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1.
Mol Psychiatry ; 23(11): 2156-2166, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-28993710

RESUMO

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible 'knockdown' mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3-4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin-5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder.


Assuntos
Claudina-5/genética , Claudina-5/fisiologia , Esquizofrenia/metabolismo , Síndrome da Deleção 22q11/genética , Síndrome da Deleção 22q11/psicologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Esquizofrenia/fisiopatologia , Junções Íntimas
2.
J Telemed Telecare ; 5(1): 18-22, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10505365

RESUMO

Emergency physicians and nurses were trained in telemedicine techniques in two emergency departments, one rural (low volume) and one suburban (high volume). Fifteen patient complaints were selected as appropriate for the study. Of 122 patients who met the inclusion criteria, 104 (85%) consented to participate. They were randomized to control and experimental groups. The suburban emergency physician diagnosed and treated the control patients. Experimental patients presenting to the high-volume emergency department were evaluated and treated by the telemedicine nurse in person and the rural emergency physician via the telemedicine link. Immediately before discharge all telemedicine patients were re-evaluated by the suburban emergency physician. Data collected on each patient included: diagnosis; treatment; 72 h return visits; need for additional care; and satisfaction of patient, physicians and nurses. There were no significant differences (P > 0.05) for occurrence of 72 h return visits, need for additional care or overall patient satisfaction. The average patient throughput time (from admission to discharge) was 106 min for the telemedicine group and 117 min for the control group. Telemedicine was a satisfactory technique for the chosen group of patients in the emergency department and was acceptable to the participants.


Assuntos
Serviço Hospitalar de Emergência , Telemedicina/métodos , Feminino , Hospitais Rurais , Hospitais Urbanos , Humanos , Masculino , Satisfação do Paciente , Telemedicina/instrumentação , Resultado do Tratamento
3.
J Telemed Telecare ; 4 Suppl 1: 18-20, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9640721

RESUMO

A prospective study of emergency department telemedicine was carried out at two hospitals in northern New Jersey. One hundred and twenty-two patients met the inclusion criteria. One hundred and four (85%) consented to participate, with 54 being randomized to the telemedicine group and 50 to the control group. Four patients did not complete the protocol. No significant differences were seen between the groups for: occurrence of 72 h emergency department return visits (0% vs 0%); need for additional care (2.3% vs 2.4%); positive patient-physician interaction (98% vs 100%); positive patient-nurse interaction (98% vs 98%); positive overall patient satisfaction (98% vs 95%). The average patient throughput time (time from admission to discharge) for the telemedicine group was 106 min; the average for the control group was 117 min. Telemedicine was found to be a satisfactory technique for pre-selected emergency department patients and was viewed by the physicians as an acceptable method of complementary care.


Assuntos
Serviços Médicos de Emergência/métodos , Telemedicina/métodos , Feminino , Humanos , Masculino , New Jersey , Relações Enfermeiro-Paciente , Satisfação do Paciente , Relações Médico-Paciente , Estudos Prospectivos , Resultado do Tratamento
4.
Am J Emerg Med ; 7(2): 150-4, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2920076

RESUMO

Ambulatory patients frequently ingest liquids or smoke just before temperature measurement. The change in body temperature measurements over time following ingestion of ice water, hot water, and smoking were investigated. Twenty-two healthy, afebrile study subjects sequentially ingested temperature-controlled water and smoked a cigarette. Simultaneous oral and auditory canal temperatures were measured over 15 minutes following ingestion. Auditory canal temperatures were obtained with an infrared detection probe; we designated this process a tympanic membrane-derived (TMD) temperature. To determine the correlation between rectal and TMD temperatures, 100 patients had simultaneous measurements at both sites. Mean initial temperatures were rectal, 37.1 +/- 0.5 degrees C (mean +/- S.D.); oral, 36.4 +/- 0.4 degrees C; and TMD, 37.4 +/- 0.4 degrees C. Maximal mean oral temperature change was greatest at 1.5 minutes after hot, +0.9 +/- 0.1 degrees C, and cold, -1.2 +/- 0.2 degrees C, water. This change was statistically significant for seven minutes at the 95% confidence level (analysis of variance test with Dunnett's multiple range test for significance). There was no significant change in the TMD temperature with any ingestion. The Pearson correlation coefficient for 107 pairs of rectal and TMD temperatures, r = 0.90 (P less than .001), was excellent. It was concluded that hot and cold liquids significantly influence oral temperature measurement for seven to nine minutes following ingestion. TMD temperature is unaffected by liquid ingestion and may allow accurate measurement of body temperature. Further studies are needed to determine the accuracy of TMD temperature over a wide range of body temperature in diverse clinical settings.


Assuntos
Temperatura Corporal , Ingestão de Líquidos , Fumar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Lactente , Recém-Nascido , Masculino , Métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
5.
Am J Vet Res ; 39(1): 185-6, 1978 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-629444

RESUMO

Attempts were made to create salivary cysts by ligation of the mandibular salivary duct at the angle of the mandible and near the frenulum of the tongue, by rupture of the mandibular duct at the angle of the mandible and near the frenulum of the tongue, and by direct trauma to the mandibular salivary gland. Cysts were not formed as a result of the experimental procedures, but observations are made on the results obtained.


Assuntos
Cistos/veterinária , Doenças do Cão/etiologia , Glândula Submandibular , Animais , Cães , Ligadura , Ruptura , Doenças das Glândulas Salivares/etiologia , Doenças das Glândulas Salivares/veterinária , Glândula Submandibular/lesões
6.
Can Vet J ; 15(10): 264-70, 1974 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-4421236
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