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The effect of chitosan bead encapsulating calcium sulfate as an injectable bone substitute on consolidation in the mandibular distraction osteogenesis of a dog model.

PURPOSE: The purpose of this project was to study the effect of chitosan bead encapsulating calcium sulfate, which provides a sustained release of chitosan and calcium sulfate after implantation, on early bony consolidation in distraction osteogenesis of a dog model. MATERIALS AND METHODS: Forty-five dogs were used for this study. An external distraction device was applied to the mandibular body after a vertical osteotomy and mandibular distraction was initiated 5 days after the operation at a rate of 1 mm/day up to a 10-mm distraction. The experimental group was divided into a control group (I), hyaluronic acid group (II), chitosan group (III), calcium sulfate group (IV), and chitosan bead encapsulating calcium sulfate group (V). Normal saline was injected in group I. In group II, 1 mL of hyaluronic acid solution was injected into the distracted region. In group III, 1 mL of injectable solution of chitosan mixed with hyaluronic acid was implanted. In group IV, 1 mL of injectable solution of calcium sulfate mixed with hyaluronic acid was implanted. In group V, an injectable form of powdered chitosan bead encapsulating calcium sulfate mixed with 1 mL volume of hyaluronic acid was implanted. RESULTS: Bone mineral density was 12% of the contralateral normal mandible at 3 weeks, 23.4% at 6 weeks in group I, 15% at 3 weeks, 29.1% at 6 weeks in group II, 16% at 3 weeks and 32% at 6 weeks in group III, 30.4% at 3 weeks and 52.8% at 6 weeks in group IV, and 33.6% at 3 weeks and 55% at 6 weeks in group V with statistical significance (P < .005). The mean 3-point failure load was compared with the intact contralateral mandible and noted to be 12% in the control group, 16% in group II, 18% in group III, 34.3% in group IV, and 31.7% in group V. Difference of mean percentages between one group and another was statistically significant (P < .005). In the histologic findings, new bone was generated in all groups. In groups IV and V, the formation of active woven bone was observed throughout the distracted region at 6 weeks. The amount of new bone formation in the distracted zone was in the order of group IV and V, III and II, and the control group. CONCLUSIONS: These findings suggest that chitosan bead encapsulating calcium sulfate appears to facilitate early bony consolidation in distraction osteogenesis.

Analysis of Variance↗

The use of a retrievable self-expanding stent in treating childhood benign esophageal strictures.

BACKGROUND/PURPOSE: Esophageal stenting is a popular form of treatment of esophageal strictures in adults but is not widely used in children. The aim of the current study was to investigate whether esophageal stents could be used safely and effectively in the treatment of esophageal stenosis in children. METHODS: Covered retrievable expandable nitinol stents were placed in 8 children with corrosive esophageal stenosis. The stents were removed 1 to 4 weeks after insertion. RESULTS: The stents were placed in all patients without complications and were later removed successfully. After stent placement, all patients could take solid food without dysphagia. Stent migration occurred in one patient and so the insertion procedure was repeated to reposition the stent. During the 3-month follow-up period after stent removal, all children could eat satisfactorily. After 6 months, 2 children required balloon dilation (3 times in one and 5 times in the other). The dysphagia score improved in all patients. CONCLUSIONS: The use of the covered retrievable expandable stent is an effective and safe method in treating childhood corrosive esophageal stenosis.

Alloys↗

The N-terminal substrate-binding domain of ClpA unfoldase is highly mobile and extends axially from the distal surface of ClpAP protease.

ClpAP is a barrel-like complex consisting of hexameric rings of the ClpA ATPase stacked on the double heptameric ring of ClpP peptidase. ClpA has two AAA+ domains (Dl and D2) and a 153-residue N-domain. Substrate proteins bind to the distal surface of ClpA and are unfolded and translocated axially into ClpP. To gain insight into the functional architecture of ClpA in the ATPgammaS state, we have determined its structure at 12A resolution by cryo-electron microscopy. The resulting model has two tiers, corresponding to rings of Dl and D2 domains: oddly, there is no sign of the N-domains in the density map. However, they were detected as faint diffuse density distal to the Dl tier in a difference image between wild-type ClpAP and a mutant lacking the N-domain. This region is also accentuated in a variance map of ClpAP and in a difference imaging experiment with ClpAP complexed with ClpS, a 12kDa protein that binds to the N-domain. These observations demonstrate that the N-domains are highly mobile. From molecular modeling, we identify their median position and estimate that they undergo fluctuations of at least 30A. We discuss the implications of these observations for the role of N-domains in substrate binding: either they effect an initial transient binding, relaying substrate to a second site on the Dl tier where unfolding ensues, or they may serve as an entropic brush to clear the latter site of non-specifically bound ligands or substrates bound in non-productive complexes.

