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SUMMARYSurveillance of acute hepatitis B in England is necessary to estimate incidence, determine routes of transmission and inform public health actions. Here we describe an automated process to extract information on testing for markers of hepatitis B infection in English sentinel laboratories between 2002 and 2008. The resulting data were used to identify individuals with acute infections, describe their characteristics and estimate the incidence of infection. Two-thirds of acute infections were in males. Heterosexual exposure and injecting drug use were the main risks reported. Annual incidence was estimated at 1·3/100 000 person-years overall (1·7 and 0·6 for males and females, respectively) and declined each year. Automated extraction of hepatitis B markers, including quantitative results where available, can help to classify HBV status more accurately for surveillance. HBV incidence in England is at its lowest level in recent years. [ABSTRACT FROM AUTHOR]

This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25-44 years. Overall 5.7% (3333/58144, range 2.8-7.7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance. [ABSTRACT FROM AUTHOR]

Background: Current knowledge of age-associated increases in blood pressure is based primarily on unscreened population studies that may not be representative of healthy men and women. We examined longitudinal patterns of change in blood pressure in healthy male and female volunteers from the Baltimore Longitudinal Study of Aging (BLSA).Methods: Longitudinal mixed-effects regression models are used to estimate the age-associated changes in blood pressure in 1307 men (age 17-97) and 333 women (age 18-93) who have been followed for up to 32 years (mean: 8.4 years for men and 3.4 years for women) and who have been screened for health problems or medications that affect blood pressure.Results: On average, systolic pressure is relatively stable in men and women until approximately age 45, increases at 5-8 mm Hg per decade in middle age, then accelerates in men and stabilizes in women. Diastolic pressure increases at 1 mm Hg per decade at all ages in men, whereas in women the rate of change in diastolic pressure increases in middle age and then plateaus and may decline after age 70. Additional findings include: (a) BLSA cross-sectional and longitudinal findings are more similar than has been observed in studies of unscreened samples; (b) there is no evidence of a gender cross-over in this group of healthy men and women; and (c) compared to previous studies of unscreened samples, healthy BLSA men and women show a weaker association between baseline blood pressure and subsequent rate of blood pressure change.Conclusions: These findings suggest that several previously described age-associated patterns of blood pressure change partially reflect the effects of hypertension and its treatment, rather than intrinsic age changes in the blood pressure of healthy individuals. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine heterogeneity in 1-year functional recovery following postacute rehabilitation among older adults with hip fracture. METHODS: Two hundred twenty-five community-dwelling older adults with hip fracture who received postacute rehabilitation in 5 rehabilitation facilities in Baltimore, Maryland, were recruited during postacute rehabilitation (baseline) and follow-up at 2, 6, and 12 months following postacute rehabilitation discharge. Functional recovery was measured by the activities of daily living (ADL) and instrumental activities of daily living (IADL) scores. A mixed-effect model was used to examine factors associated with postacute rehabilitation functional recovery; fixed and random effects estimates from the models were used to demonstrate heterogeneity in functional recovery. RESULTS: Results indicated that there was an overall trend in both ADL and IADL functional improvement at 2 months following postacute rehabilitation, with continued improvement to 6 months, after which functional recovery slowed down and remained constant through the year. Individuals whose functional recovery did not conform to these patterns were identified and their functional recovery that deviated substantially from the group mean was demonstrated. CONCLUSIONS: Functional recovery patterns in elderly hip fracture patients are heterogeneous. To foster functional independence, health care professionals should consider individual recovery trajectories using a modeling approach appropriate for longitudinal or repeated measurement data such as a linear mixed-effects model when designing individualized rehabilitation and postacute rehabilitation care plans. [ABSTRACT FROM AUTHOR]

Purpose: Previous DTI studies reported microstructural changes in white matter of patients receiving treatment for brain malignancies. The primary aim of this prospective pilot longitudinal study was to examine if DTI can detect microstructural changes in deep gray matter (as evaluated by the apparent diffusion coefficient, ADC) between pediatric patients treated with cranial radiation therapy and typically developing healthy children. The relationship between ADC and neurobehavioral performance was also examined., Methods: ADC was measured at 1.5 T in the caudate, putamen, globus pallidus, thalamus, and hippocampus in nine patients (mean age 11.8 years) and nine age-matched healthy controls. The study was designed with four visits: baseline, 6-month, 15-month, and 27-month follow-ups., Results: Patients had 24 % higher overall mean ADC in the hippocampus compared with controls (p = 0.003). Post hoc analyses revealed significantly elevated ADC at baseline (p = 0.003) and at the 27-month follow-up (p = 0.006). Nevertheless, patients performed normally on a verbal memory test considered to be a hippocampus-related function. Relative to controls, patients' performance on the tests of the visual-spatial working memory decreased over time (group by visit, p = 0.036). Both patients and controls showed a decline in motor speed with increasing ADC in the globus pallidus and putamen., Conclusions: Childhood brain malignancies and their treatment may affect gray matter microstructure as measured by water diffusion. Significant findings in the hippocampus but not other regions suggest that differences in tissue sensitivity to disease- and treatment-related injury among gray matter regions may exist. ADC in basal ganglia may be associated with motor performance.

Using several variables known to be related to prostate cancer, a multivariate classification method is developed to predict the onset of clinical prostate cancer. A multivariate mixed-effects model is used to describe longitudinal changes in prostate specific antigen (PSA), a free testosterone index (FTI), and body mass index (BMI) before any clinical evidence of prostate cancer. The patterns of change in these three variables are allowed to vary depending on whether the subject develops prostate cancer or not and the severity of the prostate cancer at diagnosis. An application of Bayes' theorem provides posterior probabilities that we use to predict whether an individual will develop prostate cancer and, if so, whether it is a high-risk or a low-risk cancer. The classification rule is applied sequentially one multivariate observation at a time until the subject is classified as a cancer case or until the last observation has been used. We perform the analyses using each of the three variables individually, combined together in pairs, and all three variables together in one analysis. We compare the classification results among the various analyses and a simulation study demonstrates how the sensitivity of prediction changes with respect to the number and type of variables used in the prediction process.

