RESUMEN
Autism spectrum disorders (ASDs) comprise a constellation of highly heritable neuropsychiatric disorders. Genome-wide studies of autistic individuals have implicated numerous minor risk alleles but few common variants, suggesting a complex genetic model with many contributing loci. To assess commonality of biological function among rare risk alleles, we compared functional knowledge of genes overlapping inherited structural variants in idiopathic ASD subjects relative to healthy controls. In this study we show that biological processes associated with synapse function and neurotransmission are significantly enriched, with replication, in ASD subjects versus controls. Analysis of phenotypes observed for mouse models of copy-variant genes established significant and replicated enrichment of observable phenotypes consistent with ASD behaviors. Most functional terms retained significance after excluding previously reported ASD loci. These results implicate several new variants that involve synaptic function and glutamatergic signaling processes as important contributors of ASD pathophysiology and suggest a sizable pool of additional potential ASD risk loci.
Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/genética , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad/genética , Proteínas del Tejido Nervioso/genética , Sinapsis/genética , Transmisión Sináptica/genética , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudio de Asociación del Genoma Completo/métodos , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Técnicas de Genotipaje/métodos , Técnicas de Genotipaje/psicología , Humanos , Masculino , Ratones , FenotipoRESUMEN
Interleukin 12 (IL-12) is a heterodimeric cytokine that has been demonstrated to have a major role in stimulating a cell-mediated antitumor response. IL-10, a product of T helper 2 lymphocytes, is its most potent inhibitor. The aim of this study was to investigate whether patients with colorectal cancer had an imbalance in production of IL-12 and IL-10 preoperatively, and whether this was associated with advanced disease at surgery. Blood was obtained before surgery from 60 patients with colorectal cancer and from 30 controls. Peripheral blood mononuclear cells were incubated with Staphylococcus aureus Cowan's strain 1 in vitro for 24 h to assess IL-12 expression after stimulation, and serum was used for IL-10 measurement. IL-12 and IL-10 levels were assessed by ELISA. A single pathologist staged the tumors according to the tumor-node-metastasis (TNM) and Dukes' classifications. Patients with colorectal cancer had significantly lower levels of IL-12 (P <0.001) and higher levels of IL-10(P = 0.004) compared to controls. In addition, lower levels of IL-12 were detected in those patients who were node positive (P<0.05), had Dukes' C lesions (P < or = 0.001), and T3 or T4 lesions (P<0.033) when compared to controls. Patients with Dukes' B and C lesions (P<0.01) and T3 and T4 lesions (P<0.05) also had higher levels of IL-10 compared to controls. This study is the first to demonstrate that patients with colorectal cancer have decreased IL-12 production and increased serum IL-10. This suggests an impaired T helper 1 cell-mediated antitumor response and provides some justification for exogenous IL-12 therapy or anti-IL-10 therapy in these patients.
Asunto(s)
Neoplasias Colorrectales/sangre , Interleucina-10/biosíntesis , Interleucina-12/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/metabolismo , Neoplasias Colorrectales/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-12/sangre , Células Asesinas Naturales/citología , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Monocitos/citología , Monocitos/metabolismo , Estadificación de NeoplasiasRESUMEN
INTRODUCTION: Despite development of many chemotherapeutic regimens, colorectal cancer continues to have a high mortality. One of the major new potential therapies is interleukin-12, a heterodimeric cytokine produced by antigen presenting cells. In vitro and in vivo studies have demonstrated the role of interleukin-12 in stimulating a cell-mediated anti-tumor response against a number of colon adenocarcinoma tumor models. However, it is unknown whether patients with colorectal cancer have impaired interleukin-12 production. A study was performed to investigate production of interleukin-12 preoperatively and the relationship between these levels and disease stage at surgery. METHODS: Preoperative peripheral blood mononuclear cells from colorectal cancer patients and age-matched controls were stimulated by Staphylococcus aureus Cowan's Strain 1 (0.0075 percent wt/vol) in vitro for 24 hours. Expression of interleukin-12 was then assessed by enzyme-linked immunosorbent assay. A single pathologist assessed the tumors for stage according to TNM and Dukes classifications. RESULTS: Twenty-eight patients with colorectal cancer and 14 controls were recruited for the study. Interleukin-12 production was significantly impaired in patients with colorectal cancer compared with controls (P = 0.014), especially those with advanced disease: Dukes C, P = 0.001 and T4, P < 0.05. CONCLUSION: Interleukin-12 production is impaired in patients with colorectal cancer, especially those with advanced disease, suggesting a defective Thl-mediated anti-tumor response. These patients may well benefit from exogenous interleukin-12 treatment.
