Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Validation of low-cost models for minimal invasive surgery training of congenital diaphragmatic hernia and esophageal atresia

BackgroundMinimal invasive surgery (MIS) is increasingly used for the correction of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA). It is important to master these complex procedures, preferably preclinically, to avoid complications. The aim of this study was to validate recently developed models to train these MIS procedures preclinically.MethodsTwo low cost, reproducible models (one for CDH and one for EA) were validated during several pediatric surgical conferences and training sessions (January 2017–December 2018), used in either the LaparoscopyBoxx or EoSim simulator. Participants used one or both models and completed a questionnaire regarding their opinion on realism (face validity) and didactic value (content validity), rated on a five-point-Likert scale.ResultsOf all 60 participants enrolled, 44 evaluated the EA model. All items were evaluated as significantly better than neutral, with means ranging from 3.7 to 4.1 (p < 0.001). The CDH model was evaluated by 48 participants. All items scored significantly better than neutral (means 3.5–3.9, p < 0.001), with exception of the haptics of the simulated diaphragm (mean 3.3, p = 0.054). Both models were considered a potent training tool (means 3.9).ConclusionThese readily available and low budget models are considered a valid and potent training tool by both experts and target group participants.Type of studyProspective study.Level of evidenceLevel II.     

Inhibition of monocyte esterase activity by organophosphate insecticides

Organophosphate insecticides, such as Vapona, Naled, and Rabon, are highly potent inhibitors of an enzyme found in human monocytes. The enzyme, a specific monocyte esterase, could be inhibited by Vapona in blood samples via airborne contamination at levels easily achieved from commercial slow-release insecticide strips. Fifty percent inhibition (I50)--as measured on the Hemalog D (Technicon Corp.)--occurred at solution concentrations of 0.22, 1.5, and 2.6 X 10(-6) g/liter for Vapona, Rabon, and Naled, respectively. Parathion (a thiophosphate) and Baygon (a carbamate) were less potent, with I50 values of 3.7 X 10(-5) and 1.5 X 10(-4) g/liter, respectively. Dursban (another thiophosphate) and Carbaryl (a carbamate) showed only marginal inhibition. Eserine, malathion, nicotine and pyrethrum had no inhibitory effect up to 0.5 g/liter. The occurrence of this effect in vivo has not yet been shown, nor is it clear what the implications of such an effect would be. The inhibition of this enzyme by airborne contaminants, however, may interfere with the proper functioning of the Hemalog D.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

Percutaneous cecostomy: controlled transperitoneal approach

The authors present two cases of percutaneous cecostomy performed with a modified approach previously described for percutaneous gastrostomy and cholecystostomy. T-fastener devices were used to affix the cecum to the anterior abdominal wall; thus, the potential problem of fecal spillage was prevented. In both cases, adequate fecal drainage was provided without complication.