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Background Lyme disease (LD) caused by Borrelia burgdorferi is the most prevalent tick-borne disease. There is evidence that vaccines based on tick proteins that promote tick transmission of B. burgdorferi could prevent LD. As Ixodes scapularis nymph tick bites are responsible for most LD cases, this study sought to identify nymph tick saliva proteins associated with B. burgdorferi transmission using LC-MS/MS. Tick saliva was collected using a non-invasive method of stimulating ticks (uninfected and infected: unfed, and every 12 h during feeding through 72 h, and fully-fed) to salivate into 2% pilocarpine-PBS for protein identification using LC-MS/MS. Results We identified a combined 747 tick saliva proteins of uninfected and B. burgdorferi infected ticks that were classified into 25 functional categories: housekeeping-like (48%), unknown function (18%), protease inhibitors (9%), immune-related (6%), proteases (8%), extracellular matrix (7%), and small categories that account for B. burgdorferi infected ticks secreted high number of saliva proteins (n=645) than uninfected ticks (n=376). Counter-intuitively, antimicrobial peptides, which function to block bacterial infection at tick feeding site were suppressed 23-85 folds in B. burgdorferi infected ticks. Similar to glycolysis enzymes being enhanced in mammalian cells exposed to B. burgdorferi : eight of the 10-glycolysis pathway enzymes were secreted at high abundance by B. burgdorferi infected ticks. Of significance, rabbits exposed to B. burgdorferi infected ticks acquired potent immunity that caused 40-60% mortality of B. burgdorferi infected ticks during the second infestation compared to 15-28% for the uninfected. This might be explained by ELISA data that show that high expression levels of immunogenic proteins in B. burgdorferi infected ticks. Conclusion Data here suggest that B. burgdorferi infection modified protein content in tick saliva to promote its survival at the tick feeding site. For instance, enzymes; copper/zinc superoxide dismutase that led to production of H2O2 that is toxic to B. burgdorferi were suppressed, while, catalase and thioredoxin that neutralize H2O2, and pyruvate kinase which yields pyruvate that protects Bb from H2O2 killing were enhanced. We conclude data here is an important resource for discovery of effective antigens for a vaccine to prevent LD.

Introducción: el síndrome coronario agudo (SCA) es una serie de signos y síntomas que se refieren a isquemia miocárdica repentina. Estas condiciones clínicas son Síndrome Coronario agudo sin Elevación del Segmento ST (SCASEST) y Síndrome Coronario Agudo con Elevación del Segmento ST (SCACEST). A nivel mundial hay hallazgos controversiales con respecto a la diferencia de presentación de SCA en hombres y mujeres. Objetivo: determinar las diferencias en presentación del síndrome coronario agudo según el género en República Dominicana. Métodos: en este estudio observacional retrospectivo unicéntrico, 3,548 pacientes con SCA llevados al laboratorio de cateterismo fueron observados durante el período de agosto de 2016 a septiembre de 2019. Resultados: la edad promedio de presentación fue mayor en las mujeres, con una media de 63 años (DE ± 12.2). El SCACEST fue más frecuente en hombres (69.35 %) y la Angina Inestable en mujeres (50.14 %, p

Immune checkpoint inhibitors (ICIs) are approved for microsatellite unstable colorectal cancer (CRC), however, microsatellite stable (MSS) CRC that make up the majority of tumors in clinical practice have not seen any benefit with ICI. This is in part due to the lack of sufficient tumor infiltrating immune cells, particularly CD8+ T cells, in the milieu. Immunogenic cell death (ICD) is a particular form of cell death that elicits robust cross-priming of CD8 T cells against antigens expressed by dying cells in the absence of exogenous adjuvants. ICD-inducing drugs such as poly (ADP-ribose) polymerase inhibitors (PARPis) are poised to enhance cancer cell killing, boost tumor immunogenicity, increase in vivo immune infiltration, and thereby accelerate a tumor response to ICI treatment. Here, we tested the combinatorial therapeutic efficacy of a PARPi, olaparib (OLA), and an ICI, anti-PD-1, in in vitro and in vivo conditions. Combined treatment of OLA and anti-mouse PD-1 reduced tumor growth and increased survival in an immunocompetent, syngeneic animal model of BALB/c carrying allograft CT26 tumor that is MSS. Flow cytometry analysis revealed that the combo treatment significantly reduced percentages of anti-inflammatory macrophages and increased inflammatory monocytes. There was no significant difference in dendritic cell populations. We observed increased anti-tumor lymphocyte response via activation of CD4 and CD8 T cell populations upon combo treatment with OLA and anti-mouse PD-1. In addition, we noticed an increased association of expression of PD-L1 and its receptor PD-1 with OLA treatment in CRC cell lines and CT26 tumors. Our preliminary data suggests altered expressions of the CD8+ T cell exhaustion marker TIM-3 and its ligands galectin-9 and high mobility group protein 1 (HMGB1), an indicator of ICD. The pilot studies also revealed increased levels of STING-dependent type I interferon signaling initiator cGAS upon treatment with OLA in vivo. Mechanistically, OLA might induce DNA damage among tumor cells and trigger innate immune signaling including NF-κB activation and STING-dependent type I interferon signaling, both of which contribute to the maturation of myeloid antigen-presenting cells and subsequent activation of T cells. In conclusion, OLA potentiated the antitumor efficacy of anti-PD-1 in CT26 induced syngeneic CRC mouse model. Our findings indicate that OLA might trigger tumor immunogenicity, and enable a potential targeted-immunotherapeutic angle for exercising ICD and activating cytotoxic T lymphocytes in CT26 syngeneic CRC mouse model; however, further studies are needed to elucidate the mechanism. Despite ICD markers' identification as immuno-stimulating characteristics of dead cells, whether ICD-associated molecules can be used as a prognostic biomarker or therapeutic target, and the rational for such markers on tumor cells in eliciting antitumor immunity are still under investigation. Citation Format: Chintal Bhavsar, Peter John, Magnolia Abreu, Laura Bencosme, Radhashree Maitra, Sanjay Goel, Titto Augustine. Potentiating effect of olaparib on anti-PD-1 treatment in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1606.

