Hormone replacement therapy is not associated with an increased risk of leukemia (United States)

Objective Recent studies have reported an increased risk of certain cancers associated with hormone replacement therapy (HRT), possibly due to stimulation of estrogen receptors. Since estrogen receptors are expressed on certain hematopoietic cells, it is possible that HRT use may also increase the risk of leukemia.Methods A cohort of 37,172 post-menopausal Iowa women ages 55–69 years with no history of prior cancer was linked annually to the population-based state cancer registry through 2001. In addition to other self-reported cancer risk factors, participants were asked about current and former use of HRT in 1986 and on four subsequent follow-up questionnaires. A total of 201 cases of leukemia were identified over 16 years of follow-up including 74 acute myeloid leukemias (AMLs) and 87 chronic lymphocytic leukemias (CLLs).Results Compared to never users of HRT at study baseline, current [multivariate relative risk (RR), 1.09; 95% confidence interval (CI) 0.70–1.71)] and former users (RR=0.82, 95% CI=0.59–1.15) were at no increased risk of developing leukemia. For AML, current users also had no increased risk (RR=0.83, 95% CI=0.37–1.84) and there was a suggestion that former users had a slightly decreased risk (RR=0.66, 95% CI=0.37–1.17). For CLL, all RRs were around unity.Conclusion We conclude that HRT is unlikely to be an appreciable risk factor for leukemia.     

Prostatic tissue ablation by injection: a literature review

PURPOSE: Most men 50 to 80 years old will have development of some degree of benign prostatic hyperplasia (BPH). Many who experience lower urinary tract symptoms (LUTS) will be treated medically. However, significant numbers will have more severe and progressive disease requiring surgery. Transurethral resection of the prostate is the current gold standard of treatment for BPH. Minimally invasive therapies for symptomatic BPH emerge and fade continuously. However, intraprostatic injection for BPH has been used for more than 100 years and may be on the verge of a rebirth. The goal of this review is to familiarize the reader with the origins and history of intraprostatic injection, and its evolution using transperineal, transrectal and transurethral routes with multiple injectants. Initially used to treat urinary retention in men with BPH, its primary indication is now for LUTS. MATERIALS AND METHODS: We performed a structured MEDLINE review of the literature on intraprostatic injections from 1966 to 2003, augmented with relevant articles from select journals and documents dating to 1832. RESULTS: In patients with BPH transperineal and transurethral injections have the most systematic evaluation. Most injectants will cause localized prostatic necrosis and gland volume reduction with varying degrees of LUTS relief. Anhydrous ethanol is the most widely studied injectable to date. There are advantages and disadvantages associated with each route of injection. CONCLUSIONS: Examined for more than a century, the potential for using injectables for prostatic tissue ablation remains significant. More systematic laboratory research and clinical trials, currently ongoing, need to be completed.     

B vitamin status and inflammatory markers

Limited evidence has suggested that low levels of circulating pyridoxal-5'-phosphate (PLP) may be associated with elevation of the inflammatory marker, C-reactive protein (CRP). We sought to determine whether the reported association of CRP with PLP was specific versus generalizable to other inflammation or hemostasis markers. Among 519 healthy middle aged adults in the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed the cross-sectional relation of homocysteine, plasma and dietary B vitamin levels with multiple markers implicated in inflammation, endothelial dysfunction, or thrombogenesis: CRP, fibrinogen, white blood cell count, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, factor VIII, and von Willebrand factor. There was no significant association (P>0.05) of von Willebrand factor, I-CAM, or V-CAM with any of the plasma or dietary measures examined, and no marker was associated significantly with serum homocysteine. Contrary to our hypothesis, plasma PLP was not associated with CRP concentration. A higher white blood cell count was associated with lower B vitamin status (lower plasma PLP and folate, lower dietary B6 and B12), though not with use of vitamin supplements. In ostensibly healthy adults, B-vitamin status is not a strong correlate of circulating levels of inflammatory markers, cellular adhesion molecules, or thrombogenic factors.     

Anticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study

Anticardiolipin antibodies, one of the family of 'antiphospholipid' antibodies, increase the risk of venous thromboembolism in the presence of autoimmune disease. Our objective was to determine prospectively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults. We conducted a nested case-control study (n = 317 patients and n = 655 control subjects) in a longitudinal study of over 20 000 participants. Baseline (prediagnosis) anticardiolipin IgG and IgM antibodies were assessed by enzyme-linked immunoassays. Venous thromboembolism was validated using standardized criteria for venous thrombosis and pulmonary embolism. There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence, overall or in any subgroup. For example, the multivariate-adjusted relative risk was 0.88 (95% confidence interval, 0.43, 1.78) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion, in this general population sample, an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism.     

Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study

To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the approximately 9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01-2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.     

A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study

Increased iron stores may play a role in the development of coronary heart disease (CHD) by increasing lipoprotein oxidation. Recently, mutations have been discovered in the gene (HFE) for hereditary hemochromatosis, an autosomal recessive condition of disordered iron metabolism, absorption, and storage. It is possible that people who carry HFE mutations have increased risk of CHD. We used a prospective case-cohort design (243 CHD cases and 535 non-cases) to determine whether the HFE C282Y mutation was associated with incident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in the ARIC study population were 0.2% (one homozygous person) and 6%, respectively. The C282Y mutation was associated with nonsignificantly increased risk of CHD (relative risk=1.60, 95% CI 0.9-2.9). After adjusting for other confounding risk factors (age, race, gender, ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, and triglycerides), the association became stronger (relative risk=2.70, 95% CI 1.2-6.1). However, a sensitivity analysis showed that this estimate of relative risk was somewhat unstable due to few subjects in some strata. Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.     

Dietary linolenic acid and carotid atherosclerosis: the National Heart,Lung, and Blood Institute Family Heart Study

BACKGROUND: Dietary intake of linolenic acid is associated with a lower risk of cardiovascular disease mortality. However, it is unknown whether linolenic acid is associated with a lower risk of carotid atherosclerosis. OBJECTIVE: The objective was to examine the association between dietary linolenic acid and the presence of atherosclerotic plaques and the intima-media thickness of the carotid arteries. DESIGN: In a cross-sectional design, we studied 1575 white participants of the National Heart, Lung, and Blood Institute Family Heart Study who were free of coronary artery disease, stroke, hypertension, and diabetes mellitus. High-resolution ultrasound was used to assess intima-media thickness and the presence of carotid plaques beginning 1 cm below to 1 cm above the carotid bulb. We used logistic regression and a generalized linear model for the analyses. RESULTS: From the lowest to the highest quartile of linolenic acid intake, the prevalence odds ratio (95% CI) of a carotid plaque was 1.0 (reference), 0.47 (0.30, 0.73), 0.38 (0.22, 0.66), and 0.49 (0.26, 0.94), respectively, in a model that adjusted for age, sex, energy intake, waist-to-hip ratio, education, field center, smoking, and the consumption of linoleic acid, saturated fat, fish, and vegetables. Linoleic acid, fish long-chain fatty acids, and fish consumption were not significantly related to carotid artery disease. Linolenic acid was inversely related to thickness of the internal and bifurcation segments of the carotid arteries but not to the common carotid artery. CONCLUSION: Higher consumption of total linolenic acid is associated with a lower prevalence odds of carotid plaques and with lesser thickness of segment-specific carotid intima-media thickness.