CH bond activation in aromatic ketones mediated by iridium-tris(pyrazolyl)borate complexes.

Reaction of complex [TpMe2Ir(η4-CH2C(Me)C(Me)C2)] (1) with a series of aromatic ketones at 130 °C renders, by means of a selective ortho-CH activation, Ir(III)-metallacycles 2-5, which display an Ir-H bond. When [TpMe2Ir(C6H5)2N2] (6) is treated with 2-(trifluoromethyl)acetophenone and 2-fluoroacetophenone at 80 °C, the formation of dimeric (7) and trimeric architectures (8) is achieved through the meta- and para-CH activation of the aromatic ketone, respectively. The generation of complexes 2-5 is proposed to occur by the initial formation of Ir(III) η1-ketone adducts as key intermediates, followed by aromatic CH activations and the release of a butadiene ligand. The formation of complexes 7 and 8 involves an assisted process in which a metal center activation of the less sterically hindered C-H bond of the aromatic ketone takes place (releasing a benzene molecule), followed by the coordination of the carbonyl group, which generates the respective dimeric and trimeric structures. Complexes 7 and 8 are efficient catalysts for the transfer hydrogenation of ketones and aldehydes using isopropanol as the hydrogen source. All complexes have been fully characterized by NMR spectroscopy, FT-IR, elemental analysis and, in the cases of 7 and 8, X-ray crystallography. Details of the reaction conditions, isolation of the products, and proposals for the pathways of formation of complexes 2-5 and 7-8 are discussed.

Performance estimation of two in-house ELISA assays for COVID-19 surveillance through the combined detection of anti-SARS-CoV-2 IgA, IgM, and IgG immunoglobulin isotypes.

The main objective of this study was to estimate the performance, under local epidemiological conditions, of two in-house ELISA assays for the combined detection of anti-SARS-CoV-2 IgA, IgM, and IgG immunoglobulins. A total of 94 serum samples were used for the assessment, where 44 corresponded to sera collected before the pandemic (free of SARS-CoV-2 antibodies), and 50 sera were collected from confirmed COVID-19 patients admitted to the main public hospital in the city of Valdivia, southern Chile. The Nucleocapsid (Np) and the receptor-binding domain (RBD) proteins were separately used as antigens (Np and RBD ELISA, respectively) to assess their diagnostic performance. A receiver operating characteristic (ROC) analysis was performed to estimate the optical density (OD) cut-off that maximized the sensitivity (Se) and specificity (Sp) of the ELISA assays. Np ELISA had a mean Se of 94% (95% CI = 83.5-98.8%) and a mean Sp of 100% (95% CI = 92.0-100%), with an OD 450 nm positive cut-off value of 0.88. On the other hand, RBD ELISA presented a mean Se of 96% (95% CI = 86.3-99.5%) and a mean Sp of 90% (95% CI = 78.3-97.5%), with an OD 450 nm positive cut off value of 0.996. Non-significant differences were observed between the Se distributions of Np and RBD ELISAs, but the latter presented a significant lower Sp than Np ELISA. In parallel, collected sera were also analyzed using a commercial lateral flow chromatographic immunoassay (LFCI), to compare the performance of the in-house ELISA assays against a commercial test. The LFCI had a mean sensitivity of 94% (95% CI = 87.4-100%) and a mean specificity of 100% (95% CI = 100-100%). When compared to Np ELISA, non-significant differences were observed on the performance distributions. Conversely, RBD ELISA had a significant lower Sp than the LFCI. Although, Np ELISA presented a similar performance to the commercial test, this was 2.5 times cheaper than the LFCI assay (labor cost not considered). Thus, the in-house Np ELISA could be a suitable alternative tool, in resource limited environments, for the surveillance of SARS-CoV-2 infection, supporting further epidemiological studies.

