Process evaluation results from the HEALTHY nutrition intervention to modify the total school food environment.

The process evaluation of HEALTHY, a large multi-center trial to decrease type 2 diabetes mellitus in middle school children, monitored the implementation of the intervention to ascertain the extent that components were delivered and received as intended. The purpose of this article is to report the process evaluation findings concerning the extent to which the HEALTHY nutrition intervention was implemented during the HEALTHY trial. Overall, the observed fidelity of implementing nutrition strategies improved from baseline to the end of the study. By the last semester, all but two nutrition process evaluation goals were met. The most challenging goal to implement was serving high fiber foods, including grain-based foods and legumes. The easiest goals to implement were lowering the fat content of foods offered and offering healthier beverages. The most challenging barriers experienced by research dietitians and food service staff were costs, availability of foods and student acceptance. Forming strong relationships between the research dietitians and food service staff was identified as a key strategy to meet HEALTHY nutrition goals.

The effect of alphaxalone-alphadolone, propofol, and pentobarbitone anaesthesia on the ß-endorphin and ACTH response to haemorrhage in the pig.

In the literature there appears to be variability in reported levels of certain hormones during haemorrhage, specifically adrenocorticotrophic hormone (ACTH) and ß-endorphin. It is possible that this variability may be due to the choice of anaesthetic. Therefore, the effect of 3 common research-only anaesthetic agents (alphaxalone-alphadolone, propofol, and pentobarbitone) on ACTH and ß-endorphin levels during haemorrhage was assessed in pigs. Animals were divided into 3 groups: group I received alphaxalone-alphadolone (n = 5), group II received propofol (n = 6), and group III received pentobarbitone (n = 6). Pigs were subjected to a continuous fixed-volume haemorrhage under one of the above anaesthetics while being mechanically ventilated. ACTH and ß-endorphin levels increased significantly during haemorrhage under propofol and pentobarbitone anaesthesia but not with alphaxalone-alphadolone. For ACTH there was no significant difference between the groups, whereas for ß-endorphin there was a significant difference between the propofol- and pentobarbitone-anaesthetized pigs. The increase in heart rate during haemorrhage was significantly different between the alphaxalone-alphadolone and propofol as well as between the propofol and pentobarbitone groups. The drop in blood pressure was only significantly different between the alphaxalone-alphadolone- and propofol-anaesthetized pigs. These results indicate that the choice of anaesthetic agent can affect the hormone response to haemorrhage and may account for the variable hormone levels reported in the published literature to date.

Studies on tuberculin fever. IV. The passive transfer of reactivity with various tissues of sensitized donor rabbits.

Utilizing techniques of passive transfer, we have investigated the factors responsible for production of fever when tuberculin is given intravenously to specifically sensitized rabbits. The ability to develop a febrile response to tuberculin could be passively transferred to normal recipients with viable mononuclear cells from peritoneal exudates, spleen, or lymph nodes of donor rabbits sensitized with BCG. Sensitivity was usually apparent 48 hr after transfer, maximal at 7 to 14 days, and rapidly declined thereafter. Granulocytes and nonviable, sonicated, mononuclear cells from similarly sensitized donors were unable to transfer this form of reactivity. Passive transfer of reactivity was also effected with plasma and serum, suggesting that the reaction of antibody with antigen contained in tuberculin is one of the initial steps by which the host cells are activated to release the endogenous pyrogen (EP) that mediates this form of hypersensitivity fever. An intravenous infusion of granulocytes, as well as of several types of mononuclear cells from sensitized donors, made most recipients responsive to the pyrogenic effect of old tuberculin (OT) given 2 hr later. Some of these passively transferred cells, such as the granulocyte and alveolar macrophage, may be activated in vivo by OT, as they are in vitro. However, in the case of splenic and lymph node cells that cannot be activated by OT to produce EP in vitro, it seems likely that an intravenous injection of OT causes these transferred, sensitized cells to liberate an intermediate substance that either directly, or in association with antigen, activates the host's normal cells to produce EP. In support of previous suggestions that leukocytes of several types, as well as phagocytic cells of the reticuloendothelial system, serve as potential sources of EP in tuberculin-induced fever, evidence was presented that OT also activates both granulocytes and mononuclear cells from sterile exudates of BCG-sensitized donors to produce EP in vitro.