Previously, the REDLINC VI study showed that the main reason for the low use of menopausal hormone therapy (MHT) was its low rate of prescription by doctors.To determine the use of MHT and perceived related risks among gynecologists.A self-administered and anonymous questionnaire was delivered to certified gynecologists in 11 Latin American countries.A total of 2154 gynecologists were contacted, of whom 85.3% responded to the survey (n = 1837). Mean age was 48.1 ± 11.4 years; 55.5% were male, 20.3% were faculty members and 85% had a partner. Overall, 85.4% of gynecologists responded that they would use MHT if they had menopausal symptoms (81.8% in the case of female gynecologists) or prescribe it to their partner (88.2% in the case of male gynecologists; p0.001). Perceived risk related to MHT use (on a scale from 0 to 10) was higher among female than among male gynecologists (4.06 ± 2.09 vs. 3.83 ± 2.11, p0.02). The top two perceived reported risks were thromboembolism (women 33.6% vs. men 41.4%, p0.009) and breast cancer (women 38.5% vs. men 33.9%, p0.03). Overall, gynecologists reported prescribing MHT to 48.9% of their symptomatic patients (women 47.3% vs. men 50.2%, p0.03) and 86.8% currently prescribed non-hormonal remedies and 83.8% alternative therapies for the management of the menopause. Gynecologists who were older and academic professionals prescribed MHT more often.Although this Latin American survey showed that gynecologists are mostly supporters of MHT use (for themselves or their partners), this is not necessarily reflected in their clinical practice.

Background The prevalence of obesity increases during female mid-life and although many factors have been identified, data from Latin America is lacking. Objective To assess factors related to obesity among middle-aged women and determine the association with depressive symptoms, sedentary lifestyle and other factors. Methods A total of 6079 women aged 40–59 years of 11 Latin American countries were asked to fill out the Goldberg Anxiety and Depression Scale, the Menopause Rating Scale, the Athens Insomnia Scale, the Pittsburgh Sleep Quality Index and a general questionnaire containing personal socio-demographic data, anthropometric measures and lifestyle information. Obesity was defined as a body mass index (BMI) ≥30 kg/m 2 . Results Obesity was observed in 18.5% and sedentary lifestyle in 63.9%. A 55.5% presented vasomotor symptoms, 12.2% had severe menopausal symptoms and 13.2% used hormone therapy for the menopause. Prevalence of depressive symptoms was 46.5% and anxiety 59.7%. Our logistic regression model found that significant factors associated to obesity included: arterial hypertension (OR: 1.87), depressive symptoms (OR: 1.57), sedentary lifestyle (OR: 1.50) diabetes mellitus (OR: 1.34), higher number of individuals living at home (OR: 1.31), sleep problems (OR:1.22), anxiety (OR: 1.21), having a stable partner (OR: 1.20), parity (OR: 1.16) and vasomotor symptoms (OR:1.14). A lower risk for obesity was found among women using hormonal contraceptives (OR: 0.69). Conclusion Obesity in middle-aged women is the consequence of the interaction of multiple factors. It was associated to hypertension, depressive symptoms, sedentary lifestyle, climacteric symptoms and other factors.

