Systemic effects of Subtilase cytotoxin produced by Escherichia coli O113:H21.

Subtilase cytotoxin (SubAB) is a member of the AB5 cytotoxin family and is produced by certain strains of Shiga toxigenic Escherichia coli. The toxin is known to be lethal to mice, but the pathological mechanisms that contribute to Uremic Hemolytic Syndrome (HUS) are poorly understood. In this study we show that intraperitoneal injection of a sublethal dose of SubAB in rats triggers a systemic response, with ascitic fluid accumulation, heart hypertrophy and damage to the liver, colon and kidney. SubAB treated rats presented microalbuminuria 20 days post inoculation. At this time we found disruption of the glomerular filtration barrier and alteration of the protein reabsorption mechanisms of the proximal tubule. In the kidney, SubAB also triggered an epithelial to mesenchymal transition (Wuyts et al., 1996). These findings indicate that apart from direct cytotoxic effects on renal tissues, SubAB causes significant damage to the other organs, with potential consequences for HUS pathogenesis. IMPORTANCE: Uremic Hemolytic Syndrome is an endemic disease in Argentina, with over 400 hundred new cases each year. We have previously described renal effects of Shiga Toxin and its ability to alter renal protein handling. Bearing in mind that Subtilase Cytotoxin is an emerging pathogenic factor, that it is not routinely searched for in patients with HUS, and that to the date its systemic effects have not been fully clarified we decided to study both its systemic effects, and its renal effects to assess whether SubAB could be contributing to pathology seen in children.

[Rapid identification of microorganisms by mass spectrometry in a blood culture system. Comparison of two procedures]. / Identificación rápida de microorganismos de frascos de hemocultivos por espectrometría de masas. Comparación de 2 procedimientos diagnósticos.

Rapid identification of microorganisms is critical in hospitalized infected patients. Blood culture is currently the gold standard for detecting and identifying microorganisms causing bacteremia or sepsis. The introduction of mass spectrometry by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS) in microbiology laboratories, especially in microorganisms growing in blood culture bottles, provides rapid identification. This study evaluates the performance of the Maldi Sepsityper Biotyper procedure (hereinafter, MS) compared to that of an in-home method (hereinafter, HF). Eight hundred and forty (840) positive blood culture bottles were processed using the HF procedure, 542 of which were also processed using MS. The organisms were identified in 670 (79.76%) and 391 (72.14%) bottles respectively (p = 0,0013). This study demonstrates the effectiveness of both procedures for identifying microorganisms directly from positive blood culture bottles. However, the HF procedure proved to be more effective than MS, especially in the presence of Gram positive organisms.

[High frequency of thyroid abnormalities in polycystic ovary syndrome]. / Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p<0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities (p<0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Identificación rápida de microorganismos de frascos de hemocultivos por espectrometría de masas: Comparación de 2 procedimientos diagnósticos / Rapid identification of microorganisms by mass spectrometry in a blood culture system: Comparison of two procedures

La identificación rápida de microorganismos es crítica, en especial en pacientes sépticos hospitalizados. La espectrometría de masas conocida como matrix-assisted laser desorption/ionization time-of- flight mass spectrometry (MALDI-TOF MS) permite la identificación directa desde botellas de hemocultivos positivos en forma rápida y sencilla. Este estudio evaluó el desempeño del procedimiento basado en el sistema MALDI Biotyper que utiliza el kit comercial MALDI Sepsityper de Bruker Daltonics (en adelante, MS) frente a uno artesanal (en adelante, HF). Se procesaron 840 botellas de hemocultivos positivos con HF y 542 de estas fueron evaluadas también con MS. Se logró la identificación de los microorganismos en 670 (79,76 %) y 391 (72,14 %) botellas, respectivamente (p = 0,0013). Se demostró la efectividad de ambos procedimientos para la identificación de microorganismos desde frascos de hemocultivos positivos. Sin embargo, el procedimiento HF fue superior al MS, en especial frente a bacterias gram positivas.

Rapid identification of microorganisms is critical in hospitalized infected patients. Blood culture is currently the gold standard for detecting and identifying microorganisms causing bacteremia or sepsis. The introduction of mass spectrometry by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS) in microbiology laboratories, especially in microorganisms growing in blood culture bottles, provides rapid identification. This study evaluates the performance of the Maldi Sepsityper Biotyper procedure (hereinafter, MS) compared to that of an in-home method (hereinafter, HF). Eight hundred and forty (840) positive blood culture bottles were processed using the HF procedure, 542 of which were also processed using MS. The organisms were identified in 670 (79. 76 %) and 391 (72. 14 %) bottles respectively (p = 0,0013). This study demonstrates the effectiveness of both procedures for identifying microorganisms directly from positive blood culture bottles. However, the HF procedure proved to be more effective than MS, especially in the presence of Gram positive organisms.

Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico / High frequency of thyroid abnormalities in polycystic ovary syndrome

La prevalencia de trastornos tiroideos (TT) no ha sido suficientemente evaluada en mujeres con síndrome de ovario poliquístico (SOP). El propósito de esta investigación fue examinar dicha relación. En este estudio prospectivo de diseño caso-control, se incluyeron 194 mujeres. El grupo SOP consistió en 142 pacientes diagnosticadas por criterios Rotterdam 2003, y el grupo control incluyó a 52 mujeres sanas apareadas por edad. Se extrajeron muestras de sangre en ayuno para dosajes de T4 libre, tirotrofina, anticuerpos antiperoxidasa (ATPO), insulinemia y glucemia y se calculó el índice HOMA. Un total de 52 pacientes con SOP presentó autoinmunidad tiroidea (AIT+) y/o hipotiroidismo subclínico (HSC) (36.6%) (TT+) en comparación con 7 mujeres del grupo de control (13.5%), lo que representa una frecuencia cinco veces mayor de TT en pacientes con SOP en comparación con los controles (odds ratio ajustado: 5.6; IC 95%: 2.1-14.9; p < 0.001). Las pacientes TT+ tuvieron valores de insulinemia y HOMA significativamente más altos que aquellas sin trastornos tiroideos (TT-) (p < 0.05).Este estudio muestra una alta tasa de TT en mujeres con SOP asociada a mayores niveles de insulinemia y HOMA. Teniendo en cuenta que el SOP, el hipotiroidismo y la autoinmunidad tiroidea pueden tener un profundo impacto en la salud reproductiva, nuestros datos sugieren que las pacientes con SOP deberían ser evaluadas para descartar TT.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p < 0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities(p < 0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Prueba piloto de validación del método portátil PIMA para el recuento de células CD4 en comparación con la citometría de flujo / Pilot validation study of the PIMA portatil platform for the CD4 T-cell enumeration compared to flux cytometry

Objetivo: comparar la metodología PIMA con la citometría de flujo convencional para el recuento de linfocitos CD4 en pacientes con infección por HIV. Métodos: se realizaron determinaciones pareadas en sangre veno-sa de pacientes con HIV y se comparó la correlación entre ambos re-sultados. Resultados: se realizaron 223 determinaciones en forma pareadas. La concordancia fue muy buena, con una correlación lineal de Pear-son de 0,974, correlación por rangos de Spearman de 0,971 y con un coeficiente de determinación lineal (R cuadrado) de 0,949 (p < 0,01). El coeficiente de correlación intraclases para las medidas individua-les fue de 0,965 (IC 95 % 0,926-0,980) y para medidas promedio 0,982 (IC95 % 0,961-0,990). El coeficiente de variación para medidas duplicadas fue bajo siendo 11,4 %.Discusión: este estudio demuestra una buena correlación entre la de-terminación de células CD4 con el sistema PIMA frente a la citometría de flujo y apoya el uso de estas metodologías donde no hay acceso a citometría convencional

Objective: To compare PIMA methodology to the standard CD4 FACSCalibur flow cytometry for CD4 testing. Method: Paired blood samples were collectedamong HIV patients and tested using PIMA and Becton Dickinson FACSCalibur. Results: 223 samples were studied in parallel. There was a high concordance, being Pearson Linear Correlation 0.974, the Spearman Rank Correlation Coefficient 0.971. The Intraclass Correlation Coefficient for individual measures was 0.965 (95%CI 0.926-0.980) and for average measures 0.982 (95%CI 0.961-0.990). There was a low coefficient of variation from duplicate measurements (11.4%).Conclusion: This study shows a good correlation between the PIMA CD4 count and the Becton Dickinson FACSCalibur. By being a point of care methodology that produces same-day results, PIMA CD4 might be an alternative for sites without access to standard CD4 count methodology

Routine HIV testing among hospitalized patients in Argentina. is it time for a policy change?

