[Hypersensitivity reactions associated with the use of asparaginase in children with acute lymphoblastic leukemia]. / Reacciones de hipersensibilidad asociadas al uso de asparaginasa en niños con leucemia linfoblástica aguda.

INTRODUCTION: The treatment of acute lymphoblastic leukemia (ALL) includes the use of asparaginase (ASP), a drug associated with hypersensitivity reactions (HSR) that requires discontinuing its use. OBJECTIVE: To determine the incidence of HSR associated with ASP that require discontinuation of its use and des cribe them, and to verify if there is a relationship between HSR incidence and protocols or survival. PATIENTS AND METHOD: Retrospective study. Clinical records of all patients (1-15 years) diagnosed with ALL between January 2010 and December 2015 at the Hospital Luis Calvo Mackenna were reviewed. The incidence of HSR to ASP was determined and classified according to the CTCAE v5.0 severity score. We analyzed the relative risk of HSR using Fisher's test and the survival with the Kaplan-Meier estimator. RESULTS: 110 patients were collected. During the first treatment (ALL-IC- BFM), the incidence of HSR to L-ASP was 55%, therefore it was changed to PEG-ASP as second-line treatment, and 44% of them had HSR, and ASP should discontinued in 25% of patients. Of all the HSR to ASP, 77% were anaphylactic (CTCAE 3-5). Patients treated with augmented IB protocol were at higher risk of not completing ASP treatment due to HSR, RR 3.81 (95% CI, 1.98-7.31, p = 0.0001). Patients without HSR in ALL-IC-BFM were at lower risk of relapse, HR 0.29 (95% CI, 0.14-0.62, p = 0.0013). Considering all treatments (ALL-IC-BFM and relapse), patients who completed the ASP treatment had higher overall survival, HR 0.20 (95% CI, 0.07-0.57, p = 0.0026). CONCLUSIONS: HSR to ASP that require discontinuation of treatment are frequent in children with ALL, most of them were severe anaphylactic reactions. This study suggests a better prognosis in patients without HSR to ASP.

Porous Nanogold/Polyurethane Scaffolds with Improved Antibiofilm, Mechanical, and Thermal Properties and with Reduced Effects on Cell Viability: A Suitable Material for Soft Tissue Applications.

The use of implants carries on a series of problems, among them infections, poor biocompatibility, high levels of cytotoxicity, and significant mechanical differences between implants and host organs that promote stress shielding effects. These problems indicate that the materials used to make implants must meet essential requirements and high standards for implantations to be successful. In this work, we present the synthesis, characterization and evaluation of the antibiofilm, mechanical, and thermal properties, and cytotoxic effect of a nanocomposite-based scaffold on polyurethane (PU) and gold nanoparticles (AuNPs) for soft tissue applications. The effect of the quantity of AuNPs on the antibacterial activity of nanocomposite scaffolds was evaluated against Staphylococcus epidermidis and Klebsiella spp., with a resulting 99.99% inhibition of both bacteria using a small quantity of nanoparticles. Cytotoxicity was evaluated with the T10 1/2 test against fibroblast cells. The results demonstrated that porous nanogold/PU scaffolds have no toxic effects on fibroblast cells to the 5 day exposition. With respect to mechanical properties, stress-strain curves showed that the compressive modulus and yield strength of PU scaffolds were significantly enhanced by AuNPs (by at least 10 times). This is due to changes in the arrangement of hard segments of PU, which increase the stiffness of the polymer. Thermogravimetric analysis showed that the degradation onset temperature rises with an increase in the quantity of AuNPs. These properties and characteristics demonstrate that porous nanogold/PU scaffolds are suitable material for use in soft tissue implants.

Polyethylene/silver-nanofiber composites: A material for antibacterial films.

