Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers.

Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.

Immunosuppression and Chagas disease; experience from a non-endemic country.

Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality.

Trypanosoma cruzi infection in a non-endemic country: epidemiological and clinical profile.

Chagas disease has been increasingly diagnosed in non-endemic countries. This is a prospective observational study performed at the Tropical Medicine Units of the International Health Program of the Catalan Health Institute, Barcelona (PROgrama de Salud Internacional del Instituto Catalán de la Salud, PROSICS Barcelona, Spain), that includes all patients with Chagas disease who attended from June 2007 to May 2012. Clinical and epidemiological data were collected. Overall, 1274 patients were included, the mean age of the patients was 37.7 years, 67.5% were women and 97% came from Bolivia. Thirteen patients had immunosuppressive conditions. The prevalence of cardiac involvement was 16.9%, lower than in previous studies performed in endemic areas (20-60%). Cardiac alterations were found in 33.8% of symptomatic and 14.1% of asymptomatic patients. The prevalence of digestive involvement was 14.8%. The rate of digestive involvement is very different among previous studies because of different diagnostic tools and strategies used. Barium enema alterations were found in 21.4% of symptomatic and 10.3% of asymptomatic patients, and oesophageal alterations were found in 3.7% of symptomatic and in 2.3% of asymptomatic patients. As shown in previous studies, Chagas disease in non-endemic countries affects younger patients and has lower morbidity.

Adenomas Ectópicos de paratiroides. Sensibilidad y Valor de las pruebas diagnósticadas para el tratamiento quirúrgico / Ectopic parathyroid adenomas. Sensitivity and value of the diagnostic tests for surgical treatment

OBJETIVOS. Presentar las peculiaridades clínico-quirúrgicas de los adenomas ectópicos de paratiroides relacionándolas con las de los adenomas normotópicos. Determinar el valor de las pruebas diagnósticas para asegurar el éxito terapéutico. MATERIAL Y MÉTODOS. Estudio prospectivo de 158 pacientes intervenidos por hiperparatiroidismo primario (1998-2010). 83% mujeres. Edad media 62,8 años±13,7. Para el diagnóstico topográfico se usaron la gammagrafía con Tecnecio-sestaMIBI, ECO y TAC (ocasional) y para asegurar la exéresis quirúrgica, la monitorización intraoperatoria de PTH y, eventualmente en los ectópicos, la cirugía radioguiada. Se seleccionaron 15 pacientes (80% mujeres) con adenomas ectópicos y se compararon con 143 adenomas ortotópicos. Se evaluaron: sexo, edad, localización, clínica, diagnóstico bioquímico y topográfico, peso glandular, vías de abordaje quirúrgico, gradientes de descenso de PTH en la monitorización y resultados postoperatorios. Para la comparación de medias se utilizó la U de Mann-Whitney y para las variables cualitativas el test de Fisher aceptando valores de p≤0,05. RESULTADOS. Fueron ectópicos el 9,5% de los adenomas. 86,7% en paratiroides inferiores (4 mediastínicas) y 13,3% en superiores. La ectopia no modificó el comportamiento clínico de los adenomas (ambas series fueron similares). La sensibilidad diagnóstica de la gammagrafía, en los ectópicos, fue 100% y para los normotópicos 80,5%. La TAC alcanzó el 66,7%, en los ectópicos, y 48,6% en los normotópicos y la Ecografía el 36,4% y 54%, respectivamente. En el grupo de adenomas ectópicos se utilizó la cervicotomía bilateral en 12 pacientes (80%), el abordaje selectivo en 3 y la sonda radioisotópica en 4. Las glándulas ectópicas extirpadas fueron adenomas. En el grupo normotópico se eligió el abordaje selectivo en el 55%. La comparación de grupos no mostró diferencias de los parámetros evaluados, salvo en la localización de los adenomas, mayor en las paratiroides inferiores (86,7% vs 68%) (p<0,05), en la sensibilidad de la gammagrafía con MIBI, también mayor (100% vs 80,5%) (p<0,001) en el grupo de los ectópicos, y en el tipo de abordaje quirúrgico CONCLUSIONES: 1. Los adenomas ectópicos constituyeron el 9,5% y fueron más frecuentes en las glándulas inferiores (86,4%). 2. No hubo diferencias clínicas entre los ectópicos y normotópicos. 3. La gammagrafía fue la prueba más sensible (100%) para detectarlos (AU)

