Pattern formation and traveling waves in myxobacteria: theory and modeling.

Recent experiments have provided new quantitative measurements of the rippling phenomenon in fields of developing myxobacteria cells. These measurements have enabled us to develop a mathematical model for the ripple phenomenon on the basis of the biochemistry of the C-signaling system, whereby individuals signal by direct cell contact. The model quantitatively reproduces all of the experimental observations and illustrates how intracellular dynamics, contact-mediated intercellular communication, and cell motility can coordinate to produce collective behavior. This pattern of waves is qualitatively different from that observed in other social organisms, especially Dictyostelium discoideum, which depend on diffusible morphogens.

Prognostic value of a normal or nonspecific initial electrocardiogram in acute myocardial infarction.

CONTEXT: Although previous studies have suggested that normal and nonspecific initial electrocardiograms (ECGs) are associated with a favorable prognosis for patients with acute myocardial infarction (AMI), their independent predictive value for mortality has not been examined. OBJECTIVE: To compare in-hospital mortality among patients with AMI who have normal or nonspecific initial ECGs with that of patients who have diagnostic ECGs. DESIGN, SETTING, AND PATIENTS: Multihospital observational study in which 391 208 patients with AMI met the study criteria between June 1994 and June 2000 and had ECGs that were normal (n = 30 759), nonspecific (n = 137 574), or diagnostic (n = 222 875; defined as ST-segment elevation or depression and/or left bundle-branch block). A logistic regression model was constructed using a propensity score for ECG findings and data on demographics, medical history, diagnostic procedures, and therapy to determine the independent prognostic value of a normal or nonspecific initial ECG. MAIN OUTCOME MEASURES: In-hospital mortality; composite outcome of in-hospital death and life-threatening adverse events. RESULTS: In-hospital mortality rates were 5.7%, 8.7%, and 11.5% while the rates of the composite of mortality and life-threatening adverse events were 19.2%, 27.5%, and 34.9% for the normal, nonspecific, and diagnostic ECG groups, respectively. After adjusting for other predictor variables, the odds of mortality for the normal ECG group was 0.59 (95% confidence interval [CI], 0.56-0.63; P<.001) and for the nonspecific group was 0.70 (95% CI, 0.68-0.72; P<.001), compared with the diagnostic ECG group. CONCLUSION: In this large cohort of patients with AMI, patients presenting with normal or nonspecific ECGs did have lower in-hospital mortality rates than those of patients with diagnostic ECGs, yet the absolute rates were still unexpectedly high.

Axial characteristics of circular external skeletal fixator single ring constructs.

OBJECTIVE: Evaluate the effects of varying ring diameter, wire tension, and wire-divergence angle on the axial stiffness characteristics of circular external skeletal fixator single-ring constructs. Study Design-Biomechanical evaluation using circular fixator components and a Delrin cylinder bone model. METHODS: Single ring constructs using two 1.6 mm diameter Kirschner wires to secure a 19 mm Delrin cylinder centered within the ring were examined. Component variables evaluated were ring diameter (50 mm, 66 mm, 84 mm, and 118 mm), wire-divergence angle (30 degrees, 60 degrees, and 90 degrees ), and wire tension (0 kg, 30 kg, 60 kg, and 90 kg). A total of 48 constructs were examined. Rings were rigidly mounted on a universal testing system and the cylinder loaded in axial compression (7.4 N/s) to 220 N. Load/displacement curves were analyzed to determine the following: the displacement (mm) that occurred before the slope of each load/displacement curve became linear, the stiffness (N/mm) of the linear portion of each load/deformation curve, and the total displacement (mm) produced at maximal load. Least-squares linear regression was used to model response variables as linear functions of ring diameter, wire divergence angle, and wire tension. Three-way interactions and 2-way interactions among independent component variables were evaluated first in the modeling process and included in a best model if response variables were found to have statistically significant regression coefficients. The regression coefficients and corresponding standard errors and covariances were used to estimate the maximal effect and standard error attributable to wire divergency angle (change from 30 degrees to 90 degrees ) and wire tension (change from 0 to 90 kg) for each ring diameter. RESULTS: All load/deformation curves had an initial exponential increase in stiffness, with the slope becoming linear at higher loads. The exponential phase was more pronounced in larger-diameter ring constructs and was mitigated by tensioning the wires. Ring diameter had the greatest influence on displacement that occurred before the curve became linear (semipartial r(2) [sp-r2] = .89), stiffness (sp-r2 = .94), and total displacement (sp-r2 = .93). Wire tension exerted a smaller influence on displacement that occurred before the curve became linear (sp-r2 =.06), stiffness (sp-r2 = .03), and total displacement (sp-r2 = .05). Wire divergence angle had a nominal effect on displacement that occurred before the curve became linear (sp-r2 = .0001), on stiffness (sp-r2 = .004), and on total displacement (sp-r2 =.003). CONCLUSIONS: Ring diameter had a profound effect on the axial stiffness characteristic of single ring constructs. Tensioning of the fixation wires can improve the axial stiffness characteristics of these constructs, particularly in larger diameter ring constructs, by mitigating the initial exponential phase of the load/deformation curve. Wire divergence angle had only a nominal differential effect on axial stability. CLINICAL RELEVANCE: Understanding how individual component variables and their interactions influence bone segment stability should help surgeons to optimize interfragmentary strain. Tensioning fixation wires is probably unnecessary in 50 mm diameter ring constructs, but assumes greater importance as ring diameter increases.

