The epidemiology of polycystic ovary syndrome. Prevalence and associated disease risks.

Polycystic ovary syndrome is a common problem affecting approximately 5% of women of reproductive age when defined by clinical features of anovulation and hyperandrogenism. Metabolic derangements associated with this condition may predispose to a range of diseases with attendant morbidity and mortality risks. In general, available data support significantly increased rates of type II diabetes mellitus, dyslipidemia, and endometrial cancer in PCOS that are not completely explained by obesity; data also suggest that rates of hypertension, gestational diabetes, and pregnancy-induced hypertension may likewise be increased, although the extent to which obesity mediates these risks is not clear. The increased prevalence of several cardiovascular risk factors in PCOS and limited cross-sectional data suggest that cardiovascular disease should be more likely in PCOS, but prospective data are lacking to confirm this supposition. Limited data have suggested an association between PCOS and ovarian cancer risk and require further study. The present data do not support an increased risk for breast cancer in this condition. Long-term prospective data are clearly needed to better delineate the nature and magnitude of disease risks associated with PCOS, with appropriate adjustment for associated obesity. Such information is a necessary background for understanding the role of established and emerging PCOS therapies, including oral contraceptives, intermittent progesterone, ovulation induction agents, and insulin sensitizers, in modifying such risks. In the meantime, close follow-up of women with PCOS and encouragement of lifestyle practices likely to reduce disease risks, such as regular exercise and weight control, should be standard practice.     

Vitamin D: epidemiology of cardiovascular risks and events

Vitamin D may influence blood pressure through the renin-angiotensin system, parathyroid hormone levels, myocardial function, inflammation, and vascular calcification. In the past several years, a number of high-quality prospective studies have examined 25(OH)vitamin D (25(OH)D) levels in relation to risk of cardiovascular disease (CVD). Studies consistently show that levels of 25(OH)D below 20-25 ng/mL are associated with an increased risk of CVD incidence or mortality. Risk appears especially elevated at 25(OH)D levels below 10 or 15 ng/mL. It is unclear if levels higher that 25 ng/mL provide further benefits for CVD disease. Currently, results from randomized clinical trials are sparse and do not allow a definitive conclusion. Given other potential benefits of vitamin D, and low potential for toxicity, deficient levels below 25-30 ng/mL should be avoided and treated when identified. Further observational and randomized clinical trial data are important to better characterize the optimal range for 25(OH)D.     

Solid tumor risks after high doses of ionizing radiation

There is increasing concern regarding radiation-related second-cancer risks in long-term radiotherapy survivors and a corresponding need to be able to predict cancer risks at high radiation doses. Although cancer risks at moderately low radiation doses are reasonably understood from atomic bomb survivor studies, there is much more uncertainty at the high doses used in radiotherapy. It has generally been assumed that cancer induction decreases rapidly at high doses due to cell killing. However, recent studies of radiation-induced second cancers in the lung and breast, covering a very wide range of doses, contradict this assumption. A likely resolution of this disagreement comes from considering cellular repopulation during and after radiation exposure. Such repopulation tends to counteract cell killing and accounts for the large discrepancies between the current standard model for cancer induction at high doses and recent second-cancer data. We describe and apply a biologically based minimally parameterized model of dose-dependent cancer risks, incorporating carcinogenic effects, cell killing, and, additionally, proliferation/repopulation effects. Including stem-cell repopulation leads to risk estimates consistent with high-dose second-cancer data. A simplified version of the model provides a practical and parameter-free approach to predicting high-dose cancer risks, based only on data for atomic bomb survivors (who were exposed to lower total doses) and the demographic variables of the population of interest. Incorporating repopulation effects provides both a mechanistic understanding of cancer risks at high doses and a practical methodology for predicting cancer risks in organs exposed to high radiation doses, such as during radiotherapy.     

Stereological Studies on Chronic Lymphocytic Leukaemia and Hairy Cell Leukaemia

Using stereological techniques at the ultrastructural level, 7 quantitative parameters for 7 patients with hairy cell leukaemia, 27 patients with chronic lymphocytic leukaemia, and 8 normal individuals. These quantitative data show clear differences between normal lymphocytes, CLL cells and the abnormal cells of HCL. They also show that it may be possible to subdivide CLL into distinct groups on quantitative criteria.     

Long-term risks for thyroid cancer and other neoplasms after exposure to radiation

Radiation-related thyroid cancer continues to be a clinical concern for two reasons: the risks associated with the widespread use of radiation treatments for benign conditions in the middle of the last century persist for decades after exposure; and radiation continues to be an effective component of the treatment of several childhood malignancies. Patients who were irradiated in the head and neck area need to be evaluated for thyroid cancer, benign thyroid nodules, hyperparathyroidism, salivary-gland neoplasms and neural tumors, including acoustic neuromas. Radiation-related thyroid cancers appear to have the same clinical behavior as other thyroid cancers, but many irradiated patients are entering the age range when more aggressive neoplasms occur. In this paper, we review how to approach the clinical management of a patient with a history of radiation exposure in the thyroid area, and how to treat radiation-exposed patients who develop related neoplasms, especially thyroid cancer.     

Chronic Lymphocytic Leukaemia Associated with Acute Myelomonocytic Leukaemia

S ummary . An elderly male, with no previous medical history of note, presented with haematological changes of chronic lymphocytic leukaemia combined with acute myelomonocytic leukaemia. This patient had never received cytotoxic drugs or radiotherapy.     

Prolymphocytic Leukaemia

S ummary . The clinical and haematological features of 15 patients with a rare variant of chronic lymphocytic leukaemia (CLL) are described. The disease predominantly affects males in the sixth and seventh decades of life and presenting symptoms include fatigue, weakness, weight loss, sweats and fevers. Massive enlargement of the spleen (mean weight at autopsy 1383 g, range 227–3500 g) and to a lesser extent of the liver (mean weight 2445 g, range 2030–3079 g) are regular findings. In contrast, peripheral lymphadenopathy is inconspicuous or absent. The characteristic cell in the peripheral blood is a relatively large lymphoid cell with a large vesicular nucleolus, relatively well-condensed nuclear chromatin and moderate amount of cytoplasm. The counts of these cells in the peripheral blood at the time of diagnosis are very high (mean 355 000/μl, range 26000–1 11 000/μl). The clinical response to methods of treatment that are usually effective in classical CLL (particularly alkylating agents and corticosteroid drugs) is uniformly poor and the patients'survival after diagnosis is in most cases quite short.
We believe that the clinical and haematological features of this condition justify its recognition separately from classical CLL, from lymphosarcoma cell leukaemia and from acute lymphoblastic leukaemia. We have therefore designated it 'prolymphocytic leukaemia'. On the basis of a single case we suggest that further trials of splenectomy are indicated.