Increased tissue factor and thrombomodulin expression and histopathological changes in placentas of pregnancies with preeclampsia.

INTRODUCTION: Preeclampsia has a global frequency of 2-8% and a frequency of 10% in developing countries. In Colombia, preeclampsia causes 42% of maternal mortality. Alterations in placental homeostasis have been proposed to be involved in its pathophysiology. The aim of this study was to compare mRNA and protein levels of tissue factor (F3) and thrombomodulin (THBD) and the histopathological findings of placentas. MATERIALS AND METHODS: We studied 16 placentas from patients with preeclampsia and 19 term placentas with uncomplicated pregnancy. An expert pathologist, who was masked to the group assignment, conducted an evaluation to determine specific histological changes. Assessments of mRNA and protein levels of F3 and THBD were performed using real-time PCR and ELISA, respectively. RESULTS: Cases and controls differed in the frequency of decidual arteriopathy (p = 0.027), acute infarction (p = 0.001) and hyperplasia of the syncytiotrophoblast (p = 0.0017). Cases had increased levels of F3 mRNA (p = 0.0124) and protein (p <  0.0001) and THBD mRNA (p <  0.0001) and protein (p <  0.0001). CONCLUSION: In placenta of patients with preeclampsia, we detected abnormal expression of F3 and THBD with increased protein and mRNA levels. The role of these molecules in the pathogenesis of this disease and in alterations of hemostatic and histopathological aspects of placentas need further studying.

Expression of cystathionine beta-synthase and histopathological observations in placentas of patients with Down syndrome.

UNLABELLED: Down syndrome is the most frequent aneuploidy in live births, with an overall frequency of 1/600-700 births. The overexpression of cystathionine ß-synthase is thought to participate in the presentation of some phenotypes observed in Down syndrome. OBJECTIVE: The aim of this study was to compare the expression levels of cystathionine ß-synthase and histopathological observations from placentas of infants with Down syndrome and healthy newborns. MATERIALS AND METHODS: Six placentas of fetuses/infants with Down syndrome and sixteen placentas of healthy fetuses were studied. Cystathionine ß-synthase mRNA and protein expression were performed by real-time PCR and immunohistochemistry, respectively. RESULTS: We observed an increase in cystathionine ß-synthase mRNA expression (p = 0.0465) and protein levels (p = 0.009) in placentas of fetus/infants with Down syndrome compared with controls. Significantly more circinate edges (p = 0.0007) and trophoblast inclusions (p = 0.0037) were observed in the group with Down syndrome compared with control group. CONCLUSION: The results demonstrate overexpression of cystathionine ß-synthase mRNA and protein in placentas of fetuses/infants with trisomy 21. Further histological abnormalities were found in placentas of patients with Down syndrome, suggesting an alteration in the development of placenta.

Detección de ácidos nucleicos fetales en plasma materno: hacia un diagnóstico prenatal no invasivo / Detection of fetal nucleic acids in maternal plasma: toward a non-invasive prenatal diagnosis

A partir del descubrimiento de la presencia de ácidos nucleicos fetales libres circulantes en el plasma materno se ha generado un gran interés sobre su origen, naturaleza y posibles usos médicos. En este artículo de revisión realizamos un amplio y conciso resumen sobre los resultados de los estudios de ADN y ARN fetal libre en plasma materno, sus perspectivas futuras, principalmente orientadas hacia el diagnóstico prenatal no invasivo, área donde se espera un impacto importante en el futuro inmediato. También se reportan resultados prometedores en la evaluación de la función placentaria y como marcadores predictores y de severidad en complicaciones del embarazo (AU)

The discovery of circulating free fetal nucleic acids in maternal plasma has sparked wide interest in their origin, characteristics and possible medical uses. This review provides a comprehensive and concise summary of the results of studies of free fetal DNA and RNA in maternal plasma and discusses future possibilities for their use, mainly aimed at non-invasive prenatal diagnosis, an area where this discovery is expected to have a major impact in the very near future. Promising results have been reported in the assessment of placental function and in the use of these nucleic acids as predictive markers of the severity of pregnancy complications (AU)

Course of metabolic syndrome following the biliopancreatic diversion of Larrad.

