Pregnant woman from southern Peru with rabies infection who delivered a healthy baby.

Rabies in pregnancy is rare with a high mortality. We report a pregnant woman who developed urban rabies from the bite of an infected dog. An emergency Cesarean section was performed at 31 weeks of gestation, and a premature baby was delivered who survived and did not develop rabies. The mother, however, suffered a rapid clinical deterioration and was admitted to intensive care where a Milwaukee protocol was followed. The patient survived 19 months but developed severe neurological sequelae secondary to rabies encephalitis and finally died of respiratory failure.

Placental Proinflammatory State and Maternal Endothelial Dysfunction in Preeclampsia.

OBJECTIVE: To evaluate the placental and decidual gene expression and maternal and umbilical serum concentrations of tumor necrosis factor alpha, interleukin 6 (IL-6), IL-8, IL-10, IL-1 receptor antagonist (IL-1RA), intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1), along with the proinflammatory/anti-inflammatory cytokine ratios in women with preeclampsia (PE) vs. women with normal pregnancy (NP), and to analyze PE classified as early- (EO) and late-onset (LO). METHODS: This cross-sectional study was performed with 50 women with PE (EO n = 30, LO n = 20) and 50 women with NP. Tissue gene expression levels were measured by real-time RT-PCR. Cytokines and adhesion molecules serum concentrations were measured by immunoassays. RESULTS: In PE, placental expression of IL-10 and IL-1RA was lower, while placental IL-8/IL-1RA ratio and maternal concentrations of VCAM-1 were higher vs. NP. In EO, placental expression of IL-10 was lower, while placental IL-8/IL-10 and IL-8/IL-1RA ratios were higher than LO and NP. Maternal concentrations of IL-6 were higher in LO than EO and NP. Throughout PE, maternal VCAM-1 concentrations were higher vs. NP. No significant differences were observed in the decidual expression and umbilical concentrations of the markers between the groups. CONCLUSION: PE associates with a proinflammatory placental state; however, EO associates with a proinflammatory placental state, while LO associates with systemic maternal inflammation. Both subtypes associated with maternal endothelial dysfunction.

Similar to Adiponectin, Serum Levels of Osteocalcin are Associated with Mammographic Breast Density in Postmenopausal Women.

OBJECTIVE: Breast cancer is the most common type of cancer in Canadian women and worldwide. Mammographic density is a well-established breast cancer risk. Recent evidence suggested inverse correlations among adiponectin, osteocalcin, and the risk developing breast cancer. The objective of the study was to evaluate the relationship between breast density and adiponectin and osteocalcin concentrations. METHODS: A cross-sectional study was performed in 239 women, age range 40 to 60. Mammographic density, serum adiponectin, and osteocalcin levels were measured. According to the Wolfe method, participants were divided into those with low-risk and high-risk pattern mammograms. RESULTS: The study population included 107 premenopausal and 132 postmenopausal women. Parameters were no different between women with low-risk and high-risk patterns. In obese postmenopausal women, the high-risk pattern mammogram group had significantly higher values of adiponectin and osteocalcin compared with the low-risk pattern group. Multiple linear regression analyses showed that adiponectin and osteocalcin levels were associated with high-risk pattern mammograms. CONCLUSION: Adiponectin and osteocalcin levels were directly associated with high-risk pattern mammograms in obese postmenopausal women. These results do not support the use of adipokines as biomarkers; nevertheless, the most important factor is to assess the risk through breast density.

[Dienogest usefulness in pelvic pain due to endometriosis. A meta-analysis of its effectiveness]. / Evaluación de dienogest en el tratamiento del dolor pélvico asociado a la endometriosis. Un metaanálisis de su efectividad.

BACKGROUND: Endometriosis is the presence of functional endometrial tissue in the pelvic peritoneum and it affects several age groups. That is why the impact of endometriosis in quality of life is considerable. The objective of this study was to evaluate the effectiveness of dienogest in patients with pelvic pain associated to endometriosis (PPAE). METHODS: The evaluation of the effectiveness was carried out through a systematic review using the Cochrane methodology. It was used Markov model, which considers two states of health (with and without PPAE), with the possibility of weekly transition. Women between 18 and 45 years with PPAE were included, in a temporary horizon of 26 weeks. A level of statistical significance of 95% was used for a p < 0.05, with a multivariate probabilistic analysis of sensibility, as well as a univariate analysis of sensibility in several scenarios. RESULTS: The probability that the female patient did not experience PPAE with the initial treatment was 87.91% with dienogest, 80.07% with danazol, 84.93% with medroxyprogesterone (injectable and oral) and 89.17% with gosereline. The probability that the female patient abandoned her initial treatment was 9% with dienogest, 12.07% with danazol, 9.6 and 6.75% with medroxyprogesterone injectable and oral, respectively, and 10.8 and 3.6% 3-monthly and monthly with gosereline. CONCLUSION: Compared to danazol, medroxiprogesterone and gosereline, dienogest is the most efficient alternative to treat PPAE.

