Intracranial atherosclerotic disease.

Atherosclerotic disease of the intracranial arteries is responsible for at least 10% of ischaemic strokes worldwide. Symptomatic disease has been extensively studied in the past few years, using diagnostic methods including multi-slice computed tomography and high resolution magnetic resonance imaging. A literature search was performed using PubMed and OvidSP between 1984 and May 2013. Variations of the terms 'intracranial atherosclerosis' plus 'ischemic stroke', 'plaque', 'morphology', 'imaging' were used and a combination of them. The reference lists of identified articles were also consulted for additional references. Amongst symptomatic patients the prevalence of intracranial atherosclerotic disease is around 10%, depending on race ethnicity, and the diagnosis requires the presence of ≥50% stenosis in the territory of the symptomatic vessel in a patient with stroke or transient ischaemic attack. The prognosis of intracranial atherosclerotic disease related stroke is poor. Although risk factor control can lead to a better outcome of intracranial atherosclerotic disease related strokes, the significance of asymptomatic disease is still a matter of debate.

Outcomes of intravenous tissue plasminogen activator for acute ischaemic stroke in HIV-infected adults.

BACKGROUND AND PURPOSE: To our knowledge there are no studies reporting the use and short-term outcomes of intravenous tissue plasminogen activator (IV-TPA) for the treatment of acute ischaemic stroke (AIS) in people living with HIV. METHODS: The US Nationwide Inpatient Sample (NIS) (2006-2010) was searched for HIV-infected AIS patients treated with IV-TPA. RESULTS: In the NIS, 2.2% (62/2877) of HIV-infected AIS cases were thrombolyzed with IV-TPA (median age 52 years, range 27-78, 32% female, 22% Caucasian) vs. 2.1% (19 335/937 896) of HIV-uninfected cases (median age 72 years, range 17-102 years, 50% female, 74% Caucasian; P = 0.77). There were more deaths in HIV-infected versus uninfected patients with stroke (220/2877, 7.6% vs. 49 089/937 547, 5.2%, P < 0.001) but no difference in the proportion of deaths amongst IV-TPA-treated patients. The age- and sex-adjusted odds ratio for death following IV-TPA administration in HIV-infected versus uninfected patients was 2.26 (95% CI 1.12, 4.58), but the interaction on mortality between HIV and IV-TPA use was not statistically significant, indicating no difference in risk of in-hospital death by HIV serostatus with IV-TPA use. A higher number of HIV-infected patients remained in hospital versus died or were discharged at both 10 and 30 days (P < 0.01 at 10 and 30 days). No difference in the proportion of intracerebral hemorrhage in the two groups was found (P = 0.362). CONCLUSIONS: The in-hospital mortality is higher amongst HIV-infected AIS patients than HIV-uninfected patients. However, the risk of death amongst HIV-infected patients treated with IV-TPA is similar to HIV-uninfected groups.

Impact of monocytic cells on recovery of uncultivable bacteria from atherosclerotic lesions.

OBJECTIVE: Epidemiological evidence suggests that infections may contribute to atherogenesis. However, with the exception of Chlamydophila pneumoniae, cultivable bacteria have not been recovered from atherosclerotic lesions. Therefore, we aimed at developing an approach to recover uncultivable bacteria from atherectomy tissues. METHODS: We cultured homogenates from atherectomy specimens from seven nonseptic patients undergoing surgery for arterial obstruction either alone or together with THP-1 monocyte-like cells. We performed 16S rDNA analysis, biochemical tests, random amplification of polymorphic DNA PCR analysis, quantitative polymerase chain reaction (qPCR) and immunohistofluorescence to identify the cultivated bacteria. Wilcoxon signed-rank tests were used to determine whether THP-1 treatment yielded a higher number of isolates than did the untreated controls. RESULTS: We recovered more bacteria from cocultures of atherectomy specimens with THP-1 cells than atherectomy specimens cultured alone. On average, tissue homogenates incubated with THP-1 cells versus control yielded 124 vs. 22 colony-forming units, a median of 140 vs. 7, respectively (P = 0.02). We recovered 872 isolates of limited number of species, including Propionibacterium acnes, Staphylococcus epidermidis and Streptococcus infantis and the fastidious anaerobe Porphyromonas gingivalis, and confirmed its presence in tissue using double immunofluorescence imaging. qPCR demonstrated the presence of ≥3.5 × 10(3) P. gingivalis genomes per gram of atheromatous tissue. CONCLUSIONS: These results indicate that viable previously uncultivable bacterial species are present within atheromas. Our results suggest revisiting the hypothesis that infections may have a causative role in atherosclerotic inflammation and have implications for research regarding novel diagnostics and treatments for cardiovascular disease.

Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III.

BACKGROUND: Periodontitis is ubiquitous and associated with serological evidence of exposure to periodontal organisms, systemic inflammation and vascular disease. Dementia is a major public health problem likely related to a complex interaction between genetics and diseases associated with systemic inflammation, including diabetes, smoking and stroke. METHODS: To assess relationships between systemic exposure to periodontal pathogens and cognitive test outcomes, data were analysed from the Third National Health and Nutrition Examination Survey (NHANES-III), a nationally representative cross sectional observational study among older adults. We included 2355 participants >or=60 years who completed measures of cognition and Poryphyromonas gingivalis IgG. Using SUDAAN, logistic regression models examined the association of P gingivalis IgG with cognitive test performance. RESULTS: Poor immediate verbal memory (<5/9 points) was prevalent in 5.7% of patients, and 6.5% overall had impaired delayed recall (<4/9); 22.1% had difficulty with serial subtractions (<5/5 trials correct). Individuals with the highest P gingivalis IgG (>119 ELISA Units (EU)) were more likely to have poor delayed verbal recall (OR 2.89, 95% CI 1.14 to 7.29) and impaired subtraction (OR 1.95, 95% CI 1.22 to 3.11) than those with the lowest (

Cell killing by actinomycin D in relation to the growth cycle of chinese hamster cells.

Using Chinese hamster cells in culture, we have measured the effectiveness of actinomycin D to suppress division as a function of the position, or age, of a cell in its growth cycle. Cells were first exposed to millimolar concentrations of hydroxyurea in order to produce a synchronized population just before the onset of DNA synthesis. Thereafter, the survival response after 30 min exposures to actinomycin D was measured. Cells become resistant as they enter the S phase and then sensitive again in the latter part of S. When they reach G(2) (or G(2)-mitosis) they are maximally resistant; at 1.0 microg/ml, for example, the survival in G(2) is 30-fold greater than it is in G(1). These results, plus measurements reported earlier on the interaction of damage in S cells due to actinomycin D and X-irradiation, suggest that the age-response pattern of the toxic effects of this drug probably reflects both the functional capacity of DNA-actinomycin complexes and the ability of this antibiotic to penetrate chromatin and bind to DNA.

Sulfur mustard and x-rays: differences in expression of lethal damage.

Before or after treatment with sulfur mustard, simple changes in the incubation conditions of cultured Chinese hamster cells lead to changes as great as a factor of 6 in survival-curve slopes. With x-ray treatment, changes are similar but much smaller in magnitude. These results suggest that the modes of action of these agents are not entirely the same.

Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

BACKGROUND AND PURPOSE: Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. MATERIALS AND METHODS: Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. RESULTS: The Northern Manhattan Study participants who had MR imaging data available for review (n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. CONCLUSIONS: In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population.

Transformation of mouse C3H/10T1/2 cells by single and fractionated doses of X-rays and fission-spectrum neutrons.

