Neural systems underlying the recognition of familiar and newly learned faces.

Memory for famous faces can be used to examine the neural systems underlying retrieval from long-term memory. To date, there have been a limited number of functional neuroimaging investigations examining famous face recognition. In this study, we compared recognition of famous faces to recognition of newly learned faces. Whole-brain, event-related functional magnetic resonance imaging was used to image regional changes in neural activity in 11 subjects during the encoding of unfamiliar faces and during familiarity judgments for: (1) newly learned faces, (2) unfamiliar face distractors, and (3) famous faces. Image analyses were restricted to correct recognition trials. Recognition accuracy and response time to famous and recently learned faces were equivalent. Recognition of famous faces was associated with a widespread network of bilateral brain activations involving the prefrontal, lateral temporal, and mesial temporal (hippocampal and parahippocampal regions) regions compared to recognition of recently encoded faces or unfamiliar faces seen for the first time. Findings are discussed in relation to current proposals concerning the neural regions thought to participate in long-term memory retrieval and, more specifically, in relation to retrieval of information from the person identity semantic system.

Body weight patterns from 20 to 49 years of age and subsequent risk for diabetes mellitus: the Johns Hopkins Precursors Study.

BACKGROUND: Obesity in middle age is a well-known risk factor for the development of type 2 diabetes mellitus. However, the importance of weight and weight gain at younger ages is less certain. OBJECTIVE: To determine the relationship of body weight patterns from 20 to 49 years of age with the subsequent risk for type 2 diabetes mellitus. SETTING: An ongoing longitudinal study of former medical students. PARTICIPANTS: Nine hundred sixteen white men without diabetes at 50 years of age. MEASUREMENTS: Weight and height measured in medical school, then assessed by mailed questionnaire to 49 years of age. MAIN OUTCOME: Incident type 2 diabetes mellitus based on physician self-report. RESULTS: During 14 255 person-years of follow-up, there were 35 incident cases of type 2 diabetes mellitus (2.5 per 1000 person-years). After simultaneous adjustment for age, physical activity, lifetime maternal history of diabetes, and smoking, body mass indexes (BMIs; calculated as weight in kilograms divided by the square of height in meters) at 25, 35, and 45 years of age were all strongly associated with diabetes risk (relative risks for overweight [BMI> or =25.0] vs. not overweight, >3.0; all Ps<.05), as were maximum and average BMI to 49 years of age. The relationship of BMI at 25 years of age to diabetes risk was substantially attenuated by adjustment for BMI at 45 years of age and average BMI, but was independent of weight change, weight variability, or maximum BMI. CONCLUSION: In men, overweight at 25 years of age strongly predicts diabetes risk in middle age, largely through its association with overweight at 45 years of age and high average BMI to 49 years of age.

Physician, heal Thyself? Regular source of care and use of preventive health services among physicians.

BACKGROUND: Little is known about the regular source of care (RSOC) among physicians, a group whose self-care may reflect the attitudes and recommendations they convey to their patients. METHODS: We performed a cohort study of physicians who graduated from the Johns Hopkins School of Medicine from 1948 through 1964 to identify predictors of not having an RSOC, and to determine whether not having an RSOC was associated with subsequent receipt of preventive services. The RSOC was assessed in a 1991 survey; use of cancer screening tests and the influenza vaccine was assessed in 1997. RESULTS: The response rate in 1991 was 77% (915 respondents); 35% (312) had no RSOC. Internists (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.58-6.74), surgeons (OR, 2.42; 95% CI, 1.17-5.02), and pathologists (OR, 5.46; 95% CI, 2.09-14.29) were significantly more likely to not have an RSOC than pediatricians. Not having an RSOC was inversely related to the belief that health is determined by health professionals (OR, 0.45; 95% CI, 0.29-0.68) and directly related to the belief that chance (OR, 1.90; 95% CI, 1.28-2.82) determines health. Not having an RSOC in 1991 predicted not being screened for breast, colon, and prostate cancer, as well as not receiving an influenza vaccine at 6 years of follow-up. CONCLUSIONS: A large percentage of physicians in our sample had no RSOC, and this was associated with both medical specialty and beliefs about control of health outcomes. Not having an RSOC was significantly associated with failure to use preventive services several years later. Arch Intern Med. 2000;160:3209-3214.

