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Background: Although the association of clinical hypothyroidism with cognitive deficits is well known, the cognitive effects of thyroid hormones in euthyroid subjects are less studied and understood. The purpose of this study was to examine thyroid-cognition relationships in healthy, euthyroid older men.Methods: We examined healthy men (N = 44, mean age = 72), excluding clinically hypothyroid/hyperthyroid or diabetic/hyperglycemic subjects and those with dementia, depression, CNS medications, or recent illness. Plasma samples obtained across a 24-hour period were pooled, then assayed for total thyroxine (TT4), total triiodothyronine (TT3), and T3 resin uptake. Free thyroxine index (FT4I) was calculated. A broad cognitive battery (including the Wechsler Adult Intelligence Scale-Revised [WAIS-R], the Dementia Rating Scale [DRS], and the Rivermead Behavioral Profile [PROFILE]) was administered to all subjects.Results: Regression analyses controlling age and education showed TT4 and FT4I to have significant positive relationships with measures of overall cognition; TT4 accounted for 8% to 12% of the variance in omnibus cognitive measures such as WAIS Performance, WAIS Verbal score, and GLOBAL cognitive scores.Conclusions: Our findings suggest that within "normal" range of variation in plasma thyroid hormones, TT4 but not T3 positively associates with general cognition in healthy elderly men. [ABSTRACT FROM AUTHOR]

Purpose: Cases of chemotherapy-induced peripheral neuropathy (CIPN) under-reporting have been sporadically described in the literature, but no studies have focused on actively examining this behavior. Our primary aim was to identify women who purposefully under-reported CIPN, along with reasons for doing so. A secondary aim was to explore factors enabling or hindering communication of CIPN to clinicians., Methods: Semi-structured interviews were conducted with women with breast cancer who had received paclitaxel in a prospective observational study. The interview guide was developed based on factors hypothesized to influence side effect disclosure to clinicians. Interviews were recorded, transcribed verbatim, and thematically content analyzed., Results: Thirty-four women were interviewed. Three main themes emerged from the analysis: (1) enablers of CIPN reporting (e.g., positive relationship with the oncology team, sufficient appointment time, existence of alternative communication channels to office visits, expectation of CIPN as a side effect); (2) deterrents to CIPN reporting (e.g., perception of need to complete the full course of therapy, fear of treatment discontinuation, lack of knowledge of long-term consequences of CIPN); and (3) balancing survival versus functional impairment due to CIPN. Women prioritized efficacy over CIPN until physical functioning was meaningfully affected. No patients reported purposeful CIPN under-reporting, but three women admitted having considered doing so., Conclusions: Despite the lack of evidence of CIPN withholding, women considered both the effectiveness and the toxicity of paclitaxel treatment, as well as beliefs about treatment and long-term consequences of CIPN and relationship with the oncology team, when deciding whether to report CIPN symptoms.

Purpose: Discrepancies between clinicians' assessment of chemotherapy-induced peripheral neuropathy (CIPN) and patient-reported outcomes (PRO) have been described, though the underlying reasons are unknown. Our objective was to identify potential patient-specific factors associated with under-describing of CIPN to clinicians in women with non-metastatic breast cancer treated with paclitaxel., Methods: Patients enrolled in an observational study (n = 60) completed weekly CIPN PRO using the EORTC CIPN20. Clinician-documented CIPN using the NCI CTCAE were abstracted from the electronic medical record and paired with CIPN20 data at weeks 7 and 10. Patients were classified as under-describers if their CIPN20 was above the 80th percentile of the CIPN20 distribution for that CTCAE grade from an independent clinical trial (N08CA). Demographics, Assessment of Survivor Concerns (ASC), Trust in Oncologist Scale (TiOS), and health literacy assessment were collected post-treatment via survey. Repeated measures cumulative logistic regression models were used to identify factors associated with under-describing CIPN., Results: Forty-two women completed the survey (response rate 70%). Three and 9 patients were categorized as under-describers at weeks 7 and 10, respectively. Women who were not working (OR = 9.00, 95%CI 1.06-76.15), had lower income (OR = 7.04, 95%CI 1.5-32.99), and displayed higher trust in their oncologist's competence (OR = 1.29, 95%CI 1.03-1.62 for a 0.1-unit increase in score) were more likely to under-describe CIPN symptoms., Conclusions: This preliminary study identified non-working status, low income and trust in oncologist's competence as potential factors influencing under-description of CIPN to the clinical team. Further work is needed to clarify these relationships and test additional factors., Competing Interests: Declaration of competing interest Syverson owns stock in Pfizer Inc. and AbbVie Inc. Loprinzi received personal fees from Pled Pharma, Metys, Disarm Therapeutics, and Asahi Kasei. Farris is a consultant and received remuneration from Quio Technologies. All other authors declare that they have no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We evaluated provider adherence to practice guidelines for inpatients diagnosed with Clostridoides difficile infection (CDI) before and after implementation of a best practice alert (BPA) linking a positive test result to guideline-based orders. After implementation of the BPA, guideline-based prescribing increased from 39.4% in 2013 to 67.7% in 2016 (P = .014).

Purpose: This study examined municipal officials' participation in built environment policy initiatives focused on land use design, transportation, and parks and recreation., Design: Web-based cross-sectional survey., Setting: Eighty-three municipalities with 50,000 or more residents in eight states., Subjects: Four hundred fifty-three elected and appointed municipal officials., Measures: Outcomes included self-reported participation in land use design, transportation, and parks and recreation policy to increase physical activity. Independent variables included respondent position; perceptions of importance, barriers, and beliefs regarding physical activity and community design and layout; and physical activity partnership participation., Analysis: Multivariable logistic regression models., Results: Compared to other positions, public health officials had lower participation in land use design (78.3% vs. 29.0%), transportation (78.1% vs. 42.1%), and parks and recreation (67.1% vs. 26.3%) policy. Perceived limited staff was negatively associated with participation in each policy initiative. Perceptions of the extent to which physical activity was considered in community design and physical activity partnership participation were positively associated with participation in each. Perceived lack of collaboration was associated with less land use design and transportation policy participation, and awareness that community design affects physical activity was associated with more participation. Perceived lack of political will was associated with less parks and recreation policy participation., Conclusion: Public health officials are underrepresented in built environment policy initiatives. Improving collaborations may improve municipal officials' policy participation.

