Mutations in Mycobacterium tuberculosis Isolates with Discordant Results for Drug-Susceptibility Testing in Peru.

Evaluation of resistance to antituberculosis drugs is routinely performed with genotypic or phenotypic methods; however, discordance can be seen between these different methodologies. Our objective was to identify mutations that could explain discordant results in the evaluation of susceptibility to rifampicin and isoniazid between molecular and phenotypic methods, using whole genome sequencing (WGS). Peruvian strains showing sensitive results in the GenoType MTBDRplus v2.0 test and resistant results in the proportions in the agar-plaque test for isoniazid or rifampin were selected. Discordance was confirmed by repeating both tests, and WGS was performed, using the Next Generation Sequencing methodology. Obtained sequences were aligned "through reference" (genomic mapping) using the program BWA with the algorithm "mem", using as a reference the genome of the M. tuberculosis H37Rv strain. Discordance was confirmed in 14 strains for rifampicin and 21 for isoniazid, with 1 strain in common for both antibiotics, for a total of 34 unique strains. The most frequent mutation in the rpoB gene in the discordant strains for rifampicin was V170F. The most frequent mutations in the discordant strains for isoniazid were katG R463L, kasA G269S, and Rv1592c I322V. Several other mutations are reported. This is the first study in Latin America addressing mutations present in strains with discordant results between genotypic and phenotypic methods to rifampicin and isoniazid. These mutations could be considered as future potential targets for genotypic tests for evaluation of susceptibility to these drugs.

The fourth national anti-tuberculosis drug resistance survey in Peru.

BACKGROUND: Peru has one of the highest burdens of multidrug-resistant tuberculosis (MDR-TB), but universal drug susceptibility testing (DST) has not yet been achieved.OBJECTIVE: To estimate the proportion of drug resistance among smear-positive TB patients in Peru.DESIGN: From September 2014 to March 2015, we performed a national drug resistance survey of patients aged ≥15 years; TB was diagnosed based on sputum smear positivity. We performed DST at the National Reference Laboratory of the Peruvian National Institute of Health, Lima, Peru, using the proportion method in Middlebrook 7H10 agar for four first-line drugs and six second-line drugs, and the Wayne method for pyrazinamide.RESULTS: Of the 1908 new and 272 previously treated patients included in the analysis, 638 (29.3%) patients had resistance to at least one first-line drug. MDR-TB was diagnosed in 7.3% of new and 16.2% of previously treated patients (P < 0.001). There were five (0.2%) patients with extensively drug-resistant TB.CONCLUSION: MDR-TB has increased to 7.3% in new patients from 5.3% in the previous survey, indicating that resistance to anti-tuberculosis drugs is increasing in Peru. Ongoing community transmission of resistant strains highlights an urgent need for early diagnosis, optimised treatment and effective contact tracing of MDR-TB patients.

The effects of hydraulic works and wetlands function in the Salado-River basin (Buenos Aires, Argentina).

Man-made activities exert great influences on fluvial ecosystems, with lowland rivers being substantially modified through agricultural land use and populations. The recent construction of drainage canals in the upper stretch of the Salado-River basin caused the mobilization of huge amounts of salts formerly stored in the groundwater. The main aim of this work was to analyze the effect of the discharges of those canals into the Salado-River water, under different hydrologic conditions, and the role of the wetlands and shallow lakes placed along the canals' system. Physicochemical variables were measured and water samples were taken during times of high water, mean flows, drought, and extreme drought. The environmental variables and the plankton development were related to the hydrologic regime and reached minimum values during floods because of low temperatures and dilution. Local effects on the water's ionic composition became pronounced during droughts because of groundwater input. Nutrient concentrations were mainly associated with point wastewater discharges. Conductivity, ion concentrations, total plankton biomass, and species richness increased in the Salado-River downstream site, after the canals' discharges. The artificial-drainage system definitely promotes the incorporation of salts into the Salado-River basin. In this scenario, a careful hydraulic management is needed to take into account this issue of secondary salinization that threatens the economic exploitation of the region. The wetlands present in this study acted as service environments not only helping to reduce salt, nutrient, and suspended-solid concentrations downstream but also contributing a plethora of species and plankton biomass into the Salado-River main course.