Gout and risk for subsequent coronary heart disease. The Meharry-Hopkins Study.

BACKGROUND: Patients with gout are encountered frequently in clinical practice. Previous studies have suggested that hyperuricemia and gout may represent risk factors for coronary heart disease (CHD), the most common cause of death in American men. METHODS: Prospectively collected data from 2 longitudinal cohort studies of former medical students--371 black men in the Meharry Cohort Study and 1181 white men in the Johns Hopkins Precursors Study--were analyzed. The development of gout and of CHD was determined by physician self-report, and validated by using published criteria. The risk for CHD associated with gout was evaluated using Cox proportional hazards analysis. RESULTS: During a median follow-up of 30 years, there were 38 gout cases and 44 CHD events among the Meharry men, and 68 gout cases and 138 CHD events among the Hopkins men. Prior gout was not associated with an increased risk for incident CHD (relative risk = 1.20; 95% confidence interval, 0.37-3.92) among the Meharry men or among the Hopkins men (relative risk = 0.66; 95% confidence interval, 0.24-1.79). Multivariate analysis adjusted for known CHD risk factors did not alter these findings. CONCLUSION: These results, in black and white male physicians, do not suggest a role in men for targeting gout identification in the primary prevention of CHD.

Depression is a risk factor for coronary artery disease in men: the precursors study.

BACKGROUND: Several studies have found that depression is an independent predictor of poor outcome after the onset of clinical coronary artery disease. There are few data concerning depression as a risk factor for the development of coronary artery disease. OBJECTIVE: To determine if clinical depression is an independent risk factor for incident coronary artery disease. PATIENTS AND METHODS: The Johns Hopkins Precursors Study is a prospective, observational study of 1190 male medical students who were enrolled between 1948 and 1964 and who continued to be followed up. In medical school and through the follow-up period, information was collected on family history, health behaviors, and clinical depression. Cardiovascular disease end points have been assessed with reviews of annual questionnaires, National Death Index searches, medical records, death certificates, and autopsy reports. RESULTS: The cumulative incidence of clinical depression in the medical students at 40 years of follow-up was 12%. Men who developed clinical depression drank more coffee than those who did not but did not differ in terms of baseline blood pressure, serum cholesterol levels, smoking status, physical activity, obesity, or family history of coronary artery disease. In multivariate analysis, the men who reported clinical depression were at significantly greater risk for subsequent coronary heart disease (relative risk [RR], 2.12; 95% confidence interval [CI], 1.24-3.63) and myocardial infarction (RR, 2.12; 95% CI, 1.11-4.06). The increased risk associated with clinical depression was present even for myocardial infarctions occurring 10 years after the onset of the first depressive episode (RR, 2.1; 95% CI, 1.1-4.0). CONCLUSION: Clinical depression appears to be an independent risk factor for incident coronary artery disease for several decades after the onset of the clinical depression.

Vascular reactivity in young adults and cardiovascular disease. A prospective study.

Cardiovascular reactivity in response to the cold pressor test has been associated with an increased risk of coronary heart disease in middle-aged men. We studied 905 white male medical students, median age 22 years, in the Johns Hopkins Precursors Study. Systolic blood pressure, systolic blood pressure change during the cold pressor test, smoking, cholesterol, Quetelet index, and family history of coronary heart disease were measured on enrollment during 1948-1964. Incidence of cardiovascular morbidity and mortality was ascertained by annual questionnaires and death certificates. There was no association between change in systolic blood pressure during the cold pressor test, whether examined as a continuous variable or a 20 mm Hg or more rise, and the risk of subsequent cardiovascular disease or coronary heart disease. These findings did not change after adjustment for cardiovascular disease risk factors. Previously reported associations may have been due to preexisting arteriosclerosis, which increases the rise in systolic blood pressure during the cold pressor test. We conclude that cardiovascular reactivity to the cold pressor test in young adulthood is not a strong predictor of future cardiovascular disease.