A mouse embryo-derived cell line, C3H/10T1/2, was used to measure the frequency of in vitro neoplastic transformation induced by 50-kVp X-rays and by fission-spectrum neutrons from the JANUS reactor at the Argonne National Laboratory. The transformation frequency after single X-ray doses rises exponentially, reaching a plateau at about 3 X 10(-3) transformant/survivor. The induction curve following single neutron doses, while qualitatively similar, initially rises more steeply and levels off at a maximum of about 6 X 10(-3) transformant/survivor. For both radiations, transformation frequency varies with changes in the number of viable cells per dish, showing about a 10-fold decrease in transformation frequency when the number of viable cells per 90-mm dish was increased from about 300 to about 1000. Fractionation of a total X-ray dose of 700 rads results in an approximately 6-fold increase in survival and reduction in transformation frequency over a 16-hr interval. Fractionation of the total neutron dose of 378 rads has no effect upon cell survival, and transformation frequency declines by a factor of only about 1.7 at most over a 24-hr period. Cells derived from transformed foci formed fibrosarcomas when injected into appropriately treated mice.

Enhanced transformation of mouse 10T1/2 cells by 12-O-tetradecanoylphorbol-13-acetate following exposure to X-rays or to fission-spectrum neutrons.

Addition of the tumor promoter of 12-O-tetradecanoylphorbol-13-acetate (TPA) to C3H/10T1/2 cells after exposure to either X-rays or to fission-spectrum neutrons increases significantly the frequency of transformation without any effect on cell survival. However, treatment of unirradiated cells with 0.1 micrograms of TPA per ml alone results in a small increase in transformation frequency above background (i.e., from 1.1 x 10(-5) to 1.0 x 10(-4). Thus, besides being a promoter, TPA is also a weak initiator. Enhancement of radiation-induced transformation by TPA was relatively greater after low compared to high doses of either radiation. In addition, TPA causes the relative biological effectiveness of neutrons compared to X-rays to increase with increasing dose or with increasing frequency of transformation rather than to decrease, when TPA is not used. For X-ray doses from zero to approximately 120 rads, TPA raises transformation to frequencies approximately equal to those due to neutrons alone. Analysis of TPA enhancement in the context of the combined effect of two inducing agents, i.e., TPA plus a radiation, indicates that with either radiation TPA acts synergistically. Lastly, TPA was found to alter the dependence of transformation frequency on the density of viable cells. As opposed to a constant frequency of transformants per surviving (or viable) cell, which we observed after a fixed dose of X-rays or neutrons for a range of cell inocula, the addition of TPA increased the frequency of transformation for cell inocula (i.e., from approximately 20 to 6000 viable cells per 90-mm Petri dish). However, the frequency of transformation decreases with increasing size of the inoculum, a result that we interpret to indicate the combined effect of an interference with cell-to-cell communication by TPA plus the fading of initiation events due to the radiation.

Enhanced cytochrome P450 (Cyp1b1) expression, aryl hydrocarbon hydroxylase activity, cytotoxicity, and transformation of C3H 10T1/2 cells by dimethylbenz(a)anthracene in conditioned medium.

The basal and benz(a)anthracene-induced aryl hydrocarbon hydroxylase activities of C3H 10T1/2 mouse embryo fibroblasts have been shown to vary with population growth. We report here that, in the case of dimethylbenz(a)anthracene, cytotoxicity and transformation (neoplastic/morphological transformation and focus formation) increased as a consequence of population growth and, at high cell densities, DNA adduct formation was elevated. Among the factors that may contribute to these changes, we have found that conditioning of the medium with population growth plays a significant role. Cells treated with medium conditioned by several days of cell growth supported increases in the dimethylbenz(a)anthracene induction of mRNA expression of a new mouse cytochrome P450 gene designated Cyp1b1, aryl hydrocarbon hydroxylase activity, cytotoxicity, and the frequency of neoplastic transformation. These results suggest a cause and effect relationship between the enhanced expression of Cyp1b1 due to medium conditioning and the enhanced expression of the cellular endpoints cytotoxicity and transformation.

Repair of cell killing and neoplastic transformation at reduced dose rates of 60Co gamma-rays.