Rationale, design and methods for process evaluation in the HEALTHY study.

The HEALTHY study was a multi-site randomized trial designed to determine whether a 3-year school-based intervention targeting nutrition and physical activity behaviors could effectively reduce risk factors associated with type 2 diabetes in middle school children. Pilot and formative studies were conducted to inform the development of the intervention components and the process evaluation methods for the main trial. During the main trial, both qualitative and quantitative assessments monitored the fidelity of the intervention and motivated modifications to improve intervention delivery. Structured observations of physical education classes, total school food environments, classroom-based educational modules, and communications and promotional campaigns provided verification that the intervention was delivered as intended. Interviews and focus groups yielded a multidimensional assessment of how the intervention was delivered and received, as well as identifying the barriers to and facilitators of the intervention across and within participating schools. Interim summaries of process evaluation data were presented to the study group as a means of ensuring standardization and quality of the intervention across the seven participating centers. Process evaluation methods and procedures documented the fidelity with which the HEALTHY study was implemented across 21 intervention schools and identified ways in which the intervention delivery might be enhanced throughout the study.

The effect of ketamine and saffan on the beta-endorphin and ACTH response to hemorrhage in the minipig.

The endocrine response is an important component of the physiological response to blood loss. There is some variability in reported levels of certain hormones during hemorrhage such as the stress hormone adrenocorticotrophic hormone (ACTH). Therefore, the effect of two anesthetic agents, ketamine and saffan, on ACTH and beta-endorphin levels during hemorrhage was assessed in 12 minipigs. The animals were divided into two groups, group I saffan and group II ketamine (n=6). Pigs were subjected to a continuous fixed volume hemorrhage under one of the above anesthetics while spontaneously breathing. Blood pressure and heart rate responses were recorded together with beta-endorphin and ACTH levels both before and at 10, 20, 30, 40 min after the onset of bleeding. ACTH levels were higher in the ketamine-anesthetized pigs and rose significantly faster with falling blood pressure than ACTH measured in pigs under saffan anesthesia. In contrast, the hemorrhage induced beta-endorphin increase was not significantly different between the two anesthetic groups. These results indicate that choice of anesthetic agent is important when investigating the hormone response to hemorrhage and may account for the variable hormone levels in the published literature to date.

Pulmonary abnormalities in intermediate alpha-1-antitrypsin deficiency.

Pulmonary function studies were carried out in a group of asymptomatic nonsmoking adults with intermediate alpha-1-antitrypsin deficiency who were attending an early disease detection unit in Rochester, N. Y. All subjects were identified by specific protease inhibitor (Pi) typing. Fifteen MZ and 14 MS subjects who had never smoked cigarettes were matched by sex and age to MM controls. Spirometry, static lung volumes, and single breath-diffusing capacity were identical in all Pi type groups with no statistically significant differences noted. Maximal expiratory flow volume curves were obtained in all subjects. MZ subjects demonstrated statistically impaired maximal flow rates at 75%, 50%, and 25% of vital capacity compared to their MM controls. Total pulmonary resistance by the oscillometric method was measured at 3, 5, 7, and 9 cycle/s in the same subjects. Increased frequency dependence of resistance (defined as the difference between total pulmonary resistance at 3 cycle/s and 9 cycle/s) was observed in MZ subjects compared to MM controls. No differences were noted by this method in MS-MM pairs. The data suggest that detectable mechanical abnormalities are present in subjects with the MZ phenotype, even in the absence of established risk factors such as cigarette smoking and high air pollution.

Pyrolysis of waste electrical and electronic equipment: effect of antinomy trioxide on the pyrolysis of styrenic polymers.