Performance estimation of two in-house ELISA assays for COVID-19 surveillance through the combined detection of anti-SARS-CoV-2 IgA, IgM, and IgG immunoglobulin isotypes

The main objective of this study was to estimate the performance, under local epidemiological conditions, of two in-house ELISA assays for the combined detection of anti-SARS-CoV-2 IgA, IgM, and IgG immunoglobulins. A total of 94 serum samples were used for the assessment, where 44 corresponded to sera collected before the pandemic (free SARS-CoV-2 antibodies), and 50 sera were collected from confirmed COVID-19 patients admitted to the main public hospital in the city of Valdivia, southern Chile. The Np and RBD proteins were separately used as antigens (Np and RBD ELISA, respectively) to assess their diagnostic performance. A receiver operating characteristic (ROC) analysis was performed to estimate the optical density (OD) cut-off that maximized the sensitivity (Se) and specificity (Sp) of the ELISA assays. Np ELISA had a mean Se of 94% (95% CI = 83.5 - 98.8%) and a mean Sp of 100% (95% CI = 92.0 - 100%), with an OD 450 nm positive cut-off value of 0.88. On the other hand, RBD ELISA presented a mean Se of 96% (95% CI = 86.3 - 99.5%) and a mean Sp of 90% (95% CI = 78.3 - 97.5%), with an OD 450 nm positive cut off value of 0.996. Non-significant differences were observed between the Se distributions of Np and RBD ELISAs, but the latter presented a significant lower Sp than Np ELISA. In parallel, collected sera were also analyzed using a commercial lateral flow chromatographic immunoassay (LFCI), to compare the performance of the in-house ELISA assays against a commercial test. The LFCI had a mean sensitivity of 94% (95% CI = 87.4 - 100%) and a mean specificity of 100% (95% CI = 100 - 100%). When compared to Np ELISA, non-significant differences were observed on the performance distributions. Conversely, RBD ELISA had a significant lower Sp than the LFCI. Although, Np ELISA presented a similar performance than the commercial test, this was 2.5 times cheaper than the LFCI assay. Thus, the in-house Np ELISA could be a suitable alternative tool, in resource limited environments, for the surveillance of SARS-CoV-2 infection, supporting further epidemiological studies.

Estudio en vida real de una plataforma «online» para la prescripción de ejercicio físico a pacientes obesos: efecto sobre los parámetros antropométricos y bioquímicos, y sobre la calidad de vida / Real-world study of an online platform for the prescription of physical exercise to obese patients - Effect on anthropometric, biochemical parameters and quality of life

Introducción: uno de los factores de riesgo relacionados con la obesidad es el sedentarismo. La realización de ejercicio físico produce beneficios metabólicos; no obstante, su prescripción mediante herramientas online se ha evaluado escasamente. Objetivo: el objetivo de nuestro trabajo fue valorar el efecto de la prescripción de ejercicio físico mediante una plataforma online sobre los parámetros antropométricos, los factores de riesgo cardiovascular y la calidad de vida de pacientes obesos sedentarios. Material y métodos: en un total de 35 pacientes obesos se recogieron de manera basal y a las 12 semanas datos antropométricos, la masa muscular por ecografía a nivel del cuádriceps, una determinación analítica, la presión arterial y la calidad de vida con el test SF-36. Durante 12 semanas se prescribió un programa de ejercicio físico estructurado a través de una plataforma online (www.vibraup.com). Resultados: tras el programa de ejercicio físico se produjo una mejoría significativa del índice de masa corporal (-1,51 ± 0,1 kg/m2; p = 0,01), el peso (-3,7 ± 0,6 kg; p = 0,01), la circunferencia de la cintura (-6,9 ± 0,3 cm; p = 0,01), la masa grasa (-3,9 ± 0,2 kg; p = 0,01), la masa muscular (5,5 ± 1,6 kg; p = 0,01), la tensión arterial diastólica (-4,5 ± 0,4 mm Hg; p = 0,01), la insulina (-2,8 ± 0,1 UI/L; p = 0,04) y la resistencia a la insulina (HOMA-IR) (-0,9 ± 0,1 unidades; p = 0,03) . Los diferentes parámetros ecográficos del recto anterior del cuádriceps mejoraron significativamente. La prevalencia del síndrome metabólico disminuyó del 27,3 % al 12,1 % (p = 0,03). En el test de calidad de vida SF36 se obtuvo una mejoría significativa en las dimensiones de salud general (20,9 ± 4,1 puntos; p = 0,001), rol físico (6,9 ± 0,9 puntos; p = 0,01) y salud mental (14,0 ± 1,3 puntos; p = 0,01). Conclusión: la prescripción de ejercicio físico con una plataforma online a pacientes obesos mejora el peso y la masa grasa corporal, y aumenta la masa muscular (AU)

