Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. METHODS: We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. RESULTS: 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. CONCLUSIONS: A tertiary care cohort of psoriasis patients have a high prevalence of early atherosclerosis, increased hsCRP, and psoriasis remains a risk factor for the presence of atherosclerosis even after adjustment of key confounding clinical factors. Psoriasis may contribute to an accelerated systemic inflammatory cascade resulting in increased risk of CVD and CV events.

Lipoprotein-associated phospholipase A2 and cardiovascular disease risk in HIV infection.

OBJECTIVES: HIV-infected patients on antiretroviral therapy (ART) have an increased cardiovascular disease (CVD) risk as a result of heightened inflammation and immune activation, despite at times having normal lipids and few traditional risk factors. Biomarkers are needed to identify such patients before a clinical event. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA2 and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection. METHODS: One hundred subjects on stable ART with normal fasting low-density lipoprotein (LDL) cholesterol were enrolled in the study. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; > 200 ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated. RESULTS: The median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA2 was 209 (71-402) ng/mL. Fifty-seven per cent of patients had Lp-PLA2 concentrations > 200 ng/mL. Lp-PLA2 was positively correlated with soluble markers of inflammation or immune activation (tumour necrosis factor receptor-II, intercellular and vascular cellular adhesion molecules, and CD14; all R = 0.3; P < 0.01), and negatively correlated with coagulation markers (D-dimer and fibrinogen; both R = -0.2; P < 0.04). Lp-PLA2 was not correlated with lipids, coronary artery calcium score, or flow-mediated vasodilation, but trended towards a significant correlation with carotid intima-media thickness (R = 0.2; P = 0.05). CONCLUSIONS: In this population with stable ART and normal LDL cholesterol, Lp-PLA2 was in the high CVD risk category in the majority of subjects. Lp-PLA2 appears to be associated with inflammation/immune activation, but also with anti-thrombotic effects. Lp-PLA2 may represent a valuable early biomarker of CVD risk in HIV infection before subclinical atherosclerosis can be detected.

Sputum Mycobacterium tuberculosis mRNA as a marker of bacteriologic clearance in response to antituberculosis therapy.

mRNA is a marker of cell viability. Quantifying Mycobacterium tuberculosis mRNA in sputum is a promising tool for monitoring response to antituberculosis therapy and evaluating the efficacy of individual drugs. mRNA levels were measured in sputum specimens from patients with tuberculosis (TB) receiving monotherapy in an early bactericidal activity study of fluoroquinolones and in those receiving a standard rifampin-based regimen in an interleukin-2 (IL-2) trial. In the early bactericidal activity study, sputum for quantitative culture and mRNA analysis was collected for 2 days before and daily during 7 days of study drug administration. In the IL-2 trial, sputum was collected for quantitative culture, Bactec 460 liquid culture, and mRNA analysis throughout the intensive treatment phase. RNA was isolated from digested sputum and tested in quantitative reverse transcription-PCR assays for several gene targets. mRNA for the glyoxylate cycle enzyme isocitrate lyase declined at similar rates in patients receiving isoniazid, gatifloxicin, levofloxacin, and moxifloxacin monotherapy. Isocitrate lyase mRNA correlated highly with CFU in sputum prior to therapy and during 7 days of monotherapy in all treatment arms. Isocitrate lyase mRNA was detectable in sputum of culture-positive TB patients receiving a rifampin-based regimen for 1 month. At 2 months, sputum for isocitrate mRNA correlated more closely with growth in liquid culture than did growth on solid culture medium. Data suggest that isocitrate lyase mRNA is a reliable marker of M. tuberculosis viability.

Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.

