Miguel Ángel Villasís-Keever

Salmonella porins induce a sustained, lifelong specific bactericidal antibody memory response

We examined the ability of porins from Salmonella enterica serovar typhi to induce a long‐term antibody response in BALB/c mice. These porins triggered a strong lifelong production of immunoglobulin G (IgG) antibody in the absence of exogenous adjuvant. Analysis of the IgG subclasses produced during this antibody response revealed the presence of the subclasses IgG2b, IgG1, IgG2a and weak IgG3. Despite the high homology of porins, the long‐lasting anti‐S. typhi porin sera did not cross‐react with S. typhimurium. Notably, the antiporin sera showed a sustained lifelong bactericidal‐binding activity to the wild‐type S. typhi strain, whereas porin‐specific antibody titres measured by enzyme‐linked immunosorbent assay (ELISA) decreased with time. Because our porin preparations contained the outer membrane proteins C and F (OmpC and OmpF), we evaluated the individual contribution of each porin to the long‐lasting antibody response. OmpC and OmpF induced long‐lasting antibody titres, measured by ELISA, which were sustained for 300 days. In contrast, although OmpC induced sustained high bactericidal antibody titres for 300 days, postimmunization, the bactericidal antibody titre induced by OmpF was not detected at day 180. These results indicate that OmpC is the main protein responsible for the antibody‐mediated memory bactericidal response induced by porins. Taken together, our results show that porins are strong immunogens that confer lifelong specific bactericidal antibody responses in the absence of added adjuvant.

Triggering receptor expressed on myeloid cells (TREM-1) is regulated post-transcriptionally and its ligand is present in the sera of some septic patients

Inflammation is necessary for survival, but it is also an important cause of human morbidity and mortality, as exemplified by sepsis. During inflammation, cells of the innate immune system are recruited and activated in response to infection, trauma or injury. These cells are activated through receptors, such as Toll‐like receptors (TLRs), which recognize microbial ligands such as lipopolysaccharide (LPS). Triggering receptor expressed on myeloid cells (TREM)‐1 amplifies the inflammatory response initiated by TLRs, and its expression on the surface of monocytes increases in the presence of TLR ligands. Here we have shown that in monocytes TREM‐1 mRNA levels, measured by reverse transcription–polymerase chain reaction (RT–PCR), remained unchanged and TREM‐1 protein levels, measured by flow cytometry, increased, indicating that LPS increases TREM‐1 expression by a post‐transcriptional mechanism. We also showed that TREM‐1/Fc fusion protein decreased the ability of the sera of some patients with sepsis to activate monocytes, indicating that the TREM‐1 ligand, whose identity is unknown, may be present in the sera of some of these patients. We describe a mechanism for the regulation of TREM‐1 expression on monocytes and the possible presence of its ligand in serum; these findings help to explain the contribution of TREM‐1 during systemic inflammation.

Palonosetron Hydrochloride Is an Effective and Safe Option to Prevent Chemotherapy-induced Nausea and Vomiting in Children

BACKGROUND Emesis and nausea are common adverse effects of chemotherapy. Consequences include dehydration, acute renal failure, esophageal rupture, electrolyte imbalance and undernutrition, among others. First-generation 5-HT3 antagonists significantly reduce these symptoms but are expensive and require administration every 8-12h. Palonosetron, a second generation 5-HT3 antagonist has proven better results in adult populations. Other benefits include a one-dose administration with effect for up to 7 days and a lower treatment cost. No clinical studies have evaluated the safety and efficacy of palonosetron in children. METHODS Prior to every course, patients were randomized to receive palonosetron or ondansetron. Patients or guardians recorded the number of emetic events and the intensity of nausea over a 7-day period. They also reported any possible adverse effects. Statistical analysis included chi(2) test, relative risk, and Students t test. RESULTS Fifty courses were analyzed for each group. There was a significant reduction in emesis on the first 3 days and in the intensity of nausea in the first four days in the palonosetron group. There was an increased risk of presenting emesis and nausea in the acute phase when treated with ondansetron. No adverse effects were reported. The cost of treatment was also reduced when using palonosetron. CONCLUSIONS Palonosetron is a safe and effective antiemetic treatment in children, as well as being cost effective.