Sepsis is the 11th leading cause of death in the United States. The authors evaluated the dependence of all-cause in-hospital mortality on sepsis mortality. A retrospective observational cohort design and All Patient Refined Diagnosis Related Groups were used to evaluate 150 410 patients (>17 years of age) over 6 years. The hospital standardized mortality ratio (HSMR) decreased from 0.80 ± 0.04 to 0.65 ± 0.04 (observed/expected [O/E]). The HSMR was correlated with the standardized sepsis mortality ratio (SSMR), accounting for 61% of the variation (P < .0001). The mortality rate for sepsis declined from 14.54 ± 1.60% to 8.57 ± 1.88% (P < .002), and the SSMR decreased from 0.82 ± 0.09 to 0.48 ± 0.07 (O/E; P < .002). The months of sepsis mortality matched the months of hospital mortality for the lowest of each (odds ratio = 0.30, 95% confidence interval = 0.14-0.65; P < .003) and the highest of each (odds ratio = 1.47, 95% confidence interval = 1.18-1.84; P < .0007). Monitoring monthly mortality of sepsis can provide insight for timely intervention into variation of total in-hospital mortality., (© 2013 by the American College of Medical Quality.)

Background: The United States National Physical Activity Plan (NPAP; 2010), the country's first national plan for physical activity, provides strategies to increase population-level physical activity to complement the 2008 physical activity guidelines. This study examined state public health practitioner awareness, dissemination, use, challenges, and recommendations for the NPAP., Methods: In 2011-2012, we interviewed 27 state practitioners from 25 states. Interviews were recorded and transcribed verbatim. Transcripts were coded using a standard protocol, verified and reconciled by an independent coder, and input into qualitative software to facilitate development of common themes., Results: NPAP awareness was high among state practitioners; dissemination to local constituents varied. Development of state-level strategies and goals was the most frequently reported use of the NPAP. Some respondents noted the usefulness of the NPAP for coalitions and local practitioners. Challenges to the plan included implementation cost, complexity, and consistency with other policies. The most frequent recommendation made was to directly link examples of implementation activities to the plan., Conclusions: These results provide early evidence of NPAP dissemination and use, along with challenges encountered and suggestions for future iterations. Public health is one of eight sectors in the NPAP. Further efforts are needed to understand uptake and use by other sectors, as well as to monitor long-term relevance, progress, and collaboration across sectors.

School-based physical education (PE) and physical activity (PA) policies can improve PA levels of students and promote health. Studies of policy implementation, communication, monitoring, enforcement, and evaluation are lacking. To describe how states implement, communicate, monitor, enforce, and evaluate key school-based PE and PA policies, researchers interviewed 24 key informants from state-level organizations in 9 states, including representatives from state departments of health and education, state boards of education, and advocacy/professional organizations. These states educate 27% of the US student population. Key informants described their organizations' roles in addressing 14 school-based PE and PA state laws and regulations identified by the Bridging the Gap research program and the National Cancer Institute's Classification of Laws Associated with School Students (C.L.A.S.S.) system. On average, states had 4 of 14 school-based PE and PA laws and regulations, and more than one-half of respondents reported different policies in practice besides the "on the books" laws. Respondents more often reported roles implementing and communicating policies compared with monitoring, enforcing, and evaluating them. Implementation and communication strategies used included training, technical assistance, and written communication of policy to local education agency administrators and teachers. State-level organizations have varying roles in addressing school-based PE and PA policies. Opportunities exist to focus state-level efforts on compliance with existing laws and regulations and evaluation of their impact.

Introduction: Changing the built environment to promote active lifestyles requires collaboration among diverse sectors. Multisectoral collaborative groups in the United States promote active lifestyles through environmental and policy changes. The objective of this study was to examine the characteristics of these collaborative groups and the extent to which they have achieved change., Methods: We identified, recruited, and interviewed the coordinators of active living collaborative groups in the United States. We used descriptive statistics to characterize groups by composition, stakeholder engagement, and the extent of environmental and policy change in 8 strategic areas., Results: Fifty-nine groups from 22 states participated in the study. Most groups had a diverse set of partners and used a range of activities to advance their agendas. Most groups achieved some form of environmental or policy change. On average, groups reported working on 5 strategy areas; parks and recreation (86%) and Safe Routes to School (85%) were named most frequently. More than half of groups reported their environmental initiatives as either in progress or completed. Groups reported the most success in changing policy for public plazas, street improvements, streetscaping, and parks, open space, and recreation. Complete Streets policy and zoning ordinances were the most frequently cited policy types. Engaging in media activities and the policy-making process in addition to engaging stakeholders appear to influence success in achieving change., Conclusion: Although many groups successfully worked on parks and recreation improvements, opportunities remain in other areas, including transit and infill and redevelopment. Additional time and resources may be critical to realizing these types of changes.

A brief review of laminar flow control techniques is given and a strategy for achieving laminarization for transonic transport aircraft is discussed. A review of some flight-test results on swept-wing transition is presented. It is also shown that polished leading edges can create large regions of laminar flow because the flight environment is relatively turbulence free and the surface finish reduces the initial amplitude of the stationary crossflow vortex.

Discover a formulaic approach to paying for call that a health system in Tacoma, Washington, uses that quantifies, monitors and budgets the costs of call coverage.

