Codon Usage Heterogeneity in the Multipartite Prokaryote Genome: Selection-Based Coding Bias Associated with Gene Location, Expression Level, and Ancestry.

Prokaryotes represent an ancestral lineage in the tree of life and constitute optimal resources for investigating the evolution of genomes in unicellular organisms. Many bacterial species possess multipartite genomes offering opportunities to study functional variations among replicons, how and where new genes integrate into a genome, and how genetic information within a lineage becomes encoded and evolves. To analyze these issues, we focused on the model soil bacterium Sinorhizobium meliloti, which harbors a chromosome, a chromid (pSymB), a megaplasmid (pSymA), and, in many strains, one or more accessory plasmids. The analysis of several genomes, together with 1.4 Mb of accessory plasmid DNA that we purified and sequenced, revealed clearly different functional profiles associated with each genomic entity. pSymA, in particular, exhibited remarkable interstrain variation and a high density of singletons (unique, exclusive genes) featuring functionalities and modal codon usages that were very similar to those of the plasmidome. All this evidence reinforces the idea of a close relationship between pSymA and the plasmidome. Correspondence analyses revealed that adaptation of codon usages to the translational machinery increased from plasmidome to pSymA to pSymB to chromosome, corresponding as such to the ancestry of each replicon in the lineage. We demonstrated that chromosomal core genes gradually adapted to the translational machinery, reminiscent of observations in several bacterial taxa for genes with high expression levels. Such findings indicate a previously undiscovered codon usage adaptation associated with the chromosomal core information that likely operates to improve bacterial fitness. We present a comprehensive model illustrating the central findings described here, discussed in the context of the changes occurring during the evolution of a multipartite prokaryote genome.IMPORTANCE Bacterial genomes usually include many thousands of genes which are expressed with diverse spatial-temporal patterns and intensities. A well-known evidence is that highly expressed genes, such as the ribosomal and other translation-related proteins (RTRPs), have accommodated their codon usage to optimize translation efficiency and accuracy. Using a bioinformatic approach, we identify core-genes sets with different ancestries, and demonstrate that selection processes that optimize codon usage are not restricted to RTRPs but extended at a genome-wide scale. Such findings highlight, for the first time, a previously undiscovered adaptation strategy associated with the chromosomal-core information. Contrasted with the translationally more adapted genes, singletons (i.e., exclusive genes, including those of the plasmidome) appear as the gene pool with the less-ameliorated codon usage in the lineage. A comprehensive summary describing the inter- and intra-replicon heterogeneity of codon usages in a complex prokaryote genome is presented.

Biochemical parameters of silver catfish (Rhamdia quelen) after transport with eugenol or essential oil of Lippia alba added to the water / Parâmetros bioquímicos do jundiá (Rhamdia quelen) após transporte com eugenol ou óleo essencial de Lippia alba adicionado à água

The transport of live fish is a routine practice in aquaculture and constitutes a considerable source of stress to the animals. The addition of anesthetic to the water used for fish transport can prevent or mitigate the deleterious effects of transport stress. This study investigated the effects of the addition of eugenol (EUG) (1.5 or 3.0 µL L1) and essential oil of Lippia alba (EOL) (10 or 20 µL L1) on metabolic parameters (glycogen, lactate and total protein levels) in liver and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported for four hours in plastic bags (loading density of 169.2 g L1). The addition of various concentrations of EUG (1.5 or 3.0 µL L1) and EOL (10 or 20 µL L1) to the transport water is advisable for the transportation of silver catfish, since both concentrations of these substances increased the levels of NPSH antioxidant and decreased the TBARS levels in the liver. In addition, the lower liver levels of glycogen and lactate in these groups and lower AChE activity in the brain (EOL 10 or 20 µL L1) compared to the control group indicate that the energetic metabolism and neurotransmission were lower after administration of anesthetics, contributing to the maintenance of homeostasis and sedation status.(AU)