BACKGROUND: The authors assessed the effect of Larrad's biliopancreatic diversion (BPD) on the main components of the metabolic syndrome. PATIENTS AND METHODS: Plasma concentrations of glucose, insulin, total cholesterol (TC), HDL and LDL cholesterol, triglycerides, LDL/HDL and TC/HDL ratios, and blood pressure and body weight were retrospectively evaluated in 40 patients 3-6, 12, 24 and 60 months after undergoing BPD for morbid obesity with metabolic syndrome. RESULTS: 3-6 months after BPD, glycemia and insulinemia had normalized in 97.5% of the patients and remained stable over the following 5 years. Over this period of 3-6 months to 5 years following BPD, total and LDL cholesterol levels fell by 45.2% and 53.1%, respectively. From 12 months onwards, triglyceride levels decreased appreciably, dropping by 57.4% at 5 years. HDL cholesterol concentrations failed to vary significantly or increased to normal levels in patients showing low initial values. At 5 years, high blood pressure had resolved in 75% of patients and the amount of excess weight lost was 65.5% (+/-14.6). No patient required reversal of the BPD due to severe gastrointestinal or metabolic complications. CONCLUSIONS: Technically adapted to the patient's weight, the Larrad BPD effectively stabilizes the main components of the metabolic syndrome. The BPD has low morbidity rate and should be considered a therapeutic option for patients who do not respond to medical treatment.

Síndrome de blefarofimosis-ptosis-epicanto inverso tipo I / Type 1 blepharophimosis.ptosis-epicanthus inversus syndrome

El síndrome de blefarofimosis-ptosis-epicanto inverso (SBPEI) es una afección genética rara transmitida de manera dominante. El SBPEI de tipo I está asociado con una incidencia elevada de alteraciones menstruales y con esterilidad. La sintomatología se atribuye a una resistencia ovárica a las gonadotropinas o a una verdadera menopausia precoz. Se discuten dos mecanismos fisiopatológicos: uno implica un proceso inicial de inhibición del desarrollo de los folículos y un aumento de la tasa de atresia folicular; la otra hipótesis es una modificación del material genético situado sobre al menos dos genes independientes. Aportamos un caso familiar de SBPEI de tipo I objetivado en el nacimiento y operado en numerosas ocasiones. Otros miembros de la familia están igualmente afectados. Tras el diagnóstico de SBPEI en una familia está indicado el consejo genético. En este síndrome, el único tratamiento adecuado es un abordaje temprano, para poder ayudar a las pacientes infértiles (AU)

Linfangiectasia intestinal, enfermedad de Waldmann y gestación / Intestinal lymphagiectasis- Waldmann disease and pregnancy

La enfermedad de Waldmann o linfangiectasia intestinal primitiva es una enteropatía exudativa producida por anomalía de los canales linfáticos de la pared intestinal. Existen formas familiares de transmisión autosómica dominante. El tratamiento dietético que aporta triglicéridos de cadena media ha modificado su evolución. Esta afección aparece en la primera infancia, pero observaciones de alteración más precoz han sido publicadas, entre ellas un caso diagnosticado prenatalmente. Aportamos un caso de paciente afectada de enfermedad de Waldmann que tuvo una gestación a término sin mayores complicaciones, lo que confirma que el embarazo no agrava la evolución de una enteropatía exudativa, como ha sido demostrado por varios autores (AU)

Administración transdérmica combinada continua de estradiol-acetato de noretindrona frente a estradiol solo en mujeres menopáusicas / Transdermal administration of continuous combined oestradiolnorethindrone acetate versus oestradiol only in post-menopausal women

