Sleepiness is a signal to go to bed: data and model simulations.

STUDY OBJECTIVES: Assess the validity of a subjective measure of sleepiness as an indicator of sleep drive by quantifying associations between intraindividual variation in evening sleepiness and bedtime, sleep duration, and next morning and subsequent evening sleepiness, in young adults. METHODS: Sleep timing and sleepiness were assessed in 19 students in late autumn and late spring on a total of 771 days. Karolinska Sleepiness Scales (KSS) were completed at half-hourly intervals at fixed clock times starting 4 h prior to participants' habitual bedtime, and in the morning. Associations between sleepiness and sleep timing were evaluated by mixed model and nonparametric approaches and simulated with a mathematical model for the homeostatic and circadian regulation of sleepiness. RESULTS: Intraindividual variation in evening sleepiness was very large, covering four or five points on the 9-point KSS scale, and was significantly associated with subsequent sleep timing. On average, a one point higher KSS value was followed by 20 min earlier bedtime, which led to 11 min longer sleep, which correlated with lower sleepiness next morning and the following evening. Associations between sleepiness and sleep timing were stronger in early compared to late sleepers. Model simulations indicated that the directions of associations between sleepiness and sleep timing are in accordance with their homeostatic and circadian regulation, even though much of the variance in evening sleepiness and details of its time course remain unexplained by the model. CONCLUSION: Subjective sleepiness is a valid indicator of the drive for sleep which, if acted upon, can reduce insufficient sleep.

Sleep Timing in Late Autumn and Late Spring Associates With Light Exposure Rather Than Sun Time in College Students.

Timing of the human sleep-wake cycle is determined by social constraints, biological processes (sleep homeostasis and circadian rhythmicity) and environmental factors, particularly natural and electrical light exposure. To what extent seasonal changes in the light-dark cycle affect sleep timing and how this varies between weekdays and weekends has not been firmly established. We examined sleep and activity patterns during weekdays and weekends in late autumn (standard time, ST) and late spring (daylight saving time, DST), and expressed their timing in relation to three environmental reference points: clock-time, solar noon (SN) which occurs one clock hour later during DST than ST, and the midpoint of accumulated light exposure (50% LE). Observed sleep timing data were compared to simulated data from a mathematical model for the effects of light on the circadian and homeostatic regulation of sleep. A total of 715 days of sleep timing and light exposure were recorded in 19 undergraduates in a repeated-measures observational study. During each three-week assessment, light and activity were monitored, and self-reported bed and wake times were collected. Light exposure was higher in spring than in autumn. 50% LE did not vary across season, but occurred later on weekends compared to weekdays. Relative to clock-time, bedtime, wake-time, mid-sleep, and midpoint of activity were later on weekends but did not differ across seasons. Relative to SN, sleep and activity measures were earlier in spring than in autumn. Relative to 50% LE, only wake-time and mid-sleep were later on weekends, with no seasonal differences. Individual differences in mid-sleep did not correlate with SN but correlated with 50% LE. Individuals with different habitual bedtimes responded similarly to seasonal changes. Model simulations showed that light exposure patterns are sufficient to explain sleep timing in spring but less so in autumn. The findings indicate that during autumn and spring, the timing of sleep associates with actual light exposure rather than sun time as indexed by SN.

Serum iron and iron stores in non-anemic patients with fibromyalgia.

The aim of the study was to assess iron serum levels and markers of iron stores in non-anemic fibromyalgia (FM) patients and to evaluate their impact on the prevalence and clinical manifestations of FM patients. Eighty-four patients with primary FM and 87 controls were investigated. Demographic and clinical data were collected from all participants. All patients completed the fibromyalgia impact questionnaire (FIQ). Patients evaluated the effect of the disease on their daily activity (DA) and judged the severity (DS) of the disease on a 0-10 scale. Venous blood was tested for serum iron, transferrin, ferritin, and soluble transferrin receptors (sTfR). Iron deficiency was defined if any of the following were present: serum iron <40 µg/dL, serum ferritin levels <10 ng/mL, or sTfR levels >28.1 nmol/L. Analysis at a cutoff level of serum ferritin levels ≤30 ng/mL and sTfR/ferritin ratio was also performed. Hemoglobin, iron, transferrin, sTfR, ferritin levels, and sTfR/ferritin ratios did not differ between the groups. The mean FIQ score was 57.13 ± 20.21 and the DA and DS scores were 6.79 ± 2.97 and 6.74 ± 3.09, respectively. No correlations were found between the parameters studied and the FIQ or its ten individual items. Thirty-eight controls (43.7%) and 23 FM patients (27.4%) had ferritin levels of ≤30 (p < 0.04). Within the FM group, lower levels were associated with lower total FIQ score and FIQ subscale scores. Patients with FM do not have reduced serum levels of iron or surrogate markers of iron stores. At present, there is no evidence to support iron supplementation in the treatment of FM.

Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism.

OBJECTIVE: To evaluate the effect of parathyroidectomy on metabolic abnormalities associated with cardiovascular disease in patients with primary hyperparathyroidism (PHPT). METHODS: Thirty-four patients with PHPT (aged 51.0 ± 11.8 years, mean ± standard deviation) underwent assessment before and 1 year after successful parathyroidectomy. A control group of 42 normocalcemic healthy subjects, matched for age and body mass index, was also examined at baseline. We measured serum lipids, glucose, insulin, uric acid, calcium, parathyroid hormone, C-reactive protein, and bone density. Insulin resistance index was evaluated by homeostasis model assessment, and the presence of metabolic syndrome was determined. Because of multiple tests, the level of statistical significance was set at .01. RESULTS: After parathyroidectomy, there was a decrease in diastolic blood pressure (P<.02) and in serum concentrations of uric acid (P<.04) and insulin (P<.009). No difference was observed in rates of metabolic syndrome in patients before and 1 year after parathyroidectomy (23.5% versus 17.6%; P>.46). Insulin resistance index values were also unchanged from before to after parathyroidectomy (1.3 ± 0.9 and 1.1 ± 0.9, respectively; P>.68). A substantial increase in spine bone density (5%; P<.05) was noted postoperatively. Multivariate logistic regression analysis, after adjustment for age and body mass index, revealed that parathyroidectomy did not lead to a significant decrease in likelihood of cardiovascular risk-odds ratio (OR), 1.82; 95% confidence interval (CI), 0.53 to 6.21 (P>.34) for the metabolic syndrome and OR, 0.82; 95% CI, 0.17 to 3.88 (P>.8) for the insulin resistance index. CONCLUSION: In this study, surgical treatment had no beneficial effect on cardiovascular risk, as assessed by the metabolic syndrome and insulin resistance markers in patients with PHPT 1 year after parathyroidectomy.

Nonarticular tenderness and functional status in patients with diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: To investigate the degree of nonarticular tenderness and functional status in patients with diffuse idiopathic skeletal hyperostosis (DISH). We assessed these variables' correlation with their clinical, radiographic, and constitutional measurements and with metabolic syndrome (MS). METHODS: Eighty-seven patients with DISH were compared with 65 controls without DISH. Examination of nonarticular tenderness was performed by thumb palpation. Tenderness was scored for the 18 fibromyalgia tender points (TP), and 4 control points. Nonarticular tenderness was expressed by the number of TP and by the total tenderness score (TTS). The Short Health Assessment Questionnaire (HAQ II) was administered to all participants. Clinical and laboratory data were collected from all patients. Patients were classified as having MS by both the National Cholesterol Education Program and World Health Organization definitions. RESULTS: There was a statistically significant difference in TTS between controls and patients with DISH. The mean tenderness of many individual TP was significantly higher in the DISH group compared with the control group. TP counts, TTS, and body mass index (BMI) positively correlated with the HAQ II. There was a linear trend in intensity of T-spine bony bridges (BB) and the total number of TP as well as many individual TP. Patients with DISH were more likely to be affected by MS. No correlation was found between TP count, TTS, and MS. CONCLUSION: Patients with DISH have a lower pain threshold than patients who do not have DISH. TP count and TTS correlate with the functional status, BMI, waist circumference, and high-grade BB. No correlation was observed between pain threshold and MS.

Shift work in nursing: is it really a risk factor for nurses' health and patients' safety?

