Association between cardiovascular risk-factors and venous thromboembolism in a large longitudinal study of French women.

BACKGROUND: Previous studies have shown conflicting results regarding the influence of cardiovascular risk-factors on venous thromboembolism. This study aimed to determine if these risk-factors, i.e. physical activity, smoking, hypertension, dyslipidaemia, and diabetes, were associated with the risk of venous thromboembolism, and to determine if these associations were confounded by BMI. METHODS: We used data from the E3N cohort study, a French prospective population-based study initiated in 1990, consisting of 98,995 women born between 1925 and 1950. From the women in the study we included those who did not have prevalent arterial disease or venous thromboembolism at baseline; thus 91,707 women were included in the study. Venous thromboembolism cases were self-reported during follow-up, and verified via specific mailings to medical practitioners or via drug reimbursements for anti-thrombotic medications. Hypertension, diabetes and dyslipidaemia were self-reported validated against drug reimbursements or specific questionnaires. Physical activity, and smoking were based on self-reports. Cox-models, adjusted for BMI and other potential risk-factors were used to determine hazard ratios for incident venous thromboembolism. RESULTS: During 1,897,960 person-years (PY), 1, 649 first incident episodes of thrombosis were identified at an incidence rate of 0.9 per 1000 PY. This included 505 cases of pulmonary embolism and 1144 cases of deep vein thrombosis with no evidence of pulmonary embolism. Hypertension, dyslipidaemia, diabetes, smoking and physical activity were not associated with the overall risk of thrombosis after adjustment for BMI. CONCLUSIONS: Traditional cardiovascular risk factors were not associated with the risk of venous thromboembolism after adjustment for BMI. Hypertension, dyslipidaemia and diabetes may not be risk-factors for venous thromboembolism.

Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study.

BACKGROUND: Current use of menopausal hormone therapy (HT) increases the risk of venous thromboembolism (VTE) and the formulations used may affect risk. METHODS: A total of 1,058,259 postmenopausal UK women were followed by record linkage to routinely collected National Health Service hospital admission and death records. HT use and risk of VTE was examined using Cox regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: During 3.3 million years of follow-up, 2200 women had an incident VTE, diagnosed, on average, 1.5 years after last reporting HT use. RRs in current vs. never users at last reporting varied by HT formulation: the risk was significantly greater for oral estrogen-progestin than oral estrogen-only therapy (RR = 2.07 [95%CI, 1.86-2.31] vs. 1.42 [1.21-1.66]), with no increased risk with transdermal estrogen-only therapy (0.82 [0.64-1.06]). Among users of oral estrogen-progestin, the risk from HT varied by progestin type, with significantly greater risks for preparations containing medroxyprogesterone acetate than other progestins (2.67 [2.25-3.17] vs. 1.91 [1.69-2.17]; Pheterogeneity = 0.0007). Current users of oral HT at last reporting had twice the risk of VTE in the first 2 years after starting HT than later (Pheterogeneity = 0.0006). Associations were similar for deep vein thrombosis with and without pulmonary embolism. Over 5 years, 1 in 660 who had never used HT were admitted to hospital for (or died from) pulmonary embolism, compared with 1 in 475 current users of oral estrogen-only HT,1 in 390 users of estrogen-progestin HT containing norethisterone/norgestrel, and 1 in 250 users of estrogen-progestin HT containing medroxyprogesterone acetate. CONCLUSIONS: The risk of VTE varied considerably by HT formulation, being greatest in users of oral estrogen-progestin HT, especially formulations containing medroxyprogesterone acetate.

Effect of NFE2L2 genetic polymorphism on the association between oral estrogen therapy and the risk of venous thromboembolism in postmenopausal women.

Oral, but not transdermal, estrogen therapy increases the risk of venous thromboembolism (VTE) in women who are past menopause. Data from the Estrogen and Thromboembolism Risk (ESTHER) study were used to investigate the effects of the genetic polymorphism of NFE2L2 rs6721961, which may impair Nrf2-dependent hepatic conjugation of estrogen metabolites. As compared with nonusers, the odds ratio (OR) for VTE in current users of oral estrogens was 2.5 (95% confidence interval (CI): 1.3-4.8) in patients with wild-type NFE2L2 and 17.9 (95% CI: 3.7-85.7) in those with the polymorphism (interaction, P = 0.01).

Protein S inherited qualitative deficiency: novel mutations and phenotypic influence.