Using the C3H/10T1/2 mouse embryo-derived cell line, we measured the survival and incidence of neoplastic transformation following exposures of the cells to 60Co gamma-rays at an acute (100 rads/min) and at reduced (2.5, 0.5, and 0.1 rad/min) dose rates. Typical of what is generally observed with mammalian cells, at reduced dose rates, the survival of 10T1/2 cells increases as the dose rate is decreased due to the repair of sublethal damage during irradiation. The induction curve following acute exposures of 60Co gamma-rays is similar to that previously reported for 50-kV X-rays; the frequency initially rises rapidly, reaching a plateau of about 3 X 10(-3) transformants/survivor. The transformation induction curves for the reduced dose rates, while similar in shape to that for the high dose rate, exhibit a strong dependence on dose rate. All of the induction frequencies for reduced dose rates lie below those for 100 rads/min. In the low-dose region (i.e., 0 to 150 rads), our results are most extensive at 100 and at 0.1 rad/min. While each set of data in the low-dose region is fitted quite well by a linear dose dependence, the slope of the regression line at 0.1 rad/min is about one-half of that at 100 rads/min. We conclude that subeffective transformation damage, as well as sublethal damage, is repaired during low-dose-rate irradiation.

Inhibitors of poly(adenosine diphosphoribose) synthetase, examination of metabolic perturbations, and enhancement of radiation response in Chinese hamster cells.

3-Aminobenzamide, a specific inhibitor of poly(adenosine diphosphoribose) synthesis, has been shown to enhance the response of mammalian cells to ionizing radiation and alkylating agents. Observations such as these usually have been taken to be an indication of the involvement of poly(adenosine diphosphoribose) in the repair of DNA damage. It has been reported that some inhibitors of adenosine diphosphoribosyl transferase (ADPRT) affect cell viability, glucose metabolism, and DNA synthesis when present at low concentrations in the growth medium for extended periods (e.g., lymphoid cells exposed to a few millimolar for 24 h [Milam, K. M., and Cleaver, J. E. Science (Wash. DC), 223: 589, 1984]). The latter report questioned previous interpretations of radiation results based on the use of ADPRT inhibitors which enhance cell killing. We have studied the enhanced radiation lethality of Chinese hamster cells using higher concentrations of these inhibitors, but for shorter periods, in an effort to determine if metabolic perturbations are produced and if they are relatable to enhanced cell killing. The compounds used were 2-aminobenzamide, 3-aminobenzamide, 4-aminobenzamide, benzamide, and nicotinamide, compounds which show a large variation in their potency as inhibitors of ADPRT. It was found that none of the compounds was toxic at the highest doses used (20 mM for 2 h) and that, during a 2-h period, the potent inhibitor 3-aminobenzamide had little or no effect on DNA synthesis. Two h is long enough to yield a near-maximum radiosensitization with 3-aminobenzamide. Although glucose metabolism was affected to varying degrees (up to a 50% inhibition by 4-aminobenzamide in 2 h), there was no correlation between effectiveness in inhibiting ADPRT and effectiveness in inhibiting glucose metabolism. A correlation was observed, however, between the inhibitory potential of ADPRT and the enhancement of radiation response. When used for sufficiently short times, we conclude that the effects at even high concentrations of a potent inhibitor of ADPRT (e.g., 3-aminobenzamide) are consistent with an involvement of poly(adenosine diphosphoribose) synthesis in the expression of a radiation-induced end point like cell killing.

Spectral dependencies of killing, mutation, and transformation in mammalian cells and their relevance to hazards caused by solar ultraviolet radiation.