We examined the physiological and psychological status of men and women who spent the summer (n=100) and/or winter (n=85) seasons in Antarctica at McMurdo (latitude 78.48 S, elevation 12 m) and South Pole (latitude 90 S, elevation 3880 m) stations to determine whether there were any significant differences by severity of the stations' physical environment. Physiological measures (body mass index, blood pressure, heart rate, tympanic temperature), serum measures of thyroid hormones, cortisol, and lipids and plasma catecholamines were obtained at predeployment (Sep-Oct) and the beginning of the summer (November) and winter (Mar-Apr) seasons. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments (ANAM-ICE), a computerized test battery. South Pole residents had a lower body mass index (p<0.05) and body temperature (p<0.01) and higher levels of plasma norepinephrine (p<0.05) in summer and winter than McMurdo residents. Upon deployment from the United States and during the summer, South Pole residents experienced significantly higher thyroid hormone values (free and total T(3) and T(4)) (p<0.01) than McMurdo residents; in summer they also experienced lower levels of triglycerides (p<0.01) cortisol (p<0.05) and LDL (p<0.05). In winter, South Pole residents also experienced a 39% decrease in serum TSH compared with a 31.9% increase in McMurdo (p<0.05). South Pole residents also were significantly more accurate (p<0.05) and efficient (p<0.01) in performance of complex cognitive tasks in summer and winter. Higher thyroid hormone levels, combined with lower BMI and body temperature, may reflect increased metabolic and physiological responses to colder temperatures and/or higher altitude at South Pole with no apparent adverse effect on mood and cognition.

Objectives: We previously reported that cognitive function improves with thyroxine and that there is a circannual pattern to mood and human TSH during Antarctic residence. To extend these findings, we examined the effects of tyrosine and a combined levothyroxine/liothyronine supplement in euthyroid men and women who spent the austral summer (n = 43) and/or winter (n = 42) in Antarctica., Study Design: Randomized, placebo-controlled, clinical trial., Methods: Subjects were randomized to receive the following each day for 91.6 +/- 3.2 days in summer and/or 138.0 +/- 3.2 days in winter: (1) 12g tyrosine mixed in 113g applesauce; (2) 50 microg of levothyroxine and 12.5 microg of liothyronine (T4-T3 Supplement); or (3) placebo. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments., Results: With placebo in summer, mood did not change while TSH decreased by 28%; in winter, there was a 136% degradation in mood (p < 0.01) and TSH increased by 18%. With combined T4-T3 supplement, there was a 51% degradation in mood in summer compared with placebo (p < 0.05) and TSH decreased by 57%; in winter there was a 135% degradation in mood while TSH was reduced by 26% (p < 0.05). Tyrosine use in summer was associated with no change in mood and a 30% decline in TSH, while in winter there was a 47% improvement in mood and TSH decreased by 28% along with a 6% increase in fT3 (p < 0.05)., Conclusions: Administration of tyrosine leads to a significant reduction in serum TSH and improvement in mood in winter compared with placebo, while the combined T4-T3 supplement leads to a worsening of mood in summer and no improvement in winter. There appears to be a seasonal influence on the psychological response to interventions and the relationship to changes in TSH reductions.

Objective: To determine the impact of energy restriction (ER) upon the previously reported increased resting and exercise-related oxygen utilization, reduced body temperature, increased serum TSH, and reduced serum free T3 concentrations found during Antarctic residence (AR)., Design: Prospective, intervention with both paired controls and a similar reference control group (RG)., Patients and Measurements: Seven subjects were assessed before and after a 50% ER period of 60 h. This ER was carried out within 30 days of arriving in Antarctica in October (OCT) and again after 10 months AR in August (AUG). During the periods of ER, mean energy consumption was 5662 +/- 1344 kJ/day in OCT and 5529 +/- 967 kJ/day in AUG. Resting metabolic rate (RMR), a calculated resting metabolic rate (RMR(reg)) using a submaximal work regression, serum TSH, FT3 and tympanic temperature (Tty) were measured. These values were compared with a similar RG of 12 subjects reported previously who were studied in California, USA before and then again during AR., Results: Weight declined by 1.1 +/- 0.1 kg/day (OCT) and 0.92 +/- 0.2 kg/day (AUG) with ER, resulting in a reduction of body weight by 3.1 +/- 0.4% in OCT (P = 0.0001) and 2.5 +/- 0.4% in AUG (P = 0.0015) during AR. The RMR before ER did not change with AR and it was not significantly different from the RG studied in California. With ER the RMR tended to decline in both OCT (132 +/- 5 to 122 +/- 4 mlO2/min/m2) and AUG (134 +/- 5 to 126 +/- 5 mlO2/min/m2), but these were not significant. By contrast, RMR(reg) obtained before ER was increased with AR by 22.5 +/- 7.8% (P = 0.01) in OCT and by 28.1 +/- 7.0% (P = 0.0008) in AUG over the RG values obtained in California. RMR(reg) did not decrease with ER in either OCT or AUG. The total energy expenditure derived from these measures of weight loss suggests that 24-h energy requirements are 74.4%[95% confidence interval (CI) 2.6-146.3; P < 0.05] more than those expected in temperate climates. Tty declined by 0.6 +/- 0.2 degrees C (P < 0.01) with AR compared with the RG measured in California, but was not affected by either period of ER. ER had no effect on FT3 but tended to decrease serum TSH in AUG (P = 0.06)., Conclusions: Exercise-related energy requirements are increased with AR. Moderate ER may reduce resting but not exercise-related energy expenditure and it is associated with a weight loss exceeding expectations for 50% restriction of temperate climate energy predictions.

Objective: To evaluate a community-based, not-for-profit medical group's effectiveness with diabetic management while using an electronic medical record and financial incentives., Design: Descriptive retrospective study over 2 years with published reference standards., Methods: There were 5,316 diabetic patients in the medical group (MG) compared with 5,069 diabetic patients reported in the literature (CT). The main outcome measures included serum hemoglobin A1C (HbA1C), total (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) cholesterol, and clinic measures of systolic (SBP) and diastolic blood pressure. We determined a mean 10-year composite multivariable cardiovascular risk score based upon these parameters., Results: The mean MG serum HbA1C (7.10+/-0.02; 8.18+/-0.23%), TC (193.2+/-0.64; 218.3+/-6.09 mg/dl), LDL-C (109.2+/-0.52; 137.8+/-4.24 mg/dl), and SBP (132.8+/-0.25; 141.6+/-2.36 mmHg) were below those for the CT (p<0.001). The MG mean overall coronary heart disease risk of 14.9+/-1.4% over 10 years was below that for the CT group of 22.7+/-2.3%, representing a 34.7+/-4.4% reduction (p<0.0002). The electronic medical record and the use of a financial award may have contributed to these results., Conclusion: Improvement of cardiovascular risk variables can be achieved in the primary care setting. Electronic tools and incentives may facilitate this improvement.