Binding Sites↗

A link between sequence conservation and domain motion within the AAA+ family.

The AAA+ family of proteins play fundamental roles in all three kingdoms of life. It is thought that they act as molecular chaperones in aiding the assembly or disassembly of proteins or protein complexes. Recent structural studies on a number of AAA+ family proteins have revealed that they share similar structural elements. These structures provide a possible link between nucleotide binding/hydrolysis and the conformational changes which are then amplified to generate mechanical forces for their specific functions. However, from these individual studies it is far from clear whether AAA+ proteins in general share properties in terms of nucleotide induced conformational changes. In this study, we analyze sequence conservation within the AAA+ family and identify two subfamilies, each with a distinct conserved linker sequence that may transfer conformational changes upon ATP binding/release to movements between subdomains and attached domains. To investigate the relation of these linker sequences to conformational changes, molecular dynamics (MD) simulations on X-ray structures of AAA+ proteins from each subfamily have been performed. These simulations show differences in both the N-linker peptide, subdomain motion, and cooperativity between elements of quaternary structure. Extrapolation of subdomain movements from one MD simulation enables us to produce a structure in close agreement with cryo-EM experiments.

Adenosine Triphosphatases↗

High flexibility of the actomyosin crossbridge resides in skeletal muscle myosin subfragment-2 as demonstrated by a new single molecule assay.

Popular views of force generation in muscle indicate that a lever arm in the myosin head initiates displacement of the thin filament. However, this lever arm is attached to the thick filament backbone by a flexible combination of coiled coils and hinges in the myosin subfragment-2 (S2); therefore, efficient force generation depends on tension development in this linking structure. Herein, a single molecule assay is developed to examine the flexibility of the intact S2 relative to that of the myosin head. Fluorescently labeled myosin rod is polymerized onto a single myosin molecule that is bound to actin, and the resulting Brownian motion of the rod is analyzed at video rates by digital image processing. Complete rotations of the rod suggest significant amounts of random coil in the linking structure. The close similarity of twist rates for double-headed and single-headed myosin indicates that most of the flexibility originates at or beyond the first pitch of coiled coil in S2 and most likely at the hinge connecting S2 and the light meromyosin. The myosin head has a smaller but still detectable impact on this flexibility, since the addition of ADP to the rigor crossbridge produces differential effects on the torsional characteristics of double-headed versus single-headed myosin.

Actins↗

Loss of flexion after radial head replacement.

Prosthetic radial head replacement is a well-documented procedure; however, loss of elbow flexion after radial head arthroplasty has only recently been reported. This study reviews 6 patients who received modular prosthetic radial heads and had a clinically significant decrease in elbow flexion. The implant was removed in 4 of these patients because of reduced elbow motion and pain. This clinical finding is correlated with biomechanical data obtained by use of matched-pair, fresh-frozen upper extremity specimens loaded to 330 N with the forearm in positions of neutral, pronation, and supination for each of three elbow positions (0 degrees, 90 degrees, and 135 degrees). The radiocapitellar gap was monitored and was significantly smaller under load during elbow flexion compared with extension. This study indicates the need for verification of the radiocapitellar gap throughout elbow range of motion in order to prevent these complications.

Arthroplasty, Replacement↗

Interface pressure and stiffness of ready made compression stockings: comparison of in vivo and in vitro measurements.

OBJECTIVE: It is unknown if the pressure values of compression stockings indicated by the producers correspond to the actual compression pressure exerted in vivo. This study compared pressure and stiffness of ready-made compression stockings (Venosan) of different classes, measured on the leg and by laboratory testing. METHODS: This was an experimental study conducted in a textile laboratory of a company that manufactures compression stockings. Twelve legs from healthy volunteers were fitted with ready-made calf-length compression stockings of the European classes I, II and III. In addition, two class I stockings were applied over each other. The in vivo interface pressure was measured using the medical stocking tester (MST) in position B1, eight cm proximal to the inner ankle. Stiffness was defined by an increase of pressure due to an increase of stretch that reflects the elastic property of the textile and was assessed by measuring the difference of interface pressure between standing and supine position at B1. In the laboratory, the MST was used to check the pressure of these stockings on wooden leg models. Then circular slices were cut out from the stockings at the B1 level and stretched by a Zwick dynamometer in the transverse direction. Force/extension-curves were plotted, from which the pressure and stiffness of each individual stocking was calculated. RESULTS: The pressure profile measured on four positions along the leg by MST showed a degressive gradient on the wooden model but not on the human leg due to the measuring geometry in the ankle region. Pressure values on the leg correspond to the in vitro measurements calculated from the force/extension-curve with a bias (difference of the means) of -2.1 and 4.1 mm Hg. In 95% of the subjects, the difference was between -10.1 and 5.8 mm Hg (Bland Altman plot). The correlation between in vivo and in vitro measurement was highly significant (P < .0001, Spearman correlation coefficient; r = .8161). In vivo and in vitro measurement shows an increase of stiffness with increasing compression classes. The highest values are found for two class I stockings applied over each other. CONCLUSION: Pressure and stiffness can be measured in vivo, correlate well with laboratory findings, and should be used in future studies, especially when different compression devices are to be compared.

