Examining the relationship of concurrent obesity and tobacco use disorder on the development of substance use disorders and psychiatric conditions: Findings from the NESARC-III.

Background: Multimorbidity is linked to worse health outcomes than single health conditions. However, recent studies show that obesity may reduce the risk of developing substance use disorders (SUDs), particularly in vulnerable populations. We investigated how comorbid obesity and tobacco use disorder (TUD) relate to the risk of SUDs and psychiatric conditions. Methods: Data was used from 36,309 individuals who completed the National Epidemiological Survey on Alcohol and Related Conditions - Wave III. Individuals who met the DSM-5 criteria for TUD in the last year were defined as the TUD group. Obesity was defined as having a body mass index (BMI) greater than 30 kg/m2. Using this information, individuals were grouped into categories, with people being identified as either having obesity, TUD, both obesity and TUD, or not having either obesity or TUD (comparison). Groups were compared against their comorbid diagnoses of either an additional SUD or psychiatric conditions. Results: Controlling for demographic characteristics, we found that individuals with obesity including those individuals with TUD, had lower rates of comorbid SUD diagnosis than individuals with TUD alone. Additionally, individuals with combined TUD and obesity, and those with TUD alone, had the highest rates of comorbid psychiatric disorder diagnosis. Conclusions: The current study aligns with previous research suggesting that obesity may reduce risk of substance use disorders, even in individuals who have other risk factors promoting harmful substance use (e.g., tobacco use). These findings may inform targeted intervention strategies for this clinically relevant subpopulation.

Effects of a brief mindfulness intervention on negative affect and urge to drink among college student drinkers.

Several theories have proposed that negative affect (NA) plays a large role in the maintenance of substance use behaviors - a phenomenon supported in laboratory-based and clinical studies. It has been demonstrated that mindfulness meditation can improve the regulation of NA, suggesting that mindfulness may be very beneficial in treating problematic substance use behavior. The current study tested whether a brief mindfulness meditation would lower levels of NA, increase willingness to experience NA, lower urges to drink, and increase time to next alcoholic drink in a sample of at-risk college student drinkers (N = 207). Participants were randomized to one of three brief interventions (mindfulness, relaxation, or control) followed by an affect manipulation (negative or neutral stimuli). Affect and urge were measured prior to intervention (Time 1 [T1]), after intervention but prior to affect manipulation (Time 2 [T2]), and immediately after the affect manipulation (Time 3 [T3]). Levels of mindfulness and relaxation were assessed from T1-T3. The additional measures of willingness to continue watching NA images and time to next alcoholic drink were examined at T3. Results indicated that the mindfulness intervention increased state mindfulness and relaxation, and decreased NA immediately following the mindfulness intervention. However, the mindfulness intervention did not influence responses to NA induction on any of the outcome variables at T3. One potential explanation is that the mindfulness intervention was not robust enough to maintain the initial gains made immediately following the intervention.

Carbon monoxide attenuates bacteria-induced Endothelin-1 expression in second trimester placental explants.

INTRODUCTION: The pro-inflammatory mediator and potent vasoconstrictor Endothelin-1 (ET-1) is known to be expressed in the placenta. We have recently demonstrated that very low, non-toxic doses of carbon monoxide (CO), prevented infection-induced preterm birth in mice. However the effect(s) of CO on human gestational tissues is yet to be fully explored. We hypothesize that CO will have a protective role against inflammation-induced E. coli by down-regulating the ET axis in placental explants. METHODS: Twenty placentas from elective termination of pregnancy in the second trimester were analyzed with or without exposure to heat killed E. coli over the course of 30 h. Placental ET-1, along with its biologically inactive precursor Big ET-1, and Endothelin Converting Enzyme-1 (ECE-1, responsible for the cleavage of Big ET-1 to ET-1), were analyzed by ELISA. Gene expression for ET-1 (EDN1), ECE-1 and the ETA receptor (EDNRA) were analyzed using qPCR. Localization of ET-1 expression was also demonstrated using immunohistochemistry. RESULTS: E. coli significantly increased ET-1 transcription and secretion of BIG ET-1 and ET-1 in a time dependant manner which was ameliorated when exposed to CO at later time points. In the presence of CO, mRNA levels of ECE-1 were significantly reduced at 3 and 24 h, while EDNRA was significantly reduced at 6 and 18 h. CONCLUSIONS: Up-regulation of ET-1 production in human placenta in the setting of infection can be attenuated by low doses of CO. Our results further explore the anti-inflammatory and regulatory mechanism(s) of CO on the ET axis components at the maternal fetal interface.

Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta.

Polybrominated diphenyl ether(s) (PBDE) are ubiquitous environmental contaminants that bind and cross the placenta but their effects on pregnancy outcome are unclear. It is possible that environmental contaminants increase the risk of inflammation-mediated pregnancy complications such as preterm birth by promoting a proinflammatory environment at the maternal-fetal interface. We hypothesized that PBDE would reduce IL-10 production and enhance the production of proinflammatory cytokines associated with preterm labor/birth by placental explants. Second-trimester placental explants were cultured in either vehicle (control) or 2 µM PBDE mixture of congers 47, 99 and 100 for 72 h. Cultures were then stimulated with 10(6) CFU/ml heat-killed Escherichia coli for a final 24 h incubation and conditioned medium was harvested for quantification of cytokines and PGE(2). COX-2 content and viability of the treated tissues were then quantified by tissue ELISA and MTT reduction activity, respectively. PBDE pre-treatment reduced E. coli-stimulated IL-10 production and significantly increased E. coli-stimulated IL-1ß secretion. PBDE exposure also increased basal and bacteria-stimulated COX-2 expression. Basal, but not bacteria-stimulated PGE(2), was also enhanced by PBDE exposure. No effect of PBDE on viability of the explants cultures was detected. In summary, pre-exposure of placental explants to congers 47, 99, and 100 enhanced the placental proinflammatory response to infection. This may increase the risk of infection-mediated preterm birth by lowering the threshold for bacteria to stimulate a proinflammatory response(s).

["On and off" hypoxaemia]. / Hypoxémie « on-off ¼

INTRODUCTION: A right to left shunt caused by a patent foramen ovale (PFO) must be considered when patients present with symptoms of platypnoea-orthodeoxia. The most useful investigation is saline contrast transthoracic or transoesophageal echocardiography. CASE REPORT: We report a case of an eighty-year-old woman with the platypnoea-orthodeoxia syndrome, but without signs of a right to left shunt caused by a PFO. (99m)Tc-macroaggregated albumin lung scintigraphy and saline contrast transthoracic echocardiography were considered normal in the supine position. The clinical suspicion of PFO was so strong that the examinations were repeated in the upright position. This revealed a systemic uptake of the isotope on lung scintigraphy, confirmed by saline contrast echocardiography. The atrial septal defect was due to displacement of the interatrial septum by an aneurysm of the ascending aortic. In the upright position blood flowed directly from the inferior cava vena through a PFO into the left atrium. CONCLUSION: The diagnosis of PFO may be difficult and it is important to repeat saline contrast echocardiography in the upright position when it is negative supine. It is possible to confirm the diagnosis by contrast infusion through the femoral veins.

[Which are the predictive factors to be ranked within the 500 first medical students at the national ranking exam? A cross-sectional study of the 2009 class]. / Quels sont les facteurs prédictifs d'être reçu dans les 500 premiers à l'examen classant national (ECN) ? Une étude transversale au sein des étudiants en médecine de la promotion 2009.