Impact of technetium-99m sestamibi imaging on the emergency department management and costs in the evaluation of low-risk chest pain.

OBJECTIVES: To assess the impact of rest sestamibi scanning on emergency physicians' (EPs') diagnostic certainty and decision making (as assessed by the hypothetical disposition of patients) for 69 consenting stable patients with suspected acute cardiac ischemia and nondiagnostic electrocardiograms. The resultant impact on costs was examined as a secondary outcome. METHODS: Patients with suspected acute cardiac ischemia were injected with 25 mCi of sestamibi within two hours of active pain in one of three emergency department study sites. The probability of acute myocardial infarction (AMI) and unstable angina (UA), and hypothetical disposition decisions were recorded immediately before and after physicians were notified of scan results. Changes in disposition were classified as optimal or suboptimal. For the cost determinations, a cost-based decision support program was used. RESULTS: For the subgroup found to be free of acute cardiac events (ACEs) (n = 62), the EPs' post-sestamibi scan probabilities for AMI decreased by 11% and UA by 18% (p < 0.001 for both conditions). In seven patients with ACEs, the post-scan probabilities of AMI and UA increased, but neither was statistically significant. Scan results led to hypothetical disposition changes in 29 patients (42%), of which 27 (93%) were optimal (nine patients were reassigned to a lower level of care, two to a higher level, and 16 additional patients to "discharge-home" status). The strategy of scanning all patients who were low to moderate risk for acute cardiac ischemia would result in an increase of direct costs of care of $222 per patient evaluated, due to added cost of sestamibi scanning. CONCLUSIONS: Sestamibi scanning results appropriately affected the EPs' estimates of the probability of AMI and UA and improved disposition decisions. Scanning all low-risk patients would likely be associated with increased costs at this medical center.

Effect of rhythm and level of distraction on muscle structure: an animal study.

To determine the optimal rhythm of distraction and level of osteotomy for maximal muscle preservation during limb lengthening, histologic and ultrastructural analysis of the peroneus tertius muscle was performed in 46 goats. Thirty-nine animals with 20% or 30% tibial lengthening at the rate of 0.75 mm per day at each osteotomy level were divided in two groups. The first group included 15 animals undergoing tibial middiaphyseal lengthening with automated distractor producing one (n = 5), four (n = 5), or 720 (n = 5) increments per day. The second group included 24 animals in which lengthening was performed at the proximal (n = 4), middle (n = 6), distal (n = 6), or double (n = 8) level of the tibia with distraction rhythm of three times per day. The remaining seven animals served as controls. Histomorphologic features of the lengthened muscles were characterized by a polymorphous appearance with foci of necrosis, atrophy, and sclerosis scattered among apparently normal muscle fibers. The intensity and dispersion of degenerative changes were in direct proportion to the amount of lengthening but in reverse proportion to the frequency of distraction. Tibial lengthening at the diaphysis caused intense fibroblast proliferation and remarkable muscle sclerosis, whereas metaphyseal distraction was associated with a predominance of muscle tissue regeneration over atrophy and sclerosis. Bifocal lengthening and a more fractionated rhythm of distraction were associated with enhanced preservation of existing muscle fibers and greater regenerative activity of the muscle.