High Rates of Thromboembolic Events in Patients with Germ Cell Cancer Undergoing Cisplatin-Based Polychemotherapy.

BACKGROUND: We examined whether or not extended prophylaxis with low molecular weight heparin (LMWH) would significantly reduce thromboembolic event (TEE) rates in germ cell cancer patients undergoing cisplatin-based chemotherapy. PATIENTS AND METHODS: LMWH prophylaxis was given from the first day of chemotherapy until 21 days after completing the last chemotherapy cycle to 45 out of 93 (48.4%) patients (extended), and to 48 out of 93 (51.6%) patients during their hospitalization only (limited) between January 2008 and December 2013. Patients were analyzed retrospectively for TEEs such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) or peripheral arterial thrombosis. RESULTS: A total of 22/93 (23.7%) patients experienced 30 TEE during chemotherapy: 12 out of 30 (40%) deep vein thrombosis, 4 out of 30 (13.3%) MI, 10 out of 30 (33.3%) PE and 4 out of 30 peripheral arterial thrombosis (13.3%). TEE rates in both groups did not differ significantly (extended: 26.7 vs. limited: 20.8%). CONCLUSIONS: The introduction of extended LMWH prophylaxis did not significantly reduce TEE rates in our patient cohort.

Asimetrías craneofaciales: análisis radiográfico en los planos frontal y basal en individuos de ambos sexos de 18 a 22 años / Craniofacial asymmetry: radiographic analysis in the frontal and transverse planes in subjects aged 18 to 22 years of both sexes

El objetivo de este trabajo fue determinar el tipo y magnitud deasimetrías craneofaciales a partir del análisis cefalométrico de planos múltiples.Se trabajó con una muestra de 207 individuos de ambos sexos de 18 a22 años, que fueron radiografiados en plano frontal con incidencia posteroanterior.Sobre cada radiografía se realizaron tres calcos tomando como referenciaestructuras en tres planos: A (superficial), B (medio) y C (profundo).Se trazó una línea media virtual. Las líneas medias reales fueron superpuestascomparadas con la línea media virtual, determinándose así la dirección yla magnitud de la desviación en cada plano. Estos individuos fueron radiografiadosen plano basal. Sobre cada radiografía se realizaron tres calcostomando como referencia estructuras en tres planos diferentes: A (orbital),B (maxilar) y C (mandibular). Se trazó una línea media virtual que se comparócon la línea media real. Plano frontal: Los resultados indicaron una mayorfrecuencia de desviación hacia la derecha en los tres planos, siendo estas desviacionesmayores en el plano B, respecto de los planos C y A tanto en direccióncomo en magnitud. Plano basal: Los resultados indicaron una mayorfrecuencia de desviación hacia la izquierda en los tres planos, siendo estasdesviaciones mayores en el plano C, respecto de los planos B y A tanto endirección como en magnitud. Estos resultados muestran la generalidad delas asimetrías craneofaciales y resaltan la importancia de su estudio para ladetección de patologías de crecimiento craneofacial(AU)