Most industrialized countries maintain surveillance programs for monitoring transmissible infection in blood donations, revising approaches to methodology and risk assessment as new threats emerge. A comparison of programs in the United States, Canada, France, the UK, and Australia indicates that they have similar function, although the structure of blood programs vary as does the extent and nature of formal ties with public health. The emergence of HIV in the late 1970s and early 1980s was key in recognizing that surveillance systems specific to blood transfusion were essential. Hence, most industrialized countries monitor transfusion-transmissible infections in donors and evaluate the impact of new testing and of predonation screening strategies. Emerging infections since HIV have had different transmission pathways and challenged blood programs to draw upon resources for a rapid and effective response, with recognition that the original focus on sexual/drug-related risk of HIV and hepatitis was inadequate. The focus of surveillance programs on new and emerging pathogens fulfills a key role in risk assessment and policy formulation. The precise nature of such activities varies by country because of the structure of the blood programs and surveillance systems, the strategic focus of the blood programs, and the epidemiology of disease in each country., (Copyright © 2012. Published by Elsevier Inc.)

Human T-lymphotropic virus (HTLV) infection is rare in the United Kingdom (UK) and few studies are available worldwide. Following introduction of blood donation testing in 2002, a cohort of individuals could be identified and prospectively recruited to describe progression and onset of disease. Here we describe baseline characteristics of participants, and evaluate recruitment into the UK HTLV National Register over the first six years, from July 2003 to June 2009. A multicentre cohort study recruited participants from the UK blood services (recipients and donors) and specialist HTLV clinics. Almost half of the 148 participants recruited were blood donors, nine were blood transfusion recipients, 40 contacts and 29 clinic attendees (nine asymptomatic and 20 symptomatic). Most participants were HTLV-1 positive (n=115); 11 had HTLV-2 and 22 were HTLV-negative. Baseline self-completion questionnaires were received for 83%. The most commonly reported condition was a past operation/serious illness (69%). Twenty-six participants reported four or more possible signs/symptoms of HTLV-1-associated myelopathy/tropical spastic paraparesis. Recruitment into a study of a rare, long-term infection is challenging. This cohort will enable descriptions of HTLV-associated disease progression amongst people recruited from varying sources; it is the first prospective study of its kind in Europe.

BACKGROUND AND OBJECTIVES  One component of the rationale for lifetime exclusion of men who have sex with men (MSM) from blood donation in the UK is the probable reduction in the risk of transfusion-transmitted HIV; this exclusion has recently been questioned. MATERIALS AND METHODS  Data about HIV in blood donors and MSM were analysed to estimate the risk of infectious donations entering the blood supply under different scenarios of donor selection criteria (and donor compliance) for MSM and a heterosexual group with increased risk of HIV. RESULTS  In 2005-2007, a change from lifetime exclusion of MSM to 5-year deferral or no deferral increased the point estimate of HIV risk by between 0·4% and 7·4% depending on compliance with the deferral (range -4% to 15%) and 26·5% (range 18% to 43%) respectively. A change from a 12-month deferral of the high-risk heterosexual group to lifetime exclusion reduced the estimated risk by about 7·2% (range 6% to 9%). Each point estimate was within the probable range of risk under the current criteria. CONCLUSION  If prevalence is the only factor affected by a reduced deferral, then the increased risk of HIV is probably negligible. However, the impact of a change depends on compliance; if this stays the same or worsens, the risk is expected to increase because of more incident infections in MSM who donate blood. The risk of transfusion-transmitted HIV could probably be reduced further by improving compliance with any exclusion, particularly after recent risk behaviours., (© 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.)

Background: Globally, of all infections that donations are tested for, hepatitis B has the highest residual risk of transfusion transmission, despite donor selection criteria and advances in testing. Every blood donation in England and Wales is tested for hepatitis B surface antigen. Knowledge of infections being detected can inform donor selection and testing strategies., Study Design and Methods: Data on donation testing and infections detected are collated by the NHS Blood and Transplant and Health Protection Agency Epidemiology Unit. Infected donors are classified as having acute or chronic hepatitis B virus (HBV) by a clinician; their demographic characteristics were described. The prevalence (by acute or chronic HBV status, ethnicity, and geography) and incidence of infection were calculated between 1996 and 2008. The residual risk was calculated for four periods using a modification of the incidence and window period model; the effects of modifying variables were investigated., Results: Most infections (1047/1155) detected were chronic and seen in new donors. People with acute infections were more likely to be white and/or born in Western Europe. Prevalence was highest in donors from minority ethnic communities and in London. Incidence in repeat donors has halved in recent years. The estimated frequency of an infectious donation being missed was 1.37 per million donations (2006-2008), the lowest since surveillance began or three per year., Conclusion: Many HBV infections in England and Wales were detected among new donors, who had chronic infection and were born overseas. The residual risk of infection declined over the 13 study years, but is still higher for HBV than other viral infections for which testing is undertaken., (© 2011 American Association of Blood Banks.)

Background: Lookback is considered when human immunodeficiency virus (HIV) is detected in a repeat blood donor in case the immediately previous negative donation was donated in the infectious window period (IWP) or the assay(s) produced a false-negative result. HIV lookback investigations undertaken by NHS Blood and Transplant and the Welsh Blood Service between October 1995 and December 2008 are described., Study Design and Methods: Investigations were undertaken into the previous negative donations of 113 HIV-infected donors, including retrospective testing of archive samples, tracing of components, and identification of recipients who were offered HIV testing when appropriate. Data were collated on HIV seroconverters and outcome of the lookback was summarized., Results: Two previous negative donations given before the introduction of minipool nucleic acid testing (MP-NAT) screening were confirmed positive by individual retrospective polymerase chain reaction (PCR) testing of the archive specimen. Red blood cell components had been transfused from both donations. One recipient died after transfusion, and the other was alive and tested HIV positive. All 23 (20%) donations previously testing negative by MP-NAT were confirmed to be PCR negative on individual testing of an archive specimen and none of the tested recipients of these donations had evidence of transfusion-transmitted HIV., Conclusion: The yield of lookback was low with one positive recipient identified over 13 years of surveillance: HIV transmission occurred from a window period donation given before the introduction of MP-NAT screening and would have been detected using current testing methods. Current residual risk estimates for the United Kingdom predict that HIV lookback will be of limited benefit, as demonstrated by our data., (© 2010 American Association of Blood Banks.)