There is evidence in the scientific literature of the adverse physiological and psychological effects of shift work, including disruption to biological rhythm, sleep disorders, health problems, diminished performance at work, job dissatisfaction, and social isolation. In this study, the results of health problems and sleep disorders between female and male nurses, between daytime and shift nurses, and between sleep-adjusted and non-sleep-adjusted shift nurses were compared. Also the relationship between adjustment to shift work and organizational outcomes (errors and incidents and absenteeism from work) was analyzed. Gender, age, and weight were more significant factors than shift work in determining the well-being of nurses. Shift work by itself was not found to be a risk factor for nurses' health and organizational outcomes in this study. Moreover, nurses who were identified as being "non-adaptive" to shift work were found to work as effectively and safely as their adaptive colleagues in terms of absenteeism from work and involvement in professional errors and accidents. This research adds two additional findings to the field of shift work studies. The first finding is that female shift workers complain significantly more about sleep disorders than male shift workers. Second, although high rates of nurses whose sleep was not adapted to shift work were found, this did not have a more adverse impact on their health, absenteeism rates, or performance (reported errors and incidents), compared to their "adaptive" and "daytime" colleagues.

Mortality risk factors in sleep apnoea: a matched case-control study.

Sleep apnoea syndrome was reported to be associated with increased mortality but it is not known if this association is independent of obesity and co-morbidities. The present study investigated predictors of mortality in a large cohort of men with sleep apnoea using a case-control design. The study population consisted of 10,981 men diagnosed during 1991-2000 by whole-night polysomnography with sleep apnoea; 331 men died prior to 1 September 2001, of whom 277 were matched by age, gender, site and time of study to patients who were alive in September 2001. Multivariate analysis revealed that all-cause mortality was associated with chronic obstructive pulmonary disease (COPD) (odds ratio, OR: 7.07, 95% CI 2.75-18.16), chronic heart failure (CHF) (OR: 5.47, 95% CI 1.06-28.31), diabetes mellitus (DM) (OR: 3.30, 95% CI 1.51-7.20) and body mass index (BMI) (increase of 5 kg m(-2), OR: 1.44, 95% CI: 1.04-1.99). Chronic upper airway problems were associated with survival (OR: 0.45, 95% CI 0.23-0.90). There were significant interactions between respiratory disturbance index and BMI and COPD. Mortality of patients younger than the median age (62 years) was associated with COPD, DM and an interaction between BMI and apnoea severity. Predictors of mortality for the older patients were COPD, CHF and DM. We conclude that all-cause mortality in sleep apnoea is associated with co-morbidities and obesity. Severity of sleep apnoea affects mortality by interacting with obesity and lung disease.

Altered luteinizing hormone and testosterone secretion in middle-aged obese men with obstructive sleep apnea.

OBJECTIVE: To elucidate the causes for the decline in testosterone levels observed in men with obstructive sleep apnea (OSA). RESEARCH METHODS AND PROCEDURES: We determined serum luteinizing hormone (LH) and testosterone levels every 20 minutes between 7 pm and 7 am with simultaneous sleep recordings in five obese middle-aged men with OSA, in five age- and BMI-matched controls, and in six lean young healthy men. RESULTS: The mean and area under the curve (AUC) values of LH and testosterone were significantly lower in men with OSA compared with controls. Young controls had significantly more testosterone pulses of shorter interpulse duration than OSA subjects and middle-aged controls. After adjusting for age and BMI, the three groups differed in mean and AUC values of LH and testosterone. Analysis of covariance, using BMI as a covariate, revealed a statistically significant group effect on mean and AUC testosterone values (p = 0.03; p < 0.003, respectively). Eliminating young controls, there was a significant positive correlation between the amount of LH and testosterone secreted at night. After partialling out age alone and BMI alone, the mean LH and mean testosterone were still positively correlated. DISCUSSION: Thus, OSA is associated with decreased pituitary-gonadal function. The decline in testosterone concentrations is due to obesity and advanced age and to a lesser degree to sleep fragmentation and hypoxia.

Cardiovascular risk factors in middle-aged women with subclinical hypothyroidism.