Introducción: La endometriosis es la presencia de tejido endometrial funcional en el peritoneo pélvico y afecta a varios grupos de edad, por lo que su impacto en la calidad de vida es considerable. El objetivo fue evaluar la efectividad del dienogest en pacientes con dolor pélvico asociado a endometriosis (DPAE), al compararlo con danazol, medroxiprogesterona y goserelina. Métodos: se hizo una revisión sistemática de la literatura con la metodología Cochrane. Se usó el modelo de Markov, que considera dos estados de salud: con y sin DPAE, con posibilidad de transición semanal. Se consideraron mujeres entre 18 y 45 años con DPAE, en un horizonte de 26 semanas; se utilizó un nivel de significación estadística de 95% (p < 0.05), con un análisis probabilístico multivariante de sensibilidad y uno univariante de sensibilidad en varios escenarios. Resultados: la probabilidad de que la mujer se encontrara sin DPAE con el tratamiento inicial fue de 87.91% para dienogest, 80.07% para danazol, 84.93% para medroxiprogesterona inyectable y oral y 89.17% para goserelina; la probabilidad de que la mujer abandonara su tratamiento inicial fue de 9% para dienogest, 12.07% para danazol, 9.6 y 6.75% para medroxiprogesterona inyectable y oral, respectivamente, y 10.8 y 3.6% para goserelina trimestral y mensual, respectivamente. Conclusiones: Comparado con el danazol, la medroxiprogesterona y la goserelina, el dienogest es la alternativa más eficiente para el DPAE.

[Persists the controversy concerning the rutinary use of diagnostic tests in asymptomatic persons]. / Persiste la controversia acerca del uso rutinario de pruebas de detección en personas asintomáticas.

Currently, in medicine there is an environment replete with controversy and debate, partially due to the popular concept Evidence-Based Medicine, and to the development of technological advances and, apparently, better therapeutic resources. This has led to the establishment of an over-diagnosis epidemic and to an excess of therapeutic interventions, which do not necessarily lead to a longer life expectancy. Some medical controversies, which have called the attention of physicians and even of common people are those related with dislipoproteinemias, pre-diabetes and detection of cancer in asymptomatic persons. The debate and the controversy will surely continue and that is why it is very important to emphasize that clinical practice should be personalized, taking into account risks and implied benefits.

En la actualidad existe en medicina un ambiente repleto de controversias y debates, en parte generado por la popularidad del concepto de medicina basada en evidencia y por la aparición de avances tecnológicos y aparentemente mejores recursos terapéuticos. Esto ha llevado a la instalación de una epidemia diagnóstica y a una excesiva politerapéutica que no se traducen en una más larga expectativa de vida. Algunas controversias médicas que han llamado la atención de los médicos e incluso del público en general son las relacionadas con los tópicos de dislipoproteinemia, prediabetes y detección de cáncer en personas asintomáticas. El debate y la controversia seguramente continuarán y por ello resalta la importancia de la práctica médica en la individualidad, tomando en cuenta los riesgos y los beneficios implicados.

Gene variants in the FTO gene are associated with adiponectin and TNF-alpha levels in gestational diabetes mellitus.

BACKGROUND: Obesity may have a role in the development of gestational diabetes mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and obesity associated) gene have been associated with obesity. The aim of this study was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in women with GDM and their associations with maternal pre-pregnancy weight and body mass index, gestational weight gain and mediators of insulin resistance in GDM like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha), compared with healthy pregnant controls. METHODS: 80 women with GDM and 80 women with normal pregnancy were considered for the present study. Genotyping of selected SNPs in all study subjects was done using the Taq-Man assay and the adipokines and ghrelin were measured by immunoassays. Chi square test, odds ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between FTO SNPs and GDM. RESULTS: There was no association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying the risk alleles of the three SNPs had increased TNF-alpha, and decreased adiponectin levels; these associations remained significant after adjusting for pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was also associated with increased weight gain during pregnancy. CONCLUSIONS: The FTP SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the etiology of GDM in the studied ethnic group. However, these SNPs were associated with adiponectin and TNF-alpha concentrations in GDM subjects.