Background: The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period., Methods: We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up., Results: Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001]., Conclusion: Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection.

Background: Previous studies on blood pressure (BP) indices as a predictor of coronary heart disease (CHD) have provided equivocal results and generally relied on Cox proportional hazards regression methodology, with age and sex accounting for most of the predictive capability of the model., Objective: The aim of the present study was to use serially collected BP measurements to examine age-and gender-related differences in BP indices for predicting CHD., Methods: The predictive accuracy of time-dependent BP indices for CHD was investigated using a method of risk prediction based on posterior probabilities calculated from mixed-effects regression to utilize intraindividual differences in serial BP measurements according to age changes within gender groups. Data were collected prospectively from 2 community-dwelling cohort studies in the United States (Baltimore Longitudinal Study of Aging [BLSA]) and Europe (Vorarlberg Health Monitoring and Promotion Program [VHM&PP])., Results: The study comprised 152,633 participants (aged 30-74 years) and 610,061 BP measurements. During mean follow-up of 7.5 years, 2457 nonfatal and fatal CHD events were observed. In both study populations, pulse pressure (PP) and systolic blood pressure (SBP) performed best as individual predictors of CHD in women (area under the receiver operating characteristic curve [AUC(ROC)] was between 0.83 and 0.85 for PP, and between 0.77 and 0.81 for SBP). Mean arterial pressure (MAP) and diastolic blood pressure (DBP) performed better for men (AUC(ROC) = 0.67 and 0.65 for MAP and DBP, respectively, in the BLSA; AUC(ROC) = 0.77 and 0.75 in the VHM&PP) than for women (AUC(ROC) = 0.60 for both MAP and DBP in the BLSA; AUC(ROC) = 0.75 and 0.52, respectively, in the VHM&PP). The degree of discrimination in both populations was overall greater but more varied for all BP indices for women (AUC(ROC) estimates between 0.85 [PP in the VHM&PP] and 0.52 [DBP in the VHM&PP]) than for men (AUC(ROC) estimates between 0.78 [MAP + PP in the VHM&PP] and 0.63 [PP in the BLSA])., Conclusion: Our findings indicate differences in discrimination between women and men in the accuracy of longitudinally collected BP measurements for predicting CHD, implicating the usefulness of gender-specific BP indices to assess individual CHD risk., (Copyright © 2010. Published by EM Inc USA.)

Background: Identification of HCV genotype is a prerequisite for anti-viral treatment in England. Treatment length and sustained virological response rates vary by genotype. Therefore knowledge of circulating HCV genotypes is important for health-care providers., Objectives: To describe the HCV genotypes identified in English laboratories and to investigate changes over time; sub-analysis of young adults (15-24 years) to provide information on recently circulating genotypes., Study Design: Data from the national reference laboratory and 19 English laboratories participating in the sentinel surveillance of hepatitis testing study were analysed. Multinomial regression was used to investigate trends in genotypes identified between 2002 and 2007., Results: HCV genotypes were available for 18,031 individuals. The majority (89%) of people were genotypes 1 and 3; 3a was the single largest subtype. Half of people born between 1960 and 1989 were genotype 3a and the majority of South Asian people were genotype 3a. People born pre-1940 were nine times more likely to have genotype 1b than 3a. The proportion of 1b infections, relative to 3a, declined over time, but, after adjusting for birth cohort, this effect disappeared. There was no evidence of a relative change in 1a infections., Conclusions: This is the largest study of genotypes identified in England to date. Changes in genotypes over time were due to decreased genotyping of older individuals. As the population ages, the proportion of more difficult to treat genotypes may decline, leading to possible cost-savings for health-care providers, with a higher chance of achieving sustained virological response., (Copyright 2010 Elsevier B.V. All rights reserved.)

Epidemiologic studies indicate that elevated levels of gamma-glutamyltransferase (GGT), a key enzyme of glutathione metabolism, might be associated with increased cancer risk. Furthermore, preclinical studies support a role for GGT in tumor invasion and progression. However, the relationship between GGT and risks of cervical intraepithelial neoplasia III (CIN-III) and invasive cervical cancer (ICC) have not been evaluated. We investigated the association of enzymatically determined GGT in blood serum with subsequent incidence of CIN-III and ICC in a prospective population-based cohort of 92,843 women ages 18 to 95, of whom 79% had at least one gynecologic examination including Pap smear testing during follow-up. Cox regression was used to compute adjusted hazard ratios (HR) with 95% confidence intervals for the association of GGT with CIN-III and ICC. During median follow-up of 13.8 years, 702 CIN-III and 117 ICC diagnoses were observed. Compared with normal low GGT (<17.99 units/L), risk of ICC was significantly elevated for all other baseline GGT categories, with adjusted HRs of 2.31 (1.49-3.59) for normal high GGT (18.00-35.99 units/L), 2.76 (1.52-5.02) for elevated GGT (36.00-71.99 units/L), and 3.38 (1.63-7.00) for highly elevated GGT [>72.00 units/L; P trend < 0.0001, HR log unit increase 3.45 (1.92-6.19)]. In contrast, associations between GGT serum levels and CIN-III risk were not statistically significant in the main analysis. Exclusion of the first 2 or 5 years of follow-up did not change the results. Effects did not differ by age, body mass index, or socioeconomic status. Our findings implicate GGT in the progression of premalignant cervical lesions to invasive cancer., ((c)2010 AACR.)

