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Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars.

OBJECTIVE: To investigate induction of matrix metalloproteinases (MMPs) during mechanical compression of hypertrophic scars. Mechanical pressure blocks hypertrophy inducted on extracellular matrix in scars by a mechanism that involves MMP-2 (gelatinase A) and MMP-9 (gelatinase B). DESIGN: We assayed conditioned media obtained from normotrophic and hypertrophic scars during 24 hours of in vitro mechanical compression using gelatin zymography. SETTING: Scars from various areas of the bodies of hospitalized patients. PATIENTS: We obtained 3 normotrophic and 7 hypertrophic biopsy specimens from 10 patients (5 men and 5 women). INTERVENTION: In vitro compression at a pressure of 35 mm Hg/cm(2) for 24 hours. MAIN OUTCOME MEASURES: Vitality of scars was analyzed by means of lactic dehydrogenase test; medium samples were collected for zymographic analysis of MMP activity. RESULTS: We found MMP-2 in basal (uncompressed) samples from normotrophic and hypertrophic scars. Mechanical compression induced MMP-9 release and activation (range, 86.7%-78.7%) in hypertrophic scars after 4 hours. CONCLUSION: Production, release, and activation of MMP-9 in hypertrophic scars could be an effector mechanism responsible for hypertrophy regression induced by mechanical compression.

Adult↗

Predictive value of compression ultrasonography for deep vein thrombosis in symptomatic outpatients: clinical implications of the site of vein noncompressibility.

BACKGROUND: Compression ultrasonography has a high negative predictive value for deep vein thrombosis in symptomatic outpatients. Limited data are available on factors influencing positive predictive value. The objective of this study was to evaluate the positive predictive value of compression ultrasonography according to the anatomic site of vein noncompressibility. METHODS: We performed a prospective cohort study of 756 consecutive outpatients with suspected first-episode deep vein thrombosis. Compression ultrasonography was performed at the initial visit: results were abnormal if a noncompressible segment was identified or normal if all segments were fully compressible. Venography was performed in patients with abnormal compression ultrasonography results. Positive predictive value was determined according to the site of noncompressibility: common femoral vein only, popliteal vein only, or both sites. Venography was the reference standard for the presence of deep vein thrombosis. RESULTS: Positive predictive value was 16.7% (95% confidence interval, 0.4%-64.1%) for noncompressibility isolated to the common femoral vein compared with 91.3% (95% confidence interval, 72.0%-98.9%) for the popliteal vein only and 94.4% (95% confidence interval, 72.7%-99.9%) for both sites (P<.001). Of 15 patients with isolated noncompressibility of the common femoral vein, 8 (53%) had pelvic neoplasm or abscess compared with 2 (5%) of 42 with noncompressibility of the popliteal vein only and 6 (13%) of 47 with noncompressibility of both sites (P<.001). CONCLUSIONS: The positive predictive value of noncompressibility isolated to the common femoral vein is too low to be used alone as the diagnostic end point for giving anticoagulant therapy. Noncompressibility isolated to the common femoral vein is a diagnostic marker for pelvic disease.

Adult↗

Effects of supine intermittent compression on arterial inflow to the lower limb.

