RESUMEN

Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.

Asunto(s)

Enfermedad de Chagas , Enfermedades Transmisibles , Trypanosoma cruzi , Femenino , Animales , Ratones , Humanos , Trypanosoma cruzi/metabolismo , Pepsina A/metabolismo , Parasitemia , Modelos Animales de Enfermedad , Cromatografía Liquida , Espectrometría de Masas en Tándem , Enfermedad de Chagas/parasitología , Mucinas

RESUMEN

INTRODUCTION: Sarcomatoid urothelial carcinoma (SUC) is a rare and aggressive variant of bladder cancer with limited data regarding epidemiology and survival. In this study, we explored clinicopathologic factors and oncologic outcomes of patients with SUC derived from Survival, Epidemiology and End Results (SEER) database, in comparison to conventional UC (CUC). MATERIALS AND METHODS: SEER database was searched for patients with invasive (≥T1) SUC or CUC using the topography codes C67.0 to C67.9 for bladder cancer and the morphologic codes 8120/8122 for CUC/SUC respectively. Demographic/clinicopathologic/treatment/survival data were extracted. Disease-specific survival (DSS) was estimated with the Kaplan-Meier method. Chi-squared tests were used for comparative analysis and Cox proportional hazards model for identifying clinical covariates associated with DSS. RESULTS: A total of 569 patients with SUC and 37,740 with CUC were identified. Overall, there was a male predominant population in both cohorts, although a higher proportion of women were noted in the SUC cohort (32 vs. 25%). Patients with SUC had significantly higher incidence of non-bladder confined disease (T3/4, 37% vs. 22%) and nodal invasion (18% vs. 12%) in comparison to those with CUC (all P < .05). Median DSS was 16 months (95% CI: 12.4-19.6) in the SUC vs. 82 months (95% CI; 75.9-88.1) in the CUC cohort. Presence of SUC histology was independently associated with shorter DSS in the multivariate analysis, when adjusted for other significant clinicopathologic factors. CONCLUSION: SUC was associated with advanced stage and shorter DSS compared to CUC. Further studies are needed to better understand biological underpinnings behind its aggressive behavior and the role of novel systemic treatments.

Asunto(s)

Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/cirugía , Cistectomía/métodos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/patología

RESUMEN

Staphylococcus aureus is the main pathogen associated with bovine mastitis, an intramammary inflammation that leads to significant economic losses in dairy herds. Efforts have been made to identify the bacterial determinants important to the infective process but most of the studies are focused on surface and secreted proteins. Considering that virulence is affected by metabolism, in this study we contrasted the proteome of strains of S. aureus causing persistent subclinical (Sau302 and Sau340) and clinical bovine mastitis (RF122). Protein expressions from cytosolic fractions of bacteria grown under conditions mimicking the mastitic mammary glands are reported. A total of 342 proteins was identified, 52 of which were differentially expressed. Among those down-regulated in the subclinical strains were the two-component sensor histidine kinase SaeS and PurH, both involved in bacterial virulence. The ribosome hibernation promotion factor and the 50S ribosomal protein L13 were up-regulated suggesting that Sau302 and Sau340 modulate protein translation, a condition that may contribute to bacterial survival under stressful conditions. TRAP, a regulator possibly involved in pathogenesis, was expressed only in RF122 while proteins from the Isd system, involved in heme acquisition, were exclusive to Sau302 and Sau340. In summary, the metabolic differences suggest a reduced virulence of the strains causing subclinical mastitis which may contribute to the persistent infection seen in the animals.