Management of traumatically injured patients in the emergency department observation unit.

An EDOU may be an ideal setting for the short-term monitoring and treatment of certain acutely injured patients. The patients choosen for observation, and the diagnostic studies used, will be specific to a particular institution's availability and expertise. Pathways should be developed in conjunction with all services caring for these patients.

Pretest probability assessment for selective rest sestamibi scans in stable chest pain patients.

The objective of this study was to determine whether pretest probability assessments permit more selective testing of chest pain patients with technetium-99m sestamibi scanning. Pretest probabilities of cardiac ischemia were measured both objectively (Acute Cardiac Ischemia Time-Insensitive Predictive Instrument [ACI-TIPI]) and subjectively (physician's estimate of the probability of unstable angina). Two groups were defined: patients whose postsestamibi scan led to a "downgrade" of the intensity of monitoring and those that resulted in no change in monitoring intensity. Sixty-five patients met study criteria; 25 had a disposition downgrade and 40 had no change. Pretest ACI-TIPI scores were similar in the two groups (29% +/- 18% versus 27% +/- 11%, mean +/- standard deviation; P = .95) as were the physician's assessment of unstable angina (39% +/- 22% versus 40% +/- 24%; P = .75). Objective or subjective pretest probabilities are not significantly different in patients who are likely to have their disposition altered by sestamibi scanning.

Distraction osteogenesis.

Distraction osteogenesis and the use of circular external skeletal fixation has increased the capacity of veterinary surgeons to manage difficult orthopedic conditions including limb-length discrepancies, angular deformity, distal and severely comminuted fractures, and bone defects. This article discusses the historical developments of the Ilizarov method of distraction osteogenesis in veterinary surgery, circular external skeletal instrumentation, and the biological principles. There is also discussion of use of this method for correction of angular deformity and bone transport and complications associated with this technique.

Regulation of glucose transporters by estradiol in the immature rat uterus.

A series of metabolic changes within the immature rat uterus begins minutes after the administration of microgram quantities of estradiol (E2). One of the earliest effects that has been measured is an increase in the rate at which the uterus takes up glucose. To characterize the effect of E2 on glucose transport stimulation, whole protein preparations were examined for the presence of mammalian glucose transport proteins Glut1 through Glut5. E2-stimulated changes in the steady state levels of messenger RNA (mRNA) and protein were measured for Glut1 and Glut4 by quantitative competitive RT-PCR and Western blots. Both Glut1 mRNA and protein increased approximately 3- to 4-fold within 4-8 h. This increase in Glut1 mRNA and protein agrees with the maximal stimulation of the glucose transport rate that was observed. No translocation of either Glut1 or Glut4 was observed 2 h after E2 injection, indicating that translocation is not the mechanism responsible for the initial E2-stimulated increase in glucose transport observed in immature rat uterus. These data support the conclusion that the prolonged increase in glucose transport rate is due to either the transcriptional activation of Glut1 and/or the increased Glut1 mRNA half-life.

Simultaneous measurement of multiple mRNAs with a single control by quantitative competitive reverse transcriptase-polymerase chain reaction: glucose transporters Glut1 and Glut4.

Theoretical considerations for extending the application of quantitative competitive polymerase chain reaction (qc-PCR) to include the simultaneous measurement of multiple mRNAs, specifically the mammalian glucose transporters Glut1 and Glut4, are presented with experimental data in which the accuracy and flexibility of the system are examined. This method reliably measures changes in the initial concentration for each of three target DNA sequences. The reaction is not acutely sensitive to variations in either the primer sites or internal sequence, and although the initial concentrations of the target DNAs did affect the relative amplification efficiencies, the effect was limited and did not prohibit quantification. This PCR system was able to reliably detect differences as little as 50% in the initial concentration of the Glut1 target DNA sequence. Therefore, with the appropriate controls, PCR can be extended to include the simultaneous quantification of more than one target DNA with a single internal control.

