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PubMed2005

Working late: the impact of work after 70 on longevity, health and function.

BACKGROUND AND AIMS: Although many older persons choose to postpone retirement, the health consequences of this decision are still debated. This study aimed at determining the impact of continued employment on life-style, well-being, health and survival in a cohort of community-dwelling 70-year-olds. METHODS: A longitudinal study of a homogeneously aged cohort was conducted in two stages. Data from extensive interviews, physical examinations and clinical laboratory information were obtained from west Jerusalem residents born in 1920-1 through home-based examinations. In 1990-1, 162 women and 218 men were examined, at age 70, and in 1997-8, 390 women and 398 men at age 77. Two hundred and thirty one subjects participated in both study stages and were available for longitudinal analysis. For each subject at each study stage, a comprehensive profile detailed social characteristics, including life-style and personal functions, and medical status including illnesses and use of medical services. At each stage, employed subjects were compared with those who neither worked for compensation nor as volunteers. Logistic regression compared health outcomes at age 77 for subjects who worked at age 70 with those of subjects who had not. RESULTS: At age 70, 37 women and 98 men were gainfully employed, whereas 125 women and 120 men did not work. At age 77, wage-earners numbered 26 women and 95 men, and non-workers 364 women and 303 men. In the cross-sectional analyses at ages 70 and 77, work correlated with better perceived health and greater independence for both women and men. Independent of pre-existing economic difficulties, education, illnesses, functional dependence and self-assessed health, workers at age 70 after seven years were in better health (OR 2.12, 95% CI 1.04, 4.30), had more ADL independence, (OR 2.60, 95% CI 1.08, 6.29) and increased survival rates (OR 2.13, 95% CI 1.06, 4.28). CONCLUSIONS: Independent of baseline status, working at age 70 correlates with health, self-sufficiency and longevity.

Activities of Daily Living↗
PubMed2005

Mortality risk from squamous cell skin cancer.

PURPOSE: To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality. PATIENTS AND METHODS: Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality. RESULTS: We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor. CONCLUSION: Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.

Adult↗
PubMed2001

Risk factors for cardiovascular and cerebrovascular death among African Americans and Hispanics in Los Angeles, California.

OBJECTIVE: To describe the risk factors associated with cardiovascular mortality in the African American (AA) and Hispanic populations in Los Angeles County in an effort to define causes for the excess mortality seen in AAs. METHODS: This was a longitudinal analysis of all-cause, cardiovascular, and cerebrovascular mortality in a large, prospective multiethnic cohort of individuals aged 45-74 years. Death rates between AA and Hispanic men and women during the six-year period from 1993 to 1998 due to hypertension, cardiomyopathy, acute myocardial infarction (AMI), ischemic heart disease, and stroke were compared. RESULTS: There were 1,157 deaths due to cardiovascular disease (CVD) or cerebrovascular disease among the 71,798 eligible members of the cohort included in these analyses. Age-adjusted mortality rates were two to five times higher in AAs as compared with Hispanics (e.g., 373.15 in AAs for hypertensive disease vs 50.37 in Hispanics). A history of hypertension was the most common significant risk factor for CVD; other risk factors significantly associated with CVD mortality included cigarette smoking and a past history of diabetes and stroke. Adjusting for these factors did not remove the significance of AA ethnicity as a risk factor for CVD mortality in either subjects reporting or subjects not reporting hypertension at baseline. CONCLUSIONS: The evidence for both higher relative severity and higher incidence of hypertensive disease among AAs, and the consistency of the effect across gender, suggests that a major determinant of risk may be a gene environment interaction.

Black or African American↗
PubMed2002

Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men.

Although catastrophic weight loss is no longer common in HIV-infected men, we hypothesized that a more gradual process of cachexia [loss of lean body mass (LBM) without severe weight loss, often accompanied by elevated resting energy expenditure (REE)] is still common and is driven by excessive production of the catabolic cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). We performed a longitudinal analysis of an ongoing cohort study of nutritional status in 172 men with HIV infection. LBM loss of >1 kg occurred in 35% of the cohort, and LBM loss of >5% occurred in 12.2% over 8 mo of observation, but classical wasting (loss of approximately 10% of weight) was rare (2%). Both TNF-alpha (-150 g LBM. ng(-1) x ml(-1), P < 0.02) and IL-1 beta production (-130 g LBM x ng(-1) x ml(-1), P < 0.01) by peripheral blood mononuclear cells predicted loss of LBM. A rise in REE of >200 kcal/day was found in 17.7% of the subjects regardless of weight change. IL-1 beta (+9 kcal/day per ng/ml, P < 0.002) and TNF-alpha (+10 kcal/day per ng/ml, P < 0.02) production predicted Delta REE. Serum free testosterone was inversely associated with TNF-alpha production and was not an independent predictor of either Delta LBM or Delta REE after adjustment for cytokine production. Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism.