Asunto(s)

Mastitis Bovina , Infecciones Estafilocócicas , Animales , Bovinos , Femenino , Proteómica , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureus/genética , Virulencia

RESUMEN

The age-adjusted mortality rate for cancer in the US Hispanic population is two thirds that of the non-Hispanic white population, probably because of differences in smoking rates. We aimed to determine whether Hispanic white (HW) cancer mortality in the US-Mexico Border Region was also lower than that of the non-Hispanic white (NHW) border population, particularly in the younger population less likely to develop smoking-related cancer. We obtained age-adjusted cancer mortality rates from 1999 to 2017 for the 44 border counties, the four US-Mexico border states, and the rest of the US. We obtained cancer incidence rates for 1999-2016 from state registries. We stratified rates by age group, ethnicity, border state, urbanization, and cancer site. Age-adjusted border cancer mortality rates were 139.1/100,000 in the HW and 171.4 in the NHW populations, a ratio of 0.8. HW mortality rates were higher than NHW rates only for the 0-34 age group. State-specific HW cancer incidence rates for people 0-34 years old were 77%-80% of NHW rates. We also calculated mortality-incidence ratios (MIR) for the 0-34 population. Border mortality-incidence ratios were higher in the HW population. HW rates exceeded NHW rates for all cancer sites except skin cancer. The HW cancer disparity is due to poorer survival in the HW population, which might be due to limited access to prevention and treatment in a medically underserved area. Mortality among young border Hispanic residents might be reduced through efforts to improve insurance coverage and increase access to medical providers .

Asunto(s)

Neoplasias , Población Blanca , Adolescente , Adulto , Niño , Preescolar , Etnicidad , Hispánicos o Latinos , Humanos , Incidencia , Lactante , Recién Nacido , México/epidemiología , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

Ferroptosis has emerged as a new type of cell death in different pathological conditions, including neurological and kidney diseases and, especially, in different types of cancer. The hallmark of this regulated cell death is the presence of iron-driven lipid peroxidation; the activation of key genes related to this process such as glutathione peroxidase-4 (gpx4), acyl-CoA synthetase long-chain family member-4 (acsl4), carbonyl reductase [NADPH] 3 (cbr3), and prostaglandin peroxidase synthase-2 (ptgs2); and morphological changes including shrunken and electron-dense mitochondria. Iron overload in the liver has long been recognized as both a major trigger of liver damage in different diseases, and it is also associated with liver fibrosis. New evidence suggests that ferroptosis might be a novel type of non-apoptotic cell death in several liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), drug-induced liver injury (DILI), viral hepatitis, and hemochromatosis. The interaction between iron-related lipid peroxidation, cellular stress signals, and antioxidant systems plays a pivotal role in the development of this novel type of cell death. In addition, integrated responses from lipidic mediators together with free iron from iron-containing enzymes are essential to understanding this process. The presence of ferroptosis and the exact mechanisms leading to this non-apoptotic type of cell death in the liver remain scarcely elucidated. Recognizing ferroptosis as a novel type of cell death in the liver could lead to the understanding of the complex interaction between different types of cell death, their role in progression of liver fibrosis, the development of new biomarkers, as well as the use of modulators of ferroptosis, allowing improved theranostic approaches in the clinic.

Asunto(s)

Apoptosis , Ferroptosis , Hígado/patología , Animales , Autofagia , Biomarcadores/metabolismo , Humanos , Hierro/metabolismo

RESUMEN

OBJECTIVES: Little is known about the mortality of children along the US-Mexico border. The objective of our study was to determine whether mortality rates among Hispanic children along the border ("border Hispanic children") exceeded mortality rates among non-Hispanic white children along the border. METHODS: We examined mortality rates from 2001-2015 for children aged 1-4 years in US-Mexico border counties and in the United States overall. We compared mortality rates among Hispanic and non-Hispanic white children by county urbanization level (large central, medium, and small metropolitan; micropolitan nonmetropolitan; and noncore nonmetropolitan). RESULTS: During 2001-2015, 1811 children aged 1-4 years died in the border region. The mortality rate per 100 000 children among border Hispanic children (28.3; 95% confidence interval [CI], 26.8-29.9) exceeded the mortality rate of US Hispanic children (24.7; 95% CI, 24.3-25.1) and border non-Hispanic white children (23.2; 95% CI, 20.8-25.6). When stratified by county urbanization level, however, mortality rates of border Hispanic children were not significantly different from mortality rates of US Hispanic or border non-Hispanic white children. Mortality rates in noncore nonmetropolitan counties were twice those in large central metropolitan counties, with injury mortality accounting for most of the excess. Mortality rates increased in nonmetropolitan border counties after 2010. CONCLUSIONS: Increased risk for injury and disease in noncore nonmetropolitan counties might be related to poverty, reduced access to care, or poorer quality of care. Future research should identify the remediable risk factors in such communities as the next step in preventing deaths among children aged 1-4 years.