Effect of recombinant human bone morphogenetic protein-2 on fracture healing in a goat tibial fracture model.

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.

Histomorphometry of distraction osteogenesis in a caprine tibial lengthening model.

Standardized histomorphometry of bone formation and remodeling during distraction osteogenesis (DO) has not been well characterized. Increasing the rhythm or number of incremental lengthenings performed per day is reported to enhance bone formation during limb lengthening. In 17 skeletally immature goats, unilateral tibial lengthenings to 20 or 30% of original length were performed at a rate of 0.75 mm/day and rhythms of 1, 4, or 720 times per day using standard Ilizarov external fixation and an autodistractor system. Two additional animals underwent frame application and osteotomy without lengthening and served as osteotomy healing controls. Histomorphometric indices were measured at predetermined regions from undecalcified tibial specimens. Within the distraction region, bone formation and remodeling activity were location dependent. Intramembranous bone formed linearly oriented columns of interconnecting trabecular plates of woven and lamellar type bone. Total new bone volume and bone formation indices were significantly increased within the distraction and osteotomy callus regions (Tb.BV/TV, 226% [p < 0.05]; BFR/BS, 235-650% [p < 0.01]) respectively, compared with control metaphyseal bone. Bone formation indices were greatest adjacent to the mineralization zones at the center of the distraction gap; mineral apposition rate 96% (p < 0.01); mineralized bone surfaces 277% [p < 0.001]); osteoblast surfaces 359% [p < 0.001]); and bone formation rate (650% [p < 0.01]). There was no significant difference (p < 0.14; R = 0.4) in the bone formation rate of the distracted callus compared with the osteotomy control callus. Within the original cortices of the lengthened tibiae, bone remodeling indices were significantly increased compared with osteotomy controls; activation frequency (200% [p < 0.05]); osteoclast surfaces (295% [p < 0.01]); erosion period (75%); porosity (240% [p < 0.001]). Neither the rhythm of distraction nor the percent lengthening appeared to significantly influence any morphometric parameter evaluated. Distraction osteogenesis shares many features of normal fracture gap healing. The enhanced bone formation and remodeling appeared to result more from increased recruitment and activation of bone forming and resorbing cells rather than from an increased level of individual cellular activity.

In vitro strength comparison of hydroxyapatite cement and polymethylmethacrylate in subchondral defects in caprine femora.

Hydroxyapatite cement was investigated in situ for the reconstruction of juxta-articular defects. Polymethylmethacrylate is currently the most commonly used material for the reconstruction of bone defects following the exteriorization and curettage of aggressive benign tumors. In vitro, we compared the effects of hydroxyapatite cement and polymethylmethacrylate in restoring the stiffness of the subchondral plate in a caprine femoral defect model. Ten matched pairs of caprine femora underwent nondestructive compression testing normal to the load-bearing surface. A standardized subchondral defect 12 mm in diameter was created in the medial femoral condyle. Compression testing was repeated to determine the reduction in stiffness caused by the defect. Each femur from each pair was randomly assigned to one of two groups (n=9), and the defects were augmented with either polymethylmethacrylate or hydroxyapatite cement. After 12 hours, compression testing was repeated to determine the subchondral stiffness after augmentation. Compared with intact femora, the defect specimens that were later treated with either polymethylmethacrylate or hydroxyapatite cement exhibited stiffness values of 70 (386+/-107 N/mm) and 59% (343+/-94 N/mm) respectively, which represented a significant reduction in stiffness (p=0.05). Augmentation with polymethylmethacrylate or hydroxyapatite cement restored stiffness by 81 (450+/-111 N/mm) and 71% (413+/-115 N/mm), respectively, of the values of intact specimens. Hydroxyapatite cement restored stiffness significantly (p=0.05) over the stiffness of the nonaugmented defect compared with the stiffness after augmentation with polymethylmethacrylate (p=0.12). Neither polymethylmethacrylate nor hydroxyapatite cement restored stiffness to that of intact femora (p=0.05). In the current detect model, hydroxyapatite cement was comparable with polymethylmethacrylate in restoring subchondral stiffness. Unlike polymethylmethacrylate, however, hydroxyapatite cement has the following advantages: it is osteoconductive, is replaced by host bone, and avoids the potential for thermal necrosis. Hydroxyapatite cement may therefore provide a viable alternative to polymethylmethacrylate for augmentation of juxta-articular and other bone defects.