O transporte de peixes vivos é uma prática rotineira na aquicultura e constitui uma fonte considerável de estresse para os animais. A adição de anestésicos na água utilizada para o transporte de peixes pode prevenir ou mitigar os efeitos nocivos do estresse de transporte. Este estudo investigou os efeitos da adição de eugenol (EUG) (1,5 ou 3,0 mL L1) e óleo essencial de Lippia alba (OEL) (10 ou 20 mL L1) em parâmetros metabólicos (níveis de glicogênio, lactato e proteína total) no fígado e músculos, a atividade da acetilcolinesterase (AChE) no músculo e no cérebro, e os níveis de proteína carbonil (PC), ácido tiobarbitúrico (TBARS) e grupos tióis não proteicos (NPSH) e atividade da glutationa-S-transferase no fígado de jundiás (Rhamdia quelen; Quoy e Gaimard, 1824) transportados por quatro horas em sacos plásticos (densidade de carga de 169,2 g L1). A adição de várias concentrações de EUG (1,5 ou 3,0 mL L1) e OEL (10 ou 20 mL L1) na água de transporte é aconselhável para o transporte do jundiá, uma vez que ambas concentrações destas substâncias aumentaram os níveis do antioxidante NPSH e diminuíram os níveis de TBARS no fígado. Além disso, os níveis mais baixos de glicogénio e lactato no fígado destes grupos e menor atividade de AChE no cérebro (EOL 10 ou 20 mL L1) em comparação com o grupo controle indicam que o metabolismo energético e neurotransmissão foram menores após a administração dos anestésicos, contribuindo para a manutenção do estado de homeostase e sedação.(AU)

Biochemical parameters of silver catfish (Rhamdia quelen) after transport with eugenol or essential oil of Lippia alba added to the water / Parâmetros bioquímicos do jundiá (Rhamdia quelen) após transporte com eugenol ou óleo essencial de Lippia alba adicionado à água

Abstract The transport of live fish is a routine practice in aquaculture and constitutes a considerable source of stress to the animals. The addition of anesthetic to the water used for fish transport can prevent or mitigate the deleterious effects of transport stress. This study investigated the effects of the addition of eugenol (EUG) (1.5 or 3.0 µL L-1) and essential oil of Lippia alba (EOL) (10 or 20 µL L-1) on metabolic parameters (glycogen, lactate and total protein levels) in liver and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported for four hours in plastic bags (loading density of 169.2 g L-1). The addition of various concentrations of EUG (1.5 or 3.0 µL L-1) and EOL (10 or 20 µL L-1) to the transport water is advisable for the transportation of silver catfish, since both concentrations of these substances increased the levels of NPSH antioxidant and decreased the TBARS levels in the liver. In addition, the lower liver levels of glycogen and lactate in these groups and lower AChE activity in the brain (EOL 10 or 20 µL L-1) compared to the control group indicate that the energetic metabolism and neurotransmission were lower after administration of anesthetics, contributing to the maintenance of homeostasis and sedation status.

Resumo O transporte de peixes vivos é uma prática rotineira na aquicultura e constitui uma fonte considerável de estresse para os animais. A adição de anestésicos na água utilizada para o transporte de peixes pode prevenir ou mitigar os efeitos nocivos do estresse de transporte. Este estudo investigou os efeitos da adição de eugenol (EUG) (1,5 ou 3,0 mL L-1) e óleo essencial de Lippia alba (OEL) (10 ou 20 mL L-1) em parâmetros metabólicos (níveis de glicogênio, lactato e proteína total) no fígado e músculos, a atividade da acetilcolinesterase (AChE) no músculo e no cérebro, e os níveis de proteína carbonil (PC), ácido tiobarbitúrico (TBARS) e grupos tióis não proteicos (NPSH) e atividade da glutationa-S-transferase no fígado de jundiás (Rhamdia quelen; Quoy e Gaimard, 1824) transportados por quatro horas em sacos plásticos (densidade de carga de 169,2 g L-1). A adição de várias concentrações de EUG (1,5 ou 3,0 mL L-1) e OEL (10 ou 20 mL L-1) na água de transporte é aconselhável para o transporte do jundiá, uma vez que ambas concentrações destas substâncias aumentaram os níveis do antioxidante NPSH e diminuíram os níveis de TBARS no fígado. Além disso, os níveis mais baixos de glicogénio e lactato no fígado destes grupos e menor atividade de AChE no cérebro (EOL 10 ou 20 mL L-1) em comparação com o grupo controle indicam que o metabolismo energético e neurotransmissão foram menores após a administração dos anestésicos, contribuindo para a manutenção do estado de homeostase e sedação.