Background Type II diabetes mellitus causes metabolic changes that may lead to early menopause and worsen climacteric symptoms. Objectives To determine the risk factors for type II diabetes mellitus and assess the impact of this disease on the age of menopause and on climacteric symptoms. Methods A total of 6079 women aged between 40 and 59 years from 11 Latin American countries were requested to answer the Menopause Rating Scale and Goldberg Anxiety-Depression Scale. Results The prevalence of diabetes was 6.7%. Diabetes mellitus was associated with arterial hypertension (odds ratio (OR) 4.49; 95% confi dence interval (CI) 3.47 – 5.31), the use of psychotropic drugs (OR 1.54; 95% CI 1.22 – 1.94), hormonal therapy (OR 1.46; 95% CI 1.11 – 1.92), 50 years of age (OR 1.48; 95% CI 1.17 – 1.86), overweight or obese (OR 1.47; 95% CI 1.15 – 1.89), and waist circumference 88 cm (OR 1.32; 95% CI 1.06 – 1.65). Factors associated with lower risk of diabetes were the use of hormonal contraceptives (OR 0.55; 95% CI 0.35 – 0.87), alcohol (OR 0.73; 95% CI 0.54 – 0.98) and living in cities 2500 meters above sea level (OR 0.70; 95% CI 0.53 – 0.91) or with high temperatures (OR 0.67; 95% CI 0.51 – 0.88). In turn, diabetes tripled the risk of menopause in women under 45 years of age. Diabetes did not increase the risk of deterioration of quality of life due to climacteric symptoms. Conclusion Menopause does not increase the risk of type II diabetes mellitus. Diabetes is associated with early menopause in women under 45 years of age.

Objective: To evaluate associations between anxiety and severe impairment of quality of life (QoL) in Latin American postmenopausal women. Methods: This was a secondary analysis of a multicenter cross-sectional study among postmenopausal women aged 40 to 59 from 11 Latin American countries. We evaluated anxiety (The Goldberg Depression and Anxiety Scale), and QoL (Menopause Rating Scale [MRS]), and included sociodemographic, clinical, lifestyle, and anthropometric variables in the analysis. Poisson family generalized linear models with robust standard errors were used to estimate prevalence ratios (PRs) and 95% CIs. There were two adjusted models: a statistical model that included variables associated with the outcomes in bivariate analyses, and an epidemiologic model that included potentially confounding variables from literature review. Results: Data from 3,503 women were included; 61.9% had anxiety (Goldberg). Severe QoL impairment (total MRS score >=17) was present in 13.7% of women, as well as severe symptoms (MRS subscales): urogenital (25.5%), psychological (18.5%), and somatic (4.5%). Anxiety was independently associated with severe QoL impairment and severe symptoms in the epidemiological (MRS total score: PR 3.6, 95% CI, 2.6-5.0; somatic: 5.1, 95% CI, 2.6-10.1; psychological: 2.8, 95% CI, 2.2-3.6; and urogenital: 1.4, 95% CI, 1.2-1.6) and the statistical model (MRS total score: PR 3.5, 95% CI, 2.6-4.9; somatic: 5.0, 95% CI, 2.5-9.9; psychological: 2.9, 95% CI, 2.2-3.7; and urogenital: 1.4; 95% CI, 1.2-1.6). Conclusions: In this postmenopausal Latin American sample, anxiety was independently associated with severe QoL impairment. Hence, screening for anxiety in this population is important. Revisión por pares

Musculoskeletal pain (MSP) has been recently linked with high plasma leptin levels. Our objective was to study if obese women, who have higher leptin levels, could have a higher frequency of MSP. We studied 6079 Latin-American women, 40-59 years old. Their epidemiological data were recorded and the Menopause Rating Scale (MRS), Golberg Anxiety and Depression Scale and Insomnia Scale were applied. MSP was defined as a score ≥2 on MRS11. Women with MSP were slightly older, had fewer years of schooling and were more sedentary. They also complained of more severe menopausal symptoms (29.2% versus. 4.4%, p 0.0001). Furthermore, they had a higher abdominal perimeter (87.2 ± 12.0 cm versus 84.6 ± 11.6 cm, p 0.0001) and a higher prevalence of obesity (23.1% versus 15.2%, p 0.0001). Compared to normal weight women, those with low body weight (IMC 18.5) showed a lower risk of MSP (OR 0.71; 95%CI, 0.42-1.17), overweight women had a higher risk (OR 1.64; 95%CI, 1.44-1.87) and obese women the highest risk (OR 2.06; 95%CI, 1.76-2.40). Logistic regression analysis showed that obesity is independently associated to MSP (OR 1.34; 95%CI, 1.16-1.55). We conclude that obesity is one identifiable risk factor for MSP in middle-aged women.

Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P/=70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of >/=100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P

To evaluate whether menopausal status and symptoms among female gynecologists would influence their clinical behavior related to menopausal hormone therapy (MHT).Female gynecologists of 11 Latin American countries were requested to fill out the Menopause Rating Scale and a questionnaire containing personal information and that related to MHT use.A total of 818 gynecologists accepted to participate (86.4%). Overall, the mean age was 45.0 ± 10.7 years, 32.2% were postmenopausal, and 17.6% worked in an academic position; 81.8% reported that they would use MHT if they have symptoms, regardless of menopausal status. Academic gynecologists favor personal MHT use at a higher rate (p = 0.04) and have a higher MHT prescription rate as compared to non-academic ones (p = 0.0001). The same trend was observed among post- as compared to premenopausal ones (p = 0.01) and among those who had hysterectomy alone as compared to those experiencing natural menopause (p = 0.002). The presence of menopausal symptoms did not influence their MHT prescription. Current use of MHT and alternative therapy was higher among post- than premenopausal gynecologists (both, p = 0.0001) and among those who had undergone hysterectomy than those experiencing natural menopause. A 38.5% perceived breast cancer as the main risk related to MHT, and a high proportion prescribed non-hormonal drugs (86.4%) or alternative therapies (84.5%).Most female gynecologists in this survey would use MHT if menopausal symptoms were present. Postmenopausal physicians use MHT and prescribe it to their symptomatic patients at a higher rate than premenopausal physicians.

Few Latin American studies have described menopausal symptoms in detail by means of a standardized assessment tool. The objective of this study was to assess the prevalence and severity of menopausal symptoms and their impact over quality of life among mid-aged Latin American women.In this cross-sectional study, 8373 otherwise healthy women aged 40-59 years from 12 Latin American countries were asked to fill out the Menopause Rating Scale (MRS) and a questionnaire containing personal sociodemographic data. Menopause status (pre-, peri- and postmenopausal) was defined according to the criteria of the Stages of Reproductive Aging Workshop.Of all the studied women, 90.9% had at least one menopausal symptom (complaint) that they rated. Muscle and joint discomfort, physical and mental exhaustion and depressive mood were highly prevalent and rated as severe-very severe (scores of 3 and 4), at a higher rate than vasomotor symptoms (15.6%, 13.8% and 13.7% vs. 9.6%, respectively). Of premenopausal women (40-44 years), 77.0% reported at least one rated complaint, with 12.9% displaying MRS scores defined as severe (16). The latter rate increased to 26.4% in perimenopausal, 31.6% in early postmenopausal and 29.9% among late postmenopausal women. As measured with the MRS, the presence of hot flushes increased the risk of impairment of overall quality of life in both premenopausal (odds ratio 12.67; 95% confidence interval 9.53-16.83) and peri/postmenopausal women (odds ratio 9.37; 95% confidence interval 7.85-11.19).In this large, mid-aged, female Latin American series, muscle/joint discomfort and psychological symptoms were the most prevalent and severely rated menopausal symptoms. The symptoms appear early in the premenopause, significantly impair quality of life and persist 5 years beyond the menopause.

Background Several studies indicate that quality of life (QoL) is impaired in middle aged women. Assessment of QoL using a single validated tool in Latin American climacteric women has not been reported to date at large scale. Objective The Menopause Rating Scale (MRS) was used to assess QoL among middle aged Latin American women and determine factors associated with severe menopausal symptoms (QoL impairment). Methods In this cross-sectional study, 8373 healthy women aged 40–59 years, accompanying patients to healthcare centres in 18 cities of 12 Latin American countries, were asked to fill out the MRS and a questionnaire containing socio-demographic, female and partner data. Results Mean age of the entire sample was 49.1 ± 5.7 years (median 49), a 62.5% had 12 or less years of schooling, 48.8% were postmenopausal and 14.7% were on hormonal therapy (HT). Mean total MRS score (n = 8373) was 11.3 ± 8.5 (median 10); for the somatic subscale, 4.1 ± 3.4; the psychological subscale, 4.6 ± 3.8 and the urogenital subscale, 2.5 ± 2.7. The prevalence of women presenting moderate to severe total MRS scorings was high (>50%) in all countries, Chile and Uruguay being the ones with the highest percentages (80.8% and 67.4%, respectively). Logistic regression determined that impaired QoL (severe total MRS score ≥17) was associated with the use of alternatives therapies for menopause (OR: 1.47, 95% CI [1.22–1.76], p = 0.0001), the use of psychiatric drugs (OR: 1.57, 95% CI [1.29–1.90], p = 0.0001), attending a psychiatrist (OR: 1.66, 95% CI [1.41–1.96], p = 0.0001), being postmenopausal (OR: 1.48, 95% CI [1.29–1.69, p = 0.0001]), having 49 years or more (OR: 1.24, 95% CI [1.08–1.42], p = 0.001), living at high altitude (OR: 1.43, 95% CI [1.25–1.62, p = 0.0001]) and having a partner with erectile dysfunction (OR: 1.69, 95% CI [1.47–1.94, p = 0.0001]) or premature ejaculation (OR: 1.34, 95% CI [1.16–1.55, p = 0.0001]). Lower risk for impaired QoL was related to living in a country with a lower income (OR: 0.77, 95% CI [0.68–0.88], p = 0.0002), using HT (OR: 0.65, 95% CI [0.56–0.76], p = 0.0001) and engaging in healthy habits (OR: 0.59, 95% CI [0.50–0.69], p = 0.0001). Conclusion To the best of our knowledge this is the first and largest study assessing QoL in a Latin American climacteric series with a high prevalence of impairment related to individual female and male characteristics and the demography of the studied population.