Effects of external fixation and limb lengthening on peripheral nerve function.

To identify factors affecting peripheral nerve function during limb lengthening, serial somatosensory evoked potentials studies were performed in 18 goats and correlated with gross appearance of the soft tissues at necropsy. In 15 goats, a 20% or 30% tibial lengthening was done using the Ilizarov apparatus at a rate of 0.75 mm per day and rhythm of 1, 4, or 720 times per day. Three animals served as frame/corticotomy controls. Seven lengthened and 2 control animals maintained normal somatosensory evoked potentials throughout the study. At necropsy, the peroneal and tibial nerves appeared grossly normal. In one control animal with irreversible loss of evoked potentials documented intraoperatively, peroneal nerve impalement by a transfixion wire was identified at necropsy. Eight lengthened animals experienced significant changes of peroneal nerve conduction. In 6 of these 8 animals, transfixion wires were found to be disrupting the nerve in some way. In the remaining 2 animals, no offending wires were identified, but there was extensive diffuse soft tissue fibrosis within the extremity. The rhythm of distraction did not have an important influence on evoked potential changes during the course of distraction. Although there was a correlation between the amount of lengthening performed and the degree of evoked potentials deterioration, the anatomic relationship between the wires and nerves was a more important factor in the development of these abnormalities.

Intraosseous infusion of prostaglandin E2 prevents disuse-induced bone loss in the tibia.

We investigated whether intraosseous injection of prostaglandin E2 would preserve tibial bone mass in the skeletally unloaded limb of a large animal model. Skeletal unloading of one rear limb was produced by unilateral Achilles tenectomy in the goat. Prostaglandin E2 was injected at 0.5 or 1.0 mg (1 ml of volume) twice daily, beginning on day 7 and continuing for 10 days, through an implant that had been surgically placed in the proximal tibial metaphysis. Thirty-five days after surgery, the tibiae were harvested for measurement of static and dynamic bone parameters and mechanical characteristics using transmission ultrasound. Prostaglandin E2 produced a dose-dependent increase in the formation of woven new bone at all bone envelopes. The 1.0 mg dosage prevented and partially reversed the effects of skeletal unloading and added new bone (p < 0.05) compared with the unloaded tibiae. Because prostaglandin E2 increased both bone formation and resorption and the new bone produced was primarily woven bone, the material properties of the tibiae infused with prostaglandin E2 did not increase significantly during the study compared with the unloaded and weight-bearing tibiae.

Effect of spinal construct stiffness on short segment fusion mass incorporation.

STUDY DESIGN: Three segment (L3-L5) pedicle screw constructs were implanted in caprine spines, and the resulting ankylosis evaluated mechanically and compared 12 weeks after surgery. OBJECTIVES: To determine if a construct of maximal stiffness could impair the biologic process of spinal arthrodesis by "stress-shielding." SUMMARY OF BACKGROUND DATA: Fusion mass stiffness is believed to be enhanced by increasing construct stiffness, although previous studies have used semirigid, nonconstrained constructs, which lose stiffness through cyclical loading. Device-related osteoporosis, reported to occur with stiff, constrained implants, may be more related to the presence of fusion induced by the implants rather than the implants themselves. METHODS: In 15 goats, L3-L5 segments were instrumented with pedicle screws, and four different diameters of rods (3.2 cm, 4.8 cm, 6.4 mm, and no rods) were implanted as longitudinal connections to vary the stiffness of the constructs. After 12 weeks, animals were killed and the segments were tested to determine their stiffness. RESULTS: In lateral bending, spines "fused" with rods (any size) were significantly stiffer (P = 0.03) than nonrodded spines. There was a trend toward stiffer segments with larger rods (4.8 cm or 6.4 mm) compared with 3.2 mm or no rods. There was a highly significant (P < 0.0001) increase in stiffness of all operated (rodded or nonrodded) segments compared with unoperated controls. CONCLUSIONS: The enhancement of segmental stiffness by stiffer constructs was confirmed, suggesting a beneficial effect on spinal arthrodesis by increasing stiffness. Stress shielding could not be shown.

