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artery disease. Although well timed and adequate antithrombotic treatment, especially with GPIIb/IIIa (glycoprotein) antagonists, might eventually lead to such a result, no current evidence suggests this outcome. Non-ST segment elevation ACS vary widely and have different outcomes, and adverse events after presentation, affected by multiple factors, should be taken into account in the clinical decision-making to ensure an appropriate use of resources for each patient.4 Early conservative management of these difficult patients does not preclude an appropriate indication for further invasive procedures. However coronary arteriography is unnecessary in patients at low risk of future cardiac events, especially when the rate of periprocedural complications may exceed that of natural events. In the Veterans Affairs Non-Q-wave Infarction Strategies in Hospital (VANQWISH) trial,5 patients were screened before discharge by stress perfusion scintigraphy: among patients deemed at low-risk and treated conservatively the rate of non-fatal myocardial infarction or death by 30 days, and 1 year was close to the 1-year rate in the invasive FRISC II group, despite the greater baseline risk of VANQWISH patients. *Michele Galli, Diego Ardissino *Fondazione Maugeri IRCCS, Via per Revislate 13, 28010 Veruno, Italy, and Ospedale Maggiore, Parma 1

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Wallentin L, Lagerqvist B, Husted S, et al. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. Lancet 2000; 356: 9–16. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Trialists Collaboration. Lancet 1994; 344: 563–67. Beller GA, Zaret BL. Contributions of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease. Circulation 2000; 101: 1465–78. Boersma E, Pieper K, Steyerberg E, et al. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation: results from an international trial of 9461 patients. Circulation 2000; 101: 2557–67. Boden WE, O’Rourke RA, Crawford MH, et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. N Engl J Med 1998; 338: 1785–92.

Depressive state and common cold Sir—In their July 8 Commentary, Cornelius Katona and Gill Livingston1

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Depressive state

Absence (n=68) Presence (n=40)

Common cold (%) ⫺

+

21 (30·9) 5 (12·5)

47 (69·1) 35 (87·5)

Adjusted odds ratio (95% CI)

p

·· 3·3 (1·1–9·9)*

·· 0·03

Relative risk of common cold according to the presence or absence or depressive state.

state that the prevalence of depression among old people who are physically ill or in institutional care is about 30%. It has been reported that people with depression have a weak immune system and are prone to many diseases compared with non-depressed people.2 In the study of antibody-specific and virus-specific T-cell responses to an influenza virus vaccine, depressed people showed significant deficits compared with controls. Depressed people were less likely to show a satisfactory increase in antibody titre 4 weeks after vaccination, because they had lower in-vitro interleukin 1␤ responses to stimuli, and their peripheral-blood leucocytes produced less interleukin 2 in response to vaccine Kiecolt-Glaser and stimulation.2 colleagues reported that wound healing took significantly longer in depressed people than in controls.3 Depression in old people can be treated effectively by physical or psychological means.4 Most elderly people with depression, however, remain untreated. Screening instruments for depression may help in the recognition of the disorder. We therefore assumed that depression weakened human immune capability and depressed people were prone to developing colds. We assessed depressive state with the geriatric depression scale (GDS), in which the highest score is 15. The GDS scale was used to assess 108 people (mean age 74·1 years [SD 5·8], 31 women) in October, 1999 (see table). We interviewed them about how many times they caught colds over 6 months. Of the 108 people, 68 (mean age 74·0 years [SD 5·9]) were diagnosed as being non-depressed with GDS scores of 4 or less and 40 (mean age 74·3 years [SD 5·5]) were diagnosed as being depressed with GDS scores of 5 or more.5 During follow-up, 47 (69·1%) people who were non-depressed caught colds compared with 35 (87·5%) depressed people (relative risk 3·3 [95% CI 1·1–9·9], p=0·03 by logistic regression). In the Mann-Whitney U test, the median frequency of developing colds was once and the frequency in depressed people was twice (p=0·02). We suggest that depressive state is one of the risk factors for catching a cold in old people.