OBJECTIVES. To present the clinical-surgical peculiarities of ectopic parathyroid adenomas, comparing them to those of the normotopic adenomas. To determine the value of the diagnostic tests in ensuring therapeutic success. MATERIAL AND METHODS. Prospective study of 158 patients operated on for primary hyperparathyroidism (1998-2010), in which 83% were women, average age 62.8 years±13.7. For the topographic diagnostic, the gammagraph was used with Tecnecio-sestamibi, ultrasound and CAT (occasional) and to ensure the surgical exeresis, the intraoperative monitoring of PTH and, possible radio-guided surgery in the ectopic adenomas. Fifteen patients were selected (80% women) with ectopic adenomas and they were compared with 143 orthotopic adenomas. The following were evaluated: Gender, age, location, clinical symptoms, biochemical diagnosis, and topography, glandular weight, channels for surgical approach, degrees of decrease of PTH in the monitoring and postoperative results. For the comparison of means, the U of Mann-Whitney was used and the Fisher test was used for the qualitative variable, accepting values of p≤0.05. RESULT. Of the adenomas, 9.5% were found to be ectopic; 86.7% in inferior parathyroids (4 mediastinal) and 13.3% in superior parathyroids. The ectopia did not change the clinical behaviour of the adenomas (both series were similar). The diagnostic sensitivity of the gammagraphy, in the ectopic adenomas, was 100% and for the normotopic 80.5%. The CAT achieved 66.7% in the ectopic and 48.6% in the normotopic; and the ultrasound achieved 36.4% and 54%, respectively. In the group of ectopic adenomas, the bilateral cervicotomy was used on 12 patients (80%), the selective approach on 3 and the radioisotopic probe on 4. The removed ectopic glands were adenomas. In the normotopic group, the selective approach was chosen in 55%. The comparison of the groups did not show differences of the evaluated parameters, except in the location of the adenomas, greater in the inferior parathyroids (86.7% vs. 68%) (p<0.05), in the sensitivity of the gammagraph with MIBI also greater (100% vs. 80.5%) (p<0.001) in the group of ectopic adenomas, and in the type of surgical approach. CONCLUSIONS: 1. The ectopic adenomas constituted 9.5%. More frequent in the inferior glands (86.4%). 2. There were no clinical differences between the ectopic and normotopic adenomas. 3. The gammagraph was the most sensitive test (100%) for detecting them (AU)

Resistance training increases glucose uptake and transport in rat skeletal muscle.

The aim of this investigation was to determine if resistance training exercise improved glucose uptake and transport in rodent skeletal muscle. Sprague-Dawley rats were assigned to one of the three groups: control (CON), resistance trained (RT) and aerobic exercise trained (AT). Resistance trained rats were placed in a rodent squat apparatus and performed three sets of 10 repetitions at 75% of their one repetition maximum 3 days week-1 for 12 weeks. Aerobic exercise training consisted of running the rats 3 days week-1 for 45 min over a 12-week period on a motor-driven treadmill (32 m min-1, 15% grade). Following the training period, all animals were subjected to hind limb perfusion in the presence of 500 microU mL-1 insulin. Hind limb glucose uptake was similar in the RT (9.91 +/- 0.7 micromol g-1 h-1) and AT (10.23 +/- 1.0 micromol g-1 h-1) animals and significantly greater than control (CON) (6.40 +/- 0.6 micromol g-1 h-1). Rates of 3-O-methyl-d-glucose transport in the RT animals were elevated in the muscles utilized for RT while in the AT animals rates of 3-O-methyl-d-glucose transport were increased in those muscles recruited for running. The increased rates of 3-O-methyl-d-glucose transport in the skeletal muscles of the resistance trained and aerobic exercise trained animals appeared to be, in part, because of an increased GLUT4 protein concentration. These findings suggest that both resistance or aerobic training exercise can improve insulin-stimulated skeletal muscle glucose uptake and transport, but the training adaptations are restricted to the muscles recruited for the exercise performance.

Leptin administration improves skeletal muscle insulin responsiveness in diet-induced insulin-resistant rats.

In addition to suppressing appetite, leptin may also modulate insulin secretion and action. Leptin was administered here to insulin-resistant rats to determine its effects on secretagogue-stimulated insulin release, whole body glucose disposal, and insulin-stimulated skeletal muscle glucose uptake and transport. Male Wistar rats were fed either a normal (Con) or a high-fat (HF) diet for 3 or 6 mo. HF rats were then treated with either vehicle (HF), leptin (HF-Lep, 10 mg. kg(-1). day(-1) sc), or food restriction (HF-FR) for 12-15 days. Glucose tolerance and skeletal muscle glucose uptake and transport were significantly impaired in HF compared with Con. Whole body glucose tolerance and rates of insulin-stimulated skeletal muscle glucose uptake and transport in HF-Lep were similar to those of Con and greater than those of HF and HF-FR. The insulin secretory response to either glucose or tolbutamide (a pancreatic beta-cell secretagogue) was not significantly diminished in HF-Lep. Total and plasma membrane skeletal muscle GLUT-4 protein concentrations were similar in Con and HF-Lep and greater than those in HF and HF-FR. The findings suggest that chronic leptin administration reversed a high-fat diet-induced insulin-resistant state, without compromising insulin secretion.

