283 research outputs found
The transition of smooth muscle cells from a contractile to a migratory, phagocytic phenotype : direct demonstration of phenotypic modulation
Atherosclerotic plaques are populated with smooth muscle cells (SMCs) and macrophages. SMCs are thought to accumulate in plaques because fully-differentiated, contractile SMCs reprogram into a ‘synthetic’ migratory phenotype, so-called phenotypic modulation, whilst plaque macrophages are thought to derive from blood-borne myeloid cells. Recently, these views have been challenged, with reports that SMC phenotypic modulation may not occur during vascular remodelling and that plaque macrophages may not be of haematopoietic origin. Following the fate of SMCs is complicated by the lack of specific markers for the migratory phenotype and direct demonstrations of phenotypic modulation are lacking. Therefore, we employed long-term, high-resolution, time-lapse microscopy to track the fate of unambiguously identified, fully-differentiated, contractile SMCs in response to the growth factors present in serum. Phenotypic modulation was clearly observed. The highly-elongated, contractile SMCs initially rounded up, for 1-3 days, before spreading outwards. Once spread, the SMCs became motile and displayed dynamic cell-cell communication behaviours. Significantly, they also displayed clear evidence of phagocytic activity. This macrophage-like behaviour was confirmed by their internalisation of 1µm fluorescent latex beads. However, migratory SMCs did not uptake acetylated low-density lipoprotein or express the classic macrophage marker CD68. These results directly demonstrate that SMCs may rapidly undergo phenotypic modulation and develop phagocytic capabilities. Resident SMCs may provide a potential source of macrophages in vascular remodelling
Changes in vitamin biomarkers during a 2-year intervention trial involving increased fruit and vegetable consumption by free-living volunteers
Peer reviewedPublisher PD
Malignant pheochromocytoma in a pig
Abstract. Endocrine tumors are rarely observed in pigs, and pheochromocytomas have been only punctually described. The
current report describes a white and firm, 15-cm in diameter, neoplastic mass located in the adrenal gland with metastasis to
regional lymph nodes in a 2.5-year-old sow. The masses had marked desmoplasia that supported a population of polygonal-tospindle–
shaped neoplastic cells arranged into cords and packets within a delicate fibrovascular stroma. Immunohistochemical
staining of the tumor was positive for chromogranin and negative for neurofilament protein in adrenal and lymph node masses,
which was characteristic of a malignant pheochromocytoma
Development of a Proton Radiation Therapy Facility at IUCF
This research was sponsored by the National Science Foundation Grant NSF PHY-931478
Status of the IUCF Proton Radiation Therapy Facility
This research was sponsored by the National Science Foundation Grant NSF PHY-931478
Protective effi cacy of prolonged co-trimoxazole prophylaxis in HIV-exposed children up to age 4 years for the prevention of malaria in Uganda: a randomised controlled open-label trial
Background WHO recommends daily co-trimoxazole for children born to HIV-infected mothers from 6 weeks of age
until breastfeeding cessation and exclusion of HIV infection. We have previously reported on the eff ectiveness of
continuation of co-trimoxazole prophylaxis up to age 2 years in these children. We assessed the protective effi cacy and
safety of prolonging co-trimoxazole prophylaxis until age 4 years in HIV-exposed children.
Methods We undertook an open-label randomised controlled trial alongside two observational cohorts in eastern
Uganda, an area with high HIV prevalence, malaria transmission intensity, and antifolate resistance. We enrolled HIVexposed
infants between 6 weeks and 9 months of age and prescribed them daily co-trimoxazole until breastfeeding
cessation and HIV-status confi rmation. At the end of breastfeeding, children who remained HIV-uninfected were
randomly assigned (1:1) to discontinue co-trimoxazole or to continue taking it up to age 2 years. At age 2 years, children
who continued co-trimoxazole prophylaxis were randomly assigned (1:1) to discontinue or continue prophylaxis from
age 2 years to age 4 years. The primary outcome was incidence of malaria (defi ned as the number of treatments for new
episodes of malaria diagnosed with positive thick smear) at age 4 years. For additional comparisons, we observed
48 HIV-infected children who took continuous co-trimoxazole prophylaxis and 100 HIV-unexposed uninfected children
who never received prophylaxis. We measured grade 3 and 4 serious adverse events and hospital admissions. All
children were followed up to age 5 years and all analyses were by intention to treat. This study is registered with
ClinicalTrials.gov, number NCT00527800.
Findings 203 HIV-exposed infants were enrolled between Aug 10, 2007, and March 28, 2008. After breastfeeding ended,
185 children were not infected with HIV and were randomly assigned to stop (n=87) or continue (n=98) co-trimoxazole
up to age 2 years. At age 2 years, 91 HIV-exposed children who had remained on co-trimoxazole prophylaxis were
randomly assigned to discontinue (n=46) or continue (n=45) co-trimoxazole from age 2 years to age 4 years. We
recorded 243 malaria episodes (2·91 per person-years) in the 45 HIV-exposed children assigned to continue cotrimoxazole
until age 4 years compared with 503 episodes (5·60 per person-years) in the 46 children assigned to stop
co-trimoxazole at age 2 years (incidence rate ratio 0·53, 95% CI 0·39–0·71; p<0·0001). There was no evidence of
malaria incidence rebound in the year after discontinuation of co-trimoxazole in the HIV-exposed children who stopped
co-trimoxazole at age 2 years, but incidence increased signifi cantly in HIV-exposed children who stopped co-trimoxazole
at age 4 years (odds ratio 1·78, 95% CI 1·19–2·66; p=0·005). Incidence of grade 3 or 4 serious adverse events, hospital
admissions, or deaths did not signifi cantly diff er between HIV-exposed, HIV-unexposed, and HIV-infected children.
Interpretation Continuation of co-trimoxazole prophylaxis up to 4 years of age seems safe and effi cacious to protect
HIV-exposed children living in malaria-endemic areas
Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children
BACKGROUND: Artemisinin combination therapy has become the standard of care for uncomplicated malaria in most of Africa. However, there is limited data on the safety and tolerability of these drugs, especially in young children and patients co-infected with HIV. METHODS: A longitudinal, randomized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4-22 months in Tororo, Uganda. Participants were randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes. Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment. This study was registered in ClinicalTrials.gov (registration # NCT00527800). RESULTS: A total of 122 children were randomized to AL and 124 to DP, resulting in 412 and 425 treatments, respectively. Most adverse events were rare, with only cough, diarrhoea, vomiting, and anaemia occurring in more than 1% of treatments. There were no differences in the risk of these events between treatment groups. Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms. Retreatment for malaria within 17-28 days was associated with an increased risk of vomiting in the DP treatment arm (HR = 6.47, 95% CI 2.31-18.1, p < 0.001). There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis. CONCLUSION: Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00527800; http://clinicaltrials.gov/ct2/show/NCT00527800
Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial
Objective To evaluate the protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children (uninfected children born to HIV infected mothers) in Africa
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