Background: The relationship between serum cholesterol and cancer incidence remains controversial., Patients and Methods: We investigated the association of total serum cholesterol (TSC) with subsequent cancer incidence in a population-based cohort of 172 210 Austrian adults prospectively followed up for a median of 13.0 years. Cox regression, allowing for time-dependent effects, was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the association of TSC with cancer., Results: We observed pronounced short-term associations of TSC and overall cancer incidence in both men and women. For malignancies diagnosed shortly (<5 months) after baseline TSC measurement, the highest TSC tertile (>235.0 mg/dl in men and >229.0 in women) compared with the lowest tertile (<194.0 mg/dl in men and <190.0 in women) was associated with a significantly lower overall cancer risk [HR = 0.58 (95% CI 0.43-0.78, P(trend) = 0.0001) in men, HR = 0.69 (95% CI 0.49-0.99, P(trend) = 0.03) in women]. However, after roughly 5 months from baseline measurement, overall cancer risk was not significantly associated with TSC. The short-term inverse association of TSC with cancer was mainly driven by malignancies of the digestive organs and lymphoid and hematopoietic tissue., Conclusion: The short-term decrease of cancer risk seen for high levels of TSC may largely capture preclinical effects of cancer on TSC.

Objectives: It is recognized that ethnic group is important in describing differences in infection and disease, but is often not routinely available to surveillance systems. Computerized programmes, such as NamPehchan, can assign ethnicity according to name; however, sensitivity and positive predictive value (PPV) can vary. The aim of this study was to assess whether the sensitivity and PPV of NamPehchan had changed, after an observation that surnames previously associated with South Asians were increasingly reported as Black., Study Design: Cross-sectional., Methods: NamPehchan was used to classify women as South Asian using name, and compared with the gold standard (midwife-reported ethnicity). Sensitivity and PPV were calculated overall and by year. Frequency of infection by ethnic group was estimated., Results: A total of 627 women positive for hepatitis B surface antigen were identified. The majority were from minority ethnic groups, particularly Asian. The overall sensitivity of NamPehchan was 74.5% and PPV was 68.5%. Almost 50% of Black African women were classified as South Asian by NamPehchan., Conclusions: Immigration from African countries has reduced the sensitivity of NamPehchan in this group. Care is needed when using NamPehchan for groups which include Africans from Muslim areas, as misclassification is likely to occur.

Matching individuals reported to a sentinel surveillance scheme for hepatitis C between 2000 and 2005 to individuals with a hospital episode for hepatitis C-related liver disease in the same hospitals, we estimated that the number of cases of hepatitis C-related end-stage liver disease in these English hospitals was 42% (597/419) higher than Hospital Episode Statistics (HES) would indicate. Further, matching records of hepatitis C-related deaths in HES to death certificates, we estimated that, between 2000 and 2005, the true number of deaths from hepatitis C-related end-stage liver disease was between 185% (353/124) and 257% (378/106) higher than the number recorded in routine mortality statistics. We provide estimates of under-recording that can be used to modify existing models of disease burden due to hepatitis C and provide a simple approach to improve the monitoring of trends in severe hepatitis C-related morbidity over time.

Background: This article examines how different parameterizations of age and time in modeling observational longitudinal data can affect results., Methods: When individuals of different ages at study entry are considered, it becomes necessary to distinguish between longitudinal and cross-sectional differences to overcome possible selection biases., Results: Various models were fitted using data from longitudinal studies with participants with different ages and different follow-up lengths. Decomposing age into two components-age at entry into the study (first age) and the longitudinal follow-up (time) compared with considering age alone-leads to different conclusions., Conclusions: In general, models using both first age and time terms performed better, and these terms are usually necessary to correctly analyze longitudinal data.

Purpose: We sought to investigate the effect of serum uric acid (SUA) levels on risk of cancer incidence in men and to flexibly determine the shape of this association by using a novel analytical approach., Methods: A population-based cohort of 78,850 Austrian men who received 264,347 serial SUA measurements was prospectively followed-up for a median of 12.4 years. Data were collected between 1985 and 2003. Penalized splines (P-splines) in extended Cox-type additive hazard regression were used to flexibly model the association between SUA, as a time-dependent covariate, and risk of overall and site-specific cancer incidence and to calculate adjusted hazard ratios with their 95% confidence intervals., Results: During follow-up 5189 incident cancers were observed. Restricted maximum-likelihood optimizing P-spline models revealed a moderately J-shaped effect of SUA on risk of overall cancer incidence, with statistically significantly increased hazard ratios in the upper third of the SUA distribution. Increased SUA (>/=8.00 mg/dL) further significantly increased risk for several site-specific malignancies, with P-spline analyses providing detailed insight about the shape of the association with these outcomes., Conclusions: Our study is the first to demonstrate a dose-response association between SUA and cancer incidence in men, simultaneously reporting on the usefulness of a novel methodological framework in epidemiologic research.

Recently, we developed an improved comet assay protocol for evaluating single-strand break repair capacity (SSB-RC) in unstimulated cryopreserved human peripheral blood mononuclear cells (PBMCs). This methodology facilitates control of interexperimental variability [A.R. Trzeciak, J. Barnes, M.K. Evans, A modified alkaline comet assay for measuring DNA repair capacity in human populations. Radiat. Res. 169 (2008) 110-121]. The fast component of SSB repair (F-SSB-RC) was assessed using a novel parameter, the initial rate of DNA repair, and the widely used half-time of DNA repair. The slow component of SSB repair (S-SSB-RC) was estimated using the residual DNA damage after 60 min. We have examined repair of gamma-radiation-induced DNA damage in PBMCs from four age-matched groups of male and female whites and African-Americans between ages 30 and 64. There is an increase in F-SSB-RC with age in white females (P<0.01) and nonsignificant decrease in F-SSB-RC in African-American females (P=0.061). F-SSB-RC is lower in white females than in white males (P<0.01). There is a decrease in F-SSB-RC with age in African-American females as compared to white females (P<0.002) and African-American males (nonsignificant, P=0.059). Age, sex, and race had a similar effect on intercellular variability of DNA damage in gamma-irradiated and repairing PBMCs. Our findings suggest that age, sex, and race influence SSB-RC as measured by the alkaline comet assay. SSB-RC may be a useful clinical biomarker.

The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.

Preliminary findings suggest ongoing HCV transmission among MSM infected with human immunodeficiency virus (HIV) and that enhanced surveillance for newly acquired HCV in MSM is feasible.