INTRODUCTION: The Argentinean AIDS Program estimates that 110,000 persons are living with HIV/AIDS in Argentina. Of those, approximately 40% are unaware of their status, and 30% are diagnosed in advanced stages of immunosuppression. Though studies show that universal HIV screening is cost-effective in settings with HIV prevalence greater than 0.1%, in Argentina, with the exception of antenatal care, HIV testing is always client-initiated. OBJECTIVE: We performed a pilot study to assess the acceptability of a universal HIV screening program among inpatients of an urban public hospital in Buenos Aires. METHODS: Over a six-month period, all eligible adult patients admitted to the internal medicine ward were offered HIV testing. Demographics, uptake rates, reasons for refusal and new HIV diagnoses were analyzed. RESULTS: Of the 350 admissions during this period, 249 were eligible and subsequently enrolled. The enrolled population was relatively old compared to the general population, was balanced on gender, and did not report traditional high risk factors for HIV infection. Only 88 (39%) reported prior HIV testing. One hundred and ninety (76%) patients accepted HIV testing. In multivariable analysis only younger age (OR 1.02; 95%CI 1.003-1.05) was independently associated with test uptake. Three new HIV diagnoses were made (undiagnosed HIV prevalence: 1.58%); none belonged to a most-at-risk population. CONCLUSIONS: Our findings suggest that universal HIV screening in this setting is acceptable and potentially effective in identifying undiagnosed HIV-infected individuals. If confirmed in a larger study, our findings may inform changes in the Argentinean HIV testing policy.

[CHROMagar KPC. Comparison with the method proposed by the Centers for Disease Control and Prevention (CDC, USA) for rectal screening and evaluation of false positive results]. / CHROMagar Kpc. Comparación con el método propuesto por los Centros para el Control y Prevención de Enfermedades (CDC, EE.UU.) para el estudio de portación rectal y evaluación de falsos positivos.

Eighty one rectal swabs (RS) were cultured on CHROMagar KPC and the CDC method. Of the 81 samples, 9 were positive for KPC-producing Klebsiella pneumoniae on CHROMagar KPC, and 6 for the CDC method. CHROMagar KPC had two false positive (FP) results: 1 K. pneumoniae and 1 Acinetobacter sp. FP results on the CDC method were: 25 Acinetobacter spp., 2 Escherichia coli and 4 K. pneumoniae: CHROMagar KPC yielded a better recovery of KPC-producing bacteria and less FP results than CDC method. In order to evaluate FP results on CHROMagar KPC, 1247 RS were cultured and yielded 1021 negatives, 171 KPC-producing K. pneumoniae and 55 FP (4.4 %). Because of the FP results growing on CHROMagar KPC, KPC must be phenotypically confirmed in the bacteria isolated.

CHROMagar KPC. Comparación con el método propuesto por los Centros para el Control y Prevención de Enfermedades (CDC, EE.UU.) para el estudio de portación rectal y evaluación de falsos positivos / CHROMagar KPC. Comparison with the method proposed by the Centers for Disease Control and Prevention (CDC, USA) for rectal screening and evaluation of false positive results

Se cultivaron 81 hisopados rectales en el medio CHROMagar KPC y por el método del CDC. Fueron positivos para Klebsiella pneumoniae KPC en CHROMagar KPC, 9/81 y 6/81 con el método del CDC. El medio CHROMagar KPC tuvo dos falsos positivos: 1 K. pneumoniae y 1 Acinetobacter sp. Los falsos positivos del método CDC fueron: 25 Acinetobacter spp., 2 Escherichia coli y4K. pneumoniae. El empleo del medio CHROMagar KPC resultó ser un método con mayor recuperación de aislamientos productores de KPC y menos falsos positivos que el método del CDC. Para evaluar los falsos positivos en el medio CHROMagar KPC se cultivaron 1247 hisopados rectales. Se obtuvieron 1021 negativos, 171 K. pneumoniae KPC y 55 (4,4 %) falsos positivos. Debido al desarrollo de falsos positivos en el medio CHROMagar KPC, se debe confirmar por caracterización fenotípica la presencia de KPC en las bacterias aisladas.

Eighty one rectal swabs (RS) were cultured on CHROMagar KPC and the CDC method. Of the 81 samples, 9 were positive for KPC-producing Klebsiella pneumoniae on CHROMagar KPC, and 6 for the CDC method. CHROMagar KPC had two false positive (FP) results: 1 K. pneumoniae and 1 Acinetobacter sp. FP results on the CDC method were: 25 Acinetobacter spp., 2 Escherichia coli and 4 K. pneumoniae. CHROMagar KPC yielded a better recovery of KPC-producing bacteria and less FP results than CDC method. In order to evaluate FP results on CHROMagar KPC, 1247 RS were cultured and yielded 1021 negatives, 171 KPC-producing K. pneumoniae and 55 FP (4.4 %). Because of the FP results growing on CHROMagar KPC, KPC must be phenotypically confirmed in the bacteria isolated.