[Malnutrition in pre-school infants in migrant families]. / Desnutrición en prescolares de familias migrantes.

OBJECTIVE: To compare malnutrition rates between migrant and non-migrant children. MATERIAL AND METHODS: One-hundred and sixty children 1-6 years old were selected at random from schools located in highly marginated areas. Excluded were infants with congenital malformations or under nutritional intervention. Migration was defined as any geographical movement during the last 6 years. Malnutrition was assessed through the weight/height and height/age indicators, as recommended by the World Health Organization. RESULTS: Fifty-nine percent of the infants belonged to families whose father had a non-qualified occupation, 27.5% of them did not finish elementary school. Fifty-three referred migration; malnutrition rate was 51.3% among migrant infants and 28.8%, among non-migrant infants (OR = 2.6, CI 95% = 1.2, 5.2, p = 0.006). Migrant children registered a mean Z score of -2.4 +/- .40 and non-migrant children, -2.3 +/- .33, based on the indicator height for age. CONCLUSIONS: Chronic malnutrition among migrant infants justifies a nutritional intervention, they constitute a specific group at risk. Migration should be considered for health planning.

[Inguinal tumor as the first manifestation of a pancreatic pseudocyst]. / Tumoración inguinal como primera manifestación de un seudoquiste pancreático.

We report a case of pancreatic pseudocyst in alcoholic pancreatitis, that presented as a mass in the inguinal region. The mechanism of this peculiar clinical presentation was the dissemination of the content of the pseudocyst along the psoas muscle. We review the involvement of psoas muscle in pancreatic pathology, giving emphasis to reports of inguinal or thigh masses as initial manifestations.

A simple and rapid solvent extraction method for determining total lipids in fish tissue.

Solvent systems that have been developed for lipid extraction include chloroform-methanol, n-hexane-isopropyl alcohol, and methylene chloride-methanol. The extraction methods are labor intensive, lack precision, or require a large volume of solvent. Correct computation of lipid content calls for full recovery of solvent after extraction, but recovery always is incomplete because of unaccounted solvent residue that remains in jar, filter paper, and homogenized tissue. A rapid and simple extraction method coupled with correct computation was developed for determining total lipids in fish tissue. The method uses chloroform-methanol and an Eberbach blending jar. Variables examined were chloroform-methanol ratio, solvent-to-sample ratio, and phase separation time. Precision was within 0.5%. Conventional computation of lipid content depends on the volume of chloroform measured after filtration. This volume does not include unaccounted solvent residue. Thus, a time-consuming second extraction is required for complete recovery. The mass balance of each extraction and filtration step confirmed that the correct volume of chloroform (measured plus unaccounted) was close to the theoretical volume. The procedure eliminates problems associated with laborious filtration and variation in chloroform volume readings and does not require an exact reading of chloroform volume. Instead it allows use of a theoretical volume, which depends on solvent volume and ratio used.

[Malaria imported by immigrants in Catalonia]. / Paludismo importado por inmigrantes en Cataluña.

BACKGROUND: The aim of the present study was to analyze the epidemiologic aspects and particular features of malaria in immigrants in Catalonia, Spain. METHODS: All the immigrants who visited the Unit of Tropical and Imported Diseases "Drassanes" in Barcelona from endemic zones of malaria from 1990 to 1993 were studied. The diagnosis of malaria was based on the thick blood film, peripheral blood smear exam and, since 1991, the QBC (Quantitative Buffy Coat). RESULTS: One hundred three cases of malaria were diagnosed in 100 individuals from a total of 2,453 visited immigrants. Forty-four percent of the patients presented febrile syndrome, 11% cutaneous syndrome accompanied by other manifestations justifying the same, 9% presented other clinical manifestations and 36% were asymptomatic. Ninety-six percent of the subjects with parasites by Plasmodium were from sub-Saharan Africa and in 2 cases, both were produced by Plasmodium falciparum, with the length of time having been in Spain at the time of diagnosis being more than one year. P. falciparum represented 70% of the total cases, followed by P. malariae (15%), P. vivax (8%), Plasmodium spp. (6%) and P. ovale (1%). CONCLUSIONS: Malaria by P. falciparum in semi-immune immigrants is not usually severe and follows an asymptomatic course in more than one third of the cases. The usual analysis for Plasmodium is recommended in immigrants from sub-Saharan Africa due to the high frequency of presentation and the absence of symptoms. Such analysis is not advised in groups from other areas except when suggestive symptoms are present.