OBJECTIVES: Overt hypothyroidism (OH) is associated with premature atherosclerosis and coronary heart disease (CHD). Recently, C-reactive protein (CRP) and total homocysteine (tHct) emerged as additional independent cardiovascular risk factors. Subclinical hypothyroidism (SH), affecting as many as 15% of middle-aged women is not known to be associated with risk for CHD. DESIGN AND MEASUREMENTS: We measured CRP and tHct levels as well as conventional cardiovascular risk markers in 44 middle-aged women with newly diagnose SH. Results were compared with those obtained in 10 patients with OH and 19 euthyroid controls. RESULTS: In SH, tHct and CRP levels were not as augmented as compared to controls. Their mean systolic and diastolic blood pressure values were increased vs. controls (p<0.04;p<0.01, respectively). Mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, TC/HDL-C and LDL-C/HDL-C were not different in patients with SH compared to controls. Individual analysis revealed that the percentage of patients with SH having hypertension, hypertriglyceridemia, hypercholesterolemia, elevated TC/HDL-C and LDL-C/HDL-C ratios were higher than the percentage in controls. CRP positively correlated with BMI(r=0.29,p<0.02), and tHct positively correlated with age (r=0.24, p<0.05). CONCLUSIONS: Our findings suggest that subclinical hypothyroidism in middle-aged women is associated with hypertension and dyslipidemia. CRP and tHct do not appear to contribute to the increased risk for CHD in these patients.

Evaluation of the pituitary-adrenal axis in hyperandrogenic women with polycystic ovary syndrome.

OBJECTIVES: Impaired adrenal function is common in patients with polycystic ovary syndrome (PCOS). Abnormal regulation of cytochrome P450 17 alpha is believed to cause the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation. The aim of the study was to evaluate cortisol and 17OHP response to low dose (1 microg) ACTH test and to compare it with the standard ACTH (250 microg) test in hyperandrogenic women with PCOS. DESIGN AND MEASUREMENTS: We studied 27 PCOS and 22 control women. All participants were examined for mutations of the CYP21 gene, Cortisol and 17OHP levels before, 30 and 60 minutes after the IV injection of 250 microg ACTH (SDT) and after 1 microg ACTH (LDT). Fasting serum levels of LH, FSH, testosterone, DHEAS were determined in all participants. RESULTS: Basal and ACTH stimulated Cortisol during the SDT (470+/-138 nmol/L and 761+/-143, respectively) were significantly higher in PCOS vs. controls (232+/-124 and 670+/-130, respectively) (p<0.03, p<0.02, respectively). Basal 17OHP (6.1+/-2.1 nmol/L) and the peak response to SDT (14.2+/-3.6 nmol/L) were significantly higher in PCOS vs. controls (4.2+/-2.1, 10.9+/-3.0, respectively) (p<0.003, p<0.004, respectively). Abnormally elevated 17OHP response to SDT was detected in 6/27 PCOS women (22%). No statistically significant difference between the PCOS and control groups were noted during the LDT in both cortisol and 17OHP levels. CONCLUSIONS: These data suggest that the exaggerated 17-hydroxyprogesterone (17OHP) response to ACTH stimulation in PCOS is revealed by stimulation at a pharmacological dose (250 microg) but not by a physiological dose (1 microg).

Haptoglobin polymorphism is a risk factor for cardiovascular disease in patients with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Obstructive sleep apnea syndrome is associated with a marked increase in the risk for cardiovascular disease. Increased oxidative stress and leukocyte adhesiveness have been implicated as fundamental pathophysiologic mechanisms underlying the increased susceptibility in these patients. Haptoglobin is an antioxidant and immunomodulatory protein encoded by 2 alleles with profoundly different biophysical and biochemical properties. We therefore sought to determine if the haptoglobin phenotype was a determinant of cardiovascular disease in patients with obstructive sleep apnea syndrome. DESIGN: Haptoglobin phenotype was determined by gel electrophoresis in 465 patients with and 757 individuals without obstructive sleep apnea syndrome. SETTING: Eight-bed Technion Sleep Medicine Center in Haifa, serving the northern part of Israel. PARTICIPANTS: Patients referred for sleep recordings because of suspected breathing disorders in sleep and healthy industry workers. MEASUREMENTS AND RESULTS: Patients with obstructive sleep apnea syndrome and cardiovascular disease had a significantly different distribution of the 3 haptoglobin phenotypes as compared to patients with obstructive sleep apnea syndrome but without cardiovascular disease. No difference in the haptoglobin phenotype frequency was found between controls with and without cardiovascular disease. Log linear analysis revealed a significant interaction effect of haptoglobin phenotype and the presence of sleep apnea on the presence of cardiovascular disease. Logistic regression analysis revealed that the risk of cardiovascular disease in sleep apnea patients younger than 55 years with haptoglobin 2-2 was 2.32-fold higher than in their counterparts with haptoglobin 2-1. CONCLUSIONS: These results suggest that haptoglobin phenotype is an important risk factor in determining susceptibility to cardiovascular disease in obstructive sleep apnea syndrome, which may be mediated by the decreased antioxidant and antiinflammatory actions of the haptoglobin 2 allelic protein product.