Se estudia si un sistema administración continuo de estradiol/acetato de noretindrona transdérmico reduce la incidencia de hiperplasia endometrial en mujeres postmenopáusicas en mayor medida que el estradiol (E2) transdérmico solo. Doscientas mujeres posmenopáusicas fueron asignadas aleatoriamente a uno de cuatro tratamientos, 50 µg/día de E2 transdérmico, o E2-acetato de noretindrona transdérmico, con 50 µg/día de E2 y 140, 250, o 400 µg/día de acetato de noretindrona. Las visitas de seguimiento para recoger información sobre seguridad y eficacia fueron efectuadas a los 3, 6, 9 y 12 meses tras el inicio de la terapia. Las biopsias endometriales para la evaluación histológica fueron hechas con valores basales y tras la salida del estudio (acabado o supresión). La histología endometrial fue evaluada por dos anatomopatólogos independientes. Se encontró hiperplasia en el 13,33% (6 de 45) en el grupo de E2 solo frente al 1,81 (1 de 55), 0, y 2,56% (uno de 39) en los grupos E2-acetato de noretindrona 50-140, 50-250, y 50-400 µg/día, respectivamente (p < 0,001). La hemorragia uterina fue menos frecuente en el grupo E2-acetato de noretindrona 50-140 µg/día que con los otros tratamientos. El número de sofocos por día decreció a menos de uno en el final de cada tratamiento. Los parches de E2-acetato de noretindrona mostraron una tolerancia dérmica comparable a los de E2 únicamente. La administración continua transdérmica de E2 combinado con acetato de noretindrona previene de forma eficaz la hiperplasia endometrial en mujeres posmenopáusicas sanas. Los sistemas de administración transdérmica combinada continua proporcionan una mayor flexibilidad en la dosificación y podrían mejorar la conveniencia y confianza en la terapia hormonal sustitutiva (AU)

Rotura de aneurisma de la arteria esplénica durante el embarazo / Rupture of a splenic artery aneurysm during pregnancy

La rotura de un aneurisma de la arteria esplénica durante el embarazo es una afección rara, pero de pronóstico grave, imponiéndose la cesárea y la esplenectomía de urgencia. El cuadro clínico típico, que asocia dolor abdominal, hipotensión y anemia, es muy engañoso para el obstetra, pues simula otros procesos, como un hematoma retroplacentario o una rotura uterina (AU)

[Relationship between severity of essential arterial hypertension and the prevalence hyperuricemia]. / Relación entre la gravedad de la hipertensión arterial esencial y la prevalencia de hiperuricemia.

BACKGROUND: Hyperuricemia has been associated with an increased risk of cardiovascular disease in hypertensive patients. However, the relation between serum urate and severity of hypertension has not been conclusively defined as yet. We aimed at finding out whether there exists an independent relationship between changes in the prevalence of hyperuricemia and severity of hypertension. PATIENTS AND METHOD: We studied 3 cohorts of patients aged 35 to 60 years with essential hypertension diagnosed at a university hospital in Madrid, Spain. The first cohort (before 1981) included 325 patients, the second (from 1981 to 1989) comprised 271 patients and the third cohort (from 1990 to 1999) included 545 patients. Disease severity ranged from 1 to 6 according to blood pressure levels at diagnosis (WHO/ISH grades 1, 2 or 3 were assigned 1, 2 or 3 points, respectively) and target organ damage (left ventricular hypertrophy, hypertensive retinal vascular changes, and proteinuria above 300 mg/day; one point each). RESULTS: Mean serum urate concentrations in the 3 cohorts were 6.6, 5.8 and 5.5 mg/dL, respectively (p < 0.05 for all comparisons). 39% of patients in the first cohort had a serum urate concentration > 7.0 mg/dL whereas only 18.1% patients in the third group showed hyperuricemia (difference: 20.9%; 95% CI, 10.1 to 32.3; p < 0.05). Severity of hypertension was higher in the first cohort (mean SD, 2.50 1.31 points) than in the third group (1.96 1.06 points; p < 0.05), with the second cohort showing an intermediate severity (2.23 1.01 points). Serum urate levels were directly related to the severity of hypertension in the 3 groups (r = 0.08, p < 0.05). In a multivariate analysis, after adjustment for confounding variables, serum urate had no significant association with severity of hypertension. However, target organ damage, systolic blood pressure and serum creatinine were all independent predictors of severity. CONCLUSIONS: Favourable changes in the severity of hypertension for a time period significantly correlate with decreases in hyperuricemia prevalence in the same period. On the other hand, hyperuricemia appears to be an indirect marker of hypertensive renal damage.