Introduction: one of the risk factors related to obesity is a sedentary lifestyle. Physical exercise produces metabolic benefits. Its prescription through online tools has been poorly evaluated, though. Objective: the objective of our study was to assess the effect of the prescription of physical exercise through an online platform on anthropometric parameters, cardiovascular risk factors, and quality of life in sedentary obese patients. Material and methods: in a total of 35 obese patients, anthropometric data, muscle mass by ultrasound at the quadriceps level, laboratory parameters, blood pressure, and quality of life using the SF36 tool were collected at baseline and at 12 weeks. For 12 weeks, a structured physical exercise program was prescribed through an online platform - www.vibraup.com. esults: after the physical exercise program with the online platform, there was a significant improvement in body mass index (-1.51 ± 0.1 kg/m2; p = 0.01), weight (-3.7 ± 0.6 kg; p = 0.01), waist circumference (-6.9 ± 0.3 cm; p = 0.01), fat mass (-3.9 ± 0.2 kg ; p = 0.01), muscle mass (5.5 ± 1.6 kg; p = 0.01), diastolic blood pressure (-4.5 ± 0.4 mm Hg; p = 0.01), insulin (-2.8 ± 0.1 IU/L; p = 0.04), and insulin resistance (HOMA-IR) (-0.9 ± 0.1 units; p = 0.03). The ultrasound parameters of the anterior rectus muscle also improved significantly. The prevalence of metabolic syndrome decreased from 27.3 % to 12.1 % (p = 0.03). The SF36 quality of life test showed a significant improvement in general health (20.9 ± 4.1 points; p = 0.001), physical role (6.9 ± 0.9 points; p = 0 .01), and mental health (14.0 ± 1.3 points; p = 0.01). Conclusion: the prescription of physical exercise with an online platform to obese patients improves weight, decreases body fat mass and increases muscle mass, with a decrease in insulin resistance and an improvement in quality of life (AU)

Molar pregnancy in the last 50 years: A bibliometric analysis of global research output.

Molar pregnancy is a gestational trophoblastic disease characterized by an abnormal growth of placental tissues because of a nonviable pregnancy. The understanding of the pathophysiology and management of molar pregnancy has significantly increased in the recent years. This study aims to determine the characteristics and trends of published articles in the field of molar pregnancy through a bibliometric analysis. Using the Scopus database, we identified all original research articles on molar pregnancy from 1970 to 2020. Bibliographic and citation information were obtained, and visualization of collaboration networks of countries and keywords related to molar pregnancy was conducted using VOSviewer software. We obtained a total of 2009 relevant papers published between 1970 and 2020 from 80 different countries. The number of publications continued to increase through the years. However, the number of publications in molar pregnancy is still low compared to the other research fields in obstetrics and gynecology. The USA (n = 421, 32.1%), Japan (n = 199, 15.2%), and the UK (n = 191, 14.6%) contributed the greatest number of publications in this field. The top journals which contributed to the field of molar pregnancy include AJOG (n = 91), Obstetrics and Gynecology (n = 81), and the Gynecologic Oncology (n = 57). The most cited articles in molar pregnancy include papers on the genetics and chromosomal abnormalities in molar pregnancies. The focus of current research in this field was on elucidating the molecular mechanism of hydatidiform moles. Our bibliometric analysis showed the global research landscape, trends and development, scientific impact, and collaboration among researchers in the field of molar pregnancy.

Hyperammonemia syndrome associated with Ureaplasma spp. Infections in immunocompromised patients and transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Hyperammonemia syndrome (HS) is reported to occur in patients with Ureaplasma spp. infections. We performed a systematic review and meta-analysis of studies reporting HS in patients with Ureaplasma spp. infection. METHODS: We searched several databases (CINAHL, OVID, ProQuest, and Scopus) from inception to January 2021. We described case reports and series, and performed a meta-analysis for all cohort studies. The pooled risk ratio (RR) for the association between HS and Ureaplasma spp. infections was derived using a random-effects model. RESULTS: The systematic review yielded 18 studies. HS was reported in 53 patients with Ureaplasma spp. infections. The most common clinical manifestations were neurologic. Meta-analysis showed a higher incidence of HS (41.67%) and peak ammonia concentration among Ureaplasma spp.-infected lung transplant recipients compared with Ureaplasma spp.-negative recipients (2.84%). The risk of HS was significantly increased in Ureaplasma spp.-infected recipients compared with Ureaplasma spp.-negative recipients (RR: 14.64; CI: 2.85-75.24). Mortality from Ureaplasma-associated HS was 27.27% compared with 5.24% in those with HS from other causes. CONCLUSIONS: The risk of developing HS is higher among Ureaplasma-infected patients compared with uninfected patients. Lung transplant recipients appear to be disproportionally affected, and HS should be suspected in those who present with neurologic symptoms.

