Thyrotropin Receptor Antibody Levels at Diagnosis and After Thionamide Course Predict Graves' Disease Relapse.

BACKGROUND: Thionamides are associated with a high risk of recurrence following cessation. Thyrotropin receptor-stimulating antibody (TRAb) levels at diagnosis and/or after thionamides may be biomarkers of this risk. This study assesses the natural history of Graves' thyrotoxicosis following thionamide withdrawal and factors that predict recurrence, particularly TRAb levels at diagnosis and cessation. METHODS: An observational study was conducted of patients with a first presentation of Graves' disease, who were prescribed (and completed) a course of primary thionamide treatment (n = 266) in a university teaching hospital endocrine clinic. Recurrence rates over four years and factors predictive of recurrent thyrotoxicosis were assessed. RESULTS: The relapse rate was 31% at one year and 70% at four years. Younger age (39 years [range 30-49 years] vs. 47 years [range 37-53 years]; p = 0.011), higher TRAb levels at diagnosis (8.8 IU/L [range 5.3-17.0 IU/L] vs. 5.7 IU/L [range 4.1-9.1 IU/L]; p = 0.003), and higher TRAb levels at cessation of therapy (1.2 IU/L [range 0-2.3 IU/L] vs. <0.9 IU/L [range 0-1.3 IU/L]; p = 0.003) were associated with a higher risk of relapse. By four years, cessation TRAb <0.9 IU/L was associated with a 58% risk of recurrence compared with 82% with TRAb >1.5 IU/L (p = 0.001). TRAb at diagnosis >12 IU/L was associated with an 84% risk of recurrence over four years compared with 57% with TRAbs <5 IU/L (p = 0.002). CONCLUSION: High TRAb at diagnosis and/or positive TRAb at cessation of therapy suggest a high likelihood of relapse, mostly within the first two years. They stratify patients likely to need definitive therapy (radioiodine or surgery).

Testing and Linking Foreign-Born People with Chronic Hepatitis B Virus Infection to Care at Nine U.S. Programs, 2012-2014.

OBJECTIVE: Hepatitis B virus (HBV) infection continues to be a public health threat in the United States. As many as 2.2 million people are infected, approximately 70% of whom are foreign-born, and fewer than one-third are aware of their infection. We launched an HBV testing and linkage-to-care initiative among foreign-born people. METHODS: As part of the Hepatitis Testing and Linkage to Care (HepTLC) initiative, which promoted viral hepatitis B and hepatitis C screening, posttest counseling, and linkage to care at 34 U.S. sites, nine U.S. programs in seven states conducted HBV screening from October 2012 to September 2014. The nine programs partnered with health-care centers and community-based organizations to recruit foreign-born people recommended for HBV testing. We assessed patient characteristics, region of origin, risk factors, hepatitis B surface antigen (HBsAg) status, and referral to medical care. RESULTS: Of 23,144 participants tested for HBV, 1,317 (5.7%) were HBsAg positive. Of these, the median age was 47 years, 1,205 (91%) had at least one risk factor for HBV infection, 1,117 (85%) received posttest counseling, 1,098 (83%) were referred to care, and 606 (46%) attended a first medical appointment. The proportion of HBsAg-positive participants by region of origin included Africa (10%, 206/2,129), Western Pacific (6%, 616/9,673), Eastern Mediterranean (5%, 174/3,337), Southeast Asia (5%, 191/3,891), South America (2%, 6/252), Eastern Europe (2%, 6/262), and North America (1%, 17/1,936). CONCLUSION: Community-based HBV testing initiatives can identify substantial numbers of people with chronic HBV infection, inform them of their infection status, and provide posttest counseling and linkage to care. However, strategies are needed to improve linkage to HBV-directed medical care for foreign-born individuals living with chronic HBV infection.

Early Identification and Linkage to Care for People with Chronic HBV and HCV Infection: The HepTLC Initiative.

