Evaluation of a new method of small fragment fixation in a medial malleolus fracture model.

OBJECTIVE: To evaluate a new method of small fragment fixation in a medial malleolus fracture model. DESIGN/METHODS: The authors measured the pullout strength, resistance to shear stress, and speed of insertion of 4.0-millimeter partially threaded cancellous screws, 2.4-millimeter smooth K-wires, and a small fragment fixation system with 2.2-millimeter threaded K-wires. Pullout strength was tested in eighty-one synthetic foam blocks and resistance to shear stress in thirty synthetic tibias by use of a servohydraulic testing machine. Six randomized time trials with the threaded K-wires and cancellous screws were also conducted. RESULTS: Pullout strength increased with increasing foam density, increasing insertion depth, and varied with fixation method (p < 0.05). Maximum pullout strengths were as follows: partially threaded cancellous screws, 730+/-4 Newtons; threaded K-wires, 316+/-12 Newtons; and smooth K-wires, 172 +/-5 Newtons. Percent difference in pullout strength between the partially threaded cancellous screw and threaded K-wire diminished with increased depth of insertion and increased foam density. Offset axial load to initiate fracture displacement in a synthetic tibia model averaged 1540+/-138 Newtons for the partially threaded cancellous screws, 1,318+/-117 Newtons for the threaded K-wires, and 1,287+/-121 Newtons for the smooth K-wires (p > 0.05). Average time of fixation of a medial malleolar fragment by orthopedic surgeons with a variety of experience levels in a synthetic tibia with two threaded K-wires (114+/-8 seconds) was significantly faster (p < 0.05) than with two partially threaded cancellous screws (207+/-20 seconds). CONCLUSIONS: Threaded K-wires show substantial pullout strength and similar resistance to offset axial load when compared with partially threaded cancellous screws. These threaded K-wires offer an alternative for the internal fixation of medial malleolus fractures.

Mechanism for the posture-specific plasma volume increase after a single intense exercise protocol.

To test the hypothesis that exercise-induced hypervolemia is a posture-dependent process, we measured plasma volume, plasma albumin content, and renal function in seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h after exercise. Plasma volume decreased during exercise but returned to control levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume increased 2.4 +/- 0.8 ml/kg in Up but decreased 2.1 +/- 0.8 ml/kg in Sup. The plasma volume expansion in Up was accompanied by an increase in plasma albumin content (0.11 +/- 0.04 g/kg; P < 0.05). Plasma albumin content was unchanged in Sup. Urine volume and sodium clearance were lower in Up than Sup (P < 0.05) by 5 h of recovery. These data suggest that increased plasma albumin content contributes to the acute phase of exercise-induced hypervolemia. More importantly, the mechanism by which exercise influences the distribution of albumin between extra- and intravascular stores after exercise is altered by posture and is unknown. We speculate that factors associated with postural changes (e.g., central venous pressure) modify the increase in plasma albumin content and the plasma volume expansion after exercise.

Albumin infusion in humans does not model exercise induced hypervolaemia after 24 hours.

We rapidly infused 234 +/- 3 mL of 5% human serum albumin in eight men while measuring haematocrit, haemoglobin concentration, plasma volume (PV), albumin concentration, total protein concentration, osmolality, sodium concentration, renin activity, aldosterone concentration, and atrial natriuretic peptide concentration to test the hypotheses that plasma volume expansion and plasma albumin content expansion will not persist for 24 h. Plasma volume and albumin content were expanded for the first 6 h after infusion (44.3 +/- 1.9-47.2 +/- 2.0 mL kg-1 and 1.9 +/- 0.1-2.1 +/- 0.1 g kg-1 at pre-infusion and 1 h, respectively, P < 0.05), but by 24 h plasma volume and albumin content decreased significantly from 1 h post-infusion and were not different from pre-infusion (44.8 +/- 1.9 mL kg-1 and 1.9 +/- 0.1 g kg-1, respectively). Plasma aldosterone concentration showed a significant effect of time over the 24 h after infusion (P < 0.05), and showed a trend to decrease at 2 h after infusion (167.6 +/- 32.5(-1) 06.2 +/- 13.4 pg mL-1, P = 0.07). These data demonstrate that a 6.8% expansion of plasma volume and 10.5% expansion of plasma albumin content by infusion does not remain in the vascular space for 24 h and suggest a redistribution occurs between the intravascular space and interstitial fluid space.