Background and Objectives: Infections can be transmitted through donated tissue products, such as femoral heads. Here we describe infections detected through microbiological testing of English surgical bone and deceased donors (2001-2006) and estimate the residual risk of infection., Materials and Methods: Data on infected tissue donors identified by NHS Blood and Transplant (NHSBT) were collected through the NBS/Health Protection Agency Infection Surveillance programme. The blood donor model for estimating risk was adapted for tissue donors. Incidence among surgical bone donors was derived from new blood donor data and estimates of residual risk presented for surgical bone donors only., Results: Fifty-seven surgical bone and four deceased donors were identified with 60 and five infections, respectively, during the 6 years. Syphilis was the most common infection detected, with no human T-lymphotropic virus infections and one HIV infection in a deceased donor. Hepatitis B virus, hepatitis C virus and syphilis prevalence was higher among surgical bone and deceased donors than new blood donors for the same period. The overall estimated risk of undetected hepatitis B and hepatitis C virus among surgical bone donors (2001-2006) on initial screening was 0.426 and 0.048 per 100 000 donors, respectively. Testing a follow-up sample made these risks almost negligible., Conclusion: The prevalence of infections was low among English tissue donors. Risk estimates were higher for surgical bone donors on first screening than among new blood donors. However, the probability of an infectious donation entering the tissue supply became negligible after obtaining a follow-up sample 6 months post-donation and were well below that of new blood donors.

Summary: Many people infected with hepatitis C virus (HCV) are unaware of their infection and are, therefore. potentially infectious to others. To enable effective case-finding policies to be developed, an understanding of where people, and injecting drug users (IDUs) in particular, are accessing HCV antibody testing is needed. HCV antibody testing data were collected electronically from 21 sentinel laboratories in England between 2002 and 2006 in this cross-sectional study. Service types of the physician requesting the HCV test were identified and classified. Differences in people being tested in each service type and over time were investigated. Over half a million people were tested in 5 years. Whilst most testing took place in hospital, a large proportion of people were tested in community care, particularly in general practice surgeries and genito-urinary medicine clinics. Younger people were more likely to be tested in community care, and there was evidence that testing differed according to ethnic status. IDUs were tested in all parts of the health services, although the highest proportion positive were from prisons and specialist services for drug users. Testing increased between 2002 and 2005 whilst the proportion of people testing positive declined. Routine laboratory data can provide valuable information on where people are being tested for HCV. Risk exposures should be investigated and testing targeted to people at higher risk for infection. Local laboratories should review data on testing locations and proportion positive to inform local initiatives to improve testing and yield.

Objective: The purpose of this study was to investigate the association of longitudinal change in serum gamma-glutamyltransferase (GGT) with mortality from cardiovascular disease (CVD)., Methods and Results: A population-based cohort of 76,113 Austrian men and women with 455,331 serial GGT measurements was prospectively followed-up for a median of 10.2 years after assessment of longitudinal GGT change during an average period of 6.9 years. Cox proportional hazards regression with time-varying covariates was used to evaluate GGT change as an independent predictor for CVD death. Independently of baseline GGT and other classical CVD risk factors, a pronounced increase in GGT (7-year change >9.2 U/L) was significantly associated with increased total CVD mortality in men (P=0.005); the adjusted hazard ratio (95% confidence interval) in comparison to stable GGT (7-year change -0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly, total CVD risk was elevated for increasing GGT in women, although effects were less pronounced and statistically significant only in subanalyses regarding coronary heart disease. Age of participants significantly modified the relation between GGT change and CVD mortality, with markedly stronger associations to be observable for younger individuals., Conclusions: Our study is the first to demonstrate that a longitudinal increase in GGT, independently of baseline GGT and even within its normal range, significantly increases risk of fatal CVD.

Although several epidemiologic studies have shown that gamma-glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase < 0.0001; P for trend < 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P < 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P < 0.001), revealing markedly stronger associations in participants ages

Background: The role of serum uric acid (SUA) as a risk factor for cardiovascular disease (CVD) remains controversial. Little is known about its predictive value for mortality from congestive heart failure (CHF) and stroke, particularly in elderly, post-menopausal women., Methods: The relation of SUA to risk of death from total CVD, CHF, stroke and coronary heart disease (CHD) was examined prospectively in a large cohort of 28613 elderly Austrian women (mean age 62.3 years), followed-up for a median of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events., Results: SUA in the highest quartile (>or=5.41 mg/dL) was significantly associated with mortality from total CVD (p<0.0001), showing a clear dose-response relationship; the adjusted hazard ratio (95%CI) in comparison to the lowest SUA quartile was 1.35 (1.20-1.52). In subgroup analyses SUA was independently predictive for deaths from acute and subacute (p<0.0001) and chronic forms (p=0.035) of CHD, yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 (1.19-2.10) and 1.25 (1.01-1.56), respectively. SUA was further significantly related to fatal CHF (p<0.0001) and stroke (p=0.018); the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 (1.04-2.17) and 1.37 (1.09-1.74), respectively., Conclusions: These findings, for the first time, demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute, subacute and chronic forms of CHD, CHF and stroke in elderly, post-menopausal women.

Background and Purpose: Noninvasive diagnosis of brain lesions is important for the correct choice of treatment. Our aims were to investigate whether 1) proton MR spectroscopic imaging ((1)H-MRSI) can aid in differentiating between tumors and nonneoplastic brain lesions, and 2) perfusion MR imaging can improve the classification., Materials and Methods: We retrospectively examined 69 adults with untreated primary brain lesions (brain tumors, n = 36; benign lesions, n = 10; stroke, n = 4; demyelination, n = 10; and stable lesions not confirmed on pathologic examination, n = 9). MR imaging and (1)H-MRSI were performed at 1.5T before biopsy or treatment. Concentrations of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the lesion were expressed as metabolite ratios and were normalized to the contralateral hemisphere. Dynamic susceptibility contrast-enhanced perfusion MR imaging was performed in a subset of patients (n = 32); relative cerebral blood volume (rCBV) was evaluated. Discriminant function analysis was used to identify variables that can predict inclusion in the neoplastic or nonneoplastic lesion groups. Receiver operator characteristic (ROC) analysis was used to compare the discriminatory capability of (1)H-MRSI and perfusion MR imaging., Results: The discriminant function analysis correctly classified 84.2% of original grouped cases (P < .0001), on the basis of NAA/Cho, Cho(norm), NAA(norm), and NAA/Cr ratios. MRSI and perfusion MR imaging had similar discriminatory capabilities in differentiating tumors from nonneoplastic lesions. With cutoff points of NAA/Cho < or =0.61 and rCBV > or =1.50 (corresponding to diagnosis of the tumors), a sensitivity of 72.2% and specificity of 91.7% in differentiating tumors from nonneoplastic lesions were achieved., Conclusion: These results suggest a promising role for (1)H-MRSI and perfusion MR imaging in the distinction between brain tumors and nonneoplastic lesions in adults.