Middle-aged men secrete less testosterone at night than young healthy men.

Aging men largely maintain their testicular androgen production. Cross-sectional studies have demonstrated that after the age of 40 yr a 0.2-2% annual decline is observed in morning total testosterone. In elderly males, the coordinate release of LH and testosterone became asynchronous despite normal serum levels of these hormones. The aim of this study was to test the reproductive hormone rhythm at night in middle-aged men. We studied seven healthy middle-aged (46.6 +/- 6.7 yr) and six healthy young (23.9 +/- 2.4 yr) men by determining their serum levels of LH and testosterone levels every 15 min from 1900-0700 h with simultaneous sleep recordings. The nocturnal rise in testosterone occurred earlier in young men (2235 +/- 0022 h) and at 2331 +/- 0057 h in middle-aged men (P < 0.04). In young men, the mean testosterone level at night (5.0 +/- 1.3 ng/ml; 17.4 +/- 4.4 nmol/liter) and the integrated nocturnal secretion [area under the curve (AUC); 60.6 +/- 8.9 ng/ml.h; 210 +/- 31 nmol/liter.h] were significantly higher compared with the values (3.6 +/- 1.1 and 31.1 +/- 7.2 ng/ml.h; 12.6 +/- 3.8 and 108 +/- 24.8 nmol/liter.h, respectively) observed in middle-aged men (P < 0.04 and P < 0.01, respectively). The mean (3.5 +/- 0.3 mIU/ml; 3.5 +/- 0.3 IU/liter) and AUC (43.4 +/- 8.3 mIU/ml.h; 43.4 +/- 8.3 IU/liter.h) LH values in middle-aged men were significantly higher than the values observed in young men (2.0 +/- 0.7 and 30.8 +/- 6.1 mIU/ml.h; 2.0 +/- 0.7 and 30.8 +/- 6.1 IU/liter.h; P < 0.05 and P < 0.01, respectively). Young men had significantly more testosterone pulses at night (6.7 +/- 1.6/12 vs. 3.8 +/- 1.1/12 h in middle-aged men; P < 0.005) of shorter interpulse interval (88.5 +/- 23.6 vs. 137.4 +/- 46.4 min; P < 0.02). LH pulse characteristics and sleep quality were similar in both groups. However, the first rapid eye movement (REM) sleep episode occurred earlier in middle-aged men (2303 +/- 0034 h) vs. young men (0010 +/- 0054 h; P < 0.04). As a consequence, the testosterone rise antedated the first REM episode by 90 min in young men. The link between testosterone rise and REM sleep episode was not observed in middle-aged men. Linear regression analysis revealed that the LH AUC was significantly related to age (P < 0.02). Analysis of covariance revealed that the two groups differed significantly in testosterone AUC (P < 0.04). Comparison of LH and testosterone concentrations showed significant and positive cross-correlations between LH and testosterone only in young men, with the testosterone rise lagging 60 min after the rise in LH. Our findings suggest that in middle-aged men, less pulsatile testosterone and more LH are secreted at night than in young men, with disruption of the association between testosterone rhythm and REM sleep. The decline in nocturnal testosterone secretion appears to involve a combination of testicular and pituitary hypogonadism.

Cyproterone acetate-ethinyl estradiol treatment alters urinary 6-sulfatoxymelatonin excretion in hyperandrogenic women.