HYPOTHESIS: Intermittent pneumatic compression will affect the arterial blood flow in the lower limb at moderate pressure, without requiring dependency. DESIGN: Before-after trial. SETTING: Vascular ultrasound unit of a university hospital. PATIENTS: A volunteer sample of 19 healthy subjects without symptoms or history of vascular disease and 17 patients with peripheral arterial disease were studied. Six patients and 1 healthy volunteer were not included in the study group because of measurement difficulties or refusal when approached. INTERVENTIONS: Common femoral artery blood flow velocities were measured with Doppler ultrasound during 10 minutes of intermittent compression of the calf and thigh at 60 mm Hg, while the subject was supine. The data were collected every 5 seconds from 4 minutes before to 4 minutes after the therapy period, and toe temperatures were also measured with an infrared radiometer. MAIN OUTCOME MEASURES: Resting to postcompression percentage increases in flow velocity were measured, along with more representative measures of the total flow change during the intermittent compression period. RESULTS: On compression, the blood flow velocity decreased slightly (15% in healthy subjects and 6% in patients) and increased on release (21% and 29%, respectively). Overall, blood flow did not decrease during therapy as expected (increases of 1% and 2%, respectively), and the toes of the patients warmed (by 2.2 degrees C). CONCLUSIONS: This work confirms the initial hypothesis in both subject groups. There appears to be physiological justification for investigating intermittent compression as a therapy for patients with intermittent claudication and rest pain in the supine position as well as seated.

Adult↗

Ultrasound-guided compression repair for treatment of femoral artery pseudoaneurysm: acute and follow-up results.

Femoral artery pseudoaneurysm is a significant problem in patients undergoing arterial diagnostic or therapeutic catheterization. The aim of this investigation was to report the incidence of pseudoaneurysm after arterial catheterization and the success rate of ultra-sound-guided compression repair. During a 3-year period (11/91-11/94) 9,051 patients underwent 7,312 cardiac catheterizations and 1,739 peripheral percutaneous transluminal coronary angioplasty procedures. Patients suspect of pseudoaneurysm were referred for a color Doppler ultrasound examination. All patients with pseudoaneurysm were considered for ultrasound-guided compression repair. Pseudoaneurysm occurred more frequently after interventional procedures with new devices (valvuloplasty 2.3%, stent 3.2%) than after conventional catheterization diagnostic cardiac catheterization 0.2%, electrophysiology 1.3%, percutaneous transluminal coronary angioplasty 0.2%). The incidence of pseudoaneurysm after peripheral percutaneous coronary transluminal angioplasty, including intra-arterial lysis and stent, was 1%. Ultrasound-guided compression repair was successfully performed in 37 of 41 cases with pseudoaneurysm (90%). Ultrasound-guided compression repair was successfully performed in 30 of 31 patients (97%) without anticoagulation and in 7 of 10 patients (70%) receiving anticoagulants (P < 0.05). There was no correlation between mean diameter of the pseudoaneurysm, age of the lesion, or antiplatelet therapy. Color Doppler ultrasound re-examination at up to 3 months indicated successful treatment in all patients. The use of complex interventional catheterization procedures leads to an increased frequency of pseudoaneurysms compared with conventional angiography and percutaneous transluminal coronary angioplasty. Ultrasound-guided compression repair is a non-invasive, efficient, safe and cost-effective therapy for post-catheterization pseudoaneurysm.

Adult↗

Peripheral vascular complications after intracoronary stent placement: prevention by use of a pneumatic vascular compression device.

Peripheral vascular complications are a significant source of morbidity after coronary artery stent implantation. The goal of this study was to assess the incidence, risk factors, and management of vascular complications after stent placement. The study population consisted of 101 consecutive patients who underwent stent placement for either elective or bailout indications. All patients received a standardized anticoagulation regimen of aspirin, dipyridamole, low molecular weight dextran, heparin, and warfarin. Peripheral vascular access sites were examined daily until hospital discharge. Vascular complications occurred in 16 of 101 (16%) patients, including femoral artery pseudoaneurysm (n = 11), hematoma requiring transfusion or surgery (n = 4), and arteriovenous fistula (n = 1). Intervention was required in 14 of 16 (88%) patients with complications. These included transfusion (n = 7), ultrasound-guided compression (n = 8), and/or vascular surgery (n = 7). Length of hospital stay was prolonged in patients with complications (14 +/- 9 vs. 8 +/- 5 d, P < 0.001). The development of peripheral vascular complications did not correlate with clinical or procedural variables such as age, cardiovascular risk factors, arterial sheath size, or elective vs. bailout indication. After the introduction of a pneumatic vascular compression device (FEMOSTOP, C.A. Bard, Billerica, MA), a significant reduction in vascular complications was observed. Complications occurred in only 1 of 41 (2.4%) patients in whom the compression device was used in contrast to 13 of 58 (22.4%) patients compressed manually (P < 0.01). Thus peripheral vascular complications are frequent after coronary artery stent placement and are associated with serious morbidity and prolongation of hospital stay. These complications are significantly reduced by the use of a pneumatic vascular compression device despite intensive systemic anticoagulation.

