Prevention of collagen-induced arthritis by gene delivery of soluble p75 tumour necrosis factor receptor.
Collagen type II-induced arthritis (CIA) in DBA/1 mice can be passively transferred to SCID mice with spleen B- and T-lymphocytes. In the present study, we show that infection ex vivo of splenocytes from arthritic DBA/1 mice with a retroviral vector, containing cDNA for the soluble form of human p75 receptor of tumour necrosis factor (TNF-R) before transfer, prevents the development of arthritis, bone erosion and joint inflammation in the SCID recipients. Assessment of IgG subclass levels and studies of synovial histology suggest that down-regulating the effector functions of T helper-type 1 (Th1) cells may, at least in part, explain the inhibition of arthritis in the SCID recipients. In contrast, the transfer of splenocytes infected with mouse TNF-alpha gene construct resulted in exacerbated arthritis and enhancement of IgG2a antibody levels. Intriguingly, infection of splenocytes from arthritic DBA/1 mice with a construct for mouse IL-10 had no modulating effect on the transfer of arthritis. The data suggest that manipulation of the immune system with cytokines, or cytokine inhibitors using gene transfer protocols can be an effective approach to ameliorate arthritis. (+info)
Heart rate and subsequent blood pressure in young adults: the CARDIA study.
The objective of the present study was to examine the hypothesis that baseline heart rate (HR) predicts subsequent blood pressure (BP) independently of baseline BP. In the multicenter longitudinal Coronary Artery Risk Development in Young Adults study of black and white men and women initially aged 18 to 30 years, we studied 4762 participants who were not current users of antihypertensive drugs and had no history of heart problems at the baseline examination (1985-1986). In each race-sex subgroup, we estimated the effect of baseline HR on BP 2, 5, 7, and 10 years later by use of repeated measures regression analysis, adjusting for baseline BP, age, education, body fatness, physical fitness, fasting insulin, parental hypertension, cigarette smoking, alcohol consumption, oral contraceptive use, and change of body mass index from baseline. The association between baseline HR and subsequent systolic BP (SBP) was explained by multivariable adjustment. However, HR was an independent predictor of subsequent diastolic BP (DBP) regardless of initial BP and other confounders in white men, white women, and black men (0.7 mm Hg increase per 10 bpm). We incorporated the part of the association that was already present at baseline by not adjusting for baseline DBP: the mean increase in subsequent DBP was 1.3 mm Hg per 10 bpm in white men, white women, and black men. A high HR may be considered a risk factor for subsequent high DBP in young persons. (+info)
Antiphospholipid, anti-beta 2-glycoprotein-I and anti-oxidized-low-density-lipoprotein antibodies in antiphospholipid syndrome.
Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared. (+info)
Different factors influencing the expression of Raynaud's phenomenon in men and women.
OBJECTIVE: To determine whether the risk profile for Raynaud's phenomenon (RP) is different between men and women. METHODS: In this cross-sectional study of 800 women and 725 men participating in the Framingham Offspring Study, the association of age, marital status, smoking, alcohol use, diabetes, hypertension, and hypercholesterolemia with prevalent RP was examined in men and women separately, after adjusting for relevant confounders. RESULTS: The prevalence of RP was 9.6% (n = 77) in women and 5.8% (n = 42) in men. In women, marital status and alcohol use were each associated with prevalent RP (for marital status adjusted odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4-3.9; for alcohol use OR 2.2, 95% CI 1.0-5.2), whereas these factors were not associated with RP in men (marital status OR 1.4, 95% CI 0.6-3.5; alcohol use OR 1.0, 95% CI 0.2-4.4). In men, older age (OR 2.3, 95% CI 1.0-5.2) and smoking (OR 2.6, 95% CI 1.1-6.3) were associated with prevalent RP; these factors were not associated with RP in women (older age OR 0.8, 95% CI 0.4-1.6; smoking OR 0.7, 95% CI 0.4-1.1). Diabetes, hypertension, and hypercholesterolemia were not associated with RP in either sex. CONCLUSION: The results indicate that risk factors for RP differ between men and women. Age and smoking were associated with RP in men only, while the associations of marital status and alcohol use with RP were observed in women only. These findings suggest that different mechanisms influence the expression of RP in men and women. (+info)
Evidence of improving survival of patients with rectal cancer in france: a population based study.
BACKGROUND: Over the past 20 years there have been many changes in the management of rectal cancer. Their impact on the overall population is not well known. AIMS: To determine trends in management and prognosis of rectal cancer in two French regions. SUBJECTS: 1978 patients with a rectal carcinoma diagnosed between 1978 and 1993. METHODS: Time trends in treatment, stage at diagnosis, operative mortality, and survival were studied on a four year basis. A non-conditional logistic regression was performed to obtain an odds ratio for each period adjusted for the other variables. To estimate the independent effect of the period a multivariate relative survival analysis was performed. RESULTS: Over the 16 year period resection rates increased from 66.0% to 80.1%; the increase was particularly noticeable for sphincter saving procedures (+30.6% per four years, p=0.03). The percentage of patients receiving adjuvant radiotherapy increased from 24.0% to 40.0% (p=0.02). The proportion of patients with Dukes' type A cancer increased from 17. 7% to 30.6% with a corresponding decrease in those with more advanced disease. Operative mortality decreased by 31.1% per four years (p=0.03). All these improvements have resulted in a dramatic increase in relative survival (from 35.4% for the 1978-1981 period to 57.0% for the 1985-1989 period). CONCLUSIONS: Substantial advances in the management of rectal cancer have been achieved, but there is evidence that further improvements can be made in order to increase survival. (+info)
Illness behaviour in elite middle and long distance runners.