[Debate persists over the use of mammogram in the detection of breast cancer in asymptomatic women]. / Persiste el debate del uso rutinario de la mamografía en la detección de cáncer de mama en mujeres asintomáticas.

In this opinion article, it is discussed the importance of questioning the use of mammogram in the detection of breast cancer in asymptomatic women.

En el presente artículo de opinión se discute acerca de la necesidad de cuestionar la práctica rutinaria del empleo de la mamografía para detectar cáncer de mama en mujeres asíntomáticas.

Lower Plasma Ghrelin Levels are Found in Women with Diabetes-Complicated Pregnancies.

OBJECTIVE: To evaluate the associations of glycemic control and gestational age with ghrelin and proinsulin levels in cord blood and mothers' peripheral blood during pregnancy. METHODS: This is a cross-sectional comparative study of twenty-four pregnant women with gestational diabetes (GD), 18 with type 2 diabetes mellitus (T2DM), and 36 without diabetes, as well as their neonates. Levels of proinsulin, ghrelin, and glycated hemoglobin A1c (HbA1c) were measured from maternal blood during the last week before caesarian delivery and in neonatal umbilical cord blood samples. RESULTS: Mothers with GD and T2DM had significantly lower ghrelin levels compared to the healthy mothers (p<0.001). Maternal proinsulin was lower in women with GD than in women without diabetes (p<0.001). Proinsulin was significantly elevated in the neonates of women with GD and in women with HbA1c ≥6.5% (p<0.001). However, maternal ghrelin levels were higher (p=0.031) and neonate proinsulin levels lower in the pre-term offspring of mothers with GD (p=0.033). There was a negative correlation between HbA1c levels and birth weight (r=-0.407, p<0.001). CONCLUSION: Ghrelin levels were lower in pregnant women with diabetes, although pre-term birth appeared to reverse this trend in GD. Proinsulin levels were also low in pregnant women with diabetes and even lower in pre-term vs. at-term births. Both ghrelin and proinsulin levels were lower in pregnant women with diabetes and HbA1c of <6.5%. Thus, ghrelin participates in the adaptation to the caloric imbalance of diabetic pregnancy and may play a similar role in pregnancy-related complications, since high ghrelin concentrations may be necessary for normal fetal development.

Colesterol y aterosclerosis. Consideraciones históricas y tratamiento / Cholesterol and atherosclerosis. Historical considerations and treatment

Resumen El colesterol es un esteroide precursor de hormonas, componente esencial de la membrana celular, sin embargo, alteraciones en la regulación de la síntesis, absorción y excreción del colesterol predisponen al desarrollo de enfermedades cardiovasculares de origen aterosclerótico. De esta manera, reconociendo los acontecimientos históricos desde hace 200 años, con Michel Chevreul que le dio el nombre "colesterina", más tarde Lobstein que acuñó el término aterosclerosis y Marchand que lo introduce, Anichkov que identifica el colesterol en las placas de ateroma, y el descubrimiento del receptor LDL por Brown y Goldstein; además de la aparición de los diferentes fármacos que han surgido desde los fibratos, las estatinas y en esta década cetrapibs, muy prometedores para aumentar el HDL, en forma más reciente, ezetimibe y anti-PCSK9 para inhibir el proceso de degradación del receptor LDL; no obstante, estos avances no han sido suficientes para disminuir la morbilidad en enfermedades cardiovasculares.

Abstract Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming "cholesterol"; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

[Cholesterol and atherosclerosis. Historical considerations and treatment]. / Colesterol y aterosclerosis. Consideraciones históricas y tratamiento.

Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming «cholesterol¼; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

[Scientific contributions of Jules Hirsch regarding the physiopathogenesis of obesity]. / Contribuciones científicas de Jules Hirsch sobre la fisiopatogenia de la obesidad.

Jules Hirsch was born in New York City and died at age 88 after a long illness. He was considered notorious leader in the study of human metabolism mainly in the area of lipids and obesity. His research at The Rockefeller University helps establish the mechanism of obesity and lipids metabolism. Hirsch joined Rockefeller´s faculty in 1954 and remained there for the rest of his career. Hirsch´s research helped to support the idea of dynamic interactions among diet, physical activity, general metabolism and obesity. At that time most scientific considered adipose tissue to be biologically inert such as a passive insulator in which the body reserved energy in the form of triglycerides. Hirsch had a natural characteristic of showing a nice smile and greeting for everyone he worked with at the university. Another important contribution was there relationship between diet and cardiovascular ailments as well as metabolism disturbance.