Using germicidal lamps and Westinghouse sunlamps with and without filtration, the effectiveness of ultraviolet and near-ultraviolet light in inducing molecular and cellular changes was measured. Cell survival and the induction of resistance to 6-thioguanine or to ouabain were measured with V79 Chinese hamster cells, cell survival and neoplastic transformation were measured with C3H mouse 10 T 1/2 cells, and the induction of pyrimidine dimers containing thymine was measured in both cell lines. The short-wavelength cutoff of the sunlamp emission was shifted from approximately 290 nm (unfiltered) to approximately 300 and approximately 310 nm by appropriate filters. Although it was found that the efficiency with which all end points were induced progressively decreased as the short-wavelength cutoff was shifted to longer wavelengths, the rates of decrease differed appreciably. For example, doses of near-ultraviolet light longer than approximately 300 nm that were effective in mutating or in transforming cells were ineffective in killing them. In respect to pyrimidine dimer induction, several but not all cellular end points were induced by dose ratios of sunlamp light (short-wavelength cutoff, approximately 290 nm) to germicidal lamp light (254 nm) in fairly close accord with the doses required to produce equivalent proportions of dimers. However, for near-ultraviolet light having cutoffs at longer wavelengths, the biological action observed was appreciably greater than what would be predicted from the proportion of dimers induced. From the latter observation, it is inferred that increasing intensities of short-wavelength ultraviolet light, as would be expected from reductions in stratospheric ozone around the earth, would result in smaller increases in biological action, e.g., skin cancer, compared to current levels of action than would be predicted from an action spectrum completely corresponding to that of a pyrimidine dimer induction spectrum in DNA.

Abrogation by novobiocin of cytotoxicity due to the topoisomerase II inhibitor amsacrine in Chinese hamster cells.

Using cultured V79 Chinese hamster cells, we found that novobiocin (or 2,4-dinitrophenol) can abrogate, almost completely, the cytotoxicity due to the topoisomerase II inhibitor amsacrine (mAMSA). V79 cells were sensitive to mAMSA killing at all stages in the cell cycle but mainly in S phase followed by late G1 phase; however, novo rescued cells of all ages. The properties of two kinds of radiation-sensitive Chinese hamster cells were also examined, i.e., the line of V79 cells that can be rescued by caffeine, designated S-10 (H. Utsumi and M.M. Elkind, Radiat. Res., 96: 348-358, 1983); and Chinese hamster ovary cells (P.A. Jeggo and L.M. Kemp, Mutat. Res., 112: 313-327, 1983) which are also sensitive to other DNA-damaging agents. As is the case for exposure to radiation, after mAMSA treatment caffeine rescued V79/S-10 cells. Although Jeggo's Chinese hamster ovary cells were more responsive to mAMSA, novo still abrogated mAMSA toxicity in the mutant cells as well as in the parental Chinese hamster ovary cells 2,4-Dinitrophenol acted similarly to novo with respect to mAMSA killing, but neither compound reduced the ATP content of V79 cells. We propose that one reason for the rescue from mAMSA killing of at least S-phase cells by novo or 2,4-dinitrophenol is their ability transiently to inhibit replicative DNA synthesis.

Amsacrine-induced lesions in DNA and their modulation by novobiocin and 2,4-dinitrophenol.

The cancer chemotherapeutic agent amsacrine, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA), is thought to effect cytotoxicity by inhibiting the ATP-dependent enzyme topoisomerase II in the act of its duplex strand-passing action. Upon protein denaturation, the arrested "cleavable complex" that results gives rise to double- and single-strand breaks (dsbs and ssbs) and DNA-protein cross-links (dpcs). Simultaneous cotreatments with 2,4-dinitrophenol (DNP) or novobiocin (novo) abrogates mAMSA cytotoxicity in Chinese hamster cells (H. Utsumi et al., Cancer Res., 50:2577-2581, 1990). Pulsed-field gel electrophoresis was used to estimate dsbs, velocity sedimentation in alkaline sucrose gradients for ssbs, and alkaline elution without protease digestion for dpcs. Although cotreatment with DNP or novo modulated somewhat the yield of DNA lesions due to mAMSA, quantitatively these changes did not correlate at all with, and therefore could not account for, the reduced lethality that resulted from cotreatments. For example, DNA cotreatment markedly increased the yields of dsbs, ssbs, and dpcs, even though cell killing was appreciably reduced. Furthermore, neither DNP nor novo cotreatment affected the rate, or the completeness of, the repair of mAMSA-induced DNA damage, and neither cotreatment lowered total cellular ATP. Hence, the arresting of the cleavable complex by mAMSA, made evident by lesions in DNA, did not correlate with cytotoxicity. However, cotreatment with either DNP or novo resulted in an enhanced recovery of the mAMSA-induced inhibition of replicative DNA synthesis. Because DNP and novo (transiently) slow down DNA synthesis, it is proposed that these compounds abrogate mAMSA killing of S phase cells by reducing the disorganization of the processing of replicated DNA by topoisomerase II.