Silver nanofibers (Ag-Nfbs)~80nm in diameter were synthesized by hydrothermal treatment. The nanofibers (3 and 5wt%) were added in the initial feed together with the catalytic system. Polymerizations in an ethylene atmosphere were performed, yielding PE nanocomposites in situ with 3 and 5wt% content of Ag-Nfbs. The antibacterial effect of the silver-nanofiber composites was evaluated after incubation of Escherichia coli ATCC 25923 for 8h on their surface. Bacterial viability tests showed that the silver-nanofiber composites inhibited the growth of Escherichia coli ATCC 25923 by 88 and 56%. This behavior is attributed to increased silver ions release from the nanocomposite. TEM analysis showed that the antibacterial effect is associated with membrane disruption but not with changes in shape.

Antibacterial and non-cytotoxic effect of nanocomposites based in polyethylene and copper nanoparticles.

In this study, an antibacterial, but not cytotoxic nanomaterial based on polyethylene and copper nanoparticles was prepared by in situ polymerization. PE-CuNps nanocomposites against Escherichia coli, completely suppressed the number of live bacteria after 12 h incubation compared to neat PE. TEM images showed that nanocomposites damage the plasma membrane of the bacteria, revealing a bacteriolytic effect. Toxic effects of copper nanoparticles on viability of neuroblastoma line cell also was evaluated, revealing a non cytotoxic effect for the doses used, showing that this nanocomposite is a ideal material for medical devices.

Release of silver and copper nanoparticles from polyethylene nanocomposites and their penetration into Listeria monocytogenes.

Since infection is a major cause of death in a patient whose immune responses have been compromised (immunocompromised patient), considerable attention has been focused on developing materials for the prevention of infections. This has been directed primarily at suppressing or eliminating the host's endogenous microbial burden and decreasing the acquisition of new organisms. In this study, the antibacterial properties of two nanocomposites, polyethylene modified with silver nanoparticles (PE-AgNps) or copper nanoparticles (PE-CuNps), against Listeria monocytogenes have been investigated. In order to elucidate the antibacterial mechanism, specifically whether this mechanism corresponds to bactericidal or bacteriolytic activities, we have determined the extent of release of metal ions (Ag(+) and Cu(2+)) and, also, the morphology of the bacteria. The metal ion release from nanocomposites was followed by inductively coupled plasma spectrometry and the morphology of the bacteria was revealed through examination of ultramicrotomed sections of bacteria in a transmission electron microscope. The study of metal ion release from the nanocomposites shows that for both nanocomposites the amount of ions released varies with time, which initially displays a linear behavior until an asymptotic behavior is reached. Further, TEM images show that silver nanoparticles (AgNps) and copper nanoparticles (CuNps), which are released from the nanocomposites, can penetrate to the cell wall and the plasma membrane of bacteria. Resulting morphological changes involve separation of the cytoplasmic membrane from the cell wall, which is known to be an effect of plasmolysis. It was revealed that the antibacterial abilities of the two nanocomposites against L. monocytogenes are associated with both bactericidal and bacteriolytic effects.

Antibacterial, kinetics and bacteriolytic properties of silver(I) pyridinedicarboxylate compounds.

Antibacterial properties of silver(I)-pyridinedicarboxylate compounds (with Pyridine-2,3-dicarboxylic(Lutidinic acid), pyridine-2,4-dicarboxylic (Quinolinic acid) and pyridine-2,5-dicarboxylic (Isocinchomeronic acid)) were studied against Escherichia coli, Listeria monocytogenes (ISP-65-08), Salmonella typhi and Staphylococcus aureus (ATCC 25923) using kinetics of grown inhibition, viability assays, minimum inhibitory concentration and optical microscopy. The 3 silver compounds were tested toward UV-radiation in order to characterize their light insensitivity for potential medical devices: UV-radiation curable polymers. Photophysical measurements show remarkable differences toward UV-radiation, which were explained based on their polymeric structures with multiple nature bonds between pyridinedicarboxylic ligands and Ag(I) centers. We found a bacteriolytic effect and differences in the antibacterial efficiency depending on the structure of the complexes and the nature of AgX (X=oxygen and nitrogen) bonds: AgQuinol>AgLutidin>AgIsocinchom.

Kt/V and nPNA in pediatric peritoneal dialysis: a clinical or a mathematical association?