Influence of hydrostatic pressure gradients on regulation of plasma volume after exercise.

The impact of posture on the immediate recovery of intravascular fluid and protein after intense exercise was determined in 14 volunteers. Forces which govern fluid and protein movement in muscle interstitial fluid pressure (PISF), interstitial colloid osmotic pressure (COPi), and plasma colloid osmotic pressure (COPp) were measured before and after exercise in the supine or upright position. During exercise, plasma volume (PV) decreased by 5.7 +/- 0.7 and 7. 0 +/- 0.5 ml/kg body weight in the supine and upright posture, respectively. During recovery, PV returned to its baseline value within 30 min regardless of posture. PV fell below this level by 60 and 120 min in the supine and upright posture, respectively (P < 0. 05). Maintenance of PV in the upright position was associated with a decrease in systolic blood pressure, an increase in COPp (from 25 +/- 1 to 27 +/- 1 mmHg; P < 0.05), and an increase in PISF (from 5 +/- 1 to 6 +/- 2 mmHg), whereas COPi was unchanged. Increased PISF indicates that the hydrostatic pressure gradient favors fluid movement into the vascular space. However, retention of the recaptured fluid in the plasma is promoted only in the upright posture because of increased COPp.

Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice.

This study sought to determine whether angiogenic blood vessels in disease models preferentially bind and internalize cationic liposomes injected intravenously. Angiogenesis was examined in pancreatic islet cell tumors of RIP-Tag2 transgenic mice and chronic airway inflammation in Mycoplasma pulmonis-infected C3H/HeNCr mice. For comparison, physiological angiogenesis was examined in normal mouse ovaries. We found that endothelial cells in all models avidly bound and internalized fluorescently labeled cationic liposomes (1,2-dioleoyl-3-trimethylammonium-propane [DOTAP]/cholesterol or dimethyldioctadecyl ammonium bromide [DDAB]/cholesterol) or liposome-DNA complexes. Confocal microscopic measurements showed that angiogenic endothelial cells averaged 15-33-fold more uptake than corresponding normal endothelial cells. Cationic liposome-DNA complexes were also avidly taken up, but anionic, neutral, or sterically stabilized neutral liposomes were not. Electron microscopic analysis showed that 32% of gold-labeled liposomes associated with tumor endothelial cells were adherent to the luminal surface, 53% were internalized into endosomes and multivesicular bodies, and 15% were extravascular 20 min after injection. Our findings indicate that angiogenic endothelial cells in these models avidly bind and internalize cationic liposomes and liposome-DNA complexes but not other types of liposomes. This preferential uptake raises the possibility of using cationic liposomes to target diagnostic or therapeutic agents selectively to angiogenic blood vessels in tumors and sites of chronic inflammation.

Transcapillary escape rate of albumin in humans during exercise-induced hypervolemia.

To test the hypotheses that plasma volume (PV) expansion 24 h after intense exercise is associated with reduced transcapillary escape rate of albumin (TERalb) and that local changes in transcapillary forces in the previously active tissues favor retention of protein in the vascular space, we measured PV, TERalb, plasma colloid osmotic pressure (COPp), interstitial fluid hydrostatic pressure (Pi), and colloid osmotic pressure in leg muscle and skin and capillary filtration coefficient (CFC) in the arm and leg in seven men and women before and 24 h after intense upright cycle ergometer exercise. Exercise expanded PV by 6.4% at 24 h (43.9 +/- 0.8 to 46.8 +/- 1.2 ml/kg, P < 0.05) and decreased total protein concentration (6.5 +/- 0.1 to 6.3 +/- 0.1 g/dl, P < 0.05) and COPp (26.1 +/- 0.8 to 24.3 +/- 0.9 mmHg, P < 0.05), although plasma albumin concentration was unchanged. TERalb tended to decline (8.4 +/- 0.5 to 6.5 +/- 0.7%/h, P = 0.11) and was correlated with the increase in PV (r = -0.69, P < 0.05). CFC increased in the leg (3.2 +/- 0.2 to 4.3 +/- 0.5 microl . 100 g-1 . min-1 . mmHg-1, P < 0. 05), and Pi showed a trend to increase in the leg muscle (2.8 +/- 0. 7 to 3.8 +/- 0.3 mmHg, P = 0.08). These data demonstrate that TERalb is associated with PV regulation and that local transcapillary forces in the leg muscle may favor retention of albumin in the vascular space after exercise.

Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice.

This study identified the organ and cellular distribution of cationic liposome-DNA complexes injected intravenously into CD-1 mice for gene delivery. DOTIM-cholesterol liposomes were labeled with the fluorescent dye CM-Dil and complexed with plasmid DNA encoding the chloramphenicol acetyltransferase reporter gene. The distribution of the complexes was examined in 29 organs and tissues by fluorescence, confocal, and electron microscopy from 5 min to 24 h after injection. The complexes formed clusters in blood, which were cleared within 20 min. Complexes visible by fluorescence microscopy were taken up by endothelial cells, leukocytes, and macrophages and did not leave the vasculature except in the spleen. At 5 min, the complexes formed a patchy coating on the endothelial surface, but by 4 h, they were internalized into endosomes and lysosomes in organ- and vessel-specific patterns. Uptake by capillary endothelial cells was greatest in the lung, ovary, and anterior pituitary, less in muscle and the heart, and nearly absent in the brain and pancreatic islets. In lymph nodes and intestinal Peyer's patches, the uptake was sparse in capillaries but abundant in high endothelial venules. In the liver and spleen, most of the uptake was in Kupffer cells and macrophages. Measurements of chloramphenicol acetyltransferase reporter gene expression were generally consistent with the pattern of uptake by endothelial cells. The uptake and gene expression were accompanied by a decrease in circulating leukocytes and platelets. Overall, our results showed that the complexes were internalized by endothelial cells in organ- and vessel-specific patterns that did not match any previously identified properties of the microvasculature. The unusual distribution of endothelial cell uptake may be explained by a heterogeneously distributed membrane receptor for which the complexes are ligands.

Information management: a long-term investment.

Conventional information processes are inadequate to meet today's health care demands. To allocate scarce resources, new approaches to information management are needed. This article explains how tapping the horizontal flow of information--across departments, services and programs--presents the greatest opportunities and challenges for health care management. New information infrastructures can integrate the entire health care system, and ultimately lead to enhanced affordability.

Distractibility in schizophrenia: state and trait aspects.

This report compared the selective attention of 19 schizophrenic in-patients, 10 recently discharged schizophrenic out-patients, 21 schizophrenic out-patients in stable clinical remission, 33 first-degree relatives of schizophrenics from 15 families, 25 students who scored deviantly on questionnaire measures of magical ideation, perceptual aberrations, and physical anhedonia, and 20 normal controls. Results indicated that distractors only disrupted the performance of schizophrenic in-patients, suggesting that differential deficits in selective attention are a marker of episodes of schizophrenia. A propensity to interject phonemes from the distracting message was found not only in patients in or just emerging from a psychotic episode, but also in the remaining vulnerable but non-psychotic groups, suggesting that intrusion errors might be a mediating vulnerability marker. The findings suggest both state and possibly trait aspects to distractibility in schizophrenia.

Changes in epithelial secretory cells and potentiation of neurogenic inflammation in the trachea of rats with respiratory tract infections.