Asunto(s)

Hispánicos o Latinos/estadística & datos numéricos , Mortalidad/tendencias , Urbanización , Población Blanca/estadística & datos numéricos , Causas de Muerte , Preescolar , Femenino , Humanos , Lactante , Masculino , México , Estados Unidos

RESUMEN

The development of multiple vascular endothelial growth factor- and mammalian target of rapamycin-targeted therapies in advanced renal cell carcinoma has resulted in significant clinical benefit. However, the availability of multiple treatment options has led to a more complicated clinical decision-making process. Prognostic factors have been incorporated into the inclusion criteria for pivotal clinical trials and have thus provided some guidance regarding the selection and sequencing of therapy. Even within a given patient risk group and particular line of therapy, questions remain regarding the optimal choice of a targeted agent. The present review provides a practical, clinician-oriented assessment of pharmacologic factors that should be considered when a receptor tyrosine kinase or mammalian target of rapamycin kinase inhibitor is used to treat patients with advanced or metastatic renal cell carcinoma. Although these 2 classes of agents have different mechanisms of action, they are metabolized by similar pathways, resulting in broadly similar pharmacokinetic and drug-drug interaction profiles. To further individualize therapy and optimize clinical benefit, an enhanced understanding of the key pharmacologic features that differentiate these agents is important.

Asunto(s)

Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Carcinoma de Células Renales/metabolismo , Toma de Decisiones Clínicas , Ensayos Clínicos como Asunto , Interacciones Farmacológicas , Humanos , Neoplasias Renales/metabolismo , Medicina de Precisión , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del Tratamiento

RESUMEN

PURPOSE: Drug overdose deaths are epidemic in the U.S. Prescription opioid pain relievers (OPR) and heroin account for the majority of drug overdoses. Preventing death after an opioid overdose by naloxone administration requires the rapid identification of the overdose by witnesses. This study used a state medical examiner database to characterize fatal overdoses, evaluate witness-reported signs of overdose, and identify opportunities for intervention. METHODS: We reviewed all unintentional drug overdose deaths that occurred in New Mexico during 2012. Data were abstracted from medical examiner records at the New Mexico Office of the Medical Investigator. We compared mutually exclusive groups of OPR and heroin-related deaths. RESULTS: Of the 489 overdose deaths reviewed, 49.3% involved OPR, 21.7% involved heroin, 4.7% involved a mixture of OPR and heroin, and 24.3% involved only non-opioid substances. The majority of OPR-related deaths occurred in non-Hispanic whites (57.3%), men (58.5%), persons aged 40-59 years (55.2%), and those with chronic medical conditions (89.2%). Most overdose deaths occurred in the home (68.7%) and in the presence of bystanders (67.7%). OPR and heroin deaths did not differ with respect to paramedic dispatch and CPR delivery, however, heroin overdoses received naloxone twice as often (20.8% heroin vs. 10.0% OPR; p<0.01). CONCLUSION: OPR overdose deaths differed by age, health status, and the presence of bystanders, yet received naloxone less often when compared to heroin overdose deaths. These findings suggest that naloxone education and distribution should be targeted in future prevention efforts.

Asunto(s)

Analgésicos Opioides/envenenamiento , Sobredosis de Droga/epidemiología , Servicios Médicos de Urgencia/estadística & datos numéricos , Heroína/envenenamiento , Adulto , Factores de Edad , Sobredosis de Droga/etiología , Sobredosis de Droga/prevención & control , Servicios Médicos de Urgencia/métodos , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , New Mexico/epidemiología

