The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case-control study

BACKGROUND: Statin use has increased dramatically in the U.S. in the past decade. Animal and mechanistic studies suggested that statins may have an inhibitory effect on cancer proliferation, including breast carcinoma. However, statins have been found to be carcinogenic in rodents and one clinical trial found an excess of breast carcinoma cases in the treatment group. METHODS: The current study assessed whether the use of statins altered the risk of breast carcinoma in older women. The population-based, case-control study comprised female residents from three western Washington State counties. Cases included 975 women identified from the Cancer Surveillance System who were diagnosed with primary invasive breast carcinoma between 1997-1999, whose names appeared on a list of Social Security recipients provided by the Centers for Medicare and Medicaid Services. The cases were ages 65-79 years at the time of diagnosis. The comparison group was comprised of 1007 women without breast carcinoma who were randomly selected from the same list of Social Security recipients. Information pertaining to statin use, medical history, and health behaviors was ascertained through an in-person interview. RESULTS: Compared with nonusers, women who were currently using statins or had ever used statins were not found to be at an increased risk for breast carcinoma (odds ratios [OR] = 0.9; 95% confidence interval [95% CI], 0.7-1.2). There was some indication that long-term statin use (> 5 years) was related to a slight decrease in breast carcinoma risk (OR = 0.7; 95% CI, 0.4-1.0). CONCLUSIONS: The results of the current study provided some degree of reassurance to the increasing numbers of women using statins that such use is not associated with an increased risk of breast carcinoma. Although the data gave some support to a reduced risk of breast carcinoma among long-term users of statins, further research is needed to confirm this association.     

Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis?

Telomere length was evaluated by terminal repeat fragment method (TRF) in 50 patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) arising from MDS and in 21 patients with untreated primary AML to ascertain, whether telomere erosion was associated with progression of MDS towards overt leukemia. Heterogeneity of TRF among MDS FAB subgroups (P=0.004) originated from its shortening in increased number of patients during progression of the disease. Chromosomal aberrations were present in 32% MDS patients with more eroded telomeres (P=0.022), nevertheless a difference between mean TRF in the subgroups with normal and abnormal karyotype diminished during progression of MDS. A negative correlation between individual TRF and IPSS value (P=0.039) showed that telomere dynamics might serve as a useful prognostic factor for assessment of an individual MDS patient's risk and for decision of an optimal treatment strategy.     

Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft

After therapeutic hormone deprivation, most prostate cancer (PrCa) cells develop androgen-independent (AI) growth. PrCa is highly heterogeneous and multifocal, suggesting that several molecular processes or pathways may be contributing to AI. The human LuCaP 23.1 xenograft model retains clinical hallmarks of PrCa, including heterogeneous growth, PSA production, androgen-responsiveness and progression to AI. In this work, we studied the effect of androgen depletion (castration) on the growth of LuCaP 23.1 xenografts. A total of 100 nude mice were implanted and analysed for their growth profiles before and after castration. By 11 and 15 weeks, tumours were harvested and assessed for molecular marker expression specific for PrCa. Prior to castration we found 37 fast growing (FG) tumours (948.9+/-76.9 mm(3)) and 63 slow growing (SG) tumours (229.6+/-18.4 mm(3)), a previously undescribed result for this PrCa model. Quantitative RT-PCR showed that in comparison to SGs, FGs contained high HER1, uPA and thymidilate synthetase (TS) expression with low levels of 5alpha-reductase 2 mRNA. All FG tumours progressed rapidly to AI growth 5 weeks after castration (FG-P). In SG castrated tumours, 66% of tumours (SG-P) showed retarded progression (by 12 weeks) to AI, whereas 34% responded to castration (SG-R). Molecular analysis permitted us to define distinct molecular profiles integrating different pathways associated with AI progression. FG-P, and a subgroup of SG-P tumours, presented significantly high levels of peptidylglycine alpha-amidating monooxygenase (PAM), HER1, HER2, TS, and uPA mRNA, all of which correlated with AR expression. The second subgroup of SG-P tumours showed overexpression of the antiapoptotic gene Bcl-2. A third subgroup of SG-P tumours showed significant expression of hypoxia-related gene (adrenomedullin) after castration. This work permitted to define distinct molecular profiles related to different AI growth in the LuCaP 23.1 xenograft.     

Coronary artery disease in chronic kidney disease patients: assessing the evidence for diagnosis, screening and revascularization

The prevalence of chronic kidney disease (CKD) is increasing in North America, with an attendant increase in cardiovascular complications. The bulk of the mortality and morbidity in CKD patients can be attributed to coronary artery disease (CAD), especially in the presence of diabetes mellitus. Thus, screening and diagnosis of CAD is particularly important in the management of these patients, especially during evaluation for renal transplantation. However, numerous limitations exist with noninvasive tests that cloud the ideal strategy for diagnosis. In addition, the optimal revascularization strategy (surgery versus percutaneous intervention) for CAD is controversial for these patients. Randomized trials are clearly needed; unfortunately, major cardiovascular trials usually exclude patients with significant renal dysfunction. The current diagnostic and revascularization strategy for CAD in CKD patients is discussed, highlighting current controversies that warrant further investigation.     

Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI)

BACKGROUND: Subclinical depression, often clinically unrecognized, may pose increased risk of cardiovascular disease. Few studies have prospectively investigated cardiovascular events related to depression in older women. We describe prevalence, cardiovascular correlates, and relationship to subsequent cardiovascular events of depressive symptoms among generally healthy postmenopausal women. METHODS: The Women's Health Initiative Observational Study followed up 93 676 women for an average of 4.1 years. Depression was measured at baseline with a short form of the Center for Epidemiological Studies Depression Scale. Risks of cardiovascular disease (CVD) events were estimated from Cox proportional hazards models adjusting for multiple demographic, clinical, and risk factor covariates. RESULTS: Current depressive symptoms above the screening cutoff point were reported by 15.8% of women. Depression was significantly related to CVD risk and comorbidity (odds ratios ranging from 1.12 for hypertension to 1.60 for history of stroke or angina). Among women with no history of CVD, depression was an independent predictor of CVD death (relative risk, 1.50) and all-cause mortality (relative risk, 1.32) after adjustment for age, race, education, income, diabetes, hypertension, smoking, high cholesterol level requiring medication, body mass index, and physical activity. Taking antidepressant medications did not alter the depression-associated risks associated. CONCLUSIONS: A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD death and all-cause mortality, even after controlling for established CVD risk factors. Whether early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.     

Prion diseases: Update on mad cow disease,variant creutzfeldt-jakob disease,and the transmissible spongiform encephalopathies

Transmissible spongiform encephalopathies (TSEs) are a group of progressive, fatal neurodegenerative disorders that share a common spongiform histopathology. TSEs may be transmitted in a sporadic, familial, iatrogenic, or zoonotic fashion. The putative infectious agent of TSE, the prion, represents a novel paradigm of infectious disease with disease transmission in the absence of nucleic acid. Several small but spectacular epidemics of TSEs in man have prompted widespread public health and food safety concerns. Although TSEs affect a comparatively small number of individuals, prion research has revealed fascinating insights of direct relevance to common illnesses. This paper reviews recent advances that have shed new light on the nature of prions and TSEs.     

Photo recall effect in association with cefazolin

Patients in remission from local dermatitis secondary to external beam radiation treatments occasionally experience recurrence with systemic chemotherapy, a reaction termed radiation recall. Chemotherapy-induced photo recall from a prior exposure to the sun also has been reported. Rare reports describe photo recall effects from more commonly used medications. We report the case of a patient who developed a photo recall reaction after treatment with cefazolin. Results of the shave biopsy were consistent with a mild phototoxic eruption.     

Lupus erythematosus induced by medications, ultraviolet radiation, and other exogenous agents: a review, with special focus on the development of subacute cutaneous lupus erythematosus in a genetically predisposed individual

Exogenous agents implicated in or suspected of precipitating subacute cutaneous lupus erythematosus (SCLE) and lupus erythematosus (LE) are reviewed. An illustrative case of environmentally induced SCLE is presented. A previously healthy 30-year male homozygous for the tumor necrosis factor-alpha (TNF-alpha) 308. A promoter allele developed SCLE after spending several hours removing fertilizer- and pesticide-containing hay from an agricultural barn in the springtime. The cutaneous eruption soon resolved, only to reappear 3 weeks later on the day the patient re-entered the barn. An environmental agent present in the barn, coupled with springtime ultraviolet light, likely triggered the disease in this immunogenetically susceptible individual.     

Combined dialectical behavior therapy and fluoxetine in the treatment of borderline personality disorder

BACKGROUND: This study examines the therapeutic effect of fluoxetine, a selective serotonin reuptake inhibitor, added to dialectical behavior therapy (DBT), an empirically supported psychosocial therapy, for the treatment of borderline personality disorder. METHOD: This is a 12-week, randomized, double-blind, placebo-controlled study of patients with borderline personality disorder (identified using the Structured Clinical Interview for DSM-IV Axis II Disorders). All subjects received individual and group DBT. Of the 20 subjects that completed treatment, 9 were randomly assigned to receive up to 40 mg/day of fluoxetine and 11 were randomly assigned to the placebo condition. Subjects were evaluated at baseline and at week 10 or 11 on self-report measures of depression, anxiety, anger expression, dissociation, and global functioning. The study was conducted between January 1998 and February 2000. RESULTS: Time-by-group interaction effects revealed no significant group differences in scores from pre-treatment to posttreatment on any measure. However, within the DBT/placebo group, there were significant pretreatment/posttreatment differences in the direction of improvement on all measures. No significant pre-treatment/posttreatment differences were found within the DBT/fluoxetine condition. CONCLUSION: The data suggest that adding fluoxetine to an efficacious psychosocial treatment does not provide any additional benefits. Further studies with larger sample sizes are warranted.