Silent cerebral ischemia detected by diffusion-weighted MRI after carotid endarterectomy

BACKGROUND AND PURPOSE: Small emboli arising from a friable plaque during carotid endarterectomy (CEA) constitute an important risk of perioperative ischemic complications. To evaluate the incidence and significance of silent cerebral ischemic lesions of embolic origin after CEA, we prospectively examined a series of surgical patients with high-grade carotid stenosis by using diffusion-weighted MRI (DWI). We also tried to correlate postoperative ischemic lesions with the occurrence of sonographic cerebral embolic signals, the presence of plaque ulcerations, and the use of intraoperative shunting. METHODS: Of a consecutive series of 53 patients undergoing elective CEA for high-grade carotid stenosis, 48 patients with unchanged postoperative neurological status were prospectively studied with DWI of the brain the day before and the day after the operation. The magnetic resonance images were analyzed by 2 neuroradiologists blinded to the clinical result of the operation. Any new hyperintense signal was interpreted as a postoperative ischemic lesion. RESULTS: Forty-six (95.8%) of 48 patients had unchanged postoperative brain DWI. In 2 patients (4.2%), a new single asymptomatic hyperintense signal was observed on the side of the operation. Both lesions were small and presumably of embolic origin. They were not related to sonographic embolic signals, plaque ulcerations, or intraoperative shunting. CONCLUSIONS: These results suggest that the incidence of silent ischemic brain lesions of embolic origin after CEA is low and does not correlate with the occurrence of intraoperative sonographic microemboli. They confirm that CEA is a safe procedure that carries a low risk of postoperative cerebral events.     

Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA.

A vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (alpha-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and cervical cancer cell lines are exceptions, with alpha-TEA exhibiting greater proapoptotic effects. Although both VES and alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, only alpha-TEA is an effective inducer of apoptosis. VES or alpha-TEA treatment of cp70 cells with 5, 10, or 20 microg/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by alpha-TEA than VES. Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of alpha-TEA were demonstrated by high-performance liquid chromatography analyses that showed alpha-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-alpha-tocopherol. Pretreatment of cp70 cells with bis-(p-nitrophenyl) phosphate, an esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show alpha-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-alpha-tocopherol, an ineffective apoptotic-inducing agent.     

Sperm number and condition affect the number of basal cells and their expression of macrophage antigen in the murine epididymis

Unilateral ligation of the mid-corpus epididymis, the proximal vas deferens and imposition of an abdominal temperature for 6 days as well as bilateral castration for 3, 6 or 14 days, resulted in a change in epithelial composition of the adult murine epididymis with regard to the number and antigen expression of basal cells. There were fewer basal cells per tubule cross-section with fewer expressing F4/80 antigen when spermatozoa were absent from the proximal lumen following short-term castration. Conversely, more basal cells with more of them demonstrating macrophage antigen expression were evident when more or damaged spermatozoa were in the proximal lumen after corpus ligation and exposure to abdominal temperature or in the cauda after long-term withdrawal of androgen support. By contrast, ligation of the vas deferens did not lead to tubule distension, and hence sperm accumulation, and did not alter the basal cell population in the cauda epididymis. The data suggest that epididymal basal cells respond in number and macrophage antigen expression to the presence of sperm autoantigens in the lumen with little dependence on circulating androgens. These changes may represent responses to minimise the interaction of sperm autoantigens with the immune system and the risk of immunological infertility.     

Comparing Medications in a Therapeutic Area Using an NNT Model

OBJECTIVES: Clinicians are told to use the number needed to treat (NNT) to compare the benefits of therapeutic strategies, and researchers are asked to report results this way, generally without considering differences among the studies from which these were derived. METHODS: The crude NNT currently advocated is compared to the NNT standardized for a common outcome, follow-up time, study population and comparator. An NNT model for cardiovascular disease is described as an example that addresses differences among studies of secondary prevention of cardiovascular disease. Crude NNTs are compared to those obtained from the model. RESULTS: Follow-up in the 18 trials identified varied from 1.0 to 6.2 years; rates of cardiovascular events in the untreated subgroups ranged from 4.8% to 45.9%. The crude NNTs were more variable (9.1-163.7) than those obtained from the model (9.1-75.2). The effect of standardization was substantial in some cases, with proportional changes ranging from a 91% decrease to a 223% increase. CONCLUSION: Using an NNT model to account for differences in study design allows for more meaningful comparisons.     