OBJECTIVE: To evaluate the early bactericidal activity (EBA) of the new fluoroquinolones levofloxacin, gatifloxacin and moxifloxacin in patients with pulmonary tuberculosis (PTB). DESIGN: Randomized, open-label trial. Forty adults with newly diagnosed smear-positive PTB (10 per arm) were assigned to receive isoniazid (INH) 300 mg, levofloxacin 1000 mg, gatifloxacin 400 mg, or moxifloxacin 400 mg daily for 7 days. Sputum for quantitative culture was collected for 2 days before and daily during 7 days of monotherapy. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (EBA 0-2) and last 5 days of monotherapy (extended EBA, EBA 2-7). Laboratory staff were blinded to treatment assignment. RESULTS: The EBA 0-2 of INH (0.67 log10 cfu/ml/day) was greater than that of moxifloxacin and gatifloxacin (0.33 and 0.35 log10 cfu/ml/day, respectively), but not of levofloxacin 1000 mg daily (0.45 log10 cfu/ml/day) (P = 0.14). Bactericidal activity between days 2 and 7 was similar for all three fluoroquinolones. In a pooled comparison, the EBA 2-7 of the fluoroquinolones was greater than for INH. CONCLUSION: Moxifloxacin, gatifloxacin, and high-dose levofloxacin have excellent EBA, only slightly less than for INH, and greater extended EBA. These drugs warrant further study in the treatment of drug-susceptible TB.

Long-term follow-up after recovery from acute myocardial infarction. Observations on survival, ventricular arrhythmias, and sudden death.

A long-term 12-year follow-up of 248 patients surviving acute myocardial infarction indicated a cumulative survival of 89%, 68%, 53%, and 45% for 1, 5, 10, and 12 years, respectively. When patients were assessed with five routinely obtained clinical factors, significant prognostic stratification of high- and low-risk survival groups extended throughout the follow-up period. Sudden cardiac death was found to be twice as frequent as nonsudden cardiac death, but a significant relationship between sudden death and complex ventricular ectopic beats could not be defined. The extent of complex features of ventricular ectopic beats such as pairs, multiform, repetitive, and R-on-T was inversely related to survival. During the first year after acute myocardial infarction, frequency of ventricular ectopic beats was also inversely related to survival. A long-term effect of frequency on survival, however, could not be demonstrated.

Enzyme-linked immunosorbent assay using Mycobacterium tuberculosis antigen 5 and PPD for the serodiagnosis of tuberculosis.

Enzyme-linked immunosorbent assays (ELISA) of immunoglobulin G antibody to Mycobacterium tuberculosis antigen 5 and tuberculin purified protein derivative (PPD) were assessed for the serodiagnosis of tuberculosis in 41 patients with active tuberculosis, 19 patients with inactive tuberculosis, and 59 healthy control subjects. Patients with active tuberculosis were studied serially at monthly intervals following the initiation of therapy. When contrasted with our earlier studies of sera from patients in Bolivia and Argentina, serum titers in Cleveland patients with active tuberculosis were somewhat lower. Geometric mean titer in patients with active tuberculosis was 1:68 with antigen 5 and 1:46 with PPD. Titer was correlated with patient age, male sex, extent of tuberculosis, and history of prior tuberculosis. However, these associations were not statistically significant. During monthly follow-up for 16 months after the initiation of therapy, ELISA titers remained essentially stable. Thus, no convincing evidence was acquired to support the hypothesis that higher titers in sera from South American patients related to more chronic or more extensive disease. Receiver operating characteristics of ELISA with antigen 5 were better than those obtained using PPD and were similar to those reported by others for sputum smear. In a situation where tuberculosis screening is warranted, ELISA with antigen 5 might have a place if it recognizes a different population than does sputum smear.

Smoking and cognitive impairment: a population-based study.

OBJECTIVE: To test the hypothesis that there is an inverse relationship between smoking and cognitive impairment by examining the prevalence and incidence of such impairment in a representative cohort of older urban residents. DESIGN: Survey follow-up with three interviews over a 4-year period. SETTING: City of Cleveland, Ohio. PARTICIPANTS: Six hundred forty-seven survivors of a population-based, multi-stage probability sample of urban residents, aged 74 years and older in 1984. MEASUREMENTS: Past and present cigarette smoking was measured in 1984 by direct questioning. Cognitive impairment was measured in 1984, 1987, and 1988 by the 10-item Short Portable Mental Status Questionnaire. Mortality was determined at each interview date, and death certificates were obtained. Data were analyzed by univariate analysis, stratified analysis, and multivariate logistic regression. RESULTS: There were 99 cases of cognitive impairment at baseline among 628 individuals for whom complete data were available. Crude data suggest that the prevalence of cognitive impairment was lower among smokers than among non-smokers, but logistic regression, adjusted for age, income, and gender, showed this difference to be non-significant, OR 0.73; 95% CI (0.42, 1.29). Fifty-one new cases of cognitive impairment occurred during the 4-year observation period. Neither the crude data nor logistic regression showed any significant relationship between smoking and the incidence of cognitive impairment, OR 1.03; 95% CI (0.54, 1.99). Four-year mortality did not differ significantly between these older smokers and non-smokers, but smokers died at a relatively younger age and were more likely to die of diseases associated with smoking.