BACKGROUND: Only a few mutations associated with qualitative protein S deficiency have already been described. Sensitivity and specificity for type II PROS1 mutations of commercially available reagents for measuring Protein S (PS) activity are not well established. Whether these mutations are significant risk factors for thrombosis remains an unresolved question. METHODS: In order to address the first point, we present and discuss the results of PROS1 analysis performed in the 30 probands with type II PS-inherited deficiency suspicion and 35 relatives, studied in our laboratory between 2000 and 2008. In order to investigate the influence of type II mutations on the coagulability level, thrombin generation tests were performed on plasma from 102 PROS1 type II, type I/III or PS Herleen mutation heterozygous carriers and controls. RESULTS: Mutations (12 novel, six already described) which probably explain the qualitative phenotype, were found in 27 (90%) out of the 30 probands studied. In relatives, 78% of heterozygotes presented with a type II phenotype. An APC resistance phenotype was documented in type II and type I/III defects heterozygous carriers; however, the effect of type II was milder than the effect of type I/III PS mutations. CONCLUSIONS: A PS functional assay (Staclot PS, Stago) was efficient in screening for PROS1 type II defects, particularly in probands. A significant positive influence of type II mutations on ex vivo thrombin generation was demonstrated. However, whether these mutations increase the risk of venous thromboembolism requires further investigation.

Hormone therapy and risk of venous thromboembolism among postmenopausal women.

Venous thromboembolism, either deep vein thrombosis or pulmonary embolism, is a serious side-effect of postmenopausal hormone therapy. Current use of oral estrogens increases the risk of venous thromboembolism, especially during the first year of treatment, but past users of hormone therapy have a similar risk as never-users. Among women at high risk for venous thromboembolism (for example, thrombogenic mutations, obesity), oral estrogens use further enhances the thrombotic risk. Recent studies have shown that transdermal estrogens might be safe with respect to thrombotic risk. The difference in thrombotic risk between oral and transdermal estrogens may be partially explained by changes in hemostasis. Few data are currently available regarding the impact of progestogens on venous thromboembolism risk, but norpregnane derivatives might be thrombogenic. Individual assessment of the benefit-risk ratio is needed before initiating treatment and oral estrogens should be avoided among women at high risk for venous thromboembolism.

Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. The ESTHER Study.

BACKGROUND: Oral estrogen use and elevated body mass index (BMI) increase the risk of venous thromboembolism (VTE). Recent data suggest that transdermal estrogen might be safe with respect to thrombotic risk. However, the impact of transdermal estrogen on the association between overweight (25 kg m(-2) < BMI < or = 30 kg m(-2)) or obesity (BMI >30 kg m(-2)) and VTE risk has not been investigated. METHODS: We carried a multicenter case-control study of VTE among postmenopausal women aged 45-70 years, between 1999 and 2005, in France. Case population consisted of women with a first documented idiopathic VTE. We recruited 191 hospital cases matched with 416 hospital controls and 62 outpatient cases matched with 181 community controls. RESULTS: The odds ratio (OR) for VTE was 2.5 [95% confidence interval (CI):1.7-3.7] for overweight and 3.9 (95% CI: 2.2-6.9) for obesity. Oral, not transdermal, estrogen was associated with an increased VTE risk (OR = 4.5; 95% CI: 2.6-7.7 and OR = 1.1; 95% CI: 0.7-1.7, respectively). Compared with non-users with normal weight, the combination of oral estrogen use and overweight or obesity further enhanced VTE risk (OR = 10.2; 95% CI: 3.5-30.2 and OR = 20.6; 95% CI: 4.8-88.1, respectively). However, transdermal users with increased BMI had similar risk as non-users with increased BMI (OR = 2.9; 95% CI: 1.5-5.8 and OR = 2.7; 95% CI: 1.7-4.5 respectively for overweight; OR = 5.4; 95% CI: 2.1-14.1 and OR = 4.0; 95% CI: 2.1-7.8 respectively for obesity). CONCLUSIONS: In contrast to oral estrogen, transdermal estrogen does not confer an additional risk of idiopathic VTE in women with increased BMI. The safety of transdermal estrogen on thrombotic risk has to be confirmed.

Indicators of lifetime endogenous estrogen exposure and risk of venous thromboembolism.

BACKGROUND: Lifetime estrogen exposure has been related to breast cancer risk, osteoporosis, and cardiovascular disease but data on venous thromboembolism (VTE) risk are limited. METHODS: Data from a hospital-based case-control study among 608 postmenopausal women (191 with a first episode of idiopathic VTE and 417 age-matched controls) were used to determine whether estrogen exposure, as assessed by age at menopause [classified as early (< or = 45 years), normal (46-54 years) and late menopause (> or = 55 years)] and parity, was associated with the risk of VTE. RESULTS: After adjustment for potential confounding variables, the risk of VTE was increased with each year's delay in the menopause [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.02-1.10, P < 0.0075]. When compared with women with normal menopause used as a reference, the adjusted OR for VTE was 0.59 (95% CI = 0.36-0.97) and 2.53 (95% CI = 1.28-4.99) for women with early menopause and late menopause, respectively (P = 0.001). Adjusted OR for VTE was also higher for women with more than two children when compared with those with less than or equal to two children (1.56, 95% CI = 1.03-2.34, P = 0.03). The lowest risk of VTE was observed in women with early menopause and lower parity (adjusted OR = 0.60, 95% CI = 0.30-1.24), the highest risk was among women with late menopause who have had more than two children (adjusted OR = 3.41, 95% CI = 1.46-9.25). CONCLUSION: These results show that the longer exposure to endogenous estrogen is associated with an increased VTE risk.

