Time course of pro- and anti-inflammatory cytokine levels in patients with burns--prognostic value of interleukin-10.

INTRODUCTION: Trends and the prognostic value of cytokine responses to severe burns have not been fully examined in humans. Therefore, the aim of this study was to determine the time course and prognostic value of pro- and anti-inflammatory cytokines in the immediate post-burn period. PATIENTS AND METHODS: Blood samples were taken for measuring IL-1 beta, IL-6, IL-8, IL-10, IL-12p70 and TNF-alpha concentrations from patients with more than 20% burned surface area on admission and on 5 consecutive days. Development of sepsis was assessed using standard criteria twice a day. RESULTS: IL-12p70 remained under assay detection levels in the study period. IL-1 beta and TNF-alpha could be detected in stimulated blood samples with higher levels in survivors (n=21). IL-6 on days 4-5 and IL-8 on days 4-6 in non-stimulated plasma showed significant elevation in non-survivors (n=18) whereas in stimulated blood its levels did not differ significantly. IL-10 levels were significantly higher in non-survivors during the study period in non-stimulated, and except day 6 in stimulated blood. Using the cut-off level of 14 pg ml(-1) for IL-10 predicted ICU mortality with 85.4% sensitivity and 84.2% specificity on admission. CONCLUSION: Early anti-inflammatory excess had a bad prognosis for patients suffering from severe burns.

Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis.

OBJECTIVE: To investigate the association between serum levels and clinical signs of lung fibrosis in patients with systemic sclerosis and inflammatory myopathies. METHODS: ELISA tests for a mucin-like glycoprotein KL-6, von Willebrandt factor (vWF), soluble E-selectin (sES) and surfactant protein D (SP-D) were performed in sera of 104 patients with systemic sclerosis, 31 patients with poly/dermatomyositis) and 24 patients with Raynaud's phenomenon as controls. The clinical and laboratory data were evaluated by a simple standard protocol including chest x-ray, lung function tests, echocardiography and, in selected cases, high resolution computer tomography (HRCT). Clinically significant pulmonary fibrosis (PF) defined as a simultaneous presence of radiological sign of pulmonary fibrosis and restrictive impairment. Severe PF was established if HRCT scans showed diffuse interstitial lung disease with low diffusing capacity. End stage PF was determined as severe PF with very low diffusing capacity. RESULTS: Patients with pulmonary fibrosis on chest x-ray showed significantly elevated serum levels of KL-6, SP-D and vWF. Inverse correlation was found between serum levels of KL-6/SP-D and lung function parameters, such as DLCO% and FVC. With regard to HRCT findings, patients with elevated serum level of KL-6 showed significantly more frequently ground glass opacity, diffuse and honeycombing fibrosis than patients with normal level of KL-6. The sensitivity of KL-6 for PF in SSc is increased with the severity of PF (PF on chest x-ray < severe PF < end stage of PF). Lung fibrosis occurred more frequently in patients with simultaneously elevated KL-6 and sES compared to cases with a single positivity of either KL-6 or sES. CONCLUSION: KL-6, SP-D, vWF and ES are good surrogate factors of pulmonary fibrosis but can not replace conventional diagnostic procedures. However, these markers are suitable for the assessment of progression and severity of pulmonary fibrosis in systemic autoimmune disorders once the diagnosis is established.

A prospective study of Type 2 diabetes and depressive symptoms in the elderly: the Rancho Bernardo Study.

AIMS: The association between Type 2 diabetes and depressive symptoms was examined prospectively to assess possible causal relationships between the two diseases. METHODS: A cohort of 971 men and women aged 50 and older from the adult population of Rancho Bernardo, California had an oral glucose tolerance test and completed the Beck Depression Inventory (BDI) at two clinic visits, 1984-87 and 1992-96. RESULTS: Depressive symptoms at baseline were associated with higher follow-up levels of non-fasting plasma glucose (P = 0.001) and an increased risk of developing Type 2 diabetes [odds ratio (OR) = 2.50; 95% confidence interval (CI) = 1.29-4.87], independent of sex, age, exercise and body mass index. Conversely, baseline non-fasting plasma glucose was not significantly associated with follow-up depressive symptoms and Type 2 diabetes at baseline was not significantly associated with the onset of BDI scores > or = 11 by the second visit (OR = 0.73; 95% CI = 0.41-1.30). CONCLUSIONS: Depressed mood is more likely to be a risk factor for Type 2 diabetes in older adults than the reverse.