Association of Alzheimer's disease and smoking: the case for sibling controls.

OBJECTIVES: To study the association between cigarette smoking and Alzheimer's Disease (AD). DESIGN: Intrafamily case-control, with sibling controls and a variable number of controls per case. SETTING: AD cases were identified through the Research Registry of the University Hospitals of the Cleveland/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Study subjects were 86 probable AD cases (index cases) and all of their full siblings, alive or dead, aged > or = 50 years, a total of 238 subjects. MEASUREMENTS: Exposure for each individual was ascertained with a questionnaire answered by several informants. Cognitive status of siblings of the AD cases (impaired or intact) was ascertained by telephone using validated instruments. Diagnosis of dementia in cognitively impaired siblings of index cases was not attempted. RESULTS: Chi-square analysis tested for departure from a random distribution of disease across smokers and nonsmokers within families. No significant departure was found utilizing all families (P > .40) nor utilizing those families where only the index case was affected (P > .90). Conditional logistic regression evaluated the association within families, controlling for age, sex, and education. Analyses both included and excluded secondary cases of cognitive impairment. No association was found between smoking and disease (OR = 1.26; 95% confidence interval, 0.66-2.42, and OR = 1.42; 95% confidence interval, 0.69-2.89, respectively). CONCLUSIONS: No significant association was found between smoking and cognitive status. Further, analyses based on the comparison of persons with AD with their unaffected siblings also suggest that smoking does not decrease the risk of AD.

Validation of a Telephone Cognitive Assessment Battery.

OBJECTIVE: To present and evaluate an instrument, the Telephone Cognitive Assessment Battery (TCAB), designed to be administered over the telephone to assess the cognitive status of older individuals. The TCAB addresses mental status, reasoning and executive ability, primary and secondary memory, and language. It consists of six neuropsychological tests and takes approximately 15 to 20 minutes to complete. DESIGN: The instrument is evaluated with a comparative cross-sectional design, with data collected both prospectively and retrospectively. SETTING: The University Hospitals of Cleveland/Case Western Reserve University Alzheimer Center Research Registry. PARTICIPANTS: Forty Alzheimer's Disease cases selected from among those most recently recruited into the Registry and 40 cognitively intact Registry controls. Controls were selected randomly so that the two groups had similar distributions of age, sex, and education. MEASUREMENTS: The cognitive status of all participants was assessed utilizing both the TCAB and the usual in-person Registry evaluation, which includes medical history data and in-person assessment of cognitive status. In order to measure the potential learning effect of repeated testing, half of the cases and half of the controls were recruited and assessed over the telephone with the TCAB before their in-person Registry evaluation (with a waiting period of at least 2 weeks between evaluations), whereas the other two halves received the TCAB after they had become part of the Registry. The TCAB was administered to all participants by a single investigator. Two clinical evaluators, blinded to the Registry diagnosis of the subjects, independently classified the subjects as cognitively impaired, normal, or questionable on the basis of the results of the TCAB and a brief listing of medical illness and depressive symptoms. A final classification was achieved through consensus and subsequently compared with the Registry diagnosis, taken here to be the gold standard. RESULTS: Test scores of subjects assessed by TCAB before receiving the in-person assessment were compared with those of subjects receiving the in-person assessment first. There were no significant differences between mean scores of the two groups (those with TCAB first and those with TCAB last) for either cases or normal controls. High values of the kappa statistic were obtained for the two initial evaluators of the TCAB classification, demonstrating excellent interrater reliability. Regarding the reconciled TCAB classification, the ability of the TCAB to correctly classify subjects according to cognitive status, while controlling for potential confounders such as age and educational level, was assessed by means of discriminant analysis techniques. Knowledge of the TCAB classification and age allowed the correct classification of 95% of the participants; this was not significantly improved by knowledge of other potential determinants. Sensitivity and specificity were calculated under two schema for classifying those subjects in the "questionable" category. Positive and negative predictive values of the TCAB were computed assuming a prevalence of cognitive impairment of 10% in the older population. High negative predictive values (over 99%) were obtained under both schema, whereas the positive predictive values were seen to be more dependent on the classification of questionables. CONCLUSION: Research studies involving ascertainment of cognitive status of older people, particularly those that require periodic follow-up, such as those focusing on healthy aging, commonly suffer from lack of representativeness of subjects, often brought about by problems related to mobility of potential participants. It is also crucial that normal individuals who are recruited initially to serve as controls in epidemiologic studies of dementing illnesses be reevaluated periodically, and this may be hindered by the same obstacles. (ABSTRACT TRUNCATED)

On the use of surrogate respondents for controls in a case-control study of Alzheimer's disease.

