Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Traumatic Injury of the Superior Mesenteric Vein: Ligate,Repair or Shunt?

Abstract We report a case of SMV injury in a critically ill patient. The patient was a 19-year-old woman involved in a motor vehicle collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections. At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral venous drainage limits the surgeon’s ability to ligate. In these situations, bypass shunts may be successful.     

Policy Perspective on Housing and HIV/AIDS

For persons battling HIV/AIDS a stable place to live may decide the length and quality of life itself. It is nearly impossible for a person on the streets to engage in a needed continuous AIDS treatment regimen when the very basic question of where that person will rest his or her head when darkness comes in just a few hours is unresolved. When danger lurks on the streets, when cold numbs the limbs, when tiredness overwhelms the mind, when fear breaks the spirit, a place to call home would make all the difference.     

Pelvic Ring Fractures: Utility of Clinical Examination in Patients with Impaired Consciousness or Tracheal Intubation

Abstract Objective: To define the diagnostic accuracy of clinical examination in patients with impaired consciousness or endotracheal intubation to detect pelvic ring fractures and to identify those with severe bleeding. Methods: Included in this prospective data collection with retrolective data analysis were a consecutive series of blunt trauma victims with either a Glasgow Coma Scale ≤ 13 or tracheal intubation. Clinical examination comprised testing for stability of the iliac wings. Results: From 784 subjects (injury severity score 23.3 ± 17.4) 93 patients (11.9%) were found to have a pelvic ring fracture. Clinical instability of the pelvic ring was found in 42 patients. There was only one false positive. Fifty-two fractures could not be identified by clinical examination, including nine fractures (17%) that required surgical fracture stabilization (sensitivity of clinical examination 44.1%). Seventeen fractures (18.3%) were associated with a blood loss larger than 20% of circulating blood volume. Sixteen of those were identified by clinical instability of the pelvic ring (sensitivity 94.1%, specificity 97.0%, positive predictive value 38.1%, negative predictive value 99.9%). Conclusions: Clinical examination for stability of the pelvis in this selected group of patients missed a significant number of pelvic ring fractures including fractures that require surgical stabilization. The finding of a clinically unstable identifies most of the patients with the pelvic ring fracture being a major source of bleeding. A stable pelvis makes pelvic ring fracture as being the source of bleeding quite unlikely.     

Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.