Earthworm leukocyte populations specifically harbor lysosomal enzymes that may respond to bacterial challenge.

Earthworm leukocytes (coelomocytes) are responsible for innate cellular immune functions such as phagocytosis and encapsulation against parasites and pathogens. Microbial killing results from the combined action of the phagocytic process with humoral immune factors such as agglutinins (e.g., lectins), lysosomal enzymes (e.g., acid phosphatase, lysozyme), and various cytotoxic and antimicrobial molecules. There is also evidence of weak adaptive immune responses against foreign transplants. This study focused on aspects of the innate immune response. First, anti-human acid phosphatase (anti-AcP) polyclonal antibody characterized different acid hydrolase patterns in coelomocytes. Second, flow cytometry identified a strongly immunoreactive coelomocyte population. Third, ultrastructural and cytochemical analyses revealed acid phosphatase in discrete granules (lysosomes) of effector hyaline and granular coelomocytes but not in mature chloragocytes. Coelomocytes were exposed to bacteria to assess how phagocytosis influences: (a) the production of acid phosphatase using Western blot, and (b) release of acid phosphatase using ELISA from cell-free coelomic fluid. Fourth, after phagocytosis, acid phosphatase levels differed between controls and experimentals. Fifth, we found a 39-kDa molecule that reacted intensely with anti-AcP. Our results suggest that effector earthworm coelomocytes may not eliminate pathogens only by phagocytosis but also by extracellular lysis.

Galactoside-specific misletoe lectin modulates dexamethasone-induced apoptosis and glucocorticoid receptor level in Balb/c thymocytes.

The galactoside-specific plant lectin, Viscum album agglutinin-(VAA)-I has been shown to activate the natural immune system and modulate the maturation of thymocytes in vivo. However the mechanism of this immunobiological action is not yet understood. In our previous study we demonstrated the VAA-I-induced enhancement of proliferation and selection of thymocytes which inhibited the dexamethasone (DX)-induced thymocyte depletion. In this present work we investigated the effect of 1, 4 and 21 days of VAA-I treatment on DX-induced apoptosis of thymocytes in Balb/c mice. The number of early apoptotic cells was detected with Annexin V staining while the late apoptotic cells were identified according to their propidium iodide incorporation into DNA using flow cytometry. The expression of glucocorticoid receptor (GCR) in double-negative (DN), double-positive (DP) and CD4 or CD8 single-positive (SP) cell populations was assessed. The additive effect of lectin on DX-induced apoptosis of thymocytes consisted of two different actions of VAA-I and DX. One-day VAA-I treatment caused enhanced apoptosis in SP mature cells in contrast to the apoptotic effect of DX, which was mainly directed towards immature DN and DP cells. Treatment with 30 ng/kg VAA-I for four days elevated the GCR level (mean fluorescence intensity) in DP thymocytes. Lectin treatment for 21 days caused more than 20% elevation of GCR expression in all thymocyte subpopulations (DN, DP, CD4+ and CD8+). These results suggest that VAA-I may alter the sensitivity of thymocytes to glucocorticoids and this effect may play a role in the bell-shaped dose-response curve of lectin-induced immunological effects.

Mental and cognitive performance in the cold.

Vigilance, attention, memory, and motivation are essential to adapting to the physiological changes that occur with prolonged exposure to the cold and to avoiding both the environmental hazards associated with cold and the health-related consequences of these hazards. This paper summarizes the effects of cold temperatures on cognitive performance and mood. Although the effects of hypothermic-induced cold temperatures on cognitive performance and mood have been well documented, evidence of nonhypothermic effects has been inconsistent. There is evidence of a dose-response relation involving decrements in cognitive performance with respect to decline in core body temperature and complexity of tasks performed. However, it is unclear whether these effects are due to distraction or increased arousal. Likewise, further research is required to test the efficacy of existing and proposed pharmacologic and nutritional countermeasures.

Impairment in cognitive and exercise performance during prolonged antarctic residence: effect of thyroxine supplementation in the polar triiodothyronine syndrome.