OBJECTIVE: To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case-control study of Alzheimer's disease (AD). DESIGN: Comparative study of matched responses to questionnaire ascertaining lifestyle issues. SETTING: University Hospitals/Case Western Reserve University Alzheimer Center. PARTICIPANTS: Controls (n = 50) were identified through the Research Registry. Surrogates (n = 50) were their healthy relatives or friends. MEASUREMENTS: Answers in the areas of demographic and occupational history, smoking habits, medical history, dietary intake, and leisure and work activities were recorded. The analysis was based on methods for paired data. Continuous variables were analyzed, focusing on paired differences between self and surrogate responses. RESULTS: For occupations and exposures, over 80% of the surrogates agreed with the subjects on over 80% of the questions. On smoking history, over 90% of the surrogates agreed with the subjects on over 70% of the questions. On leisure and work activities, over 70% of the surrogates agreed with the subjects on over 50% of the questions. There was less agreement regarding medical history. For continuous variables, most paired t-tests of zero mean difference between self and surrogate responses resulted in nonrejection of this hypothesis. Computed mean differences were not always positive or always negative. CONCLUSION: We did not find systematic under- or overreporting by the surrogates of the controls. Therefore, if there are biases in the responses of surrogates of the AD cases in our case-control study, they would not be canceled out by using surrogates for the controls.

Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report.

A prospective, randomized clinical trial of three treatment regimens: (1) Cytoxan, methotrexate, and 5-fluorouracil (CMF), (2) CMF plus the antiestrogen drug, tamoxifen (CMFT), and (3) CMFT plus bacillus Calmette-Guerin (BCG) vaccinations in women with stage 22 breast cancer is reported. All patients underwent mastectomy and estrogen receptor (ER) analysis was performed. The results of this study show that patients with ER- tumors have recurrences more rapidly and have a higher mortality rate than patients with ER+ tumors (P less than 0.0001). In ER+ patients CMFT treatment is more effective in delaying recurrence than CMF alone at 33 months (P = 0.0176). This effect appears to be occurring in both premenopausal and postmenopausal women. In ER- patients the recurrence rate is high, and there is no significant difference among the three treatment groups. In premenopausal patients treated with CMF alone, however, ER- patients recur more rapidly than ER+ patients (P = 0.0313) and suggests that the effect of CMF may be related to the suppression of ovarian function. These findings have demonstrated a significant role for the use of antiestrogen therapy in patients with state II, ER+ breast cancer.

Arrest disorders and infant brain damage.

In the past, difficult labors have been associated with maternal and infant damage. Today, changing patient management is associated with less trauma and more frequent use of cesarean births to avoid potential fetal neurologic damage. In this report, arrests of dilatation and descent and prolongation of the decelerative phase of labor were reviewed with respect to the later appearance of brain damage in infants after 2 years of age, in association with obstetric interventions including cesarean birth, forceps, and oxytocin. Charts of 413 infants born after abnormal labors were studied. Log-linear analysis was performed to determine the contribution of method of delivery and oxytocin use to the presence of neurologic abnormalities. Statistical testing ruled out the presence in the model of a three-way interaction, and excluded the two-way interactions of neurologic abnormalities-oxytocin use and neurologic abnormalities-method of delivery. Chi-square tests of partial association and marginal association for the delivery-oxytocin interaction yielded values of 33.54 (P less than .0001) and 33.78 (P less than .00001). This model asserted that method of delivery and use of oxytocin were unrelated to the presence of neurologic abnormalities, but were related to each other.

Abnormal labor and infant brain damage.

