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Therapeutic approaches seeking to limit the exposure to antiretroviral drugs while retaining the benefits of continuous therapy have become an active area of investigation in HIV therapy research. Although early attempts to use interruptions of therapy as auto-vaccination strategies have shown little success, much has been discovered in regards to immunological correlates of viral control in acute and chronic infection, viral evolution, and the safety of single or multiple therapy interruptions in different patient sub-groups (acutely infected, chronically infected, and multi-drug resistant). Here we review safety data and candidate factors that may contribute to the striking differences observed between patients that undergo similar treatment interruption strategies but achieve different outcomes in controlling HIV replication. Differences between acute and chronic infection in the viral component (e.g. diversity of the viral pool) and the host immune system (e.g. low avidity CTL memory response), which may not be reversed by ART, may determine the potential for suppressive immune response upon therapy interruption. Consistent with goals of limiting toxicity and cost of antiretroviral drug regimens, safety outcomes to date indicate that intermittent therapy strategies may safely continue to be investigated in early and chronically infected patients. Based on ongoing research, we identify the topics to be targeted in future studies. 相似文献
93.
Molecular signatures of brain injury after intracerebral hemorrhage 总被引:53,自引:0,他引:53
Castillo J Dávalos A Alvarez-Sabín J Pumar JM Leira R Silva Y Montaner J Kase CS 《Neurology》2002,58(4):624-629
BACKGROUND: The mechanisms of cellular death in the tissue surrounding an intracerebral hemorrhage (ICH) are not defined. OBJECTIVE: To investigate the relationship of markers of excitotoxicity and inflammation to brain injury after ICH. METHODS: A total of 124 consecutive patients with spontaneous ICH admitted within 24 hours of stroke onset were prospectively investigated. The volumes of the initial ICH, peripheral edema on days 3 to 4, and the residual cavity at 3 months were measured on CT scan. Glutamate, cytokines, and adhesion molecules were measured in blood samples obtained on admission. Stroke severity and neurologic outcome were evaluated with the Canadian Stroke Scale. RESULTS: Poor neurologic outcome at 3 months (Canadian Stroke Scale < 7) was observed in 53 patients (43%). Stroke severity and glutamate concentrations (by each increment of 10 micromol/L, odds ratio 1.23; 95% CI 1.09 to 1.41), but not the initial volume of ICH, were independent predictors of poor outcome. In the multiple linear regression analyses, tumor necrosis factor-alpha concentration was correlated (r = 0.83, p < 0.0001) with the volume of perihematoma edema, and glutamate concentrations were correlated (r = 0.78, p < 0.0001) with the volume of the residual cavity. These same results were observed when lobar (n = 58) and deep (n = 66) ICH were analyzed separately. CONCLUSIONS: High plasma levels of proinflammatory molecules within 24 hours of intracerebral hemorrhage onset are correlated with the magnitude of the subsequent perihematoma brain edema, whereas poor neurologic outcome and the volume of the residual cavity are related to increased plasma glutamate concentrations. 相似文献
94.
Ribó M Montaner J Molina C Abilleira S Arenillas J Alvarez Sabín J 《Neurología (Barcelona, Spain)》2002,17(6):342-344
Chronic subdural hematoma that generally happens after cranial trauma doesn't have clinical manifestations until days or weeks after the traumatism. Due to the lesions nature, symptoms are almost always progressive and presentation as transient ischemic attacks (TIA) is very uncommon. We describe 2 cases of chronic subdural hematoma that started simulating TIA and we discuss its implications in the management of those patients who had presented transient neurological deficit. 相似文献
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Evan Wood Mark W Tyndall Calvin Lai Julio SG Montaner Thomas Kerr 《Substance abuse treatment, prevention, and policy》2006,1(1):13-4
North America's first medically supervised safer injecting facility (SIF) recently opened in Vancouver, Canada. One of the
concerns prior to the SIF's opening was that the facility might lead to a migration of drug activity and an increase in drug-related
crime. Therefore, we examined crime rates in the neighborhood where the SIF is located in the year before versus the year
after the SIF opened. No increases were seen with respect to drug trafficking (124 vs. 116) or assaults/robbery (174 vs. 180),
although a decline in vehicle break-ins/vehicle theft was observed (302 vs. 227). The SIF was not associated with increased
drug trafficking or crimes commonly linked to drug use. 相似文献
98.
Mark W Tyndall Evan Wood Ruth Zhang Calvin Lai Julio SG Montaner Thomas Kerr 《Harm reduction journal》2006,3(1):36-5
North America's first government sanctioned medically supervised injection facility (SIF) was opened during September 2003
in Vancouver, Canada. This was in response to a large open public drug scene, high rates of HIV and hepatitis C transmission,
fatal drug overdoses, and poor health outcomes among the city's injection drug users. Between December 2003 and April 2005,
a representative sample of 1,035 SIF participants were enrolled in a prospective cohort that required completing an interviewer-administered
questionnaire and providing a blood sample for HIV testing. HIV infection was detected in 170/1007 (17%) participants and
was associated with Aboriginal ethnicity (adjusted Odds Ratio [aOR], 2.70, 95% Confidence Interval [95% CI], 1.84–3.97), a
history of borrowing used needles/syringes (aOR, 2.0, 95% CI, 1.37–2.93), previous incarceration (aOR, 1.87, 95% CI, 1.11–3.14),
and daily injection cocaine use (aOR, 1.42, 95% CI, 1.00–2.03). The SIF has attracted a large number of marginalized injection
drug users and presents an excellent opportunity to enhance HIV prevention through education, the provision of sterile injecting
equipment, and a supervised environment to self-inject. In addition, the SIF is an important point of contact for HIV positive
individuals who may not be participating in HIV care and treatment. 相似文献
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100.
Brandon DL Marshall Thomas Kerr Chris Livingstone Kathy Li Julio SG Montaner Evan Wood 《Harm reduction journal》2008,5(1):35
Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less
is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth.
We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline,
15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection
(odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals
reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants
(p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved
Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention
among Aboriginal young people are urgently required. 相似文献