The aim of this study was to determine the type andmagnitude of craniofacial asymmetry by multiplanar cephalometricanalysis. The sample comprised 207 subjects of both sexes aged18 to 22 years, who were radiographed in the frontal plane atposteroanterior incidence. Three separate acetate tracings weremade on the same radiograph based on three planar structures:A (superficial), B (intermediate), C (deep). A virtual midline wastraced. Real midlines were overlapped and compared with the virtualmidline to determine the type and magnitude of the deviation oneach plane.The subjects were radiographed on the transverse plane. Threeseparate acetate tracings were made on the same radiograph basedon three planar structures: A (orbital), B (maxillary superior), C(maxillary inferior). A virtual midline was traced and compared withthe real midline.Frontal plane: Results indicated a greater frequency of right deviationin the three planes, B being the plane with the largest percentageof deviation (type and magnitude) compared to C and A.Transverse plane: Results indicated a greater frequency of left deviationin the three planes, C being the plane with the largest percentageof deviation (type and magnitude) compared to B and A.These results show that craniofacial asymmetry was widespreadand emphasize the importance of its study in the detection ofcraniofacial growth pathology(AU)

A clinical prediction rule for pulmonary tuberculosis in emergency departments.

SETTING: University-affiliated hospital located in an area with a high incidence of pulmonary tuberculosis (PTB). OBJECTIVE: To develop a clinical prediction rule (CPR) based on information obtainable on admission, to permit rapid identification of patients with PTB. DESIGN: Information from patients with respiratory symptoms who attended the emergency department of Cayetano Heredia Hospital, Lima, Peru, was collected prospectively. Clinical symptoms, past medical history, demographic data and results of chest X-rays (CXRs), sputum smear and culture in Löwenstein-Jensen media were obtained. Based on logistic regression, we constructed a scoring system to predict PTB. RESULTS: A total of 345 patients were enrolled in the study, including 109 (31%) culture-proven PTB cases. In logistic regression analysis, we found age, previous history of PTB, weight loss, presence of cavities, upper lobe infiltrate and miliary pattern on CXR as independent predictors of PTB. We designed a scoring system with these variables, taking into account their statistical weight. The score attained 93% sensitivity and 42% specificity. CONCLUSION: The CPR that was developed performed well in our population. It merits further validation in other settings. It should not, however, replace, but should complement sputum microscopy when deciding on isolation, and it does not preclude microbiology in making a definitive diagnosis.

[Early release of the antiinflammatory cytokine IL-10 in traumatic brain injury]. / Liberación precoz de la citokina antiinflamatoria IL10 en el trauma severo de cráneo.

It has been reported that upwards of 50% of patients who survive an initial brain traumatic insult subsequently die due to infection and multiple organ failure. A paralysis of cell-mediated immunity following trauma, partially induced by anti-inflammatory cytokine release, appears to be responsible for the increased susceptibility to infections. We determined the plasma levels of the anti-inflammatory cytokine IL-10 and the pro-inflammatory TNF-alpha in 15 patients admitted with severe traumatic brain injury (TBI). None of the patients had received glucocorticoid or catecholamine treatment. Thirteen volunteers served as controls. At study entry the IL-10 plasma levels were significantly higher than in controls: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p < 0.001 (Mann-Whitney test). There was no difference between the first (at study entry) and second sample (4 hours later) (Wilcoxon test). TNF-alpha plasma levels were similar in patients and controls at study entry and 4 hours later. We conclude that severe TBI patients present an early response, with a significant increase of IL-10 plasma levels. These results could partially explain the immunodepression following TBI.

Liberación precoz de la citokina antiinflamatoria IL10 en el trauma severo de cráneo. / [Early release of the antiinflammatory cytokine IL-10 in traumatic brain injury]

It has been reported that upwards of 50

of patients who survive an initial brain traumatic insult subsequently die due to infection and multiple organ failure. A paralysis of cell-mediated immunity following trauma, partially induced by anti-inflammatory cytokine release, appears to be responsible for the increased susceptibility to infections. We determined the plasma levels of the anti-inflammatory cytokine IL-10 and the pro-inflammatory TNF-alpha in 15 patients admitted with severe traumatic brain injury (TBI). None of the patients had received glucocorticoid or catecholamine treatment. Thirteen volunteers served as controls. At study entry the IL-10 plasma levels were significantly higher than in controls: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p < 0.001 (Mann-Whitney test). There was no difference between the first (at study entry) and second sample (4 hours later) (Wilcoxon test). TNF-alpha plasma levels were similar in patients and controls at study entry and 4 hours later. We conclude that severe TBI patients present an early response, with a significant increase of IL-10 plasma levels. These results could partially explain the immunodepression following TBI.