Somatosensory evoked potential evaluation of acute nerve injury associated with external fixation procedures.

The effects of different mechanisms of acute nerve injury on peripheral nerve function during K wire application and 1 stage limb lengthening were evaluated prospectively in 24 goats using somatosensory evoked potentials. Stable somatosensory evoked potential recordings throughout 3-day experiments were obtained in animals with wires placed at a distance from or directly adjacent to a nerve but without producing any tension or pressure. Complete loss of the peroneal nerve somatosensory evoked potentials occurred if this nerve was perforated by wire, underwent excessive pressure by wire, or had been over-stretched due to acute 10% limb lengthening. Acute distraction resulted only in peroneal nerve dysfunction, while the tibial nerve was relatively unaffected. Although somatosensory evoked potential changes were not specific for the type of injury produced and the time of waveform disappearance varied, significant somatosensory evoked potential changes (> 50% amplitude reduction, > 10% latency delay or both) were seen within the first 15 minutes after injury in 90% of the cases. The somatosensory evoked potential changes did not reverse if the offending wire or distraction was left in place for the full duration of the experiment. Variable nerve conduction recovery was observed in all animals who had the insult removed immediately after the somatosensory evoked potentials disappearance. The greatest improvement occurred after discontinuation of nerve distraction. The worst somatosensory evoked potential waveform recovery was noted in animals with nerve perforation. Intraoperative somatosensory evoked potential monitoring proved to be a reliable and useful technique for earlier detection of acute nerve injury during external fixation procedures.

Upward fixation of the patella in cattle: 38 cases (1984-1990).

Case records of cattle admitted to 2 university veterinary hospitals during 6 years were evaluated to determine the age, breed, sex, and treatment of cattle with upward fixation of the patella. Affected cattle were compared with those from the respective hospital populations of cattle admitted during the same time. Of 38 cattle with upward fixation of the patella, 34 were treated surgically. Follow-up evaluation was obtained from owners of 28 of the treated cattle. Surgery was successful in eliminating all clinical signs in 25 of the 28 cattle. There was an increased risk of upward fixation of the patella associated with Brahman and Brahman-type cattle, compared with non-Brahman cattle.

Bone changes associated with intraosseous hypertension in the caprine tibia.

We investigated the effects of increased intraosseous pressure on new-bone formation in the proximal metaphysis of the caprine tibia. Intraosseous hypertension was produced by obstruction of venous outflow by ligation of the popliteal vein draining the proximal aspect of the tibia and occlusion of the medullary space with bone cement (groups 1 and 2). After the obstruction of venous outflow (day 0), the intraosseous pressure measured at the proximal tibial metaphysis increased significantly from a mean of 15.5 millimeters of mercury before the obstruction to a mean of 28.7 millimeters of mercury in groups 1 and 2. In group 1, obstruction of venous outflow was combined with intraosseous infusion of autogenous whole blood under pressure to maintain the intraosseous pressure between thirty and forty-five millimeters of mercury during days 0 through 5. The time for venous drainage was still prolonged and intraosseous pressures were still increased on days 5 and 10 (means, 26.8 and 26.2 millimeters of mercury, respectively) in groups 1 and 2. The intraosseous hypertension produced in group 1 was associated with a significant increase in periosteal (138 per cent), endocortical (369 per cent), and cancellous new-bone formation (889 per cent) at the tibial metaphysis compared with control values. Osseous necrosis within the metaphysis was not observed.