Relationships among inflammatory cytokines, obesity, and insulin sensitivity in the horse.

Recent studies associate obesity and insulin resistance in horses with development of abnormal reproductive function and debilitating laminitis. The factors contributing to insulin resistance in obese horses are unknown. However, human studies provide evidence that elevated inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), IL1, and IL6 play direct roles in development of obesity-associated insulin resistance. Thus, inflammation may be a key link between obesity and insulin resistance in horses. The aim of the current investigation was to examine possible relationships between obesity, inflammatory cytokines, and insulin sensitivity (IS) in the horse. Age was recorded and BCS and percent body fat (% FAT) were determined as measures of obesity in 60 mares. In addition, blood mRNA expression of IL1, IL6, and TNFalpha and circulating concentrations of TNFalpha protein (TNFp) were determined in each mare. Finally, fasted concentrations of insulin were determined, and IS was determined using the hyperinsulinemic, euglycemic clamp. Significant correlations between several variables provided evidence for the design of 4 population regression models to estimate relationships between measures of obesity, inflammatory factors, and IS in the sample population. The results of these analyses revealed that IS decreased as BCS and % FAT increased (P < 0.001) in the sample population. Additionally, increased IL1 (P < 0.05) and TNFp (P < 0.01) were associated with decreased IS. However, increased TNFalpha (P < 0.001) was associated with decreased IS only in mares 20 yr of age and older. Increased BCS and % FAT were associated with increased expression of TNFalpha (P = 0.053) and IL1 (P < 0.05), and increased TNFp (P < 0.05). Surprisingly, increased BCS and % FAT were associated with decreased IL6 expression (P = 0.05) in mares <20 yr of age. Finally, evaluation of the influence of obesity and inflammatory cytokines on IS within the same model suggested that BCS and % FAT (P < 0.001) with TNFalpha [mRNA (P = 0.07) and protein (P < 0.05)] are inversely associated with IS independently of one another. Combined, these results provide the first evidence associating obesity with increased inflammatory factors in the horse. Furthermore, the results suggest that an interrelationship exists among obesity, inflammatory cytokines, and IS in the horse and emphasize the need for further studies to elucidate the nature of these relationships.

Tooth loss occurring at a place other than a health-care facility: 72-month incidence.

Dental care can occur within or outside the formal health-care system. We hypothesized that certain subject characteristics would partly explain one type of dental self-care, non-professional extractions. A representative sample of diverse groups of dentate adults was studied. In-person interviews and clinical examinations were conducted at baseline, 24, 48, and 72 months, with semi-annual telephone interviews in between. Of 699 participants, 291 (42%) reported loss of at least one tooth, of whom 42 (14% of those with tooth loss) reported having lost the tooth at a place other than a health-care facility. Ninety-four percent of non-professionally lost teeth were self-extracted; relatives extracted the remainder. Fifty-eight percent of these teeth were deliberately removed; the remainder came out while subjects were eating or brushing their teeth, or due to injury. Attachment loss and mobility at previous examination were consistent with the occurrence of non-professional extraction. The incidence magnitude was substantive and persistent throughout follow-up.

Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women's Health Study.

OBJECTIVE: To determine whether rheumatoid arthritis (RA) is associated with excess mortality among older women. METHODS: RA associated mortality was examined in a prospective cohort study that was started in 1986, and included 31 336 women aged 55-69 years without a history of RA at baseline. Up to 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (CI) were calculated as measures of association between RA onset and subsequent mortality (overall and cause-specific) using Cox proportional hazards regression. RESULTS: Compared with non-cases, women developing RA during follow up had a significantly increased mortality risk (RR=1.52; 95% CI 1.05 to 2.20). Mortality was higher among rheumatoid factor (RF) positive cases (RR=1.90; 95% CI 1.24 to 2.92) than among RF negative cases (RR=1.00; 95% CI 0.45 to 1.99). There were trends towards increased proportions of RA related deaths from infection (RR=3.61; 95% CI 0.89-14.69) and circulatory disease (RR=1.46; 95% CI 0.76 to 2.81) but not malignancy (RR=0.97; 95% CI 0.46 to 2.04). CONCLUSIONS: RA was associated with significantly increased mortality in a cohort of older women, and the association appeared to be restricted to those with RF positive disease.