Adult↗
PubMed1998

Differential typology and prognosis for dissexual behavior--a follow-up study of previously expert-appraised child molesters.

In terms of identifying socially-dysfunctional forms of sexuality--regardless of the legal valuation--dissexuality is defined as "an expression of social failure in sexual behavior." This failure was the subject of a longitudinal analysis of 186 expert-appraised pedophile sexual delinquents at the University of Kiel from 1945 through 1981. Of the child molesters 121 were followed up between September 1990 and September 1992 and 100 were personally contacted. The goal was to empirically develop prognosis criteria, given knowledge of the former delinquents' social development as well as sexual/dissexual practices, which could be of both forensic and interdisciplinary use. Among the bi- and homosexually-orientated pedophiles, the number of offenders for which the act is one of "compensation" was half of the initial collective. In contrast, this number was three-quarters for the heterosexually-orientated perpetrators. Correspondingly, the other half of the bi- and homosexually-orientated pedophiles were either exclusive-type or non-exclusive-type pedophiles (the so-called "true" pedophiles). Among the heterosexually-orientated offenders, the number was only one-quarter. According to the empirical data, we may expect a biographically continuing potential of dissexual behavior for only the exclusive and the non-exclusive type of pedophilia. Most of the relapsed dissexual activities showed up a long time after the expert's report. This is true for both the heterosexually- and the bi- and homosexually orientated groups. The present evaluation of the results allows assignment of behavior for certain delinquent typologies restricted to life phases or lifelong dissexual behavior.

Adolescent↗
PubMed2003

Diabetes as a predictor of change in functional status among older Mexican Americans: a population-based cohort study.

OBJECTIVE: Epidemiological studies have demonstrated that older Mexican Americans are at high risk for type 2 diabetes and its complications. Type 2 diabetes leads to a more rapid decline in functional status among older Mexican Americans with diabetes. This study was designed to examine the impact of diabetes on change in self-reported functional status over a 2-year period among older Mexican Americans with diabetes. RESEARCH DESIGN AND METHODS: We performed a longitudinal analysis with repeated measurements of functional limitations in a cohort of Mexican Americans aged > or =60 years in the Sacramento Area Latino Study on Aging (SALSA). Diabetes was diagnosed on the basis of self-report of physician diagnosis, medication use, and fasting plasma glucose. Functional status was measured by assessment of activities of daily living (ADL) and instrumental activities of daily living (IADL) at baseline and 1 and 2 years. RESULTS: Of 1,789 SALSA participants, 585 (33%) had diabetes at baseline. Diabetic subjects reported 74% more limitations than nondiabetic subjects in ADL (summary score for number of limitations, 0.99 vs. 0.57; P = 0.002) and 50% more limitations in IADL (summary score for number of limitations, 7.83 vs. 5.25; P < 0.0001). The annual rate of increase in limitations of ADL and IADL was 0.046 and 0.033 (log scale) on each scale among diabetic subjects compared with 0.013 and 0.003 (log scale) among nondiabetic subjects (P < 0.0005). Complications of diabetes were found to increase ADL and IADL limitations among diabetic subjects. Longer duration of diabetes was also associated with an increase in ADL and IADL limitations. CONCLUSIONS: There was lower baseline functional status and a more rapid decline in functional status among older Mexican Americans with diabetes versus those without diabetes.

Activities of Daily Living↗
PubMed1999

Variation in inpatient resource use in the treatment of HIV: do the privately insured receive more care?