Galectin-3 Is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes.

INTRODUCTION: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. METHODS: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. RESULTS: Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113-195) vs. 133 (105-173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5-10.5) vs. 7.8 (5.9-9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81-6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07-2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04-1.42); p = 0.017 and HR 1.23 (1.05-1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. CONCLUSION: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.

Sun exposure influences the prognostic power of components of mineral metabolism in patients with coronary artery disease.

BACKGROUND AND AIM: Calcidiol (vitamin D metabolite) plasma levels vary with sun exposure (SE). However, it is not known if SE influences its prognostic ability. We have studied the effect of SE on plasma levels of the components of mineral metabolism (calcidiol, fibroblast growth factor-23 [FGF-23], parathormone [PTH], and phosphate [P]) and on their prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: We studied prospectively 704 patients with stable CAD. Clinical variables and baseline calcidiol, FGF-23, PTH, and P plasma levels were assessed. We divided the population in two subgroups, according to the period of plasma extraction: High SE (HSE) (April-September) and low SE (LSE) (October-March). The outcome was the development of acute ischemic events (acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Mean follow-up was 2.15 ± 0.99 years. Calcidiol and P levels were higher in HSE group. In the whole population, calcidiol (HR = 0.84 for each 5 ng/ml increase, 95% CI = 0.71-0.99; p = 0.038) and FGF-23 (HR = 1.14 for each 100 RU/ml increase, 95% CI = 1.05-1.23; p = 0.009) were predictors of the outcome, along with age, hypertension, body-mass index, peripheral artery disease, and P levels. In the LSE subgroup, calcidiol (HR = 0.75; 95% CI = 0.57-0.99; p = 0.034) and FGF-23 (HR = 1.34; 95% CI = 1.13-1.58; p = 0.003) remained as predictors of the outcome. In the HSE group calcidiol and FGF-23 had not independent prognostic value. CONCLUSIONS: In patients with stable CAD, low calcidiol and high FGF-23 plasma levels predict an adverse prognosis only when the sample is obtained during the months with LSE. SE should be taken into account in the clinical practice.

Leiomiosarcoma del estroma intestinal: presentación de un caso / Intestinal stromal Leiomyosarcoma: a case presentation

Se presenta un paciente de 51 años de edad, alcohólico, con molestias en flanco y fosa ilíaca derechos donde se nota un aumento de volumen. Al examen físico se constata una tumoración abdominal gigante que ocupa todo el flanco y fosa ilíaca derechos y se proyecta a mesogastrio e hipogastrio. Se realizan estudios imagenológicos, incluyendo Tomografía Axial Computarizada contrastada de abdomen, y se somete a laparotomía exploradora con diagnóstico preoperatorio de linfoma abdominal, para realizar exéresis tumoral y estudio histológico, concluyéndose como un tumor del estroma gastrointestinal, específicamente un leiomiosarcoma de mesenterio. Se pone tratamiento con quimioterapia y la evolución clínica es favorable.

A 51 years, alcoholic patient is presented, with right flank and iliac fossa annoyances where a volume increase is noticed. To the physical examination of the area it has been confirmed a giant abdominal tumor, and it is projected to mesogastrio and hypogastrium. Imagenologic studies are realized, including Computerized Axial Tomography of abdomen, and it is underwent exploratory laparotomy with preoperative abdominal linfoma diagnosis, to realize tumoral exeresis and histological study, concluding as a gastrointestinal stromal tumor, specifically a mesentery leiomyosarcoma. It was treated with chemotherapy and the clinical evolution is favorable.