Cardiovascular reactivity to the cold pressor test as a predictor of hypertension.

Cardiovascular reactivity to stress is hypothesized to be a marker for subsequent neurogenic cardiovascular disease, but few prospective studies of this hypothesis are available. We studied 910 white male medical students who had their blood pressure and pulse rate measured before and during a cold pressor test in the years 1948-1964. Hypertensive status (requiring drug treatment) was ascertained by annual questionnaires in the 20- to 36-year follow-up period. An association was observed between maximum change in systolic blood pressure and later hypertension, with a cumulative incidence of hypertension by age 44 of 6.7%, 3.0%, and 2.4% for a change in systolic blood pressure in the upper, middle two, and lowest quartiles, respectively (Kaplan-Meier, p less than 0.02). After adjustment for study entry age, Quetelet Index, cigarette smoking, pretest systolic blood pressure, and paternal or maternal history of hypertension in a Cox model, the association persisted. The excess risk associated with systolic blood pressure reactivity was not apparent until the population aged some 20 years and was most apparent among those in whom hypertension developed before age 45 (relative risk = 2.5, 95% confidence intervals = 1.47, 4.71 for a 20 mm Hg change). Diastolic blood pressure and heart rate changes were not associated with later hypertension. These data suggest that persons prone to later hypertension manifest an altered physiology at a young age.

Body mass index in young men and the risk of subsequent knee and hip osteoarthritis.

PURPOSE: Obesity in middle age is associated with an increased risk of osteoarthritis of the knees in later life. We sought to determine whether body mass index in young men was a risk factor for the subsequent development of osteoarthritis of the knee and hip. SUBJECTS AND METHODS: Body mass index was assessed in 1,180 male medical students at age 23 +/- 2 (mean +/- SD) years and at several times during follow-up. The incidence of knee and hip osteoarthritis was ascertained by self-report and corroborated with information on symptoms and radiographic findings. RESULTS: During a median follow-up of 36 years, 62 participants developed knee osteoarthritis and 27 developed hip osteoarthritis. The incidence of knee, but not hip, osteoarthritis was strongly associated with body mass index assessed at ages 20 to 29 years and 30 to 39 years (both P <0.001). For body mass index assessed at ages 20 to 29 years, the incidence of knee osteoarthritis at age 65 years was 12.8% among the heaviest subjects (range 24.7 to 37.6 kg/m2), threefold greater than the incidence of 4.0% in the leanest (15.6 to 22.8 kg/m2) category of body mass index (P = 0.0001). Thus, for a man who was 180 cm (5'11") tall, each 8 kg (18 lb) greater weight at ages 20 to 29 years was associated with an increased risk of subsequent knee osteoarthritis (relative risk = 1.7, 95% confidence interval 1.3 to 2.1), after adjustment for year of birth, physical activity, and knee injury. Body mass index at ages 20 to 29 years was more predictive of future osteoarthritis than at ages 30 to 39 or 40 to 49 years. CONCLUSION: Greater body mass index in young men ages 20 to 29 years is associated with an increased risk of subsequent knee, but not hip, osteoarthritis, suggesting that cumulative exposure to greater weight during young adult life is an important cause of osteoarthritis.

Dyslipidemias with desirable plasma total cholesterol levels and angiographically demonstrated coronary artery disease.

