RESUMEN
Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders.
Asunto(s)
Endofenotipos/sangre , Aminoácidos Excitadores/sangre , Predisposición Genética a la Enfermedad/genética , Trastornos Psicóticos/sangre , Trastornos Psicóticos/genética , Transmisión Sináptica/genética , Adulto , Análisis de Varianza , Cromatografía Liquida , Femenino , Ácido Glutámico/sangre , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Metabolómica , Pruebas Neuropsicológicas , Análisis de Componente Principal , Trastornos Psicóticos/fisiopatología , Tiempo de Reacción , Receptores de N-Metil-D-Aspartato/sangre , Transmisión Sináptica/fisiología , Adulto JovenRESUMEN
OBJECTIVE: This study evaluated treatment strategies for head and neck cancers in a predominantly African American population. METHODS: Data were collected utilizing medical records and the tumour registry at the Howard University Hospital. Kaplan-Meier method was used for survival analysis and Cox proportional hazards regression analysis predicted the hazard of death. RESULTS: Analysis revealed that the main treatment strategy was radiation combined with platinum for all stages except stage I. Cetuximab was employed in only 1% of cases. Kaplan-Meier analysis revealed stage II patients had poorer outcome than stage IV while Cox proportional hazard regression analysis (p = 0.4662) showed that stage I had a significantly lower hazard of death than stage IV (HR = 0.314; p = 0.0272). Contributory factors included tobacco and alcohol but body mass index (BMI) was inversely related to hazard of death. CONCLUSIONS: There was no difference in survival using any treatment modality for African Americans.
Asunto(s)
Negro o Afroamericano , Carcinoma de Células Escamosas/etnología , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/etnología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias Laríngeas/etnología , Neoplasias Faríngeas/etnología , Anciano , Carcinoma de Células Escamosas/mortalidad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Laríngeas/terapia , Masculino , Persona de Mediana Edad , Neoplasias Faríngeas/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: Guillain-Barré syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute inflammatory demyelinative polyneuropathy [AIDP]) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy [AMAN]) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City. METHODS: We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed. RESULTS: Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) (p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) (p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP (p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP (p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni. Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases. CONCLUSIONS: This study confirms that acute motor axonal neuropathy is an important Guillain-Barré syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally.
Asunto(s)
Síndrome de Guillain-Barré/epidemiología , Síndrome de Guillain-Barré/fisiopatología , Adolescente , Infecciones por Campylobacter/epidemiología , Niño , Preescolar , Diarrea/etiología , Femenino , Gangliósido G(M1)/análogos & derivados , Gangliósido G(M1)/inmunología , Síndrome de Guillain-Barré/microbiología , Humanos , Inmunoglobulina G/sangre , Lactante , Masculino , México/epidemiología , Neuronas Motoras/patología , Estaciones del AñoRESUMEN
Guillain-Barré syndrome (GBS) is recognized as a complication that occurs after Campylobacter infection. Certain Penner serotypes, such as HS:19, are linked particularly to GBS in some parts of the world, and there is good evidence for restricted genetic diversity in these isolates. However, GBS also occurs after Campylobacter infection due to other serotypes. Therefore, we asked whether Campylobacter jejuni non-HS:19 serotypes associated with GBS have a clonal structure and differ from strains isolated from patients with Campylobacter gastroenteritis. A worldwide selected population of C. jejuni non-HS:19 strains associated with GBS and gastroenteritis was analyzed by use of multilocus enzyme electrophoresis, automated ribotyping, pulsed-field gel electrophoresis, and flagellin gene typing. The results show that these isolates represent a heterogenic population and do not constitute a unique population across serotypes. No epidemiologic marker for GBS-associated strains was identified.
