Factores asociados al fracaso de la terapia con cánulas nasales de alto flujo en pacientes pediátricos con insuficiencia respiratoria en dos unidades de cuidados críticos pediátricos a gran altitud / Factors associated to high-flow nasal cannula treatment failure in pediatric patients with respiratory failure in two pediatric intensive care units at high altitude

Introducción: El fallo respiratorio agudo es la principal causa de hospitalización en pediatría. Las cánulas nasales de alto flujo (CNAF) ofrecen una nueva alternativa, pero sigue existiendo debate en torno a la evidencia e indicaciones. No se ha descrito su comportamiento en gran altitud. Objetivo Describir el uso de CNAF en pacientes pediátricos que ingresan con insuficiencia respiratoria y explorar los factores asociados al fracaso de la terapia. Metodología Estudio de cohortes prospectivo. Pacientes entre un mes y 18 años manejados con CNAF. Se describieron datos demográficos y se evaluó la respuesta al inicio, 1.a, 6.a y 24.a horas. Se determinó el número de fracasos, así como estancia, complicaciones y mortalidad. Se compararon los pacientes con fracaso al tratamiento. Resultados Ingresaron 539 pacientes. Fueron más frecuentes los lactantes (70,9%) de sexo masculino (58,4%) con afecciones respiratorias como asma y bronquiolitis (61,2%). Se presentaron 53 fracasos (9,8%), 21 en las primeras 24 horas. La mediana de estancia fue de 4 días (RIQ 4), hubo 5 éxitus (0,9%) y 13 eventos adversos –epistaxis– (2,2%). Se observó mejoría de signos vitales y gravedad en el tiempo con diferencias en el grupo que fracasó, pero sin interacciones. El modelo logístico final estimó una relación independiente del fracaso, entre el hospital (OR 2,78; IC95% 1,48-5,21) y la frecuencia respiratoria inicial (OR 1,56; IC95% 1,21-2,01). Conclusión La CNAF es un sistema con buena respuesta clínica, pocas complicaciones y una baja tasa de fracasos. Las diferencias entre las instituciones sugieren una relación subjetiva de la decisión del fracaso. (AU)

Introduction: Acute respiratory failure is the leading cause of hospitalization in pediatrics. High-flow nasal cannulas (HFNCs) offer a new alternative, but the evidence and indications are still debated. The performance of HFNCs at high altitude has not been described to date. Objective To describe the use of HFNCs in pediatric patients admitted with respiratory failure and explore the factors associated with treatment failure. Methodology A prospective cohort study was carried out in patients between 1 month and 18 years of age managed with HFNCs. The demographic and treatment response data were recorded at baseline and after 1, 6 and 24hours. The number of failures was determined, as well as the length of stay, complications and mortality. Patients with treatment failure were compared with the rest. Results A total of 539 patients were enrolled. Infants (70.9%) of male sex (58.4%) and airway diseases such as asthma and bronchiolitis (61.2%) were more frequent. There were 53 failures (9.8%), with 21 occurring in the first 24hours. The median length of stay was 4 days (IQR 4); there were 5 deaths (0.9%) and 13 adverse events (epistaxis) (2.2%). Improvement was observed in vital signs and severity over time, with differences in the group that failed, but without interactions. The final logistic model established an independent relationship of failure between the hospital (OR 2.78, 95%CI 1.48-5.21) and the initial respiratory rate (OR 1.56, 95%CI 1.21-2.01). Conclusions HFNCs afford good clinical response, with few complications and a low failure rate. The differences found between institutions suggest a subjective relationship in the decision of therapy failure. (AU)

[Factors associated to high-flow nasal cannula treatment failure in pediatric patients with respiratory failure in two pediatric intensive care units at high altitude]. / Factores asociados al fracaso de la terapia con cánulas nasales de alto flujo en pacientes pediátricos con insuficiencia respiratoria en dos unidades de cuidados críticos pediátricos a gran altitud.