CHROMagar KPC. Comparación con el método propuesto por los Centros para el Control y Prevención de Enfermedades (CDC, EE.UU.) para el estudio de portación rectal y evaluación de falsos positivos / CHROMagar KPC. Comparison with the method proposed by the Centers for Disease Control and Prevention (CDC, USA) for rectal screening and evaluation of false positive results

Se cultivaron 81 hisopados rectales en el medio CHROMagar KPC y por el método del CDC. Fueron positivos para Klebsiella pneumoniae KPC en CHROMagar KPC, 9/81 y 6/81 con el método del CDC. El medio CHROMagar KPC tuvo dos falsos positivos: 1 K. pneumoniae y 1 Acinetobacter sp. Los falsos positivos del método CDC fueron: 25 Acinetobacter spp., 2 Escherichia coli y4K. pneumoniae. El empleo del medio CHROMagar KPC resultó ser un método con mayor recuperación de aislamientos productores de KPC y menos falsos positivos que el método del CDC. Para evaluar los falsos positivos en el medio CHROMagar KPC se cultivaron 1247 hisopados rectales. Se obtuvieron 1021 negativos, 171 K. pneumoniae KPC y 55 (4,4 %) falsos positivos. Debido al desarrollo de falsos positivos en el medio CHROMagar KPC, se debe confirmar por caracterización fenotípica la presencia de KPC en las bacterias aisladas.(AU)

Eighty one rectal swabs (RS) were cultured on CHROMagar KPC and the CDC method. Of the 81 samples, 9 were positive for KPC-producing Klebsiella pneumoniae on CHROMagar KPC, and 6 for the CDC method. CHROMagar KPC had two false positive (FP) results: 1 K. pneumoniae and 1 Acinetobacter sp. FP results on the CDC method were: 25 Acinetobacter spp., 2 Escherichia coli and 4 K. pneumoniae. CHROMagar KPC yielded a better recovery of KPC-producing bacteria and less FP results than CDC method. In order to evaluate FP results on CHROMagar KPC, 1247 RS were cultured and yielded 1021 negatives, 171 KPC-producing K. pneumoniae and 55 FP (4.4 %). Because of the FP results growing on CHROMagar KPC, KPC must be phenotypically confirmed in the bacteria isolated.(AU)

Microalbuminuria and early renal response to lethal dose Shiga toxin type 2 in rats.

In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. Approximately 2%-4% of patients die during the acute phase, and one-third of the 96% who survive are at risk of chronic renal sequelae. Little information is available about the direct effect of Shiga toxin type 2 (Stx2) on the onset of proteinuria and the evolution of toxin-mediated glomerular or tubular injury. In this work, rats were injected intraperitoneally with recombinant Escherichia coli culture supernatant containing Stx2 (sStx2; 20 µg/kg body weight) to induce HUS. Functional, immunoblotting, and immunohistochemistry studies were carried out to determine alterations in slit diaphragm proteins and the proximal tubule endocytic system at 48 hours post-inoculation. We detected a significant increase in microalbuminuria, without changes in the proteinuria values compared to the control rats. In immunoperoxidase studies, the renal tubules and glomerular mesangium showed an increased expression of transforming growth factor ß(1)(TGF-ß(1)). The expression of megalin was decreased by immunoperoxidase and the cytoplasm showed a granular pattern of megalin expression by immunofluorescence techniques. Western blot analysis performed in the renal cortex from sStx2-treated and control rats using anti-nephrin and anti-podocalyxin antibodies showed a decreased expression of these proteins. We suggest that the alterations in slit diaphragm proteins and megalin expression could be related to the development of microalbuminuria in response to lethal doses of Stx2.

Role of nitric oxide in young patients with vasovagal syncope.