OBJECTIVE: To estimate the impact of insurance status on inpatient resource use after adjusting for health upon admission and site of care. DESIGN: Detailed patient information linked to billing records from the AIDS Cost and Service Utilization Survey (ACSUS), a longitudinal analysis of inpatient and outpatient care between March 1991 and August 1992. SETTING: Hospitalizations of human immunodeficiency virus (HIV) patients from 10 US cities with high incidence of AIDS. PATIENTS: One thousand, nine hundred and forty nine adolescents and adults at various stages of HIV. MAIN OUTCOME MEASURES: We estimate inpatient charges, payments and length of stay as a function of patient, and provider and reimbursement characteristics for more than 1,500 hospitalizations to HIV patients. We control for patient characteristics and underlying risk factors including disease stage, CD4 percentage, mode of transmission, discharge status, type of admission, and region. We use hospital-fixed effects to control for unmeasured differences across facilities. RESULTS: Unadjusted means indicate that uninsured patients or patients covered by public insurance have significantly lower charges and payments than privately insured patients with similar medical conditions. We find that those differences are substantially reduced after controlling for the hospital in which care is received. Further, we find little evidence that "underinsured" patients are discharged sooner on average. CONCLUSIONS: Inpatient resource use is affected by both the hospital in which care is received and the type of patient admitted. Failure to control for unmeasured differences across hospitals is likely to overstate the impact of insurance substantially.

Adolescent↗
PubMed2005

Parental pressure, dietary patterns, and weight status among girls who are "picky eaters".

OBJECTIVE: To determine whether mothers' fruit and vegetable intake and mothers' use of pressure in the feeding domain when their daughters were 7 years old predicted picky eating and dietary intake when their daughters were 9 years old, and to examine diet and weight status in picky and nonpicky eaters. DESIGN/SUBJECTS: Participants were 173 9-year-old non-Hispanic white girls and their mothers. A longitudinal analysis was used to assess maternal influences on picky eating and diet. A cross-sectional analysis was used to examine diet and weight status between picky and nonpicky eaters. Measures included maternal feeding practices, daughters' pickiness, mothers' fruit and vegetable intake, daughters' food intake, and weight status. STATISTICAL ANALYSES: t tests examined differences between picky and nonpicky eaters. Structural equation modeling examined relationships among mothers' fruit and vegetable intake; child feeding practices; daughters' pickiness; and fruit, vegetable, micronutrient, and fiber intakes. RESULTS: Mothers consuming more fruits and vegetables were less likely to pressure their daughters to eat and had daughters who were less picky and consumed more fruits and vegetables. Picky eaters consumed fewer fruits and vegetables, but also fewer fats and sweets. All girls consumed low amounts of vitamin E, calcium, and magnesium, but more picky girls were at risk for not meeting recommendations for vitamins E and C and also consumed significantly less fiber. In addition, picky eaters were less likely to be overweight. CONCLUSIONS: Mothers influenced daughters' fruit and vegetable intake via their own patterns of fruit and vegetable intake and by influencing their daughters' tendencies to be picky eaters. Both picky and nonpicky eaters had aspects of their diets that did not meet recommendations. Taken together, these findings suggest that parents should focus less on "picky eating" behavior and more on modeling fruit and vegetable consumption for their children.

Adult↗
PubMed2002

Effect of radiation dose on the height of atomic bomb survivors: a longitudinal study.

We conducted a longitudinal analysis of height after age 20 for atomic bomb survivors in the Adult Health Study (AHS) cohort. The measurements we used were made from July 1958 to June 1998 (AHS examination cycles 1-20). We analyzed only the subjects with known atomic bomb radiation doses, excluding those who were not in the city at the time of bombing (ATB) and those exposed in utero. We also excluded from the analysis measurements made after the occurrence of vertebral fracture. The total number of subjects was 11,862, and the total number of measurements was 109,770; the mean number of measurements per subject was 9.25. Assuming that stature after age 20 is approximately constant, a simple mixed-effects model was fitted to stature after age 20, and linear dose effects for young ATB subjects were modeled for both sexes. The estimated mean heights for subjects born in 1945 in Hiroshima were 166.0 cm for men and 155.4 cm for women. The sex difference in height was 10.6 cm, with men significantly taller than women (P < 0.001). The difference between the cities was not significant (P = 0.162). The birth cohort effects per decade were -1.7 cm for men (P < 0.001) and -2.1 cm for women (P < 0.001). A reduction of stature due to radiation exposure was observed for individuals of both sexes who were below 19 years of age ATB (95% confidence interval, 17-21 years), and the dose effect was larger for women than for men (P = 0.028). The estimated effects per gray for those who were age 0 ATB were -1.2 cm for men and -2.0 cm for women and for those who were age 10 ATB were-0.57 cm for men and -0.96 cm for women.

Adolescent↗
PubMed2003

Managing costs, managing benefits: employer decisions in local health care markets.

