The epidemiology of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults and is characterized by neurodegeneration of motor neurons in the brain and spinal cord. The incidence of ALS is approximately 1-2.6 cases per 100 000 persons annually, whereas the prevalence is approximately 6 cases per 100 000. The average age of onset of ALS is currently 58-60 years and the average survival from onset to death is 3-4 years. Between October 19, 2010 and December 31, 2011, there were an estimated 12 187 prevalent cases diagnosed with definite ALS in the USA alone. Sporadic ALS (90-95%) constitutes the large majority of cases, while the remaining 5-10% are hereditary and termed familial ALS. Sporadic ALS is suspected to involve genetic susceptibility to environmental risk factors. The purpose of this review is to present a clinical overview of ALS and provide an epidemiologic summary of personal and environmental risk factors shown to be related to the risk of disease. A discussion of the most recent research initiatives is also included.

The prevalence of benign breast disease in women with polycystic ovary syndrome: a review of a 12-year follow-up.

A cross-sectional study of benign breast disease (BBD) was conducted to determine the actual prevalence and follow-up importance of BBD among women with polycystic ovary syndrome (PCOS) in conjunction with an ongoing prospective cohort study. The present study involved a subset of the original group of 244 women with a diagnosis of PCOS and 244 control women matched by age and race. A total of 240 women (116 cases and 124 controls) were included in the present analysis. The majority of women in each group were Caucasians (93 and 96%, respectively). The median age was 46 years in the cases and 47 years in the controls. Screening mammography begins at the age of 40 and has been carried out in 69% of cases and 66% of controls since the study began. Family history of breast disease was observed in 27 cases of both the groups (p > 0.05). Neither fibrocystic breast disease, lump thickening, calcification, fibroadenoma, pain, redness, discharge nor hyperplasia showed a significantly higher prevalence rate in cases than in controls. Eleven (9%) women with PCOS and 21 (17%) controls underwent diagnostic or curative surgery (relative risk: 0.56). These results, in contrast to the previously published literature, do not allow us to conclude that there is a higher risk for BBD among women with PCOS, and the proportion of women with a positive family history of breast cancer was significantly greater in women with PCOS compared with controls. Our observation is that having PCOS does not appear to affect surgeons' decisions to remove BBD.

The relationship between C-reactive protein and carotid intima-media wall thickness in middle-aged women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with premature carotid atherosclerosis. C-Reactive protein (CRP) has been implicated as a vascular disease risk factor. The objective of this study was to determine whether elevated CRP is associated with increased carotid intima-media wall thickness (IMT) in PCOS women. Forty-seven PCOS patients and 59 similarly aged controls were screened for cardiovascular risk factors and concurrently underwent carotid ultrasonography (1996-1999). The main outcome measure was carotid IMT. CRP was significantly higher in PCOS patients than in controls (3.4 vs. 2.1 mg/dl; P = 0.002). In regression modeling, PCOS associated with IMT independently of CRP and age (P = 0.019). Body mass index reduced the association of PCOS and CRP with IMT and was also associated with IMT (P = 0.029). The CRP-IMT relationship was attenuated when either insulin or visceral fat was included in the PCOS-age-CRP model (P = 0.197 and P = 0.550, respectively). PCOS remained associated with IMT independent of insulin (P = 0.033) or visceral fat (P = 0.040). CRP does not appreciably mediate the effect of PCOS on IMT. Obesity partially explained the influence of PCOS and CRP on IMT. The effect of body mass index on the PCOS-IMT relationship was not completely determined by hyperinsulinemia or visceral fat, and might be mediated by other aspects of PCOS-related adiposity.

Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) exhibit an adverse cardiovascular risk profile, characteristic of the metabolic cardiovascular syndrome (MCS). The aim of this study was to determine the prevalence of coronary artery (CAC) and aortic (AC) calcification among middle-aged PCOS cases and controls and to explore the relationship among calcification, MCS, and other cardiovascular risk factors assessed 9 yr earlier. This was a prospective study of 61 PCOS cases and 85 similarly aged controls screened in 1993-1994 for risk factors and reevaluated in 2001-2002. The main outcome measures were CAC and AC, measured by electron beam tomography. Women with PCOS had a higher prevalence of CAC (45.9% vs. 30.6%) and AC (68.9% vs. 55.3%) than controls. After adjustment for age and body mass index, PCOS was a significant predictor of CAC (odds ratio = 2.31; P = 0.049). PCOS subjects were also 4.4 times more likely to meet the criteria for MCS than controls. High-density lipoprotein cholesterol and insulin appeared to mediate the PCOS influence on CAC. Interestingly, total testosterone was an independent risk factor for AC in all subjects after controlling for PCOS, age, and body mass index (P = 0.034). We conclude that women with PCOS are at increased risk of MCS and demonstrate increased CAC and AC compared with controls. Components of MCS mediate the association between PCOS and CAC, independently of obesity.