This work has investigated the effect that antimony trioxide has on the pyrolysis of styrenic polymers and the effect that different types of brominated flame retardants used in plastics have on the composition of the pyrolysis products. Brominated high impact polystyrene (Br-HIPS) which contained either 5% or 0% antimony trioxide and either decabromodiphenyl oxide (DDO) or decabromodiphenyl ethane (DDE) was pyrolysed in a fixed bed reactor at 430 degrees C. Some experiments on the fixed bed reactor involved mixing the Br-HIPS with polystyrene. The gaseous products were analysed by GC-FID and GC-TCD and it was found that antimony trioxide caused an increase in the proportion of ethane and ethene and suppressed the proportion of butane and butene. When DDE was the flame retardant increased proportions of ethane and ethene were found in the pyrolysis gas compared to when DDO used. When polystyrene was mixed with the Br-HIPS it suppressed the trends observed in the gas composition during the pyrolysis of Br-HIPS. The pyrolysis oils were characterised using FT-IR, GC-MS, GC-FID, and GC-ECD. It was found that the plastic which did not contain antimony trioxide pyrolysed to form mainly toluene, ethylbenzene, styrene, cumene, and alpha-methylstyrene. The oils produced from the pyrolysis of the plastic that contained antimony trioxide did not contain any styrene or alpha-methylstyrene, but instead contained greater concentrations of ethylbenzene and cumene. The absence of styrene and alpha-methylstyrene from the pyrolysis oil occurred even when the Br-HIPS was mixed with polystyrene. GC-ECD analysis of the oils showed that the plastics which did not contain antimony trioxide pyrolysed to form (1-bromoethyl)benzene, which was totally absent from the pyrolysis oils when antimony trioxide was present in the plastic.

Neoplasms in persons treated with x-rays in infancy: fourth survey in 20 years.

The incidence of neoplastic disease was determined by a mail survey of 2,872 young adults given X-ray treatments in infancy and of their 5,005 nonirradiated siblings. Newly diagnosed benign and malignant neoplasms appeared more frequently in the irradiated subjects than in their siblings or the age- and sex-matched general population of upstate New York. Only thyroid neoplasms occurred in sufficient numbers to permit statistical analysis for the effects on incidence of sex, age, and dose, and of being in a high-risk group (sub-group C). Thyroid cancers developed earlier in life than did benign neoplasms, especially in boys; benign goiters occurred after smaller doses, predominantly in females. Females had a greater risk of developing thyroid cancer than males--2,3 times for females of all ages and 5 times for young adults. Except for young adult females, there was no definite age effect. The risk of cancer (but not of benign goiter) was proportional to the thyroid dose, with a linear risk coefficient of 2.5/year/million people exposed to 1 rad for the entire irradiated population and 4.0 for subgroup C. The high risk of thyroid cancer in subgroup C may be the result of the high percentage of Jews, who had a 3.4-fold greater risk than non-Jews. Young adult Jewish females had a 17-fold increased risk. An incidental observation was an apparent increased incidence of asthma and rare diseases with abnormal immunologic features in the irradiated population.

Clinical implications for affected parents and siblings of probands with long-QT syndrome.

BACKGROUND: Whenever a proband is identified with long-QT syndrome (LQTS), his or her parents and siblings should be evaluated regarding the possibility of carrying the disorder. In the majority of cases, one of the proband's parents and one or more siblings are affected. The aim of this study was (1) to determine whether the clinical severity of LQTS in the proband is useful in identifying first-degree family members at high risk for cardiac events, and (2) to evaluate the clinical course of affected parents and siblings of LQTS probands. METHODS AND RESULTS: The clinical and ECG characteristics of 211 LQTS probands and 791 first-degree relatives (422 parents and 369 siblings) were studied to determine if the clinical profile of the proband is useful in determining the clinical severity of LQTS in affected parents and siblings. Affected female parents of an LQTS proband had a greater cumulative risk for a first cardiac event than affected male parents. The probability of a parent or sibling having a first cardiac event was not significantly influenced by the severity of the proband's clinical symptoms. Female sex and QT(c) duration were risk factors for cardiac events among affected parents, and QT(c) was the only risk factor for cardiac events in affected siblings. CONCLUSIONS: The severity profile of LQTS in a proband was not found to be useful in identifying the clinical severity of LQTS in affected first-degree relatives of the proband.

Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome.

BACKGROUND: beta-blockers are routinely prescribed in congenital long-QT syndrome (LQTS), but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated. METHODS AND RESULTS: The study population comprised 869 LQTS patients treated with beta-blockers. Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy, and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers. After initiation of beta-blockers, there was a significant (P<0.001) reduction in the rate of cardiac events in probands (0.97+/-1.42 to 0.31+/-0.86 events per year) and in affected family members (0. 26+/-0.84 to 0.15+/-0.69 events per year) during 5-year matched periods. On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers (n=598) had a hazard ratio of 5.8 (95% CI, 3.7 to 9.1) for recurrent cardiac events (syncope, aborted cardiac arrest, or death) during beta-blocker therapy compared with asymptomatic patients; 32% of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers. Patients with a history of aborted cardiac arrest before starting beta-blockers (n=113) had a hazard ratio of 12.9 (95% CI, 4.7 to 35.5) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients; 14% of these patients will have another arrest (aborted or fatal) within 5 years on beta-blockers. CONCLUSIONS: beta-blockers are associated with a significant reduction in cardiac events in LQTS patients. However, syncope, aborted cardiac arrest, and LQTS-related death continue to occur while patients are on prescribed beta-blockers, particularly in those who were symptomatic before starting this therapy.

Marked reduction in long-term cardiac deaths with aspirin after a coronary event. Multicenter Myocardial Ischemia Research Group.

OBJECTIVES: We sought to assess the role of aspirin in a precisely defined cohort with coronary disease receiving current therapy. BACKGROUND: Prior results suggest that aspirin modestly decreases cardiac mortality in patients with coronary disease. However, these findings reflect heterogeneous study conditions and earlier management strategies. METHODS: We utilized findings from the Multicenter Study of Myocardial Ischemia, which enrolled 936 subjects 1 to 6 months after an acute myocardial infarction (n = 651 [70%]) or unstable angina (n = 285 [30%]). The follow-up period averaged 23 months, with treatment determined by referring physicians. RESULTS: At enrollment, 751 patients (80%) took aspirin regularly, usually 250 to 325 mg/day. Before enrollment, 291 patients (31%) had thrombolysis, and 352 (38%) had coronary angioplasty. During follow-up, cardiac death occurred in 22 patients, all-cause mortality in 31 and cardiac death or nonfatal myocardial infarction in 70. Each of these outcomes was significantly less frequent among aspirin users. Cardiac death rate was markedly reduced: 1.6% for aspirin users and 5.4% for nonusers (p = 0.005). These differences were not explained by imbalances in predictors of postinfarction risk or therapy other than aspirin (Cox hazard ratio 0.37, p = 0.023). They persisted at least 2 years after enrollment. The difference in mortality rate was particularly prominent after thrombolysis: 0.9% for aspirin users and 8.8% for nonusers (p = 0.004). CONCLUSIONS: Reduction in cardiac deaths among aspirin users is substantially greater than that reported previously. Although derived secondarily, our findings suggest that current practice leads to situations in which aspirin exerts a long-term, life-protecting action, particularly after thrombolysis.

T wave alternans in idiopathic long QT syndrome.