AIMS: Nitric oxide (NO) formed in the vascular endothelium produces, among other effects, a strong vasodilation. In order to evaluate the possible role of NO in hypotension induced by head-up tilt test (HUT), we measured plasma levels of its metabolites, nitrites and nitrates (NOx), during the test. METHODS AND RESULTS: Twelve patients with vasovagal syncope and positive HUT [HUT(+)] (mean age: 23+/-5 years) and 13 healthy volunteers with negative HUT (controls) (mean age: 24+/-5 years) were included. Venous blood samples were obtained during the baseline stage for biochemical measurements. Plasma values of NOx were obtained under baseline conditions (T0), at the end of the HUT (T1), and 15 min after the end of the HUT (T2). The baseline biochemical values as well as haemodynamic parameters were similar in HUT(+) patients and controls. NOx plasma values (in micromol/L) were as follows [HUT(+) vs. controls]: T0: 5.7+/-1.6 vs. 8.8+/-4.7 (P=0.05), T1: 6.1+/-3.2 vs. 8.5+/-3.6 (P=NS), and T2: 6.1+/-3 vs. 10.2+/-8.9 (P=NS). The NOx levels were directly correlated with the insulin levels (Spearman's R=0.53, P=0.008). CONCLUSION: Baseline plasma levels of NOx were significantly lower in HUT(+) patients than in controls. However, since the expected increase in NOx values during HUT-induced syncope was not observed, the possible role of NO in vasovagal hypotension is uncertain.

Results of intracytoplasmic sperm injection in two infertile patients with abnormal organization of sperm mitochondrial sheaths and severe asthenoteratozoospermia.

OBJECTIVE: To report assisted reproduction technologies (ART) outcome and characterize severe mitochondrial sheath (MS) anomalies in two infertile asthenoteratozoospermic patients. DESIGN: Case reports. SETTING: Private IVF clinic and academic research institution. PATIENT(S): Two infertile men with asthenoteratozoospermia. INTERVENTION(S): Intracytoplasmic sperm injection (ICSI) was performed in both cases. MAIN OUTCOME MEASURE(S): Clinical and laboratory evaluation were performed and spermatozoa studied by epifluorescence microscopy and transmission electron microscopy (TEM). RESULT(S): Patient 1 had sperm with acute bendings at the level of the narrow midpieces. Mitochondria were either scarce or absent. Three ICSI embryos were transferred. A pregnancy was achieved followed by a miscarriage at the end of the first trimester. Patient 2 had sperm with very long MSs. The number of gyres was increased to more than 30. Two ICSI cycles were performed with good fertilization rates and embryo quality, but no pregnancy was achieved. CONCLUSION(S): MS defects were studied by phase-contrast, epifluorescence microscopy, and TEM that afforded a detailed view of the sperm midpiece and the topography of the whole flagellum. The results indicate that midpiece defects, while causing severe asthenozoospermia and lower fertilizing potential, may not necessarily represent negative prognostic factors in ART.

[Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome]. / Evaluacion critica del test de tolerancia oral a la glucosa para el diagnostico de resistencia insulinica en pacientes con sindrome de ovario poliquistico.

Oral glucose tolerance test (OGTT) is the most commonly used method to evaluate insulin resistance (IR) in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in women with PCO, and the ability of fasting tests to detect postprandial hyperglycemia. One hundred fourteen women with PCO and 29 normal women were evaluated by a 2 hours OGTT. Fasting plasma insulin (INS) and glucose were measured during the test. GLU:INS ratio (r) (fasting glucose/fasting insulin), HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) (fasting tests), as well as the AUCI (area under the curve of INS) and ISI composite (ISI) (insulin sensitivity index) (OGTT tests), were determined. A significant correlation between fasting tests and OGTT tests was found. Normal fasting tests with abnormal OGTT tests were found in 9 patients. No patient with fasting insulin levels less than 9.9 Ul/ml were IR, and all women with fasting insulin levels over 18.4 UI/ml were classified as having IR. We found glucose levels 120 min post glucose load (G 120) > or = 140 mg/dl in 14 patients (12.2%). Fasting glucose and insulin levels and the fasting tests, were poor predictors of impaired glucose tolerance (IGT) and type 2 diabetes (DBT 2). Thus, fasting tests are useful in the diagnostic of IR in PCO patients. OGTT is necessary when the fasting insulin levels range between 9.9 and 18.4 Ul/ml. Women with PCO should undergo periodic screening for abnormal glucose tolerance.

Evaluación crítica del test de tolerancia oral a la glucosa para el diagnóstico de resistencia insulínica en pacientes con síndrome de ovario poliquístico / Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome

El test de tolerancia oral a la glucosa (TTOG) es el más frecuentemente utilizado en la práctica clínica para el diagnóstico de resistencia insulínica (RI). El objetivo del presente trabajo fue la evaluación de la utilidad de los índices basales e índices TTOG, en mujeres con síndrome de ovario poliquístico (SOP) y del valor predictivo de los índices basales sobre la glucemia a los 120 minutos postprandial (G 120). Se estudiaron 114 pacientes con diagnóstico de SOP y 29 mujeres normales. A todas se les realizó un TTOG. Se dosó insulina y glucosa séricas cada 30 min durante las 2 horas del test y se determinaron los siguientes índices: Indices basales: GLU/lNS (glucemia en ayunas / insulinemia en ayunas), HOMA (modelo homeostático) y QUICKI (índice cuantitativo de sensibilidad insulínica) e índices TTOG: AI (área bajo la curva de insulina) e ISI composite (índice de sensibilidad insulínica). Se observaron correlaciones significativas entre los índices basales y los índices TTOG. Hubo 9 pruebas con índices basales normales que presentaban índice TTOG patológicos. Ninguna paciente con niveles de insulina menores a 9.9 Ul/ml presentó RI, mientras que todas las pacientes con niveles de insulina mayores a 18.4 Ul/ml tuvieron RI. Catorce pacientes (10.5%) presentaron G 120 ³ a 140 mg%. En 4 de los 14 casos (12.2%), los valores basales no hicieron sospechar la posibilidad del diagnóstico de hiperglucemia post prandial. En conclusión, en pacientes con SOP, los índices basales son útiles para diagnosticar RI. Proponemos realizar TTOG para diagnóstico de RI en aquellas pacientes que presenten insulinemias en ayunas entre 9.9 y 18.4 Ul/ml. En pacientes con SOP, se recomienda la evaluación periódica de la G 120.

Oral glucose tolerance test (OGTT) is the most commonly used method to evaluate insulin resistance (IR) in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in women with PCO, and the ability of fasting tests to detect postprandial hyperglycemia. One hundred fourteen women with PCO and 29 normal women were evaluated by a 2 hours OGTT. Fasting plasma insulin (INS) and glucose were measured during the test. GLU:INS ratio (r) (fasting glucose/fasting insulin), HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) (fasting tests), as well as the AUCI (area under the curve of INS) and ISI composite (ISI) (insulin sensitivity index) (OGTT tests), were determined. A significant correlation between fasting tests and OGTT tests was found. Normal fasting tests with abnormal OGTT tests were found in 9 patients. No patient with fasting insulin levels less than 9.9 UI/ml were IR, and all women with fasting insulin levels over 18.4 UI/ml were classified as having IR. We found glucose levels 120 min post glucose load (G 120) ³ 140 mg/dl in 14 patients (12.2%). Fasting glucose and insulin levels and the fasting tests, were poor predictors of impaired glucose tolerance (IGT) and type 2 diabetes (DBT 2). Thus, fasting tests are useful in the diagnostic of IR in PCO patients. OGTT is necessary when the fasting insulin levels range between 9.9 and 18.4 UI/ml. Women with PCO should undergo periodic screening for abnormal glucose tolerance.

Evaluación crítica del test de tolerancia oral a la glucosa para el diagnóstico de resistencia insulínica en pacientes con síndrome de ovario poliquístico / Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome

El test de tolerancia oral a la glucosa (TTOG) es el más frecuentemente utilizado en la práctica clínica para el diagnóstico de resistencia insulínica (RI). El objetivo del presente trabajo fue la evaluación de la utilidad de los índices basales e índices TTOG, en mujeres con síndrome de ovario poliquístico (SOP) y del valor predictivo de los índices basales sobre la glucemia a los 120 minutos postprandial (G 120). Se estudiaron 114 pacientes con diagnóstico de SOP y 29 mujeres normales. A todas se les realizó un TTOG. Se dosó insulina y glucosa séricas cada 30 min durante las 2 horas del test y se determinaron los siguientes índices: Indices basales: GLU/lNS (glucemia en ayunas / insulinemia en ayunas), HOMA (modelo homeostático) y QUICKI (índice cuantitativo de sensibilidad insulínica) e índices TTOG: AI (área bajo la curva de insulina) e ISI composite (índice de sensibilidad insulínica). Se observaron correlaciones significativas entre los índices basales y los índices TTOG. Hubo 9 pruebas con índices basales normales que presentaban índice TTOG patológicos. Ninguna paciente con niveles de insulina menores a 9.9 Ul/ml presentó RI, mientras que todas las pacientes con niveles de insulina mayores a 18.4 Ul/ml tuvieron RI. Catorce pacientes (10.5%) presentaron G 120 ³ a 140 mg%. En 4 de los 14 casos (12.2%), los valores basales no hicieron sospechar la posibilidad del diagnóstico de hiperglucemia post prandial. En conclusión, en pacientes con SOP, los índices basales son útiles para diagnosticar RI. Proponemos realizar TTOG para diagnóstico de RI en aquellas pacientes que presenten insulinemias en ayunas entre 9.9 y 18.4 Ul/ml. En pacientes con SOP, se recomienda la evaluación periódica de la G 120. (AU)