RESUMEN

UNLABELLED: Nontyphoidal Salmonella enterica (NTS) infections are a major burden to global public health, as they lead to diseases ranging from gastroenteritis to systemic infections and there is currently no vaccine available. Here, we describe a highly effective component vaccine against S. enterica serovar Typhimurium in both gastroenteritis and systemic murine infection models. We devised an approach to generate supernatants of S. enterica serovar Typhimurium, an organism that is highly abundant in virulence factors. Immunization of mice with this supernatant resulted in dramatic protection against a challenge with serovar Typhimurium, showing increased survival in the systemic model and decreased intestinal pathology in the gastrointestinal model. Protection correlated with specific IgA and IgG levels in the serum and specific secretory IgA levels in the feces of immunized mice. Initial characterization of the protective antigens in the bacterial culture supernatants revealed a subset of antigens that exhibited remarkable stability, a highly desirable characteristic of an effective vaccine to be used under suboptimal environmental conditions in developing countries. We were able to purify a subset of the peptides present in the supernatants and show their potential for immunization of mice against serovar Typhimurium resulting in a decreased level of colonization. This component vaccine shows promise with regard to protecting against NTS, and further work should significantly help to establish vaccines against these prevalent infections. IMPORTANCE: Salmonella enterica infections other than typhoid and paratyphoid fever are a major global health burden, as they cause high morbidity and mortality worldwide. Strategies that prevent Salmonella-related diseases are greatly needed, and there is a significant push for the development of vaccines against nontyphoidal Salmonella enterica serovars. In this work, we describe an S. Typhimurium supernatant-derived vaccine that is effective in reducing bacterial colonization in mouse models of gastroenteritis as well as invasive disease. This is a component vaccine that shows high stability to heat, a feature that is important for use under suboptimal conditions, such as those found in sub-Saharan Africa.

Asunto(s)

Medios de Cultivo/química , Infecciones por Salmonella/prevención & control , Vacunas contra la Salmonella/administración & dosificación , Vacunas contra la Salmonella/inmunología , Salmonella typhimurium/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Bacteriemia/microbiología , Bacteriemia/prevención & control , Modelos Animales de Enfermedad , Heces/química , Gastroenteritis/microbiología , Gastroenteritis/prevención & control , Inmunoglobulina A/sangre , Inmunoglobulina A Secretora/análisis , Inmunoglobulina G/sangre , Intestinos/patología , Ratones , Infecciones por Salmonella/microbiología , Vacunas contra la Salmonella/aislamiento & purificación , Salmonella typhimurium/crecimiento & desarrollo , Análisis de Supervivencia , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/aislamiento & purificación

RESUMEN

The ATR-CHEK1 pathway is upregulated and overactivated in Ataxia Telangiectasia (AT) cells, which lack functional ATM protein. Loss of ATM in AT confers radiosensitivity, although ATR-CHEK1 pathway overactivation compensates, leads to prolonged G(2) arrest after treatment with ionizing radiation (IR), and partially reverses the radiosensitivity. We observed similar upregulation of the ATR-CHEK1 pathway in a subset of oral squamous cell carcinoma (OSCC) cell lines with ATM loss. In the present study, we report copy number gain, amplification, or translocation of the ATR gene in 8 of 20 OSCC cell lines by FISH; whereas the CHEK1 gene showed copy number loss in 12 of 20 cell lines by FISH. Quantitative PCR showed overexpression of both ATR and CHEK1 in 7 of 11 representative OSCC cell lines. Inhibition of ATR or CHEK1 with their respective siRNAs resulted in increased sensitivity of OSCC cell lines to IR by the colony survival assay. siRNA-mediated ATR or CHEK1 knockdown led to loss of G(2) cell cycle accumulation and an increased sub-G(0) apoptotic cell population by flow cytometric analysis. In conclusion, the ATR-CHEK1 pathway is upregulated in a subset of OSCC with distal 11q loss and loss of the G(1) phase cell cycle checkpoint. The upregulated ATR-CHEK1 pathway appears to protect OSCC cells from mitotic catastrophe by enhancing the G(2) checkpoint. Knockdown of ATR and/or CHEK1 increases the sensitivity of OSCC cells to IR. These findings suggest that inhibition of the upregulated ATR-CHEK1 pathway may enhance the efficacy of ionizing radiation treatment of OSCC.

