Alcohol and ovarian cancer risk: results from the Netherlands Cohort Study

OBJECTIVE: To study alcohol consumption in relation to ovarian cancer risk in a prospective cohort study. METHODS: The Netherlands Cohort Study on diet and cancer was initiated in 1986. A self-administered questionnaire on dietary habits and other risk factors for cancer was completed by 62,573 postmenopausal women. Follow-up for cancer was established by annual record linkages with the Netherlands Cancer Registry. After 9.3 years of follow-up, 214 incident invasive epithelial ovarian cancer cases and 2211 subcohort members with complete data on alcohol intake were available for analysis. All incidence rate ratios (RRs) were corrected for age, use of oral contraceptives, parity, height, body mass index, energy intake and current cigarette smoking. RESULTS: The RRs of ovarian cancer for women who consumed up to 5, 15 and >15 g of alcohol per day were 1.13 (95% confidence interval, 95% CI = 0.79-1.63), 0.85 (95% CI = 0.53-1.37) and 0.92 (95% CI = 0.55-1.54), respectively, compared to non-drinkers. Alcohol consumption in the form of wine, beer or liquor was not associated with ovarian cancer risk. CONCLUSION: These data do not suggest a major association between alcohol intake and ovarian cancer risk in this population.     

Tobacco and Alcohol Consumption and the Risk of Non-Hodgkin Lymphoma

OBJECTIVE: The aim was to test whether non-Hodgkin lymphoma (NHL) is associated with smoking or alcohol. METHODS: A case-control study recruited NHL cases aged 18-64 in parts of England between 1998 and 2001. One control was matched to each case on sex, date of birth and area of residence. Self-reported histories of tobacco and alcohol consumption were collected during face-to-face interviews. RESULTS: Among 700 cases and 915 controls, no association of smoking with the risk of NHL was observed [odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.85-1.28]. Risks were not raised with age started smoking, number of years smoked, and number of years stopped smoking. Compared with persons who drank alcohol once or twice a week, neither abstainers (OR = 1.03, 95% CI: 0.64-1.67), nor consumers of alcohol one to five times a year (OR = 1.35, 95% CI: 0.95-1.93), one to two times a month (OR = 1.20, 95% CI: 0.87-1.65), three to four times a week (OR = 0.82, 95% CI: 0.62-1.10), or most days (OR = 0.94, 95% CI: 0.70-1.25) increased their risk of developing NHL. Average daily volume or high occasional alcohol consumption were not associated with NHL. CONCLUSIONS: NHL was not associated with smoking or alcohol, but collaborative studies could further investigate the risks of rarer WHO subtypes following these exposures.     

Influence of short-term dietary weight loss on cortisol secretion and metabolism in obese men

OBJECTIVES: Obesity is associated with increased inactivation of cortisol by hepatic A-ring 5alpha- and 5beta-reductases, impaired hepatic regeneration of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), but increased subcutaneous adipose 11HSD1 activity enhancing local cortisol levels in fat. Cause and effect between obesity and abnormal cortisol metabolism is untested. DESIGN: Acute weight loss was induced by very low calorie diet (VLCD) or starvation in obese men. METHODS: Otherwise healthy males (aged 20-55 years; body mass index (BMI) 30-40 kg/m2) were studied after 6 days on a weight maintenance diet; then after either 6 days of starvation (n=6) or 3 weeks of VLCD (2.55 MJ; n=6); then after 1 week of weight maintenance; and finally after 2 weeks of being allowed to feed ad libitum. Plasma samples were obtained from indwelling cannulae at 0930 h and 1815 h and a 24 h urine collection was completed for analysis of cortisol metabolites by gas chromatography/mass spectrometry. RESULTS: Data are mean+/-S.E.M. BMI fell (kg/m3) from 34.8+/-0.8 at baseline to 31.8+/-1.4 on VLCD and 32.7+/-1.1 on starvation. Starvation caused a rise in plasma cortisol (at 0930 h from 143+/-17 to 216+/-11 nM, P<0.001) but no change in total urinary cortisol metabolites. VLCD did not alter plasma cortisol and markedly reduced cortisol metabolite excretion (from 15.8+/-1.1 mg/day at baseline to 7.0+/-1.1 mg/day, P<0.001). Relative excretion of 5alpha-reduced cortisol metabolites fell on both diets, but there were no changes in cortisol/cortisone metabolite ratios reflecting 11HSD activities. CONCLUSIONS: Weight loss with VLCD in obesity reverses up-regulation of hepatic A-ring reductases and normalises cortisol production rate; in contrast, starvation produces acute stress and further activation of cortisol secretion. We suggest that activation of cortisol secretion is not an irreversible intrinsic abnormality in obese patients, and speculate that dietary content has an important influence on the neuroendocrine response to weight loss.     