Mental health training for secondary school teachers in Haiti: a mixed methods, prospective, formative research study of feasibility, acceptability, and effectiveness in knowledge acquisition.

BACKGROUND: Engagement and training of educators in student mental health holds promise for promoting access to care as a task sharing strategy but has not been well-studied in low-income regions. METHODS: We used a prospective and convergent mixed methods design to evaluate a customized school mental health 2½ day training for teachers in rural Haiti (n = 22) as the initial component of formative research developing a school-based intervention to promote student mental health. Training prepared teachers to respond to student mental health needs by providing psychoeducational and practical support to facilitate access to care. We examined level of participation and evaluated feasibility, acceptability, and perceived effectiveness by calculating mean scores on self-report Likert-style items eliciting participant experience. We examined effectiveness of the training on improving mental health knowledge and attitudes by comparing mean scores on an assessment administered pre- and post-training. Finally, we examined self-report written open-ended responses and focus group discussion (FGD) interview data bearing on perceived feasibility, acceptability, and effectiveness to contextualize participant ratings of training and to identify recommendations for enhancing the utility of mental health training locally for educators. RESULTS: Mean scores of knowledge and attitudes significantly improved between the pre-test and post-tests; e.g., knowledge improved from 58% correct at baseline to 68% correct on the second post-test (p = 0.039). Mean ratings of the training were favorable across all categories and FGD data demonstrated widespread participant endorsement of training acceptability and effectiveness; participants recommended extending the duration and number of training sessions. CONCLUSIONS: Findings support feasibility, acceptability, and a limited scope of effectiveness of brief mental health training for secondary school teachers in Haiti. Further development of approaches to engage teachers in promoting school mental health through training is warranted.

Biochemical parameters of silver catfish (Rhamdia quelen) after transport with eugenol or essential oil of Lippia alba added to the water.

The transport of live fish is a routine practice in aquaculture and constitutes a considerable source of stress to the animals. The addition of anesthetic to the water used for fish transport can prevent or mitigate the deleterious effects of transport stress. This study investigated the effects of the addition of eugenol (EUG) (1.5 or 3.0 µL L-1) and essential oil of Lippia alba (EOL) (10 or 20 µL L-1) on metabolic parameters (glycogen, lactate and total protein levels) in liver and muscle, acetylcholinesterase activity (AChE) in muscle and brain, and the levels of protein carbonyl (PC), thiobarbituric acid reactive substances (TBARS) and nonprotein thiol groups (NPSH) and activity of glutathione-S-transferase in the liver of silver catfish (Rhamdia quelen; Quoy and Gaimard, 1824) transported for four hours in plastic bags (loading density of 169.2 g L-1). The addition of various concentrations of EUG (1.5 or 3.0 µL L-1) and EOL (10 or 20 µL L-1) to the transport water is advisable for the transportation of silver catfish, since both concentrations of these substances increased the levels of NPSH antioxidant and decreased the TBARS levels in the liver. In addition, the lower liver levels of glycogen and lactate in these groups and lower AChE activity in the brain (EOL 10 or 20 µL L-1) compared to the control group indicate that the energetic metabolism and neurotransmission were lower after administration of anesthetics, contributing to the maintenance of homeostasis and sedation status.

Perception of uncontrolled blood pressure and non-adherence to anti-hypertensive agents in diabetic hypertensive patients.

We assessed the association between adherence to antihypertensive drug treatment and patient's perception of uncontrolled blood pressure (BP) in diabetic hypertensive subjects. This was a cross-sectional study that evaluated adherence to antihypertensives (Morisky questionnaire), patients' perception of abnormal BP, office BP, and ambulatory BP monitoring in diabetic hypertensive subjects. We evaluated 323 patients, 65.2% women, aged 56.5 ± 7 years, glycosylated hemoglobin (HbA1c) 8.0% (range, 6.9%-9.6%), diabetes duration of 10 years (range, 5-17 years). Adherence to drug treatment was 51.4%. Patients who reported hypertension-related symptoms (60.4%) had a lower level of adherence (P < .001). Non-adherence occurred four times more frequently in patients who reported hypertension-related symptoms (P < .001, adjusted for use of three or more anti-hypertensives, age, and duration of diabetes). Non-adherents had higher office diastolic BP (83.6 ± 11.9 vs. 79.8 ± 9.9; P = .003), but no difference between groups was observed considering systolic, diastolic, and mean BP evaluated by ambulatory BP monitoring. Low rates of adherence to antihypertensive drug treatment were observed in outpatient hypertensive diabetic subjects. Perception of uncontrolled BP levels was strongly and independently associated with non-adherence. Non-adherence determined repercussion on office BP that may have clinical implications in cardiovascular risk.