Prior coronary artery bypass surgery and risk of death among patients with ischemic left ventricular dysfunction.

BACKGROUND: Patients with ischemic LV dysfunction are at high risk of sudden death. However, no benefit from prophylactic defibrillator therapy was observed in a group of patients with LV dysfunction undergoing CABG (CABG Patch trial). Thus, the effect of CABG on future risk of sudden death in patients with LV dysfunction is of considerable interest. METHODS AND RESULTS: Mortality and modes of death in 5410 patients with ischemic LV dysfunction who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trials were evaluated. Outcomes of patients with (n=1870, 35%) versus without (n=3540) history of prior CABG were compared, and stratification by baseline ejection fraction (EF) values (<0.25, 0.25 to 0.30, and >0.30) was performed. Prior CABG was associated with a 25% (95% CI, 15% to 36%) reduction in risk of death and a 46% (95% CI, 30% to 58%) reduction in risk of sudden death independent of EF and severity of heart failure symptoms. As baseline EF declined, absolute reduction in risk of sudden death with prior CABG increased (P<0.01). No alteration in risk of death from progressive heart failure was observed with prior CABG. When these results were applied to a group of patients with LV dysfunction who had not undergone prior surgery (Coronary Artery Surgery Study Registry) predicted annual rates of death (8.2%) and sudden death (2.4%) were similar to those observed in the CABG Patch trial (7.9% and 2.3%, respectively). CONCLUSIONS: In patients with ischemic LV dysfunction, prior CABG is associated with a significant independent reduction in mortality. These results appear to account for the lack of benefit from defibrillator therapy in the CABG Patch trial.

The association of socioeconomic status with outcomes in cystic fibrosis patients in the United States.

There is considerable variability in the clinical course of disease in cystic fibrosis (CF). Although currently unidentified modifier genes might explain some of this heterogeneity, other factors are probably contributory. Socioeconomic status (SES) is an important predictor of health status in many chronic polygenic diseases, but its role in CF has not been systematically evaluated. We performed a historical cohort analysis of pediatric CF patients in the United States using National Cystic Fibrosis Foundation Patient Registry (NCFPR) data for 1986 to 1994, and used Medicaid status as a proxy for low SES. The adjusted risk of death was 3.65 times higher (95% confidence interval [CI]: 3.03 to 4.40) for Medicaid patients than for those not receiving Medicaid. The percent predicted FEV(1) of surviving Medicaid patients was less by 9.1% (95% CI: 6.9 to 11.2). Medicaid patients were 2.19 times more likely to be below the 5th percentile for weight (95% CI: 1.91 to 2.51) and 2.22 times more likely to be below the 5th percentile for height (95% CI: 1.95 to 2.52) than were non-Medicaid patients. Medicaid patients were 1.60 times more likely to require treatment for a pulmonary exacerbation (95% CI: 1.29 to 1.98). There was no difference in the number of outpatient clinic visits for Medicaid and non-Medicaid patients. We conclude that low SES is associated with significantly poorer outcomes in children with CF. Barriers in access to specialty health care do not seem to explain this difference. Further study is indicated to determine what adverse environmental factors might cluster in CF patients of low SES to cause worse outcomes.

Alkaline pH changes in the cerebellum of asymptomatic HIV-infected individuals.

Human immunodeficiency virus (HIV) infection of the brain causes a complex cascade of cellular events involving several different cell types that eventually leads to neuronal cell death and the manifestation of the AIDS-associated dementia complex (ADC). Upon autopsy HIV-infected individuals show lesions within subcortical regions of the brain, including the cerebellum. Previously we have demonstrated, in primary and cell culture models of rat and human astrocytes, a change in intracellular pH (pH(i)) due to increased Na(+)/H(+) exchange following exposure to inactivated virus or gp120, the major HIV envelope glycoprotein. To further investigate whether any such in vivo pH(i) changes occur in human brains subsequent to HIV infection, we measured the pH(i) of the cerebellum in eight HIV-positive individuals and nine healthy volunteers using (31)P magnetic resonance spectroscopy imaging (MRSI) at high field strength (4.1 T). The results showed a significant difference between the age-adjusted mean pH(i) in the cerebellum in control group and patient groups (7.11 +/- 0.03 vs 7.16 +/- 0.04), and further HIV-infected individuals displayed a significant increase in the number of cerebellar volume elements that were alkaline. We hypothesize that this propensity towards alterations in cerebellar pH(i) may portend later neurological involvement resulting from HIV infection.