OC-02 - Risk of arterial thromboembolism in patients with breast cancer.

INTRODUCTION: Breast cancer is the most common cancer in women and clearly increases the risk of venous thromboembolism. However, its association with arterial thromboembolism is less well defined. AIM: To determine the short-term cumulative incidence and relative hazard of arterial thromboembolism in elderly patients with incident breast cancer. MATERIALS AND METHODS: Using the Surveillance Epidemiology and End Results-Medicare linked database, which includes approximately 28% of all patients diagnosed with cancer in the United States, we identified patients with a new primary diagnosis of breast cancer from 2002 through 2011. These patients were individually matched by age, sex, race, registry, and medical comorbidities to a group of Medicare enrollees without cancer, and each pair was followed through 2012. Validated diagnosis codes were used to identify a primary composite outcome of arterial thromboembolism defined as any ischemic stroke or myocardial infarction. Secondary outcomes included ischemic stroke alone and myocardial infarction alone. Cumulative incidence rates were calculated using competing risk survival statistics. The Gray test was used to compare rates between groups. The proportional hazard assumption was violated for the entirety of patient follow-up; therefore, Cox proportional hazard analysis was performed at discrete time points when the assumption was generally met. RESULTS: We identified 96,666 pairs of breast cancer patients and matched controls. Median age was 75 years and few cancers were advanced at diagnosis (12% stages 3/4). The 3-month cumulative incidence of arterial thromboembolism was 2.1% (95% confidence interval [CI] 2.0-2.2%) in cancer patients compared to 1.4% (95% CI 1.3-1.5%) in controls (hazard ratio [HR] 1.5, 95% CI 1.4-1.6, p<0.01). The short-term risk of each secondary outcome was heightened in the breast cancer group, although the relative hazard for myocardial infarction was higher than for ischemic stroke. The 3-month cumulative incidence of ischemic stroke was 1.3% (95% CI 1.2-1.4%) in cancer patients compared to 1.0% (95% CI 0.9-1.1%) in controls (HR 1.3, 95% CI 1.2-1.4, p<0.01), and the 3-month cumulative incidence of myocardial infarction was 0.9% (95% CI 0.8-0.9%) in cancer patients compared to 0.4% (0.4-0.5%) in controls (HR 2.0, 95% CI 1.8-2.3, p<0.01). Excess risks attenuated over time and were no longer present beyond 1 year. CONCLUSIONS: Patients with incident breast cancer face an increased short-term risk of ischemic stroke and myocardial infarction.

Update on antiplatelet therapy for stroke prevention.

The high rates of mortality and long-term disability associated with ischemic stroke, coupled with its prevalence, necessitate good, long-term preventive strategies. Risk-factor management is effective for individuals with preclinical and clinical cerebrovascular disease. Patients suffering from a transient ischemic attack or stroke are particularly vulnerable to subsequent stroke. Most of these individuals are candidates for antiplatelet treatment to prevent a recurrence. Available antiplatelet therapies include aspirin, ticlopidine, and clopidogrel. The combination of low-dose aspirin plus extended-release dipyridamole has been shown to offer safe, effective antiplatelet therapy for appropriate patients. In the second European Stroke Prevention Study, the combination was found to be significantly more effective than either drug alone, at the cost of relatively few treatment-related adverse effects. This combination is currently recommended as one of the first-line treatments for stroke prevention after first transient ischemic attack or stroke.

Elevated white blood cell count and carotid plaque thickness : the northern manhattan stroke study.