Bloqueo intradural (raquianestesia) con morfínicos al término del trabajo del parto / Intradural block (spinal) with morphoids in the second stage of labour

Los autores aportan una raquianestesia con 10 µg de sufentanilo, efectuada al término del trabajo de parto para el expulsivo de un niño en presentación de nalgas y de dos gemelos, en parturientas cuyo estado de agitación hacía sospechar un expulsivo por vía baja hipotético o difícil. El efecto antiálgico se instaló en 5 min y fue posible el parto por vía vaginal. La utilidad de la técnica es discutida en casos de situaciones difíciles al término del trabajo de parto, en el caso de que una analgesia peridural no se hubiera instaurado (AU)

White blood cell count and insulin resistance in patients with coronary artery disease.

White blood cell (WBC) count has been shown as a risk factor for cardiovascular disease. Decreased insulin sensitivity has been suggested as the link between these two entities. Our aim was to study the potential relation between insulin sensitivity and WBC count in patients with coronary artery disease. In order to assess insulin sensitivity, we performed 83 insulin suppression tests before and after therapy in 50 patients with coronary artery disease. Patients with glucose intolerance, arterial hypertension or obesity were excluded. Steady-state plasma glucose (SSPG) and insulin sensitivity index (ISI=1 000 x glucose infusion rate/SSPG) were considered as a measure of insulin sensitivity. WBC count, blood platelets, fibrinogen, microalbuminuria, creatinine, urea and HbA1c were also assessed. Simple and multiple correlation analysis were carried out between insulin sensitivity parameters and the other variables measured. There were significant correlation between SSPG and WBC count (r=0,32: p=0,003) and microalbuminuria (r=0,28: p=0,012). We also found statistically significant correlation between ISI and WBC count (r=0,27: p=0,015) and microalbuminuria (r=0,24: p=0,029). No correlation could be detected between either SSPG or ISI and the other variables measured. In multiple regression analysis, WBC count was found to be an independent predictor of both SSPG (p<0.01) and ISI (p<0.05). Our data show the existence of a significant relationship between decreased insulin sensitivity and WBC count in patients with coronary artery disease. The results of this study suggest that an elevated WBC count could be postulated as part of the insulin resistant syndrome.

Salpingitis bilateral por Enterobius vermicularis / Bilateral salpingitis caused by Enterobius vermicularis

Los casos de diseminación de Enterobius vermicularis (oxiuros) a los órganos internos femeninos apartir de focos primarios digestivos son numerosos en la bibliografía médica. Aportamos un raro caso desalpingitis bilateral ligada a la ascensión del parásito por el tracto genital (AU)

Un caso de meningitis por Staphylococcus aureus después de anestesia epidural obstétrica / A case of meningitis caused by Staphylococcus aureus following obstetric epidural anaesthetic

Las complicaciones infecciosas secundarias a una anestesia epidural obstétrica, absceso epidural, meningitis y espondilitis son raras y excepcionales. Estas enfermedades sobrevienen esencialmente sobre un campo frágil y como consecuencia de una contaminación directa en el lugar de la punción, o bien son debidas a una contaminación indirecta a partir de un foco infeccioso vecino, o de una contaminación indirecta por vía hematógena. Aportamos un caso de meningitis iatrógena por Staphylococcus aureus que sobrevino después de una anestesia epidural, tras una probable brecha o traumatismo en la duramadre (AU)

[The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria]. / Efecto del trandolapril, en monoterapia y asociado con verapamil, sobre la presión arterial, albuminuria y control metabólico en pacientes hipertensos con diabetes tipo 2 y albuminuria.