Objective: The aim of the study was to evaluate the association between sedentary lifestyle and the severity of menopausal symptoms and obesity in middle-aged women. Methods: The Menopause Rating Scale, the Goldberg Anxiety and Depression Scale, and the Athens Insomnia Scale were administered to 6,079 Latin American women aged 40 to 59 years. Sedentary lifestyle was defined as fewer than three weekly, 30-minute periods of physical activity. Results: Sedentary women had more severe menopausal symptoms (total Menopause Rating Scale score: 9.576.71 vs 8.01-6.27 points, P

The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS.To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability.Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015.Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability).The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P.001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P.01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P.01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage.In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.

OBJECTIVE: To assess the age at menopause (AM) in Latin America urban areas. DESIGN: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. RESULTS: The mean age of the entire sample was 49.4 ± 5.5 years. Mean educational level was 9.9 ± 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P less than 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P less than 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P less than 0.001) were more prone to an earlier onset of menopause. CONCLUSIONS: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause. © 2006 by The North American Menopause Society.

A case of accumulation of CSF into the brain parenchyma simulating a brain tumor, secondary to an obstructed ventriculoperitoneal shunt, is presented. Until now, only seven cases of this rare complication have been described.Magnetic resonance showed an expansive, low-density intracranial lesion on the right frontal and parietal lobe. This mass was biopsied, but no tumor was found and the diagnosis was brain edema.The mistake in the diagnosis was due to the clinical symptoms and to the MR images.

We report on the case of a 26-yr-old Mexican woman with a gastric stromal tumor associated with a carotid body paraganglioma who remained asymptomatic for 34 yr following partial gastric resection. She presented with a recurrent gastric stromal tumor and probable liver metastasis. She also had an ovarian serous cystadenoma and breast fibroadenoma. This case represents an incomplete form of Carney’s triad and demonstrates the usual indolent behavior of gastric stromal tumors associated with this condition.

A case of tension pneumocephalus that occurred after ventriculoperitoneal shunting is presented. We have reviewed 12 cases of pneumocephalus in association with ventriculoperitoneal shunt placement. This phenomenon occurs when air is forced through the shunt or enters through the cranial base because of: iatrogenic postsurgical connection, congenital fistula, trauma, or thinning of the cranial base. Ways of preventing and treating this problem are outlined.

BACKGROUND AND PURPOSE There has been no systematic analysis of emergency department (ED) utilization in the multiple sclerosis (MS) population. We investigated the acute-care needs of MS patients using ED as a route for entry into healthcare services. METHODS ED visits made by MS patients were identified. Data extracted included demographics, medical/neurological history, and workup/management in the ED. RESULTS The Mount Sinai ED received 569 visits from 224 MS patients during a 3-year period, of whom 33.5% were covered by Medicaid and 12.9% were uninsured. Patients with an Expanded Disability Status Scale score of ≥6 accounted for 54%, 50.5% of relapsing remitting MS patients were being treated with disease-modifying therapies, and 74.5% of the ED visits were non-neurological. Patients with mild-to-moderate MS were more likely to present to the ED for issues directly related to MS such as acute exacerbations, while those with severe MS presented more often due to medical issues indirectly related to MS, such as urinary tract infections (p

Although hypersensitivity pneumonitis is the most common pulmonary complication described during treatment with methotrexate, other complications like lymphoproliferative and infectious disease may be considered in the study of respiratory disease associated to methotrexate. The existence of an increased risk to developing infectious diseases may be similar to that observed during treatment with antagonists of tumor necrosis factor and corticosteroids, where Cytomegalovirus pneumonia is a serious complication; early diagnosis and treatment will prevent a potentially fatal outcome.