OBJECTIVES: The study evaluates the association between T wave alternans and the risk of cardiac events (syncope, aborted cardiac arrest or cardiac death) in a large population of patients with idiopathic long QT syndrome. BACKGROUND: T wave alternans is an infrequently recorded electrocardiographic (ECG) finding in patients with delayed repolarization, and its clinical significance is not clear. METHODS: A total of 4,656 ECG recordings in 2,442 patients enrolled in the International Long QT Syndrome Registry were reviewed for episodes of T wave alternans. To determine the risk associated with T wave alternans, independent of corrected QT interval (QTc) duration, patients with T wave alternans were matched for QTc value (every 0.025 s1/2) to patients with long QT syndrome without T wave alternans. RESULTS: T wave alternans was identified in 30 patients (25 of whom had a QTc interval > 0.50 s1/2). A strong association between QTc prolongation and T wave alternans was observed (odds ratio 1.23 per 0.01-s1/2 unit increase in QTc, p < 0.0001). Conditional logistic regression analyses with adjustment for age, gender, status and QTc value revealed that T wave alternans did not make a significant independent contribution to the risk of cardiac events. The risk of experiencing a major cardiac event was primarily related to length of QTc. CONCLUSIONS: T wave alternans, a marker of electrical instability and regional heterogeneity of repolarization, identifies a high risk subset of patients with prolonged repolarization. Patients with T wave alternans have an increased risk of cardiac events, but this risk is primarily related to the magnitude of repolarization delay (QTc prolongation). T wave alternans does not make an independent contribution to the risk of cardiac events after adjustment for QTc length.

Clinical implications of silent versus symptomatic exercise-induced myocardial ischemia in patients with stable coronary disease.

OBJECTIVES: This study was undertaken to better understand the functional and prognostic significance of silent relative to symptomatic ischemia. BACKGROUND: Previous studies have reached conflicting conclusions as to whether painless ischemia identified during noninvasive cardiac testing is related to a lesser extent of myocardial ischemia or a different prognosis than ischemia accompanied by angina, or both. METHODS: Nine hundred thirty-six clinically stable patients 1 to 6 months after an acute coronary event, either myocardial infarction or unstable angina, underwent ambulatory monitoring, exercise treadmill testing and stress thallium-201 scintigraphy. They were then followed up prospectively for a mean of 23 months for recurrent cardiac events (cardiac death, nonfatal myocardial infarction or unstable angina). RESULTS: Compared with patients with symptomatic ischemia during testing (n = 125), those with silent ischemia (n = 378) demonstrated less severe and extensive reversible defects on stress thallium scintigraphy (p = 0.0008), less functional impairment during treadmill testing manifested by longer exercise duration (640 +/- 173 vs. 529 +/- 190 s, p = 0.002) and longer time to ST segment depression (530 +/- 215 vs. 419 +/- 205 s, p = 0.0001) and less frequent ST segment depression during ambulatory monitoring (9% vs. 19%, p = 0.005). Patients with symptomatic ischemia had a significantly (p = 0.004) increased number of subsequent recurrent cardiac events (28.8%) versus those with silent (18.0%) or no (17.3%) ischemia. Adverse outcomes were especially concentrated in the subgroup with symptomatic ischemia and poor exercise tolerance. The difference in cardiac event rates between patients with silent versus symptomatic ischemia persisted after adjustment for baseline clinical characteristics by Cox regression analysis. CONCLUSIONS: Patients with painless ischemia during exercise testing 1 to 6 months after recovery from a coronary event have less jeopardized ischemic myocardium and fewer recurrent cardiac events than patients with symptomatic ischemia.

Risk of cardiac events in family members of patients with long QT syndrome.