The aim of this study was to analyse the effect of the ACE-1, Trandolapril, alone or with Verapamil on blood pressure, albuminuria and metabolic profile in type 2 diabetic patients with hypertension and albuminuria. It was an open multicenter, consecutive and prospective study conducted in 281 patients. There was a four-week wash-out period of antihypertensive drugs, after which we carried out a measurement over a 24-h period of the urinary excretion of albumina (UEA). Blood pressure was recorded after at least 5 minutes of rest in the sitting position at 1 to 3 minute intervals with a mercury sphygmomanometer in good condition. Average BP was obtained from three consecutive readings. Within treatment changes were analysed using descriptive statistics and t-tests on the change from baseline. Analysis of variance, chi-square and Mc Nemar tests were also used. If after 8 weeks of treatment with Trandolapril 2 mg o.q.d. the patients were non-responders (mean blood pressure reduction of 5 mmHg or less) or their blood pressure remained uncontrolled (blood pressure > or = 140/90 mmHg), Verapamil 180 mg o.q.d. was added. Two hundred and thirty patients completed the 12 weeks study. Population included 157 (55.9%) males with an average of 61.7 +/- 9.2 years. Baseline measurements were systolic 165.4 +/- 14.6 and diastolic 94.8 +/- 8.5 mmHg blood pressures, fasting glucose 162.7 +/- 43.9 mg/dL, glycosylated hemoglobin (HbAlc) 6.8 +/- 1.2%, and albuminuria 520.9 +/- 602 mg/day. UEA fell significantly (p < 0.001) after treatment to 177.9 +/- 24.3 mg/day (CI 95%, 129.9 to 225.8). The percent reduction reached 29.6%. Albuminuria was lower than 30 mg/day in 47 patients. Blood pressure was completely controlled in 125 (54%) patients. Glucemia fell significantly (p < 0.001) to 153.2 +/- 42.7 mg/dL, and the HbAlc to 6.5 +/- 1.3% (p = 0.012). In summary, in those diabetic type 2 patients with arterial hypertension and proteinuria, Trandolapril alone or associated with Verapamil significant lowered albuminuria and blood pressure facilitated the control or their metabolic profile.

High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus.

The current recommendation for strict metabolic control of type 1 diabetes mellitus requires the administration of supraphysiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis, as occurs in insulin-resistant states. At present, the prevalence of hyperandrogenic disorders in women with type 1 diabetes mellitus is unknown. Eighty-five women with type 1 diabetes mellitus were evaluated for symptoms and signs of hyperandrogenism. In 68 of the patients, several serum androgen and hormone concentrations were measured. The polycystic ovary syndrome (PCOS) was defined by the presence of menstrual dysfunction, together with clinical and/or biochemical evidence of hyperandrogenism, and exclusion of other etiologies. Eighteen healthy women, menstruating regularly, served as controls for the androgenic profiles. Thirty-three patients (38.8%) presented hyperandrogenic disorders (16 had PCOS, and 17 had hirsutism without menstrual dysfunction). Type 1 diabetic patients with PCOS presented increased serum total and free testosterone concentrations, and serum androstenedione levels, but had normal serum sex hormone-binding globulin and dehydroepiandrosterone-sulfate levels. Hirsute type 1 diabetic women without menstrual dysfunction presented normal serum androgen levels. There were no significant differences between hyperandrogenic and nonhyperandrogenic type 1 diabetes mellitus women in clinical variables such as the duration of diabetes, age at diagnosis of diabetes, conventional or intensive insulin therapy, mean daily insulin dosage, or metabolic control. In conclusion, women with type 1 diabetes mellitus have a high prevalence of hyperandrogenic disorders, including PCOS and hirsutism.