Background Muscle and joint aches (MJA) are frequently observed among menopausal women. They impair quality of life and are a burden to the healthcare system. Objective To analyze the relation between MJA and several variables related to the menopause. Methods In this cross-sectional study, 8373 healthy women aged 40–59 years, accompanying patients to healthcare centers in 18 cities of 12 Latin American countries, were asked to fill out the Menopause Rating Scale (MRS) and a questionnaire containing personal data. Results Mean age of the whole sample was 49.1 ± 5.7 years, 48.6% were postmenopausal and 14.7% used hormone therapy (HT). A 63.0% of them presented MJA, with a 15.6% being scored as severe to very severe according to the MRS (scores 3 or 4). Logistic regression model determined that vasomotor symptoms (OR: 6.16; 95% CI, 5.25–7.24), premature menopause (OR: 1.58; 95% CI, 1.02–2.45), postmenopausal status (OR: 1.43; 95% CI, 1.20–1.69), psychiatric consultation (OR: 1.93; 95% CI, 1.60–2.32) and the use of psychotropic drugs (OR: 1.35; 95% CI, 1.08–1.69) were significantly related to the presence of severe-very severe MJA. Other significant variables included: age, tobacco consumption and lower education. Self perception of healthiness (OR: 0.49; 95% CI, 0.41–0.59), private healthcare access (OR: 0.77; 95% CI, 0.67–0.88) and HT use (OR: 0.75; 95% CI, 0.62–0.91) were significantly related to a lower risk for the presence of severe-very severe MJA. Conclusion In this large mid-aged sample the prevalence of MJA was high, which was significantly associated to menopausal variables, especially vasomotor symptoms. This association may suggest a potential role of mid-life female hormonal changes in the pathogenesis of MJA.

The prognostic potential of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated in sepsis. Enzyme concentrations were determined in samples obtained from septic patients at time of diagnosis. Statistically significant increases in activities of total plasma SOD (P < 0.003, n = 32), erythrocyte (RBC) SOD (P < 0.007, n = 16), plasma CAT (P < 0.0001, n = 32), and RBC CAT (P < 0.005, n = 16) were found in septic patients when compared with healthy adult controls (n = 7). Further, within the group of septic patients, statistically significant differences were found for total plasma SOD (P < 0.05) and plasma CAT (P < 0.009) (but not for RBC determinations) when survivors (n = 15) were compared with nonsurvivors (n = 17). No significant differences were found for either plasma or RBC enzyme concentrations when patients who developed adult respiratory distress syndrome were compared with those who did not. The most striking finding was that plasma total SOD values of > 10 kU/L were found in 7 of 21 (30%) patients who did not survive their sepsis and that these values did not overlap with any surviving patients or controls. However, while high total plasma SOD activity appears to have some potential as a prognostic indicator, lower values (0.0-8.8 kU/L) do not. For plasma CAT, despite finding statistically significant differences between survivors and nonsurvivors, the substantial overlap in the values obtained for the two groups limits the practical prognostic potential of this enzyme.

The aim of this study was to determine an optimal waist circumference (WC) cutoff value for defining the metabolic syndrome (METS) in postmenopausal Latin American women.A total of 3,965 postmenopausal women (age, 45-64 y), with self-reported good health, attending routine consultation at 12 gynecological centers in major Latin American cities were included in this cross-sectional study. Modified guidelines of the US National Cholesterol Education Program, Adult Treatment Panel III were used to assess METS risk factors. Receiver operator characteristic curve analysis was used to obtain an optimal WC cutoff value best predicting at least two other METS components. Optimal cutoff values were calculated by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity). In addition, total accuracy, distance to receiver operator characteristic curve, and the Youden Index were calculated.Of the participants, 51.6% (n = 2,047) were identified as having two or more nonadipose METS risk components (excluding a positive WC component). These women were older, had more years since menopause onset, used hormone therapy less frequently, and had higher body mass indices than women with fewer metabolic risk factors. The optimal WC cutoff value best predicting at least two other METS components was determined to be 88 cm, equal to that defined by the Adult Treatment Panel III.A WC cutoff value of 88 cm is optimal for defining METS in this postmenopausal Latin American series.