OBJECTIVES: This study sought to identify risk factors for cardiac events (syncope, aborted cardiac arrest or sudden cardiac death) in family members of patients with the long QT syndrome. BACKGROUND: Patients with the long QT syndrome are known to be at high risk for cardiac events. Whenever the first member of a family is identified as having the long QT syndrome (proband), there is concern regarding the likelihood of cardiac events in other family members. METHODS: A multivariate logistic regression model was used to evaluate the risk of cardiac events in 637 family members who were first- and second-degree relatives of 151 probands with the long QT syndrome and in a subset of 513 family members who were not receiving beta-adrenergic blocking agents. There were 293 first-degree (46%) and 344 second-degree relatives (54%) (293 men [46%], 344 women [54%]). Fifteen percent of the family members had a corrected QT interval (QTc) > 0.44 s, and relative tachycardia and bradycardia were observed in 12% and 25%, respectively. RESULTS: The risk of cardiac events occurring before age 40 in family members not taking beta-blockers was influenced by the QTc interval (odds ratio [OR] 1.18/0.01 increase in QTc value; 95% confidence interval [CI] 1.12 to 1.24), relative tachycardia (OR 2.21, 95% CI 0.97 to 5.02) or bradycardia (OR 2.24, 95% CI 1.10 to 4.56) and an interaction term combining gender and closeness of the relationship to the proband (OR for female first-degree relative 3.23 vs. all second-degree relatives, 95% CI 1.67-6.22). CONCLUSIONS: Female first-degree relatives of patients with the long QT syndrome have a higher risk of cardiac events than male first- or second-degree relatives, independent of recorded electrocardiographic findings. Not only bradycardia, but also tachycardia increases risk of cardiac events in family members of patients with the long QT syndrome.

Probability of a positive transbronchial lung biopsy result in sarcoidosis.

Forty-one consecutive patients with suspected sarcoidosis underwent pulmonary function testing and transbronchial lung biopsy at three community teaching hospitals. Transbronchial biopsy disclosed noncaseating granulomas in 22 of 23 patients (96%) in whom parenchymal disease was roentgenographically apparent and in eight of 18 patients (44%) in whom it was not. The stage of the disease as determined by the chest roentgenogram was the most reliable determinant for a positive biopsy result. Not the presence of cough, dyspnea, or constitutional symptoms or pulmonary function as measured by forced vital capacity and carbon monoxide diffusing capacity served to predict a positive transbronchial biopsy finding any more accurately than did the roentgenographic staging of the disease itself. This study suggests that while transbronchial lung biopsy may be an acceptable initial diagnostic procedure in suspected sarcoid patients without parenchymal lung disease, clinical symptoms and pulmonary function abnormalities are not helpful in predicting the liklihood of a positive biopsy result.

Sensitivity, specificity, and predictive values of closed pleural biopsy.

To determine the clinical value of a nonspecific pleural biopsy specimen and fluid in malignant neoplasm and tuberculosis, we retrospectively reviewed records of all patients with pleural effusions undergoing the procedure at three community hospitals over six years. Two hundred eleven patients underwent biopsies. Adequate tissue was obtained in 207. The results were compared with the ultimate clinical and pathologic outcome by follow-up for 12 to 72 months. The initial procedure was diagnostic of malignant neoplasm in 54 patients and granulomatous disease in ten. A nonspecific or normal result was found in 143 (68%). Malignant neoplasms or tuberculosis was eventually established in 30 and excluded in 101 of the 143 patients. In 12 patients, no diagnosis was made. The procedure's sensitivities were 65% (malignant neoplasm) and 90% (tuberculosis). One false-positive result occurred in a patient with nontuberculous granulomatous pleuritis. The specificity and positive predictive value were 99% and 98%, respectively. The negative predictive value was 77%. Closed pleural biopsy with simultaneous fluid analysis is a valuable diagnostic procedure in community hospital patients, but a nonspecific result does not exclude malignant disease.

FUNCTIONAL LIMITATIONS AND ADIPOKINES IN HIV-INFECTED OLDER ADULTS.