Asunto(s)

Carcinoma de Células Escamosas/genética , Neoplasias de la Boca/genética , Proteínas Quinasas/genética , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Cromosomas Humanos Par 11/genética , Cromosomas Humanos Par 3/genética , Daño del ADN/efectos de la radiación , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de la radiación , Dosificación de Gen , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias de la Boca/metabolismo , Proteínas Quinasas/metabolismo , Tolerancia a Radiación , Transducción de Señal , Translocación Genética , Regulación hacia Arriba

Asunto(s)

Comunicación , Correo Electrónico , Internet , Competencia Profesional , Conducta , Educación de Postgrado en Medicina , Humanos , Pediatría/educación

Asunto(s)

Planificación en Desastres , Cirugía General , Sociedades Médicas , Haití , Humanos

RESUMEN

Introducción: La relación entre el estado de desarrollo económico de un país y su tasa de mortalidad por colisiones de vehículos de motor (CVM) no ha sido definida para los diferentes tipos de usuarios de las vías. Métodos: Este artículo presenta un análisis de regresión transversal con datos recientes de mortalidad en 44 países, utilizando datos de certificados de defunción provenientes de la Organización Mundial de la Salud. Resultados: Para cinco tipos de usuarios de las vías, la mortalidad por CVM es expresada como muertes por 100.000 habitantes, y muertes por 1.000 vehículos de motor. El desarrollo económico es medido como el Producto Interno Bruto (PIB) per cápita en dólares de Estados Unidos, y como vehículos de motor por 1.000 habitantes. Los resultados mostraron que la mortalidad total por CVM en los países con bajos ingresos presentó un pico a un PIB alrededor de US $2.000 per cápita, y cerca de 100 vehículos por 1.000 habitantes. Conclusiones: La mortalidad total disminuyó con el incremento del ingreso nacional alrededor de US $24.000. La mayoría de los cambios en la mortalidad por CVM asociados con el desarrollo económico fueron explicados por cambios en las tasas de usuarios no motorizados, especialmente de peatones. Las tasas totales de CVM fueron más bajas cuando la exposición de los peatones fue menor o porque hubo pocos vehículos de motor o peatones; y fueron más altas durante un periodo crítico de transición hacia transporte motorizado, cuando gran cantidad de peatones y otros usuarios vulnerables compitieron por el uso de las vías con vehículos de motor.

Asunto(s)

Humanos , Accidentes de Tránsito/estadística & datos numéricos , Accidentes de Tránsito/mortalidad , Desarrollo Económico/estadística & datos numéricos , Desarrollo Económico , Mortalidad

RESUMEN

It is believed that liver transplantation may improve the outcome of early onset methylmalonic acidemia. We report a case of methylmalonic acidemia in which successful liver transplantation in infancy failed to prevent neurologic damage caused by a metabolic stroke.

Asunto(s)

Trasplante de Hígado , Errores Innatos del Metabolismo/sangre , Errores Innatos del Metabolismo/cirugía , Ácido Metilmalónico/sangre , Complicaciones Posoperatorias , Accidente Cerebrovascular/etiología , Edad de Inicio , Preescolar , Femenino , Humanos , Factores de Tiempo

RESUMEN

Diet is one of the mainstays of the treatment of patients with urea cycle disorders. The protein intake should be adjusted to take account of the inborn error and its severity and the patient's age, growth rate, and individual preferences. Currently, the widely used standards for protein intake are probably more generous than necessary, particularly for those with the more severe variants. Most patients, except those with arginase deficiency, will need supplements of arginine, but the value of other supplements including citrate and carnitine is unclear. Any patient on a low-protein diet should be monitored clinically and with appropriate laboratory tests. All should have an emergency (crisis) regimen to prevent decompensation during periods of metabolic stress.