INTRODUCTION: Acute respiratory failure is the leading cause of hospitalization in pediatrics. High-flow nasal cannulas (HFNCs) offer a new alternative, but the evidence and indications are still debated. The performance of HFNCs at high altitude has not been described to date. OBJECTIVE: To describe the use of HFNCs in pediatric patients admitted with respiratory failure and explore the factors associated with treatment failure. METHODOLOGY: A prospective cohort study was carried out in patients between 1 month and 18 years of age managed with HFNCs. The demographic and treatment response data were recorded at baseline and after 1, 6 and 24hours. The number of failures was determined, as well as the length of stay, complications and mortality. Patients with treatment failure were compared with the rest. RESULTS: A total of 539 patients were enrolled. Infants (70.9%) of male sex (58.4%) and airway diseases such as asthma and bronchiolitis (61.2%) were more frequent. There were 53 failures (9.8%), with 21 occurring in the first 24hours. The median length of stay was 4 days (IQR 4); there were 5 deaths (0.9%) and 13 adverse events (epistaxis) (2.2%). Improvement was observed in vital signs and severity over time, with differences in the group that failed, but without interactions. The final logistic model established an independent relationship of failure between the hospital (OR 2.78, 95%CI 1.48-5.21) and the initial respiratory rate (OR 1.56, 95%CI 1.21-2.01). CONCLUSIONS: HFNCs afford good clinical response, with few complications and a low failure rate. The differences found between institutions suggest a subjective relationship in the decision of therapy failure.

HIV testing and counselling in Colombia: evidence from a national health survey and recommendations for health-care services.

The purpose of this study was to assess the prevalence of, and the factors associated with HIV testing and pre- and post-test counselling (PPTC) in Colombia. Cross-sectional data from the National Health Survey carried out during 2007 were analysed. Data were gathered from records of 29,760 individuals between the ages of 18 and 69 from the main regions of the country. Only 19.7% of the sample had taken an HIV test. Men, people with no education, those not affiliated with the health-care system, residents of rural areas and those aged older than 65 were less likely to have been tested for HIV; 42% of those tested did not receive pre-test counselling and 56.9% received no report of the results. Considering the low prevalence of HIV testing among the Colombian population, it is necessary to design and apply guidelines for HIV screening in all health-care settings and to conduct targeted testing in high-risk sub-populations. A national norm of PPTC in those who undergo HIV testing should be examined.

Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs.

Due to the growing demand of enantiomerically pure compounds, as well as the increasing strict safety, quality and environmentally requirements of industrial synthetic processes, the development of more sustainable, healthy and economically attractive strategies for the synthesis of chiral biologically active molecules is still an open challenge in the pharmaceutical industry. In this context, the biotransformations field has emerged as a real alternative to traditional synthetic routes, because of the exquisite chemo-, regio- and enantioselectivities commonly displayed by enzymes; thus, biocatalysis is becoming a widespread methodology for the synthesis of chiral compounds, not only at laboratory scale, but also at industrial scale. As hydrolases and oxido-reductases are the most employed enzymes, this review is focused on describing several industrial processes based on the use of these enzymes for obtaining chiral compounds useful for the pharmaceutical industry.

Microbial cells as catalysts for stereoselective red-ox reactions.

Enzyme catalyzed reactions are commonly used at laboratory or industrial scale. Contrarily, the whole cell catalyzed reactions are restricted to special cases. The tremendous advances in the last years in Molecular Biology and more specifically in Metabolic Engineering and Directed Enzyme Evolution have opened the door to create tailor-made microorganisms or "designer bugs" for industrial purposes. Whole cell catalysts can be much more readily and inexpensively prepared than purified enzymes and the enzymes - inside the cells - are protected from the external environment and stabilized by the intracellular medium. Three situations have traditionally been considered convenient to select the use of whole cell catalyzed processes against the free enzyme catalyzed process: i) when the enzyme is intracellular; ii) when the enzyme needs a cofactor to carry out the catalytic act and iii) in the development of multienzymatic processes. Red-ox reactions represent the molecular basis for energy generation in the cell. These reactions are catalyzed by intracellular enzymes and are cofactor dependent as red-ox reactions need electron carriers as helpers in reduction reactions (gain of electrons) or oxidation (loss of electrons). In this review we present an overview of the state of the art of red-ox biotransformations catalyzed by whole cells - wild-type or genetically engineered microorganisms. Stereoselective reductions, hydroxylations of arenes and unfunctionalized alkanes, alkene monooxygenation, and Baeyer-Villiger reactions are among the processes described along the text, focusing in their chemo-, regio- and stereoselectivity.

Análisis comparativo de la toxicidad del extracto acuoso en cocimiento de la harina de maca (Lepidium meyenii, Walp) en tres especies de animales modelos: Artemia franciscana (Crustácea, Anostraca), pez Guppy (Poecilia Reticulata) y ratón (Mus musculus) / Comparative analisis of toxicity of aqueous boiled extracts of maca flour (Lepidium meyenii, Walp) in Artemia franciscana (Crustacea anostraca), guppy (Poecilia reticulate) and mouse (Mus musculus)

Se evalúa la toxicidad del extracto acuoso en cocimiento de la harina de maca en dos organismos acuáticos, un invertebrado la Artemia franciscana y un vertebrado el pez Guppy (Poecilia reticulata). Así mismo, se evalúa la toxicidad aguda por vía intraperitoneal en el ratón (Mus musculus) que es el modelo animal comúnmente utilizado para ensayos preclínicos a nivel de laboratorios. Se comprobó que existe toxicidad del Lepidium meyenii para estos tres animales que dependen de la dosis y el tiempo de exposición.