Pond-river interactions in a pampean basin /Salado river, Buenos Aires, Argentina): an approach

Se realizó una investigación en el Río Salado en conjunto con la laguna San Miguel que se conecta con el río. Las condiciones fisico-químicas eran similares para los dos cuerpos de agua. En condiciones de alto nivel, concentraciones de fósforo y plancton. La influencia del río determinó niveles altos de nutrientes y polifenoles. En diciembre 1995-marzo 1996 hubo una sequía y la laguna se secó por completo y el flujo del río no pasó de los 100m3/segundo. La fuente del fósforo y polifenoles es el río, así que en condiciones de aguas bajas esas concentraciones disminuyeron. El plancton demostró afinidad a condiciones de alta salinidad

Pancreatitis following scoliosis surgery in children and young adults.

Forty-four patients undergoing single-stage surgery for scoliosis were monitored for biochemical and clinical evidence of pancreatitis. Six patients (14%) developed elevation of both serum amylase and lipase levels. Four of these had symptoms or signs suggestive of pancreatitis. Mean intraoperative blood loss was significantly higher in the group with pancreatitis. No significant differences were noted with regard to age, surgical technique, degree of initial or residual deformity, or length of surgery. The patients with pancreatitis required a longer average period of fasting time. Patients with prolonged ileus or abdominal pain after scoliosis surgery should be investigated for possible pancreatitis.

On the characteristics of the visible chemiluminescence following free radical lipid peroxidation.

The characteristics of the visible luminescence that follows the lipid peroxidative process were investigated either in the autoxidation of rat brain homogenates or in the azo-bis-amidinopropane initiated lipid peroxidation of erythrocyte plasma membranes and liver microsomes. In these systems the luminescence decay observed after total inhibition of the lipid peroxidation is not an iron-catalyzed process, and follows a complex kinetics comprising fast and slow components. The slow component of the decay lasts for several hours at 27 degrees C and amounts to nearly half of the total intensity measured prior to the inhibition of the oxidative process by propyl gallate. The addition of thiols (diethyldithiocarbamate, penicillamine or dithiothreitol) to a lipid peroxidizing system inhibits the chain oxidation and catalyzes the dark decomposition of one (or several) of the luminescence precursors, following first order kinetics. The effect of temperature on the slow luminescence decay corresponds to an activation energy of 18.5 kcal/mol.

Chemiluminescent and respiratory responses related to thyroid hormone-induced liver oxidative stress.

Chemiluminescent and respiratory responses were studied in the liver of rats treated with 0.1 mg of triiodothyronine (T3)/kg for 1 to 7 days. Hyperthyroidism resulted in significant increments in the spontaneous chemiluminescence of the in situ liver in animals exhibiting a calorigenic response. Microsomal NADPH-dependent oxygen uptake was enhanced by T3 treatment for 2 days, an effect that was completely abolished by the antioxidant cyanidanol. A similar microsomal antioxidant-sensitive respiratory component was observed in this situation after the addition of t-butyl hydroperoxide (t-BHP). However, basal rates of microsomal oxygen uptake and light emission in liver homogenates and microsomes were decreased by t-BHP, probably related to thyroid hormone-induced diminution in the content of cytochrome P-450 (Fernández et al.) In addition, liver superoxide dismutase and catalase activities as well as the total content of glutathione were depressed by T3. These results indicate that the calorigenic response in the hyperthyroid state is accompanied by the development of an hepatic oxidative stress characterized by enhanced spontaneous chemiluminescence, enhanced NADPH-dependent microsomal respiration and a decreased antioxidant cellular activity.