First report of methicillin-resistant Staphylococcus aureus Cordobes/Chilean clone involved in nosocomial infections in Brazil.

SUMMARY Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection in hospitalized patients. Resistance is due to the acquisition of mecA gene located on the chromosomal element SCCmec and to date 12 types have been identified. Specific epidemic clones of MRSA have emerged with enhanced ability to spread within and among hospitals and to cross national boundaries. We studied 30 isolates from patients with MRSA infections at two hospitals in Porto Alegre city from April to December, 2008 and determined their SCCmec type by PCR. Representative strains were typed by PFGE. Eighteen (60%) isolates carried SCCmec type III and had PFGE profiles clonally related to the previously characterized Brazilian epidemic clone, and 11 (36·7%) isolates with pulsotypes closely related to the Cordobes/Chilean clone harboured SCCmec type I. To the best of our knowledge, this is the first report of the appearance of Cordobes/Chilean clone involved in nosocomial infection in Brazil.

Oxidative stress parameters in silver catfish (Rhamdia quelen) juveniles infected with Ichthyophthirius multifiliis and maintained at different levels of water pH.

The aim of this study was to determine oxidative stress parameters in the liver, gill and muscle of silver catfish juveniles infected with Ichthyophthirius multifiliis and maintained at pH 5.0 or 7.0 for three days. Juveniles were infected by adding one I. multifiliis-infected juvenile and water containing theronts to tanks. After the appearance of white spots on the skin, infected juveniles exposed to pH 5.0 and 7.0 showed significantly higher thiobarbituric acid reactive substances (TBARS) levels in the liver and gills compared to uninfected juveniles. Liver of infected juveniles exposed to pH 7.0 showed higher catalase (CAT) and lower glutathione-S-transferase (GST) activities, but those maintained at pH 5.0 showed significantly higher GST activity than uninfected juveniles. The gills of infected juveniles showed significantly higher CAT (day two) and GST activity at both pH 5.0 and 7.0 compared to uninfected juveniles. Muscle of infected juveniles showed significantly lower CAT and GST activity and TBARS levels (at day three) when maintained at both pH 5.0 and 7.0 compared to uninfected juveniles. In conclusion, I. multifiliis infection induces liver and gill damage via lipid peroxidation products in silver catfish, but higher antioxidant enzyme activity could indicate a greater degree of protection against this parasite.

Isolated osseous ovarian metaplasia: case report.

BACKGROUND: Some ovarian metaplasias may contain bone or osteoid tissue. The most common tumors presenting these alterations are teratomas and mixed mesodermal tumors with heterologous elements. CASE REPORT: We report the case of a woman who, during gynecologic follow-up for chronic anovulation at the age of 31 years, presented a solid ovarian ultrasonographic image with calcifications. After laparoscopy and histological examination it was found to be an isolated ovarian osseous metaplasia. CONCLUSION: A rarely occurring condition, ovarian osseous metaplasia continues to be of uncertain clinical significance.

Cadmium-induced oxidative stress in two potato cultivars.

A hydroponic experiment was carried out to characterize the oxidative stress responses of two potato cultivars (Solanum tuberosum L. cvs. Asterix and Macaca) to cadmium (Cd). Plantlets were exposed to four Cd levels (0, 50, 100, 150 and 200 microM) for 7 days. Cd concentration was increased in both roots and shoot. Number of sprouts and roots was not decreased, whereas Cd treatment affected the number of nodal segments. Chlorophyll content and ALA-D activity were decreased in both cultivars, whereas carotenoids content was decreased only in Macaca. Cd caused lipid peroxidation in roots and shoot of both cultivars. Protein oxidation was only verified at the highest Cd level. H(2)O(2) content was increased in roots and shoot of Asterix, and apparently, a compensatory response between roots and shoot of Macaca was observed. SOD activity was inhibited in roots of Asterix at all Cd treatments, whereas in Macaca it was only increased at two highest Cd levels. Shoot SOD activity increased in Asterix and decreased in Macaca. Root CAT activity in Asterix decreased at 100 and 150 microM, whereas in Macaca it decreased only at 50 microM. Shoot CAT activity was decreased in Macaca. Root AsA content in Macaca was not affected, whereas in shoot it was reduced at 100 microM and increased at 200 microM. Cd caused increase in NPSH content in roots and shoot. Our results suggest that Cd induces oxidative stress in both potato cultivars and that of the two cultivars, Asterix showed greater sensitivity to Cd levels.