Contribution of Cardiorespiratory Fitness to the Obesity Paradox

Until recently, cardiorespiratory fitness (CRF) has been overlooked as a potential modifier of the inverse association between obesity and mortality (the so-called obesity paradox), observed in patients with known or suspected cardiovascular (CV) disease. Evidence from five observational cohort studies of 30,104 patients (87% male) with CV disease indicates that CRF significantly alters the obesity paradox. There is general agreement across studies that the obesity paradox persists among patients with low CRF, regardless of whether adiposity is assessed by body mass index, waist circumference, or percentage body fat. However, among patients with high CRF, risk of all-cause mortality is lowest for the overweight category in some, but not all, studies, suggesting that higher levels of fitness may modify the relationship between body fatness and survival in patients manifesting an obesity paradox. Further study is needed to better characterize the joint contribution of CRF and obesity on mortality in diverse populations.     

Use of the Location-Based Social Networking Application GRINDR as a Recruitment Tool in Rectal Microbicide Development Research

Mobile phone social networking applications such as GRINDR are potential tools for recruitment of men who have sex with men (MSM) for HIV prevention research. Demographics and sexual risk behaviors of men recruited through GRINDR and through traditional media were compared. GRINDR participants were younger (mean age 31 vs. 42, p?<?0.0001), more White identified (44 vs. 30?%, p?<?0.01), and had more sex partners in the previous 14 days (1.88 vs. 1.10, p?<?0.05) than other recruits. Email responses were less successful for enrollment than phone calls (5 vs. 50?%). This approach resulted in successful recruitment of younger and more educated, White identified MSM.     

Evaluation of the Heart Truth Professional Education Campaign on Provider Knowledge of Women and Heart Disease

BackgroundThe Heart Truth Professional Education Campaign was developed to facilitate education of health care providers in evidence-based strategies to prevent cardiovascular disease (CVD) in women.MethodsAs part of the 3-year campaign, lectures based on the American Heart Association's evidence-based guidelines for CVD prevention in women were presented by local speakers to healthcare providers and students in three high-risk states: Delaware, Ohio, and New York. Participants' responses to pretest and posttest questions about CVD in women are presented. We performed t-test and multivariable linear regression to assess the influence of provider characteristics on baseline knowledge and knowledge change after the lecture.ResultsBetween 2008 and 2011, 2,995 healthcare providers, students, and other participants completed the baseline assessment. Knowledge scores at baseline were highest for physicians, with obstetrician/gynecologists scoring lowest (63%) and cardiologists highest (76%). Nurses had intermediate total knowledge (56%) and students had the lowest total knowledge (49%) at baseline. Pre- and post-lecture assessments were completed by 1,893 (63%) of attendees. Scores were significantly higher after the educational lecture (p ≤ .001), with greater increase for those with lower baseline scores. Baseline knowledge of the use of statins, hormone therapy, and antioxidants, as well as approaches to smoking cessation and treatment of hypertension, differed by provider type.ConclusionTailoring of lectures for non-physician audiences may be beneficial given differences in baseline knowledge. More emphasis is needed on statin use for all providers and on smoking cessation and treatment of hypertension for nurses, students, and other healthcare professionals.     

Transmetatarsal Amputation in the Setting of Antiphospholipid Antibody Syndrome

Antiphospholipid syndrome is a hypercoagulable disease that can present foot and ankle surgeons with a unique challenge in treating patients who present with thrombosis and ischemia despite having normal pedal pulses. Appropriate perioperative management is imperative in these patients, because limb- and life-threatening complications can occur postoperatively, despite aggressive anticoagulation. We present the case of a 46-year-old male who underwent a transmetatarsal amputation and, despite aggressive therapy, developed a myriad of complications postoperatively. At 10 months postoperatively, the patient was doing well in an accommodative orthotic with minimal pain while receiving continued aggressive therapy and follow-up examinations by a number of specialists to treat his antiphospholipid syndrome.