Hemostasis, Surgical↗

Cervicobrachial disorders in certain occupations, with special reference to compression in the thoracic outlet.

One hundred ninety-one workers in three different occupations were examined regarding presence of symptoms from the cervicobrachial region. Eighteen percent of the workers (27% of the female and 11% of the male workers) had symptoms of compression in the thoracic outlet. However, only 2% of all workers had pronounced symptoms of compression in the thoracic outlet. In addition, 27% of the workers (33% of the female and 23% of the male workers) had symptoms of other cervicobrachial disorders. Thus, 45% of the workers had symptoms from the cervicobrachial region. The workers with symptoms of compression in the thoracic outlet were significantly younger than the workers with other symptoms of cervicobrachial disorders, p less than 0.01. No significant correlation was noted between vascular compression and symptoms of compression in the thoracic outlet.

Adult↗

Regional blood flow in compression-induced brain edema in rats: effect of dietary vitamin E.

Regional cerebral blood flow (rCBF) was studied autoradiographically in a murine model of focal epidural brain compression, and the effect of vitamin E administration was investigated. Mean cortical CBF was reduced to 0.48 to 0.50 ml/gm/min following 2 or 24 hours of compression. Early (2 hours) following subsequent decompression, a mixed pattern of hypoperfusion and hyperperfusion was observed. Twenty-four hours later, rCBF heterogeneities were less marked. Comparisons among animal groups raised on vitamin E-supplemented, vitamin E-normal, and vitamin E-deficient diets 2 hours after decompression revealed marked reductions in rCBF in the previously compressed cortex of the last two groups and hyperemia of the underlying hippocampus. The vitamin E-supplemented rats showed increased flow in the previously compressed cortex. In addition, vitamin E supplementation tended to eliminate rCBF gradients between subjacent zones. These data may help explain our previous observations of the beneficial effects of vitamin E on compression-induced brain edema.

Animals↗

Effect of 'antiembolism' compression hosiery on leg blood volume.

Blood volume in the legs of healthy volunteers and the ability of graduated compression hosiery to reduce that volume were investigated with gamma scintigraphy. Changing posture from supine to upright, or pneumatic thigh cuffs inflated to either 20 or 40 mmHg with the subject supine, significantly increased leg blood volumes; the mean increase was: upright 126 ml, 20 mmHg cuff 44 ml, and 40 mmHg cuff 113 ml. A significant trend in reducing these volumes was noted in three brands of commercially available stockings, with the subject supine and without thigh cuffs (Page's L trend 132.5, P < 0.01) and when cuffs were applied at 20 mmHg (Page's L trend 128, P = 0.05). Few of the commercially available stockings delivered the 'standard' compression profile of 18 mmHg at the ankle, 14 mmHg at the calf and 8 mmHg at the upper thigh. The effects of other compression profiles were assessed, using custom-made stockings, and pneumatic cuffs inflated to 20 mmHg applied to the upper thighs to impede venous return. There was no consistent reduction of blood volume in the popliteal region, although decreases were seen in the upper and lower calf. The major determinant of performance was compression at the calf; the ankle to calf compression gradient was not important. Stockings with a profile of 16.8 mmHg at the ankle, 14.5 mmHg at the calf and 6.4 mmHg at the upper thigh performed best.