Evaluation of different occlusal splints and counselling in the management of myofascial pain dysfunction.

The aim of this study was to compare the effectiveness of different occlusal splints associated with counselling and self-care in the management of signs and symptoms of myofascial pain. In a double-blind controlled clinical trial, 42 myofascial pain patients with chief complaint of pain in the masseter muscle area were randomly assigned to 1 of the 3 experimental groups: hard (HS), soft (SS) or non-occluding (NS) occlusal splints. The Modified Symptom Severity Index (Mod-SSI) and tenderness to palpation were used as outcome measures during a 90-day follow-up. All patients improved over time and all splints offered the benefit. The results showed that all the three different appliances (HS, SS, and NS) associated with counselling were able to equally reduce the Mod-SSI (symptoms-Tukey test) and digital palpation (signed Kruskal-Wallis) test between baseline and 90 days.

[Isolated manifestation of necrotizing vasculitis of the bladder: a case report]. / Isolierte Manifestation einer nekrotisierenden Vaskulitis an der Harnblase: Ein Fallbericht.

Isolated vasculitis involving the bladder is rare. We describe a case of irritative voiding and hematuria with slightly elevated inflammatory parameters. In order to exclude a neoplastic process we performed cystoscopy and computed tomography. Secondary systemic causes such as lupus erythematosus or rheumatoid arthritis were excluded. Cytopathological examination of the biopsies showed necrotizing vasculitis of the small bladder vessels, which responded to treatment with steroids and cyclophosphamide.

Histological and biochemical effects induced by sublethal doses of Bothrops jararacussu venom in mice

Snake venom is characterized by hemorrhagic, coagulant, proteolytic and myotoxic activities which in Bothrops jaracussu venom are related to intraspecific variations. In the present study, female Swiss mice were divided into two groups: treated with 25µg or 50µg venom. These were subdivided into three groups of six animals each, according to blood collection: 2, 4 or 24h after venom injection. Animals were anesthetized using diethyl-ether inhalation and 1ml of blood was collected by heart puncture. Then, the following organs were removed: spleen, skeletal muscle, kidneys, liver and lungs; histological sections were obtained and stained with hematoxylin-eosin (HE). The following biochemical parameters were analyzed: aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), total lactate dehydrogenase (LDH), glucose, creatinine and urea levels, and total protein content. Results showed significant alterations in AST, LDH, glucose and urea levels, and total protein content, as well as important tissue alterations in the liver, kidneys and lungs. It could be concluded that, even using sublethal doses of venom, there were significant changes in almost all the tested biochemical parameters as well as tissue alterations in the kidneys and lungs.

Histological and biochemical effects induced by sublethal doses of Bothrops jararacussu venom in mice

Snake venom is characterized by hemorrhagic, coagulant, proteolytic and myotoxic activities which in Bothrops jaracussu venom are related to intraspecific variations. In the present study, female Swiss mice were divided into two groups: treated with 25æg or 50æg venom. These were subdivided into three groups of six animals each, according to blood collection: 2, 4 or 24h after venom injection. Animals were anesthetized using diethyl-ether inhalation and 1ml of blood was collected by heart puncture. Then, the following organs were removed: spleen, skeletal muscle, kidneys, liver and lungs; histological sections were obtained and stained with hematoxylin-eosin (HE). The following biochemical parameters were analyzed: aspartate aminotransferase (AST/GOT), alanine aminotransferase (ALT/GPT), total lactate dehydrogenase (LDH), glucose, creatinine and urea levels, and total protein content. Results showed significant alterations in AST, LDH, glucose and urea levels, and total protein content, as well as important tissue alterations in the liver, kidneys and lungs. It could be concluded that, even using sublethal doses of venom, there were significant changes in almost all the tested biochemical parameters as well as tissue alterations in the kidneys and lungs.(AU)

Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia.