Extended Antarctic residence (AR) is associated with an increase in serum TSH, a decrease in free T(4), and an increase in T(3) production and clearance. It is not clear whether these adaptations reflect changes in clearance alone or whether intrinsic thyroidal synthetic activity also changes. Thyroglobulin (Tg) secretion is an independent marker of intrinsic thyroid activity whose kinetics are independent of those of T(3) and T(4). In this study we examined changes in Tg levels in healthy subjects before and during AR and their responses to thyroid supplementation to help determine whether alterations in thyroid activity, and not just kinetics of clearance, underlie the changes seen with the polar T(3) syndrome. In cohort 1, we compared measurements of TSH and Tg in 12 subjects before deployment and monthly for 11 months during AR. In cohort 2, we compared the same measurements in 12 subjects monthly for 11 months of AR. Subjects were randomized to receive either placebo or levothyroxine in cohort 1 for 7 months and in cohort 2 for 11 months. Tg increased over baseline during the first 4 months of AR by 17.0 +/- 4.6% and after 7 more months by 31.7 +/- 4.3% over baseline in the placebo group of both cohorts (P < 0.0002). When L-T(4) was taken, Tg returned to a value not different from baseline (4.5 +/- 3.9%). The percent changes from baseline in serum TSH and Tg during AR were highly correlated (P < 0.00003) in the placebo group for both cohorts. The rise in Tg with TSH and the reduction in Tg with L-T(4) provide evidence of target tissue response to TSH and further confirm the TSH rise as physiologically significant. The results also suggest that the adaptive changes in thyroid hormone economy with AR reflect TSH-dependent changes in thyroid synthetic activity, which may help explain a portion of the increases in T(3) production found with AR.

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.

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.

Objective: To evaluate patient- and practice-specific determinants of the thyroid nodule fine needle aspiration (FNA) insufficiency rate and malignancy yield at a tertiary-care teaching hospital., Study Design: All FNAs of thyroid nodules performed from August 1990 to October 1993 at the Walter Reed Army Medical Center Endocrinology Clinic were reviewed and the results analyzed for correlation with surgical outcome, scintiscanning result and operator experience. Provider-specific factors influencing the FNA insufficiency rate, surgical referral pattern and malignancy yield were evaluated., Results: A total of 504 aspirations in 422 patients with thyroid nodules were included in the analysis. The sensitivity of FNA for detecting malignancy was 80%, specificity was 73.2%, and accuracy was 75.2%. A significant negative correlation was found between recent aspirator experience and the insufficiency rate. Repeat aspiration of nodules previously yielding benign cytology increased the malignancy yield. Surgical excision of nodules with insufficient aspirations gave a low malignancy yield, and aspiration of nodules that were "hot" on scintiscanning rarely yielded false positive FNA results., Conclusion: Specific limitations of thyroid nodule FNA include a large number of aspirates containing insufficient cytologic material and a variable malignancy yield. Specific recommendations based on the findings in this report are: the establishment of uniform criteria for judging specimen adequacy, the performance of repeat aspiration on thyroid nodules with previously benign aspirates, the abandonment of scintiscanning in the routine management of thyroid nodules and a conservative approach to clinically indolent nodules repeatedly found to have scant cellularity on FNA. Based on these findings, an algorithm for the diagnostic evaluation of a solid thyroid nodule can be constructed.

Members of a US Navy Special Warfare platoon had blood samples drawn by venipuncture and other baseline measurements carried out prior to departure for a three-month period of field operations in Alaska. Assays of serum reverse triiodothyronine (rT3), free thyroxine (fT3), free T4 (fT4), and thyroid stimulating hormone (TSH) were subsequently done at the Naval Medical Research Institute (NMRI), Bethesda, Maryland. In the field and at baseline, hematocrits and urine specific gravities were also measured to track hydration status, and body weights and fat were recorded to track nutritional status. After plasma volume change and weight change corrections, an approximate 30% increase in serum rT3 level and 20% decrease in free T3 level over 76 days of cold exposure were recorded. The necessity for an rT3 kinetic study is indicated. The mean residence time for rT3 in the circulation is about 8 hours with respect to about 36 hours for free T3, so rT3 kinetic studies would be advantageous with respect to long term cold exposure of military personnel.

Sleep deprivation is associated with poor cognitive ability and impaired physical health, but the ways in which the brain and body become compromised are not understood. In sleep-deprived rats, plasma total T4 and T3 concentrations decline progressively to 78% and 47% below baseline values, respectively, brown adipose tissue 5'-deiodinase type II activity increases 100-fold, and serum TSH values are unknown. The progressive decline in plasma thyroid hormones is associated with a deep negative energy balance despite normal or increased food intake and malnutrition-like symptoms that eventuate in hypothermia and lethal systemic infections. The purpose of the present experiment was to evaluate the probable causes of the low plasma total T4 during sleep deprivation by measuring the free hormone concentration to minimize binding irregularities and by challenging the pituitary-thyroid axis with iv TRH to determine both 1) the pituitary release of TSH and 2) the thyroidal response of free T4 (FT4) and free T3 (FT3) release to the TSH increment. Sleep-deprived rats were awake 91% of the total time compared with 63% of the total time in yoked control rats and 50% of the total time during the baseline period. Cage control comparison rats were permitted to sleep normally. Sustained sleep deprivation resulted in a decline from baseline in plasma FT4 of 73 +/- 6% and FT3 of 45 +/- 12%, which were similar to the declines in total hormone concentrations observed previously; nonstimulated TSH was unchanged. In the yoked and cage control groups, FT4 also declined, but much less than that of the sleep-deprived group. The relative changes in free compared with total hormone concentrations over the study were also less parallel than those in the sleep-deprived group. The plasma TSH response to TRH was similar in all groups across experimental days. The plasma FT4 and FT3 concentrations in sleep-deprived rats increased after TRH-stimulated TSH release to an extent comparable to control values. Taken together, low basal FT4 and FT3 hormone concentrations and unchanged TSH and thyroidal responses to TRH suggest a pituitary or hypothalamic contribution to the hypothyroxinemia during sleep deprivation.