OBJECTIVES: To examine the illness attitudes and beliefs known to be associated with abnormal illness behaviour (where symptoms are present in excess of objective signs and pathology) in elite middle and long distance runners, in comparison with non-athlete controls. METHODS: A total of 150 athletes were surveyed using the illness behaviour questionnaire as an instrument to explore the psychological attributes associated with abnormal illness behaviour. Subjects also completed the general health questionnaire as a measure of psychiatric morbidity. A control group of 150 subjects, matched for age, sex, and social class, were surveyed using the same instruments. RESULTS: A multivariate analysis of illness behaviour questionnaire responses showed that the athletes' group differed significantly from the control group (Hotelling's T: Exact F = 2.68; p = 0.01). In particular, athletes were more somatically focused (difference between means -0.27; 95% confidence interval -0.50 to -0.03) and more likely to deny the impact of stresses in their life (difference between means 0.78; 95% confidence interval 0.31 to 1.25). Athletes were also higher scorers on the Whiteley Index of Hypochondriasis (difference between means 0.76; 95% confidence interval 0.04 to 1.48). There were no differences in the levels of psychiatric morbidity between the two groups. CONCLUSIONS: The illness attitudes and beliefs of athletes differ from those of a well matched control population. The origin of these psychological attributes is not clear but those who treat athletes need to be aware of them. (+info)
One-year survival among patients with acute myocardial infarction complicated by cardiogenic shock, and its relation to early revascularization: results from the GUSTO-I trial.
BACKGROUND: Although 30-day survival is increased in patients with acute myocardial infarction complicated by cardiogenic shock who undergo coronary revascularization, the longer-term outcome in such patients and the duration of benefit from revascularization are unknown. METHODS AND RESULTS: We analyzed 30-day survivors of acute myocardial infarction in the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial and identified 36 333 who had not had cardiogenic shock (systolic blood pressure <90 mm Hg for >/=1 hour, group 1) and 1321 patients who had shock (group 2). Group 2 patients were older and sicker. At 1 year, 97.4% of group 1 patients were alive versus 88.0% of group 2 (P=0.0001). Among group 2 patients, 578 (44%) had undergone revascularization within 30 days (group 2A) and 728 (56%) had not (group 2B). Revascularization was not required by protocol but was selected by the attending physicians. At 1 year, 91.7% of group 2A patients were alive versus 85.3% of group 2B (P=0.0003). With the use of multivariable logistic regression analysis to adjust for differences in baseline characteristics of shock patients alive at 30 days, revascularization within 30 days was independently associated with reduced 1-year mortality (odds ratio 0.6, [95% confidence interval 0.4, 0.9], P=0.007). CONCLUSIONS: Most patients (88%) with acute myocardial infarction complicated by cardiogenic shock who are alive at 30 days survived at least 1 year. Shock patients who underwent revascularization within 30 days had improved survival at 1 year compared with shock patients who did not receive revascularization, even after adjustment for differences in baseline characteristics between the 2 groups. (+info)
New-onset sustained ventricular tachycardia after cardiac surgery.
BACKGROUND: The de novo occurrence of sustained ventricular tachycardia (VT) after CABG has been described, but the incidence, mortality rate, long-term follow-up, and mechanism are not well defined. METHODS AND RESULTS: This prospective study enrolled consecutive patients undergoing CABG at a single institution. Patients were followed up for the development of sustained VT, and a detailed analysis of clinical, angiographic, and surgical variables associated with the occurrence of VT was performed. A total of 382 patients participated, and 12 patients (3.1%) experienced >/=1 episode of sustained VT 4.1+/-4.8 days after CABG. In 11 of 12 patients, no postoperative complication explained the VT; 1 patient had a perioperative myocardial infarction. The in-hospital mortality rate was 25%. Patients with VT were more likely to have prior myocardial infarction (92% versus 50%, P<0.01), severe congestive heart failure (56% versus 21%, P<0.01), and ejection fraction <0.40 (70% versus 29%, P<0.01). When all 3 factors were present, the risk of VT was 30%, a 14-fold increase. Patients with VT had more noncollateralized totally occluded vessels on angiogram (1.4+/-0.97 versus 0.54+/-0.7, P<0.01), a bypass graft across a noncollateralized occluded vessel (1.50+/-1.0 versus 0.42+/-0.62, P<0.01), and a bypass graft across a noncollateralized occluded vessel to an infarct zone (1.50+/-1.0 versus 0.17+/-0.38, P<0.01). By multivariate analysis, the number of bypass grafts across a noncollateralized occluded vessel to an infarct zone was the only independent factor predicting VT. CONCLUSIONS: The first presentation of sustained monomorphic VT in the recovery period after CABG is uncommon, but the incidence is high in specific clinical subsets. Placement of a bypass graft across a noncollateralized total occlusion in a vessel supplying an infarct zone was strongly and independently associated with the development of VT. (+info)