OBJECTIVE: In 2012, CDC's Division of Viral Hepatitis launched a public health initiative to increase hepatitis B virus (HBV) and hepatitis C virus (HCV) infection testing for those at risk and to improve linkage to medical care for those infected. We describe testing outcomes of previously unidentified people at risk for HBV and HCV infection and the lessons learned while linking patients to care. METHODS: CDC's Hepatitis Testing and Linkage to Care (HepTLC) initiative provided 34 financial awards to U.S. organizations that serve people at risk for viral hepatitis, 25 of which focused on HCV and nine of which focused on HBV. Grantees offered testing and test result notification to people at risk for HBV and/or HCV infection, as well as counseling, referral, and verification or notification of linkage to care for people with positive test results. We entered demographic data, self-reported risk factors, country of origin (for HBV), and testing outcomes into a confidential database. RESULTS: The 34 grantees tested 87,860 people at more than 260 sites in 17 states. Of the 23,144 people tested for HBV, 1,317 (6%) were positive. Of the 64,716 people tested for HCV, 57,570 (89%) received an HCV antibody (anti-HCV) test, of whom 7,580 (13%) tested anti-HCV positive. Of the 4,765 people who received an HCV RNA test, 3,449 (72%) tested positive. Of the 4,766 people who tested positive for either HBV or HCV infection, 2,116 (44%) were linked to care. CONCLUSION: Interventions targeting people at risk for HBV and HCV infection reached a substantial number of people for whom testing is recommended and identified a large proportion of those who had previously unrecognized infection. Patient navigation was critical for follow-up and linkage to care.

Early identification and linkage to care of persons with chronic hepatitis B virus infection--three U.S. sites, 2012-2014.

In the United States, an estimated 0.8-1.4 million persons are living with chronic hepatitis B virus (HBV) infection. Among these persons, as many as 70% were born in countries of Asia, Africa, or other regions where HBV is moderately or highly endemic (hepatitis B surface antigen [HBsAg] prevalence ≥2%). HBV-associated cirrhosis and liver cancer are major health problems for these populations. Most persons with HBV were infected at birth or during early childhood and are asymptomatic until advanced liver disease develops. To address these concerns, CDC recommends HBsAg testing for all persons born in these areas and linkage to medical care and preventive services for those who are infected. In 2012, CDC awarded funds to nine sites to implement this recommendation. This report describes programs at three sites (New York, New York; Minneapolis-St. Paul, Minnesota; and San Diego, California) that conducted HBV testing, in clinical or community settings, and referred for medical evaluation and care those persons whose HBsAg test results were positive. During October 2012-March 2014, the three sites tested 4,727 persons for HBV infection; 310 (6.6%) were HBsAg-positive. Among the HBsAg-positive persons, 94% were informed of their results, 90% were counseled, 86% were referred for care, and 66% attended their scheduled first medical visit. These projects demonstrate that community-based programs can identify infected persons among populations with a high prevalence of HBV infection and refer HBsAg-positive persons for care. Individualized efforts to assist patients with accessing and receiving health-care services ("patient navigation services") can increase the number of persons who follow up on referrals and receive recommended care.

The role of primary care physician assistants in managing chronic hepatitis B.

This article informs physician assistants of an algorithm designed for primary care practice to guide the screening of patients for hepatitis B virus infection. The algorithm also provides guidance on evaluation, follow-up, and referral of patients who screen positive. The algorithm is a synthesis of several published, evidence-based practice guidelines and reports.

Previous exposure to HCV among persons born during 1945-1965: prevalence and predictors, United States, 1999-2008.

OBJECTIVES: We examined HCV exposure prevalence and predictors among persons in the United States born during 1945-1965. METHODS: With data from the 1999-2008 National Health and Nutrition Examination Survey, we calculated the proportion of persons born during 1945-1965 who tested positive for HCV antibody (anti-HCV) and analyzed the prevalence by sociodemographic and behavioral risk factors. RESULTS: Anti-HCV prevalence in the 1945-1965 birth cohort was 3.2% (95% confidence interval [CI] = 2.8%, 3.8%), substantially higher than among other adults (0.9%). Within the cohort, anti-HCV prevalence was higher among non-Hispanic Blacks (6.4%; 95% CI = 5.3%, 7.7%), persons with injection drug use histories (56.8%; 95% CI = 48.4%, 64.8%), and persons with elevated alanine aminotransferase levels (12.7%; 95% CI = 10.7%, 15.1%). Injection drug use (adjusted odds ratio = 98.4; 95% CI = 58.8, 164.5) was the strongest anti-HCV prevalence predictor. Among anti-HCV-positive persons, 57.8% reported having 2 or more alcoholic drinks daily. CONCLUSIONS: With the high prevalence of HCV among persons born during 1945-1965, the increasing morbidity and mortality associated with HCV, and reductions in liver cancer and HCV-related mortality when HCV is eradicated, it is critically important to identify persons with HCV and link them to appropriate care.