Adult↗

Arthrofibrosis following total knee replacement; does therapeutic warfarin make a difference?

Arthrofibrosis following total knee replacement (TKR) is a relatively common complication which results in a reduction in knee range of movement and patient dissatisfaction. A retrospective study examined the relationship between anticoagulation with therapeutic warfarin and rates of arthrofibrosis following TKR. Arthrofibrosis was defined as less than 80 degrees of knee flexion 6-8 weeks post-TKR. Patients were warfarinised if they had a history of thrombophilic tendencies or medical conditions necessitating anti-coagulation, rather than as routine thromboprophylaxis. All other patients received thromboprophylaxis using low molecular weight heparin. A total of 728 patients underwent 874 primary TKR between 1993 and 2002 in one centre, performed by four surgeons. Mean age was 68 years (range 48-89 years) and there were 483 female and 391 male knees. Eighty cases were warfarinised post-operatively (53 female, 27 male). Overall, 83 of 874 TKRs (9%) had arthrofibrosis (57 female, 26 male) requiring manipulation under anaesthetic (MUA). In the warfarinised group, 21 knees (26%) had an MUA (15 female, 6 male). This compared to 62 cases (8%) requiring MUA in the non-warfarinised group (42 female, 20 male). There was a statistically significant difference on Fisher's exact testing (P<0.0001) between groups. Following MUA, knee flexion improved in 95% cases to a minimum 95 degrees but 8 cases had a fixed flexion deformity of 5-10 degrees . In conclusion, therapeutic warfarinisation post-TKR leads to a statistically greater chance of the patient developing arthrofibrosis compared to prophylactic low molecular weight heparin and that patients should be counseled appropriately.

Aged↗

Accuracy of implantation of components in the Oxford knee using the minimally invasive approach.

Screened postoperative X-rays of 224 Oxford knees implanted through the minimally invasive approach were analysed using 16 criteria. The technique was as recommended by the Oxford Group except that the femoral intramedullary rod was used only as a guide to flexion/extension of the femoral component. All femoral components were within the recommended range for varus/valgus and mediolateral position. Eighteen femoral components were either too flexed or extended, but by a maximum of only 10 degrees . Tibial components were inserted in slight varus (mean 1.8 degrees , S.D. 8.8, range 10 to -10). All were within the range for posterior slope in spite of difficulty in establishing objective landmarks. Tibial coverage was imprecise with the phase 3 implants which were short and broad relative to the cut surface. In 36% of knees the tibial tray was implanted too anterior resulting in posterior under hang. There have been no clinical signs to indicate tipping of the meniscus in deep flexion. The depth of cement penetration under the keel was excessive in three cases, resulting from porotic bone rather than technical error in the depth of the cut. There has been one case of femoral component loosening following a fall and no tibial loosening in spite of imprecise alignment of some components.

Arthrography↗

Reconstruction of the anterior cruciate ligament with a patella-tendon-bone graft may lead to a permanent loss of bone mineral content due to decreased patellar tendon stiffness.

Immobilisation induces bone loss. Evidence from studies in animals and healthy humans that were immobilised for a limited time indicates that, in general, bone mass may be restored even in adults. Following conservative management of partial tears of the anterior cruciate ligament (ACL), bone loss is often negligible (2-3%). After surgical reconstruction, however, there is greater bone loss (15-20%), with little or no recovery. Bones adapt to the stresses they experience. Also, the largest forces in the musculoskeletal system arise from muscle pull. Tendons transmit these forces. Many surgical techniques for ACL reconstruction use autologous tendon grafts. We hypothesise that tissue harvesting causes weakening of the formerly intact tendon, which, in turn, leads to reduced muscle pull and subsequent bone loss in those parts of the bone that are loaded by the tendon. If our hypothesis holds true, it may change patients' and surgeons' choice of management. Clinical follow-up should assess the functional result with greater scrutiny, possibly including the assessment of bone mineral content. This may be particularly important since there is accumulating evidence that a decrease in bone mineral density (BMD) preceedes, and hence may be a cause of, osteoarthritis.