BACKGROUND: There is a significant increase in the number of HIV-infected older adults (HOA). This population may experience functional decline at a much younger age. Little is known about the relationship between functional limitations and systemic adipokines in HOA. OBJECTIVE: Our study aimed to evaluate the relationship between functional limitations and systemic adipokine levels in HOA population. DESIGN: Cross-sectional. SETTING: Academic hospital-based infectious disease clinic. PARTICIPANTS: The study investigated community-dwelling HIV-infected adults >50 years old and compared this group with age, gender and BMI comparable healthy controls. MEASUREMENTS: We measured functional status, body composition and plasma concentrations of adipokines. RESULTS: Fifty-four HOA were studied (mean: age 57 years, BMI 29 kg/m2, CD4 604, duration of HIV 17 years) and compared with thirty-two age, gender and BMI comparable healthy controls. The HOA group showed significantly higher functional limitations compared to the age, gender and BMI comparable controls (p<0.05). Levels of adipokines were significantly different between the two groups (p<0.05). Multiple regression analyses indicated that adiponectin and visfatin were significantly correlated with several physical function measures after controlling for age, sex, and metabolic comorbidities. Adiponectin was negatively correlated with functional limitations, and this relationship was stronger in the control group compared to the HOA group. Conversely, visfatin was positively correlated with functional limitations only in the HOA group. CONCLUSION: HOA have significant functional limitations and alteration in adipokine levels compared to controls. Adiponectin and visfatin were associated with functional limitations. Visfatin was a correlate of physical function only in the HOA group. Prospective longitudinal studies could provide further insight on the role of adipokines in HIV-related functional decline.

A genetic marker and family history study of the upstate New York multiple sclerosis cluster.

We report nine additional cases of new-onset multiple sclerosis (MS) among employees of an upstate New York manufacturing plant that uses zinc as a primary metal. These cases, identified during the decade 1980 to 1989, had clinical onset of the disease between 1979 and 1987. The new cases confirm the increased incidence of MS previously reported in the plant population for the 1970 to 1979 decade. The MS subjects in this occupationally based cluster do not seem different from other MS patients with regard to rates of familial MS or the frequencies of alleles for human leukocyte (HLA-DR) antigens or transferrin. The frequency distribution of alleles for transferrin (an iron- and zinc-binding protein) may differ in these and other MS subjects compared with controls.

Multiple sclerosis and the workplace: report of an industry-based cluster.

Eleven cases of MS occurred within a 10-year period in a zinc-related manufacturing plant. The observed disease incidence was greater than expected from population data, using multiple approaches to statistical analysis (p less than or equal to 0.01). A case-control study, performed to examine several zinc parameters in blood, failed to indicate specific abnormalities among the MS patients, but all subjects (both MS and controls) working in the plant demonstrated higher serum zinc levels than all subjects (MS and controls) not working there.

Protein S declines during winter respiratory infections.

There is an increase in cardiovascular and cerebrovascular morbidity and mortality in the older adult population during the winter that could be related to prothrombotic changes caused by seasonal effects or acute respiratory tract infections. Therefore, a prospective cohort study was conducted to assess the effect of acute winter respiratory infection on hemostatic parameters including complement 4b-binding protein (C4-BP), functional protein S, total protein S, free protein S, and the inflammatory marker, interleukin-6 (IL-6), in younger and older adults. The changes in the levels of hemostatic and inflammatory markers during winter respiratory infections in the younger and older adults were compared with matched, non-infected controls. In younger and older adults (combined), total protein S increased from 83% [95% confidence interval (CI); 77-88] to 98% (95% CI; 91-106, P < 0.001) while free protein S decreased from 100% (95% CI; 95-105) to 70% (95% CI; 66-75, P < 0.001). There were no significant changes in C4-BP (P = 0.622), functional protein S (P = 0.061) or IL-6 (P = 0.651) from baseline. In a multivariate analysis, only total protein S and free protein S showed significant association with seasonal change after adjusting for the effect of infection. The estimated effect of season on total protein S was 15 +/- 4%, P < 0.001 and on free protein S was -27 +/- 3%, P < 0.001. After adjusting for seasonal effect, only functional protein S showed a significant association with infection, with the estimated effect of -17 +/- 5%, P < 0.001. The results in the younger and older adults were similar to those in the combined groups. Seasonal and infection-related changes in hemostatic parameters including an increase in fibrinogen and a decrease in free protein S, observed in this study, may contribute to thrombotic risk and excess vascular disease morbidity and mortality in older populations in the winter season.