Objective: The aim of this study was to determine vasomotor symptom (VMS) prevalence, duration, and impacton quality of life in middle-aged women using a validated menopausal tool.Methods: The Menopause Rating Scale (MRS) and an itemized questionnaire containing personal sociodemo-graphic data were used to examine 8,373 women aged 40 to 59 years from 22 healthcare centers in 12 LatinAmerican countries.Results: Less than half (48.8%) of all women studied were postmenopausal, 14.7% used hormone therapy (HT),54.5% presented VMS of any degree, and 9.6% presented severe/bothersome symptoms. The rate of VMS (anydegree) significantly increased from one menopausal stage to the next. HT users presented more VMS (any degree)than did nonusers (58.6% vs 53.8%, P = 0.001). When surgical postmenopausal women were compared, nonYHTusers displayed a higher prevalence of severe VMS (16.1% vs 9.0%, P = 0.0001). The presence of VMS of anydegree was related to a more impaired quality of life (higher total MRS score; odds ratio, 4.7; 95% CI, 4.1-5.3). Thiseffect was even higher among women presenting severe VMS. Logistic regression analysis determined that thepresence of severe psychological/urogenital symptoms (MRS), lower educational level, natural perimenopause-postmenopause status, nulliparity, surgical menopause, and living at high altitude were significant risk factors forsevere VMS. HT use was related to a lower risk. A second regression model determined that surgical menopause,intense psychological/urogenital symptoms, and a history of psychiatric consultation were factors related to severeVMS persisting into the late postmenopausal stage (5 or more years).Conclusions: In this Latin American middle-aged series, VMS prevalence was high, persisting into the late post-menopausal phasein ahighrate andseverelyimpairingqual ity of life. HTusewas related toalower riskof severeVMS.Key Words: Vasomotor symptoms Y Prevalence Y Menopause Rating Scale Y Menopause Y Latin America.

We report on the case of a 50-year old woman with two intracranial meningiomas and two spinal ones. All were diagnosed at the same time and there were no signs of neurofibromatosis. Multiple meningiomas in different neural spaces are extremely rare, and even rarer is the simultaneous diagnosis of separate coincident lesions. The literature in this regard is reviewed.

Introduccion. Las hernias discales son una patologia habitual dentro de la Neurocirugia, pero la presentacion suele producirse en la edad adulta y las series publicadas en ninos son pocas y con un numero de casos pequeno. Se ha invocado un factor genetico, pero en ninguno de nuestros casos existia antecedente familiar de hernia de disco. Pacientes y metodos. Se presentan 10 hernias discales lumbares (HDL) en adolescentes en una serie de 1.920 HDL, que abarca desde 1988 hasta 1998. Todos los casos de la serie se presentaron asociados a la realizacion de algun tipo de deporte. Las edades estaban comprendidas entre los 12 y los 16 anos. La clinica fue un cuadro de dolor lumbar con irradiacion por el territorio radicular asociado (L5 o S1). Todos los casos se estudiaron con resonancia magnetica y su localizacion fue, en el 100%, entre L4-L5 y L5-S1; todas eran hernias subligamentosas y el 81,5% aparecieron en posicion posterolateral. La anatomia patologica demostro una consistencia elastica y alto contenido en agua, sin fenomenos degenerativos. Resultados. En todos los casos desaparecia el cuadro doloroso y se hacian asintomaticas tras la realizacion de extirpacion por el procedimiento de microdisectomia. No se preciso reintervencion en ningun caso, y el control postoperatorio fue de entre 2 y 5 anos. Conclusiones. La HDL del adolescente es una patologia poco frecuente y en todos los casos los resultados fueron buenos despues de la intervencion quirurgica. La localizacion generalmente es subligamentosa posterolateral.

We have studied 450 cases of human breast carcinoma at the histochemical and ultrastructural level. The breast biopsies were obtained from Canada, Mexico and Dominican Republic. This study was undertaken to evaluate the prognostic significance of classification of breast tumors, proposed in 1971 by Murad, based on their cell of origin. Under this classification, ATPase positive tumors represent those of myoepithelial origin, while the remainder are designated ductal or ductular based upon defined ultrastructural characteristics. We observed a distribution of tumor types essentially similar to that reported by Murad, and no significant differences were observed between the contributing centers. No correlation was observed between this classification and the histological classification described by Stewart. We found no evidence that ATPase positive tumors were myoepithelial in origin. They showed histochemical similarities to ductal and ductular tumors, and had features indicating their secretory nature. Estrogen receptor levels were measured in 20 cases, and did not reveal any correlation with tumor type. An interesting feature requiring further investigation was the high incidence of endocrine-like secretory granules in all histological types of tumors studied.

A twenty-one year old woman with severe and prolonged renal failure associated with the acute onset of jaundice following delivery is described. The clinical, pathological and biochemical findings were consistent with fatty liver of pregnancy complicated by renal failure. The ultrastructural morphology of the renal lesion is described in detail and the changes in the glomeruli are interpreted as compatible with a lesion produced by intraglomerular fibrin formation. Such an event may have been the cause of the renal failure in this case.