Jules Hirsch nació en la ciudad de Nueva York y murió en Julio 23 de 2015, a la edad de 88 años. Es considerado como un notable y eminente líder en el estudio del metabolismo; particularmente centró su interés en la obesidad ocasionada por un acumulo excesivo de grasa por exceso de alimento y falta de actividad física. Hirsch ingresó a la facultad como profesor en la Universidad Rockefeller en 1954 y permaneció por el resto de su carrera como investigador clínico hasta su jubilación como emérito. Los estudios de Hirsch apoyaron la idea de que existía una interrelación entre la dieta, la actividad física, el metabolismo y la obesidad. En ese tiempo la mayor parte de los científicos pensaba que el tejido adiposo era simplemente una reserva inerte en donde se almacenaba la grasa en forma de triglicéridos para proporcionar energía al organismo. Una de las características personales de Hirsch era una agradable sonrisa y el buen trato a todas las personas que trabajaban en la universidad. Hirsh también advirtió, y esta es otra contribución importante, que la obesidad, la falta de actividad física y el exceso de lípidos contribuyen al desarrollo de trastornos metabólicos y enfermedad cardiovascular.

Hypercholesterolemia As a Risk Factor for Cardiovascular Disease: Current Controversial Therapeutic Management.

Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane; however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite the recognition of historical events for 200 years starting with Chevreul naming "cholesterine"; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor (r-LDL), as well as the emergence of different drugs such as fibrates, statins and cetrapibs during this decade promising to increase HDL, and the most recent, ezetimibe and anti-PCSK9 to inhibit the degradation of r-LDL, morbidity has not been reduced in cardiovascular disease. To date, the controversy continues regarding the best and appropriate medical therapy for hypercholesterolemia; likewise, there is the recommendation of a healthy dietary content regarding the amount of sugar as well as the type of fats, either saturated or polyunsaturated. Together, control of circulating cholesterol, amelioration of hypertension, regulation of diabetes, and dietary recommendations might prevent atherosclerosis.

[Clinical implications of basic research in preeclampsia: immunological tolerance]. / Implicaciones clínicas de la investigación básica de la preeclampsia: tolerancia inmunológica.

Preeclampsia is one of the main causes of maternal and perinatal mortality in the world; however, the pathophysiologic pathways haven't been clearly elucidated. It is thought to result from a breakdown of maternal tolerance to paternal antigens in placenta that start an immune response against the trophoblast inducing a defective placentation and a hipoxic/isquemic environment which in turn triggers a systemic inflamatory response. This review gives an overview of the mechanims involved in maternal tolerance, how these are disrupted in preeclampsia, and how they contribute to the inflamatory response.

Morphological changes of red blood cells in peripheral blood smear of patients with pregnancy-related hypertensive disorders.

BACKGROUND AND AIMS: Pregnancy-related hypertensive disorders are complications in which risk factors are identified such as nulliparity, age, malnutrition, obesity and social issues. Those statements are explained by theories of abnormal placentation, immunological inadequacy, genetics and oxidative stress, but all theories converge in endothelial damage, which is able to mechanically deform and hemolyze erythrocytes as they pass through the capillaries. Given the effects of endothelial damage, the aim of the study was to determine erythrocyte alterations in peripheral blood smear of patients with hypertensive disorders of pregnancy that could be used as prognostic condition. METHODS: We performed a prospective, descriptive and observational study where all patients with hypertensive disorders admitted to the obstetrics and gynecology service of a specialty hospital were recruited. Patients who provided signed informed consent underwent peripheral blood smear. Results were tabulated in percentage graphics and analyzed with Cramer's V based on χ(2). The peripheral blood smear consisted of an extended drop of peripheral blood from the patient with subsequent hematological staining done with Romanowsky stain. RESULTS: A total of 119 samples were analyzed; 74% showed abnormal morphology of erythrocytes and the most frequent abnormality was the presence of schistocytes in up to 39% of samples. Descriptive analysis showed a degree of association to independent variables with Cramer's V = 0.41 value (p <0.05). CONCLUSIONS: A high percentage of patients with hypertensive disorders of pregnancy show some morphologic alterations of erythrocytes in peripheral blood smear.

[A tribute to Carl Djerassi]. / Tributo a Carl Djerassi.

