Obesity, estrone, and coronary artery disease in postmenopausal women

Objectives: The link between obesity and endogenous estrogen with coronary artery disease (CAD) in postmenopausal women is uncertain. In this prospective study we analyzed the association of body mass index (BMI) and blood levels of estrone in postmenopausal women with known CAD or with a high risk factor score for CAD. Methods: Participants were 251 female clinic patients aged 50-90 years who were postmenopausal and not using estrogen therapy. Clinical and behavioral characteristics and fasting blood for estrone and heart disease risk factors were collected at baseline, and again at I and 2 years. Women were grouped according to their BMI (kg/m(2)) as normal (18.5 <= BMI < 25), overweight (25 <= BMI < 30) or obese (BMI >= 30), and by low and high estrone levels (< 15 and >= 15 pg/mL, respectively). Fatal and nonfatal events were recorded for 2 years after baseline. Results: Women with a low estrone level were older, thinner, and had less hypertension, diabetes, and lower triglyceride and glucose levels. BMI was positively associated with estrone levels, hypertension, and diabetes and inversely associated with HDL cholesterol. There were 14 deaths, 8 attributed to CAD. The Kaplan-Meier survival curve showed a nonsignificant trend (p = 0.074) of greater all cause mortality in women with low estrone levels (< 15 mL). In this model, adjusted for BMI, age [OR 1.08; p = 0.03], C-reactive protein [OR = 1.24; p = 0.024] and hypertension [OR = 6.22; p = 0.003] were independent predictors of all cause mortality. Conclusions: Postmenopausal women with low estrone levels (< 15 pg/mL) had a trend for increased mortality over the next 2 years. Larger, longer studies are needed. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis

Background and Purpose-Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H-2) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. Methods-The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. Results-Over half of CVT patients (52.1%) were heterozygous (H1H2) or homozygous (H2H2) carriers of the H-2 haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H2 haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). Conclusions-These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.

Conjugated equine estrogen, raloxifene and arterial stiffness in postmenopausal women

Methods We analyzed the influence of conjugated equine estrogen (CEE) and raloxifene on arterial stiffness. Sixty-seven healthy, normotensive women 1-10 years into menopause were assigned to receive oral placebo, conjugated equine estrogen 0.625mg, or raloxifene 60mg. Arterial stiffness was evaluated by measuring the carotid-femoral and femoral-dorsalis pedis pulse wave velocity (CF PWV, FP PWV). Systolic pressure augmentation index (AI) at the carotid artery was obtained with applanation tonometry. Results Arterial stiffness was not affected by any treatment regimen: placebo (CF PWV before vs. after: 644 vs. 626 cm/s, p = 0.09; FP PWV before vs. after: 1006 vs. 1012 cm/s, p = 0.77; AI before vs. after = 30 vs. 29%, p = 0.55), CEE (CF PWV before vs. after: 642 vs. 600 cm/s, p = 0.11; FP PWV before vs. after: 952 vs. 971 cm/s, p = 0.66; AI before vs. after: 25 vs. 32%, p = 0.82), and raloxifene (CF PWV before vs. after: 636 vs. 601 cm/s, p = 0.12; FP PWV before vs. after: 964 vs. 941 cm/s, p = 0.62; AI before vs. after: 25 vs. 25%, p = 0.65). A correlation occurred between basal stiffness and the degree of reduction in indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: CF PWV (r = -0.602, p = 0.001); FP PWV (r = -0.455, p = 0.022); AI (r = -0.410, p = 0.042). Conclusions Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women less than 10 years since menopause. Reduction in arterial stiffness seems related to its basal level.

The association between osteoporosis and static balance in elderly women

This study aimed at answering the question: do people with high bone loss have greater postural instability? Groups were separated into group 1: women with normal bone mineral density, group 2: women with osteopenia, and group 3: women with osteoporosis. The balance was evaluated in four upright postural situations. Osteoporosis group had greater oscillation in the anteroposterior displacement in all situations compared to control group and the greatest mediolateral displacement in all situations compared to other groups. It is not known whether the presence of osteoporosis can be considered a factor aggravating the postural control. This study aimed at answering the question: do people with high bone loss have greater postural instability? This study was divided into three groups: group 1 (n = 20) consisting of women with normal bone mineral density, group 2 (n = 20) women with osteopenia, and group 3 (n = 20) women with osteoporosis. All the participants were submitted to evaluation of the balance using the Polhemus system in four upright postural situations. Osteoporosis group had greater oscillation in the anteroposterior displacement in all situations compared to control group. The osteoporosis group also showed the greatest mediolateral displacement in all situations compared to other groups. The results suggest that osteoporotic women had the worst balance, possibly due to the more pronounced body changes compared to non-osteoporotic women.