Oral glucose tolerance test (OGTT) is the most commonly used method to evaluate insulin resistance (IR) in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in women with PCO, and the ability of fasting tests to detect postprandial hyperglycemia. One hundred fourteen women with PCO and 29 normal women were evaluated by a 2 hours OGTT. Fasting plasma insulin (INS) and glucose were measured during the test. GLU:INS ratio (r) (fasting glucose/fasting insulin), HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) (fasting tests), as well as the AUCI (area under the curve of INS) and ISI composite (ISI) (insulin sensitivity index) (OGTT tests), were determined. A significant correlation between fasting tests and OGTT tests was found. Normal fasting tests with abnormal OGTT tests were found in 9 patients. No patient with fasting insulin levels less than 9.9 UI/ml were IR, and all women with fasting insulin levels over 18.4 UI/ml were classified as having IR. We found glucose levels 120 min post glucose load (G 120) ³ 140 mg/dl in 14 patients (12.2%). Fasting glucose and insulin levels and the fasting tests, were poor predictors of impaired glucose tolerance (IGT) and type 2 diabetes (DBT 2). Thus, fasting tests are useful in the diagnostic of IR in PCO patients. OGTT is necessary when the fasting insulin levels range between 9.9 and 18.4 UI/ml. Women with PCO should undergo periodic screening for abnormal glucose tolerance. (AU)

Insulin sensitivity in young women with vasovagal syncope.

BACKGROUND: Insulin, in addition to its known metabolic effects, has sympatho-excitatory and vasodilatory actions on muscular blood vessels. The goal of this study was to evaluate insulin sensitivity in young women with vasovagal syncope and positive tilt test results (HUT+) and to compare it with that in patients with negative tilt test results (HUT-) and in control subjects without a history of syncope. METHODS: Different indices of insulin sensitivity were obtained by an oral glucose tolerance test (OGTT) in 13 young women with syncope and HUT+ (age 26.8 +/- 9.1 years, body mass index 20.4 +/- 2.1), 8 patients with HUT- (age 26 +/- 5.6 years, body mass index 21.9 +/- 2.4), and 13 control subjects without syncope and HUT- (age 28.9 +/- 8.8 years, body mass index 23.1 +/- 1.7). The following parameters were assessed: fasting glucose and insulin levels (G(0), I(0)); G(0)/I(0) ratio; G(0) x I(0); areas under the curve for glucose and insulin; homeostatic model assessment (HOMA); quantitative insulin sensitivity check index (QUICKI); and composite whole-body insulin sensitivity index (ISI). RESULTS: G(0) and I(0) values were significantly lower in patients with HUT+ than in control subjects (G(0) 4.9 vs 81.9, P <.05, I(0) 4.7 vs 9.1, P <.005). All the fasting values-based indices (ie, HOMA 0.9 vs 1.9, P <.005) and the ISI (12.8 vs 7.1, P =.01) differed significantly in both groups. None of the parameters showed significant differences between patients with HUT- and control subjects. Sixty-one percent of patients with HUT+ had a vasovagal reaction during OGTT. CONCLUSIONS: Young women with vasovagal syncope and HUT+ have a greater insulin sensitivity. They have a propensity to reproduce symptoms during the OGTT. This hypersensitivity could be one of the predisposing factors for vasovagal episodes.

[Leptin in patients with polycystic ovary syndrome. Direct correlation with insulin resistance]. / Leptina en pacientes con síndrome de ovario poliquístico. Correlacíon directa con la resistencia insulínica.

Up to now it is unclear whether there is a relationship between insulin resistance and circulating leptin levels (LEP) in women with polycystic ovary syndrome (PCOS). To assess the role of LEP in PCOS and to clarify the relationship between plasma LEP levels and insulin resistance (IR) in PCOS patients, we studied 49 women with PCOS and 14 normal premenopausal women. All subjects were evaluated by a 2 hours, 75 g, oral glucose tolerance test. Fasting plasma LEP, insulin, glucose, insulin sensitivity indexes and LEP:body mass index (BMI) were determined. Results were analyzed by ANOVA and the Pearson's correlation test when appropriate. The results indicate that: 1) no differences were found in basal plasma LEP levels (ng/ml) between normal (17.6 +/- 4.9) and PCOS (21.9 +/- 2.8) women; 2) in PCOS patients, a significant (P < 0.01) correlation between plasma LEP levels and BMI and insulin sensitivity indexes were found; and 3) seventeen PCOS patients were insulin resistant (IR) and showed higher basal plasma LEP levels (32.8 +/- 4.3, P < 0.01) and LEP:BMI (0.95 +/- 0.09, P < 0.05) than non insulin resistant (non IR) PCOS subjects (16.2 +/- 3.2 and 0.61 +/- 0.08, respectively). Our results suggest that PCOS seems to be associated with normoleptinemia, however, if IR are analyzed separately from non IR PCOS patients, there is a clear relationship between IR PCOS and hyperleptinemia, regardless of the BMI. The present study strongly supports bi-directional relationship between fat and carbohydrate metabolisms under a very particular physiopathological condition (PCOS).