A previous examination, done by others, of the endocrine cells of the canine pyloric antrum following its transplantation to the colon evidenced an increase in their number; the cell types involved, however, were not individualized. The present study further characterizes the changes occurring in the endocrine cells of the pyloric antrum of dogs following transplantation to the colon. The main change observed consists of hyperplasia of the enterochromaffin cells, with minor qualitative modifications in the antral gastrin-producing cells being noted only by electron microscopy. The response of the enterochromaffin cells cannot be readily explained but might be related to similar enterochromaffin cell hyperplasias found in human stomachs with peptic ulcers. Antrum transplantation to the colon in dogs appears to provide a promising experimental model for the study of the relationship between gastrin and other humoral factors (probably biogenic amines) in the mechanism of gastric secretion under normal as well as abnormal circumstances.

Although histochemical, immunohistochemical, and electron microscopic methods have led to the identification of a large variety of endocrine cells in the upper gastrointestinal mucosa, no conventional light microscopic technique capable of the simultaneous identification of these cells has been reported. Such a staining method would be of considerable value to the pathologist as the malfunction of the endocrine cells of the gut, which produce numerous digestive hormones and biogenic amines, is closely related to a number of clinical conditions afflicting man. In this work, after testing three different polychrome staining methods, it has been concluded that a slightly modified Herlant's tetrachrome in tissues fixed in Zenker-formol is the procedure of choice. This method allows the distinction of several different cell types in the upper gastrointestinal mucosa of man and dog and permits the easy identification of the gastrin-producing cells on a routine basis. This identification has been confirmed in the case of two patients with gastrin cell hyperplasia, seen by both light and electron microscopy. Herlant's tetrachrome has proven valuable in the screening of human as well as experimental gastrointestinal tissues and it has been found to be very suitable for recognizing gastrin-producing cell hyperplasias. The usefulness of this method is expected to increase with the establishment of further correlations between the light and electron microscopy of the endocrine cells of the gut.

A 67-year-old man with a 1 1/2;-month history of spastic paraparesis caused by a dorsal intradural disc herniation underwent surgical treatment via a posterior approach. Dorsal herniated discs are rare, and intradural dorsal disc herniations are even more infrequent. Including this case, the medical literature reviewed describes only four such cases.

✓ A case of a cerebrovascular varix located in the right lateral ventricle is reported. The patient suffered intraventricular and subarachnoid hemorrhages. The intraventricular varix was coagulated and excised.

Skeletal muscle biopsy specimens from diabetic and nondiabetic subjects were examined by light and electron microscopy. Distinctive lesions in the capillaries were found in twelve of sixteen specimens from diabetic subjects but in only three of nineteen from nondiabetic subjects. The development of the concept of diabetic microangiopathy is reviewed and discussed in relation to other vascular lesions complicating diabetes, and in relation to an abnormal response of the peripheral circulation to adrenalin infusion which has recently been described in human diabetes.

A series of recent observations on different aspects of the chemistry and metabolic actions of bile have led us to investigate the possibility that bile may induce pancreatitis through the physicochemical detergent properties of its salts. To determine the relative importance of proteolytic enzymes on the one hand, and the detergent action of bile on the other, in the pathogenesis of bile-induced experimental pancreatitis in the dog, the early morphologic changes (1–30 min) produced by the intraductal injection of the following substances were investigated: (1) autogenous bile; (2) bile salt; (3) an anionic detergent, sodium lauryl sulfate (SLS); (4) trypsin; (5) a cationic detergent, cetrimide; (6) a neutralized mixture of SLS and cetrimide; and (7) saline solution. Autogenous bile, bile salts and SLS produce pancreatitis of similar morphologic appearance, characterized by punched-out areas of coagulation necrosis. Trypsin-induced pancreatitis was distinctly different from that produced by bile, bile salts and SLS. In trypsin pancreatitis, irregular areas of necrosis and hemorrhage were seen. Inactivation of the detergent activity of SLS by mixing it with the cationic detergent, cetrimide, reduced the capacity of SLS to induce pancreatitis similar to that induced by bile and bile salts. These data seem to indicate that the early phases of bile-induced pancreatitis in our experiments are unlikely to result from the liberation of trypsin, but are related instead to the detergent activity of bile salts.

Summary1. Cortisone acetate administered intramuscularly to rabbits caused the gradual appearance of glycosuria which reached a maximum at the 5th to 9th days and then declined. Increased dosage reestablished the glycosuria but it again regressed. Morphologically, the most prominent lesion observed was ductular and centroacinar proliferation and the formation of irregularly shaped and “Mulberry” islets. In addition, numerous mitotic beta cells were observed up to 10 days after starting cortisone treatment.Similarly, degranulation of the beta cells was most prominent at early stages. Glycogen infiltration seemed to appear first in the ductular tissue and required a greater degree and duration of diabetes before affecting the beta cells. 2. The degranulation and increased mitotic activity of the beta cells are thought to be a response to hyperglycemia as is the glycogen infiltration of ducts and beta cells. The proliferative activity on the other hand is considered to represent a more direct action of corti...