Cervical Mobility in Women With Migraine

Objective.-To contrast the cervical range of motion (CROM) in women with episodic migraine (EM), transformed migraine (TM), and controls without migraine headaches. Background.-Migraineurs often complain about neck pain. Furthermore, neck problems can worsen the headaches in individuals with migraine. Individuals with neck pain usually have reduced CROM. Nonetheless, studies assessing the CROM in migraineurs are scarce. Methods.-Our sample was selected in an outpatient headache clinic, and consisted of 45 women aged 20-54 years old, 15 per group. Cervical mobility was evaluated in movements of flexion, extension, right lateral flexion, left lateral flexion, right rotation, and left rotation using the CROM technique, and was contrasted among the groups. Migraine clinical patterns were also evaluated ( frequency, duration of migraine, pain in the moment of evaluation, pain in movement, and pain localization) as a function of CROM. Results.-Compared with controls, individuals with TM had numerically inferior CROM in all parameters, and significant reduction in 3 of them: extension (59.3 vs 68.1, P = .02), left lateral flexion (44.5 vs 49.1, P = .03), and right rotation (62.2 vs 69.6, P = .02). Compared with individuals with migraine, the TM group presented significantly reduced mobility only for extension ( 59.3 vs 68.4, P = .02). Migraineurs also had numerically inferior ROM, contrasted to controls, in 5 of the 6 parameters, although significance was seen just for right rotation (60.8 vs 68.6 P < .01). There was no correlation between cervical mobility and migraine parameters. The CROM was not reduced for the symptomatic side of migraine, in cases of unilateral pain. Conclusion.-Contrasted to controls, individuals with episodic and TM have decreased cervical range of motion.

A subunit vaccine based on biodegradable microspheres carrying rHsp65 protein and KLK protects BALB/c mice against tuberculosis infection

Of the hundreds of new tuberculosis ( TB) vaccine candidates some have therapeutic value in addition to their prophylactic properties. This is the case for the DNA vaccine encoding heat-shock protein 65 (DNAhsp65) from Mycobacterium leprae. However, there are concerns about the use of DNA vaccines in certain populations such as newborns and pregnant women. Thus, the optimization of vaccination strategies that circumvent this limitation is a priority. This study evaluated the efficacy of a single dose subunit vaccine based on recombinant Hsp65 protein against infection with M. tuberculosis H37Rv. The Hsp65 protein in this study was either associated or not with immunostimulants, and was encapsulated in biodegradable PLGA microspheres. Our results demonstrate that the protein was entrapped in microspheres of adequate diameter to be engulfed by phagocytes. Mice vaccinated with a single dose of Hsp65-microspheres or Hsp65 + CpG-microspheres developed both humoral and cellular-specific immune responses. However, they did not protect mice against challenge with M. tuberculosis. By contrast, Hsp65+KLK-microspheres induced specific immune responses that reduced bacilli loads and minimized lung parenchyma damage. These data suggest that a subunit vaccine based on recombinant protein Hsp65 is feasible.

The ""single-section"" Golgi method adapted for formalin-fixed human brain and light microscopy

The Golgi method has been used for over a century to describe the general morphology of neurons in the nervous system of different species. The ""single-section"" Golgi method of Gabbott and Somogyi (1984) and the modifications made by Izzo et al. (1987) are able to produce consistent results. Here, we describe procedures to show cortical and subcortical neurons of human brains immersed in formalin for months or even years. The tissue was sliced with a vibratome, post-fixed in a combination of paraformaldehyde and picric acid in phosphate buffer, followed by osmium tetroxide and potassium dicromate, ""sandwiched"" between cover slips, and immersed in silver nitrate. The whole procedure takes between 5 and 11 days to achieve good results. The Golgi method has its characteristic pitfalls but, with this procedure, neurons and glia appear well-impregnated, allowing qualitative and quantitative studies under light microscopy. This contribution adds to the basic techniques for the study of human nervous tissue with the same advantages described for the ""single-section"" Golgi method in other species; it is easy and fast, requires minimal equipment, and provides consistent results. (C) 2010 Elsevier B.V. All rights reserved.

Utility of Ictal Single Photon Emission Computed Tomography in Mesial Temporal Lobe Epilepsy With Hippocampal Atrophy: A Randomized Trial

BACKGROUND: The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). OBJECTIVE: To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. METHODS: MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. RESULTS: The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). CONCLUSION: Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.