BACKGROUND AND PURPOSE: Elevated leukocyte count has been associated with cardiovascular and cerebrovascular disease in several epidemiological studies. We sought to determine whether white blood cell count (WBC) is associated with carotid plaque thickness in a stroke-free, multiethnic cohort. METHODS: For this cross-sectional analysis, WBC was measured in stroke-free community subjects undergoing carotid duplex Doppler ultrasound. Maximal internal carotid plaque thickness (MICPT) was measured for each subject. Demographic and potential medical confounding factors were analyzed with linear and logistic regression to calculate the effect of quartile of WBC on MICPT. Odds ratios (ORs) and 95% confidence intervals (CIs) for the effect of quartile of WBC on MICPT >/=75th percentile were calculated. All analyses were stratified by race-ethnicity. RESULTS: The mean age of the 1422 subjects was 68.6+/-10.2 years; 40.0% were men; 24.4% were white, 46.9% Hispanic, and 26.7% black. Among Hispanics, compared with the lowest quartile of WBC, those in the highest quartile had significantly increased MICPT (mean difference=0.30 mm, P:=0.0086) after adjustment for age, sex, and other atherosclerotic risk factors. There was no significant increase for blacks or whites. The OR for MICPT >/=75th percentile (1.9 mm) was significantly increased for Hispanics (OR, 2.8; 95% CI, 1.4 to 5.6), marginally elevated for black non-Hispanics (OR, 1.6; 95% CI, 0.8 to 3.2), and not increased for white non-Hispanics (OR, 0.5; 95% CI, 0.2 to 1.1). CONCLUSIONS: Relative elevation in WBC is associated with carotid atherosclerosis, but this relationship differs by race-ethnicity. The association is strongest in Hispanics, intermediate in black non-Hispanics, and not present in white non-Hispanics in this population. Chronic subclinical infection or inflammation may account for this association.

Race-ethnic disparities in the impact of stroke risk factors: the northern Manhattan stroke study.

BACKGROUND AND PURPOSE: Stroke risk factors have been determined in large part through epidemiological studies in white cohorts; as a result, race-ethnic disparities in stroke incidence and mortality rates remained unexplained. The aim in the present study was to compare the prevalence, OR, and etiological fraction (EF) of stroke risk factors among white, blacks, and Caribbean Hispanics living in the same urban community of northern Manhattan. METHODS: In this population-based incident case-control study, cases (n=688) of first ischemic stroke were prospectively matched 1:2 by age, sex, and race-ethnicity with community controls (n=1156). Risk factors were determined through in-person assessment. Conditional logistic regression was used to calculate adjusted ORs in each race-ethnic group. Prevalence and multivariate EFs were determined in each race-ethnic group. RESULTS: Hypertension was an independent risk factor for whites (OR 1.8, EF 25%), blacks (OR 2.0, EF 37%), and Caribbean Hispanics (OR 2.1, EF 32%), but greater prevalence led to elevated EFs among blacks and Caribbean Hispanics. Greater prevalence rates of diabetes increased stroke risk in blacks (OR 1.8, EF 14%) and Caribbean Hispanics (OR 2.1 P<0.05, EF 10%) compared with whites (OR 1.0, EF 0%), whereas atrial fibrillation had a greater prevalence and EF for whites (OR 4.4, EF 20%) compared with blacks (OR 1.7, EF 3%) and Caribbean Hispanics (OR 3.0, EF 2%). Coronary artery disease was most important for whites (OR 1.3, EF 16%), followed by Caribbean Hispanics (OR 1.5, EF 6%) and then blacks (OR 1.1, EF 2%). Prevalence of physical inactivity was greater in Caribbean Hispanics, but an elevated EF was found in all groups. CONCLUSIONS: The prevalence, OR, and EF for stroke risk factors vary by race-ethnicity. These differences are crucial to the etiology of stroke, as well as to the design and implementation of stroke prevention programs.

Modifiers of radiation response in tumor therapy: strategies and expectations.

The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissue, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifiers. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement required from a response modifier to effect significant improvements in tumor cure rates.