Humans who work in Antarctica display deficits in cognition, disturbances in mood, increased energy requirements, a decline of thyroid hormone products, and an increase of serum TSH. We compared measurements in 12 subjects, before deployment (baseline), with 11 monthly studies during Antarctic residence (AR). After 4 months of AR (period 1), half of the subjects (T(4) group) received L-thyroxine [64 nmol.day(-)(1) (0.05 mg.day(-)(1))]; and the other half, a placebo (placebo group) for the next 7 months of AR (period 2). During period 1, there was a 12.3 +/- 5.1% (P < 0.03) decline on the matching-to-sample (M-t-S) cognitive task and an increase in depressive symptoms, compared with baseline. During the intervention in period 2, M-t-S scores for the T(4)-treated group returned to baseline values; whereas the placebo group, in contrast, showed a reduced M-t-S score (11.2 +/- 1.3%; P < 0.0003) and serum free T(4) (5.9 +/- 2.4%; P < 0.02), compared with baseline. The change in M-t-S score was correlated with the change in free T(4) (P < 0.0003) during both periods, and increases in serum TSH preceded worsening scores in depression, tension, anger, lack of vigor, and total mood disturbance (P < 0.001) during period 2. Additionally, the submaximal work rate for a fixed O(2) use decreased 22.5 +/- 4.9% in period 1 and remained below baseline in period 2 (25.2 +/- 2.3%; P < 0.005) for both groups. After 4 months of AR, the L-thyroxine supplement was associated with improved cognition, which seems related to circulating T(4). Submaximal exercise performance decrements, observed during AR, were not changed with this L-thyroxine dose.

Circannual pattern of hypothalamic-pituitary-thyroid (HPT) function and mood during extended antarctic residence.

The seasonal variation in thyroid function and mood was examined in 10 men and two women who spent the 1997 or 1998 austral winter at McMurdo Station, Antarctica. Serum samples of TSH, free T3 and free T4 were collected each month over a 10-month period (October-August), along with responses to the Profile of Mood States (POMS) and the Center for Epidemiologic Studies - Depression (CES-D) Scale. Both TSH and mood (a summary score created from the POMS depression, anger, fatigue and confusion subscales) exhibited a circannual pattern with peaks during the months of November and July and a trough during the months of March and April. High levels of tension-anxiety and confusion were preceded by declines in free T3 and T4. However, increases in tension-anxiety and total mood disturbance also preceded a decline in free T3 levels, suggesting a feedback of mood on T3 levels. Levels of free T4 were independently associated with preceding increases in anger scores. These results support the hypothesis that the symptoms characteristic of the winter-over syndrome is a state of relative CNS hypothyroidism. This model of seasonal variation in thyroid function and mood also has implications for an understanding of potential mechanisms underlying the association between latitude and SAD or S-SAD.

Psychosocial issues in long-term space flight: overview.

Anecdotal evidence of the individual and interpersonal problems that occurred during the Shuttle-Mir Space Program (SMSP) and other long-duration Russian/Soviet missions, and studies of personnel in other isolated and confined extreme (ICE) environments suggest that psychosocial elements of behavior and performance are likely to have a significant impact on the outcome of long-duration missions in space. This impact may range from individual decrements in performance, health and well being, to catastrophic mission failure. This paper reviews our current understanding of the psychosocial issues related to long duration space missions according to three different domains of behavior: the individual domain, the interpersonal domain and the organizational domain. Individual issues include: personality characteristics that predict successful performance, stress due to isolation and confinement and its effect on emotions and cognitive performance, adaptive and maladaptive coping styles and strategies, and requirements for the psychological support of astronauts and their families during the mission. Interpersonal issues include: impact of crew diversity and leadership styles on small group dynamics, adaptive and maladaptive features of ground-crew interactions, and processes of crew cohesion, tension and conflict. Organizational issues include: the influence of organizational culture and mission duration on individual and group performance, and managerial requirements for long duration missions. Improved screening and selection of astronaut candidates, leadership, coping and interpersonal skills training of personnel, and organizational change are key elements in the prevention of performance decrements on long-duration missions.

Relationship of climate, ethnicity and socioeconomic status to Kawasaki disease in San Diego County, 1994 through 1998.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in children in the United States. By monitoring trends in patient numbers and demographics during a 5-year period, we were able to explore the relationship between climate, ethnicity, socioeconomic status and susceptibility to KD. METHODS: We conducted active surveillance for all patients hospitalized with KD in San Diego County from 1994 through 1998. Data on seasonal variation in monthly rainfall and temperature were obtained from the US Meteorological Service. Patient sex, age, date of admission and self-reported ethnicity were identified from patient medical records. Socioeconomic status was assessed on the basis of insurance status among patients hospitalized at a single institution. RESULTS: During the 5-year period there were 169 cases of KD in San Diego County. The overall annual incidence of KD in children < 5 years of age ranged from 8.0 to 15.4/100 000. KD incidence was inversely associated with average monthly temperature (r = -0.47, P < 0.001) and positively associated with average monthly precipitation (r = -0.52, P < 0.001). Asian/Pacific Islanders < 5 years of age were 2.7 times as likely and Hispanics were one-third as likely to be hospitalized for KD than children from all other ethnic groups combined. Children with private or military insurance in all ethnic groups were more likely to have a diagnosis of KD than children with government assistance or no insurance. After controlling for insurance status, only Asian/Pacific Islanders remained at increased risk (rate ratio, 2.14) for KD relative to all other ethnic groups combined. CONCLUSION: KD is a common childhood vasculitis of unknown etiology. The skewed ethnic distribution and seasonality are consistent with the hypothesis that KD is an infectious disease that is influenced by environmental and genetic factors.

