RESUMEN
OBJECTIVE: There is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors. DESIGN: A case-control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls. METHODS: We assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT. RESULTS: The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08-8.38%], p<0.0001) or 0.044 mm [0.021-0.066 mm] (p=0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5-29.4%] or 0.250 mm [0.198-0.303 mm] higher in HIV patients (p<0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART). CONCLUSIONS: HIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4-14% greater and the "vascular age" 4-5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Aterosclerosis/etiología , Enfermedades de las Arterias Carótidas/etiología , Infecciones por VIH/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Antirretrovirales/efectos adversos , Aterosclerosis/patología , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/patología , Estudios de Casos y Controles , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/efectos adversos , Factores de Riesgo , Túnica Íntima/patologíaRESUMEN
OBJECTIVE: There is growing evidence that, in high-grade internal carotid artery (ICA) stenosis, continuous fibrous cap thinning is not mandatory for plaque rupture and symptom development. The possibility that smooth muscle cell (SMC) apoptosis is involved in loss of fibrous cap volume has only been examined in a limited number of patients with high grade carotid artery stenosis. METHODS: Endarterectomy specimens from n = 38 consecutive patients undergoing surgery for high-grade ICA stenosis (> or = 70%) were transversely sectioned at 2 mm intervals. Plaque instability was defined clinically, by a history of recent ischemic symptoms (< 60 days before surgery; n = 19) attributable to the stenosis, or histopathologically by the presence of plaque rupture (n = 14). Detailed morphometric analyses of the fibrous cap was based on routine stains; for DNA in situ end labeling the TUNEL technique was used. SMCs were identified by immunostaining for SMC actin. RESULTS: We found no significant difference between symptomatic/asymptomatic or ruptured/unruptured plaque with respect to various morphometric measures of the fibrous cap (i.e. mean area, number of plaque sections with fibrous cap, necrotic core-to-lumen distance at its thinnest or thickest part). The mean (+/- SD) apoptotic SMCs per thousand within the fibrous cap was significantly higher in symptomatic vs. asymptomatic (64.53 +/- 77.3 vs. 6.71 +/- 11.9; P<0.001) but not in ruptured plaques (43.3 +/- 64.4 vs. 30.1 +/- 60.9; P=0.117). CONCLUSIONS: These data suggest that continuous thinning of the fibrous cap is not an essential prerequisite for plaque rupture in ICA stenosis. Symptomatic, but not ruptured plaque, were associated with the highest number of apoptotic SMC. Thus, it seems unlikely that SMC apoptosis promotes plaque rupture by fibrous cap thinning.
Asunto(s)
Estenosis Carotídea/patología , Músculo Liso Vascular/patología , Anciano , Apoptosis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
In acute carotid artery occlusion, hemodynamic compromise in addition to artery-artery thromboembolism is the mechanism of ischemia that may lead to a progressive clinical course with enlarging infarcts. The natural course of carotid artery occlusion with a progressive stroke is unfavorable with only about 10% of patients making a good recovery. We report on two patients in whom emergency recanalization of acute carotid artery occlusion with self-expanding stents restored cerebral blood flow and held up progressive stroke.
Asunto(s)
Trombosis de las Arterias Carótidas/terapia , Accidente Cerebrovascular/prevención & control , Trombosis de las Arterias Carótidas/fisiopatología , Arteria Carótida Interna , Circulación Cerebrovascular , Urgencias Médicas , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The objective of our study was to assess the gene expression of the antiproliferative systems neuronal nitric oxide synthase (nNOS) and adrenomedullin (AM) in human neuroblastoma. A novel real-time PCR method was evaluated using neuropeptide Y (NPY) for validation. Glyceraldehyd-3-phospate dehydrogenase (GAPDH) and NPY gene expression in neuroblastomas of 50 patients were measured in parallel by competitive quantitative and TaqMan real-time RT-PCR. AM and nNOS mRNA were determined by real-time PCR. Our results showed a linear relationship between competitive quantitative and real-time RT-PCR measurements of NPY and GAPDH (r = 0.87 and r = 0.92, respectively). AM and nNOS mRNA was found in all tumor samples. AM/GAPDH mRNA increased with higher differentiation according to Shimada (p = 0.013). There was no relation between MYCN amplification nor with the tumor stage (p = 0.78 and p = 0.30, respectively). AM/GAPDH did not relate to recurrence or death in a 5-year follow-up period. Neuronal NOS/GAPDH expression did not relate to any biological or clinical parameter of prognosis or differentiation. Similar results were obtained when the neuronal marker protein gene product 9.5 (PGP9.5) was used to normalize mRNA concentration. In conclusion, TaqMan real-time PCR appears to be a reliable method to quantify gene expression in neuroblastomas. Adrenomedullin mRNA in neuroblastoma is linked to tumor differentiation but not to prognostic markers.