In England, a large number of individuals are infected with the hepatitis C virus (HCV) and may develop future liver complications, such as decompensated cirrhosis and hepatocellular carcinoma (HCC). Estimates of the magnitude of this future burden are required to plan healthcare resources. We have estimated past incidence of HCV infection in England and predict future burden of end-stage liver disease in the HCV-infected population. A model of the natural history of HCV as a series of disease stages was constructed. A back-calculation approach was performed, using the natural history model and data on annual HCC deaths in England from 1996 to 2004 with mention of HCV and hospital episode statistics for end-stage liver disease with HCV. The number of HCV-infected people living with compensated cirrhosis is predicted to rise from 3705 [95% credible interval (CrI): 2820-4975] in 2005 to 7550 (95% CrI: 5120-11,640) in 2015. The number of decompensated cirrhosis and/or HCC cases is also predicted to rise, to 2540 (95% CrI: 2035-3310) by 2015. HCV incidence increased during the 1980s, with an annual incidence of 12 650 (95% CrI: 6150-26,450) by 1989. HCV-related cirrhosis and deaths from HCC in England are likely to increase dramatically within the next decade. If patients are left undiagnosed and untreated, the future burden of the disease on healthcare resources will be substantial.

Background and Objectives: Syphilis can be transmitted by blood. We describe syphilis infections detected in blood donors and investigate the epidemiology of syphilis in English, Welsh and Northern Irish blood donors., Materials and Methods: This article analyses routine surveillance data regarding syphilis infections in blood donors from England, Wales and Northern Ireland between 1998 and 2004. Infections are classified as recently acquired or past syphilis and donor characteristics and trends examined., Results: A total of 518 syphilis-infected donors were identified; 40 had recently acquired infection and 407 had past syphilis (71 were unclassified). Thirteen times more recently acquired syphilis infections were identified among people who donated between 2002 and 2004 compared to 1998 to 2001. Young, white and regular donors were most likely to have recently acquired syphilis infections. Heterosexual sex was the main risk exposure identified overall; in contrast, the greatest proportion of recently acquired infections were in men who have sex with men., Conclusion: The increase in recently acquired syphilis, although low, indicates that risky sexual behaviours are increasing in the blood donor population, with implications for the microbiological safety of blood. Continued vigilance is required by blood services as the risk of syphilis increases in the general population.

Background: Recent reports suggest an increase in sexually-transmitted hepatitis C infection among HIV-infected men who have sex with men (MSM) in European cities. We investigated whether current national surveillance systems in England and Wales (E&W) are able to monitor sexual transmission of hepatitis C infection among HIV-infected MSM., Methods: Routine laboratory reports of hepatitis C diagnoses and data from sentinel hepatitis C testing surveillance were matched to HIV diagnosis reports to determine: (i) the number of MSM diagnosed with HIV and hepatitis C (1996-2003); (ii) the number of HIV-diagnosed MSM tested for hepatitis C and found to be positive at sentinel sites (2003)., Results: (i) Between 1996-2003, 38,027 hepatitis C diagnoses were reported; 25,938 (68%) were eligible for matching with HIV diagnoses. Thirty-one men (four in London) had both a HIV and hepatitis C diagnosis where the only risk was sex with another man. Numbers of "co-diagnosed" MSM increased from 0 in 1996 to 14 in 2003. The majority of MSM (22/31) tested hepatitis C positive after HIV diagnosis. (ii) Of 78,058 test results from sentinel hepatitis C testing sites in 2003, 67,712 (87%) were eligible for matching with HIV diagnoses. We identified 242 HIV-diagnosed MSM who did not inject drugs who tested for hepatitis C in 2003; 11 (4.5%) tested hepatitis C positive (95% CI: 2.3%-8.0%). Applying this percentage to all MSM seen for HIV-related care in E&W in 2003, an estimated 680 MSM living with diagnosed HIV would have tested positive for sexually-transmitted hepatitis C (95% CI: 346-1208)., Conclusion: Matching routine laboratory reports of hepatitis C diagnoses with HIV diagnoses only identified 31 HIV infected MSM with sexually-transmitted hepatitis C infection. Clinical studies suggest that this is an underestimate. On the other hand, matching sentinel surveillance reports with HIV diagnoses revealed that in E&W in 2003 nearly 5% of HIV-diagnosed MSM tested hepatitis C positive where the only risk was sex with another man. Reports of sexually-transmitted hepatitis C infection were not confined to London. Enhanced surveillance is needed to monitor sexually-transmitted hepatitis C among HIV-infected MSM in E&W.

Purpose: To investigate whether in vivo proton magnetic resonance spectroscopic imaging (MRSI) can differentiate between 1) tumors and nonneoplastic brain lesions, and 2) high- and low-grade tumors in children., Materials and Methods: Thirty-two children (20 males and 12 females, mean age = 10 +/- 5 years) with primary brain lesions were evaluated retrospectively. Nineteen patients had a neuropathologically confirmed brain tumor, and 13 patients had a benign lesion. Multislice proton MRSI was performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the contralateral hemisphere. Normalized lesion peak areas (Cho(norm), Cr(norm), and NAA(norm)) expressed relative to the contralateral hemisphere were also calculated. Discriminant function analysis was used for statistical evaluation., Results: Considering all possible combinations of metabolite ratios, the best discriminant function to differentiate between nonneoplastic lesions and brain tumors was found to include only the ratio of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases correctly classified). The best discriminant function to differentiate between high- and low-grade tumors included the ratios of NAA/Cr and Cho(norm) (Wilks' lambda, P = 0.001; 89.5% of original grouped cases correctly classified). Cr levels in low-grade tumors were slightly lower than or comparable to control regions and ranged from 53% to 165% of the control values in high-grade tumors., Conclusion: Proton MRSI may have a promising role in differentiating pediatric brain lesions, and an important diagnostic value, particularly for inoperable or inaccessible lesions., (Published 2005 Wiley-Liss, Inc.)