Dietary intake, physical activity, and obesity in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether dietary intake and physical activity contribute to obesity in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SUBJECTS: A total of 84 cases and 79 neighborhood controls of similar age. MEASUREMENTS: Fasting insulin, body mass index (BMI, kg/m2), waist/hip ratio, Block Food Frequency Questionnaire, Paffenbarger Physical Activity Questionnaire. RESULTS: Although women with PCOS had a higher BMI than control women, an overall comparison of women with and without PCOS showed no significant difference in dietary intake. However, stratification by BMI revealed that lean women with PCOS reported significantly lower energy intake than lean women without PCOS. CONCLUSION: Differences in dietary intake and physical activity alone are not sufficient to explain differences in weight between women with and without PCOS. Further research is necessary to determine the relative contributions of lifestyle factors and metabolism to obesity in PCOS.

Do women with polycystic ovary syndrome have an increased risk of cardiovascular disease? Review of the evidence.

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder found in ~5% of the general population and is characterized by chronic anovulation, hyperandrogenism, and insulin resistance. Women with PCOS are at increased risk for the development of Type II diabetes and may represent a unique group of women at high risk for the development of coronary heart disease (CHD). More adverse CHD risk profiles of women with PCOS have been demonstrated in several studies, yet actual health outcome studies have been inconclusive as to whether this translates into increased rates of cardiovascular disease in PCOS cases when compared to controls. This review focuses on the controversy surrounding the potential relationship between cardiovascular disease outcomes and polycystic ovary syndrome.

Assessment of the disturbances in metabolic homeostasis: a hypothesis of synergism.

Based on the hypothesis that a synergistic interaction between triiodothyronine (T(3)) and insulin contributes to abnormalities in glucose and other metabolic pathways, the mechanisms underlying the impairment of metabolic homeostasis (MH) and the development of type-2 diabetes (DM) were investigated via a proposed homeostatic model, [(FG*TG)/T3*FI)]. The MH model characterizes the relationship between T(3) and insulin and the levels of triglycerides (TG), fasting insulin (FI), and fasting glucose (FG) and is introduced as a clinical method to assess insulin sensitivity and the status of metabolic homeostasis in lieu of current screening models advocated by the by American Diabetic Association (ADA). The present study validated the hypothetical model in a sample of 110 African-American women.

A hypothesis of synergism: the interrelationship of T3 and insulin to disturbances in metabolic homeostasis.

While the role of abnormal insulin homeostasis in the pathogenesis of Type-2 diabetes mellitus is well established, the importance of the canonical role of T(3) on Type-2 diabetes or the homeostasis of glucose, lipid, and energy balance has not been addressed. Based on the available evidence from molecular biology, the pivotal regulatory role of T(3) in major metabolic pathways and glycemic control can be delineated by mapping the specific action sites of T(3) and insulin on the metabolic pathways of the glucose-lipid cycle. The current paper presents an integrative hypothesis of the synergistic relationship of T(3) and insulin in metabolic homeostasis and abnormalities.

Cardiovascular risk in women with polycystic ovary syndrome.

Compared with normal cycling women of similar age, women with polycystic ovary syndrome (PCOS) have an adverse lipid profile and an increased prevalence of Type II diabetes and hypertension. These woman also appear to have greater subclinical atherosclerotic disease, as demonstrated by greater carotid intimamedia wall thickness and higher levels of coronary calcification. Given the high prevalence of PCOS in the female population, this condition may potentially account for a significant proportion of the atherosclerotic heart disease observed in younger women. This article reviews the issues and uncertainties surrounding the PCOS-CHD association.

Polycystic ovary syndrome, androgen excess, and the impact on bone.

Polycystic ovary syndrome (PCOS) is a unique, natural model for the study of the influence of androgen excess on bone mass among women. Both thin and obese women develop PCOS, a presentation that allows for the evaluation of the effects of life-long obesity, alterations in body composition (central adiposity), and related metabolic abnormalities (hyperandrogenemia, hyperinsulinemia) on the skeleton. The relatively high prevalence of PCOS and its manifestation early in life render this disorder of particular importance in assessing the influence of androgens and androgen-estrogen balance on the attainment of maximal bone mass and subsequent development of osteoporosis later in life.

Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. An adverse lipid profile has also been observed in PCOS-affected women, suggesting that these individuals may be at increased risk for coronary heart disease at a young age. The objective of the present study was to evaluate subclinical atherosclerosis among women with PCOS and age-matched control subjects. A total of 125 white PCOS cases and 142 controls, aged >/=30 years were recruited. Collection of baseline sociodemographic data, reproductive hormone levels, and cardiovascular risk factors was conducted from 1992 to 1994. During follow-up (1996 to 1999), these women underwent B-mode ultrasonography of the carotid arteries for the evaluation of carotid intima-media wall thickness (IMT) and the prevalence of plaque. A significant difference was observed in the distribution of carotid plaque among PCOS cases compared with controls: 7.2% (9 of 125) of PCOS cases had a plaque index of >/=3 compared with 0.7% (1 of 142) of similarly aged controls (P=0.05). Overall and in the group aged 30 to 44 years, no difference was noted in mean carotid IMT between PCOS cases and controls. Among women aged >/=45 years, PCOS cases had significantly greater mean IMT than did control women (0.78+/-0.03 versus 0.70+/-0.01 mm, P:=0. 005). This difference remained significant after adjustment for age and BMI (P:<0.05). These results suggest that (1) lifelong exposure to an adverse cardiovascular risk profile in women with PCOS may lead to premature atherosclerosis, and (2) the PCOS-IMT association is explained in part by weight and fat distribution and associated risk factors. There may be an independent effect of PCOS unexplained by the above variables that is related to the hormonal dysregulation of this condition.

Do polycystic-appearing ovaries affect the risk of cardiovascular disease among women with polycystic ovary syndrome?

OBJECTIVE: To determine if polycystic-appearing ovaries (PAO) are associated with differences in risk factors for cardiovascular disease among women with polycystic ovary syndrome (PCOS). DESIGN: Case-control sub-study. SETTING: Division of Reproductive Endocrinology, Magee-Womens Hospital. PATIENT(S): Women with PCOS (n = 63) and non-PCOS controls (n = 56). INTERVENTION: Transvaginal ultrasonography and single sample venipuncture. MAIN OUTCOME MEASURE(S): Ultrasound ovarian appearance, fasting insulin, lipoproteins, androgens, LH/FSH ratio, anthropomorphic measurements, and blood pressure. RESULT(S): Women with PCOS had higher androgen and fasting insulin levels, a more adverse lipid profile, greater waist-hip and LH/FSH ratios, and a larger ovarian volume than controls. Thirty-three percent of the cases with PCOS, but only 5% of controls, showed PAO on ultrasound study (P<.01). PCOS cases with and without PAO had comparable levels of fasting insulin, lipids, and blood pressures. PCOS cases with PAO had a higher LH/FSH ratio (P=.028), increased levels of serum androstenedione (P=.029) and testosterone (P=.055), and greater ovarian volume (P=.024) compared to non-PAO patients. CONCLUSION: Women with PCOS have greater cardiovascular risk than controls. Within PCOS cases, however, the ultrasound appearance of polycystic ovaries does not appear to further intensify the cardiovascular disease risk profile of these women.

Chronic low back pain assessment using surface electromyography.

This investigation examined surface electromyography as an additional tool in the comprehensive clinical evaluation of patients with chronic low back pain (CLBP). Electromyographic signals from electrodes placed in the lumbar area of 30 CLBP patients and 30 non-pain control subjects were compared. Patients and controls were matched for age, gender, and body mass index. Paired t test showed a statistically significant difference between the two groups. The muscle activity mean values were threefold higher in CLBP patients than in controls (P < 0.00001) in the static testing, and twofold higher in CLBP patients than in controls (P < 0.00001) in the dynamic testing. Our findings indicate that surface electromyography assessment of the paraspinal muscle activity may be a useful objective diagnostic tool in the comprehensive evaluation of CLBP.

Mortality among the residents of the Three Mile Island accident area: 1979-1992.