PURPOSE: The objective of this study was to analyze, during a transversal study, the predictive sociodemographic and individual factors to be ranked within the first 500 medical students in the 2009 French national ranking exam (NRE). METHODS: In September 2009, 5570 medical students have chosen their subspecialty. They were invited to fill-up a questionnaire that included sociodemographics and educational items. Logistic regression was used to identify factors that were associated with being ranked within the first 500 medical students. RESULTS: A total of 4712 students (two third of women) responded to the questionnaire (92.3% response rate). The mean age of respondents was 24.7 years (±1.79). In the multivariate analysis, independent factors associated with being ranked within the first 500 medical students at the NRE were: being less than 25-year-old (odds ratio [OR]: 1.8; 95%CI: 1.3-2.5; P<0.001), region of origin (Île de France) (OR: 3.7; 95%CI: 2.3-5.8; P<0.0001), to succeed at the first medical year examination for the first time (OR: 1.7; 95%CI: 1.2-2.4; P<0.001), being in the first 20% of the medical students during externship (P<0.0001), critical reading test (CRT) teaching by graduate doctors (OR: 1.5; 95%CI: 1.05-2.1; P<0.001), and to participate in a national practicing ranking exam with a CRT (OR: 1.96; 95%CI: 1.3-3.03; P=0.002). CONCLUSION: Our study identified six factors independently associated with being ranked within the first 500 medical students in the French NRE. Education and training of the CRT, newly introduced test in 2009, seem to play an important role.

In-hospital mortality and prognostic factors in patients admitted for new-onset heart failure with preserved or reduced ejection fraction: a prospective observational study.

INTRODUCTION: Heart failure (HF) is associated with high morbidity and mortality. A significant component of HF-related adverse outcome occurs during hospitalization. Objective. - To assess features and in-hospital outcomes of patients hospitalized for a first episode of HF. METHODS: We prospectively recruited 799 consecutive patients hospitalized for a first episode of HF during 2000 in the Somme department (France). We evaluated in-hospital mortality in this cohort, identified factors predictive for hospital death, and compared the mortality in patients with preserved or reduced ejection fraction (EF). RESULTS: The mean age of the study population was 75+/-12 years. EF, assessed in 662 patients (83%), was preserved (> or = 50%) in 56% of cases. During hospitalization, 64 deaths (8%) were recorded. The major causes of in-hospital death were acute pulmonary oedema (50%) and cardiogenic shock (22%). Coronary artery disease, low systolic blood pressure on admission, increased heart rate on admission, renal failure, reduced EF (<50%) and older age were identified as independent predictors of in-hospital mortality. Patients with preserved EF were older and comprised a greater proportion of women. In-hospital mortality of the reduced EF group was higher than that of the preserved EF group (8.2% versus 2.7%, p=0.002). On multivariable analysis, reduced EF was independently associated with in-hospital death (odds ratio 2.32; 95% confidence interval 1.06-5.11; p=0.03). In propensity-matched patients, in-hospital mortality was higher in the reduced EF group (7.6% versus 2.2% p=0.02). CONCLUSION: The in-hospital outcome of patients admitted for new-onset HF is poor. Patients with preserved EF are older but have lower in-hospital mortality.

Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: a prospective five-year study.

OBJECTIVE: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with heart failure and preserved ejection fraction (HFPEF) DESIGN: A five-year prospective observational study SETTING: Population of 368 consecutive patients from 11 healthcare establishments PATIENTS: All patients hospitalised for a first episode of HFPEF in 2000 in the Somme department, France. INTERVENTIONS: Diagnosis of heart failure (HF) was validated during the index hospitalisation by two independent cardiologists. Diabetic and non-diabetic groups were compared. After discharge, patients were managed by the general practitioner or referring cardiologist. MAIN OUTCOME MEASURES: Overall and cardiovascular mortality. RESULTS: The 96 diabetic patients (26%) were younger and had a higher prevalence of clinical coronary artery disease (CAD) than non-diabetic patients. Patients with DM had higher discharge prescription rates of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, nitrates and statins. During the five-year follow-up, 208 patients died (43.5%). DM was a potent independent predictor of five-year overall mortality (HR 1.77, 95% CI 1.27 to 2.48, p = 0.001). Compared to the expected survival of the age-matched and gender-matched general population, the five-year survival of patients with DM was dramatically lower (32% vs 79%). The five-year relative survival (observed/expected survival) of diabetic patients was lower than that of the non-diabetic group (41% vs 68%). Cardiovascular causes were responsible for >60% of deaths in the DM group. DM was associated with an increased risk of death in patients with clinical CAD (HR 1.82, 95% CI 1.02 to 3.25, p = 0.04), as well as in patients without clinical CAD (HR 1.85, 95% CI 1.22 to 2.82, p = 0.004). CONCLUSION: In patients with HFPEF, DM is a strong predictor of poorer long-term survival.