Norethisterone interference in testosterone assays.

BACKGROUND: This article describes three patients in whom measured serum testosterone concentrations were found to be artifactually high due to interference from norethisterone medication. This interference was investigated further by distributing samples containing norethisterone through an external quality assessment scheme. METHODS: Serum samples containing different concentrations of norethisterone were distributed to participants in the UK external quality assessment scheme (UK NEQAS) for female testosterone in order to assess the degree of interference from norethisterone in different commercially available immunoassay and liquid chromatography-tandem mass spectrometry methods for measurement of testosterone. RESULTS: The results have shown that apparent serum testosterone concentrations in excess of 5 nmol/L may be obtained using the Roche E170 Modular immunoassay method for samples collected from patients taking norethisterone medication and this interference can be reproduced by adding norethisterone to serum samples. CONCLUSIONS: Although the biggest interference is seen with the Roche system, there is a small effect in the Siemens ADVIA Centaur assay and some of the other immunoassays may also be affected to a much lesser extent. Norethisterone does not interfere in testosterone measurements obtained by liquid chromatography-tandem mass spectrometry.

Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention.

DESCRIPTION: The Centers for Disease Control and Prevention (CDC) and a group of governmental and private sector partners developed these evidence-based recommendations to increase the proportion of hepatitis C virus (HCV)-infected persons who know their status and are linked to appropriate care and treatment. The recommendations also address brief alcohol screening, as alcohol accelerates progression of liver disease among HCV-infected individuals. These recommendations augment CDC's 1998 and 1999 recommendations based on risk and medical indications and are not meant to replace those recommendations. METHODS: These recommendations are based on systematic reviews of evidence published from 1995 through February 2012 in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Database of Abstracts of Reviews of Effects. Selected studies included cross-sectional and cohort studies that addressed either prevalence of hepatitis C in the United States or clinical outcomes (for example, hepatocellular carcinoma and serious adverse events) among treated patients and systematic reviews of trials that assessed effectiveness of brief screening interventions for alcohol consumption. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess quality of the evidence. RECOMMENDATION 1: Adults born during 1945-1965 should receive 1-time testing for HCV without prior ascertainment of HCV risk. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 2: All persons with identified HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Grade: strong recommendation; moderate-quality evidence).

Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965.

Hepatitis C virus (HCV) is an increasing cause of morbidity and mortality in the United States. Many of the 2.7-3.9 million persons living with HCV infection are unaware they are infected and do not receive care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945-1965 comprise an estimated 27% of the population, they account for approximately three fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. With the advent of new therapies that can halt disease progression and provide a virologic cure (i.e., sustained viral clearance following completion of treatment) in most persons, targeted testing and linkage to care for infected persons in this birth cohort is expected to reduce HCV-related morbidity and mortality. CDC is augmenting previous recommendations for HCV testing (CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19]) to recommend one-time testing without prior ascertainment of HCV risk for persons born during 1945-1965, a population with a disproportionately high prevalence of HCV infection and related disease. Persons identified as having HCV infection should receive a brief screening for alcohol use and intervention as clinically indicated, followed by referral to appropriate care for HCV infection and related conditions. These recommendations do not replace previous guidelines for HCV testing that are based on known risk factors and clinical indications. Rather, they define an additional target population for testing: persons born during 1945-1965. CDC developed these recommendations with the assistance of a work group representing diverse expertise and perspectives. The recommendations are informed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, an approach that provides guidance and tools to define the research questions, conduct the systematic review, assess the overall quality of the evidence, and determine strength of the recommendations. This report is intended to serve as a resource for health-care professionals, public health officials, and organizations involved in the development, implementation, and evaluation of prevention and clinical services. These recommendations will be reviewed every 5 years and updated to include advances in the published evidence.

Centers for Disease Control and Prevention initiatives to prevent hepatitis C virus infection: a selective update.

Hepatitis C virus (HCV) infection is a complex public health problem, characterized by a high prevalence of chronic infection, an increasing burden of HCV-associated disease, low rates of testing and treatment, and the prospect of increasing incidence associated with the epidemic of injection drug use. Three-quarters of chronic HCV infections occur among persons born from 1945 through 1965. Prevention efforts are complicated by limited knowledge among health care professionals, persons at risk and in the public at large. At the Centers for Disease Control and Prevention, efforts to improve primary and secondary prevention effectiveness center on policy development, education and training initiatives, and applied research. This report provides a brief overview of some of these efforts, including the development of testing recommendations for the 1945-1965 birth cohort, research and evaluation studies in settings where persons who inject drugs receive services, and a national viral hepatitis education campaign that targets health care professionals, the public, and persons at risk.