The relationship between dialysis dose and nutrition is a field of particular interest in chronic pediatric dialysis (PD), and a positive correlation between ureaKt/V and nPNA has been published, suggesting a better nutritional status is associated with higher dialysis doses. However, this relationship has also been criticized as being the result of a mathematical coupling resulting from the same variables. The objective of the study was to establish the relationship between dialysis dose (Kt/V) and nutritional variables: daily protein intake (DPI), protein catabolic rate (PCR), protein equivalent of total nitrogen appearance (PNA) and nitrogen balance (NB) in dialyzed children. A cohort, prospective, observational study was carried out, for which 223 biochemical measurements were performed in 20 patients, ages 1 month to 14.3 years old (13 males), under PD for a 12-month period of follow-up. Monthly residual and total ureaKt/V, DPI, PCR, nPNA and NB were calculated, and the correlation between Kt/V and the nutritional parameters was evaluated. The Borah equation was used to calculate the nPNA. The data are reported as the mean plus or minus the standard error. All statistical comparisons were done with a paired t test, and two-way ANOVA for repeated measures was used to calculate correlations. A P <0.05 was considered significant. Mean total and residual Kt/V was 3.4+/-1.3 and 1.69+/-1.27, respectively; nPNA and PCR were 1.38+/-0.44 and 1.39+/-0.43 g/kg/day, daily protein intake (DPI) was 3.25+/-1.27 g/kg/day, and NB showed a value of 1.86+/-1.25 g/kg/day. A significant positive correlation was found between Kt/V and DPI, PCR, DPC and nPNA (all values P <0.0001), but no correlation was found between total and residual Kt/V vs. nitrogen balance ( P:ns). Total Kt/V showed a significant positive correlation with nPNA, but it did not show any correlation with nitrogen balance, suggesting that the relationship with nPNA is the result of a mathematical association calculated from the same variables.

Pediatric renal transplantation: 13 years of experience--report from the Chilean Cooperative Multicenter Group.

Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.

[Measurement of 17 OH progesterone in blood in Chilean newborns: antecedents for implementing a grogram for the neonatal detection of congenital adrenal hyperplasia]. / Medición de 17-OH progesterona sanguínea en recién nacidos chilenos: antecedentes para implementar un programa de detección neonatal de hiperplasia suprarrenal congénita.

BACKGROUND: The early diagnosis and therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can prevent adrenal crises and erroneous gender assignment in affected newborns. To achieve this goal neonatal mass-screening programs have been developed, measuring blood 17 alpha-hydroxyprogesterone (17OHP). In Chile there is no experience with this type of screening. AIM: To develop a method for measuring 17OHP in filter paper blood specimens. To obtain reference ranges and determine neonatal 17OHP threshold levels according to gestational age and birth weight. To analyze factors affecting the cost-efficiency ratio and suggest recommendations for the organization of a neonatal screening program for CAH in Chile. MATERIAL AND METHODS: Nine hundred twenty two newborns were studied. 17OHP was measured using double antibody radioimmunoassay in filter paper blood samples obtained 48 h after birth. Reference ranges were determined according to gestational age and birth weight and a cutoff point of 25 ng/ml was established. RESULTS: Seventeen newborns had 17OHP over the cutoff value. They were assessed by a pediatric endocrinologist and in none of them, CAH was confirmed. Therefore the false positive rate of the determination was 1.8%. Among these newborns with elevated 17OHP, 66% had a birth weight below 1.5 kg and 5.8%, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ 1. Timing of the recall was between the 3 and 10 days of life. No newborn missed the follow-up. DISCUSSION: To increase the cost-efficiency ratio of an eventual neonatal screening program, newborns with birth weights below 1.5 kg should be excluded and cutoff points should be defined according to birth weight (Rev Méd Chile 2000; 128: 1113-18).

[Negative appendectomy: experience at a university hospital]. / Apendicectomía negativa: experiencia en un hospital universitario.