Asunto(s)
Infecciones por Campylobacter/complicaciones , Infecciones por Campylobacter/microbiología , Campylobacter jejuni/clasificación , Gastroenteritis/microbiología , Síndrome de Guillain-Barré/microbiología , Campylobacter jejuni/aislamiento & purificación , Canadá , China , Clonación Molecular , Dinamarca , Electroforesis en Gel de Campo Pulsado , Flagelina/genética , Humanos , Japón , México , Serotipificación , Sudáfrica , Emiratos Árabes Unidos , Reino Unido , Estados UnidosRESUMEN
Infection with Campylobacter jejuni serotype HS:19 is associated with the development of Guillain-Barré syndrome (GBS). To determine whether a particular HS:19 clone is associated with GBS, multilocus enzyme electrophoresis (MLEE) was used to analyze a worldwide collection of isolates. There were 34 electropherotypes (ETs) in 3 phylogenetic clusters among 83 C. jejuni isolates. Cluster I contained all HS:19 strains, and a single ET (ET4) accounted for most HS:19 strains. HS:19 strains did not occur in any of the other clusters. ET4 contained isolates from different geographic locations, indicating global spread of this clone. Furthermore, ET4 contained isolates from patients with uncomplicated enteritis and GBS, as well as isolates from animal sources. The results of this study show that HS:19 strains comprise a clonal, although not monomorphic, population, which is distinct from non-HS:19 strains within C. jejuni. A unique clone associated with GBS was not identified by use of MLEE.
Asunto(s)
Infecciones por Campylobacter/complicaciones , Campylobacter jejuni/genética , ADN Bacteriano/genética , Gastroenteritis/complicaciones , Síndrome de Guillain-Barré/microbiología , Infecciones por Campylobacter/microbiología , Campylobacter jejuni/clasificación , Campylobacter jejuni/enzimología , Campylobacter jejuni/aislamiento & purificación , Canadá , China , ADN Bacteriano/análisis , Dinamarca , Electroforesis/métodos , Gastroenteritis/microbiología , Amplificación de Genes , Humanos , Japón , México , Sudáfrica , Reino Unido , Estados UnidosRESUMEN
OBJECTIVES: The second Primary Angioplasty in Myocardial Infarction (PAMI-II) study evaluated the hypothesis that primary percutaneous transluminal coronary angioplasty (PTCA), with subsequent discharge from the hospital 3 days later, is safe and cost-effective in low risk patients. BACKGROUND: In low risk patients with myocardial infarction (MI), few data exist regarding the need for intensive care and noninvasive testing or the appropriate length of hospital stay. METHODS: Patients with acute MI underwent emergency catheterization with primary PTCA when appropriate. Low risk patients (age <70 years, left ventricular ejection fraction >45%, one- or two-vessel disease, successful PTCA, no persistent arrhythmias) were randomized to receive accelerated care (admission to a nonintensive care unit and day 3 hospital discharge without noninvasive testing [n = 237] or traditional care [n = 234]). RESULTS: Patients who received accelerated care had similar in-hospital outcomes but were discharged 3 days earlier (4.2+/-2.3 vs. 7.1+/-4.7 days, p = 0.0001) and had lower hospital costs ($9,658+/-5,287 vs. $11,604+/-6,125 p = 0.002) than the patients who received traditional care. At 6 months, accelerated and traditional care groups had a similar rate of mortality (0.8% vs. 0.4%, p = 1.00), unstable ischemia (10.1% vs. 12.0%, p = 0.52), reinfarction (0.8% vs. 0.4%, p = 1.00), stroke (0.4% vs. 2.6%, p = 0.07), congestive heart failure (4.6% vs. 4.3%, p = 0.85) or their combined occurrence (15.2% vs. 17.5%, p = 0.49). The study was designed to detect a 10% difference in event rates; at 6 months, only a 2.3% difference was measured between groups, indicating an actual power of 0.19. CONCLUSIONS: Early identification of low risk patients with MI allowed safe omission of the intensive care phase and noninvasive testing, and a day 3 hospital discharge strategy, resulting in substantial cost savings.