The National Cholesterol Education Program treatment guidelines define a plasma total cholesterol of less than 200 mg/dl as "desirable" and recommend no further evaluation of plasma lipid or lipoprotein levels in patients with coronary artery disease (CAD). To determine the prevalence of dyslipidemias in the presence of coexistent CAD and total cholesterol less than or equal to 200 mg/dl, a retrospective case-control study of 1,000 patients who underwent diagnostic coronary angiography was performed. Of 351 patients with total cholesterol less than or equal to 200 mg/dl, 76% of the men (244) and 44% of the women (107) had angiographically demonstrated CAD. In men with CAD and total cholesterol less than or equal to 200 mg/dl, there was a significantly greater prevalence of low levels of high density lipoprotein (HDL) cholesterol (less than or equal to 35 mg/dl), age greater than 50 years, systemic hypertension and diabetes mellitus compared to non-CAD control subjects. In women with CAD and total cholesterol less than or equal to 200 mg/dl, HDL cholesterol less than or equal to 45 mg/dl and diabetes mellitus were also significantly prevalent. Multiple logistic regression analyses revealed that HDL cholesterol, hypertension and age in men and very low density lipoprotein cholesterol in women were significantly associated with CAD after adjustment for other risk factors. These results suggest that a complete lipid and lipoprotein analysis be obtained in all patients with CAD, irrespective of the plasma (or serum) total cholesterol level.

Validity of physicians' self-reports of cardiovascular disease risk factors.

To determine the accuracy of self-reported risk factors in 78 physicians, self-reported information was compared to findings on a standardized examination. Measured weight (r = 0.98), height (r = 0.95), body mass index (r = 0.96), systolic blood pressure (SBP) (r = 0.72), and diastolic blood pressure (DBP) (r = 0.60) were highly correlated with self-reported values (all P < 0.0001). Mean self-reported SBP and DBP did not differ from measured values; measured weight was 1.5 kg greater and measured height 1.4 cm less than self-reported values (both p < 0.0001). Regression of measured on self-reported values indicated excellent agreement except for DBP and heart rate. Differences between measured and self-reported values were not associated with a variety of variables except for a greater difference in SBP at higher levels of SBP. None of the 60 self-reported nonsmokers had expired carbon monoxide levels greater than 10 ppm. These results indicate that physicians' self-reports of height, body mass index, SBP, and smoking are extremely accurate and suitable for research purposes.

Coffee intake and coronary heart disease.

We examined the risk of coronary heart disease (CHD) associated with coffee intake in 1040 male medical students followed for 28 to 44 years. During the follow-up, CHD developed in 111 men. The relative risks (95% confidence interval) associated with drinking 5 cups of coffee/d were 2.94 (1.27, 6.81) for baseline, 5.52 (1.31, 23.18) for average, and 1.95 (0.86, 4.40) for most recent intake after adjustment for baseline age, serum cholesterol levels, calendar time, and the time-dependent covariates number of cigarettes, body mass index, and incident hypertension and diabetes. Risks were elevated in both smokers and nonsmokers and were stronger for myocardial infarction. Most of the excess risk was associated with coffee drinking prior to 1975. The diagnosis of hypertension was associated with a subsequent reduction in coffee intake. Negative results in some studies may be due to the assessment of coffee intake later in life or to differences in methods of coffee preparation between study populations or over calendar time.

Feasibility of using recipients of health promotional newsletters for post-marketing surveillance.

Achieving an adequate sample size is one of the major difficulties in performing post-marketing observational studies of health outcomes in persons taking specific drug preparations. We assessed the feasibility of recruiting participants for such a study of Cardizem CD from approximately 400,000 U.S. recipients of a health promotion newsletter. A three-page questionnaire was sent to a 2.5% random sample (n = 10,000) of recipients, stratified by geographic region. After two mailings, 2779 (28%) returned the questionnaire. Of the 2779 respondents, 2132 (77%) reported having high blood pressure. Eighty-seven percent indicated a willingness to participate in a long-term prospective study. In a multivariate model, calcium channel blocker (CCB) use was associated with a history of coronary heart disease, duration of hypertension medication use greater than 1 year, a rating of good or excellent hypertension care, higher systolic blood pressure, higher education level, family history of cardiovascular disease, and history of smoking. These results indicate that self-reported CCB users may be at greater risk of cardiovascular heart disease and that it is feasible to use health promotion newsletters as a source of participants in prospective studies of cardiovascular disease.

