RESUMO
OBJECTIVES AND DESIGN: To establish whether in diabetic patients with peripheral artery obstructive disease (PAOD) vasa vasorum (vv) neoangiogenesis is altered with increased arterial damage. MATERIALS: Thirty-three patients with PAOD and critical lower limb ischaemia, 22 with type II diabetes. METHODS: Immunohistochemistry for endothelial cell markers (CD34 and von Willebrand Factor); real-time reverse transcription polymerase chain reaction (RT-PCR) to quantify arterial wall expression of vascular endothelial growth factor (VEGF); enzyme-linked immunosorbent assay (ELISA) to assess blood VEGF; flow cytometry to detect circulating endothelial cells (CECs). RESULTS: Patients with PAOD and diabetes have a higher frequency (60% vs. 45%) of advanced atherosclerotic lesions and a significant reduction (p = 0.0003) in CD34(+) capillaries in the arterial media. Adventitial neoangiogenesis was increased equally (CD34(+) and vWF(+)) in all patients. Likewise, all patients have increased CEC and VEGF concentration in the blood as well as in-situ VEGF transcript expression. CONCLUSIONS: Patients with PAOD have remarkable arterial damage despite increased in-situ and circulating expression of the pro-angiogenic VEGF; a dysfunctional vv angiogenesis was seen in diabetics which also showed a higher frequency of parietal damage; it is suggested that in diabetic arterial wall, injury is worsened by vv inability to finalise an effective VEGF-driven arterial wall neoangiogenesis.
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Isquemia/fisiopatologia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/fisiopatologia , Neovascularização Fisiológica , Vasa Vasorum/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Arteriopatias Oclusivas/metabolismo , Arteriopatias Oclusivas/patologia , Estudos de Casos e Controles , Estado Terminal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Células Endoteliais/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Isquemia/metabolismo , Isquemia/patologia , Itália , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vasa Vasorum/química , Vasa Vasorum/patologia , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/genética , Fator de von Willebrand/análiseRESUMO
The authors randomly assigned 79 inpatients with nonchronic schizophrenia or affective disorder to either an intensive experimental day program called "transitional treatment" or a control treatment--weekly clinically believed to require intensive posthospital treatment to make the transition to the community. Although initially there was a significantly higher dropout rate from the control condition, at the point of discharge from the two programs as well as at 6- and 12-month follow-up there was no difference in outcome. Direct costs for the transitional treatment, however, were much higher.