Colorectal cancer screening in North Carolina: associations with diabetes mellitus and demographic and health characteristics.

BACKGROUND: Diabetes mellitus (DM) may increase the risk of colorectal cancer, a leading cause of cancer death in the United States. This report examines factors associated with colorectal cancer screening, including DM status. METHODS: Data from the 1993/1995/1997 North Carolina (NC) Behavioral Risk Factor Surveillance System were analyzed to assess self-reported screening rates within guidelines for sigmoidoscopy/proctoscopy (sig/proct) and fecal occult blood test (FOBT). RESULTS: Overall, 28.6, 27.2, and 19.7% received a sig/proct, FOBT, or either test within guidelines, respectively. Screening rates varied according to some demographic variables, but not by DM status. However, DM status changed some relationships between screening and some demographic/health characteristics. CONCLUSIONS: Colorectal cancer screening in NC is similar to national rates, but certain subgroups are less likely to get screened. Persons with DM are as likely to get colorectal cancer screening, but some groups with DM (ethnic minorities, persons of low socioeconomic status) may be at high risk for not getting screened. Educational efforts to increase screening should target these groups.

A practical stroke severity scale predicts hospital outcomes.

GOAL: To develop a practical severity scale (Wake Forest Stroke Severity Scale [WFSSS]) to predict acute hospital outcomes and resource use after acute ischemic stroke based on the admission neurologic exam. BACKGROUND: A useful scheme enabling physicians and other health care providers to stratify stroke severity on admission to predict acute hospital outcomes and improve efficiency of inpatient care has not been described. METHODS: The study subjects consisted of 271 consecutive acute stroke patients admitted to the neurology department from July 1995 to June 1996 who were prospectively examined and whose stroke severity was classified on the basis of admission neurologic exam (level of consciousness, strength, dysphasia, neglect, and gait) as mild, moderate, or severe, based on the WFSSS. National Institutes of Health stroke scale (NIHSS) was performed early in admission (70% within 24 hours). Discharge disposition (home, inpatient rehabilitation [rehab], skilled nursing facility [SNF], or death); length of stay (LOS); and hospital charges were associated with initial stroke severity ratings using chi-square and Kruskal-Wallis tests. RESULTS: Fifty-percent (136) of strokes were classified as mild, 22% (60) as moderate, and 28% (75) as severe. Initial severity ratings were significantly related to discharge disposition, LOS, and hospital charges (all P values <.001). CONCLUSIONS: A practical clinical severity scale (WFSSS) for acute ischemic stroke patients based on admission neurologic examination predicts hospital disposition, LOS, and hospital charges, and may allow more accurate severity-adjusted comparisons among institutions.

Reduction in the chondrocyte response to insulin-like growth factor 1 in aging and osteoarthritis: studies in a non-human primate model of naturally occurring disease.

