposterior (AP) and mediolateral (ML) directions, and total excursion area, and fractal dimension of the COP in the AP and ML directions--were calculated. Reliability statistics were calculated. RESULTS: Range of sway (AP) was the most reliable traditional variable (intraclass correlation coefficient model 2,1 [ICC(2,1)] range -.28 to .72.). Peak sway velocity (AP) had poorest reliability (ICC(2,1) range, .05-.29). Only 1 of the traditional variables had excellent reliability; total excursion area (firm, eyes closed) (ICC(2,1)=.95). All bar 1 fractal dimension measures had excellent ICCs. Relative technical error of measurement ranged from 4% to 7% for the fractal dimension measures. Coefficients of variation were also very good, ranging from 1.8% to 6.7%. CONCLUSIONS: Fractal dimension measures were more reliable than traditional measures of COP. Although traditional measures are used extensively to assess COP, their reliability is questionable. Fractal dimension measures show promise to reliably quantify COP and warrant further investigation.     

B-type natriuretic peptide as a biomarker beyond heart failure: speculations and opportunities

Cardiac secretion of B-type natriuretic peptide (BNP) Increases with the progression of heart failure (HF), and plasma measurement of BNP has emerged recently as a useful, cost-effective biomarker for the diagnosis and prognosis of HF. The diagnostic utility of BNP is complemented by its therapeutic use in decompensated HF. Although clinical use of BNP as a biomarker in HF is Increasing, the specificity of BNP for HF is not robust, suggesting that other mechanisms beyond simple ventricular stretch stimulate BNP release. Several studies have shown that BNP levels Increase in other cardiovascular disease states including ischemia, arrhythmias, fibrosis, cardiac hypertrophy, and coronary endothelial dysfunction. Furthermore, 2 important studies revealed recently that moderate elevations In BNP level, well below the HF range, have prognostic value for future cardiovascular events. Specifically, BNP levels greater than 20 pg/mL were associated with significantly Increased risk of HF and atrial fibrillation. These observations increase speculation that elevated BNP levels represent a final common pathway for many cardiovascular pathologic states and that BNP can be used as a biomarker for non-HF mechanisms, preclinical disease, and other pathologic states of myocardial disease.     

Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST)

BACKGROUND: Hospitalizations for worsening heart failure due to fluid overload (congestion) are common. Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed. Tolvaptan is an oral vasopressin (V 2 ) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia. The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care. METHODS AND RESULTS: Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion. Patients are randomized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days. Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the coprimary end points. Patient-assessed global clinical status and quality of life are also evaluated. EVEREST will be continued until 1065 deaths occur. As of April 18, 2005, 2260 patients have been enrolled. CONCLUSION: Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia. The results of EVEREST will determine whether these effects translate into improved clinical outcomes.