In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

Mathematical Models for Predicting the Epidemiologic and Economic Impact of Vaccination against Human Papillomavirus Infection and Disease

Infection with human papillomavirus (HPV) is the primary causeof cervical cancer, other anogenital cancers, genital warts,and recurrent respiratory papillomatosis. Clinical studies havedemonstrated that a prophylactic HPV vaccine can prevent infection,genital warts, and the precancerous lesions that lead to cervicalcancer. Given the absence of data on the long-term effectivenessof HPV vaccination, a number of mathematical models have beendeveloped to provide insight to policy makers by projectingthe long-term epidemiologic and economic consequences of vaccinationand evaluate alternative vaccination policies. This paper reviewsthe state of these models. Three types of HPV mathematical modelshave been reported in the literature: cohort, population dynamic,and hybrid. All have demonstrated that vaccination can significantlyreduce the incidence of cervical cancer in the long term. However,only the cohort and hybrid models have evaluated the cost-effectivenessof vaccination strategies for preventing cervical cancer. Thesemodels have generally shown that vaccinating females can becost-effective. None has accounted for the potential benefitsof vaccinating the population to reduce the burden of recurrentrespiratory papillomatosis and cancers of the vagina, vulva,anus, penis, and head/neck. Given that only the population dynamicmodel can account for both the direct and indirect (i.e., herdimmunity effects) benefits of vaccination in the population,future research should focus on further development of dynamicmodels by expanding the range of epidemiologic outcomes trackedand including the ability to assess the cost-effectiveness ofalternative vaccination policies. cost-benefit analysis • economics • papillomavirus, human • vaccines     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Medical care for institutionalised elderly people in Singapore

Abstract: This study examined physical and financial arrangements for medical care of institutionalised elderly people in Singapore. Chief administrators of all long-term care facilities were interviewed on the existing arrangements for medical care of their residents. Results showed that 66 out of a total of 68 (97%) homes arranged medical care for residents. Of those, 29 homes offered on-site medical care with alternative arrangements when the in-house facilities were not operating. While government-owned homes would pay for all medical costs incurred by their residents, over 48% of voluntary homes and 87% of commercial homes required residents to be financially responsible for their care. The availability of financial support given to residents for payment of medical care was found to be associated with the type of sponsorship of the homes. While there was adequate physical access to medical care, the lack of financial support would pose a potential barrier to use of medical care for institutionalised elderly people.