Tailored resections for intractable rolandic cortex epilepsy in children: a single-center experience with 48 consecutive cases

A single-center experience with pediatric patients who underwent surgery for intractable rolandic epilepsy was reviewed with the aim of identifying putative factors that could influence postoperative seizure outcome in this population. Clinical data of 48 patients under 18 years of age with diagnosis of intractable rolandic epilepsy who underwent surgery from January 1996 to September 2009 were reviewed. Patients` mean age at surgery was 9.9 +/- 5.3 years; mean age at epilepsy onset was 3.9 years; mean seizure duration prior to surgery was 6 years; and mean follow-up was 5.1 years. The most frequent etiologies were cortical dysplasia, astrogliosis, tumors, tuberous sclerosis complex, and Sturge-Weber syndrome, which were observed in 20/48 (41.6%), 10/48 (20.8%), 10/48 (20.8%), 5/48 (10.4%), and 3/48 (6.2%) of the patients, respectively. After surgery, 20 patients (41.6%) showed neurological deficits, which in turn recovered within no longer than 6 months after surgery. Seizure outcome was classified as Engel class I in 29 (60.4%), Engel class II in 10 (20.8%), and Engel class III in 9 (18.8%) of the patients. The factors significantly related with seizure outcome were histological features (tumor versus non-tumor cases, p = 0.04) and lesion site (focal lesions versus non-focal lesions, p = 0.04). Tailored resection of rolandic cortex for intractable epilepsy can be safely performed in children. Accurate mapping of both functional cortex and epileptogenic areas may lead to improved seizure outcome. Tumor as well as focal lesions in hand and face motor areas are associated with good seizure outcome.

Single-Step EUS-Guided Endoscopic Treatment for Sterile Pancreatic Collections: A Single-Center Experience

Background and Aims: Endoscopic ultrasound (EUS) is useful for the treatment of sterile pancreatic fluid collections (PFC), either by means of transmural drainage or by complete aspiration. The aim of this study was to evaluate the efficacy and safety of single-step EUS-guided endoscopic approaches for treatment of sterile PFC. Patients and Methods: During a 3-year period, 77 consecutive patients with symptomatic, persistent sterile PFC were evaluated and treated with the linear EUS. We excluded patients with grossly purulent collections, chronic pseudocyst and those whose cytology diagnostic was neoplastic cyst of pancreas. 44 patients received a single 10-Fr plastic straight stent under EUS or fluoroscopic control (group I) and 33 of these underwent a single-step complete aspiration with a 19-gauge needle (group II). Results: The mean size of the sterile PFC was 48 mm in group I and 28 mm in group II (p < 0.001). Overall, endoscopic treatment was successful in 70 (90.9%) patients. The mean volume aspirated was 25 (18-65) ml. The total number of procedures was 50 in group I and 41 punctures in group II. After a mean follow-up of 64 +/- 15.6 weeks there were 6 complications 13.6%): 2 recurrences (referred to surgery), 2 developing abscesses (submitted a new EUS-guided endoscopic drainage with success), 1 perforation that died (2.2%), and 1 case of bleeding (sent to surgery) in group I. In group II there were only 6 (18.1%) recurrences (submitted a new EUS-guided aspiration). None of the patients undergoing single-step aspiration developed infections, perforation or hemorrhage. Conclusion: The recurrence of pancreatic pseudocysts after endoscopic treatment was similar, either by means of plastic stents or by complete single-step aspiration. Copyright (C) 2009 S. Karger AG, Basel

Characteristics of women who frequently under report their energy intake: a doubly labelled water study

Background/Objectives: We applied three dietary assessment methods and aimed at obtaining a set of physical, social and psychological variables that can discriminate those individuals who did not underreport (`never under-reporters`), those who underreported in one dietary assessment method (`occasional under-reporters`) and those who underreported in two or three dietary assessment methods (`frequent under-reporters`). Participants/Methods: Sixty-five women aged 18-57 years were recruited for this study. Total energy expenditure was determined by doubly labelled water, and energy intake was estimated by three 24-h diet recalls, 3-day food records and a food frequency questionnaire. A multiple discriminant analysis was used to identify which of those variables better discriminated the three groups: body mass index (BMI), income, education, social desirability, nutritional knowledge, dietary restraint, physical activity practice, body dissatisfaction and binge-eating symptoms. Results: Twenty-three participants were `never under-reporters`. Twenty-four participants were `occasional under-reporters` and 18 were `frequent under-reporters`. Four variables entered the discriminant model: income, BMI, social desirability and body dissatisfaction. According to potency indices, income contributed the most to the total discriminant power, followed in decreasing order by social desirability score, BMI and body dissatisfaction. Income, social desirability and BMI were the characteristics that mainly separated the `never under-reporters` from the under-reporters (occasional or frequent). Body dissatisfaction better discriminated the `occasional under-reporters` from the `frequent under-reporters`. Conclusions: `Frequent under-reporters` have a greater BMI, social desirability score, body dissatisfaction score and lower income. These four variables seemed to be able to discriminate individuals who are more prone to systematic under reporting. European Journal of Clinical Nutrition (2009) 63, 1192-1199; doi:10.1038/ejcn.2009.54; published online 15 July 2009

HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus

Human papillomavirus (HPV) infection is etiologically associated with low-(LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G*0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/+14 bp and G0104/-14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/+14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer. Modern Pathology (2009) 22, 1075-1082; doi: 10.1038/modpathol.2009.67; published online 1 May 2009

Fed State Protein Turnover in Healthy Older Persons under a Usual Protein-Rich Diet

The objective of this study was to verify the protein turnover rates of healthy older persons under a usual protein-rich diet and to compare values to those described in the literature. This cross-sectional study was conducted at Metabolism Unit, Univ. Hospital of the School of Medicine of Ribeirao Preto, Univ. of Sao Paulo, Brazil. In this study, 7 healthy older persons aged 65.4 +/- 2.8 y, with BMI 22.7 +/- 2.4 kg/m(2) and a mean daily protein intake of 1.34 g of protein/kg were studied. A 9-h whole-body (15)N-glycine single-dose study was performed after an overnight fast. During the study, each subject received 6 isoenergetic, isonitrogenous meals at 2-h intervals based on their average intake. Ammonium, urea, and total nitrogen were quantified and analyzed by mass spectrometry, with the determination of total protein turnover rates by the (15)N-glycine method. The results show that total nitrogen output was 3.2 +/- 0.96 g/N and intake 7.7 +/- 1 g/N, (15)N nitrogen flux was 30.6 +/- 6.3 g/9 h. Endogenous nitrogen balance was positive (4.5g +/- g/N in 9 h). In conclusion, the protein turnover of healthy older persons under a usual protein-rich diet is positive during the fed state and has synthesis and degradation rates similar to those previously described in studies involving diet adaptation periods.

Ictal technetium-99 m ethyl cysteinate dimer single-photon emission tomographic findings in epileptic patients with polymicrogyria syndromes: A Subtraction of ictal-interictal SPECT coregistered to MRI study

Purpose To describe the ictal technetium-99 m-ECD SPECT findings in polymicrogyria syndromes (PMG) during epileptic seizures. Methods We investigated 17 patients with PMG syndromes during presurgical workup, which included long-term video-electroencephalographic (EEG) monitoring, neurological and psychiatry assessments, invasive EEG, and the subtraction of ictal-interictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM). Results The analysis of the PMG cortex, using SISCOM, revealed intense hyperperfusion in the polymicrogyric lesion during epileptic seizures in all patients. Interestingly, other localizing investigations showed heterogeneous findings. Twelve patients underwent epilepsy surgery, three achieved seizure-freedom, five have worthwhile improvement, and four patients remained unchanged. Conclusions Our study strongly suggests the involvement of PMG in seizure generation or early propagation. Both conventional ictal single-photon emission computed tomography (SPECT) and SISCOM appeared as the single contributive exam to suggest the localization of the epileptogenic zone. Despite the limited number of resective epilepsy surgery in our study (n=9), we found a strong prognostic role of SISCOM in predicting surgical outcome. This result may be of great value on surgical decision-making of whether or not the whole or part of the PMG lesion should be surgically resected.

Parathyroid hormone secretion in women in late menopause submitted to EDTA-induced hypocalcemia

Objective: The physiological role of parathormone (PTH) in the maintenance of bone mass in humans has not been fully defined. The main objective of the present study was to evaluate basal and EDTA-stimulated PTH levels in Young women (Group Y = 30.9 years, N = 7) and in women in late menopause (Group M = 64.7 years, N = 7) and their relationship to bone mineral density. Methods: The PTH secretion test was performed by induction of hypocalcemia through intravenous administration of EDTA for 2 h. Blood samples were collected every 10 min and used for ionic calcium and PTH measurements. During the basal period, an additional sample was collected for the determination of osteocalcin, FSH, and estradiol. A sample of early morning second voided urine was collected for analysis of deoxypiridinoline and creatinine Lis well as bone mass density (BMD) was determined by dual X-ray energy absorptiometry (DEXA). Results: The aged patients presented lower femoral BMD (Y = 0.860 g/cm(2) vs. M = 0.690 g/cm(2), P < 0.01), With four of them having a T score lower than - 2.5 S.D. Basal, and during the EDTA infusion, PTH values were similar in both groups. However, among aged volunteers, the rise in PTH levels was higher for subjects with normal bone mass (NM: peak = 236 pg/ml) than for subjects with osteoporosis (OM: peak = 134.4 pg/ml). Conclusions: The present results suggest that PTH can have a modulating effect on the rate of bone loss during late menopause. (c) 2007 Elsevier Ireland Ltd. All rights reserved.