The use of complementary and alternative medicine by primary care patients. A SURF*NET study.

BACKGROUND: Despite the increased use and acceptance of complementary and alternative medicine (CAM) practices and practitioners by patients and health care providers, there is relatively little information available concerning the reasons for use or its effect on patient health status and well-being. METHODS: We conducted a survey of 542 patients attending 16 family practice clinics that belong to a community-based research network in San Diego, California, to determine patients' reasons for using CAM therapies in conjunction with a visit to a family physician and the impact of these therapies on their health and well-being. RESULTS: Approximately 21% of the patients reported using one or more forms of CAM therapy in conjunction with the most important health problem underlying their visit to the physician. The most common forms of therapy were visiting chiropractors (34.5%) of CAM users), herbal remedies and supplements (26.7%), and massage therapy (17.2%). Recommendations from friends or coworkers, a desire to avoid the side effects of conventional treatments, or failure of conventional treatments to cure a problem were the most frequently cited reasons for using these therapies. Use of practitioner-based therapies was significantly and independently associated with poor perceived health status, poor emotional functioning, and a musculoskeletal disorder, usually low back pain. Use of self-care-based therapies was associated with high education and poor perceived general health compared with a year ago. Use of traditional folk remedies was associated with Hispanic ethnicity. CONCLUSIONS: Sociodemographic characteristics and clinical conditions that predict use of CAM therapies by primary care patients in conjunction with a current health problem vary with the type of therapy used.

Behavior and performance on long-duration spaceflights: evidence from analogue environments.

BACKGROUND: Analyses of data collected in Antarctica since 1963 were conducted to identify features of behavior and performance likely to occur during long-duration missions in space. METHODS: The influence of mission duration and station latitude on POMS mood scores was examined in 450 American men and women who wintered-over in Antarctica between 1991 and 1998. The influence of crewmember social characteristics, personality traits, interpersonal needs, and station environments on measures of behavior and performance at the end of the austral winter was examined in 657 American men who wintered-over between 1963 and 1974. Both data sets were used to examine the influence of crew social structure on individual performance. RESULTS: Seasonal variations in mood appear to be associated with the altered diurnal cycle and psychological segmentation of the mission. Concurrent measures of personality, interpersonal needs, and coping styles are better predictors of depressed mood and peer-supervisor performance evaluations than baseline measures because of the unique features of the station social and physical environments and the absence of resources typically used to cope with stress elsewhere. Individuals in crews with a clique structure report significantly more depression, anxiety, anger, fatigue and confusion than individuals in crews with a core-periphery structure. Depressed mood is inversely associated with severity of station physical environment, supporting the existence of a positive or "salutogenic" effect for individuals seeking challenging experiences in extreme environments. CONCLUSION: Behavior and performance on long-duration spaceflights is likely to be seasonal or cyclical, situational, social, and salutogenic.

Summary of research issues in behavior and performance in isolated and confined extreme (ICE) environments.

The papers in this section of the workshop describe behavioral and performance charges in isolated and confined extreme (ICE) environments. These changes include increased disturbances of mood, rates of psychiatric disorder, and interpersonal tension, and a disruption of circadian rhythms. The workshop ended with four specific recommendations for future research.

Sleep and mood during a winter in Antarctica.

Seasonal variations in sleep characteristics and their association with changes in mood were examined in 91 American men and women who spent the 1991 austral winter at three different research stations in Antarctica. Measures of total hours of sleep over a 24-hr period, duration of longest (i.e., "nighttime") sleep event, number of sleep events, time of sleep onset, and quality of sleep remained unchanged over the course of the austral winter (March through October). However, exposure to total darkness based on station latitude was significantly associated with total hours of sleep, duration of longest sleep event, time of sleep onset, and quality of sleep. Reported vigor the previous month was a significant independent predictor of changes in all five sleep measures; previous month's measures of all six POMS subscales were significant independent predictors of sleep quality. Sleep characteristics were significant independent predictors of vigor and confusion the following month; total sleep, longest sleep event, sleep onset and sleep quality were significant independent predictors of tension-anxiety and depression. Changes in mood during the austral winter are preceded by changes in sleep characteristics, but prolonged exposure to the photo-periodicity characteristic of the high latitudes appears to be associated with improved sleep. In turn, mood changes appear to affect certain sleep characteristics, especially sleep quality.