OBJECTIVES: To better understand employer health benefit decision making, how employer health benefits strategies evolve over time, and the impact of employer decisions on local health care systems. DATA SOURCES/STUDY SETTING: Data were collected as part of the Community Tracking Study (CTS), a longitudinal analysis of health system change in 12 randomly selected communities. STUDY DESIGN: This is an observational study with data collection over a six-year period. DATA COLLECTION/EXTRACTION METHODS: The study used semistructured interviews with local respondents, combined with monitoring of local media, to track changes in health care systems over time and their impact on community residents. Interviewing began in 1996 and was carried out at two-year intervals, with a total of approximately 2,200 interviews. The interviews provided a variety of perspectives on employer decision making concerning health benefits; these perspectives were triangulated to reach conclusions. PRINCIPAL FINDINGS: The tight labor market during the study period was the dominant consideration in employer decision making regarding health benefits. Employers, in managing employee compensation, made independent decisions in pursuit of individual goals, but these decisions were shaped by similar labor market conditions. As a result, within and across our study sites, employer decisions in aggregate had an important impact on local health care systems, although employers' more highly visible public efforts to bring about health system change often met with disappointing results. CONCLUSIONS: General economic conditions in the 1990s had an important impact on the configuration of local health systems through their effect on employer decision making regarding health benefits offered to employees, and the responses of health plans and providers to those decisions.

Cost Control↗
PubMed1994

N-ras mutation and karyotypic evolution are closely associated with leukemic transformation in myelodysplastic syndrome.

We performed a longitudinal analysis of the karyotypes and N-ras gene configuration of bone marrow cells in 35 patients with myelodysplastic syndrome (MDS). Karyotypic evolution was found in eight patients, and was associated with disease progression, including leukemic transformation, in all the patients. We identified N-ras mutations in six patients, using a polymerase chain reaction (PCR) technique, in which oligonucleotide primers were constructed with induced mismatches, followed by endonuclease digestion. Direct sequencing confirmed single base substitutions at codon 12 in two patients and at codon 13 in four. The incidence of N-ras gene mutations was significantly higher in the karyotypically evolved group (five of eight patients) than in the stable group (one of 27 patients). All of five patients harboring both karyotypic evolution and an N-ras mutation showed concomitant disease progression to overt leukemia or refractory anemia with excess of blasts in transformation (RAEB-T). Two of four patients with either karyotypic evolution or N-ras mutation and six of 26 patients without any of these alterations also progressed to overt leukemia. Our results indicate that the accumulation of these genetic alterations is closely associated with leukemic transformation of MDS, although other genetic alterations may also play a key role in the remaining patients.

Adult↗
PubMed1998

Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents.

BACKGROUND: Cardiac effects of hypertension include increased left ventricular (LV) mass and LV hypertrophy, as well as increased left atrial size, a predictor of stroke and atrial fibrillation. Although literature on reduction of LV mass with antihypertensive therapy is extensive, little information is available on effects of treatment on left atrial size. METHODS AND RESULTS: Patients with mild to moderate hypertension (diastolic blood pressure 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline, 8 weeks, and 1 and 2 years. Longitudinal analysis examined changes in left atrial size from the baseline study, statistically adjusting for age, race, pretreatment left atrial size and LV mass, and serial measurements of systolic blood pressure, body weight, urinary sodium excretion, and physical activity score. Without adjustment for covariates, only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks (-1.0 +/- 5.2 mm; P=0.052), 1 year (-2.0 +/- 5.1 mm; P=0.02), and 2 years (4.6+/-7.2 mm; P=0.002). After adjustment for effects of covariates, patients with normal left atrial size had greater reduction (-3.3 mm) in left atrial size at 2 years with hydrochlorothiazide than with any other drug. For patients with left atrial enlargement, left atrial size decreased significantly with hydrochlorothiazide, atenolol, clonidine, and diltiazem at 1 year and with all treatments at 2 years. However, reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin. CONCLUSIONS: Antihypertensive drugs differ in their effects on left atrial size. Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension. Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size, including LV mass and reduction of LV mass with treatment. The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined.

Aged↗
PubMed2007

Psychological distress after employment transitions: the role of subjective financial position as a mediator.