In rats respiratory tract infections due to Sendai virus and coronavirus usually are transient, but they can have long-lasting consequences when accompanied by Mycoplasma pulmonis infections. Morphological alterations in the tracheal epithelium and a potentiation of the inflammatory response evoked by sensory nerve stimulation ("neurogenic inflammation") are evident nine weeks after the infections begin, but the extent to which these changes are present at earlier times is not known. In the present study we characterized these abnormalities in the epithelium and determined the extent to which they are present 3 and 6 weeks after the infections begin. We also determined the magnitude of the potentiation of neurogenic inflammation at these times, whether the potentiation can be reversed by glucocorticoids, and whether a proliferation of blood vessels contributes to the abnormally large amount of plasma extravasation associated with this potentiation. To this end, we studied Long-Evans rats that acquired these viral and mycoplasmal infections from other rats. We found that the tracheal epithelium of the infected rats had ten times as many Alcian blue-PAS positive mucous cells as did that of pathogen-free rats; but it contained none of the serous cells typical of pathogen-free rats, so the total number of secretory cells was not increased. In addition, the epithelium of the infected rats had three times the number of ciliated cells and had only a third of the number of globule leukocytes. In response to an injection of capsaicin (150 micrograms/kg i.v.), the tracheas of the infected rats developed an abnormally large amount of extravasation of two tracers, Evans blue dye and Monastral blue pigment, and had an abnormally large number of Monastral blue-labeled venules, particularly in regions of mucosa overlying the cartilaginous rings. This abnormally large amount of extravasation was blocked by dexamethasone (1 mg/day i.p. for 5 days). We conclude that M. pulmonis infections, exacerbated at the outset by viral infections, result within three weeks in the transformation of epithelial serous cells into mucous cells, the proliferation of ciliated cells, and the depletion of globule leukocytes. They also cause a proliferation of mediator-sensitive blood vessels in the airway mucosa, which is likely to contribute to the potentiation of neurogenic inflammation that accompanies these infections.

Neurogenic inflammation in the rat trachea. II. Identity and distribution of nerves mediating the increase in vascular permeability.

This study addresses the question of whether increased vascular permeability, which is a prominent feature of neurogenic inflammation in the respiratory tract, is mediated by sensory axons that end near venules in the airway mucosa. In these experiments, neurogenic inflammation was produced in the tracheal and bronchial mucosa of atropine-treated Long-Evans rats by electrical stimulation of the left or right superior laryngeal nerve and/or cervical vagus nerve. The particulate tracer Monastral blue was injected intravenously to localize the sites of increased vascular permeability, and microspectrophotometry was used to measure the amount of extravasated Monastral blue in the trachea and thereby quantify the increase in vascular permeability. In some rats, selective denervations were made to locate the cell bodies of neurons that mediate the increase in vascular permeability; in others, fluorescence immunohistochemistry and quantitative electron microscopic methods were used to determine which structures in the tracheal mucosa are innervated by these neurons. The study revealed that the vagally mediated increase in vascular permeability was sudden, transient (half-life = 2.4 min) and restricted to venules. Stimulation of the left or right superior laryngeal nerve increased the permeability of venules in the extrathoracic trachea, whereas stimulation of either vagus nerve increased vascular permeability in the intrathoracic trachea and bronchi. All nerves had bilateral effects in the trachea, but the vagus nerves had largely unilateral effects in the bronchi. Neurons that mediated the increase in venular permeability had their cells bodies in the jugular (superior sensory) ganglion of the vagus nerve or rostral portion of the nodose (inferior sensory) ganglion. Preganglionic autonomic vagal neurons in the brain stem were not essential for this increase in venular permeability. Few nerves identifiable by substance P-immunohistochemistry or electron microscopy were located near the affected venules, and no nerves were within 1 micron of the walls of venules. However, the epithelium and arterioles of the airway mucosa were densely innervated. All intraepithelial nerves were within 0.1 micron of epithelial cells, and at least two-thirds of nerves near arterioles were within 1 micron of the vessel walls. We conclude that the increase in venular permeability associated with neurogenic inflammation in the trachea and bronchi of rats is mediated by sensory axons that travel in the vagus nerves and superior laryngeal nerves.(ABSTRACT TRUNCATED AT 400 WORDS)