Oxidative stress rather than triglyceride accumulation is a determinant of mitochondrial dysfunction in in vitro models of hepatic cellular steatosis.

BACKGROUND/AIMS: There is still debate about the relationship between fat accumulation and mitochondrial function in nonalcoholic fatty liver disease. It is a critical question as only a small proportion of individuals with steatosis progress to steatohepatitis. In this study, we focused on defining (i) the effects of triglyceride accumulation and reactive oxygen species (ROS) on mitochondrial function (ii) the contributions of triglyceride, ROS and subsequent mitochondrial impairment on the metabolism of energy substrates. METHODS: Human hepatoblastoma C3A cells, were treated with various combinations of oleate, octanoate, lactate (L), pyruvate (P) and ammonia (N) acutely or for 72 h, before measurements of triglyceride concentration, cell respiration, ROS production, mitochondrial membrane potential, ketogenesis and gluconeogenesis, TCA cycle metabolite analysis and electron microscopy. RESULTS: Acutely, LPON treatment enhanced mitochondrial respiration and ROS formation. After 72 h, despite the similarities in triglyceride accumulation, LPON treatment, but not oleate, dramatically affected mitochondrial function as evidenced by decreased respiration, increased mitochondrial membrane potential and ROS formation with concomitant enhanced ketogenesis. By comparison, respiration and ROS formation remained unperturbed with oleate. Importantly, this was accompanied by an increased gluconeogenesis and ketogenesis. The addition of the antioxidant N-acetyl-L-cysteine prevented mitochondrial dysfunction and reversed metabolic changes seen with LPON, strongly suggesting ROS involvement in mediating mitochondrial impairment. CONCLUSIONS: Our data indicate that ROS formation, rather than cellular steatosis per se, impairs mitochondrial function. Thus, reduction in cellular steatosis may not always be the desired outcome without concomitant improvement in mitochondrial function and/or reducing of ROS formation.

Clinical performance of the Roche cobas e411 automated assay system for thyrotropin-receptor antibodies for the diagnosis of Graves' disease.

BACKGROUND: The clinical performance of the Roche cobas e411 automated assay for the measurement of thyrotropin (TSH)-receptor antibodies (TRAbs) for the diagnosis of Graves' disease was evaluated in the setting of new referrals to a specialized thyroid clinic. METHODS: The final diagnosis of 102 new patients attending their first outpatient appointment at a thyroid clinic was correlated with the TRAbs result. In all cases, the diagnosis was made independently of the TRAbs result by the same consultant (ADT) based on clinical examination, thyroid function tests (TSH, free thyroxine, total triiodothyronine measured on Architect; Abbot Diagnostics), and a technetium-99m uptake and scan. TRAbs were measured using the cobas e411 (Roche Diagnostics). The clinical sensitivity and specificity of the assay were determined and compared with other published performance characteristics of the assay. RESULTS: Optimal sensitivity (95%) and specificity (98%) were obtained using a cut-off of 1.6 IU/L. The positive and negative predictive values at this cut-off were calculated as 98% and 94%, respectively. CONCLUSIONS: Using a cut-off of 1.6 IU/L, considered independently of thyroid function tests, the Roche cobas e411 automated immunoassay for TRAbs is a convenient, sensitive and specific tool for the differential diagnosis of hyperthyroidism.

Differential effects of doses and forms of dietary selenium on immune cell numbers in the skin of ultraviolet-irradiated and unirradiated mice.

The effect of three different doses of dietary L-selenomethionine (SM) and sodium selenite (SS) on skin selenium (Se) content, glutathione peroxidase (GPx) activity, Langerhans cell (LC) and mast cell numbers in ultraviolet radiation-B (UVB)-irradiated and unirradiated C3H/HeN mice was determined. After weaning, groups of mice were given Se-deficient, Se-adequate, or Se-high diets. Six weeks later, some animals in each group were exposed to a single UVB dose (acute), while others were exposed three times weekly for the following 40 weeks (chronic). The skin Se content and GPx activity increased in all the Se-supplemented groups, and the latter was not altered by UVB exposure. Generally, the Se-containing diets caused an increase in LC numbers at 6 weeks and a further rise at 40 weeks, but did not prevent the loss induced by acute or chronic UVB radiation. Skin mast cell numbers were highest in animals fed the Se-deficient diet after 6 and 40 weeks. Acute and chronic UVB radiation decreased the mast cell number and dietary Se did not prevent the reduction. While the present study shows that Se plays an important role in governing the number of LCs and mast cells in the skin, no protective effect against the immunomodulating properties of UVB radiation on these cell types was observed. However, this conclusion may only apply to the experimental conditions chosen, and additional studies at different Se dosages and reduced intensities of chronic UVB exposure are required to confirm the results.