Adult↗

Thrombin injection for treatment of false aneurysms after failed compression therapy in patients on full-dose antiplatelet and heparin therapy.

The aim of this study was to gauge the effectiveness of thrombin injection after failed manual compression in patients with false aneurysms receiving full-dose antiplatelet and heparin therapy. In consecutive patients with failed manual compression therapy (ultrasound-guided manual compression, compression bandage, or both), thrombin was injected under ultrasound guidance. In 23 patients, thrombin was injected into the false aneurysm (100-2,000 units; mean, 895 +/- 520 units). All patients were on aspirin (median dose, 100 mg/day), clopidogrel (median dose, 75 mg/day), and either heparin (n = 3) with a partial thromboplastin time (PTT) > 55 sec or weight-adjusted enoxaparine (0.1 ml per 10 kg; maximum, 1 ml/b.i.d.). Twelve patients had received an i.v. GB IIIb/IIa antagonist 11-72 hr prior to diagnosis of the aneurysm. The mean width of the false aneurysms was 20.8 +/- 3.2 mm (range, 8.0-52.0 mm), length 29.7 +/- 32.6 mm (range, 9.0-147 mm), and depth 19 +/- 9.1 mm (range, 5.1-35.5 mm). Thrombosis after thrombin injection occurred in 21 patients within seconds. One patient required a second injection the next day, one patient underwent surgery. Overall success rate was 96%. No in-hospital complications occurred. In patients with false aneurysms and failed compression therapy under full-dose aspirin, clopidogrel, and heparin, selective thrombin injection is highly effective and safe.

Aged↗

Effect of compressive loading and unloading on the synthesis of total protein, proteoglycan, and fibronectin by canine cartilage explants.

Full-thickness canine articular cartilage explants were subjected to compressive loads equivalent to a uniaxial stress of 0.025-1.2 MPa. A single cycle (18 h) of unconfined compression resulted in inhibition of total protein, proteoglycan, and fibronectin synthesis. The inhibition of fibronectin synthesis followed that of total protein synthesis. The magnitude of inhibition increased nonlinearly with increasing load levels. The signal that depressed synthesis remained effective for several hours after removal of load, but by 24 h proteoglycan synthesis had partially recovered and fibronectin and protein synthesis had fully recovered and sometimes exceeded the rate of synthesis in free-swelling controls. Forty-eight hours after five cycles of intermittent unconfined compression with similar loads, proteoglycan content and synthesis did not differ in loaded disks and in disks that were never loaded in vitro. Interestingly, the percentage of water in disks that had never been loaded in vitro increased significantly after 10 days in culture, relative to the percentage of water in free-swelling disks on the day of harvest. Intermittent compressive loading in the range of 0.5-1.2 MPa partially prevented this increase. Our results confirmed the previously reported inhibition of biosynthesis with static loading but also suggested that exposure to intermittent compressive loading may help to maintain the normal ratio of dry to wet weight in the explant.

Animals↗

Compressive stress-relaxation behavior of bovine growth plate may be described by the nonlinear biphasic theory.

The compressive behavior of the bovine distal femoral growth plate was studied in vitro. Strain-rate controlled, compression stress-relaxation experiments were performed on cylindrical bone-growth plate-bone specimens from the interior and periphery of the growth plate. The questions addressed in this study were (a) Can the nonlinear biphasic theory, one with strain-dependent permeability, be used to represent the compressive stress-relaxation behavior of bovine growth plate? (b) How do different assumptions concerning the permeabilities of the chondro-osseous interfaces influence the inferred material properties of the growth plate? and (c) Are there any differences in these properties between the periphery and the interior of the growth plate? Intrinsic biphasic material properties--aggregate modulus (HA), Poisson's ratio (v), and nonlinear strain-dependent permeability coefficients (ko and M)--were calculated from the compression stress-relaxation data with use of a finite element model and a least squares curve-fitting procedure. To verify this constitutive model for the growth plate, an independent set of finite element analyses was performed with use of the determined intrinsic biphasic properties, and comparisons were made between these finite element predictions and two additional sets of experimental data subsequently obtained for the same specimens with use of two slower rates of compression. Excellent agreement was achieved between these finite element predictions and the latter two sets of data. The aggregate modulus was found to be insensitive to the permeability of the chondro-osseous interface. The permeability coefficients were very sensitive to, and the Poisson's ratio was only slightly sensitive to the interface permeability condition. Therefore, the periphery of the growth plate is more compliant and permeable than the interior.