Hippocampal electrical activity in the female rat: the estrous cycle, copulation, parturition, and pup retrieval.

Hippocampal electrical activity was examined in female rats across the four phases of the estrous cycle, as well as during copulation, parturition, and pup retrieval. Possible hormonal effects on hippocampal activity were examined by recording daily during struggling and immobility throughout five estrous cycles. No differences in the characteristics of rhythmical slow activity (RSA), large-amplitude irregular activity (LIA), or their relation to behavior were found between the phases of the estrous cycle. Behaviors examined during copulation were lordosis, hopping, and ear wiggling. Lordosis and ear wiggling were both accompanied by irregular waves, with some low frequency RSA also present during lordosis. Hopping was accompanied by RSA which was greater in amplitude and frequency than RSA during walking. Parturition behaviors examined included body extensions, genital or pup licking, and 'body flattening'. Body extensions were found to be associated with irregular hippocampal activity, and appeared to be a Type 2 behavior. Interestingly, sudden suppressions of the hippocampal record lasting 1-5 s often preceded body extensions. Irregular hippocampal activity was present at all times during genital and pup licking. Body flattening was typically accompanied by very high amplitude irregular waves which, although the rats were awake, resembled a sleeping hippocampal pattern. Pup retrieval involved walking and was thus always accompanied by RSA.

A sex difference in turning bias in humans.

A large body of literature has documented the existence of individual preferences in turning direction among rodents which appear to be dependent on striatal dopaminergic mechanisms. Recent work has indicated that humans also demonstrate individual turning preferences, and that these preferences may also be related to the nigrostriatal dopamine system. We describe here a new method for measuring turning preferences in humans and report a sex difference in the magnitude of the directional preference. While both males and females tended to turn towards the right, this tendency was significantly stronger among females. Analyses of test-retest reliability across two sessions (1-2 weeks apart) indicated that, in general, the rotation task elicited consistent turning biases. However, the turning biases of males and of females using oral contraceptives were significantly more consistent than those of regularly cycling females. These results are compatible with the animal literature and provide indirect evidence that ovarian hormones may modulate the mechanism(s) underlying this motor asymmetry.

The prediction of midlife coronary heart disease and hypertension in young adults: the Johns Hopkins multiple risk equations.

Educating medical students about the identification of risk factors for coronary disease and hypertension should be enhanced by exercises in which medical students identify their own risk factors and visualize the impact of current risk status on future risk of disease. A cohort of 1,130 former Johns Hopkins medical students were examined in medical school and followed annually from 1948 to 1964 to identify youthful factors associated with the development of coronary heart disease and hypertension in midlife. In the ensuing years through 1984, 51 cases of coronary heart disease and 114 cases of hypertension developed. Multiple risk equations using Cox proportional hazards regression were developed to predict these endpoints. Incidence of coronary heart disease was predicted best by an equation containing age, serum cholesterol at baseline, cigarette smoking at baseline, and paternal history of coronary disease. Hypertension was predicted best by an equation containing age, systolic blood pressure at baseline, paternal history of hypertension, and Quetelet index. These equations were applied to a class of present-day medical students to demonstrate the considerable variability in 30-year risk of coronary disease or hypertension. Thus, coronary heart disease and hypertension in midlife can be predicted by factors identified in youth. The Johns Hopkins multiple risk equations may be valuable as tools in preventive cardiology education to illustrate risk assessment and the importance of risk factor interventions.

A multivariate assessment of spontaneous locomotor activity in the Mongolian gerbil (Meriones unguiculatus): influences of age and sex.

