RESUMO
Although allogeneic bone marrow transplantation has been shown to prevent autoimmune diabetes in heavily irradiated nonobese diabetic (NOD) mice, a similar procedure is not suitable for the treatment of patients with type 1 diabetes because of associated severe side effects. Therefore, we evaluated whether mouse newborn blood (NBB), equivalent to human umbilical cord blood, could be used for diabetes prevention without recipient preconditioning. To test this hypothesis, unconditioned, prediabetic female NOD mice were given a single injection of whole NBB derived from the allogeneic diabetes-resistant mouse strain C57BL/6. Transfusion of allogeneic NBB but not adult blood prevented diabetes incidence in a majority of treated mice for a prolonged period of time. This was accompanied by the release of insulin in response to a challenge with glucose. Invasive cellular infiltration of islets was also substantially reduced in these mice. Although NBB transfusion induced a low level of hematopoietic microchimerism, it did not strictly correlate with amelioration of diabetes. Induction of genes implicated in diabetes, such as Il18, Tnfa, and Inos but not Il4, Il17 or Ifng, was repressed in splenocytes derived from protected mice. Notably, expression of the transcription factor Tbet/Tbx21 but not Gata3 or Rorgt was upregulated in protected mice. These data indicate that allogeneic NBB transfusion can prevent diabetes in NOD mice associated with modulation of selected cytokine genes implicated in diabetes manifestation. The data presented in this study provide the proof of principle for the utility of allogeneic umbilical cord blood transfusion to treat patients with autoimmune diabetes.
Assuntos
Citocinas/biossíntese , Citocinas/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Sangue Fetal/transplante , Animais , Animais Recém-Nascidos , Antígenos Ly/biossíntese , Antígenos Ly/genética , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Autoimunes/prevenção & controle , Citocinas/antagonistas & inibidores , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Feminino , Sangue Fetal/citologia , Sangue Fetal/imunologia , Predisposição Genética para Doença , Transplante de Células-Tronco Hematopoéticas/métodos , Imunidade Inata/genética , Imunidade Inata/imunologia , Imunofenotipagem , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Estado Pré-Diabético/genética , Estado Pré-Diabético/imunologia , Estado Pré-Diabético/patologiaAssuntos
Acalasia Esofágica/diagnóstico , Acalasia Esofágica/terapia , Pneumonia Aspirativa/prevenção & controle , Idoso de 80 Anos ou mais , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Acalasia Esofágica/diagnóstico por imagem , Esofagoscopia/métodos , Feminino , Hidratação/métodos , Seguimentos , Humanos , Cuidados Paliativos/métodos , Pneumonia Aspirativa/etiologia , Medição de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodosRESUMO
INTRODUCTION: Idiopathic acute eosinophilic pneumonia (AEP) is characterized by hypoxemia, pulmonary infiltrates and pulmonary eosinophilia. Data is limited and the purpose of this study is to better understand this disorder. METHODS: A search of the computerized patient records from January 1, 1997 to October 15, 2010 for patients with suspicion of "eosinophilic pneumonia" was conducted. Included patients were 18 years or older with an acute febrile illness, hypoxemia, diffuse pulmonary infiltrates on imaging, and pulmonary eosinophilia. Patients were excluded with other known causes of pulmonary eosinophilia. RESULTS: Of 195 patients with pulmonary eosinophilia, 8 patients had "definite" or "probable" and 4 patients had "possible" idiopathic AEP. Three patients were categorized as "probable" idiopathic AEP due to exceeding expected maximal 30-day symptom duration and/or a maximal recorded temperature less than 38 °C. Four patients were defined as "possible" idiopathic AEP given histories of polymyalgia rheumatica, eczema or allergic rhinitis. Of the 8 included patients, 63% were male with a median age of 53. Median duration of symptoms was 21 days. Median nadir oxygen saturation was 83%. Median eosinophil count on bronchoalveolar lavage was 36%. Two patients required intubation. Two patients were current smokers, one of whom had reported a change in smoking habits. All patients were treated with steroids (median of two months). CONCLUSIONS: As diagnostic methods and pharmacologic knowledge improve, the number of patients meeting criteria for idiopathic AEP remains small. Much remains to be learned about this truly rare condition, and current criteria may exclude milder presentations of the disease.
RESUMO
A woman with a history of hip replacement presented 3 days prior to revision of the hip with abdominal pain, diarrhoea and haematochezia. These symptoms began 6 h after she began taking bisacodyl in preparation for her upcoming surgery. She was on low-dose estradiol for hormone replacement therapy (HRT). Subsequent colonoscopy and biopsies were consistent with acute colonic ischaemia (CI). She was treated with intravenous fluids and antibiotics and discharged and told to stop HRT and bisacodyl. Follow-up colonoscopy 1 month after discharge was normal. This case adds to the three other previously reported cases of bisacodyl-associated CI.