Trochanteric hip fracture: strong association with spinal trabecular bone mineral density measured with quantitative CT

PURPOSE: To determine the discriminatory capability for hip fracture of trabecular and integral bone mineral density (BMD) measured with quantitative computed tomography (CT) of the spine. MATERIALS AND METHODS: Fifty-six women who had sustained hip fractures and 59 control subjects underwent volumetric quantitative CT of L1 and L2 and dual x-ray absorptiometry of the hip. BMD was measured in vertebral regions of interest that encompassed trabecular, cortical, and integral bone. Logistic regression analysis was applied to each BMD measure to derive age-, weight-, and height-adjusted relative risk (RR) factors for overall hip fracture and for trochanteric fracture and cervical fracture separately. RESULTS: Spinal trabecular BMD was modestly related to overall hip fracture (RR, 1.4-1.7; P < .05) and strongly associated with trochanteric fracture (RR, 4.2-4.5; P < .005). Spinal integral BMD related similarly to overall hip fracture (RR, 1.7-1.8; P < .05) but more weakly to trochanteric fracture (RR, 2.3-3.2; P < .01). No spinal BMD measures were significantly related to cervical fracture. BMD at the hip was strongly related to overall hip fracture (RR, 3.3-4.3; P < .001), cervical fracture (RR, 2.7-5.3; P < .001), and trochanteric fracture (RR, 2.9-7.2; P < .001). CONCLUSION: Spinal trabecular BMD is strongly associated with both trochanteric and vertebral fractures.     

Encephalopathy due to capillary leak syndrome

Systemic capillary leak syndrome (SCLS) is characterized by intermittent attacks of leakage of intravascular fluids into the extravascular space. Hypovolemia, hemoconcentration, weakness, edema, and visceral congestion are resulting manifestations of SCLS. Most patients with SCLS have clear mentation during attacks, and encephalopathy is not a known manifestation of the syndrome. We report a patient with acute idiopathic capillary leak syndrome manifested in an acute encephalopathy. The possibility of SCLS should be considered in patients who have an encephalopathy and hemoconcentration.     

SNAP-25 is required for a late postdocking step in Ca2+-dependent exocytosis

The Ca2+-activated fusion of large dense core vesicles (LDCVs) with the plasma membrane is reconstituted in mechanically permeabilized PC12 cells by provision of millimolar MgATP and cytosolic proteins. Ca2+-activated LDCV exocytosis was inhibited completely by the type E but not the type A botulinum neurotoxin (BoNT) even though both BoNTs were equally effective in proteolytically cleaving the synaptosome-associated protein of 25 kDa (SNAP-25). The greater inhibition of exocytosis by BoNT E correlated with a greater destabilization of detergent-extracted complexes consisting of SNAP-25, synaptobrevin, and syntaxin. LDCVs in permeable PC12 cells can be poised at a late postdocking, prefusion state by MgATP-dependent priming processes catalyzed by N-ethylmaleimide sensitive factor and priming in exocytosis proteins. BoNT E completely blocked Ca2+-activated LDCV exocytosis in ATP-primed cells, whereas BoNT A was only slightly inhibitory, implying that the C-terminal region of SNAP-25 (Ile181-Gln197) between the cleavage sites for BoNT E and BoNT A is essential for late postdocking steps. A required role for SNAP-25 at this stage was also indicated by inhibition of Ca2+-activated LDCV fusion in ATP-primed cells by a C-terminal peptide antibody. We conclude that plasma membrane SNAP-25, particularly residues 181-197, is required for Ca2+-regulated membrane fusion at a step beyond LDCV docking and ATP utilization.     

Antigen-specific regression of established tumors induced by active immunization with irradiated IL-12- but not B7-1-transfected tumor cells

Transfection of modestly immunogenic tumors to express B7 family co-stimulator molecules results in their rejection by syngeneic mice, suggesting a possible clinical application in cancer patients. Immunization of naive mice with irradiated B7-1-transfected P1.HTR cells is sufficient to induce specific cytolytic T lymphocytes (CTL) and to protect against tumor challenge. However, patients to be treated will have an existing tumor burden; thus, preclinical models should examine therapeutic efficacy in an established tumor setting. Contrary to expectations, immunization of mice with irradiated B7-1-transfected P1.HTR cells had no impact on the growth of pre-established control-transfected tumors. Mice bearing control-transfected P1.HTR tumors successfully rejected living B7-1 transfectants on the contralateral flank, demonstrating the ability of tumor-bearing mice to respond to B7 co-stimulation. Inasmuch as IL-12 is another important factor for CTL maturation, P1.HTR transfectants expressing B7-1 and/or IL-12 were then constructed. Remarkably, regression of pre-established tumors was achieved following immunization with irradiated IL-12 transfectants, even without co-expression of B7-1. Rejection required a shared antigen with the tumor used for immunization, could not be reproduced with rIL-12 alone, depended on host T lymphocytes and correlated with a high IFN-gamma-producing T cell phenotype. In addition, IL-12-facilitated tumor rejection required co-operation with a CTLA-4 ligand provided by the host, and correlated with up-regulation of B7-1 and B7-2 on host antigen-presenting cells. Thus, active immunization in the established tumor setting is benefitted greatly by the provision of IL-12, which may recruit participation of sufficient B7 co-stimulation from the host that it need not be provided exogenously.     

Blood flow velocity changes in the middle cerebral artery induced by processing of hierarchical visual stimuli

Transcranial Doppler ultrasound was used to measure mean flow velocities in both middle cerebral arteries while 16 young subjects performed a visual task involving the processing of hierarchically structured stimuli. Specifically, large (global) letters composed of smaller (local) letters were presented, with the subjects' task being to attend either to the local or to the global level and press a button whenever a target on the designated level occurred. Each run was comprised of a 35-sec period of passive stimulation, followed by 65 sec of active task. A highly significant increase of blood flow was detected upon initiation of the active task, which was clearly present after ca. 4 sec. The flow velocity reached a maximum after 20 sec and remained stable for the remainder of the active condition. No hemispheric differences with respect to global or local conditions were observed.