Asunto(s)
Adenocarcinoma/inmunología , Neoplasias Colorrectales/inmunología , Interleucina-12/biosíntesis , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Humanos , Interleucina-12/sangre , Persona de Mediana Edad , Estadificación de Neoplasias , Estadísticas no ParamétricasRESUMEN
Current practice in this unit for a suspected breast abscess is preliminary ultrasonographic scan, aspiration of any pus, antibiotic therapy and repeat aspiration in the outpatient clinic if necessary. Inflammatory masses are treated with antibiotics alone. A retrospective review of this strategy has been made. Over a 2-year interval 53 patients were admitted to hospital with a suspected breast abscess. Twenty-two abscesses were aspirated, of which 19 resolved and three required subsequent incision and drainage. Eight patients underwent primary incision and drainage, one of whom required a second drainage procedure. In five patients the abscess discharged spontaneously before intervention. The remaining 18 patients were found on ultrasonography to have inflammation without evidence of focal pus which settled with antibiotic therapy in all but two patients. One of these was found to have an inflammatory cancer and the other developed an abscess, which was drained. Aspiration combined with ultrasonographic imaging is an effective alternative to incision and drainage.
Asunto(s)
Absceso/tratamiento farmacológico , Antibacterianos/uso terapéutico , Enfermedades de la Mama/tratamiento farmacológico , Absceso/diagnóstico por imagen , Absceso/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Mama/diagnóstico por imagen , Enfermedades de la Mama/cirugía , Drenaje/métodos , Femenino , Hospitalización , Humanos , Mastitis/diagnóstico por imagen , Mastitis/tratamiento farmacológico , Mastitis/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Ultrasonografía Intervencional , Ultrasonografía MamariaRESUMEN
Neurosyphilis today is a rare problem. We describe a man who presented with organic brain syndrome, psychosis and incontinence, and diagnosis was neurosyphilis with resultant bladder dysfunction. Urodynamic studies defined the voiding dysfunction as detrusor areflexia with a positive bethanechol test. This case reminds us of the necessity of obtaining a test for venereal disease to rule out neurosyphilis in patients with idiopathic voiding dysfunction.
Asunto(s)
Neurosífilis/complicaciones , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria/fisiopatología , Incontinencia Urinaria/etiología , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Neurosífilis/fisiopatología , Vejiga Urinaria Neurogénica/fisiopatología , UrodinámicaRESUMEN
A 62-year-old patient developed severe adhesive spinal arachnoiditis and hydrocephalus with papilledema following iophendylate injection myelography. Papilledema and hydrocephalus resolved spontaneously. The possible mechanism for hydrocephalus is discussed and the literature reviewed.
Asunto(s)
Hidrocefalia/inducido químicamente , Yodobencenos/efectos adversos , Yofendilato/efectos adversos , Mielografía/efectos adversos , Adulto , Aracnoiditis/inducido químicamente , Femenino , Fondo de Ojo , Humanos , Hidrocefalia/diagnóstico por imagen , Inyecciones Espinales , Yofendilato/administración & dosificación , Masculino , Persona de Mediana Edad , Papiledema/inducido químicamente , Remisión Espontánea , Adherencias Tisulares/inducido químicamente , Tomografía Computarizada por Rayos XRESUMEN
Most patients with motor aphasia resulting from lesions of the left frontal opercular region have weakness of the right face and arm. We report a 43-year-old man who suffered mutism and agraphia unaccompanied by right-sided weakness after embolic infarction of Broca's area.