Long-term dysregulation of circadian and 17-beta estradiol-induced LH, prolactin and corticosterone secretion after dimethylbenz (a) anthracene administration in the Sprague-Dawley female rat.

A single intragastric administration of 7,12-dimethylbenz (a) anthracene (DMBA) has been shown, when given at 55-60 days of age, to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal (HPG) axis, including attenuation of the preovulatory Luteinizing Hormone (LH) and Gonadotropin-Releasing Hormone (GnRH) release and amplification of the preovulatory 17beta-Estradiol (E(2)) surge. In this study, we examined the hypothesis that a single administration of DMBA could also, in the long range, induce disturbances of others neuroendocrine axis, like the Hypothalamic-Pituitary-Adrenal (HPA) axis and/or the Lactotroph axis. Sprague-Dawley rats, 55-60 days of age, received, on the day of Estrous of the Estrous cycle, a single administration of 15 mg of DMBA delivered by intragastric intubation. Then, they were ovariectomized 5 days later. One month later, (1) Two groups of animal were sacrificed by decapitation at 09:00 a.m. and 05:00 p.m. to record the circadian rhythm of plasma LH, Prolactin (PRL) and corticosterone, (2) Three other groups of animal were sacrificed by decapitation at three different times after a morning subcutaneous administration of 50 microg/kg of Estradiol Benzoate (EB), to induce a negative and positive feed-back of the secretion of LH. Then, plasma LH, PRL and corticosterone concentrations were measured. After DMBA administration, (1) the negative--but not the positive--LH feed-back was seen, (2) the PRL circadian rhythm was blunted and the corticosterone circadian rhythm was almost absent, (3) the increase in PRL or Corticosterone plasma concentration was significantly reduced. In conclusion, a single administration of DMBA provokes a long-term dysregulation of not only the HPG axis but also of the lactotroph and HPA axis. These dysregulations, along with the already evidenced long-term inhibition of DMBA upon Melatonin secretion from the pineal gland, might accelerate the promotion of mammary tumors induced by the mammary carcinogen.

Anomalous LO phonon lifetime in AlAs.

The temperature dependence of the frequencies and linewidths of the Raman-active longitudinal optical (LO) phonons in GaAs and AlAs have been measured. The low-temperature lifetime of the LO phonon in AlAs is found to be 9.7 ps, very close to the corresponding GaAs value of 9.5 ps. This contradicts early theoretical predictions. The agreement between theory and experiment can be restored when the accidental degeneracy between the AlAs LO phonon frequency and a feature in the two-phonon density of states is taken into account.

Use of hypnosis in controlling lumbar puncture distress in an adult needle-phobic dementia patient.

Lumbar punctures are often vital to the medical management of patients with suspected organic pathology, yet they are commonly met with such distress that medical risk is significantly increased, and patient rapport is significantly decreased, further compromising medical treatment. Although the use of hypnosis for lumbar punctures is well established in pediatric patients, no literature exists for adult patients. Similarly, there is no extant research regarding hypnosis for dementia patients, likely due to the limiting factors of impaired attention and concentration. With these factors in mind, a method for incorporating hypnosis into a lumbar puncture procedure is described for a needle-phobic adult patient suffering from dementia.

["Pseudomonas aeruginosa" in the hospital of Avellino, and the presence of colonies in the obstetric, pediatric and neonatal wards. A microbiological study of the environment and of hygienic and prophylactic measures (author's transl)]. / Ospitalismo da "Pseudomonas aeruginosa" nell'ospedale di Avellino. Colonizzazione delle divisioni di ostetricia, pediatria e della sezione neonatale. II. Studio microbiologico ambientale ed interventi di igiene e profilassi.

We observed two episodes of Pseudomonas aeruginosa colonisation taking place in a Hospital. This organism was isolated in a pure culture from the faeces of 41 newborn children, many patients and from a large part on the obstetrics and pediatry division's staff. The AA. investigated the ways of spreading of this germ which caused both in the adults and the babies, no sign of illness. Biotypes one causing the first episode and the other related to the second one were isolated them showed a wide spectrum of resistance to several antibiotics and they of disappeared after accurate measures of hygiene concerning persons and places were adopted.