BACKGROUND: Acute appendicitis still constitutes a difficult diagnostic problem. AIM: To assess the experience of an University Hospital in the diagnosis of acute appendicitis and to determine the rates of negative appendectomies. PATIENTS AND METHODS: The charts of 1,075 patients operated with the diagnosis of acute appendicitis, between 1993 and 1995, were retrospectively reviewed. All resected appendices were pathologically examined. Those cases in whom pathology did not confirm the clinical diagnosis were considered as a negative appendectomy. RESULTS: There was a 12.2% rate of negative appendectomies (18.9% in women and 6.2% in men). The difference between sexes disappears in patients over 40 years old. In 49% of patients, no abnormality was detected during the laparotomy. The most frequent differential diagnosis were gynecological illnesses or diseases of the colon. DISCUSSION: The rate of negative appendectomies can be reduced with a close clinical observation of patients during their hospitalization and the judicious use of diagnostic laparoscopy.

Sobrevida libre de enfermedad, posterior a prostatectomía radical por cáncer de próstata, para estadios precoces (T2p o menores) / Free of disease survival, after radical prostatectomy by prostatic cancer, for early stages (T2p O smaller)

Este estudio incluye una serie consecutiva de 43 enfermos, con un cáncer prostático localizado, que fueron sometidos a Prostatectomía Radical Retropúbica con tumores es estadios T1p y T2p. El objetivo fue determinar la sobrevida libre de enfermedad posterior a la cirugía radical. La edad promedio fue de 63.8 años. Hubo 8 pacientes con bordes quirúrgicos positivos (18 por ciento). El análisis estadístico mostró que existen diferencias estadísticamente significativas en la sobrevida libre de enfermedad entre los enfermos con bordes quirúrgicos positivos y los sin compromiso quirúrgico del borde. La sobrevida actuarial global libre de enfermedad, muestra que al año existe una posibilidad de sobrevida libre de enfermedad del 90 por ciento, ésta es del 85 por ciento a los 2 años, la que se mantiene hasta los 56 meses (4 años 8 meses) para obtener una sobrevida final libre de enfermedad del 71 por ciento a los 5 años. La serie tienen la particularidad de describir los estadios precoces patológicos, ya que la sobrevida libre de enfermedad en los estadios precoces clínicos (T1c-T2c), tiene gran variabilidad en los resultados debido a que la etapificación clínica presenta hasta un 30 por ciento de subetapificación lo que impide una adecuada comparación entre las distintas series. En síntesis creemos que la alternativa quirúrgica es la mejor terapia para los pacientes con cáncr de próstata clínicamente localizado, con una baja morbilidad, buenos resultados funcionales y con buena sobrevida libre de enfermedad

Nefrectomías parciales por cáncer renal: experiencia clínica / Partial nephrectomies due to renal cancer: clinical experience

Con la detección cada vez más importante de tumores renales pequeños T1 y T2 (15-30 por ciento), la nefrectomía parcial ha surgido como una nueva alternativa terapéutica en el manejo de estos tumores. El objetivo de este trabajo es mostrar nuestra experiencia y resultados. Se realizó un estudio retrospectivo descriptivo de una serie consecutiva de 29 pacientes sometidos a nefrectomía parcial por cáncer renal en un período de 11 años. De la serie hubo 21 nefrectomías parciales de necesidad (72 por ciento) obligadas por la condición clínica del enfermo como ser monorreno o Insuficiente renal. El examen de la pieza quirúrgica mostró que existe una buena correlación entre el tamaño determinado por TAC y el tamaño tumoral real, un 51 por ciento de las piezas era tumores T2. La morbilidad postoperatoria inmediata fue menor (17 por ciento) y de manejo médico. En el seguimiento sólo 1 paciente se encuentra en diálisis. No hemos registrado recurrencia local y hay 3 pacientes con recurrencia a distancia todos ellos con tumores contralaterales previamente sometidos a nefrectomía radical. En los pacientes con nefrectomía parcial electiva, no de necesidad, no se ha observado recurrencia. La nefrectomía parcial aparece como una alternativa atractiva en el manejo de pacientes con tumores renales pequeños T1 o T2, principalmente en aquellos con indicación de necesidad ya que les permite mantener una función renal aceptable sin necesidad de diálisis