Hypothyroid subjects given a constant dose of thyroxine (T4) show both an increase in serum thyrotrophin (TSH) of approximately 50% and a decline of serum T4 by approximately 15% during the winter months. Euthyroid subjects who are older than 41 years of age show an increase of approximately 30% in serum TSH during the winter months without a change in T4. Young euthyroid subjects, between the ages of 19 and 41 years, show neither a circannual pattern of TSH nor T4 but have an increase in triiodothyronine (T3) plasma clearance rate and production rate of approximately 30% during the winter seasons. Additionally, young subjects living for greater than 5 months in Antarctica show a doubling in T3 plasma clearance rate and production rate, as well as elevations of approximately 30-50% in TSH and small declines in T4. Repeated exposure to cold air has recently been reported to induce declines in serum T3, and T4 and increases in T3 clearance and production rate, thus linking a possible physiological stimulus to these seasonal observations. This collection of studies from several laboratories supports the concept that T3 kinetic changes have a seasonal dependence and that cold exposure provides one possible mechanism. As the subjects age, have a fixed thyroid hormone dosage for hypothyroxinemia, or spend an extended number of months in polar conditions, a reflex TSH rise occurs. This rise in TSH signals a hypothalamic-pituitary hypothyroxinemia whose clinical significance is unknown.

Repeated cold-air exposures increase human triiodothyronine (T3) plasma clearance rates. To study the response of the nuclear T3 receptor (NT3R) in this condition, binding characteristics were analyzed in human mononuclear leukocytes (MNL). In addition, we supplemented one group of individuals with a daily oral replacement dose of T3 to isolate the influence of serum thyroxine (T4) and thyrotropin (TSH) levels on receptor kinetics. The subjects were exposed to cold air (4 degrees C) twice/d, 30 min/exposure, for a total of 80 exposures. The T3-subjects received placebo [n = 8] and the T3 + subjects received T3 (30 micrograms/d) [n = 8] in a double-blind fashion. Mononuclear leukocytes were isolated from peripheral blood before the cold exposure and drug regimen began, and then after every 20 exposures. The dissociation constant (Kd) and maximum binding capacity (MBC) of the NT3R values were log transformed to minimize between-subject variability. In the T3+ group, serum total thyroxine (TT4), free T4 (FT4), and TSH were approx 50% lower than both basal and T3-values. The log10Kd increased 0.304 +/- 0.139 (p < 0.04) and the log10MBC increased 0.49 +/- 0.10 (p < 0.001) in the T3+ subjects compared to baseline. This change in MBC represents a 311% increase in the MBC over baseline and a fivefold increase over placebo-treated subjects. The T3- group showed no change in MBC over the study. These results describe for the first time the rapid modulation of the NT3R in response to the combined influence of cold exposure and reduced circulating T4 and TSH.

Swine exposed to cold air have elevated serum values of total triiodothyronine (TT3) and free T3 (FT3). To characterize the mechanism of these increases, we measured in vivo kinetic parameters after a bolus intravenous injection of 125I-labeled T3 by use of both multicompartmental (MC) and noncompartmental (NC) methods and in vitro hepatic type I iodothyronine 5'-deiodinase (5'D-I) activity. Ten ad libitum-fed 5-mo-old boars were divided into two groups, living for 25 days in either control (22 degrees C) or cold (4 degrees C) conditions. Cold-exposed animals consumed 50% more calories than control animals but showed no difference in total body weight, percent body fat, or plasma volume. Thyroid gland weight was increased 86% (P < 0.004), as was serum total thyroxine (TT4) (48%), free T4 (FT4) (61%), TT3 (103%), and FT3 (107%), whereas serum thyrotropin (TSH) was not different in cold-exposed compared with control animals. The T3 plasma clearance rate was similar between groups when both MC and NC techniques were used. However, T3 plasma appearance rate (PAR) was elevated in cold-treated animals 110% over controls by MC (P < 0.001) and 83% by NC methods (P < 0.001). The animal total hormone pool of T3 was increased 76% (MC) and 53% (NC) compared with control (P < 0.01). The Michaelis constant of hepatic 5'D-I was not different between groups, but the maximum enzyme velocity increased (106%; P < 0.02). Therefore cold exposure for 25 days is associated with increased energy intake, thyroid size, T3 PAR, and hepatic 5'D-I activity with little change in serum TSH.