A multivariate assessment of the spontaneous locomotor activity of male and female Mongolian gerbils (Meriones unguiculatus) was obtained using a Digiscan automated animal activity monitoring system. Spontaneous motor activity data were collected over 1 h (5-min samples) for groups of male and female gerbils ranging from 26-341 days of age (26, 38, 62, 116, 151, 172, 196, 247, and 341). Variables examined included: total distance travelled, average distance per movement, average speed, number of horizontal movements, time in horizontal movement, time per horizontal movement, number of vertical movements, time in vertical movement, and time per vertical movement. Age had a significant effect on spontaneous activity; all measures of horizontal activity increased from preadulthood (26 and 38 days) and remained relatively constant thereafter for adults (62+ days). Vertical activity (rearing) measures were found to increase from the 62-day-old group to the 151- and 172-day-old groups and then decrease among the older groups (196+ days). Across the 12 samples, within sessions, all horizontal and vertical activity measures (except average speed) declined for both males and females. Habituation was more rapid for the preadults than for the adults on all horizontal measures except average distance per movement. No consistent sex differences in locomotor activity were found.

Youthful precursors of midlife social support.

Measures of family stability, sociocultural background, and emotional ties to parents in medical students (N = 589, mean age = 22 years) predicted their social support measures, assessed 23 to 39 years later (mean age = 56 years). Father's education and family's involvement in church were positively associated with group participation (number of group memberships), whereas parental loss between the ages of 11 and 20 was negatively associated with group participation; perceived emotional closeness to parents was positively associated with social closeness (number of close contacts providing emotional and instrumental support). Thus, group participation and social closeness were influenced by distinctly different childhood factors.

The psychosocial work environment of physicians. The impact of demands and resources on job dissatisfaction and psychiatric distress in a longitudinal study of Johns Hopkins Medical School graduates.

This study examines the relationship between the psychosocial work environment and cross-sectional job dissatisfaction and prospective psychiatric distress in a cohort of Hopkins Medical School graduates in midcareer. An instrument was constructed consisting of five scales: psychological job demands, patient demands, work control, physician resources, and coworker support. The results of scale reliability and factor analysis are presented. Higher job demands were found to be associated with increases in job dissatisfaction and psychiatric distress and greater resources were associated with decreased levels of dissatisfaction and distress. In multiple-regression analysis, only work control and social support were found to be independently associated with dissatisfaction and distress. These results suggest that the presence of control and social support at work protects physicians from developing job dissatisfaction and psychiatric distress.

Turning bias in humans is influenced by phase of the menstrual cycle.

Previous studies have provided evidence that humans demonstrate subtle, but measurable, turning biases when tested in the absence of environmental constraints. Preferences for leftward or rightward rotation have been repeatedly demonstrated in rodents and appear to be modulated to a significant degree by ovarian hormones, particularly estrogen. In the present study, we examined the turning biases of adult women at the midluteal and menstrual phases of the menstrual cycle, associated with high and low levels of estradiol and progesterone, respectively. Saliva samples were collected during each test session, and salivary concentrations of estradiol and progesterone were measured using radioimmunoassays. Overall, a rightward-turning bias was evident; however, a minority of the women displayed consistent leftward biases. Among right-turning subjects, turning biases were significantly weaker at the midluteal phase than at the menstrual phase. These results suggest that the mechanisms underlying human turning biases are subject to modulation by ovarian hormones.

Familial and psychological predictors of cancer.

The hypothesis that the quality of human relationships is a component in the development of cancer was investigated in a prospective study of former medical students. Findings from two psychological measures are presented: the Closeness to Parents Scale, which showed that students who subsequently developed cancer were more likely to describe a lack of closeness with their parents than their healthy classmates; and the Rorschach Interaction Scale, which demonstrated less satisfactory relationships among male cancer victims as contrasted with the rest of the cohort. The findings suggest that internal self-other representations, as measured by these two tests, are involved as regulators of biologic systems and manifestations of illness, such as cancer.