Magnitude and impact of treatment delays on weeknights and weekends in patients undergoing primary angioplasty for acute myocardial infarction (the cadillac trial)

In 2,082 patients in the CADILLAC trial, the outcomes of patients presenting during peak hours were compared with those presenting during peak hours (Monday to Friday 8a.m. to 8 p.m., n = 1,047, 51%) were compared with those of patients presenting during off-peak hours (weeknights from 8 p.m. to 8 a.m. and weekends, n = 989, 49%). Although treatment times to percutaneous coronary intervention (PCI) were delayed approximately 21 minutes, in patients with acute myocardial infarctions occurring on weeknights and weekends, this modest delay did not adversely affect procedural success, myocardial recovery, or survival after PCI.     

Clonidine in acute aversive inner tension and self-injurious behavior in female patients with borderline personality disorder

BACKGROUND: States of strong aversive inner tension and dissociative symptoms are clinical hallmarks of borderline personality disorder and major reasons for self-injurious behavior, a severe clinical condition for which there are no established pharmacologic treatment options. METHOD: The acute effect of 75 and 150 microg of clonidine administered orally in acute states of strong aversive inner tension and urge to commit self-injurious behavior was examined in 14 female patients meeting DSM-IV criteria for borderline personality disorder. Before and 30, 60, and 120 minutes after administration of clonidine, aversive inner tension and dissociative symptoms were assessed using a self-rating instrument for aversive inner tension and dissociation (Dissociation-Tension-Scale acute), and the urge to commit self-injurious behavior and suicidal ideations were assessed using self-rating Likert scales. Blood pressure and heart rate were monitored during the trial. RESULTS: Aversive inner tension and urge to commit self-injurious behavior before administration of clonidine were strong. After administration of clonidine in both doses, aversive inner tension, dissociative symptoms, urge to commit self-injurious behavior, and suicidal ideations significantly decreased. The strongest effects were seen between 30 and 60 minutes after drug intake and correspond to the pharmacokinetics of clonidine with maximum plasma concentrations after 1 hour. Blood pressure and aversive inner tension and dissociative symptoms were positively correlated before and after administration of clonidine. CONCLUSION: Orally given clonidine may be effective for treatment of acute states of aversive inner tension, dissociative symptoms, and urge to commit self-injurious behavior in female patients with borderline personality disorder. Further placebo-controlled studies with larger populations are needed to confirm this finding.     

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.     

Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin

Pregnancy is a major risk factor for venous thromboembolism (VTE), and low-molecular weight heparin (LMWH) seems to be safe and effective in pregnant women. Normal pregnancy is accompanied by a state of hypercoagulability, indicated by an increase in markers of coagulation activation. In a prospective cohort study, we followed 61 women who received LMWH thromboprophylaxis throughout pregnancy because of a history of VTE, hereditary thrombophilia and/or previous pregnancy-related complications. The control group consisted of 113 healthy pregnant women without antithrombotics. D-Dimer, prothrombin fragment F1+2 (F1+2) and the resistance to activated protein C (APC-ratio) were measured in all women during the first, second and third trimester. Patients and controls did not significantly differ with regard to baseline characteristics and pregnancy outcome. A (recurrent) VTE was seen in one patient despite LMWH. D-Dimer levels significantly increased among patients and controls during pregnancy (p < 0.0001), and were significantly higher among patients compared with the controls (p <0.0001) [395 ng/ml (95% CI 340-458) and 249 ng/ml (95%CI 234-266); 710 ng/ml (95% CI 602-838) and 475 ng/ml (95% CI 431-523); 1089 ng/ml (95% CI 931-1273) and 822 ng/ml (95% CI 741-911); respectively]. Levels of F1+2 significantly increased while the APC-ratio significantly decreased during pregnancy among patients and controls. Despite LMWH, pregnancy is accompanied by a substantial activation of the coagulation system.     

Two visual motion processing deficits in developmental dyslexia associated with different reading skills deficits

Developmental dyslexia is associated with deficits in the processing of visual motion stimuli, and some evidence suggests that these motion processing deficits are related to various reading subskills deficits. However, little is known about the mechanisms underlying such associations. This study lays a richer groundwork for exploration of such mechanisms by more comprehensively and rigorously characterizing the relationship between motion processing deficits and reading subskills deficits. Thirty-six adult participants, 19 of whom had a history of developmental dyslexia, completed a battery of visual, cognitive, and reading tests. This battery combined motion processing and reading subskills measures used across previous studies and added carefully matched visual processing control tasks. Results suggest that there are in fact two distinct motion processing deficits in developmental dyslexia, rather than one as assumed by previous research, and that each of these deficits is associated with a different type of reading subskills deficit. A deficit in detecting coherent motion is selectively associated with low accuracy on reading subskills tests, and a deficit in discriminating velocities is selectively associated with slow performance on these same tests. In addition, evidence from visual processing control tasks as well as self-reports of ADHD symptoms suggests that these motion processing deficits are specific to the domain of visual motion, and result neither from a broader visual deficit, nor from the sort of generalized attention deficit commonly comorbid with developmental dyslexia. Finally, dissociation between these two motion processing deficits suggests that they may have distinct neural and functional underpinnings. The two distinct patterns of motion processing and reading deficits demonstrated by this study may reflect separable underlying neurocognitive mechanisms of developmental dyslexia.