Treatment practices in heart failure with preserved left ventricular ejection fraction: a prospective observational study.

BACKGROUND: Current guidelines for treatment of patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) are empirical. One of the objectives of the ETICS study was to evaluate medical treatment at discharge and after 1 year in patients hospitalised for a first episode of HF in 2000. We report the results concerning treatment of patients with preserved LVEF at discharge and at 1 year. METHODS: Two hundred and sixty three consecutive patients (75+/-10 years, 47 males) with LVEF >50% hospitalised for a first episode of HF were prospectively included. Mean LVEF was 63+/-8%. The main aetiology was hypertension (61%) followed by ischaemic heart disease (29%). Atrial fibrillation and diabetes were present in 34% and 27% of cases, respectively. Medical treatment records were complete at discharge and at 1 year after discharge. RESULTS: At discharge, as at 1 year after discharge, diuretics were the drugs most commonly prescribed (81% and 78%), followed by ACE inhibitors (49% and 46%), amiodarone (32% and 28%), beta-blockers (27% and 29%), nitrates (28% and 27%), calcium channel blockers (27% and 26%), spironolactone (21% and 25%), cardiac glycosides (19% and 24%), and angiotensin II receptor antagonists (4% and 6%). Once prescribed at hospital discharge, drug prescription rates and daily doses did not change significantly over time. Age did not influence drug prescription rates at discharge or at 1 year, except for the spironolactone prescription rate, which decreased at 1 year in patients > or =75 years of age. At discharge, ACE inhibitor and beta-blocker daily doses were lower in older patients, while, at 1 year, no differences in daily doses of these drugs were observed between patients above and below the age of 75 years. CONCLUSION: Loops diuretics are largely prescribed in HF with preserved LVEF, followed by ACE inhibitors. Future large multicentre trials are required to define the background standard treatment in addition to treatment of aetiological factors.

[Prevention of calcific aortic stenosis by statins: myth or reality?]. / Prevention de la sténose aortique calcifiée par les statines: mythe ou réalité?

Degenerative calcific aortic stenosis is the most common valvular disease in the industrialised world. During the last decade, experimental studies have improved our understanding of the physiopathology of this disease. The latest data concerns the demonstration of the mode of installation and progression which resembles that of athrosclerosis. Lipid abnormalities, especially hypercholesterolaemia, are important in the initiation of the valvular lesions and also in the calcification of the aortic orifice. Experimental data and retrospective clinical studies suggest, but without proof, that statins could slow th progression of the aortic stenosis. However, the first prospective trial, recently published, questions this hypothesis. Randomised multicenter trials are currently under way and should provide the answer to the role of stetins in the prevention of aortic stenosis.

Monocyte chemotactic protein-1 expression is increased in human gestational tissues during term and preterm labor.

OBJECTIVE: Microarray analysis was used to characterize the labor-selective transcriptome of the human myometrium during labor. One highly up-regulated transcript, monocyte chemotactic protein-1 (MCP-1), was further characterized. METHODS: Expression of MCP-1 was evaluated in the myometrium, the placenta, the gestational membranes (GM) and the amniotic fluid (AF) by real time RT-PCR, Northern blot analysis and ELISA. The level of immunoreactive (IR) MCP-1 content of primary myometrial cultures treated with inflammatory cytokines was quantified by ELISA. RESULTS: Up-regulation of the myometrial MCP-1 transcript in term laboring patients was demonstrated by microarray and confirmed by real time (RT)-PCR and Northern blot analysis. Increased MCP-1 transcripts were demonstrated in GM during term labor. The IR content of myometrial MCP-1 was increased during term labor and in the AF from patients experiencing preterm delivery. Levels of IR MCP-1 increased in myometrial cultures in response to interleukin 1-beta. CONCLUSION: The expression of myometrial MCP-1 was significantly increased during term labor and was similarly increased in vitro in response to interleukin 1-beta, a pro-inflammatory substance known to play a role in preterm birth. The increased IR content of MCP-1 within the AF preceding preterm delivery may render this protein a useful predictor of preterm birth.