OBJECTIVES: To investigate melatonin production in hyperandrogenic women before and during treatment with cyproterone acetate and ethinyl estradiol (Diane 35). MATERIAL AND METHODS: We studied 10 women with late onset adrenal hyperplasia due to 21-hydroxylase deficiency (LOCAH) and 10 women with idiopathic hirsutism (IH). Patients were treated with Diane 35 for four months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dihydroepiandrosterone sulfate (DHEAS) and 24-hour urine collections for the determination of 6-sulfatoxymelatonin (aMT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. Results were compared with those obtained in 15 control women. RESULTS: At baseline, women with LOCAH had significantly higher serum testosterone, 17-hydroxyprogesterone (17OHP) and ACTH stimulated 17OHP values than IH and control women. Their aMT6s values (51.0+/-20.5 mg/24h) were significantly higher than the values in IH (34.3+/-7.1) and control women (30.5+/-6.5) (p< 0.001). Diane 35 treatment significantly decreased serum LH, FSH and testosterone levels and aMT6s values in LOCAH patients (29.8+/-16.6 mg/24h) (p<0.0001) in LOCAH patients. CONCLUSIONS: These results indicate that hyperandrogenic women with LOCAH have increased melatonin production. The normalization of aMT6s and testosterone values during cyproterone acetate-ethinyl estradiol treatment, suggest that sex steroids either directly or through the suppression of gonadotropin, modulate melatonin secretion in these patients.

Decreased pituitary-gonadal secretion in men with obstructive sleep apnea.

Decreased libido is frequently reported in male patients with obstructive sleep apnea (OSA). The decline in morning serum testosterone levels previously reported in these patients was within the normal adult male range and does not explain the frequent association of OSA and sexual dysfunction. We determined serum LH and testosterone levels every 20 min between 2200-0700 h with simultaneous sleep recordings in 10 men with sleep apnea and in 5 normal men free of any breathing disorder in sleep. The mean levels and area under the curve of LH and testosterone were significantly lower in OSA patients compared with controls [LH, 24.9 +/- 10.2 IU/liter.h vs. 43.4 +/- 9.5 (P < 0.005); testosterone, 67.2 +/- 11.5 nmol/liter.h vs. 113.3 +/- 26.8 (P < 0.003)]. Four of 10 patients had hypogonadal morning (0700 h) serum testosterone levels. Analysis of covariance (ANCOVA) revealed that the 2 groups differed significantly in the amount of LH and testosterone secreted at night independent of age or degree of obesity. After partialing out body mass index, there was a significant negative correlation between the amounts of LH and testosterone secreted at night and the respiratory distress index, but not with degree of hypoxia. Our findings suggest that OSA in men is associated with dysfunction of the pituitary-gonadal axis. The relation between LH-testosterone profiles and the severity of OSA suggests that sleep fragmentation and, to a lesser extent, hypoxia in addition to the degree of obesity and aging may be responsible for the central suppression of testosterone in these patients.

Risk factors for cardiovascular disease in women with subclinical hypothyroidism.

Overt hypothyroidism may result in accelerated atherosclerosis and coronary heart disease (CHD) presumably because of the associated hypertension, hypercholesterolemia, and hyperhomocysteinemia. As many as 10%-15% of older women have subclinical hypothyroidism (SH) and thyroid autoimmunity. Whether SH is associated with risk for CHD is controversial. We examined 57 women with SH and 34 healthy controls. SH was defined as an elevated thyrotropin (TSH) (>4.5 mU/L) and normal free thyroxine (FT(4)) level (8.7-22.6 nmol/L). None of the patients had been previously treated with thyroxine. In all participants we determined blood pressure, body mass index (BMI), and fasting TSH, FT(4), antibodies to thyroid peroxidase and thyroglobulin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, folic acid, vitamin B(12), creatinine, and total plasma homocysteine levels. The SH and control groups did not differ in their total homocysteine values. Mean diastolic blood pressure was increased in SH patients versus controls (82 vs. 75 mm Hg; p < 0.01). Mean values of TC, HDL-C, LDL-C, triglycerides, TC/HDL-C, and LDL-C/HDL-C were not different in patients with SH compared with controls. Individual analysis revealed that the percentage of patients with SH having hypertension (20%), hypertriglyceridemia (26.9%), elevated TC/HDL-C (11.5%), and LDL-C/HDL-C (4%) ratios were higher than the percentages in controls. Hyperhomocysteinemia (> or = 10.98 micromol/L) was observed in 29.4% of SH and was not significantly different from the percentage in controls (21.4%). No significant correlation between TSH and biochemical parameters was detected. We conclude that subclinical hypothyroidism in middle-aged women is associated with hypertension, hypertriglyceridemia, and elevated TC/HDL-C ratio. This may increase the risk of accelerated atherosclerosis and premature coronary artery disease in some patients.

The effect of pyridoxine administration on melatonin secretion in normal men.