Leptina en pacientes con sindrome de ovario poliquistico: correlacion directa con la resistencia insulinica / Leptin in patients with polycystic ovary syndrome: direct correlation with insulin resistance

La presencia de resistencia insulínica (RI) es un hecho frecuentemente asociado al síndrome de ovario poliquístico (PCO), sin embargo aún no está clara la relación existente entre la RI y los niveles circulantes de leptina en estas pacientes. En este trabajo investigamos los niveles plasmáticos de leptina en pacientes con PCO y evaluamos su relación con la presencia de RI. Se seleccionaron 49 pacientes con PCO y 14 mujeres normales. A todas las pacientes se les realizó un test de tolerancia oral a la glucosa. Se dosó leptina (LEP), insulina y glucosa séricas durante las 2 hs del test y se determinaron los índices de sensibilidad insulínica y relación leptina: índice de masa corporal (LEP:BMI). 1) No observamos diferencias significativas en los niveles séricos de LEP (ng/ ml) entre las pacientes PCO (21.9 ± 2.8) y los controles normales (17.6 ± 4.9). 2) En las pacientes con PCO, los niveles séricos de LEP y el índice LEP:BMI se correlacionaron en forma significativa con el BMI y los índices de sensibilidad insulínica (P<0.01). 3) Diecisiete pacientes con PCO que presentaron RI evidenciaron niveles significativamente mayores de leptina sérica (32.8 ± 4.3 vs. 16.2 ± 3.2, P<0.01) y LEP:BMI (0.95 ± 0.09 vs. 0.61 ± 0.08, P<0.05) que las pacientes sin RI. En conclusión, nuestros resultados evidencian que el síndrome PCO pareceríacursar con normoleptinemia, sin embargo la presencia de RI podría estar relacionada con un aumento de laconcentración de leptina sérica independientemente del BMI. Estos resultados avalan la existencia de una interrelación leptina - insulina en este grupo de pacientes.

Leptina en pacientes con síndrome de ovario poliquístico. Correlacíon directa con la resistencia insulínica. / [Leptin in patients with polycystic ovary syndrome. Direct correlation with insulin resistance]

Up to now it is unclear whether there is a relationship between insulin resistance and circulating leptin levels (LEP) in women with polycystic ovary syndrome (PCOS). To assess the role of LEP in PCOS and to clarify the relationship between plasma LEP levels and insulin resistance (IR) in PCOS patients, we studied 49 women with PCOS and 14 normal premenopausal women. All subjects were evaluated by a 2 hours, 75 g, oral glucose tolerance test. Fasting plasma LEP, insulin, glucose, insulin sensitivity indexes and LEP:body mass index (BMI) were determined. Results were analyzed by ANOVA and the Pearsons correlation test when appropriate. The results indicate that: 1) no differences were found in basal plasma LEP levels (ng/ml) between normal (17.6 +/- 4.9) and PCOS (21.9 +/- 2.8) women; 2) in PCOS patients, a significant (P < 0.01) correlation between plasma LEP levels and BMI and insulin sensitivity indexes were found; and 3) seventeen PCOS patients were insulin resistant (IR) and showed higher basal plasma LEP levels (32.8 +/- 4.3, P < 0.01) and LEP:BMI (0.95 +/- 0.09, P < 0.05) than non insulin resistant (non IR) PCOS subjects (16.2 +/- 3.2 and 0.61 +/- 0.08, respectively). Our results suggest that PCOS seems to be associated with normoleptinemia, however, if IR are analyzed separately from non IR PCOS patients, there is a clear relationship between IR PCOS and hyperleptinemia, regardless of the BMI. The present study strongly supports bi-directional relationship between fat and carbohydrate metabolisms under a very particular physiopathological condition (PCOS).