OBJECTIVE: To determine whether arrest disorders result in increased neurologic abnormalities in infancy or childhood. METHODS: Four hundred thirteen infants with arrest disorders as defined by Friedman criteria were matched to a similar population without arrest disorders. The median length of follow-up was 6 years for the study infants and 5.07 years for the controls. The numbers of children with abnormalities in the groups with and without arrest disorders, as well as the specific abnormalities encountered, were stratified by method of delivery. RESULTS: Thirty neurologic abnormalities were found in the arrest group and 37 in the control group; thus, the null hypotheses could not be rejected. In addition, although the control group was not followed as long as the study population, the diagnosis of abnormalities was more frequent in the later years in the controls. This suggests that had the follow-ups been equal, there would have been stronger proof that arrest by itself was not associated with infant brain damage. CONCLUSION: Our study confirms that labor diagnoses of prolonged active phase, protractions or arrests, and failure to descend are not associated with increased neurologic abnormalities. Delivery by cesarean or vaginal birth and use of oxytocin are not factors in the etiology of major brain damage.

Evaluation of mycobacterial antigens in an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of tuberculosis.

Five mycobacterial antigens were compared in an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of tuberculosis. The antigens studied were an unheated sterile culture filtrate of Mycobacterium tuberculosis, tuberculin purified protein derivative (PPD) from M. tuberculosis (PPDa), purified cytoplasmic protein antigens 5 and 6 from M. tuberculosis, and a PPD prepared from M. kansasi (PPDk). Multivariate analysis of variance showed that geometric mean titres obtained with each of the antigens in ELISA were significantly different in tuberculosis patients and in control groups. The covariation of the ELISA results with the five antigens was highly interdependent. Analysis of receiver operating characteristics revealed that the most accurate test was obtained with antigen 5. M. tuberculosis PPD, M. tuberculosis antigen 6, and M. tuberculosis culture filtrate were, in descending order, less accurate.

Plasma homocysteine, vitamin B12 and folate in Alzheimer's patients and healthy Arabs in Israel.

High plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and stroke and Alzheimer's disease (AD). An inverse relationship has been reported between tHcy and plasma B12 and folate levels. Seventy-nine AD patients and 156 controls from three Arab villages in northern Israel participated. Plasma tHcy, B12 and folate levels were determined. Data were analyzed using univariate statistical tests and logistical regression with confounders. tHcy was significantly higher in AD patients (20.6+/-8.7 micromol/l) than in controls (16.4+/-6.5 micromol/l) (p=0.03) after correction for year of birth, gender and smoking status. Plasma B12 (322.9+/-136.0/350.5+/-175.3 pmol/l) and plasma folate (4.5+/-3.8/4.9+/-2.6 nmol/l) levels did not differ significantly between AD patients and controls. Subjects in the highest tHcy tertile or in the lowest B12 and folate tertiles did not have greater risk to develop AD. In this population residing in Arab villages in northern Israel, tHcy levels were significantly higher among AD patients than in controls. Plasma B12 and folate levels were lower among cases but were not significant. There was not a significant association between plasma tHcy, B12 and folate levels in controls or AD patients. High levels of tHcy may suggest the need for folate and vitamin B12 supplementation in this population.

Religiosity and perceived rewards of black and white caregivers.

Using data from a larger study of caregivers of the elderly, this study explores the extent to which religiosity variables function as mediators of the effects of situational/demographic factors on perceived caregiver rewards. In the parent project, random digit dialing was used to select 136 Black and 255 White caregivers of community-dwelling elders for face-to-face interviews. Regression analyses revealed that Black caregivers perceived higher levels of rewards than Whites and the relationship between race and perceived rewards was mediated by comfort from religion and prayer. Blacks and Whites with more education reported fewer perceived rewards than caregivers with less education.

Statistical certification of eradication of poliomyelitis in the Americas.