Animals↗

Effect of combined axial compressive and anterior tibial loads on in situ forces in the anterior cruciate ligament: a porcine study.

This study investigated the impact of a combination of axial compressive and anterior-posterior tibial loads on the in situ forces in the anterior cruciate ligament. An axial compressive load is believed to contribute to increased stability of the knee joint; however, its effect on in situ forces in the anterior cruciate ligament has not been clearly defined, to our knowledge. It was hypothesized that the application of an axial compressive load, when combined with an anterior tibial load, would result in larger in situ forces in the anterior cruciate ligament than those caused by an isolated anterior tibial load. With use of a porcine knee model, the results confirmed this hypothesis; the addition of a 200 N axial compressive load to a 100 N anterior tibial load increased knee stability by reducing anterior-posterior tibial translation and internal-external tibial rotation and also caused a significant increase in in situ forces in the anterior cruciate ligament (p < 0.05). Specifically, there was a 34% increase in the in situ force at 30 degrees of flexion, a 68% increase at 60 degrees of flexion, and an 84% increase at 90 degrees of flexion compared with those for an isolated anterior tibial load of 100 N. Additionally, there was a statistically significant increase of the in situ forces in the anterior cruciate ligament at 60 and 90 degrees as compared with those at 30 degrees. These results suggest that axial compressive loads on the knee may play a role in injury of the anterior cruciate ligament when the knee is flexed.

Animals↗

Stabilized compressed nitroglycerin tablets.

A stabilized compressed nitroglycerin tablet, containing microocrystalline cellulose NF and providone NF as stabilizing agents, was formulated. Bioavailability and physical tests were conducted on the compressed tablet and two leading brands of molded tablets. There was no difference in the mean pulse rate between a molded tablet formulation and the compressed tablet in a crossover study using 10 human volunteers and three tablet strengths, 0.3, 0.4, and 0.6 mg. The compressed tablet was most uniform when tested according to the USP method for weight variation and content uniformity. Various tests for nitroglycerin loss due to volatility, i.e., open dish test, thermogravimetric analysis, and simulated in-use test, all indicated that the stabilized compressed tablet was substantially more stable than partially stabilized or unstabilized molded tablets.

Adult↗

Bioavailability of sulfadiazine in rabbits using tablets prepared by direct compression and fluidized-bed granulation.

Experimental sulfadiazine tablets prepared by direct compression, using a commercially available direct compression tablet mass, were compared with experimental sulfadiazine tablets prepared by fluidized-bed granulation and commercially available sulfadiazine tablets USP. The values for friability and the time required to release 10 and 50% of the direct compression tablets were between those of the fluidized-bed tablets and the commercial product. With the commercial tablet as a standard, the extent of bioavailability was determined in rabbits; it was slightly higher for both the direct compression and fluidized-bed tablets. A statistically significant difference was found between the direct compression tablets and the standard with respect to the extent of bioavailability and the time of the peak.

Animals↗

Effects of compression force, particle size, and lubricants on dissolution rate.