Miastenia y gestación / Myasthaenia and pregnancy

Presentando un caso personal reciente de miastenia en el curso de la gestación, los autores, después de un recuerdo de la enfermedad, intentan precisar las actitudes preconizadas para una puesta al día de esta patología en el curso del embarazo, ayudados por un repaso exhaustivo de la bibliografía. La gestación de nuestra paciente se ha desarrollado en buenas condiciones, sin agravamiento de su miastenia. De acuerdo con los datos de la bibliografía, la influencia de la gestación sobre la enfermedad es muy variable: un tercio se estabiliza, un tercio mejora y otro se agrava. El período expulsivo es de alto riesgo para la descompensación de la enfermedad, y los esfuerzos durante el mismo deben ser limitados sin, necesariamente, recurrir a la cesárea, salvo indicaciones estrictamente obstétricas. Se aconseja la anestesia epidural, pues disminuye la fatiga y facilita la realización de una extracción instrumental. La lactancia materna está autorizada salvo en caso de afectación grave con una tasa de anticuerpos muy elevada. Solamente se han descrito 5 casos de preeclampsia en pacientes miasténicas. Esta situación es de alto riesgo materno y fetal, precisando vigilancia en una unidad especializada. La afectación fetal puede presentarse de dos formas: una afectación neuromuscular de mal pronóstico, pero rara, o una miastenia neonatal en el 10-20 por ciento de los casos. La miastenia es un proceso autoinmune que afecta principalmente a la mujer joven. El obstetra no está libre, pues, de enfrentarse al problema de un embarazo que sobreviene en una mujer miasténica. El seguimiento de esta asociación rara necesita un buen conocimiento de la enfermedad y una estrecha colaboración entre los diferentes especialistas (AU)

Evolution of insulin resistance in coronary artery disease patients on four different pharmacological therapies.

The objective of the study was to examine the evolution of insulin sensitivity in a group of patients with stable coronary artery disease receiving one of four different pharmacological therapies. Insulin sensitivity was evaluated using an insulin suppression test in 40 newly diagnosed patients with coronary artery disease and no previous history of metabolic disorders, who were not taking any medication which might affect insulin sensitivity. The insulin suppression test consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose concentrations during the last 60 minutes of the test. The insulin sensitivity index was calculated by the formula: insulin sensitivity index = (glucose infusion rate/steady state plasma glucose concentrations) x 10(3). A second insulin suppression test was performed after 6 months' therapy with either isosorbide mononitrate, atenolol, diltiazem or captopril in 30 of the 40 patients. There were no differences between any of the groups before therapy was initiated. After 6 months, patients treated with captopril and, to a lesser extent, those treated with diltiazem showed statistically significantly decreased steady state plasma glucose concentrations and increased insulin sensitivity index compared to basal values. No statistically significant differences were found in the other two groups. We conclude that captopril and, to a lesser extent, diltiazem improve insulin sensitivity in patients with stable coronary artery disease.

Effects of hyperinsulinemia on vascular blood flows in experimental obesity.

Human obesity, which is very common in Polycystic Ovaries Syndrome and in "X Syndrome", constitutes an insulin-resistance state in which multiple clinical, biochemical and hemodynamic alterations coexist. Insulin resistance in the obese has been recently associated with an endothelial dysfunction. To investigate the possibility that clinical and metabolic derangements related to insulin resistance could induce changes in vascular blood flows, we have studied the levels of mesenteric (MBF), renal (RBF) and femoral (FBF) blood flows in Beagle dogs kept for 2 years on a normal (control group) or high fat diet (obese group). This experimental model exhibits many of the abnormalities with the human syndrome. In addition, we have tested the effects of chronic treatment with captopril (capto group) in monotherapy or in association with pravastatin (prava+capto group) on the hemodynamic changes associated with this diet. After the two year follow-up, Transonic flow probes were placed around the three arteries to measure basal blood flows and their response to a hyperinsulinemic-normoglycemic test in anesthetized animals. During this test the degree of insulin sensitivity was estimated. In association with higher body weight, blood pressure, insulin resistance, and fasting levels of insulin and total cholesterol, the obese group exhibited decreased basal levels of FBF and a greater femoral vasoconstriction during hyperinsulinism (P < 0.05 vs control). Combined therapy with captopril and pravastatin ameliorated the reduction in basal FBF and hyperinsulinism-induced vasoconstriction (P < 0.05), in addition to the beneficial effects on insulin sensitivity, and clinical and metabolic parameters. Synergistic beneficial effects of both drugs on lipid and carbohydrate profiles may account for this positive outcome, by attenuating the atherogenic process associated with this model.