Passive surveillance in Maine, an area emergent for tick-borne diseases.

In 1989, a free-of-charge, statewide tick identification program was initiated in Maine, 1 yr after the first Ixodes scapularis Say (=I. dammini Spielman, Clifford, Piesman & Corwin) ticks were reported in the state. This article summarizes data from 18 continuous years of tick submissions during which >24,000 ticks of 14 species were identified. Data provided include tick stage, degree of engorgement, seasonal abundance, geographical location, host, and age of the person from whom the tick was removed. Maps depict the distributions of the three major species submitted. I. scapularis emerged first along the coast, and then it advanced inland up major river valleys, Dermacentor variabilis Say slowly expanded centrifugally from where it was initially reported in southwestern Maine, and the distribution of long-established Ixodes cookei Packard remained unchanged. Submissions of nymphal I. scapularis closely correlated with reported Lyme diseases cases at the county level. Annual fluctuations of nymphal submissions in Maine correlated with those of Lyme disease cases for New England, supporting the possibility of a regional influence on tick abundance. More ticks were removed from people < or =14 and > or =30 yr of age, and their degree of engorgement was greatest in people < or =20 yr of age and progressively increased in people > or =30 yr of age. This study demonstrates the usefulness and potential of tick identification programs.

Thyroid guidelines - are thyroid-stimulating hormone assays fit for purpose?

Most thyroid-stimulating hormone (TSH) assays now have the sensitivity required by thyroid guidelines and allow the reliable identification of patients with both overt and subclinical hyperthyroidism. Clinical guidelines usually quote decision limits for TSH, but often ignore the issue of whether variability in bias between assays should be considered when such decision limits are implemented. Clinicians and laboratories should appreciate that these decision limits arise largely from historical data that used TSH assays with poorly defined bias. It is thus unlikely that laboratories will be able to apply an appropriate method-related bias adjustment to these TSH cut-offs. Clinicians should appreciate that TSH decision limits should thus be regarded as typical target figures rather than an absolute cut-off and thus can be applied with some degree of flexibility. There is currently insufficient evidence to justify a significant lowering of the upper reference limit for TSH, but fine-tuning of current reference ranges is required since there appears to be no association between the ranking of the assay bias in the UK National External Quality Assessment Service scheme and the manufacturers' quoted reference ranges. There is room for further improvement in TSH assays and this can best be achieved if manufacturers, laboratories and clinicians work together to produce TSH assays and reference ranges that show closer agreement between methods. Until this is achieved, future studies that examine the relationship of TSH with symptoms and treatment should ensure that sufficient information is included in the publication to allow the method related bias of the TSH assay to be clearly described.

Selenium and sulforaphane modify the expression of selenoenzymes in the human endothelial cell line EAhy926 and protect cells from oxidative damage.

OBJECTIVE: We examined the ability of sulforaphane and selenium to modify the expression of thioredoxin reductase (TR-1) and the glutathione peroxidases (GPX-1 and GPX-4) in EAhy926 cells. The effectiveness of these agents to protect cells against peroxidative damage was also assessed. METHODS: EAhy926 cells were supplemented with 40 nM of selenite and/or sulforaphane (10 microM) for 72 h and the expression of TR-1, GPX-1, and GPX-4 was assessed. Parallel cultures of selenium- and sulforaphane-treated cells were exposed to tertiary butyl hydroperoxide (t-BuOOH; 0-500 microM) for 20 h, and cell integrity was determined by the percentage of lactate dehydrogenase retained by the cellular layer. RESULTS: Selenite treatment increased the concentration of TR-1 (1.6 +/- 0.17 fold, P < 0.05), GPX-1 activity (8.2 +/- 1.08 fold, P < 0.001), and GPX-4 activity (3.1 +/- 0.25 fold, P < 0.001). Sulforaphane induced TR-1 expression in selenium-deficient cells (1.83 +/- 0.11 fold, P < 0.001) and selenium-supplemented cells (2.90 +/- 0.17 fold, P < 0.001) but had no inductive effect on GPX-1 or GPX-4. The combination of selenite and sulforaphane produced an increase in TR-1 expression that was significantly greater (P < 0.001) than that achieved when each agent was added alone. Selenium and sulforaphane acted in a synergistic manner to protect cells from damage caused by t-BuOOH. The susceptibility of cells to damage by t-BuOOH increased in this order: control > sulforaphane > selenite > selenite + sulforaphane (P < 0.0001). CONCLUSION: In endothelial cells, sulforaphane increases TR-1 but not GPX-1 and GPX-4 and in doing so confers protection against oxidative damage induced by lipid hydroperoxides. The results highlight the potential important role of TR-1 over the GPXs in protecting endothelial cells from oxidative cell damage. We also suggest that our results indicate a potential beneficial role for sulforaphane in protecting the vascular endothelium from oxidative damage.

