Reproductive factors in Hodgkin's disease in women

Reproductive factors have been suggested to have an impact on the development of Hodgkin's disease (HD) in women. In the San Francisco Bay Area, the authors conducted a population-based case-control study addressing the effects of reproductive experience and hormone use on HD risk. Cases were 370 women with HD diagnosed at ages 19-79 years between July 1988 and December 1994. Controls were 450 community women found through random digit dialing. Among the 312 cases and 325 controls interviewed, HD risk was related to parity versus nulliparity but only among never nursers (odds ratio (OR)=2.2, 95% confidence interval (CI): 1.0, 5.0). Risk was marginally related to having uterine fibroids (OR=0.6, 95% CI: 0.5, 1.0) and long-term versus short-term hormone use (OR=0.7, 95% CI: 0.4, 1.0) and was significantly related to recurrent miscarriage (OR=2.8, 95% CI: 1.1, 7.4). Among women aged 35-54 years, for whom the sex difference in incidence is largest, nursing decreased risk; among never nursers, a parity of 1 lowered risk and higher parity increased risk; long-term hormone use lowered risk; and recurrent miscarriage increased risk. Among women under age 35 years, endometriosis lowered HD risk; the lack of significant findings for most other variables may reflect selection bias in controls. Among older women, no significant associations were observed, although hormone use appeared to be protective. These data suggest that steroid hormones may affect HD development.     

Endometrial evaluation with transvaginal US and hysterosonography in asymptomatic postmenopausal women with breast cancer receiving tamoxifen

PURPOSE: To determine performance characteristics of transvaginal ultrasonography (US) and hysterosonography for diagnosing endometrial abnormality in asymptomatic postmenopausal women with breast cancer receiving tamoxifen. MATERIALS AND METHODS: The authors prospectively examined 138 women receiving tamoxifen by using transvaginal US, hysterosonography, and office hysteroscopy. The combined hysteroscopic-histopathologic diagnosis was the reference standard. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of transvaginal US and hysterosonography were calculated. RESULTS: All 138 women underwent transvaginal US; 104, successful hysterosonography; and 117, successful hysteroscopy. Uterine abnormality was present in 47 (40.2%) of 117 women: 45 with polyps and two with submucosal fibroids. Receiver operating characteristic curve analysis revealed 6 mm to be the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities. When a thickness greater than 6 mm or a focal endometrial finding was considered abnormal, transvaginal US had a sensitivity of 85.1% and a specificity of 55.7%. In 92 women who completed transvaginal US, hysterosonography, and hysteroscopy, hysterosonography was more specific (79.2%; P =.008) but not significantly more sensitive (89.7%; P =.508) than transvaginal US. When women with abnormal transvaginal US findings were further examined with hysterosonography, the sequential combination of transvaginal US and hysterosonography was more specific (77.1%) than transvaginal US alone (P <.001), without a significant decrease in sensitivity (78.7%; P =.25). CONCLUSION: In asymptomatic postmenopausal women receiving tamoxifen, 6 mm is the optimal endometrial thickness cutoff for diagnosing endometrial abnormalities with transvaginal US. Further examination with hysterosonography can improve specificity by reducing the high false-positive rate of transvaginal US.     

Understanding the metabolome – challenges for metabolomics

Metabolomics is a comprehensive method for metabolite assessment, measuring the overall metabolic signature of biological samples. This approach opens up many possibilities in areas such as new biomarker discovery and hypothesis generation. The application of metabolomics is growing rapidly but many challenges must first be addressed before it can reach its true potential. Metabolomics organisations are currently working towards guidelines for commonality in metabolomics experiments as development of optimal methodologies and study designs are needed. Blood and urine appear to be the most useful biofluids for nutrition research, but an array of biofluids, cells and tissues can be used. The key steps required for the successful understanding of metabolomics data are compound identification and biological interpretation. Many databases of compounds are available but are still under construction with much information remaining to be populated. An understanding of the effects of normal physiological variation on metabolic profiles is essential for accurate interpretation of profile changes, particularly in human studies, because of diversity in lifestyle and environmental factors. The effects of factors such as ethnicity, gender, age, body composition, health, dietary intake, physical activity, gut microflora and stress need to be further explored in order to advance the understanding of the human metabolome and therefore improve data interpretation.     

Vasoconstriction to endothelin-1 is blunted in non-insulin-dependent diabetes: a dose-response study

The haemodynamic hypothesis for the pathogenesis of diabetic microangiopathy argues that an initial increase in microvascular blood flow leads to microvascular sclerosis and disturbed autoregulation. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide that contributes to basal vascular tone. Impairment of the vasoconstrictor response to ET-1 could result in hyperperfusion and subsequent microvascular damage. The purpose of this study was to determine whether vascular responses to ET-1 are impaired in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes). Ten patients with type 2 diabetes and nine control subjects underwent brachial artery cannulation. Forearm blood flow was measured using strain-gauge venous occlusion plethysmography. ET-1 in three doses of 5, 10, and 20 pmol/min and 0.9% saline placebo was infused in a balanced double-blind randomised manner. Vascular smooth muscle function also was assessed using sodium nitroprusside. Control subjects showed vasoconstriction to ET-1 of 5 (p < 0.05), 10 (p < 0.05), and 20 pmol/min (p < 0.01). In the diabetic group, there was no significant response to ET-1 at 5 pmol/min (p > 0.05); however, significant vasoconstriction developed at 10 and 20 pmol/min (p < 0.01). There was a significant difference in response to ET-1 at 5 pmol/min between the diabetic and control groups (p < 0.05). Responses to sodium nitroprusside were similar in both groups (p > 0.05). Patients with type 2 diabetes have a blunted vasoconstrictor response to ET-1 despite preserved vascular smooth muscle function.     

The nutritional status of ambulatory elderly type II diabetic patients

We have previously found that malnutrition is common among elderly diabetic patients in nursing homes. To determine the prevalence and nature of nutritional problems among ambulatory elderly diabetic patients, 60 Type II insulin-treated diabetic outpatients 65 years of age or older (mean ± SD 69.1±4.13 years) were evaluated consecutively. Anthropometric parameters and serum biochemical indices of protein calorie nutrition were assessed. The results were compared with those of 63 age-matched nondiabetic patients evaluated concurrently. The two groups, apart from the diagnosis of diabetes and its treatment, were comparable insofar as the number of medical problems and number of medications used. Diabetic patients were not significantly different from the controls in mean body weight and height, but mean body mass index (BMI) was slightly higher in diabetic patients. The lean body weight was not different compared to controls, but percent body fat was higher in diabetic patients. The adipose tissue was preferentially located in the upper body segment primarily in the subscapular and abdominal regions as evidenced by skinfold thickness measurements. There were no differences between the groups in midarm and midthigh muscle circumference. The serum triglyceride levels in the diabetic patients (335.8 ± 560.6 mg/dl) were significantly higher than those of controls (150.1 ± 57.7 mg/dl). There were no significant differences in total lymphocyte count or serum levels of cholesterol, albumin, prealbumin, transferrin and retinol binding protein. It is concluded that among ambulatory, elderly, diabetic patients, being underweight is rare.