OBJECTIVE: Although the development of osteoarthritis (OA) is closely associated with aging, the mechanism for this association is not clear. This study was designed to determine the effects of aging and OA on the chondrocyte response to stimulation with insulin-like growth factor 1 (IGF-1) in a non-human primate model of naturally occurring OA. METHODS: Chondrocytes were isolated from cartilage removed separately from the medial and lateral femoral condyles and tibial plateaus of cynomolgus monkeys at the time of necropsy. Each joint site was scored histologically on a scale of 0-7 for OA pathologic changes. Isolated chondrocytes were cultured in alginate in serum-free medium and stimulated with IGF-1 or des(1-3) IGF-1, which has a much lower affinity for IGF binding proteins (IGFBP) than IGF-1. Response was measured as the ability to stimulate sulfate and proline incorporation. RESULTS: Cartilage samples from 34 monkeys ranging in age from 6.7 years to 27 years and with histologic scores ranging from 0 to 7 were analyzed. A significant decline in the response to IGF-1 was noted with both increasing age and increasing OA score. Controlling for the OA score, the estimated effect of age on IGF-1 response, measured by total sulfate incorporation, was a decline of 3.81% per year (P = 0.0001), or a 75% decline over 20 years as a monkey ages from young to older adult. Controlling for age, the effect of OA score was significant only for proline incorporation in the alginate matrix (estimated slope coefficient +/-standard error -15.9 +/- 7.2; P = 0.03), suggesting a negative effect of OA on retention of 3H-proline-labeled proteins in the matrix. There was a significantly reduced response to des(1-3) IGF-1 with increasing age, but no effect of OA score on response to des(1-3) IGF-1. There was no effect of age on cell viability. CONCLUSION: These results demonstrate a significant age-related decline in the chondrocyte response to IGF-1. The finding that increasing OA score was associated with a reduced response to intact IGF-1 but not des(1-3) IGF-1 suggests a role of increased production of inhibitory IGFBP in OA. Since the cells from older animals had a reduced response to both forms of IGF-1, the mechanism of the reduced response with age cannot be attributed to changes in IGFBP. Age-related changes in IGF receptors or, more likely, age-related alterations in intracellular signal transduction may also be involved.

Factors influencing use of the prostate-specific antigen screening test in primary care.

OBJECTIVE: To evaluate the use of the prostate-specific antigen (PSA) test and digital rectal examination (DRE) in prostate cancer screening by primary care physicians. STUDY DESIGN: Physician survey and retrospective medical record review. METHODS: We randomly selected and reviewed the medical records of 3 cross-sectional samples of male patients and surveyed their primary care physicians at 1-year intervals. All the physicians practiced in Colorado. The study spanned 3 years, including late 1992, when the American Cancer Society recommended the use of PSA in a prostate cancer screening guideline. RESULTS: We reviewed the medical records of 4772 male patients and surveyed 109 primary care physicians. We found that PSA testing for men aged 50 or older increased significantly from 1992 to 1994, from 24% in 1992 to 35% in 1993 and 40% in 1994 (overall odds ratio, 2.94; P < .05). Over the same time period, the DRE rate remained relatively unchanged (39% in 1992, 41% in 1993, and 36% in 1994). Overall PSA use was positively associated with patient age greater than 59 years, patient non-smoking status, physician "readiness to change cancer screening behavior," private insurance status, and nonsolo practice. Before the release of a prostate cancer screening guideline, participating physicians cited the American Cancer Society as the organization that most influenced their practice with respect to cancer screening. The magnitude of the reported influence of the American Cancer Society was correlated with the subsequent use of PSA in 1994 by primary care physicians after adjustment for change in DRE and baseline PSA rates, although the association did not reach statistical significance in multivariable regression models. CONCLUSIONS: Primary care physicians in Colorado significantly increased their use of the PSA test from 1992 to 1994, during which time the American Cancer Society issued a guideline recommending the use of PSA for prostate cancer screening. The reported influence of the American Cancer Society on cancer screening practices correlated with the subsequent increase in PSA testing.

Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy. Studies of Left Ventricular Dysfunction.