Asunto(s)

Errores Innatos del Metabolismo de los Aminoácidos/dietoterapia , Dieta con Restricción de Proteínas , Urea/metabolismo , Niño , Preescolar , Proteínas en la Dieta , Suplementos Dietéticos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Necesidades Nutricionales

RESUMEN

OBJECTIVE: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. METHOD: As part of a collaborative European Study on GSD type I, a retrospective registry was established in 12 European countries that included all patients with GSD-I who were known at the centers and were born from 1960 to 1995. Of a total of 288 patients with GSD-I, 57 who had GSD-Ib form the basis of this study. RESULTS: Neutropenia (defined as an absolute neutrophil count <1 x 10(9)/L) was found in 54 patients. In 64% of the patients neutropenia was documented before the age of 1 year, but in 18% of the patients neutropenia was first noted between the ages of 6 and 9 years. Neutropenia was persistent in 5 patients and intermittent without any clear cyclical course in 45. Neutrophil function was investigated in 18 patients with neutropenia and was abnormal in all. Perioral infections were reported in 37 patients, perianal infections in 27 patients, and protracted diarrhea in 23 patients. Findings on colonoscopy and radiologic studies in 10 of 20 patients suspected to have IBD were abnormal in all. All patients with IBD, perioral infections, and perianal infections had neutropenia. CONCLUSIONS: Intermittent severe neutropenia is frequently found in patients with GSD-Ib. The study also indicates that IBD in GSD-Ib is underdiagnosed; up to 77% of the patients studied had evidence of IBD, all of whom had neutropenia. IBD was not detected in those with normal neutrophil counts. These findings support the notion that neutropenia and/or neutrophil dysfunction in GSD-Ib and IBD are causally related.

Asunto(s)

Enfermedad del Almacenamiento de Glucógeno Tipo I/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Neutropenia/epidemiología , Neutrófilos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Comorbilidad , Progresión de la Enfermedad , Europa (Continente)/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades Inflamatorias del Intestino/fisiopatología , Masculino , Persona de Mediana Edad , Neutropenia/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad

RESUMEN

OBJECTIVES: During intercurrent illness children with methylmalonic acidemia were found to have increased resting energy expenditure (REE). We measured REE in children with disorders of propionate metabolism (methylmalonic and propionic acidemia) when they were well and compared the values with those predicted by the Schofield equation. STUDY DESIGN: Prospective study in tertiary care facility. REE was measured with open-circuit indirect calorimetry under standardized conditions. Predicted REE values were calculated with the Schofield equation. Fourteen subjects with propionic acidemia (n = 3) and methylmalonic acidemia (n = 11) were studied. RESULTS: The median REE was 690 kcal/d (range 186 to 1687 kcal/d), which is significantly reduced, representing 80% +/- 18% of that predicted by the Schofield height and weight equation (P <.01). REE was significantly lower in female compared with male patients for unknown reasons. There were no differences with age or neurologic state. REE was not further reduced in those with chronic renal failure. CONCLUSION: REE in patients with disorders of propionate metabolism is reduced when they are well.

Asunto(s)

Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Metabolismo Energético , Ácido Metilmalónico/sangre , Propionatos/sangre , Propionatos/metabolismo , Constitución Corporal , Calorimetría Indirecta , Niño , Femenino , Humanos , Masculino

Asunto(s)

Lepra Tuberculoide/diagnóstico , Imagen por Resonancia Magnética , Nervio Cubital/patología

RESUMEN

A 13-year-old boy with non-B12-responsive methylmalonic acidemia (MMA) had chronic renal failure. Hemodialysis led to symptomatic and biochemical improvement. He subsequently received a combined liver-kidney transplant. After 16 months of follow-up he has a normal lifestyle and a marked reduction in plasma and urine methylmalonate.

Asunto(s)

Errores Innatos del Metabolismo de los Aminoácidos/cirugía , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/terapia , Trasplante de Riñón , Trasplante de Hígado , Ácido Metilmalónico/sangre , Adolescente , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Genes Recesivos , Humanos , Fallo Renal Crónico/etiología , Masculino , Metilmalonil-CoA Mutasa/deficiencia , Diálisis Renal

RESUMEN

Carnitine-acylcarnitine translocase deficiency, a rare beta-oxidation defect, is manifest in most cases by cardiomyopathy and death in early childhood. We report an affected patient, 3 years of age, who has had no serious complications. The residual enzyme activity in fibroblasts was higher than in previously reported patients, which may explain the benign clinical course.

Asunto(s)

Carnitina Aciltransferasas/deficiencia , Glucemia , Carnitina/sangre , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/genética , Fenotipo