Security and Maximal Tolerated Doses of Fluvastatin In Pediatric Cancer Patients

BACKGROUND The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. OBJECTIVE The objective of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients. METHODS This study was carried out in a third level Social Security Hospital in Mexico City. We included pediatric patients from April 1996 to May 1997. All were terminal cancer patients who did not respond to conventional therapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had increments of 2 mg/kg/day of the drug until maximal tolerated doses were found. Toxic effects of the drug were evaluated by physical exploration, laboratory assays and a questionnaire given to each patient. RESULTS Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewings sarcoma. Ten patients died within 1 to 18 months. Two are alive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses were administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. CONCLUSIONS Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials.

Frecuencia y factores de riesgo asociados a desnutrición de niños con cardiopatía congénita

Objetivo. Determinar la frecuencia y factores asociados a desnutricion en ninos con cardiopatia congenita (CC). Material y metodos. Estudio transversal analitico, hecho entre agosto de 1997 y mayo de 1998, en el servicio de cardiopatias congenitas del hospital de Cardiologia del Centro Medico Nacional Siglo XXI, del Instituto Mexicano del Seguro Social de la Ciudad de Mexico, Mexico, a 244 menores de 17 anos, de ambos sexos, con diagnostico de CC y sin otras malformaciones. El estado de nutricion se evaluo mediante los indices peso/edad (P/E), talla/edad (T/E) y peso/talla (P/T), y se definio desnutricion con puntuaciones Z mayores a -2. Se consideraron factores de riesgo: edad, sexo, antecedentes perinatales, historia de alimentacion, administracion de suplementos nutricios, estado socioeconomico y funcionalidad y composicion de la familia. Se formaron cuatro grupos de CC: acianogenas con flujo pulmonar aumentado (AFPA) o con flujo pulmonar normal (AFPN); cianogenas con flujo pulmonar aumentado (CFPA) o disminuido (CFPD). Analisis estadistico: ji cudrada, U-Mann Whitney, Kruskal-Wallis. Se aplico regresion logistica para el control de las variables de confusion y se calculo razon de momios (RM) e intervalos de confianza al 95% (IC 95%). Resultados. El grupo de AFPA (62.7%) fue el mas frecuente, seguido por CFPD (15.6%), AFPN (11.5%) y CFPA (10.2%); con P/E, 40.9% tuvieron desnutricion; con T/E, 24.6%; y con P/T, 31.1%. Los grupos mas afectados fueron los lactantes y los ninos con CFPA. Los factores asociados a desnutricion fueron: presencia de cardiopatia cianogena (RM 2.54; IC 95% 0.98-6.58) y la falta de administracion de algun complemento nutricio (RM 2.38; IC 95% 1.06-5.34). Entre mayor numero de miembros en una familia (RM 1.42; IC 95% 0.99-2.05) mayor frecuencia de desnutricion; a mayor edad menor riesgo de desnutricion (RM 0.92; IC 95% 0.89-0.96). Conclusiones. La desnutricion en ninos con CC es frecuente; es mas comun en ninos mas pequenos y con cardiopatias cianogenas. Se necesitan programas orientados a las familias para prevenir y disminuir la desnutricion en estos ninos. El texto completo en ingles de este articulo esta disponible en: http://www.insp.mx/salud/index.html

Birth prevalence of congenital hypothyroidism in Mexico

The Mexican Institute of Social Security (IMSS) provides care for more than 40% of the Mexican population. This report constitutes the first study of the incidence of congenital hypothyroidism (CH) in Mexican children. We performed a prospective study with a population base. CH screening began in 1997 with blood samples from the heel taken 72 h after birth; from 2000, the detection strategy was changed nationwide and blood samples were taken from the umbilical cord in all newborns for determination of thyroid-stimulating hormone (TSH) concentration. We evaluated the annual coverage. TSH concentration was measured by chemoluminescence; TSH values > or =30 microIU/mL in umbilical cord blood and 15 microIU/mL in capillary blood were considered positive cases and were confirmed through hormonal studies. The incidence and 95% confidence intervals [95% CI] were calculated. We found that coverage within the IMSS population was 53% from 1997 to 2000 and had increased to 95% by 2001. A total of 2,777,292 children from 2,975,157 births (93%) were studied between 2000 and 2004. Of these, 4050 had a high TSH concentration leading to suspicion of CH; CH was confirmed in 1286 (32%). The resulting incidence was 4.3/10,000 livebirths [95% CI 3.6, 5.1]. With the results obtained, we conclude that the IMSS strategy of CH screening at birth ensured 95% coverage of children in the system. The birth prevalence of CH reported is among the highest in the world.

Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

Sistema de Protección Social en Salud para la detección y atención oportuna de problemas del desarrollo infantil en México

a Comision Nacional de Proteccion Social en Salud, Secretaria de Salud, Mexico D.F., Mexico b Unidad de Investigacion en Neurodesarrollo, Hospital Infantil de Mexico Federico Gomez, Mexico, D.F., Mexico c Direccion General del Programa PROSPERA, Comision Nacional de Proteccion Social en Salud, Mexico, D.F., Mexico d Direccion General Adjunta de Seguro Medico Siglo XXI, Comision Nacional de Proteccion Social en Salud, Mexico, D.F., Mexico e Direccion de Investigacion, Hospital Infantil de Mexico Federico Gomez, Mexico, D.F., Mexico f Unidad de Investigacion en Epidemiologia Clinica, Unidad Medica de Alta Especialidad Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico, D.F., Mexico

Breastfeeding Among Patients with Congenital Malformations

BACKGROUND This study was undertaken in order to 1) determine the frequency of infants with major congenital malformations who are breastfed and 2) identify factors associated with initiating and early weaning of breastfeeding. METHODS We conducted a descriptive cohort study at a tertiary-care pediatric hospital. Subjects included infants <20 days of age with major congenital malformations. According to the feeding pattern, the following three groups were identified: exclusively breastfed (EB); alternating breast and formula (ABF), and exclusively formula (EF).Follow-up interviews were conducted on a monthly basis until the infants were 6 months of age. The feeding pattern was determined during each visit. Reasons for changing the breastfeeding pattern were explored. RESULTS A total of 120 newborns were recruited. At the time of the first interview, 29.2% were EF, 47.5% EB, and 23.3% ABF. By 6 months of age, the feeding patterns were 8.6, 18.1, and 73.3%, respectively. Median length of breastfeeding was 3 months (range: 1-6 months). The maternal prenatal decision to breastfeed (odds ratio [OR] 0.11, 95% confidence interval [95% CI] 0.02-0.52) and attendance at prenatal breastfeeding sessions (OR 0.30, 95% CI 0.17-0.87) were associated with breastfeeding initiation. Conversely, mother-child separation (OR 3.07, 95% CI 1.36-7.01) and low birth weight (OR 2.98, 95% CI 1.36-6.48) were associated with a lack of breastfeeding. The mothers sensation of low milk production was the main reason to change or to stop breastfeeding. CONCLUSIONS In this study, breastfeeding frequency and length among infants with congenital malformations during the first 6 months of life were lower than previously published reports of breastfeeding obtained from healthy infants. Healthcare professionals must encourage breastfeeding in these infants.

Escrutinio poblacional del nivel de desarrollo infantil en menores de 5 años beneficiarios de PROSPERA en México

BACKGROUND Evaluación del Desarrollo Infantil or Child Development Evaluation (CDE) test, a screening tool designed and validated in Mexico, classifies child development as normal (green) or abnormal (developmental lag or yellow and risk of delay or red). Population-based results of child development level with this tool are not known. The objective of this work was to evaluate the developmental level of children aged 1-59 months living in poverty (PROSPERA program beneficiaries) through application of the CDE test. METHODS CDE tests were applied by specifically trained and standardized personnel to children <5 years old who attended primary care facilities for a scheduled appointment for nutrition, growth and development evaluation from November 2013 to May 2014. RESULTS There were 5,527 children aged 1-59 months who were evaluated; 83.8% (n=4,632) were classified with normal development (green) and 16.2% (n=895) as abnormal: 11.9% (n=655) as yellow and 4.3% (n=240) as red. The proportion of abnormal results was 9.9% in children <1 year of age compared with 20.8% at 4 years old. The most affected areas according to age were language at 2 years (9.35%) and knowledge at 4 years old (11.1%). Gross motor and social areas were more affected in children from rural areas; fine motor skills, language and knowledge were more affected in males. CONCLUSIONS The proportion of children with abnormal results is similar to other population-based studies. The highest rate in older children reinforces the need for an early-based intervention. The different pattern of areas affected between urban and rural areas suggests the need for a differentiated intervention.