Toxicity of aqueous boiled extracts of maca flour was evaluated in two aquatic organisms: Artemia franciscana (invertebrate) and guppy (Poecilia reticulata), a vertebrate fish. Also, acute toxicity of this extract was evaluated by intraperitoneal administration in mouse (Mus musculus), a common animal model used in laboratories for preclinical tests. Results show toxic effects of Lepidium meyenii on all three animal species, depending on dose and exposure time.

New cytotype in the Simulium metallicum complex (Diptera: Simuliidae) from Cundinamarca, Colombia.

Polytene chromosomes (n = 108) and morphology (n = 22) of Simulium metallicum Bellardi were described from larvae collected in different localities in Cundinamarca, Colombia, and compared with the standard polytene chromosome banding patterns of S. metallicum A. Polytene chromosomes of S. metallicum from Cundinamarca were characterized by a fixed inversion on the IIL chromosome arm (IIL-22), by 2 sex-linked inversions (IIL-24 and IIL-25), 6 floating inversions, and a heteroband in the IIIS chromosome arm. This taxon was considered to be a cytotype distinct from the 11 members of the S. metallicum complex from Central and South America, and we propose here the name S. metallicum L, following the convention for naming cytotypes in this species complex. There were slight larval morphological differences between S. metallicum from Cundinamarca and S. metallicum A and S. horacioi Okazawa & Onishi (or S. metallicum H).

Current status of onchocerciasis in Colombia.

To assess the current epidemiologic status of onchocerciasis in Colombia two surveys were undertaken in 1995 in a suspected new focus on the border between Colombia and Ecuador and in the known focus located on the Micay River. No new focus was found along the Colombia-Ecuador border. In the known focus, communities along the upper Micay River and its tributaries were surveyed; 655 adults underwent physical examinations and skin biopsies. Infected individuals were found almost exclusively in the community of Naiciona, where prevalence of infection was 40% (36 of 91). Polymerase chain reaction detection of onchocercal DNA in skin snips correlated with the skin-snip biopsy results. The prevalence of punctate keratitis, the only ocular manifestation found, was 33%. A rapid entomologic assessment demonstrated Simulium exiguum infected with Onchocerca volvulus. This is the first finding in Colombia of naturally infected black flies and confirms S. exiguum as a vector species. These data will be used for implementing a control program using periodic ivermectin distribution.

The effects of lansoprazole, a new H+,K(+)-ATPase inhibitor, on gastric pH and serum gastrin.

This study examined the effects of dose and time of administration of lansoprazole on gastric pH and serum gastrin in healthy male volunteers. Three groups of six subjects received 10, 20 or 60 mg doses of lansoprazole or placebo. Doses were administered at 22.00 hours daily for 7 days. An additional 18 subjects received once daily 30 mg oral doses of lansoprazole or placebo; these subjects were dosed at either 08.00 hours or 22.00 hours in a randomized, crossover fashion with a 2-week washout period. Gastric pH was monitored for 24 h following the first and final dose, and 1 week following the completion of dosing. Lansoprazole, at all doses except 20 mg/day, significantly increased the median 24-hour gastric pH following 7 days of dosing (P less than 0.05). In addition, morning dosing in the 30-mg crossover group led to a higher 24-h median pH than evening dosing (P = 0.003). There was no difference in night-time median pH between morning and evening dosing. Morning dosing also led to a significant increase in gastric pH on study Day 1 (P less than 0.05). Plasma concentrations of lansoprazole were highly variable between subjects, but there was a significant correlation between AUC and the median 24-h gastric pH. Plasma concentrations and AUCs were higher on Day 7 than on Day 1 for subjects receiving 10 or 20 mg, but not for those receiving 30 or 60 mg doses. Lansoprazole bioavailability demonstrated a circadian effect manifested by higher plasma concentrations following morning dosing. Serum gastrin concentrations were elevated in all active medication groups.

Properties of the nucleic acid photoaffinity labeling agent 3-azidoamsacrine.