On January 15, 2015, Carl Djerassi, an extraordinary personality, died at the age of 91 years. He was born in Vienna, Austria, on October 29, 1923. His parents were physicians and probably he wanted to be also a physician, but sooner than later he chose to be a chemist. In 1939 he arrived to live to New York with his mother. In 1945 he became American citizen. Part of his work is the first commercial antihistamine, pyribenzamine, and the first successful combined oral contraceptive pill. With this editorial we make a tribute to this steroid pioneer.

El 30 de enero de 2015 falleció, a la edad de 91 años, Carl Djerassi, un personaje extraordinario. Nació en Viena, Austria, el 29 de octubre de 1923. Sus padres eran médicos y quizás por esa razón él también quería serlo, pero pronto escogió la química. En 1939 llegó con su madre a vivir a Nueva York y en 1945 se naturalizó estadounidense. Son obra suya el primer antihistamínico comercial (la piribenzamina) y el compuesto farmacológico de la píldora anticonceptiva. Sirva el presente editorial como un homenaje a este pionero de los esteroides sintéticos.

Lipocalin-2 plasmatic levels are reduced in patients with long-term type 2 diabetes mellitus.

BACKGROUND: De-regulation of adipocytokines synthesis and secretion appears to be involved in the pathogenesis of different metabolic diseases. AIMS: We assessed a possible association between plasmatic levels of lipocalin-2 (LCN2) and type 2 diabetes mellitus (T2DM), as well as among levels of LCN2 and those of adiponectin, ghrelin, leptin and resistin, in Mexican diabetic patients. SUBJECTS AND METHODS: Fifty-three healthy individuals and fifty-three with long-term T2DM were included. Measurements from all patients for BMI, fasting glucose, insulin, lipids and adipocytokine profiles were obtained. RESULTS: Comparison of data between the corresponding for diabetic subjects and those of healthy individuals showed significant differences in every anthropometric and metabolic parameter analyzed (P < 0.001). In diabetic subjects, lipocalin-2 and ghrelin plasmatic levels were statistically diminished (P < 0.001) in comparison with the levels registered in healthy subjects. In conclusion, in this study we found that LCN2 plasmatic levels are reduced in Mexican subjects with long-term diabetes and this reduction in circulating concentrations is similar to the one reported for anti-inflammatory adipocytokines, which suggests that lipocalin-2 is somehow involved in insulin resistance and cardiometabolic alterations through an uncharacterized mechanism generated by the inflammation process.

[Commentary on the Nobel Prize that has been granted in Medicine-Physiology, Chemistry and Physics to noteable investigators]. / Comentario sobre los Premios Nobel de Medicina-Fisiología, Química y Física otorgados a investigadoras notables.

The Nobel Prize was established by Alfred Nobel in 1901 to award people who have made outstanding achievements in physics, chemistry and medicine. So far, from 852 laureates, 45 have been female. Marie Curie was the first woman to receive the Nobel Prize in 1903 for physics and eight years later also for chemistry It is remarkable that her daughter Irene and her husband also received the Nobel Prize for chemistry in 1935. Other two married couples, Cori and Moser, have also been awarded the Nobel Prize. The present commentary attempts to show the female participation in the progress of scientific activities.

Early disturbed placental ischemia and hypoxia creates immune alteration and vascular disorder causing preeclampsia.

Preterm preeclampsia (PE) remains a leading cause of maternal death and perinatal morbidity. The pathophysiological process that underlies PE has been proposed to occur in two episodes, the first is a reduced placental perfusion and then the maternal clinical syndrome. Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors such as cytokines including TNF-α and interleukin 6, activated circulating immune cells and autoantibodies that have profound effects on blood flow and arterial pressure regulation. PE is also associated with decreased formation of vasodilators such as nitric oxide and prostacyclin. It is accompanied by widespread maternal vascular dysfunction and a chronic inflammatory response. Additionally, anti-angiogenic peptides are released, inhibiting vascular remodeling essential for increased blood flow to the growing uteroplacental unit. Although these factors accompany the clinical syndrome of PE, it is suggested that they are secondary to the maternal decrease in placental blood flow. Experimental evidence has demonstrated the importance of these soluble factors to increase blood pressure and stimulate the production of such anti-angiogenic factors, thereby eliciting a vicious cycle existing within the maternal vasculature as well as within the placental unit. These alterations in vascular function not only lead to hypertension but to multi-organ dysfunction. The quantitative importance of the various endothelial and humoral factors that mediate vascular dysfunction and hypertension during PE remains to be elucidated.