Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

Population-based epidemiologic studies have uncovered the high prevalence and wide severity spectrum of undiagnosed obstructive sleep apnea, and have consistently found that even mild obstructive sleep apnea is associated with significant morbidity. Evidence from methodologically strong cohort studies indicates that undiagnosed obstructive sleep apnea, with or without symptoms, is independently associated with increased likelihood of hypertension, cardiovascular disease, stroke, daytime sleepiness, motor vehicle accidents, and diminished quality of life. Strategies to decrease the high prevalence and associated morbidity of obstructive sleep apnea are critically needed. The reduction or elimination of risk factors through public health initiatives with clinical support holds promise. Potentially modifiable risk factors considered in this review include overweight and obesity, alcohol, smoking, nasal congestion, and estrogen depletion in menopause. Data suggest that obstructive sleep apnea is associated with all these factors, but at present the only intervention strategy supported with adequate evidence is weight loss. A focus on weight control is especially important given the expanding epidemic of overweight and obesity in the United States. Primary care providers will be central to clinical approaches for addressing the burden and the development of cost-effective case-finding strategies and feasible treatment for mild obstructive sleep apnea warrants high priority.

Epidemiology of obstructive sleep apnea: a population health perspective.

Advances in flavonoid research since 1992.

Polyphenols are the most abundant antioxidants in the diet and are widespread constituents of fruits, vegetables, cereals, dry legumes, chocolate, and beverages, such as tea, coffee, or wine. Experimental studies on animals or cultured human cell lines support a role of polyphenols in the prevention of cardiovascular diseases, cancers, neurodegenerative diseases, diabetes, or osteoporosis. However, it is very difficult to predict from these results the effects of polyphenol intake on disease prevention in humans. One of the reasons is that these studies have often been conducted at doses or concentrations far beyond those documented in humans. The few clinical studies on biomarkers of oxidative stress, cardiovascular disease risk factors, and tumor or bone resorption biomarkers have often led to contradictory results. Epidemiological studies have repeatedly shown an inverse association between the risk of myocardial infarction and the consumption of tea and wine or the intake level of some particular flavonoids, but no clear associations have been found between cancer risk and polyphenol consumption. More human studies are needed to provide clear evidence of their health protective effects and to better evaluate the risks possibly resulting from too high a polyphenol consumption.

Dietary polyphenols and the prevention of diseases

Summary
BACKGROUND AND OBJECTIVE The original Whlckham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the Incidence and natural history of thyroid disease in this cohort.

DESIGN, PATIENTS AND MEASUREMENTS Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, In addition to death certificates, two-thirds had Information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91 % were tested for clinical, biochemical and Immunological evidence of thyroid dysfunction.

RESULTS Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean Incidence (with 95% confidence Intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism In women was 0.8/1000 survivors/year (0.5.1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an Increase with age In hypothyroidism but no age relation in hyperthyroidism.

The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially.

The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors Identified at first survey. The odds ratios (with 95% confidence Intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A loglt model Indicated that Increasing values of serum TSH above 2mU/l at first survey Increased the probability of developing hypothyroidism which was further Increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with Increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism In women.

CONCLUSIONS This historical cohort study has provided Incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease Identified twenty years earlier.

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The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey

Inhibin is a gonadal glycoprotein hormone, originally isolated from bovine follicular fluid as a 58-kDa dimeric molecule (Robertson et al., 1985), and subsequently from both bovine and porcine follicular fluids as a 30 and 32-kDa species (Miyamoto et al., 1985; Rivier et al., 1985; Robertson et al., 1986). In man, the dimer is composed of an a-subunit and one of two similar /3-subunits (PA or PB), giving rise to inhibin-A or inhibin-B, respectively. The dimer suppresses the synthesis and secretion of pituitary follicle stimulating hormone (FSH). Dimers of the /3-subunit, termed the activins, have the opposite property. The major ovarian source of inhibin is the follicular granulosa cell (Erickson & Hsueh, 1978), but mRNAs for the inhibin subunits and the corresponding peptides have been identified in theca interna and in the corpus luteum (Davis et al., 1987; Roberts e t al., 1993). In the male, inhibin was originally identified as a Sertoli cell product (Steinberger & Steinberger, 1976) but it is clear that both inhibin and activin may be products of the interstitial cell (Roberts et ul., 1989). Furthermore, using the technique of S1-nuclease analysis, Meunier et al. (1988) demonstrated the expression of inhibin subunit mRNAs in both gonadal and extra-gonadal tissues, including the placenta, pituitary, adrenal, bone marrow, kidney, spinal cord and brain. Given this widespread distribution, it could be predicted that overexpression of inhibin or related substances might be demonstrable in at least some neoplasms. Interest in the possible application of inhibin as a tumour marker was stimulated by the observation of Lappohn et al. (1989) that serum immunoreactive inhibin levels were markedly raised in the sera of patients with granulosa cell tumours of the ovary. Evaluation of sera held in a tissue bank showed that in retrospect, tumour recurrence might have been predicted by inhibin assay up to 2 years earlier than clinical manifestations of such recurrence became apparent. Ohashi et al. (1990) reported that a postmenopausal woman with a virilizing Sertoli-Leydig cell tumour had high inhibin levels which became undetectable following removal of the tumour which itself contained high immunoreactive inhibin levels. Sluijmer et al. (1993) confirmed that a granulosa cell tumour contained immunoreactive inhibin and that the levels of the peptide in ovarian blood exceeded those in simultaneously sampled peripheral blood. Kauppila et al. (1992) used serum inhibin measurements to monitor the progress of four patients with granulosa cell tumour, who were treated with injections of long-acting gonadotrophin releasing hormone agonist to try to arrest disease progression. Further evidence for the utility of inhibin as an ovarian tumour marker was provided by the recent report, by Healy et al. (1993), that serum inhibin concentrations were elevated in 18 of 22 post-menopausal women with mucinous carcinomas of the ovary, including cystadenocarcinomas and borderline cystic tumours. Levels were elevated in 17% of women with serous carcinomas of the ovary and a similar percentage of those with clear cell carcinomas, undifferentiated carcinomas and other ovarian cancers. All of three women with granulosa cell tumours had greatly elevated levels. Inhibin levels were increased in 7% of patients with non-ovarian pelvic cancers and 27% of patients with benign ovarian diseases. In a control group of 23 post-menopausal women with non-gynaecological cancers, inhibin levels were moderately elevated in only one, a patient with colonic cancer. Because inhibin is normally undetectable in the serum of post-menopausal women, the potential value of the peptide as a tumour marker is particularly significant in women without endogenous ovarian function. Serum inhibin levels are clearly detectable and fluctuate throughout the menstrual cycle (McLachlan et al., 1987) and are thus of much less value during reproductive life, although concentrations in patients with granulosa cell tumours are generally substantially higher than those found during the menstrual cycle. Whether serum inhibin will be a useful marker of recurrence in patients with rnucinous cancers of the ovary or other ovarian tumours where preoperative levels are elevated remains to be determined by future prospective studies. Of particular endocrinological interest in the reports of inhibin over-production in ovarian cancer is that the nature of the tumour product may vary, for example, between granulosa and mucinous tumours. In the former, serum FSH levels were found to vary inversely with inhibin levels, consistent with the production of biologically active inhibin (Healy et al., 1993). In the rnucinous tumours, on the other hand, FSH levels were generally elevated, despite raised inhibin levels, raising the possibility that in these tumours, a biologically inactive a-subunit precursor was being produced. An alternative hypothesis is that mucinous tumours might over-secrete activin, with FSH stimulating activity, a possibility currently under investigation in the author’s laboratory.

Inhibin as a tumour marker.

Objective To investigate the associations between C-reactive protein (CRP), homocysteine levels, use of hormone therapy (HT) and other factorsMethods A 12-year prospective study of 438 Australian-born women (Melbourne Women's Midlife Health Project), who at baseline were aged 45–55 years, had menstruated in the previous 3 months and were not taking HT Fasting blood was collected in the 11th follow-up year for CRP, homocysteine, estradiol and follicle stimulating hormone (FSH) levels Physical measurements and face-to-face interviews obtained information on health and lifestyle variablesResults A total of 258 women (mean age 60 years) participated in the 11th follow-up year Multiple regression analysis found that CRP levels were positively associated with body mass index (p < 0001), HT use (p < 001), and negatively associated with statin use (p < 0005) and exercising (p < 005) In postmenopausal women currently not using HT (n = 173) and after adjusting for body mass index, exercise and smoking, CR

Serum C-reactive protein and plasma homocysteine levels are associated with hormone therapy use and other factors: a population-based study of middle-aged Australian-born women.

BACKGROUND: Testicular regulation of inhibin B may be inOuenced by the germ cell complement. METHODS: We examined the effects of gonadotrophin stimulation on serum inhibin B and pro-aC in 25 normal men at (i) control (stimulation test 1) (ii) after spermatogenic suppression induced by testosterone plus progestin treatment (stimulation test 2) and (iii) during spermatogenic recovery induced by FSH and/or hCG treatment (stimulation test 3). For each test subjects received a single injection of 1200 IU FSH or 5000 IU hCG or both. RESULTS: Inhibin B and pro-aC fell with spermatogenic suppression (75 and 51% of pre-treatment baseline respectively P < 0.05). Inhibin B response to FSH (130±144%) was similar in controls and after germ cell suppression. Pro-aC response after germ cell suppression compared with control was significantly increased (P < 0.05) with both FSH (210±229% versus 140±185%) and hCG (254±261% versus 145%). All treatments partially restored spermatogenesis with no clear relationship apparent between inhibin B and sperm count. CONCLUSIONS: We conclude that: (i) serum inhibin B and pro-aC are only partially gonadotrophin dependent (ii) spermatogenic suppression does not modify inhibin B response to FSH but enhances pro-aC response to both FSH and hCG and (iii) inhibin B is a poor marker of spermatogenesis in this model of gonadotrophic manipulation in normal men. (authors)

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Henry G. Burger

Papers

Inhibin as a tumour marker.

Serum C-reactive protein and plasma homocysteine levels are associated with hormone therapy use and other factors: a population-based study of middle-aged Australian-born women.

Response of serum inhibin B and pro‐αC levels to gonadotrophic stimulation in normal men before and after steroidal contraceptive treatment

lnhibin as a Marker for Granulosa-Cell Tumors

Treatment of estrogen deficiency symptoms in women surviving breast cancer. part 6 : executive summary and consensus statement