OBJECTIVES: To assess the relation of left ventricular (LV) and left atrial (LA) dimensions, ejection fraction (EF) and LV mass to subsequent clinical outcome of patients with LV dysfunction enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) Registry and Trials. BACKGROUND: Data are lacking on the relation of LV mass to prognosis in patients with LV dysfunction and on the interaction of LV mass with other measurements of LV size and function as they relate to clinical outcome. METHODS: A cohort of 1,172 patients enrolled in the SOLVD Trials (n = 577) and Registry (n = 595) had baseline echocardiographic measurements and follow-up for 1 year. RESULTS: After adjusting for age, New York Heart Association (NYHA) functional class, Trial vs. Registry and ischemic etiology, a 1-SD difference in EF was inversely associated with an increased risk of death (risk ratio, 1.62; p = 0.0008) and cardiovascular (CV) hospitalization (risk ratio, 1.59; p = 0.0001). Consequently, the other echo parameters were adjusted for EF in addition to age, NYHA functional class, Trial vs. Registry and ischemic etiology. A 1-SD difference in LV mass was associated with increased risk of death (risk ratio of 1.3, p = 0.012) and CV hospitalization (risk ratio of 1.17, p = 0.018). Similar results were observed with the LA dimension (mortality risk ratio, 1.32; p < 0.02; CV hospitalizations risk ratio, 1.18; p < 0.04). Likewise, LV mass > or =298 g and LA dimension > or =4.17 cm were associated with increased risk of death and CV hospitalization. An end-systolic dimension >5.0 cm was associated with increased mortality only. A protective effect of EF was noted in patients with LV mass > or =298 g (those in the group with EF >35% had lower mortality) but not in the group with LV mass <298 g. CONCLUSIONS: In patients with LV dysfunction enrolled in the SOLVD Registry and Trials, increasing levels of hypertrophy are associated with adverse events. A protective effect of EF was noted in patients with LV mass > or =298 g (those in the group with EF >35% fared better) but not in the group with LV mass <298 g. These data support the development and use of drugs that can inhibit hypertrophy or alter its characteristics.

Association of gender with symptoms and complications in type II diabetes mellitus.

Females with Type II diabetes appear more likely than males to experience symptoms and vascular complications related to their disease.

Physician and patient predictors of health maintenance visits.

BACKGROUND: Because of a strong association between health maintenance visits (HMVs) and cancer screening, knowledge of the predictors of an HMV have implications for screening. OBJECTIVE: To examine the association of an HMV with patient, physician, and practice characteristics in the primary care setting. DESIGN: A statewide study of cancer screening was conducted in Colorado to determine concordance with the National Cancer Institute's guidelines for screening for breast, cervical, prostate, and skin cancer. Medical records form patients were randomly chosen from primary care practices. Predictors of an HMV were determined by fitting a logistic model to baseline data, adjusting for the cluster sampling of patients within practices. SETTING: Nonacademic primary care practices in Colorado. PARTICIPANTS: A total of 5746 patients aged 42 to 74 years from 132 primary care practices. MAIN OUTCOME MEASURE: Whether a patient had an HMV in the previous year. RESULTS: Of all patients, 31% had an HMV in the previous year. Patient characteristics associated with having HMVs included nonsmoking status, odds ratio (OR) (95% confidence interval [CI]) of 1.27 (1.11-1.46), age, and sex. Women aged 50 to 69 years were significantly more likely to have an HMV than men aged 50 to 69 years (OR, 1.30; 95% CI, 1.10-1.54). Among adults aged 70 years and older, there were no significant sex differences in receiving HMVs. Physician and practice characteristics associated with providing HMVs included practice size (> or = 3 full-time physicians) (OR, 1.34; 95% CI, 1.01-1.77), physician contemplation of changing approaches to cancer screening (OR, 1.33; 95% CI, 1.04-1.70), and physician female sex (OR, 1.33; 95% CI, 1.04-1.70). Physician age and specialty (general internist or family physician) were not associated with the level of health maintenance delivery. CONCLUSION: Certain subgroups, such as smokers, patients in smaller practices, and physicians not yet considering changing their approach to cancer screening, could be targeted in future intervention studies designed to provide preventive services in primary care settings.

Effects of perioperative blood transfusion on prognosis in early-stage cervical cancer.

BACKGROUND: This study was designed to evaluate the prognostic effects of transfusion on patients undergoing radical hysterectomy for early cervical cancer. METHODS: This retrospective chart review analyzed 412 patients with stage IA-IIA disease, of whom 374 were evaluable. RESULTS: Three hundred (80%) patients received transfusions and 74 (20%) did not. The clinical characteristics of the two groups were similar, with the exception that the transfused group was older. Pathologic comparisons found that microscopic parametrial disease and larger cervical lesions were more common in the transfused group. Follow-up analysis revealed no difference between the two groups in recurrence or survival. Multivariate analysis found only grade, depth of invasion, and nodal status as independent predictors of recurrence and survival. Kaplan-Meier survival analysis showed no difference in overall survival or disease-free interval between the transfused and nontransfused groups. CONCLUSIONS: After correction for other prognostic factors, blood transfusion had no prognostic significance in patients with early cervical cancer undergoing radical hysterectomy.