Heart failure due to left ventricular systolic dysfunction: treatment at discharge from hospital and at one year.

BACKGROUND: The treatment of heart failure (HF) due to left ventricular systolic dysfunction has been defined in recent guidelines, but these guidelines are not always applied in routine clinical practice. One of the objectives of the ETICS study was to evaluate medical treatment at discharge and after 1 year in patients hospitalised for a first episode of congestive HF due to left ventricular systolic dysfunction in 2000. METHODS: One hundred and seventy nine patients (63% males, mean age of 69+/-13 years) with an ejection fraction < or = 40% were prospectively included. The main aetiology was ischaemic heart disease (44%). RESULTS: The drugs prescribed at discharge and at one year, respectively, were loop diuretics in 95% and 91% of cases, angiotensin-converting enzyme (ACE) inhibitors in 82% and 75%, spironolactone in 35% and 37%, beta-blockers in 25% and 41%, digitalis glycosides in 34% and 30% of cases, and nitrates in 20% and 16% of cases. ACE inhibitors were prescribed at discharge and at 1 year at dosages reaching 64+/-29% and 72+/-30% of the recommended doses, respectively, and beta-blockers were prescribed at 26+/-16% and 35+/-25% of recommended doses, respectively. CONCLUSION: Diuretics and ACE inhibitors are largely prescribed in HF due to left ventricular systolic dysfunction, followed by spironolactone. Beta-blockers are still underused both in terms of the rate of patients receiving them and the daily doses. These results highlight the value of continuing to widely circulate official practice guidelines in order to improve the management of HF due to left ventricular systolic dysfunction.

[Contrast echocardiography: from diagnosis to treatment]. / Echocardiographie de contraste: du diagnostic à la thérapeutique.

Contrast echocardiography is widely used in echocardiographic laboratories. When used at rest or with a stress test, it provides complementary information concerning myocardial perfusion not available with conventional imaging. Its applications in the evaluation of left ventricular ejection fraction, the detection of coronary stenosis and the no reflow phenomenon in acute myocardial infarction have been validated. Advances in our understanding of the interaction between the microbubbles and ultrasound have led to considering the microbubble not just as a vascular tracer but also as a vector of active molecules. The detection of angiogenesis, thrombi, or intravascular inflammation are possible with contrast echocardiography. Therefore, new perspectives in myocardial contrast echo are opening up in therapeutics. Preliminary studies in the animal suggest that it may be possible to use microbubbles to deliver drugs or genetic material to the heart of the cardiomyocytes.

[Assessing the cost of occupational exposures to blood, in a French university hospital]. / Evaluation du coût de la prise en charge des accidents exposant au sang dans un centre hospitalo-universitaire en 2000.

UNLABELLED: The management of occupational exposure to blood has an important economic impact. Few studies have estimated the real cost of these exposures. METHOD: This retrospective study was made on occupational exposures to blood reported in the Poitiers University Hospital, in 2000. Items concerning the management of these accidents were listed: consultations, post-exposure prophylaxis, laboratory testing, leave time for health care workers (HCW). RESULTS: In 2000, 243 occupational exposures to blood were reported to the Department of Occupational Medicine. Nurses (39.5%), physicians (21.8%), and students (13.6%) were the most frequently concerned. Most of these accidents occurred in the Department of Surgery (29.2%) and Department of Internal Medicine (24.3%). Deep needle-stick injuries accounted for 48.7% of occupational exposures to blood. The source patient serology was unknown in 15.6% of the cases. This study showed that the cost of these occupational exposures to blood was high in 2000 (68310 Euros). This global cost was due to consultations (11122 Euros), laboratory testing (45995 Euros), and post-exposure prophylaxis (5067 Euros). The cost of leave time for injured workers was 6126 Euros. CONCLUSION: The economic impact of occupational exposures to blood is high for a hospital. Before the introduction of safety devices, a cost-benefit analysis must be made to assess the benefits brought about by preventing accidents.

