Homocysteine stimulates monocyte chemoattractant protein-1 expression in mesangial cells via NF-kappaB activation.

Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disorders. Although renal dysfunction or failure is one of the important factors causing hyperhomocysteinemia, the role of homocysteine (Hcy) in the development of glomerulosclerosis is largely unknown. One of the key events in the pathogenesis of glomerulosclerosis is the infiltration of circulating monocytes into affected glomeruli. The objective of the present study was to investigate the effect of Hcy on the expression of monocyte chemoattractant protein-1 (MCP-1) in kidney mesangial cells and the mechanisms involved. Levels of MCP-1 and mRNA were significantly elevated in Hcy-treated rat mesangial cells. This increase was associated with activation of NF-kappaB as a result of increased phosphorylation of the inhibitor protein IkappaBalpha. Monocyte chemotactic activity in these cells was also enhanced. In addition, there was a significant elevation of superoxide anion produced by Hcy-treated cells, which preceded the increased phosphorylation of IkappaBalpha. Addition of superoxide dismutase or NF-kappaB inhibitors to the culture medium abolished Hcy-induced NF-kappaB activation and MCP-1 expression. Taken together, these results indicate that Hcy induced MCP-1 expression in mesangial cells. Such a process was mediated by oxidative stress and NF-kappaB activation. This may further aggravate renal function in patients with hyperhomocysteinemia.

Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat.

BACKGROUND: Whenever feasible, rhythm control of atrial fibrillation (AF) was generally preferred over rate control, in the belief that it offered better symptomatic relief and quality of life, and eliminated the need for anticoagulation. However, recent trials appear to challenge these assumptions. AIMS: To explore the desirability of rhythm vs. rate control of AF by systematic review of pertinent, published, randomized controlled trials (RCTs) and a meta-analysis by number needed to treat (NNT) year(-1), with respect to diverse clinically important outcomes. METHODS: RCTs of outcome primarily comparing rate vs. rhythm control in patients with spontaneous AF were identified. For each outcome and assuming rhythm control to be the active treatment, relative risk reduction (RRR) and NNT year(-1) were derived for individual trials together with an NNT year(-1) for all trials combined; corresponding 95% confidence intervals (CI) were also calculated. Adverse drug reaction (ADR) and quality of life reporting were also assessed. RESULTS: In all, data from five suitable RCTs (entailing 5239 patients) were analysed. For hospitalization, available RRRs and NNT year(-1) values were all clinically and statistically significant. Overall, one additional patient was hospitalized for every 35 assigned to rhythm control (95% CI 27, 48). For the endpoints of death, 'ischaemic' stroke and 'non-CNS' bleeding, there was no significant difference. ADRs were significantly more common in rhythm control patients, whereas quality of life assessments revealed no difference. Thromboembolism was associated with cessation of or subtherapeutic anticoagulation, irrespective of treatment assignment. CONCLUSION: Reduced risk of hospitalization and non-inferiority for other endpoints all favour rate control, the less costly strategy. If symptoms of AF are not a problem, treatment should target optimizing rate control and more widespread and effective prophylactic anticoagulation.

Screening for fever by remote-sensing infrared thermographic camera.

BACKGROUND: Following the severe acute respiratory syndrome (SARS) outbreak, remote-sensing infrared thermography (IRT) has been advocated as a possible means of screening for fever in travelers at airports and border crossings, but its applicability has not been established. We therefore set out to evaluate (1) the feasibility of IRT imaging to identify subjects with fever, and (2) the optimal instrumental configuration and validity for such testing. METHODS: Over a 20-day inclusive period, 176 subjects (49 hospital inpatients without SARS or suspected SARS, 99 health clinic attendees and 28 healthy volunteers) were recruited. Remotely sensed IRT readings were obtained from various parts of the front and side of the face (at distances of 1.5 and 0.5 m), and compared to concurrently determined body temperature measurements using conventional means (aural tympanic IRT and oral mercury thermometry). The resulting data were submitted to linear regression/correlation and sensitivity analyses. All recruits gave prior informed consent and our Faculty Institutional Review Board approved the protocol. RESULTS: Optimal correlations were found between conventionally measured body temperatures and IRT readings from (1) the front of the face at 1.5m with the mouth open (r=0.80), (2) the ear at 0.5 m (r=0.79), and (3) the side of the face at 1.5m (r=0.76). Average IRT readings from the forehead and elsewhere were 1 degrees C to 2 degrees C lower and correlated less well. Ear IRT readings at 0.5 m yielded the narrowest confidence intervals and could be used to predict conventional body temperature readings of < or = 38 degrees C with a sensitivity and specificity of 83% and 88% respectively. CONCLUSIONS: IRT readings from the side of the face, especially from the ear at 0.5 m, yielded the most reliable, precise and consistent estimates of conventionally determined body temperatures. Our results have important implications for walk-through IRT scanning/screening systems at airports and border crossings, particularly as the point prevalence of fever in such subjects would be very low.