OBJECTIVES: To determine pineal response to pyridoxine in normal men. MATERIAL AND METHODS: Twelve healthy men were given orally pyridoxine (100 mg) or placebo at 1700h. Serum melatonin levels were determined every 30 minutes with simultaneous measurement of core body temperature between 1700h to 0300h. Polysomnographic sleep recordings were performed between 1800h to 2000h. RESULTS: Serum melatonin levels after both placebo and pyridoxine showed a nocturnal rise occurring at 22:10+/-1:22h and 22:24+/-1:09h, respectively. The melatonin onset, peak, mean and area under the curve (AUC) values after pyridoxine (3.2+/-1.6 pg/ml, 47.2+/-22.6 pg/ml, 31.5+/-11.0 pg/ml and 173.5+/-138.4 pg/ml x min, respectively) were similar to the values after placebo administration (4.7+/-1.6 pg/ml, 53.9+/-26.0 pg/ml, 37.2+/-2.8 pg/ml and 205.3+/-137.8 pg/ml x min, respectively). CBT revealed a significant nocturnal decline but without significant difference between pyridoxine and placebo. Sleep amount and architecture were similar after the two treatments. CONCLUSIONS: In adult man, the oral administration of 100 mg-pyridoxine during the evening hours has no effect on melatonin secretion nor does it alter CBT or sleep quality.

Haptoglobin phenotype and the risk of restenosis after coronary artery stent implantation.

We recently demonstrated that an allelic polymorphism in the haptoglobin gene is a major determinant of susceptibility to a number of vascular disorders. We set out to determine if haptoglobin phenotype was predictive of the development of restenosis in a consecutive series of patients, all of whom underwent stent implantation followed by repeat angiography with quantitative coronary angiography analysis 6 months later. This study included 214 consecutive patients undergoing stent implantation for de novo lesions between 1998 and 1999 in Aalst, Belgium. All underwent follow-up quantitative coronary angiography analysis 6 months after the procedure. The haptoglobin phenotype was determined by electrophoresis. No significant differences were found between patients segregated by phenotype with respect to clinical, procedural, and angiographic factors previously suggested to influence the development of restenosis. None of the diabetic patients homozygous for the haptoglobin 1 allele developed restenosis compared with a >50% restenosis rate for diabetic patients with at least 1 haptoglobin 2 allele (p <0.02). In all patients (diabetic and nondiabetic), we observed a trend toward a lower incidence of restenosis in patients homozygous for the 1 allele (21% vs 33%, p <0.09). Moreover, we found a graded risk relation to the number of haptoglobin 2 alleles. The risk of developing restenosis was greater in subjects with 2 haptoglobin 2 alleles (36%) than in those with 1 haptoglobin 2 allele (31%) or no haptoglobin 2 alleles (21%). Thus, knowledge of the haptoglobin phenotype may be useful in assessing and utilizing new therapies that attempt to reduce restenosis, and may have important implications for the risk stratification algorithm used in managing diabetic patients with coronary artery disease.

Residual effects of daytime administration of melatonin on performance relevant to flight.

There is a general consensus that melatonin possesses time-dependent hypnotic effects, but there is no information yet whether it has residual effects on neurobehavioral performance, especially after daytime administration. In the present study we investigated the possible residual effects of 3 mg melatonin on performance relevant to flight and on subjective feelings of sleepiness, arousal, activation and affect after a daytime nap, as a function of nap length. Fifteen reserve pilots of the Israeli Air Force participated in the study. The experiment consisted of four sessions during which either melatonin or placebo was administered at 16:00 h. In two conditions, subjects were allowed to sleep for 2 h (17:00-19:00 h) whereas in the other two only a 0.5-h nap was allowed. After the naps they started performing a flight simulator task every 2 h. Sleep efficiency significantly increased and sleep latency significantly decreased in both melatonin conditions compared to placebo. Flight performance was only mildly affected in the 0.5-h nap condition. Subjective assessment of sleepiness significantly differed between the two treatment conditions, only in the 0.5-h nap condition. Subjects felt sleepier 2-4 h after melatonin administration. To conclude, our data suggest that administration of melatonin before a brief daytime nap (about 0.5 h) may be associated with mild residual effects on psychomotor performance and may significantly affect subjective feeling of sleepiness for 2-4 h.