The last confirmed case of paralytic poliomyelitis due to indigenous wild poliovirus in the Americas occurred in Peru in 1991. In 1994 the International Commission on Polio Eradication of the Pan American Health Organization (PAHO) deemed eradication of polio from the area to have occurred, based on its strategic efforts and the observed results. A mathematical model is presented here which relates the time elapsed since that last detected case of paralytic poliomyelitis caused by wild poliovirus to the probability that the transmission of indigenous wild poliovirus has been stopped. The appropriateness of applying the model to various geographical areas of the Americas is investigated using data about the occurrence of confirmed cases of polio since 1984, the time of the eradication initiative adopted by PAHO. The model suggests that if four year have elapsed since the last reported confirmed case of polio caused by wild poliovirus, and no other confirmed cases have been identified, the probability of undetected indigenous wild poliovirus transmission is less than 5%. An important assumption is that the eradication strategy implemented by PAHO has yielded steady improvements. A consequence of this approach is that the annual probabilities of persistence given by the model are conservative, in the sense of being higher than the true, but unknown a priori probabilities, and more so with each passing year. It is thus seen that the model results are compatible with the conclusion reached by PAHO in 1994. The model takes into account the intensity of surveillance of each country in the region, measured by the corresponding rates of acute flaccid paralysis (AFP). Because importations of wild poliovirus may occur from other regions of the world, surveillance efforts are being maintained in the Americas until global eradication has been achieved.

Plasma total homocysteine levels, dietary vitamin B6 and folate intake in AD and healthy aging.

PURPOSE: To study the association between Alzheimer s disease (AD) and plasma total homocysteine (tHcy), dietary folate and vitamin B6. METHODS: 64 AD patients were matched by gender, age, and smoking status to 64 healthy controls. tHcy was determined using an automated immunoassay. Dietary patterns for three age periods (20-39, 40-59, and 60 + yrs) were assessed using a questionnaire adapted from the Block Health Habits and History Questionnaire. Respondents (cases by proxy) reported food frequencies, which were translated into estimated daily nutrient intakes. APOE genotype, cognitive performance (CDR, MMSE), blood lipids, and albumin were obtained for patients and controls. RESULTS: tHcy did not differ significantly between controls (11.5 +/- 3.7 mmol/L) and AD patients (12.3 +/- 4.3 mmol/L)(p=0.25). tHcy levels were not related in AD patients or controls to education, CDR, MMSE, blood lipids, albumin or ApoE genotype (p>0.15). There was a negative correlation between plasma tHcy and triglyceride levels in AD patients (p=0.023), but not in controls. AD patients consumed significantly less dietary vitamin B6 (p=0.05) and folate (p=0.001) after age 60 than controls. CONCLUSIONS: Although plasma tHcy levels were higher in cases than controls, this difference was not significant. tHcy levels were not related to cognitive status. Plasma tHcy was inversely correlated with triglyceride levels in AD patients but not in controls.

Effects of educational attainment on the clinical expression of Alzheimer's disease: results from a research registry.

The "reserve" hypothesis suggests that education should affect the clinical expression of Alzheimer's disease (AD), but results from studies examining this idea are not consistent. In a single study, we evaluated the effects of educational attainment on three aspects of the clinical expression of AD: age at symptom onset, rate of cognitive decline, and survival. Subjects were 258 persons with mild- or moderate-stage Alzheimer's, drawn from our AD Research Registry. With statistical adjustment for confounding variables present in a clinic-based design, we found that higher educational attainment was associated with slightly earlier reports of symptom onset and a slower rate of cognitive decline on the Mini-Mental State Exam (MMSE). Education did not affect time of survival until death. We conclude that, for subjects in our sample, education had modest effects on aspects of the clinical expression of AD. These effects were not fully consistent with predictions derived from the "reserve" hypothesis.

Time to detection of Mycobacterium tuberculosis as an alternative to quantitative cultures.

Testing new drugs is critical to improving the treatment of tuberculosis. Quantitative cultures of Mycobacterium tuberculosis on solid media have been used in Phase 1 and 2 trials, but are time and resource intensive. Time to detection (TTD) of growth of M. tuberculosis in automated liquid culture systems is an alternative. TTD has been shown to correlate with CFU in quantitative cultures, and is faster and simpler to perform. We compared TTD in the BACTEC 460 liquid culture system with CFU in a clinical trial that included 110 subjects. Comparing all sputum cultures collected between baseline and 2 months we found a strong negative correlation between log(10) CFU and TTD (rho = -0.91). In addition, when TTD at baseline was compared with 1 and 2 month sputum culture positivity, subjects whose cultures were negative after 1 and 2 months had a significantly longer median baseline TTD compared with subjects whose cultures were positive at 1 and 2 months (5 vs. 3 days and 3 vs. 2 days, respectively). TTD compares closely with CFU and represents a faster, simpler alternative to quantitative cultures.