Leiomiosarcoma del estroma intestinal: presentación de un caso / Intestinal stromal Leiomyosarcoma: a case presentation

Se presenta un paciente de 51 años de edad, alcohólico, con molestias en flanco y fosa ilíaca derechos donde se nota un aumento de volumen. Al examen físico se constata una tumoración abdominal gigante que ocupa todo el flanco y fosa ilíaca derechos y se proyecta a mesogastrio e hipogastrio. Se realizan estudios imagenológicos, incluyendo Tomografía Axial Computarizada contrastada de abdomen, y se somete a laparotomía exploradora con diagnóstico preoperatorio de linfoma abdominal, para realizar exéresis tumoral y estudio histológico, concluyéndose como un tumor del estroma gastrointestinal, específicamente un leiomiosarcoma de mesenterio. Se pone tratamiento con quimioterapia y la evolución clínica es favorable(AU)

A 51 years, alcoholic patient is presented, with right flank and iliac fossa annoyances where a volume increase is noticed. To the physical examination of the area it has been confirmed a giant abdominal tumor, and it is projected to mesogastrio and hypogastrium. Imagenologic studies are realized, including Computerized Axial Tomography of abdomen, and it is underwent exploratory laparotomy with preoperative abdominal linfoma diagnosis, to realize tumoral exeresis and histological study, concluding as a gastrointestinal stromal tumor, specifically a mesentery leiomyosarcoma. It was treated with chemotherapy and the clinical evolution is favorable(AU)

[Maternal non-diagnosed celiac disease and risk of low birth weight]. / Enfermedad celiaca materna no diagnosticada y riesgo de tener hijos con bajo peso al nacimiento.

AIMS: In order to know the prevalence of celiac disease in mothers with newborns weighing less or more than 2,500 g at birth we carried out a case-control study. PATIENTS: mothers of newborns in Cabueñes Hospital. Case group: Mothers with babies weighing less than 2,500 g at birth. CONTROLS: Mothers with babies weighing more than 2,500 g at birth. One control for each case. METHODS: epidemiological and clinical interviews, and celiac disease serology. RESULTS: We studied 1103 women: 577 cases and 526 controls. We diagnosed 4 celiac disease cases, 2 in the case group and 2 in the control group. These 4 mothers had 3 term newborns (1 case in each 235 mothers; prevalence 0.42%) and 1 preterm newborn (1 case in each 389 mothers; prevalence 0.26%). Two cases had babies with adequate birth weight for their gestational age (1 case in each 419 mothers; prevalence 0.24%) and two cases had babies with low birth weight for their gestational age (1 in each 132 mothers; prevalence 0.75%). The odds ratio for low birth weight was 0.91 (95% CI: 0.12-6.49), the odds ratio for preterm birth was 0.61 (95% CI: 0.06-5.89), ad the odds ratio for low birth weight for gestational age was 3.19 (95% CI: 0.44-22.79). CONCLUSIONS: The prevalence of celiac disease in fertile women in our geographic area was 0.36% (1 case in each 275 mothers), and no differences were found between study groups.

Enfermedad celiaca materna no diagnosticada y riesgo de tener hijos con bajo peso al nacimiento / No disponible

Objetivo: conocer la prevalencia de enfermedad celiaca enmadres de neonatos mayores y menores de 2.500 gramos depeso al nacimiento.Pacientes: sujetos: casos: madres de neonatos menores de2.500 g al nacimiento. Controles: madres de neonatos mayoresde 2.500 g al nacimiento. Un control por cada caso. Instrumentalización:encuesta clínico-epidemiológica y serología celiaca.Métodos: estudio caso-control. Ámbito: mujeres del Área SanitariaV (Gijón) del Principado de Asturias que den a luz en elHospital de Cabueñes.Resultados: se analizaron 1.103 mujeres: 577 madres de niñosmenores de 2.500 g y 526 madres de niños mayores de 2.500 g.Se diagnosticaron 4 casos de celiaquía, 2 en cada grupo. De las 4madres, 3 dieron a luz a niños a término (1 caso cada 235 madres,prevalencia 0,42%) y 1 dio a luz a un niño prematuro (1 caso cada389 madres, prevalencia 0,26%). Dos madres dieron a luz a niñosde peso adecuado para su edad gestacional (1/419 madres, prevalencia0,24%) y 2 madres dieron a luz niños de bajo peso para suedad gestacional (1/132 madres, prevalencia 0,75%). La odds ratiopara peso menor de 2.500 g al nacimiento fue 0,91 (IC 95% 0,12-6,49), para prematuridad 0,61 (IC 95% 0,06-5,89) y para bajo pesopara su edad gestacional 3,19 (0,44-22,79).Conclusiones: la prevalencia de enfermedad celiaca en mujeresfértiles de Gijón es de un caso cada 275 madres (prevalencia0,36%), sin que hayamos encontrado diferencias entre los dosgrupos estudiados

