RESUMEN
Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10-9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5.8 × 10-10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (Pbest=1.9 × 10-9), TRANK1 (Pbest=2.1 × 10-9) and ODZ4 (Pbest=3.3 × 10-9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', Pbest~10-29, R2~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' Pbest~10-13, R2~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.
Asunto(s)
Trastorno Bipolar/genética , Adulto , Proteínas de Ciclo Celular/genética , Citocinas/genética , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Japón/epidemiología , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Herencia Multifactorial/genética , Factores de Transcripción NFI/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
The syndrome of episodic angioedema associated with eosinophilia (EAE), originally identified by Gleich et al., is characterized by recurrent attacks of angioedema, urticaria, fever, increased body weight, and eosinophilia of unknown origin. Five young (aged 23-32 years) female patients were referred to our hospital because of eosinophilia (4,900-10,400/microliter). The chief complaints in all patients were angioedema and pain in the lower extremities without urticaria. Fever and increased body weight were not evident in most of the patients. These clinical features resolved spontaneously within 3 months, and no recurrence was observed. These characteristics were consistent with nonepisodic-type EAE (NEAE), which was proposed by Chikama et al. and is observed frequently in Japan. The clinical characteristics of NEAE were studied in the present 5 cases and the 25 cases reported previously in Japan. This revealed some additional characteristics: 1) a tendency for occurrence in autumn, 2) arthritis and absence of urticaria in some patients, and 3) increased serum LDH levels in some cases. It is suggested that NEAE should be treated with antiallergic drugs or simply followed without treatment, because spontaneous remission is observed frequently.
Asunto(s)
Angioedema , Eosinofilia , Adulto , Angioedema/diagnóstico , Angioedema/fisiopatología , Antialérgicos/uso terapéutico , Eosinofilia/diagnóstico , Eosinofilia/fisiopatología , Femenino , Humanos , Recurrencia , Remisión Espontánea , SíndromeRESUMEN
We encountered a patient who showed ethylenediaminetetraacetic acid (EDTA)-induced pseudoleukocytosis without pseudothrombocytopenia. The patient had IgG-kappa type monoclonal (M) gammopathy. The total protein concentration was 77 g/l, and the gamma-globulin fraction containing M-protein was 23.2%. The white blood cell count of the patient's blood anti-coagulated with EDTA was 52300/microl as determined using an automated counter, but was within normal limits when counted manually by light microscopy using a hemacytometer. Large amounts of a transparent substance were observed on blood smears, and white precipitates were formed by an interaction of the patient's serum with EDTA. Immunofixation electrophoresis showed these precipitates to be of the IgG(2)-kappa type M-protein. Western blotting analysis showed that the IgG molecules had a molecular mass of 155 kDa and were composed of two gamma-chains of approximately 53 kDa and two kappa-chains of 27 kDa. Pseudoleukocytosis was also observed when the patient's blood was anti-coagulated with O, O'-bis(2-amino-ethyl)-ethyleneglycol-N,N,N',N'-tetraacetic acid (EGTA) or sodium citrate, but not with lithium heparin. The present case seems to be the first report of pseudoleukocytosis induced by the interaction of EDTA and IgG(2)-kappa type M-protein.
Asunto(s)
Anticuerpos Monoclonales/química , Ácido Edético/efectos adversos , Ácido Edético/química , Leucocitosis/inducido químicamente , Paraproteinemias/sangre , Trombocitopenia/inducido químicamente , Anticoagulantes/efectos adversos , Western Blotting , Médula Ósea/patología , Electroforesis en Acetato de Celulosa , Humanos , Inmunoelectroforesis , Recuento de Leucocitos , Leucocitosis/patología , Masculino , Persona de Mediana Edad , Paraproteinemias/patología , Temperatura , Trombocitopenia/patologíaAsunto(s)
Trastornos de la Coagulación Sanguínea , Plaquetas/patología , Agregación Plaquetaria , Trombocitosis , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/etiología , Calpaína/deficiencia , Diagnóstico Diferencial , Genes Dominantes , Humanos , Pronóstico , Síndrome , Trombocitosis/diagnóstico , Trombocitosis/etiologíaRESUMEN
We surveyed the literatures and discussed the legal issues whether we should administer blood for lifesaving to a patient who refuses it. The valid refusal of the transfusion requires the distinct intention of a competent patient. Minors below fifteen years of age are incompetent and their parents make a substituted judgement. Anyone must not give priority to the parents' belief and blood ought to be transfused if necessary for the children's benefits. We could evade liability for withholding blood only when we manage an operation arranged to succeed without blood transfusion, undergoing the sufficient treatments to avoid the risks, as well as on the basis of the valid refusal of a patient. The release deed and the intervention of hospital directors, ethics committees and courts are invalid for the immunity from liability. Anesthesiologists have to take the responsibility on themselves of administering blood or not. A statute law should be established to define what is a patient's valid intention and who is responsible.
