Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.     

A computational model for tracking subsurface tissue deformation during stereotactic neurosurgery

Recent advances in the field of stereotactic neurosurgery have made it possible to coregister preoperative computed tomography (CT) and magnetic resonance (MR) images with instrument locations in the operating field. However, accounting for intraoperative movement of brain tissue remains a challenging problem. While intraoperative CT and MR scanners record concurrent tissue motion, there is motivation to develop methodologies which would be significantly lower in cost and more widely available. The approach we present is a computational model of brain tissue deformation that could be used in conjunction with a limited amount of concurrently obtained operative data to estimate subsurface tissue motion. Specifically, we report on the initial development of a finite element model of brain tissue adapted from consolidation theory. Validations of the computational mathematics in two and three dimensions are shown with errors of 1%-2% for the discretizations used. Experience with the computational strategy for estimating surgically induced brain tissue motion in vivo is also presented. While the predicted tissue displacements differ from measured values by about 15%, they suggest that exploiting a physics-based computational framework for updating preoperative imaging databases during the course of surgery has considerable merit. However, additional model and computational developments are needed before this approach can become a clinical reality.     

Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow

BACKGROUND: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period (P <.05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation.     

The effect of cutaneous and deep pain on the electroencephalogram during sleep--an experimental study

The interaction between sleep and pain has been insufficiently studied, and no experiments have investigated whether pathologic sleep patterns as seen in pain patients can be replicated experimentally by well-defined pain stimuli. An experimental model would therefore be valuable for further studies on the interaction between pain and sleep. In this study, three well-defined experimental stimuli (muscle, joint, and cutaneous pain) were applied during sleep, and the electroencephalogram (EEG) pattern was quantified. The pain stimuli were applied during slow-wave sleep in 10 healthy subjects. Using nine surface recordings, the EEG was sampled before and during pain stimuli. Frequency analysis was performed, resulting in 10 EEG features describing the responses to pain. During the muscle-pain stimulus an arousal effect was observed and a decrease in delta (0.5-3.5 Hz) and sigma (12-14 Hz) as well as increases in alpha 1 (8-10 Hz) and beta (14.5-25 Hz) activities were seen. During joint pain, however, more universal EEG changes were seen with a decrease in the lowest frequency bands [delta, theta (3.5-8 Hz) and alpha 1] and an increase in the higher frequencies [alpha 2 (10-12 Hz), sigma and beta bands]. No background EEG changes were observed during the cutaneous stimulus. There were several differences in the responses from the nine EEG channels, but no derivation seemed especially sensitive to detect the evoked changes. The study highlights the complexity of pain on the sleep EEG. The experimental model has shown that pain from different body structures, as well as signals from various EEG derivations, may give different responses in sleep microstructure.     

Grain growth in capped steel

The rate of grain growth during subcritical annealing at temperatures from 550 to 700 °C was determined for three capped steel samples, each of which had been given a range of prior cold reductions. The initial recrystallized grain size was finer for a higher carbon content and higher reductions. Except for short times at 550 °C, the rate of grain growth at each temperature for each reduction/sample combination obeyed the relationshipD =kt ⁿ and the value ofn was independent of carbon content and cold reduction. The rate of grain growth was a function of instantaneous grain size only for a specific reduction/sample combination but was not the same for different reductions of the same sample which had the same grain size. The material consequently has a memory for prior cold reduction. Grain size distribution changes can account for the deviation of grain growth rates for short times at 550 °C from the general relationship. They do not explain the influence of prior cold reduction.     

Reducing inequities through participatory research and community empowerment

PURPOSE: To analyze the indocyanine green angiographic findings of drusen in the early stages of age-related macular degeneration. METHODS: Sixty-nine eyes of 53 consecutive patients with drusen but without exudative complications of age-related macular degeneration were studied. Drusen were classified into four groups: hard drusen, drusen derived from clusters of hard drusen (hard cluster-derived drusen and soft cluster-derived drusen), membranous drusen, and regressing drusen. An additional category was constituted by reticular pseudodrusen that could be associated with drusen of either the inner or outer macula. Results of contact lens biomicroscopy and fluorescein angiography were compared with findings on indocyanine green angiography. RESULTS: Hard drusen, either isolated hard drusen or hard cluster-derived drusen, were hyperfluorescent during indocyanine green angiography; in contrast, all sizes of soft drusen derived from clusters of hard drusen were hypofluorescent throughout the angiogram. Membranous drusen, visible on biomicroscopy and fluorescein angiography, were not visible during indocyanine green angiography. Regressing drusen may have showed hyperfluorescence at the early stages of indocyanine green angiography, but associated calcium and pigmentation were hypofluorescent. Reticular pseudodrusen were visible on red-free photographs; on midphase and late-phase indocyanine green angiography using the scanning laser ophthalmoscope only, reticular pseudodrusen were seen as a pattern of hypofluorescent dots. CONCLUSION: The indocyanine green angiographic findings add to and support the clinicopathologic classification of drusen. Indocyanine green angiography may help to distinguish the different types of drusen and may thus be of use in evaluating the risk of progressive age-related macular degeneration in patients with drusen.