Antarctic residence (AR) is associated with a 50% increase in the thyrotropin (TSH) response to TSH-releasing hormone (TRH) and an expanded triiodothyronine (T3) distribution volume and extravascular hormone pool, collectively called the polar T3 syndrome. To investigate the possible biologic significance of this syndrome, we studied the relationship between nonstimulated TSH and serum lipid profiles in nine subjects, once while in California and monthly during 9 months of AR. We measured serum levels of TSH, total thyroxine (TT4), free T4 (FT4), total T3 (TT3), free T3 (FT3), thyroid-binding globulin (TBG), total cholesterol (T-CHOL), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), dietary cholesterol (D-CHOL), dietary fat (D-FAT), and dietary kilocalories at each month. The paired mean monthly change from baseline was used to determine significance. The group's mean levels of TSH (approximately 30%), TBG (approximately 16%), T-CHOL (approximately 4%), HDL-C (approximately 10%), and D-CHOL (approximately 19%) increased with AR (P < .05). Small but significant decreases (P < .05) were observed in the mean changes of TT4 (approximately 8%), FT4 (approximately 6%), and TT3 (approximately 6%). FT3, D-FAT, dietary kilocalories, body weight, TG, and the calculated low-density lipoprotein (LDL-C) were unchanged with AR. A significant rate of change (P < .05) during AR was also calculated from the slope of a fitted logarithmic function for TSH (0.96 +/- 0.31 mU.L-1 x mo-1), TBG (61.19 +/- 12.29 nmol.L-1 x mo-1), TT3 (0.09 +/- 0.04 nmol.L-1 x mo-1), TT4/TBG (-0.06 +/- 0.01/mo), TT3/TBG (-8.49 +/- 1.98 x 10(-4)/mo), and TG (-0.33 +/- 0.15 mmol.L-1 x mo-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Cold exposure, activity and energy deficit have been associated with changes in body composition and/or changes in serum thyroid hormones. Because these conditions are present during the Iditarod Sled Dog Race, 10 volunteer participants were studied before and after the race. Body composition, total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and free triiodothyronine (FT) levels were determined. There was a significant decrease in body weight (p < 0.05) and a decrease in body fat (p < 0.01). There were no significant changes in TT4, FT4, TT3 or FT3. On the basis of this study, it can be concluded that the strenuous activity of the Iditarod mitigates against the classic perturbation in thyroid axis brought on by the hypocaloric state.

Objective: We studied the relationship between endurance training, aerobic capacity, and T3 metabolism in healthy euthyroid men., Design: T3 kinetic studies performed on two groups of subjects differentiated on the basis of physical activity status and aerobic capacity., Subjects: Five endurance-trained athletes and five sedentary controls (mean +/- SD VO2 max = 48.2 +/- 7.1 vs 23.2 +/- 4.5 ml/kg/min, respectively) matched for age, body surface area, lean body mass, and baseline thyroid function., Measurements: Kinetic analysis performed using serial serum T3 levels measured following oral T3 administration. Metabolic clearance rate, total volume of distribution, disposal rate, and total body pool calculated using non-compartmental analysis., Results: When normalized for lean body mass, all kinetic parameters were 25-38% greater in the athletic group compared to controls (P < 0.05). Total volume of distribution, disposal rate, and total body pool were positively correlated with aerobic capacity (r = +0.69 to +0.79; P < 0.05). Metabolic clearance rate was positively correlated to a non-significant degree., Conclusions: These results confirm the findings of prior studies that thyroid hormone metabolism is altered by physical conditioning. In addition, we demonstrated a positive correlation between aerobic capacity and several parameters of T3 kinetics. Differences in absolute lean body mass cannot explain these findings; rather it appears that there is something qualitatively different in the way endurance-trained tissue processes thyroid hormone, compared to untrained tissue. The study was not designed to elucidate these differences at the cellular level; however, it does support a link between muscle physiology and T3 activity and may suggest a physiological role for thyroid hormone in physical conditioning.

The influence of cold exposure on triiodothyronine (T3) kinetics was studied in 16 men before, during (biweekly), and after 80 (10/wk) cold (4 degrees C) air exposures. We used serum values before and up to 24 h after a pharmacological oral (o) dose of T3 [76.8 nmol (50 micrograms)] to calculate noncompartmental kinetic parameters. To assess the role of thyroxine (T4) and thyrotropin (TSH), we administered a replacement dose of T3 [46.0 nmol/day (30 micrograms)] to eight men (+T3 group) and placebo to eight others (-T3 group) for the 2-mo study. There was no group effect of T3 treatment (+T3) on oral total volume of distribution (TVdo), metabolic clearance rate (MCRo), or disposal rate (DRo). TVdo was not changed over the study. Cold increased MCRo by 5.4 +/- 2.0 l.day-1.m-2. DRo increased with cold by 10.2 +/- 4.4 nmol.day-1.m-2. Although serum TSH, total T4, and free T4 decreased by approximately 50% in the +T3 group, the changes in MCRo and DRo with cold were not different from those in -T3. We describe that human T3 kinetics are changed with brief repeated exposures to cold air and that these increases in MCRo and DRo do not appear to be dependent on TSH or T4.

Thyroxine (T4) is required in species possessing brown adipose tissue (BAT) for the maintenance of cold tolerance and adaptation. In humans, who possess negligible quantities of BAT, the importance of T4 has not been demonstrated. We studied the effects of decreased serum T4 and thyrotropin (TSH) on human cold habituation after repeated cold air exposures. Eight men (T3+) received a single daily dose of triiodothyronine (T3; 30 micrograms/day), and another eight men (T3-) received a placebo. All 16 normal thyroid men underwent a standardized cold air test (SCAT) under basal conditions in January and again in March after eighty 30-min 4.4 degrees C air exposures (10/wk). Measurements of basal metabolic rate (BMR), O2 consumption (VO2), mean arterial pressure (MAP), plasma norepinephrine (NE), serum TSH, free and total T4, and free and total T3 were repeated before and after 8 wk of exposure. TSH, free T4, and total T4 were 50% lower for T3+ than for T3- subjects. Total and free T3 were not different between groups. BMR was unchanged after habituation, whereas the cold-stimulated VO2, MAP, and NE were significantly reduced for all subjects in March. The relationship between VO2 and NE (r2 = 0.44, P less than 0.001) during the initial SCAT was unchanged with habituation. We suggest that human cold habituation is independent of major changes in circulating T4 and TSH.

