Comparative efficacies of three commercially available vaccines against West Nile Virus (WNV) in a short-duration challenge trial involving an equine WNV encephalitis model.

We used a severe challenge model that produces clinical West Nile virus (WNV) disease to test the efficacy of three commercially available equine WNV vaccines in horses. Twenty-four healthy, WNV-seronegative horses of varying ages and genders were placed, in random and blind manner, into three trial groups consisting of eight horses each; two horses in each group received (i) an inactivated WNV vaccine (K-WN), (ii) a modified-live vaccine (CP-WN) containing the WNV prM and E proteins expressed by a canarypox vector, (iii) a live-chimera vaccine (WN-FV) containing WNV prM and E proteins expressed in a YF17D vector, or (iv) a diluent control. Challenge by this model caused grave neurological signs, viremia, moderate to severe histopathologic lesions in the brain and spinal cord, and an outcome of 0% survivorship in all six control horses. In contrast, challenge in horses at between 28 days postvaccination with the chimera vaccine and 56 days postvaccination with the commercial inactivated or modified-live vaccine resulted in 100% survivorship (protection from the onset of WNV encephalitis and viremia). Horses vaccinated with the live-chimera vaccine showed significantly fewer clinical signs than did the control horses (P

Effects of disrupted beta1-integrin function on the skeletal response to short-term hindlimb unloading in mice.

The study was designed to determine whether beta1-integrin plays a role in mediating the acute skeletal response to mechanical unloading. Transgenic (TG) mice were generated to express a dominant negative form of beta1-integrin under the control of the osteocalcin promoter, which targets expression of the transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice were subjected to hindlimb unloading by tail suspension for 1 wk. Pair-fed, normally loaded WT and TG mice served as age-matched controls. Bone samples from each mouse were processed for quantitative bone histomorphometry and biomechanical testing. The skeletal phenotype of TG mice was characterized by lower cancellous bone mass in the distal femoral metaphysis (-52%) and lumbar vertebral body (-20%), reduced curvature of the proximal tibia (-20%), and decreased bone strength (-20%) and stiffness (-23%) of the femoral diaphysis with relatively normal indexes of cancellous bone turnover. Hindlimb unloading for only 1 wk induced a 10% decline in tibial curvature and a 30% loss of cancellous bone in the distal femur due to a combination of increased bone resorption and decreased bone formation in both WT and TG mice. However, the strength and stiffness of the femoral diaphysis were unaffected by short-term hindlimb unloading in both genotypes. The observed increase in osteoclast surface was greater in unloaded TG mice (92%) than in unloaded WT mice (52%). Cancellous bone formation rate was decreased in unloaded WT (-29%) and TG (-15%) mice, but, in contrast to osteoclast surface, the genotype by loading interaction was not statistically significant. The results indicate that altered integrin function in mature osteoblasts may enhance the osteoclastic response to mechanical unloading but that it does not have a major effect on the development of cancellous osteopenia in mice during the early stages of hindlimb unloading.

Management of hypertension. Effect of improving patient compliance for follow-up care.

A radomized controlled trial was conducted in a metropolitan teaching hospital to determine whether improving follow-up of emergency room patients who had hypertension led to improvements in their medical care and blood pressure control. One hundred fourty four patients were randomly assigned into an intervention group and a control group. In the former, a follow-up clerk assigned patients in returning for follow-up care. Eighty-four percent of patients in this group and 63% of control patients returned to the clinic (P less than 0.1). However, five months after the patients' emergency room visits, 51% of patients in the intervention group and 53% of control patients were normotensive. There were more diagnostic and therapeutic measures in the intervention group, but long-term management was similar in both groups. Improvement in follow-up may not be by itself lead to blood pressure control among hypertensive patients.