Aims: in order to know the prevalence of celiac disease inmothers with newborns weighing less or more than 2,500 g atbirth we carried out a case-control study.Patients: mothers of newborns in Cabueñes Hospital. Casegroup: Mothers with babies weighing less than 2,500 g at birth.Controls: Mothers with babies weighing more than 2,500 g atbirth. One control for each case.Methods: epidemiological and clinical interviews, and celiacdisease serology.Results: we studied 1103 women: 577 cases and 526 controls.We diagnosed 4 celiac disease cases, 2 in the case groupand 2 in the control group. These 4 mothers had 3 term newborns(1 case in each 235 mothers; prevalence 0.42%) and 1preterm newborn (1 case in each 389 mothers; prevalence0.26%). Two cases had babies with adequate birth weight for theirgestational age (1 case in each 419 mothers; prevalence 0.24%)and two cases had babies with low birth weight for their gestationalage (1 in each 132 mothers; prevalence 0.75%). The odds ratiofor low birth weight was 0.91 (95% CI: 0.12-6.49), the odds ratiofor preterm birth was 0.61 (95% CI: 0.06-5.89), ad the odds ratiofor low birth weight for gestational age was 3.19 (95% CI: 0.44-22.79).Conclusions: the prevalence of celiac disease in fertilewomen in our geographic area was 0.36% (1 case in each 275mothers), and no differences were found between study groups

Multicentric reference values for some quantities measured with Tina-Quant reagents systems and RD/Hitachi analysers.

Ten clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for quantities concerning ferritin, transferrin, rheumatoid factors, C-reactive protein and antistreptolysin O, using Tina-Quant reagents systems and RD/Hitachi analysers. All the logistic work has been done in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Barcelona). The reference limits produced in the virtual laboratory are derived from the blend of reference values obtained by each laboratory. The multicentric reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry. The work done is a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values.

A novel small molecule that directly sensitizes the insulin receptor in vitro and in vivo.

Insulin resistance, an important feature of type 2 diabetes, is manifested as attenuated insulin receptor (IR) signaling in response to insulin binding. A drug that promotes the initiation of IR signaling by enhancing IR autophosphorylation should, therefore, be useful for treating type 2 diabetes. This report describes the effect of a small molecule IR sensitizer, TLK16998, on IR signaling. This compound activated the tyrosine kinase domain of the IR beta-subunit at concentrations of 1 micromol/l or less but had no effect on insulin binding to the IR alpha-subunit even at much higher concentrations. TLK16998 alone had no effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low as 3.2 micromol/l, enhanced the effects of insulin on the phosphorylation of the IR beta-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3-kinase that coimmunoprecipitated with IRS-1. Phosphopeptide mapping revealed that the effect of TLK16998 on the IR was associated with increased tyrosine phosphorylation of the activation loop of the beta-subunit tyrosine kinase domain. TLK16998 also increased the potency of insulin in stimulating 2-deoxy-D-glucose uptake in 3T3-L1 adipocytes, with a detectable effect at 8 micromol/l and a 10-fold increase at 40 micromol/l. In contrast, only small effects were observed on IGF-1-stimulated 2-deoxy-D-glucose uptake. In diabetic mice, TLK16998, at a dose of 10 mg/kg, lowered blood glucose levels for up to 6 h. These results suggest, therefore, that small nonpeptide molecules that directly sensitize the IR may be useful for treating type 2 diabetes.

Fatal pulmonary embolization of a right atrial mass during transesophageal echocardiography.

Transesophageal echocardiography is a semi-invasive diagnostic technique with a very low incidence of significant complications. Only two deaths related to the procedure have been reported in the literature. We present the case of a 46-year-old man with a right atrial mass, presumably a cardiac myxoma. During attempts at esophageal intubation for a transesophageal echocardiography procedure, the mass fragmented and dislodged, causing massive pulmonary embolism and death. We believe that to avoid this potential complication, great care must be taken in the evaluation of patients with a right intracardiac mass by means of transesophageal echocardiography.

Coronary artery fistula as a bypass of a left anterior descending coronary artery stenosis.

We present a case of coronary artery fistula originating from the proximal left anterior descending coronary artery anterior to a critical atheromatous stenosis, draining into the main trunk of the pulmonary artery and with a third branch draining into the coronary vessel itself, distal to the lesion. The diagnosis was made when we were performing a diagnostic coronary arteriography on a patient with unstable angina. The possible association of the fistula and coronary atherosclerosis is discussed.