Whole blood hematocrit (HCT) decreases during multiple exposures to cold air. To better understand this finding, we have analyzed hematological profiles in 27 normal adult men exposed repeatedly to cold air in one of two experimental protocols. Experiment I was a cold air acclimatization study (CAA) conducted with two groups of 8 men in each group before, during, and after 80 separate 30-minute cold (4 degrees C) air exposures. As part of a metabolic study, half of the men received placebo daily (n = 8), and the other half received an oral daily maintenance dose of the thyroid hormone triiodothyronine (T3) (30 micrograms/day). Blood was analyzed prior to and after every 20 cold exposures. Both groups reacted similarly. When compared with basal conditions, hematocrit (HCT) and erythrocyte counts (RBC) were decreased (p less than 0.05); mean corpuscular hemoglobin concentration (MCHC) and plasma volume (PV) were increased with cold exposure (p less than 0.05). Hemoglobin (Hb), leukocyte counts (WBC), and mean corpuscular volume (MCV) were unchanged. Experiment II was carried out with 9 military volunteers during extended arctic winter field operations (EAO) in Utah and Alaska. Blood was analyzed prior to and after completion of EAO. A changing hematological profile similar to that in the CAA protocol was found. Hematocrit and RBC were decreased (p less than 0.02); MCHC and PV were increased (p less than 0.02). Hemoglobin, WBC, and MCV were unchanged. In addition, there was a negative correlation between HCT and the absolute reticulocyte count in this second experiment. It would appear that in instances of cold stress, whether induced or naturally occurring, certain blood cellular elements respond in a similar adaptive manner.

Pelting load data were collected and analysed for 304 lambs (comprising 46% ewes, 26% cryptorchids and 28% rams), all of which came from one farm. Although typically about 24% more impulse (Ns) had to be applied for pelting ram lambs than for ewe or cryptorchid lambs, only one-third of this increase was attributable to the distinct sexual category of rams; the rest was due to rams being heavier. Carcass size had a much greater effect on pelting load than animal sex: a change in dressed carcass weight of slightly less than 1 kg has the same effect on impulse requirement as the net sex effect. These findings suggest that the differences in pelting effort associated with animal sex are of relatively minor significance compared with the large differences occurring over the range of lamb size normally processed., (Copyright © 1992. Published by Elsevier Ltd.)

Cold air exposure stimulates a rise in mean arterial blood pressure (MAP) and plasma norepinephrine (NE). The specific contribution of the beta-adrenergic receptor to this pressor response is unknown. Therefore, we pretreated 12 normal men with placebo or a bradycardia-inducing amount of propranolol prior to exposing them to either 25 degrees C or 4 degrees C air. At 25 degrees C, propranolol pretreatment lowered heart rate (HR) and MAP. When we compared changes in MAP after their respective 30-min exposure at 25 degrees C and 4 degrees C, the cold elevated MAP by 18.4 +/- 1.5 mm Hg in subjects pretreated with propranolol compared with 13.0 +/- 2.5 mm Hg in subjects pretreated with placebo. Fingertip skin temperature (Tfing) measured at 4 degrees C, 9.5 +/- 0.8 degrees C in propranolol-pretreated subjects was lower than the 11.1 +/- 0.7 degrees C with that of placebo. Plasma NE increased equally during cold exposure with both placebo and propranolol pretreatment. We conclude that the beta receptor plays a minor role in generating the pressor response to cold air. Therefore, the effectiveness of acute administrations of propranolol for maintaining normotension in subjects exposed to cold environments may be attenuated.

We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported "polar T3 syndrome."

Humans who live in Antarctica for greater than 5 continuous months demonstrate alterations in the hypothalamic-pituitary-thyroid axis. These changes are characterized by 1) increased pituitary release of TSH in response to iv TRH, 2) increased serum clearance of orally administered T3, and 3) normal serum total, free T4, and unstimulated TSH levels. To clarify the mechanism responsible for these findings, serum kinetic studies of 125I-labeled T4 and T3 were carried out in a group of normal men, first in California, then after 20 and 42 weeks of continuous Antarctic residence. The kinetic parameters were calculated by noncompartmental analysis. The mean T4 residence time (MRT) was not different before and after 42 weeks (5.54 +/- 0.50 and 5.08 +/- 0.43 days). The total T4 volume of distribution (TVd) tended to fall over the same period (4.30 +/- 0.12, 3.56 +/- 0.27 L/m2), but was not significantly different (P = 0.075). In contrast to T4, there was an increase from control values for the T3 MRT from 0.83 +/- 0.03 to 1.10 +/- 0.03 days (P less than 0.002) and a more than doubling of the T3 TVd from 15.55 +/- 0.52 to 47.24 +/- 5.09 L/m2 (P less than 0.002) after 42 wk of Antarctic residence. Energy intake increased approximately 40% throughout the study without a change in body weight. The changes in T3 kinetic parameters may be accounted for by increased extravascular tissue binding. The marked increase in T3 TVd and the small increase in MRT are associated with increased T3 production and clearance and only minor changes in T4 kinetics. This is the first description of a mechanism for the change in thyroid hormone economy occurring with extended residence in Antarctica.

Norepinephrine (NE) and epinephrine (EPI) collected from dogs were sequentially and temporally measured in blood and plasma at 24 C. Heparin and EDTA anticoagulants, in combination with reduced glutathione and EDTA as a preservative, were also compared. Norepinephrine and EPI concentrations were measured by high-pressure liquid chromatography with electrochemical detection. In heparinized plasma, NE and EPI concentrations were relatively stable in the absence or presence of preservative after 24 hours at 24 C. In EDTA plasma, NE and EPI values were less stable when compared with those in heparinized samples. Norepinephrine concentrations in EDTA plasma without preservative decreased by 163.2 +/- 8.88 pg over 24 hours, compared with an 86.6 +/- 7.92 pg loss of NE in heparinized plasma. The degradation of EPI in EDTA plasma without preservative was also twofold greater, compared with that in heparinized plasma. Addition of preservative had no stabilizing effect on NE or EPI in heparinized or EDTA plasma. During long-term storage at -70 C, plasma NE and EPI values decreased less than 0.6 and less than 0.1 pg/d, respectively. Norepinephrine and EPI values were stable in heparinized blood for 6 hours but decreased to less than 25% and less than 6% of initial base line values, respectively, when plasma separation was delayed 24 hours.