The effects of compression force, particle size, and lubricant concentration on the dissolution rates of compressed disks of salicylic acid, aspirin, and an equimolar mixture of aspirin and salicylic acid were investigated. Compression forces from 450 to 9100 kg had no effect on dissolution rates. With 5% starch incorporated into an equimolar mixture of aspirin and salicylic acid, the dissolution rates were independent of compression forces from 910 to 9100 kg. A 10-fold change of particle size of the materials being compressed did not affect the dissolution rates. An increase in the concentration from 0.1 to 5% of calcium stearate, glyceryl monostearate, magnesium stearate, and stearic acid progressively slowed the dissolution rate. An increase in the concentration from 0.1 to 5% talc and polyethylene glycol 4000 did not affect the dissolution rates. An increase in the concentration of starch from 0.1 to 5% progressively increased the dissolution rates.

Aspirin↗

Sodium multiple quantum spectroscopy of articular cartilage: effects of mechanical compression.

The effects of mechanical compression on the multiple quantum coherences generated from sodium ions in articular cartilage were investigated. Cartilage samples obtained from bovine patellae were studied during compression at 0.7 MPa (100 psi) for 1 hour. The double quantum filtered spectra showed marked lineshape changes in the compressed samples. Compression did not seem to influence the lineshapes of the single quantum and triple quantum filtered spectra significantly. We found that the residual quadrupolar interaction was reduced in the compressed samples. Changes in the ordering of collagen fibers may be responsible for the observed effect.

Animals↗

Chondrocyte extracellular matrix synthesis and turnover are influenced by static compression in a new alginate disk culture system.

The goal of this study was to examine the effects of mechanical compression on chondrocyte biosynthesis of extracellular matrix (ECM) components during culture in a new alginate disk culture system. Specifically, we have examined chondrocyte biosynthesis rates, and the structure of aggrecan core protein species present in the cell-associated matrix (CM), in the further removed matrix (FRM) and in the surrounding culture medium. In this alginate disk culture system, chondrocytes can be subjected to mechanical deformations similar to those experienced in vivo. Our results show that over an 8-week culture period, chondrocytes synthesize a functional ECM and can respond to mechanical forces similarly to chondrocytes maintained in native cartilage. In the alginate disk system, static compression was shown to decrease and dynamic compression to increase synthesis of aggrecan of bovine chondrocytes. Western blot analysis of the core proteins of aggrecan molecules identified a number of different species that were present in different relative amounts in the CM, FRM, and medium. Over 21 days of culture, the predominant form of aggrecan found in the ECM was a full-length link-stabilized species. In addition, our data show that the application of 40 h of static compression caused an increase in the proportion of newly synthesized aggrecan molecules released into the medium. However, this was not accompanied by a significant change in the size and composition of aggrecan and aggrecan fragments in the different compartments, suggesting that mechanical compression did not alter the catabolic pathways. Together, these data show that chondrocyte function is maintained in an alginate disk culture system and that this culture system is a useful model to examine chondrocyte ECM assembly and some aspects of catabolism normally found in vivo.

Aggrecans↗

Dynamic compression inhibits the synthesis of nitric oxide and PGE(2) by IL-1beta-stimulated chondrocytes cultured in agarose constructs.

Both mechanical loading and interleukin-1beta (IL-1beta) are known to regulate metabolic processes in articular cartilage through pathways mediated by nitric oxide ((*)NO) and PGE(2). This study uses a well-characterized model system involving isolated chondrocytes cultured in agarose constructs to test the hypothesis that dynamic compression alters the synthesis of (*)NO and PGE(2) by IL-1beta-stimulated articular chondrocytes. The data presented demonstrate for the first time that dynamic compression counteracts the effects of IL-1beta on articular chondrocytes by suppressing both (*)NO and PGE(2) synthesis. Inhibitor experiments indicated that the dynamic compression-induced inhibition of PGE(2) synthesis and stimulation of proteoglycan synthesis were (*)NO mediated, while compression-induced stimulation of cell proliferation was (*)NO independent. The inhibition of (*)NO and PGE(2) by dynamic compression is a finding of major significance that could contribute to the development of novel strategies for the treatment of cartilage-degenerative disorders.

Animals↗