[New concepts on the physiopathology and therapy of aortic stenosis]. / Nouveaux concepts physiopathologique et thérapeutique de la sténose aortique.

Calcified "degenerative" aortic stenosis is currently the most common valvulopathy in industrialised countries. In the course of the last decade, experimental studies have allowed a better understanding of the physiopathology of this vavlulopathy. The latest development is the evidence for the initiation and progression of this disease, similar to those described for atherosclerosis. Lipid disturbances, in particular hypercholesterolaemia, constitute an important factor in the initiation of valvular lesions, but also in aortic orifice calcification. Certain preliminary clinical studies are in favour of the significance of statins for slowing the progression of aortic stenosis. This potential beneficial effect requires confirmation by randomised prospective studies and raises hopes for medical therapy in order to avoid the evolution of ordinary aortic sclerosis into tight calcified aortic stenosis.

[Epidemiology and aetiology of cardiac failure in the Somme]. / Epidémiologie et causes de l'insuffisance cardiaque dans la Somme. Résulants de l'étude ETICS.

UNLABELLED: The epidemiology of cardiac failure (CF) is little known in France. Our work, integrated in the prospective ETICS (epidemiology and therapeutics of cardiac insufficiency in the Somme) study, was aimed at determining the incidence of hospitalisation, the epidemiological profile, the causes of CF, as well as the frequency of cardiac failure with preserved systolic function in the Somme. METHOD: Patients hospitalised for a first attack of CF from January 1 to December 31, 2000 in one of the 11 medical establishments in the Somme were included. RESULTS: During this period, 799 patients were included. The male/female ratio was 1.05; the mean age was 75 +/- 12 years, for males it was less than for females (72 +/- 12 and 78 +/- 11 years respectively p < 0.001); 60% of patients were > 75 years. The average length of hospitalisation was 10.8 +/- 7 days. The hospital mortality was 8.4% (N = 67). The standardised hospital incidence was 1.92 percent per thousand of inhabitants per year and varied from 0.06 percent per thousand among those under 40 years to 14.7 percent per thousand in those over 80 years. The left ventricular ejection fraction, evaluated in 82.8% of patients, was greater than 50% in 55% of cases. The 2 principal causes found were: ischaemic (40%) and hypertensive (39%). CONCLUSION: The hospital incidence of CF in the Somme during the year 2000 was 1.92 percent per thousand. The proportions of males and females were equivalent. This disease preferentially affects the elderly. CF with preserved systolic function is common (55% of cases), particularly in elderly subjects.

Genital mycoplasmosis in rats: a model for intrauterine infection.

PROBLEM: Microbial infections of the chorioamnion and amniotic fluid have devastating effects on pregnancy outcome and neonatal morbidity and mortality. The mechanisms by which bacterial pathogens cause adverse effects are best addressed by an animal model of the disease with a naturally-occurring pathogen. METHOD OF STUDY: Intrauterine infection in humans as well as genital mycoplasmosis in humans and rodents is reviewed. We describe a genital infection in rats, which provides a model for the role of infection in pregnancy, pregnancy wastage, low birth weight, and fetal infection. RESULTS: Infection of Sprague-Dawley rats with Mycoplasma pulmonis either vaginally or intravenously resulted in decreased litter size, increased adverse pregnancy outcome, and in utero transmission of the microorganism to the fetus. CONCLUSION: Mycoplasma pulmonis is an ideal model to study maternal genital infection during pregnancy, the impact of infections on pregnancy outcome, fetal infection, and maternal-fetal immune interactions.

Immunoregulatory activity, biochemistry, and phylogeny of ovine uterine serpin.