The authors examined age trends in the 5 factors and 30 facets assessed by the Revised NEO Personality Inventory in Baltimore Longitudinal Study of Aging data (N=1,944; 5,027 assessments) collected between 1989 and 2004. Consistent with cross-sectional results, hierarchical linear modeling analyses showed gradual personality changes in adulthood: a decline in Neuroticism up to age 80, stability and then decline in Extraversion, decline in Openness, increase in Agreeableness, and increase in Conscientiousness up to age 70. Some facets showed different curves from the factor they define. Birth cohort effects were modest, and there were no consistent Gender x Age interactions. Significant nonnormative changes were found for all 5 factors; they were not explained by attrition but might be due to genetic factors, disease, or life experience., (Copyright (c) 2005 APA, all rights reserved.)

Objectives: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia., Design: Clinical history, hematological parameters, and serum erythropoietin levels were examined at 1- to 2-year intervals for 8 to 30 years., Setting: Baltimore Longitudinal Study on Aging (BLSA), National Institute on Aging., Participants: One hundred forty-three BLSA participants., Measurements: Complete blood count and serum chemistries were performed at the time of each visit, and archived serum samples were used for erythropoietin level., Results: Although all subjects were healthy and without anemia at the time of initial evaluation, some developed chronic illness-most notably hypertension and diabetes mellitus. Erythropoietin levels rose significantly for the group as a whole, and the slope of the rise was found to be greater for those who did not have associated diabetes mellitus or hypertension. During the subsequent years, subjects who developed anemia but did not have hypertension or diabetes mellitus had the greatest slope in erythropoietin rise over time, whereas those with hypertension or diabetes mellitus and anemia had the lowest erythropoietin slope., Conclusion: The increase in serum erythropoietin with aging may be compensation for subclinical blood loss, increased red blood cell turnover, or increased erythropoietin resistance of red cell precursors. It is suspected that, with very advanced age, or in those with compromised renal function (e.g., diabetes mellitus or hypertension), the compensatory mechanism becomes inadequate and anemia results.

Background: This article presents a computerized method to help predict individuals at risk for developing Alzheimer's disease (AD). This would be a valuable tool for clinicians in developing treatment plans for potential AD patients. Using the initial level and rates of change in visual memory performance, such a method could predict potential AD patients in a fast and inexpensive manner. A longitudinal case-control study of 52 female and 145 male participants was performed in a gerontology research center using premorbid tests of visual memory and neurologic examinations to identify individuals with and without dementia and AD., Methods: The classification method for each individual starts on the second examination and proceeds to compute that person's risk of AD one examination at a time based on all the follow-up information of the remaining individuals., Results: By performing a crossvalidation study, the optimal combination of sensitivity and specificity derived from a receiver operating characteristic (ROC) curve showed 65% of the Alzheimer cases and 75% of the noncases were correctly classified for females, while 65 and 60% of cases and noncases, respectively, were correctly classified for males., Conclusion: Longitudinal measurements of cognition can be useful in detecting the presence of AD.

Achondroplasia is the most common of the heritable skeletal dysplasias. Cervico-medullary compression is a frequently encountered and potentially lethal neurological complication. Cervico-medullary decompression (CMD) at the foramen magnum is often employed to relieve the pressure on the emerging cervical cord. Given the inherent risks associated with major surgery, there has been a substantial debate regarding the best criteria for CMD. Our objectives for this study are to explore the quality of life of patients who had undergone CMD, and to assess whether surgery is associated with mortality and increased long-term morbidity. A Medical Outcome Study 36-item Short Form General Health Survey designed to evaluate eight general health concepts as well as achondroplasia-related issues, was administered to patients assessed in the neurosurgery department in Johns Hopkins Hospital between 1977 and 1998. One hundred and sixty-seven patients were eligible for inclusion. Forty-three could not be contacted, and two refused consent. One hundred and twenty-two patients were assessed. Fifty-six (46%) individuals had CMD and 66 (54%) did not. There was 1 case of mortality in the CMD group and 12 cases in the non-CMD group. In the non-CMD group, all deaths, as far as we know, were unrelated to cervico-medullary compression. In this cohort of surviving patients (n = 109), the quality of life of the 55 (50.5%) who had undergone CMD is comparable to that of the 54 (49.5%) who did not have surgery, controlled for age and sex. CMD is indicated for patients with achondroplasia with significant symptomatic foramen magnum compression. It can be life saving. It can abolish profound central apnea that may cause sudden death and alleviate neurological complications associated with damage of the significantly compressed spinal cord. With regards to long-term outcome evaluation, the quality of life of individuals with achondroplasia who had CMD is similar to those age- and sex-matched patients who did not have this surgery. Moreover, CMD, with all its inherent surgical risks, does not appear to be associated with higher mortality or increased long-term morbidity.

Purpose: to compare metabolite concentrations and ratios in gray matter regions known for their anatomical/functional asymmetry and evaluate gender effect., Materials and Methods: Proton MRS imaging was performed at 1.5 T with TR/TE 2300/280 msec in 20 healthy right-handed subjects (mean age 29.6 +/- 5.3 years, 10 men). Concentrations of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), and the peak area ratios NAA/Cho, NAA/Cr, and Cho/Cr were evaluated in hippocampal and parahippocampal gyri, thalamus, insula, Broca's and Wernicke's areas (and corresponding contralateral areas), primary and secondary visual areas, temporal, inferior parietal, cingulate, supplemental motor, dorsolateral prefrontal, and sensorimotor areas. Linear mixed-effects regression models were used for statistical analyses., Results: NAA concentration and NAA/Cho were higher in the left thalamus by 21.9% and 20%, respectively (both P < 0.001). NAA concentration was 13% higher in the region contralateral to Wernicke's area (P < 0.02). No gender differences were found., Conclusion: Metabolite concentrations and ratios were symmetric and gender independent in most brain regions, however small hemispheric side differences in the thalamus and in Wernicke's area were found., (Copyright 2003 Wiley-Liss, Inc.)