Asunto(s)
Transfusión Sanguínea/legislación & jurisprudencia , Defensa del Paciente/legislación & jurisprudencia , Negativa del Paciente al Tratamiento/legislación & jurisprudencia , Anestesiología , Humanos , Japón , Responsabilidad Legal , Competencia MentalRESUMEN
Peripheral blood anti-coagulated with sodium heparin (25 U/ml) form 60 healthy volunteers invariably had a reduced platelet count, when whole blood was mixed in the presence of air. Smear findings similar to those observed in EDTA-induced pseudothrombocytopenia and the counteracting effect of prostaglandin E1 (1 microM) on thrombocytopenia suggest that this thrombocytopenia is due to platelet activation and aggregate formation. Mixing may activate platelets, because the extent of thrombocytopenia had a positive correlation with the air volume and mixing intensity. Aspirin (1.8 mM) and 5-HT2 blocker (sarpogrelate 100 microM) also inhibited this phenomenon. These findings suggest that the mechanism of platelet activation might be partly related to arachidonate metabolism and serotonin release. Oxygen appears to have no direct effects. It is suggested that red blood cells and/or white blood cells participate in platelet activation, because platelet aggregation of platelet-rich plasma was less than that of whole blood. 5-lipoxygenase inhibitor had little effect. To measure platelet counts, it appears essential to eliminate the copresence of air in blood samples anti-coagulated with heparin.
Asunto(s)
Plaquetas/efectos de los fármacos , Heparina/farmacología , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas/métodos , Aire , Aspirina/farmacología , Humanos , Activación Plaquetaria/fisiología , Antagonistas de la Serotonina/farmacología , Succinatos/farmacologíaRESUMEN
Peripheral blood count was performed by a Coulter Model S Plus STKR on six pseudothrombocytopenia patients (age: 16-70, 2 men and 4 women) using three different anticoagulants. Treatment with ethylene diamine tetraacetate (EDTA, 1 mg/ml) or sodium heparin (25 U/ml) aggregated platelets, but sodium citrate (3.8%, 1:9) had no effect. Smear examination revealed much platelet clumping but the satellite phenomenon was not present. No specific pattern was elucidated concerning cell size distribution curves between treatment by EDTA and heparin. Theophylline (10 mg/ml) and prostaglandin I2 (1 microM) inhibited EDTA-induced platelet aggregation but aspirin (1.8 mM) did not. On the other hand, these three substances inhibited heparin-induced platelet aggregation. These findings, taken together, suggested that EDTA and heparin initiated platelet activation and EDTA-induced platelet aggregation might be a process unrelated to thromboxane A2 production. Heparin may not be a suitable anticoagulant since it aggregates platelets of some healthy individuals.
Asunto(s)
Ácido Edético/efectos adversos , Agregación Plaquetaria/efectos de los fármacos , Trombocitopenia/inducido químicamente , Adolescente , Adulto , Anciano , Anticoagulantes/farmacología , Citratos/farmacología , Ácido Cítrico , Dinoprostona/farmacología , Ácido Edético/farmacología , Femenino , Heparina/farmacología , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/farmacología , Recuento de Plaquetas/efectos de los fármacos , Teofilina/farmacología , Trombocitopenia/sangre , Trombocitopenia/diagnósticoRESUMEN
The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/sangre , Leucocitosis/sangre , Neoplasias/sangre , Adulto , Anciano , Fosfatasa Alcalina/sangre , Femenino , Humanos , Hipercalcemia/sangre , Hipercalcemia/complicaciones , Recuento de Leucocitos , Leucocitosis/etiología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neutrófilos/enzimologíaRESUMEN
A 77-year-old male who had suffered from an upper respiratory infection and had been given Norfloxacin (NFLX) on May 2, 1990, developed generalized erythema which did not subside with prednisolone. He was hospitalized on May 8, and Stevens-Johnson syndrome was diagnosed. The WBC was 115,400/microliter (Ly 61.0%, Aty Ly 39.5%). Sternal tap revealed hypercellular marrow with increased lymphocytes (48.5%; Aty Ly 24.5%) and eosinophils (7.0%). Clinical chemistry revealed slightly abnormal liver and renal function with LDH (1,745 IU/l) and IgE (803 IU/ml) elevation. No pathognomonic result was obtained with several viral antibodies. CD4+, CD8+ lymphocytes and the 4/8 ratio were 39%, 43% and 0.9, respectively. Clinical and laboratory abnormalities were normalized within 3 weeks after the discontinuance of all drugs. Positive lymphocyte stimulation test results were obtained by NFLX. While drug allergy is known to be a cause of IM-like syndrome, there are few reports regarding the subset characterization of the increased T lymphocytes. In this case, T lymphocytosis was remarkable, but the 4/8 ratio declined only slightly, indicating that CD4+ as well as C8+ cells were activated and increased, unlike IM. The record of this case helps to clarify the mechanisms of the lymphocyte activation shared and not shared by EBV-induced IM and IM-like syndrome.