No abstract

Background Treatment‐related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world. Procedure A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper‐middle income country, and Dana‐Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced‐intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact. Results The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995–2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event‐free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease‐free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high‐income countries. Conclusions Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL. Pediatr Blood Cancer 2015;62:1395–1402. © 2015 Wiley Periodicals, Inc.

No abstract

The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

Introducción. El escorpionismo afecta a países tropicales como Colombia. Objetivo. Determinar los indicadores ecológicos y epidemiológicos de las picaduras por Tityus asthenes en cuatro localidades de Mutatá, Colombia, y las características clínicas del envenenamiento y toxinológicas del veneno. Materiales y métodos. Es un estudio prospectivo/retrospectivo descriptivo y experimental; se visitaron aleatoriamente 324 de las 1.448 viviendas del municipio: 188 urbanas (58,0%) y 136 rurales (42,0%), con 1.593 habitantes. En 18 meses se estudiaron prospectivamente los pacientes picados por T. asthenes que ingresaron al hospital local y, retrospectivamente en encuestas domiciliarias, se determinó el subregistro. Se recolectaron escorpiones vivos y se realizaron experimentos con el veneno. Resultados. Hubo 12,9 más probabilidades de hallar ejemplares de T. asthenes en el área rural (OR=6,5; IC95% 3,9-10,8), en el intradomicilio y peridomicilio cercano a bosques y plantaciones agrarias altas (OR=13,0; IC95% 7,5-23,0). Se reportaron 80 picaduras ocurridas en los dos últimos años (prevalencia de 4,1%; IC95% 4,8-3,3); sólo 14 personas (17,5%) consultaron al hospital (subregistro de 82,5%). La prevalencia ponderada de infestación por escorpiones en las viviendas encuestadas fue de 26,9% (112 casas) (IC95% 30,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)9). El 50% de los accidentes ocurrió en la localidad de Caucheras: 10,6% de proporción de ataque. El envenenamiento sistémico fue más frecuente en niños (67%). La dosis letal 50 del veneno en ratones de 18 a 20 g, fue 121,6 µg (IC95% 103,7-139,6). Hubo reactividad inmunológica por Western blot de los antivenenos del Instituto Bioclón, México (Alacramyn ® ) y del Instituto Butantan, Brasil (Soro antiaracnídico ® ) con los venenos de T. asthenes y Centruroides gracilis/ Centruroides margaritatus de Colombia. Conclusiones. Las picaduras por T. asthenes, con elevado subregistro, están asociadas a viviendas cercanas a bosques húmedos tropicales. Su veneno y el de C. gracilis, con diferencias de especificidad, reaccionaron con los antivenenos producidos en México y Brasil.Palabras clave: venenos de escorpión, epidemiología, toxicología, Colombia. Tityus asthenes scorpion stings: epidemiological, clinical and toxicological aspectsIntroduction. Scorpion stings are a public health problem in many countries. However, in Colombia, very few epidemiological, clinical or toxicological studies have been undertaken. Objective. Ecological and epidemiological aspects were related to the prevalence of scorpion stings by Tityus asthenes. The clinical features of envenomization were described in patients and in an experimental animal model. Materials and methods. The study was conducted in four localities of Mutatá and Urabá Counties in the province of Antioquia, Colombia. The sample consisted of 1,593 (929 urban, 664 rural) of the 5,305 exposed people, inhabitating 324 households (188 urban (58%); 136 rural (42%) of 1,448 houses total in the study area. An interview survey was perfor...

Lectins are glycan-binding receptors that recognize glycan epitopes on foreign pathogens and in the host systems. They can be involved in functions that include innate immunity, development, immune regulation and homeostasis. Several lectins have been purified and characterized from fish species. In this work, using cation-exchange chromatography, a galactose-specific lectin belonging to the family of C-type lectins was isolated from the venom of the Brazilian venomous fish Thalassophryne nattereri. Nattectin is a basic, non-glycosilated, 15 kDa monomeric protein. It exhibits hemagglutination activity that is independent of Ca(2+). We also demonstrated a lectin activity for Nattectin in the innate immune system, especially in neutrophil mobilization in mice, indicating that marine organisms are source of immunomodulator agents.

No abstract

Brazilian freshwater stingrays, Potamotrygon gr. orbigyni, are relatively common in the middle-western regions of Brazil, where they are considered an important public health threat. In order to identify some of their naturally occurring toxin peptides available in very low amounts, we combine analytical protocols such as reversed-phase high-performance liquid chromatography (RP-HPLC), followed by a biological microcirculatory screening and mass spectrometry analysis. Using this approach, one bioactive peptide was identified and characterized, and two analogues were synthesized. The natural peptide named Porflan has the primary structure ESIVRPPPVEAKVEETPE (MW 2006.09 Da) and has no similarity with any bioactive peptide or protein found in public data banks. Bioassay protocols characterized peptides as presenting potent activity in a microcirculatory environment. The primary sequences and bioassay results, including interactions with the membrane phospholipids, suggest that these toxins are a new class of fish toxins, directly involved in the inflammatory processes of a stingray sting.