The relationships between fingertip skin temperature (Tfin), brachial venous hemoglobin oxygen saturation (SVO2), and plasma catecholamines were studied by exposing 15 semi-nude men to 30 min of 5 degrees C and 48 degrees C ambient air temperature extremes. After 30 min of cold air, norepinephrine (NE) increases from 2.01 +/- 0.26 to 7.15 +/- 0.64 nmol/L, and epinephrine (Epi) increases from 201 +/- 25 to 295 +/- 34 pmol/L. In contrast, after 30 min of hot air exposure, Epi rises from 161 +/- 32 to 348 +/- 43 pmol/L, while NE rises slightly from 2.07 +/- 0.26 to 2.57 +/- 0.64 nmol/L. Heat elevates SVO2 from 68.8 +/- 0.72 to 93.3 +/- 0.66% and Tfin from 29.5 +/- 1.09 to 39.4 +/- 0.56 degrees C. Cold lowers SVO2 to 32.1 +/- 0.70% and Tfin to 11.5 +/- 0.55 degrees C. SVO2 correlates with Tfin (r = 0.895, p less than 0.0001). We conclude that exposure to an environmental temperature of 5 degrees C decreases Tfin with concurrent decreases in blood flow and SVO2 in the extremity by the vasoconstrictive action of NE. Exposure to 48 degrees C increases Tfin with increases in blood flow and SVO2 in the extremity by vasodilation of peripheral vascular beds, which may be related to the rise in the plasma concentration of Epi.

Very little is known regarding hormonal adaptation in human subjects who are exposed to the extremes of temperature and light that are found in polar latitudes. We have previously reported a 50% elevation in the serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH), a fall in serum total triiodothyronine (T3) and free T3 (fT3), and no change in serum total thyroxine (T4) or free T4 (fT4) after 42 wk of Antarctic cold exposure. To differentiate between central and peripheral mechanisms that may lead to these changes, we report the effect of sequentially increasing oral doses of T3 (Cytomel) on serum T3 and fT3 levels and on the resultant attenuation of the TSH response to TRH in nine men before, during, and after 42 wk residence in Antarctica. Serum T3 values basally and following the administration of 25, 50, and 75 micrograms/day of T3 were lower after 42 wk of cold exposure (151 +/- 4, 160 +/- 8, 189 +/- 10, and 222 +/- 14 ng/dl, respectively, compared with control values of 160 +/- 7, 178 +/- 7, 202 +/- 9, and 251 +/- 19 ng/dl, respectively, P less than 0.05). Likewise, the fT3 values measured after these three increasing T3 doses were also lower after 42 wk of cold exposure. The pituitary response to TRH was attenuated by each T3 regimen (48 +/- 6, 68 +/- 4, and 77 +/- 4% decreases in the control period), and this suppression was not different after 20 and 42 wk of Antarctic residence.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine how intraoperative hypothermia associated with coronary bypass surgery (CABS) alters sympathetic nervous system (SNS) activity, we prospectively studied 21 adult CABS patients and measured preoperative, intraoperative, and postoperative circulating catecholamine concentrations. Because thyroid hormone levels change rapidly following CABS, we also serially measured these hormone levels. The measured plasma concentrations for each of the above variables were corrected for hemodilution during CABS by using serum albumin changes as a reference. It was concluded that important alterations in SNS activity and thyroid hormone homeostasis occur in humans during CABS and deep hypothermia, and that changes in core temperature may contribute to these findings. We speculate that these hormonal changes may influence the response to adrenergic receptor therapy in hypothermic patients and may contribute to arrhythmias during rewarming and the immediate postoperative period.

The human population which lives and works in polar environments has been increasing steadily over the last 15 years. Very little is known about how these residents adjust to their environment. Cold adaptation in man is a poorly understood phenomenon. Euthermic mammals maintain body temperature during cold exposure via non-shivering thermogenesis, a process which is hormonally mediated. We studied prospectively the response of the hypothalamic-pituitary-thyroid axis in 17 euthyroid men before, during and after assignment to duty in the Antarctic. Serum total and free T4 levels fell slightly but not significantly after very prolonged Antarctic residence. Serum total and free T3 decreased significantly from basal levels of 170 +/- 3 ng/dl and 388 +/- 19 pg/dl to 155 +/- 5 ng/dl and 319 +/- 14 pg/dl respectively after Antarctic duty. Serum T3 levels increased after 42 weeks of polar living, the end of the observation period, but the change did not attain statistical significance. The integrated TSH response to TRH administration increased by 50% to 734 +/- 58 microIU.min/ml over warm climate basal response levels of 456 +/- 33 microIU.min/ml by the end of the study. The daily circadian rhythm of serum cortisol was maintained throughout the study period. The alterations in thyroid hormones which we describe, are apparently related to the chronic cold exposure which our subjects experienced in this polar environment.

Arachidonic acid metabolites and prostaglandins participate in numerous physiologic functions. An enzyme important in the control of prostaglandin production is phospholipase A2. In this study, we have investigated the changes in plasma and hepatic phospholipase A2 activity in diabetes mellitus. In uncontrolled diabetic patients, the postheparin plasma phospholipase A2 level was 18.7 +/- 4.1 U/ml; this value was significantly different from the enzyme activities in control subjects (106 +/- 9.8 U/ml) and in controlled diabetic patients (87 +/- 7.3 U/ml). In the streptozocin-induced diabetic rat model, the postheparin plasma phospholipase A2 level (1.9 +/- 0.45 U/ml) was also decreased when compared with normal (9.4 +/- 1.6 U/ml) and controlled diabetic rats (7.0 +/- 1.3 U/ml). The total hepatic enzyme activity in the uncontrolled diabetic rats was only 21.6% of that seen in control rats. Subcellular fraction studies demonstrated that the enzyme activity is decreased in all fractions in the liver. Liver perfusion studies showed that the heparin-releasable phospholipase A2 activity in the perfusate was significantly decreased in the diabetic rats when compared with control and controlled diabetic animals. We conclude that postheparin plasma and hepatic phospholipase A2 activities are decreased in uncontrolled diabetes mellitus, that the low plasma activity is related to decreased release from the liver, and that the alterations in phospholipase A2 activity in plasma and liver are restored to normal by controlling the diabetic status.