Mitsutoshi Shinkawa, Masaru Yanai, Mutsuo Yamaya, Toshihumi Matsui, *Hidetada Sasaki Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai 980–8574, Japan 1

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Katona C, Livingstone G. Impact of screening old people with physical illness for depression. Lancet 2000; 356: 91–92. Kiecolt-Glaser JK, Glaser R, Gravenstein S, Malarkey WB, Sheridan J. Chronic stress alters the immune response to Influenza virus vaccine in older adults. Proc Natl Acad Sci USA 1996; 93: 3043–47. Kiecolt-Glaser JK, Marucha PT, Malarkey WB, Mercado AM, Glaser R. Slowing of wound healing by psychological stress. Lancet 1995; 346: 1194–96. Koder DA, Brodaty H, Anstey KJ. Cognitive therapy for depression in the elderly. Int J Geriatr Psychiatry 1996; 11: 57–61. Fuh JL, Liu HC, Wang SJ, Liu CY, Wang PN. Poststroke depression among the Chinese elderly in a rural community. Stroke 1997; 28: 1126–29.

Selenium and human health Sir—The review by Margaret Rayman (July 15, p 233)1 focused primarily on the encouraging effects of selenium in cancer trials and describes current and planned selenium supplementation in cancer research. This review and the increasing attention on the possible roles of growth hormone (GH), especially insulin-like growth factor I (IGF-I), in cancer pathogenesis made us recollect a small series of studies (the latest being Grønbæk and co-workers2) of the impact in rats of selenium administration (3 mg/L in drinking water) on body growth, GH, and IGF-I secretion. Rayman emphasises that although selenium is an important trace element, it is also toxic, with a narrow therapeutic window, and some individuals are more sensitive than others. Selenium intoxication has been extensively studied in animals for more than 60 years, was termed alkali disease already in 1860, and includes, in severe cases, liver necrosis and involvement of the central nervous system. The most striking symptom in young animals is, however, growth retardation, and the American National Research Council concluded in 1976 that growth inhibition might be the best indicator of toxic effects from selenium. Selenium

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accumulated in the anterior pituitary, especially in the secretory granules of the somatotroph, and in the liver.3 Infant rats exposed to selenium intake from age 25 days to 46 days (after weaning) had a 36% lower bodyweight gain during the 3 weeks of exposure than controls (46 g vs 72 g). Serum IGF-I increased from 151 ␮g/L to 500 ␮g/L in the control rats, but no increase was seen in seleniumtreated rats.4 GH response to a stimulation test with GH releasing hormone was severely lowered (by 75%).3 We found that concomitant GH administration restored normal growth without inducing increase in serum IGFI, which suggests a GH-independent lesion in the liver IGF-I producing system.4 Withdrawal of selenium resulted in recovery of GH secretion within 2 weeks, but low circulating serum IGF-I concentrations and growth retardation persisted for much longer. We therefore wish to further stress Rayman’s warnings against high selenium intake, especially in children, because of the risk of stunting their growth. We also underscore the possibility that some of the beneficial effects of selenium in cancer are mediated by the substantial suppressive action on the GH and IGF-I system. The growing evidence of the importance of IGFs for tumourigenesis and neoplastic growth has been reviewed.5 We suggest that measurements of serum GH, and especially IGFs and their binding proteins, be included in continuing and future studies. Hans Ørskov, *Allan Flyvbjerg Institute of Experimental Clinical Research, Aarhus University Hospital, Section AKH, DK-8000 Aarhus C, Denmark 1 2

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Rayman MP. The importance of selenium to human health. Lancet 2000; 356: 233–41. Grønbæk H, Frystyk J, Ørskov H, Flyvbjerg A. Effect of sodium selenite on growth, insulin-like growth factor-binding proteins and insulin-like growth factor-I in rats. J Endocrinol 1995; 145: 105–12. Thorlacius-Ussing O, Flyvbjerg A, Esmann J. Evidence that selenium induces growth retardation through reduced growth hormone and somatomedin C production. Endocrinology 1987; 120: 659–63. Thorlacius-Ussing O, Flyvbjerg A, Jørgensen KD, Ørskov H. Growth hormone restores normal growth in selenium-treated rats without increase in circulating somatomedin C. Acta Endocrinol 1988; 117: 65–72. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 2000; 21: 215–44.