The largest U.S. population exposed to low-level radioactivity released by an accident at a nuclear power plant is composed of residents near the Three Mile Island (TMI) Plant on 28 March 1979. This paper (a collaboration of The University of Pittsburgh and the Pennsylvania Department of Health) reports on the mortality experience of the 32,135 members in this cohort for 1979-1992. We analyzed standardized mortality ratios (SMRs) using a local comparison population and performed relative risk regression modeling to assess overall mortality and specific cancer risks by confounding factors and radiation-related exposure variables. Total mortality was significantly elevated for both men and women (SMRs = 109 and 118, respectively). All heart disease accounted for 43.3% of total deaths and demonstrated elevated SMRs for heart disease of 113 and 130 for men and women, respectively; however, when controlling for confounders and natural background radiation, these elevations in heart disease were no longer evident. Overall cancer mortality was similar in this cohort as compared to the local population (male SMR = 100; female SMR = 101). In the relative risk modeling, there was a significant effect for all lymphatic and hematopoietic tissue in males in relation to natural background exposure (p = 0.04). However, no trend was noted. We found a significant linear trend for female breast cancer risk in relation to increasing levels of TMI-related likely [gamma]-exposure (p = 0.02). Although such a relationship has been noted in other investigations, emissions from the TMI incident were significantly lower than in other documented studies. Therefore, it is unlikely that this observed increase is related to radiation exposure on the day of the accident. The mortality surveillance of this cohort does not provide consistent evidence that radioactivity released during the TMI accident has a significant impact on the mortality experience of this cohort to date. However, continued follow-up of these individuals will provide a more comprehensive description of the morbidity and mortality experience of the cohort.

Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome.

OBJECTIVE: To determine whether testosterone levels change as women with the polycystic ovary syndrome (PCOS) grow older. DESIGN: A follow-up cross-sectional study of a cohort of women with PCOS identified up to 20-25 years ago. SETTING: Women with PCOS were recruited primarily from practice records between 1970 and 1990. Voter registration tapes and household directories were used to identify age-, race-, and neighborhood-matched controls. PARTICIPANT(S): Eighty-four women with PCOS, 20-57 years of age, and 37 age-matched controls participating in a study of the risk for cardiovascular disease in women with PCOS. INTERVENTION(S): Clinical data were collected by questionnaire and fasting blood samples were obtained randomly throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Total and non-SHBG-bound testosterone levels. RESULT(S): Total and non-SHBG-bound testosterone levels were similar in women with PCOS who were 20-42 years of age but were reduced by approximately 50% among women 42-47 years of age and remained stable in women older than 47 years of age. Testosterone levels were increased in younger and older women with PCOS compared with controls but were similar to controls in women 42-47 years of age. CONCLUSION(S): Hyperandrogenism partly resolves before menopause in women with PCOS. This change may explain the tendency of women with PCOS to cycle regularly as they grow older. Testosterone levels remain elevated in older women with PCOS, however, and may contribute to their increased risk for cardiovascular disease, endometrial cancer, and other diseases.

Evidence for a dose-response relationship between occupational noise and blood pressure.

In this study, we investigated the role of occupational noise exposure and blood pressure among workers at 2 plants. A noise-exposed plant (plant 1, > or = 89 dBA) and a less-noise-exposed plant (plant 2, < or = 83 dBA) were chosen. Exposure was based on department-wide average noise measures; on the basis of job location and adjusting for layoffs during their employment at the plant, a cumulative time-weighted average noise level was calculated for each worker. The study population comprised 329 males in plant 1 and 314 males in plant 2. Their ages ranged from 40 to 63 y (mean ages = 49.6 and 48.7, respectively), and they had worked at least 15 y at the plant. The clinical examination was administered prior to the workday and measured height, weight, pulse, and blood pressure. In addition, we noted medical and personal-habits histories, including alcohol intake and cigarette smoking patterns. We used a questionnaire to determine in-depth occupation, military history, noisy hobbies, and family history of hypertension. When individuals who took blood-pressure medication were removed from the analysis, t tests for differences in average blood pressure between plants showed a mean systolic blood pressure of 123.3 mm Hg in plant 1 versus 120.8 mm Hg in plant 2 (p = .06) and a mean diastolic blood pressure of 80.3 mm Hg versus 77.8 mm Hg in Plant 1 and 2, respectively (p = .014). On the basis of data from the combined plants, multivariate analysis revealed that age, body mass index, cumulative noise exposure, current use of blood pressure medications, and alcohol intake were significant predictors for systolic blood pressure. Cumulative noise exposure was a significant predictor of diastolic blood pressure in plant 1 but not in plant 2, possibly reflecting a threshold effect.