OBJECTIVE: To explore the extent to which the mental health effects of transitions into unemployment, or other forms of non-employment, and vice versa, are mediated by financial changes. METHODS: Longitudinal analysis of the British Household Panel Survey from 1991 to 2000. There were 89,264 person-years of observation from 14,686 individuals aged > or =16 years. Main outcome measure was psychological distress measured by the 12-item General Health Questionnaire. RESULTS: Transitions to unemployment were associated with increased risk of psychological distress for men (adjusted odds ratio (OR) 3.15 (95% confidence interval (CI) 2.50 to 3.98)) and for women (OR 2.60 (95% CI 1.97 to 3.43)). Women who left work to look after the family were also more likely to experience psychological distress (OR 1.72 (95% CI 1.45 to 2.05)). A reduced risk of psychological distress was seen for transitions from unemployment to paid employment for men (OR 0.52 (95% CI 0.41 to 0.68)) and for women (OR 0.68 (95% CI 0.69 to 1.40)). Financial difficulty partially mediated these relationships: men who became unemployed and were worse off financially were more likely to experience psychological distress (OR 4.19 (95% CI 3.20 to 5.50)) than men who were not (OR 1.48 (95% CI 0.95 to 2.33)). Conversely, the beneficial health effect for people who left unemployment and became employed was confined to those who were better off financially (OR 0.34 (0.25 to 0.48) for men). CONCLUSIONS: Changes in employment status have both direct and indirect effects, through changes in financial circumstances, on subsequent psychological distress. The results support the view that the direction of causation runs from employment transitions to financial difficulties and psychological distress.

Adaptation, Psychological↗
PubMed2005

A rose by any other name? Objective knowledge, perceived knowledge, and adolescent male condom use.

OBJECTIVE: To investigate the role of objective and perceived knowledge about condoms in adolescent males' condom use at first intercourse. METHODS: A longitudinal analysis was conducted of data from a nationally representative sample of 404 virgin male adolescents who were aged 15 to 17 years at wave 1 and reported becoming sexually experienced at the second wave of data collection. Objective knowledge was measured as a 5-item knowledge test about condoms. Perceived knowledge was measured as a 5-item scale regarding participants' confidence about their answers on the objective knowledge test. Condom use was assessed by self-report. RESULTS: Objective and perceived knowledge were moderately correlated with each other. Male adolescents with low objective but high perceived knowledge were identified as being at particular risk for not using a condom in that they were nearly 3 times less likely to report using a condom at first intercourse (odds ratio: 0.35) than those with other levels of objective and perceived knowledge. CONCLUSIONS: Previous evidence suggests that knowledge about sex does not accurately predict sexual behavior. This lack of predictive accuracy may be because studies have focused only on objective knowledge. Our results suggest that both objective and perceived knowledge serve as antecedents to male condom use at first intercourse. However, those with higher perceived knowledge, particularly in the context of low objective knowledge, may be at greater risk for not using condoms. Addressing not only objective but also perceived knowledge may increase the effectiveness of interventions that are designed to increase rates of condom use among male adolescents.

Adolescent↗
PubMed2003

Inpatient surgery in California: 1990-2000.

BACKGROUND: The practice environment for surgery is changing. However, little is known regarding the trends or current status of inpatient surgery at a population level. HYPOTHESIS: Inpatient surgical care has changed significantly over the last 10 years. DESIGN: Longitudinal analysis of California inpatient discharge data (January 1, 1990, through December 31, 2000). SETTING: All 503 nonfederal acute care hospitals in California. PATIENTS: All inpatients undergoing general, vascular, and cardiothoracic surgery in California from January 1, 1990, through December 31, 2000, were obtained. MAIN OUTCOME MEASURES: Volume, mean age, comorbidity profile, length of hospital stay, and in-hospital mortality were obtained for inpatient general, vascular, and cardiothoracic surgical procedures performed during the period 1990 to 2000. Rates of change and trends were evaluated for the 10-year period. RESULTS: Between January 1, 1990, and December 31, 2000, 1.64 million surgical procedures were performed. The number of surgical procedures increased 20.4%, from 135,795 in 1990 to 163,468 in 2000. Overall, patients were older and had more comorbid disease in 2000 compared with 1990. Both crude and adjusted (by type of operation) in-hospital mortality decreased from 3.9% in 1990 to 2.75% (P<.001) and 2.58% (P<.001), respectively, in 2000. Length of hospital stay decreased over the period for all operations analyzed. CONCLUSIONS: The total number of inpatient general, vascular, and cardiothoracic surgical procedures has increased over the past decade. Furthermore, our findings indicate that the outcomes of care (eg, in-hospital mortality and length of hospital stay) for patients who undergo general, vascular, and cardiothoracic surgical procedures have improved. However, continued evaluations at the population level are needed.

California↗
PubMed2005

Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection.

