Francesca Celletti

Vascular endothelial growth factor enhances atherosclerotic plaque progression

Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 μg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.

Barriers to management of cardiovascular risk in a low-resource setting using hypertension as an entry point

Objective Assess capacity of health-care facilities in a low-resource setting to implement the absolute risk approach for assessment of cardiovascular risk in hypertensive patients and effective management of hypertension Design and setting A descriptive cross-sectional study in Egbeda and Oluyole local government areas of Oyo State in Nigeria in 56 randomly selected primary- (n = 42) and secondary-level (n = 2) health-care and private health-care (n = 12) facilities. Participants One thousand consecutive, known hypertensives attending the selected facilities for follow-up, and health-care providers working in the above randomly selected facilities, were interviewed. Results About two-thirds of hypertensives utilized primary-care centers both for diagnosis and for follow-up. Laboratory and other investigations to exclude secondary hypertension or to assess target organ damage were not available in the majority of facilities, particularly in primary care. A considerable knowledge and awareness gap related to hypertension and its complications was found, both among patients and health-care providers. Blood pressure control rates were poor [28% with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg] and drug prescription patterns were not evidence based and cost effective. The majority of patients (73%) in this low socio-economic group (mean monthly income US

Educating a new generation of doctors to improve the health of populations in low- and middle-income countries.

73) had to pay fully, out of their own pocket, for consultations and medications. Conclusions If the absolute risk approach for assessment of risk and effective management of hypertension is to be implemented in low-resource settings, appropriate policy measures need to be taken to improve the competency of health-care providers, to provide basic laboratory facilities and to develop affordable financing mechanisms.

Inhibition of vascular endothelial growth factor-mediated neointima progression with angiostatin or paclitaxel.

Francesca Celletti and colleagues from WHO argue that a transformation in the scale-up of medical education in low- and middle-income countries is needed, and detail what this might look like.

Task-Shifting in HIV Care: A Case Study of Nurse-Centered Community-Based Care in Rural Haiti

PURPOSE Therapeutic angiogenesis represents a new paradigm for treatment of ischemic vascular syndromes. However, vascular endothelial growth factor (VEGF) enhances the rate and degree of plaque formation. This study evaluates the potential to block these effects nonspecifically with paclitaxel or specifically with angiostatin. MATERIALS AND METHODS Recombinant human VEGF(165) (rhVEGF) was administrated intramuscularly (2-microg/kg single injection) in combination with adventitial delivery of paclitaxel, angiostatin, or vehicle alone at the site of femoral arterial balloon overdilation injury in New Zealand White rabbits (n = 5 per treatment). Five additional animals with no rhVEGF and no adventitial delivery served as procedural controls. All rabbits were fed according to a 0.25% cholesterol diet beginning 28 days before angioplasty. Treated arteries were harvested after 7 days and evaluated to determine intima-to-media (I/M) ratios, macrophage infiltrate, and endothelial cell density. RESULTS On histologic analysis, the rhVEGF/gel control group exhibited a mean I/M ratio of 0.337 +/- 0.028, a 77% increase over procedural controls, which exhibited a mean I/M of 0.190 +/- 0.010. rhVEGF/paclitaxel reduced I/M ratios to 0.151 +/- 0.007. In contrast, specific antiangiogenic therapy (rhVEGF/angiostatin) reduced I/M ratios to 0.032 +/- 0.003, a 91% decrease relative to rhVEGF/gel and an 83% decrease relative to procedural controls (P =.001 for each comparison). Local macrophages and endothelial cells also decreased with treatment. CONCLUSIONS This study shows that paclitaxel and angiostatin each afford local protection against rhVEGF-mediated increases in neointima. Angiostatin further prevents progression of underlying neointima. These local therapies may allow broader use of therapeutic angiogenesis while avoiding and treating potentially undesirable effects.

Prevention and management of chronic disease: a litmus test for health-systems strengthening in low-income and middle-income countries

Introduction At least 36 countries are suffering from severe shortages of healthcare workers and this crisis of human resources in developing countries is a major obstacle to scale-up of HIV care. We performed a case study to evaluate a health service delivery model where a task-shifting approach to HIV care had been undertaken with tasks shifted from doctors to nurses and community health workers in rural Haiti. Methods Data were collected using mixed quantitative and qualitative methods at three clinics in rural Haiti. Distribution of tasks for HIV services delivery; types of tasks performed by different cadres of healthcare workers; HIV program outcomes; access to HIV care and acceptability of the model to staff were measured. Results A shift of tasks occurred from doctors to nurses and to community health workers compared to a traditional doctor-based model of care. Nurses performed most HIV-related tasks except initiation of TB therapy for smear-negative suspects with HIV. Community health workers were involved in over half of HIV-related tasks. HIV services were rapidly scaled-up in the areas served; loss to follow-up of patients living with HIV was less than 5% at 24 months and staff were satisfied with the model of care. Conclusion Task-shifting using a community-based, nurse-centered model of HIV care in rural Haiti is an effective model for scale-up of HIV services with good clinical and program outcomes. Community health workers can provide essential health services that are otherwise unavailable particularly in rural, poor areas.