A 24K glycoprotein, the proteolysis-inducing factor (PIF), has been identified in mice and humans with cancer cachexia. Clinical cross-sectional studies found an association between the presence of PIF in urine and tumors of patients and weight loss. For the first time, we report results from a longitudinal study establishing the relationship between a urinary PIF pattern and persistent weight loss. Over time, cancer patients positive for the PIF pattern experienced weight loss, whereas those with a negative test gained weight.

Purpose: To quantify regional variations in metabolite levels in the developing brain using quantitative proton MR spectroscopic imaging (MRSI)., Materials and Methods: Fifteen healthy subjects three to 19 years old were examined by in vivo multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), and peak area ratios were determined in selected frontal and parietal gray and white matter regions, basal ganglia, and thalamus., Results: In cortical gray matter regions, the ratio of NAA/Cho increased to a maximum at 10 years and decreased thereafter (P = 0.010). In contrast, in white matter, average ratios NAA/Cho increased linearly with age (P = 0.045). In individual brain regions, age-related changes in NAA/Cho were found in the putamen (P = 0.044). No significant age-related changes in NAA, Cho, Cr, or other metabolite ratios could be determined., Conclusion: Consistent with recent studies using other structural and functional neuroimaging techniques, our data suggest that small but significant changes occur in regional cerebral metabolism during childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal and parietal areas, resembling previously reported age related changes in rates of glucose utilization and cortical volumes, may be associated with dendritic and synaptic development and regression. Linear age-related changes of NAA/Cho in white matter are also in agreement with age-related increases in white matter volumes, and may reflect progressive increases in axonal diameter and myelination.

Background: The incidence of hypertension in postmenopausal women exceeds that in age-matched men. Longitudinal studies relating hormone replacement therapy (HRT) to blood pressure changes are sparse., Objective: To investigate the association between HRT and longitudinal changes in blood pressure in postmenopausal women., Design: Longitudinal observational study., Setting: Community-dwelling volunteers., Patients: 226 healthy, normotensive postmenopausal women from the Baltimore Longitudinal Study of Aging with a mean (+/-SD) age of 64 +/- 10 years were followed for 5.7 +/- 5.3 years. Seventy-seven women used both estrogen and progestin, and 149 used neither., Measurements: Lifestyle variables, blood pressure, and traditional cardiovascular risk factors were measured at baseline and approximately every 2 years thereafter., Results: Systolic blood pressure at baseline was similar in HRT users and nonusers (133.9 +/- 16.0 mm Hg vs. 132.4 +/- 14.8 mm Hg). Over time, average systolic blood pressure increased less in HRT users than nonusers, independent of other cardiovascular risk factors, physical activity, and alcohol use. For example, HRT users who were 55 years of age at their first Baltimore Longitudinal Study of Aging visit experienced a 7.6-mm Hg average increase in systolic blood pressure over 10 years; in contrast, the average increase in nonusers was 18.7 mm Hg. The lesser increase in systolic blood pressure in HRT users was more evident at older age. Diastolic blood pressure, which did not change statistically over time in either group, was not associated with HRT., Conclusion: Postmenopausal women taking HRT have a smaller increase in systolic blood pressure over time than those not taking HRT. This difference is intensified at older ages.

Purpose: Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain., Subjects and Methods: We measured apoE genotypes in 730 participants in the Baltimore Longitudinal Study of Aging (421 men and 309 women, mean [+/- SD] age of 52+/-17 years) who were free of preexisting coronary heart disease. A proportional hazards regression model was used to study the association between risk factors and the occurrence of coronary events, defined as angina pectoris, documented myocardial infarction by history or major Q waves on the electrocardiogram (Minnesota Code 1:1 or 1:2), or coronary death, adjusted for other risk factors, including total plasma cholesterol level., Results: The apoE4 allele was observed in 200 subjects (27%), including 183 heterozygotes and 17 homozygotes. Coronary risk factor profiles were similar in those with and without apoE4. Coronary events developed in 104 (14%) of the 730 subjects, including 77 (18%) of the 421 men during a mean follow-up of 20 years and 27 (9%) of the 309 women during a mean follow-up of 13 years. Coronary events occurred significantly more frequently in subjects with apoE4 (n = 40, 20%) than in those without this allele (64, 12%, P <0.05). In a multivariate model, apoE4 was an independent predictor of coronary events in men (risk ratio [RR]= 2.9, 95% confidence interval [CI]: 1.8 to 4.5, P<0.0001) but not in women (RR = 0.9, 95% CI: 0.4 to 1.9, P = 0.62)., Conclusion: The apoE4 genotype is a strong independent risk factor for coronary events in men, but not women. The association does not appear to be mediated by differences in total cholesterol levels.

In the past, studies utilizing within-subject comparisons of small groups of pregnant women showed that forced expiratory volume in 1 s (FEV1) remained essentially unchanged during pregnancy. However, one of the findings from an epidemiological study was that women with greater number of children experienced a faster decline of FEV1. The aim of this study was to examine the effect of parity on FEV1 in a group of healthy volunteer women. To this end, cross-sectional multiple regression analyses of data from 397 healthy women participants in the Baltimore Longitudinal Study of Aging (BLSA) with a mean (range) age of 47.7 (18-92) years were performed. Similar analyses were done using the younger (50 years or less) and the older (> 50 years) subgroups. After controlling for age, height, weight, and smoking, parity as a dichotomous variable was associated with a higher FEV1 in women of child-bearing age (0.139 1; P = 0.02) but not in the older women. There was a modest link with the number of children (P = 0.05), with the first child possibly having the greatest effect on FEV1. We could not account for the effect of parity on FEV1 by the educational level, occupation, health status of the women, or by the presence of a cohort effect. Thus the nulliparous state is associated with lower FEV1 in this group of healthy adult women of child-bearing age.