A risk prediction model for invasive bacterial infection (IBI) was prospectively evaluated among children presenting with cancer, fever, and neutropenia. The model incorporated assessment of 5 previously identified risk factors: serum level of C-reactive protein (CRP) >/=90 mg/L, hypotension, identification of relapse of leukemia as the cancer type, platelet count of

Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever.

PURPOSE: To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION: In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.

The association between respiratory viruses and symptoms in 2-week-old infants at high risk for asthma and allergy.

OBJECTIVES: The role of viral respiratory tract infections in the onset of childhood asthma and allergy is controversial, partly because of limited understanding about postnatal viral exposures. We investigated the prevalence of 3 common respiratory viruses and associated respiratory symptoms in 2-week-old infants at high risk for having asthma and allergy. STUDY DESIGN: Frozen nasal specimens from 2-week-old children at high risk (n = 495) underwent reverse transcription-polymerase chain reaction (RT-PCR) for picornavirus-, parainfluenza-, and respiratory syncytial virus-specific nucleic acid. RT-PCR findings were related to respiratory symptoms (cold, cough, and wheeze) and to characteristics implicated with increased risk for asthma and allergy. RESULTS: Viral RT-PCR was positive in 199 (40.2%) of 495 specimens examined, with picornavirus and parainfluenza significantly associated with respiratory symptoms. Viral prevalence was significantly higher in children born during the winter and summer months. CONCLUSIONS: A high percentage (40.2%) of infants at high risk for asthma and allergy had been exposed to common respiratory viruses at 2 weeks of age. RT-PCR is a powerful diagnostic method that can be used in epidemiologic studies examining the role of viral respiratory tract infections in the pathogenesis of pediatric asthma and allergy.

Riesgo de infeccion bacteriana / Bacterial infection risk

Estudio prospectivo relaizado durante 17 meses en 5 hospitales pediátricos de Santiago,Chile que reune a todos los niños con cáncer,fiebre y neutropenia severa,con el objetivo de identificar parámetros clínicos y de laboratorio al momento de ingreso capaces de predecir el riesgo de desarrollar una infección bacteriana invasiva

Improved outcome for acute lymphoblastic leukemia in children of a developing country: results of the Chilean National Trial PINDA 87.

BACKGROUND: The National Chilean Pediatric Oncology Group, PINDA, reports the first prospective, nonrandomized trial for acute lymphoblastic leukemia (ALL), using a modified version of the Berlin-Frankfurt-Munster protocol (ALL BFM 86). The aim of this study was to classify immunophenotypes, to decrease cranial irradiation, and to assess whether this protocol would improve the survival rate. PROCEDURE: From June, 1987, to June, 1992, 444 unselected children were diagnosed with ALL. Of them, 425 were evaluable. Therapy was stratified by risk. Standard-risk (SR) and high-risk (HR) patients received protocols I, M, II, and maintenance therapy. Very-high-risk (VHR) patients received protocol E instead of protocol M. All patients received a prephase treatment consisting of prednisone and intrathecal methotrexate (MTX). HR and VHR patients received cranial irradiation (12-18 Gy). The following changes were made to the ALL BFM 86 protocol: in protocol M, MTX 1 g/m2 instead of 5 g/m2; in protocol E, citarabine 1 g/m2 instead of 2 g/m2; mithoxantrone and ifosfamide were substituted by teniposide and cyclophosphamide. RESULTS: Immunophenotypes: pro-B-ALL, 14%; common ALL, 67.4%; pre-B-ALL, 4.3%; T-ALL, 10%; undifferentiated leukemia (AUL), 4.3%. The overall 5-year event-free survival (EFS) rate was 60% +/- 2% (SE). The 5-year EFS rate for each risk group was: SR 75%, HR 62%, VHR 28%, with a median follow-up of 6.5 years (range 4.5-9.5 years). The cumulative incidence of central nervous system (CNS) relapse was 5.4%. CONCLUSIONS: We have been able successfully to perform a nationwide study. Our strategy to adapt the BFM protocol to our population of patients trial was effective in improving the EFS. The immunophenotype distribution is similar to that in other reported series.