Neurohumoral variability in left ventricular dysfunction. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction--a randomized clinical trial in patients with left ventricular ejection fraction < or = 35%. The variability of these hormones has not been determined in a large cohort of patients. Immediate (short-term) variability was assessed by systematically comparing levels after 15 and 30 minutes of supine rest at the initial visit, and longer term variability was assessed by comparing 30-minute supine rest values at the initial visit with corresponding values taken at 30 minutes after 16 to 24 days of stable therapy. Initial values obtained at the first visit after 30-minute supine rest for all 209 patients were (mean +/- SEM) 512 +/- 21 pg/ml pg/ml for plasma norepinephrine, 1.9 +/- 0.2 ng/ml/hr for plasma renin activity, 3.0 +/- 0.1 pg/ml for plasma arginine vasopressin, and 129 +/- 5.3 pg/ml for plasma atrial natriuretic peptide. All variables were moderately increased relative to established normal values. There was a small but significant decrease from 15- to 30-minute supine posture in all neurohormones, except arginine vasopressin. In the presence of stable background therapy, no significant differences were found between measurements obtained after 30 minutes supine rest at the initial visit and 16 to 24 days later. Spearman correlation coefficients corresponding to immediate and longer term variability were high (range 0.55 to 0.79) (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Tolerability of enalapril initiation by patients with left ventricular dysfunction: results of the medication challenge phase of the Studies of Left Ventricular Dysfunction.

Although converting-enzyme inhibitors are useful for the treatment of congestive heart failure (CHF), there are concerns about adverse reactions especially on initiation of therapy. In the Studies of Left Ventricular Dysfunction, enalapril, 2.5 mg twice per day was given on an open-label outpatient basis for 7 days (mean 6.1, range 2 to 7, and median 7) as a prerandomization drug challenge to 7487 patients with left ventricular dysfunction (ejection fraction < or = 0.35). Four hundred forty-four (5.93%) patients reported side effects, including symptoms attributed to hypotension (in 166 patients [2.2%]). The majority (346 [77.9%] of 444 and 129 [77.7%] of 166 with symptoms attributed to hypotension) of patients who reported side effects were willing to participate in the study and to continue receiving enalapril. Thus only 98 (1.3%) of 7487 patients (0.5% because of symptoms attributed to hypotension) were not willing to continue because of side effects. Women and patients of CHF class III or IV were more likely to report side effects. In conclusion, enalapril is well tolerated by patients with left ventricular dysfunction; treatment can be initiated on an outpatient basis in the majority of patients.

Demographic and dietary determinants of constipation in the US population.

We investigated the association between self-reported constipation and several demographic and dietary variables in 15,014 men and women 12-74 years of age examined between 1971-75 during the first Health and Nutrition Examination Survey. Overall, 12.8 percent reported constipation. Self-reported constipation correlated poorly with stool frequency. Nine percent of those with daily stools and 30.6 percent of those with four to six stools/week, reported constipation. Constipation was more frequent in Blacks (17.3 percent), women (18.2 percent), and those over age 60 (23.3 percent); after adjusting for age, sex, and race it was more prevalent in those with daily inactivity, little leisure exercise, low income, and poor education. Constipated subjects reported lower consumption of cheese, dry beans and peas, milk, meat and poultry, beverages (sweetened, carbonated and noncarbonated), and fruits and vegetables. They reported higher consumption of coffee or tea. They consumed fewer total calories even after controlling for body mass and exercise.

Childbearing in prison: a behavioral analysis.

An ethnographic study of the social and psychological experiences of antepartum and postpartum prisoners was undertaken using semistructured interviews. These data, coupled with chart review data for complications experienced by the mothers and newborns, produced the following outcomes: All subjects perceived the experience as a negative one, 20 of the 26 subjects experienced a total of 72 complications, and four of the 26 newborns experienced complications requiring hospitalization in newborn intensive care units.