Dietary selenium levels determine epidermal langerhans cell numbers in mice.

Selenium (Se) is a dietary trace element that is essential for effective immunity and protection from oxidative damage induced by ultraviolet radiation (UVR). Langerhans cells (LC) represent the major antigen-presenting cells resident in the epidermis; a proportion migrate from the skin to the draining lymph nodes in response to UVR. Because it is known that Se deficiency impairs immune function, we determined what effect this has on LC numbers. CH3/HeN mice were weaned at 3 wk and placed on diets containing <0.005 ppm of Se (Se deficient) or 0.1 ppm of Se (Se adequate, control mice). After 5 wk on the diet, the epidermal LC numbers in the Se-adequate group were 966 +/- 51 cells/mm2 and LC counts in the epidermis of the Se-deficient mice were 49% lower (p<0.05). Glutathione peroxidase- I (GPx) activity was measured in the epidermis, lymph nodes, and liver. In the epidermis, the activity of GPx in the Se-deficient mice was only 39% (p<0.01) of that seen in epidermis from Se-adequate mice (1.732 U/mg protein). The mice were then irradiated with one dose of 1440 J/m2 of broadband UVB or mock irradiated. After 24 h, the decrease in LC number after UVB was greater in the Se-adequate mice, (40% decrease) compared to the Se-deficient group (10%). Thus, Se deficiency reduces epidermal LC numbers, an effect that might compromise cutaneous immunity.

Mechanisms of selenium-mediated protection from photocarcinogenesis and cell death are not solely p53-dependent.

Recent studies published in Oncogene and Proc. Natl. Acad. Sci. USA ascribe a role for selenium, acting through wild type p53, in protecting skin cells in culture from ultraviolet radiation-induced death. While selenium clearly protects cells against ultraviolet radiation-induced death, data that we present and discuss in this letter shows that wild type p53 is not required for such protection. Moreover the non-physiologically high levels of selenium used in some studies leads us to question the relevance of such effects for selenium-induced photoprotection.

Endocrine measurements in survivors and non-survivors from critical illness.

OBJECTIVE: To compare measurements of thyroid and adrenal function between survivors and non-survivors in critical illness. DESIGN AND SETTING: Prospective, observational study at the medical/surgical intensive care unit (ICU) at Royal Infirmary of Edinburgh, Scotland. PATIENTS: 163 patients admitted to the intensive care unit over a 4-month period. INTERVENTIONS: We took blood samples within 1 h of ICU admission, and at 08:00 hours on the subsequent 2 days of ICU admission. We measured serum total (TT(4)) and free (fT(4)) thyroxine, total (TT(3)) and free (fT(3)) tri-iodothyronine, thyrotropin (TSH) and plasma cortisol concentrations. MEASUREMENTS AND RESULTS: TT(3) and TT(4) concentrations were significantly less in non-survivors than in survivors on admission and on day 1 but not on day 2. Cortisol concentrations were higher in non-survivors on admission and on day 1 but not on day 2. TSH, fT(3) and fT(4) concentrations did not differ significantly between survivors and non-survivors at any time. Only TT(4) and cortisol were independent predictors of outcome. Prediction of outcome from the admission sample values was not better than using APACHE II scoring. CONCLUSIONS: Thyroid hormone and cortisol concentrations differ between survivors and non-survivors on admission to intensive care, but the values overlap. These differences do not allow accurate prediction of outcome from critical illness.