PROBLEM: During pregnancy, the endometrium of the ewe secretes a progesterone-induced member of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS) that has immunosuppressive properties. METHOD: Review of the literature. RESULTS AND CONCLUSIONS: OvUS inhibits a wide variety of immune responses, including mixed lymphocyte reaction, mitogen-stimulated lymphocyte proliferation, and T cell-dependent antibody production. Recent data have suggested that OvUS functions by inhibiting protein kinase C and interleukin-2-mediated events. OvUS and similar genes present in cattle and pigs diverged from other serpins prior to the divergence of artiodactyls. Since this time, the serpins have apparently undergone adaptive evolution that has led to a conformational state and biological functions distinct from prototypical serpins. Thus, it is likely that these proteins have an important role in the reproductive biology of Artiodactyla. Several lines of evidence suggest that, in sheep, OvUS functions to mediate the immunosuppressive effects of progesterone and prevent immunological rejection of the fetal allograft.

Plasma homocysteine and severity of thoracic aortic atherosclerosis.

STUDY OBJECTIVES: Plasma homocysteine level is a risk factor for coronary events, stroke, and peripheral atherosclerotic disease. However, few data are available concerning the relationship between homocysteine level and severity of thoracic aortic atherosclerosis. We hypothesized in this multiplane transesophageal echocardiography (TEE) study that homocysteine level is a marker of the presence and severity of thoracic aortic atherosclerosis. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Risk factors, angiographic features, and TEE findings were analyzed prospectively in 82 valvular patients. MEASUREMENTS AND RESULTS: The following risk factors were recorded: age, gender, hypertension, smoking, lipid parameters, diabetes, body mass index, and family history of coronary artery disease. Plasma levels of homocysteine, vitamin B(12), and folic acid were measured for each patient. By univariate analysis, age, diabetes, hypertension, smoking, family history of coronary artery disease, and levels of homocysteine, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were significant predictors of the presence of thoracic aortic plaques. There was a positive correlation between the plasma homocysteine levels and the score of severity of thoracic atherosclerosis (r = 0.48; p = 0.0001) as well as between the homocysteine levels and the grades of severity of aortic intimal changes (p = 0.0008). Multivariate regression analysis revealed that homocysteine was an independent predictor of the presence and severity of thoracic aortic atherosclerosis. CONCLUSION: This prospective study indicates that plasma homocysteine level is a marker of severity of thoracic atherosclerosis detected by multiplane TEE. These findings emphasize the role of homocysteine as a marker of atherosclerotic lesions in the major arterial locations.

Distinct physical and structural properties of the ovine uterine serpin.

Experiments were performed to examine the relationship between the structure and function of ovine uterine serpin (OvUS). Limited proteolytic digestion of OvUS caused cleavage of the 55-57 kDa OvUS to a 42 kDa product nearly identical in molecular weight to a naturally-occurring breakdown product of OvUS. N-terminal amino acid sequencing and MALDI-MS revealed that, unlike other serpins, OvUS was preferentially cleaved at about 70 amino acids upstream of the putative reactive center loop. Analysis of the partially-digested protein by gel filtration chromatography suggested that the C-terminal fragment of the protein was still associated under nondenaturing conditions. Partial digestion of OvUS had no effect on the protein's secondary structure, thermal stability, ability to bind lymphocytes or pepsin, or inhibitory activity towards pepsin or mitogen-induced lymphocyte proliferation. In contrast, mild denaturation of OvUS with 0.5 M guanidine HCl increased thermal stability. Unlike for other serpins, the increase in thermal stability was lost upon removal of the denaturant. Incubation of OvUS with 100 fold molar excess of a peptide corresponding to the putative P(14)-P(2) region of the RCL for 24 h at 37 degrees C to induce binary complex formation had no effect on its secondary structure and did not alter the biological activity of the protein. Synthetic peptides corresponding to the putative P(14)-P(2) region and the P(7)-P(15') region of the RCL were not inhibitory to pepsin activity or lymphocyte proliferation. Taken together, these results indicate that the conformation of OvUS is distinct from the prototypical serpin because conditions that lead to the large-scale conformational change in other serpins such as antithrombin III and alpha(1)-antitrypsin do not cause similar changes in OvUS. Moreover, the putative RCL does not seem to contain the activity required to inhibit lymphocyte proliferation or pepsin activity.