Sir—Margaret Rayman1 reports that selenium deprivation leads to depressed mood, and high dietary or supplementary selenium seems to improve mood. Rayman also states that

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selenium intake might affect metabolism of thyroid hormones. I suggest that there could be a link between the effect of selenium intake on thyroid-hormone metabolism and the influence of selenium intake on mood and brain functions. There is substantial evidence that small changes in thyroid function might be biologically meaningful and affect mood and behaviour.2–5 Esposito and colleagues2 reported a 75% lifetime prevalence of major depression in patients older than 64 years with subclinical hypothyroidism compared with an 18% prevalence in matched euthyroid controls. Haggerty and colleagues3 reported a 56% lifetime prevalence of major depression in nonelderly women with subclinical hypothyroidism, compared with 20% in euthyroid women. Similar findings have been described in other studies.4 If selenium status affects thyroidhormone metabolism, it should affect mood and cognitive functions. The effect of selenium deprivation on mood and cognition might, therefore, be partly mediated by changes induced by selenium deficiency in thyroid function. Rayman reports that selenium deficiency decreases immunocompetence and promotes vital infections. Patients who have a combination of depression, hypothyroidism, and increased susceptibility to viral infections, could reasonably, therefore, be assessed for selenium deficiency, especially if they live in an area where the soil is low in selenium. Leo Sher National Institute of Mental Health, Building 10, Room 3S–231, 9000 Rockville Pike, Bethesda, MD 20892, USA 1 2

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Rayman MP. The importance of selenium to human health. Lancet 2000; 356: 233–41. Esposito S, Prange AJ Jr, Golden RN. The thyroid axis and mood disorders: overview and future prospects. Psychopharmacol Bull 1997; 33: 205–17. Haggerty JJ Jr, Stern RA, Mason GA, Beckwith J, Morey CE, Prange AJ Jr. Subclinical hypothyroidism: a modifiable risk factor for depression? Am J Psychiatry 1993; 150: 508–10. Joffe RT, Levitt AJ. The thyroid and depression. In: Joffe RT, Levitt AJ, eds. The thyroid axis and psychiatric illness. Washington, DC: American Psychiatry Press, 1993: 195–254. Sher L, Rosenthal NE, Wehr TA. Free thyroxine and thyroid-stimulating hormone levels in patients with seasonal disorder and matched controls. J Affect Disord 1999; 56: 195–99.

Sir—Margaret Rayman’s review1 on the importance of dietary selenium underlines the possible inverse correlation between low selenium status and the risk of cardiovascular disease,

especially the cardiomyopathy associated with selenium deficiency in China (Keshan disease), where crops are raised on soils that are poor in this essential trace nutrient. Another clinical selenium deficiency arises in patients maintained on total parenteral nutrition (TPN) because of long-term management with nutritive fluid that is inadequate in selenium. Fleming and co-workers2 reported a man aged 24 years with chronic idiopathic intestinal pseudoobstruction who had been maintained on TPN for 6 consecutive years. Similarly, Johnson and colleagues3 described the case of a man aged 43 years who had been receiving TPN for 4 years after undergoing several gastrointestinal operations. These two patients died of a cardiomyopathy, which at necropsy bore a striking resemblance to the specific myocardial damage seen in Keshan disease.2,3 Extremely low concentrations of selenium (15–34% of normal) and selenium-dependent glutathione peroxidase activity (<10% of normal) were found in the heart tissue and blood (<10% of normal) in each patient. In a third example, a selenium-responsive syndrome was seen in a woman aged 37 years who developed myopathy while on long-term TPN. The disorder was reversed by intravenous selenomethionine.4 This evidence supports the hypothesis that a long-term dietary selenium deficiency probably adversely affects the heart. Michael J Fryer Department of Biology, John Tabor Laboratories, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK (e-mail: [email protected]) 1 2

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Rayman MP. The importance of selenium to human health. Lancet 2000; 356: 233–41. Fleming CR, Lie JT, McCall JT, et al. Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition. Gastroenterology 1982; 83: 689–93. Johnson RA, Baker SS, Fallon JT, et al. An occidental case of cardiomyopathy and selenium deficiency. N Engl J Med 1981; 304: 1210–12. van Rij AM, Thomson CD, McKenzie JM, Robinson MF. Selenium deficiency in total parenteral nutrition. Am J Clin Nutr 1979; 32: 2076–85.

Sir—Margaret Rayman1 briefly mentions the relation of selenium with Keshan disease, a dilated cardiomyopathy that is endemic in selenium-deficient areas and is responsive to selenium supplements.2 No mention is made, however, of selenium-deficient cardiomyopathy (pathologically similar to Keshan disease), which develops in malnourished patients and those on total parenteral nutrition (TPN), of which many reports exist from 1981 onwards. An increasing number of patients

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