Studies in acute human immunodeficiency virus type 1 (HIV-1) infection indicate viral evolution under CD8 T-cell immune selection pressure, but the effects of ongoing immune pressure on epitope evolution during chronic infection are not well described. In this study, we performed a detailed longitudinal analysis of viral sequence variation within persistently targeted cytotoxic T-lymphocyte (CTL) epitopes in two HIV-1-infected persons during 6 years of persistent viremia. Responses were quantitated using freshly isolated peripheral blood lymphocytes in direct lytic assays as well as by gamma interferon (IFN-gamma) Elispot assays on cryopreserved cells. Seven targeted epitopes were identified in each person. In the majority of cases, the dominant epitope sequence did not change over time, even in the presence of responses of sufficient magnitude that they were detectable using fresh peripheral blood mononuclear cells in direct lytic assays. Only 4 of the 14 autologous epitopes tested represented potential CTL escape variants; however, in most cases strong responses to these epitopes persisted for the 6 years of study. Although persistent IFN-gamma responses were detected to all epitopes, direct lytic assays demonstrated declining responses to some epitopes despite the persistence of the targeted sequence in vivo. These data indicate limited viral evolution within persistently targeted CD8 T-cell epitopes during the chronic phase of infection and suggest that these regions of the virus are either refractory to sequence change or that persistently activated CD8 T-cell responses in chronic infection exert little functional selection pressure.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Intrahepatic CD8+ T-lymphocyte response is important for therapy-induced viral clearance in chronic hepatitis B infection.

BACKGROUND/AIMS: To determine which immune cells contribute to HBV-clearance during antiviral therapy, we performed a longitudinal analysis of intrahepatic immune cells during interferon-alpha therapy of chronic HBV-patients using the FNAB technique. METHODS: Twenty chronic HBeAg+-patients were treated with pegylated alpha-interferon combined with lamivudine or placebo for 52 weeks. FNAB and blood specimens were obtained at week 0, 2, 8 and 52. CD4+- and CD8+ T-lymphocytes, CD56+ cells, IFNgamma and granzyme B (GrB) were immunocytochemically quantified. RESULTS: The relative numbers of CD56+ cells and CD8+ T-lymphocytes were significantly higher in FNAB compared to blood at all time-points. Responders (n=9) exhibited significant increases in intrahepatic CD8+ and CD8+GrB+ lymphocytes, a small elevation in CD8+IFNgamma+ T-lymphocytes, no change in CD4+ T-lymphocytes, and a decrease in intrahepatic CD56+ cells during the first weeks of therapy. In non-responders (n=11) no significant changes in CD4+- and CD8+ T-lymphocytes and an increase in intrahepatic and CD56+ cells were observed during therapy. CONCLUSIONS: The intrahepatic CD8+ T-lymphocyte, but not the CD4+ T-lymphocyte or NK/NKT-cell response, is important for HBV clearance during interferon-alpha therapy, and the antiviral effect may be mediated by both cytolytic and non-cytolytic mechanisms.

Adult↗
PubMedDate not supplied

Blood pressure as a cardiovascular risk factor: prevention and treatment.

OBJECTIVE: - To examine the prevalence, incidence, predisposing factors for hypertension, its hazards as an ingredient of the cardiovascular risk profile, and the implications of this information for prevention and treatment. METHODS: - Prospective longitudinal analysis of 36-year follow-up data from the Framingham Study of the relation of antecedent blood pressure to occurrence of subsequent cardiovascular morbidity and mortality depending on the metabolically linked burden of associated risk factors. RESULTS: - Hypertension is one of the most prevalent and powerful contributors to cardiovascular diseases, the leading cause of death in the United States. There is, on average, a 20 mm Hg systolic and 10 mm Hg diastolic increment increase in blood pressure from age 30 to 65 years. Isolated systolic hypertension is the dominant variety. There is no evidence of a decline in the prevalence of hypertension over 4 decades despite improvements in its detection and treatment. Hypertension contributes to all of the major atherosclerotic cardiovascular disease outcomes increasing risk, on average, 2- to 3-fold. Coronary disease, the most lethal and common sequela, deserves highest priority. Hypertension clusters with dyslipidemia, insulin resistance, glucose intolerance, and obesity, occurring in isolation in less than 20%. The hazard depends on the number of these associated metabolically linked risk factors present. Coexistent overt cardiovascular disease also influences the hazard and choice of therapy. CONCLUSION: - The absence of a decline in the prevalence of hypertension indicates an urgent need for primary prevention by weight control, exercise, and reduced salt and alcohol intake. The urgency and choice of therapy of existing hypertension should be based on the multivariate cardiovascular risk profile that more appropriately targets hypertensive persons for treatment and prevention of cardiovascular sequelae.

Blood Pressure↗