This paper reports the study of the photochemical, physical, and biological properties of 3-azidoamsacrine. The binding of 3-azidoamsacrine to DNA was studied with UV spectroscopy. The UV spectral behavior is quite similar to that of the parent amsacrine and argues that 3-azidoamsacrine is a good photoaffinity labeling agent for amsacrine. The biological properties (cytotoxicity and mutagenicity) of 3-azidoamsacrine in the mammalian mutagenesis V79 and L5178Y assay systems were measured. Light-activated 3-azidoamsacrine is toxic, but not mutagenic, to V79 cells. 3-Azidoamsacrine with and without light activation, as well as amsacrine, are toxic and mutagenic to L5178Y cells. To probe the interactions of 3-azidoamsacrine with DNA, studies of the photoreactivity of this compound were conducted. 3-Azidoamsacrine was photolyzed in the presence of the plasmid pBR322, and the effect of the photoadducts on restriction endonuclease cleavage was investigated. Amsacrine and 3-azidoamsacrine, without light activation, did not block any of the restriction endonucleases. Light-activated 3-azidoamsacrine blocked cleavage by the restriction endonucleases AluI, HinfI, NciI, NaeI, DraI, Sau96I, HpaII, and HaeIII. Photolysis experiments with mononucleosides, blocked mononucleosides, dinucleotides, and DNA all indicated that 3-azidoamsacrine formed adducts with G and A. The structures of these adducts are discussed based upon mass spectral data. Thus, it appears that 3-azidoamsacrine covalently attaches to DNA and that this covalent binding results in the production of toxic and, in some cases, mutagenic lesions in mammalian cells and the inhibition of restriction endonuclease cleavage of DNA.

Hemodynamic and humoral effects of the new renin inhibitor enalkiren in normal humans.

The effect of the renin inhibitor enalkiren (Abbott-64662) was evaluated in eight normal volunteer subjects on a standardized sodium diet (100 mmol/day) by measurement of various components of the renin-angiotensin system and drug levels in plasma. On day 1, vehicle and doses of 0.001, 0.003, and 0.01 mg/kg i.v. were administered within 2 minutes at 90-minute intervals. On day 2, vehicle and doses of 0.01, 0.03, and 0.1 mg/kg i.v. were given. With the higher doses, blood pressure tended to decrease slightly with no change in heart rate. Plasma renin activity and plasma angiotensin-(1-8)octapeptide (angiotensin II) fell markedly in a dose-dependent manner. Inhibition of plasma renin activity was maximal 5 minutes after administration of the drug and persisted 90 minutes after the doses of 0.03 and 0.1 mg/kg. Not surprisingly, there was a close correlation between plasma renin activity and plasma angiotensin II levels (r = 0.81, n = 28, p less than 0.001). In contrast, active and total renin measured directly by monoclonal antibodies rose in dose-related fashion in response to renin inhibition. Pharmacokinetic parameters were calculated using the plasma drug concentrations obtained up to 6 hours after the 0.1 mg/kg dose. By means of a two-compartment model, plasma mean half-life of the drug was estimated at 1.60 +/- 0.43 hours.

Development of Mansonella ozzardi in a black fly species of the Simulium sanguineum group from Eastern Vaupés, Colombia.

Development of the microfilaria of Mansonella ozzardi to the infective stage in a species of the Simulium sanguineum group from the Mitú area, Comisaría del Vaupés, Colombia is described. Development was synchronous, and by day 6 third-stage larvae were observed in the head of flies which had fed on two naturally infected volunteers. Simulium biting activity was high from January-March, during the dry season. Only 261 blood-fed Culicoides were collected from an infected volunteer; 40% of 43 dissected on day 0 had ingested microfilariae. However, only one of 129 C. caprilesi specimens dissected after day 2 was positive, containing a second-stage larva thought to be M. ozzardi. It is concluded that Simulium, rather than Culicoides are the principal vectors of mansonelliasis in the Mitú area.

Simulium exiguum, the vector of Onchocerca volvulus on the Rio Micay, Colombia.

Simulium exiguum were collected in the San Antonio area on the Rio Micay as they blood-fed on a volunteer naturally infected with Onchocerca volvulus. The daily dissection of specimens revealed that delayed larval development was common and 23% of the larvae were abnormally formed. However, third-stage larvae were recovered by late day 5 (140 hours) following engorgement. It is concluded that S. exiguum is the vector of O. volvulus at this Colombian endemic focus even though its host efficiency is somewhat limited. S. metallicum collected near Cali from a naturally infected San Antonio volunteer was shown to be a relatively poor experimental host for O. volvulus.