Predictors of behavior and performance in extreme environments: the Antarctic space analogue program.

BACKGROUND: To determine which, if any, characteristics should be incorporated into a select-in approach to screening personnel for long-duration spaceflight, we examined the influence of crewmember social/ demographic characteristics, personality traits, interpersonal needs, and characteristics of station physical environments on performance measures in 657 American men who spent an austral winter in Antarctica between 1963 and 1974. METHODS: During screening, subjects completed a Personal History Questionnaire which obtained information on social and demographic characteristics, the Deep Freeze Opinion Survey which assessed 5 different personality traits, and the Fundamental Interpersonal Relations Orientation-Behavior (FIRO-B) Scale which measured 6 dimensions of interpersonal needs. Station environment included measures of crew size and severity of physical environment. Performance was assessed on the basis of combined peer-supervisor evaluations of overall performance, peer nominations of fellow crew-members who made ideal winter-over candidates, and self-reported depressive symptoms. RESULTS: Social/demographic characteristics, personality traits, interpersonal needs, and characteristics of station environments collectively accounted for 9-17% of the variance in performance measures. The following characteristics were significant independent predictors of more than one performance measure: military service, low levels of neuroticism, extraversion and conscientiousness, and a low desire for affection from others. CONCLUSIONS: These results represent an important first step in the development of select-in criteria for personnel on long-duration missions in space and other extreme environments. These criteria must take into consideration the characteristics of the environment and the limitations they place on meeting needs for interpersonal relations and task performance, as well as the characteristics of the individuals and groups who live and work in these environments.

Stages of change in mood and behavior during a winter in Antarctica.

Seasonal variation in mood and behavior was examined in 87 American men and women who spent the 1991 austral winter at three different research stations in Antarctica. The South Pole station (90 degrees S) crew reported a significant decline in tension/anxiety, depression, anger, confusion, and fatigue from March to August, followed by a significant increase in tension/anxiety and fatigue and a significant decline in vigor from August to October. The McMurdo station (78 degrees 51' S) crew also reported a significant decline in tension/anxiety from March to July and a significant increase in tension/anxiety from July to August. In contrast, the Palmer station (64 degrees 46' S) crew experienced no significant changes in any mood subscale from May to October. The nonlinear pattern of change in mood suggests that adaptation to prolonged isolation and confinement in an extreme environment occurs in two or three stages.

Sociocultural change and health status among the Seri Indians of Sonora, Mexico.

The influence of changes in sociocultural status on obesity, arterial blood pressure, and depression was examined in a cohort of 81 Seri Indians living in two communities in Sonora, Mexico. Residents of the less acculturated and modernized community, Desemboque, exhibited significantly higher waist circumference and prevalence of obesity than did residents of the more acculturated and modernized community of Punta Chueca. The prevalence of obesity was also significantly associated with low levels of acculturation and modernization, while the prevalence of clinically significant depressive symptoms was associated with low levels of modernization and household income. Lifestyle incongruity was a significant independent risk factor for body mass index and depressive symptom scores but not for arterial blood pressure. The results support the notion of a curvilinear relationship between health status and sociocultural change in which health status initially declines with increasing lifestyle incongruity but eventually improves with increasing acculturation, modernization, and income.

Immigration reform and the health of Latino immigrants in California.

This paper examines Latino immigrant health within the context of the current debate over immigration reform and the resulting cultural construction of public health in California. A review of epidemiologic and ethnographic data indicates that the subordinate socioeconomic status of Latino immigrants plays a major role in both disease etiology and access to health services. However, this status does not explain why certain patterns of health services utilization and disease morbidity and mortality persist although political and economic circumstances have changed. These patterns include the reluctance to utilize certain health services despite access to health insurance and the presence of an epidemiologic paradox in which Latinos have health status indicators comparable to or better than that of other ethnic groups despite high poverty, low education, and lack of access to care. An "economy of culture" model is used to explain these inconsistencies in the political economy model of Latino immigrant health.