Asunto(s)
Angioplastia Coronaria con Balón , Hospitales/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Infarto del Miocardio/terapia , Anciano , Angioplastia Coronaria con Balón/economía , Angioplastia Coronaria con Balón/normas , Argentina , Brasil , Costo de Enfermedad , Análisis Costo-Beneficio , Femenino , Costos de Hospital , Hospitales/normas , Humanos , Japón , Tiempo de Internación/economía , Masculino , Persona de Mediana Edad , Infarto del Miocardio/economía , Selección de Paciente , Medición de Riesgo , Seguridad , España , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: To determine whether resistance to activated protein C caused by the factor V Leiden mutation (Arg506 to Gln) is associated with thrombosis occurring during childhood. STUDY DESIGN: Children with thrombosis were screened for activated protein C resistance. Children found resistant to activated protein C had DNA analysis for the factor V Leiden mutation. Family members of the children with activated protein C resistance were similarly studied. RESULTS: Three of fourteen children examined had abnormal normalized activated protein C sensitivity ratios. One child had protein S deficiency. The children had hyperlipidemia. Molecular confirmation of the factor V Leiden mutation was obtained for all three children. Family members of each of the three children were affected. CONCLUSIONS: Children have thromboses in association with the factor V Leiden mutation, as do adults. This mutation may be identified as an isolated risk factor or in association with other risk factors for thrombosis.
Asunto(s)
Factor V/genética , Trombosis/genética , Adolescente , Adulto , Pruebas de Coagulación Sanguínea , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Mutación , Linaje , Proteína C/metabolismo , Factores de Riesgo , Trombosis/sangre , Trombosis/epidemiologíaAsunto(s)
Ipeca/historia , Brasil , Historia del Siglo XVII , Historia del Siglo XVIII , Humanos , Mercurio/historia , Perú , Farmacología/historia , Portugal , Reino UnidoAsunto(s)
Anomalías Inducidas por Medicamentos/etiología , Enfermedades de la Boca/tratamiento farmacológico , Estereoisomerismo , Lepra Lepromatosa/tratamiento farmacológico , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Talidomida/efectos adversos , Talidomida/química , Talidomida/uso terapéutico , Trasplante de Médula Ósea , Ética Médica , Úlcera/tratamiento farmacológicoAsunto(s)
Enfermedades Desmielinizantes/etiología , Infecciones por VIH/complicaciones , Polineuropatías/etiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Preescolar , Enfermedades Desmielinizantes/sangre , Enfermedades Desmielinizantes/inmunología , Anticuerpos Anti-VIH/análisis , Anticuerpos Anti-VIH/inmunología , Humanos , Masculino , Polineuropatías/sangre , Polineuropatías/inmunologíaRESUMEN
Vitamin K-dependent proteins were measured sequentially by immunoassay in eight patients with acute lymphoblastic leukemia receiving L-asparaginase (1000 U/kg/day) for 10 days as induction therapy, in combination with vincristine or vindesine, daunorubicin, cyclophosphamide, and prednisone. The level of each protein was significantly decreased during L-asparaginase therapy, but both the time course of change and the severity of decrease differed among the proteins. The decrease in protein C, factor IX, and factor X was observed earlier than the decrease in protein S and factor II. In the first days of L-asparaginase therapy the protein C level was significantly lower than those of the other vitamin K-dependent proteins. The transient imbalance in the levels of plasma vitamin K-dependent proteins observed in the first days of treatment may contribute to the risk of thrombosis associated with L-asparaginase therapy.
Asunto(s)
Asparaginasa/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Leucemia Linfoide/tratamiento farmacológico , Adolescente , Asparaginasa/farmacología , Factores de Coagulación Sanguínea/metabolismo , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Glicoproteínas/metabolismo , Humanos , Leucemia Linfoide/sangre , Masculino , Proteína C , Proteína S , Vitamina K/fisiologíaRESUMEN
Concentrations of chlorinated hydrocarbons in airborne dust carried by the trade winds from the European-African land areas to Barbados range from less than 1 to 164 parts per billion. The lower limit of the average content of 1 cubic meter of air is 7.8 x 10-(14) gram. The contributions of river-borne and atmospherically transported pesticides to parts of the marine environment are calculated approximately and comtpared. The amnounts of pesticides contributed to the tropical Atlantic by the trade winds appear to be comparable to those carried to the sea by major river systems.