Animals↗

A mechanistic model for the aging of human skin.

The microinflammatory model of skin aging is described. This model accounts for the loss of elasticity, resiliene and flexibility of the dermis, as well as for the appearance of wrinkles and for the thinning of the epidermis which are associated with aging. The lack of appropriate apparatuses for the correct measurements of skin hydration does not allow one to test this model for its predictive capability of the appearance of dry skin with age. The micro-inflammatory model of skin aging fails to predict the appearance of age spots on the surface of the skin.

Dermatitis↗

Postural sway increase in low back pain subjects is not related to reduced spine range of motion.

This study questioned whether postural sway increase in low back pain subjects was related to impaired spine mobility, and especially to a decrease in the range of motion, which was assumed to represent structural spine stiffness. Ten low back pain subjects and ten healthy control subjects performed spine flexion-extension and spine side bending tests, and standing posturographic examination in different experimental conditions. Low back pain subjects showed increased postural sway along the antero-posterior axis and reduced side bending, i.e. posturographic and range of motion parameters varied in the opposite direction. Moreover, no correlation was found between these two types of parameters. Although significant, the slight decrease in spine side bending did not seem sufficiently great to disturb the low amplitude movements that maintain postural equilibrium. Hence, it was concluded that postural sway increase in low back pain is not related to a reduced spine range of motion, but might be linked to an increase in muscular active tension, which reduces dynamic mobility capacity.

Adult↗

The influence of cyclic compression and distraction on the healing of experimental tibial fractures.

Interfragmentary displacement has a main effect on callus formation in fracture healing. To test whether compressive or distractive displacements have a more pronounced effect on new bone formation, a sheep osteotomy model was created whereby the gap tissue was subjected to constant bending displacement. A diaphyseal osteotomy with a gap of 2 mm was created in 18 sheep tibiae and stabilized with a special unilateral actuator-driven external fixator. Two experimental groups with six sheep each received either 10 or 1000 cycles evenly distributed over 24 h. The third group of six sheep served as a control group without actively induced displacement. The amount and direction of cyclic displacement was kept constant throughout the observation period, resulting in 50% compressive and 50% distractive displacement within the osteotomy gap. At sacrifice, six weeks after surgery, bending stiffness was measured and new bone formation was assessed radiologically and microradiographically. In all cycled groups, the amount of periosteal callus formation was up to 25 times greater on the compression compared to the distraction side (p < 0.001). The application of the higher number of daily cycles resulted in an up to 10-fold greater amount of periosteal new bone formation on the compression side (p < 0.012), while the difference on the distraction side was not significant. Ten cycles applied a day were sufficient to create an abundant periosteal callus on the compression side. In the 1000 cycle group, bending stiffness revealed slightly lower values but the difference was not significant. Solid periosteal bridging of the gap was observed in two sheep in the control group, whereas bridging in the cycled groups was observed exclusively at the medullary side. In conclusion, cyclic compressive displacements were found to be superior over distractive displacements. A higher number of enforced and maintained compressive displacements enhanced periosteal callus formation but did not allow bony bridging of the gap.

Animals↗

Consequences of increased rigidity in palatal implants for snoring: a randomized controlled study.

OBJECTIVE: Palatal implants have seen an increased role in the treatment of snoring. In this study, we evaluate the safety and possible treatment effect of adding further stiffness to the palate through the use of a more rigid implant. STUDY DESIGN: Randomized double-blind study of 20 patients with primary snoring. Three polyethylene teralphate implants were placed in the soft palate with the patient under local anesthesia. Ten patients received regular implants (rigidity 1.0) and 10 patients received stiffer implants (rigidity 1.8). The patients and their bed partners were followed for 6 months with questionnaires and office visits. A sleep study was performed preoperatively and at the last follow-up. RESULTS: Four of the 10 patients with stiffer implants had 5 partial extrusions in the observation period. There was a nonsignificant reduction in snoring intensity from 8.1 to 6.1 evaluated by the bed partner on a visual analogue scale in this group. No extrusions were seen in the group with regular implants. This group showed a significant reduction in snoring intensity from 7.7 to 4.7. No other major adverse events were observed. CONCLUSIONS AND SIGNIFICANCE: Rigid implants cause short time extrusions with loss of treatment effect. Regular implants reduce palatal snoring intensity with high patient and bed partner satisfaction. EBM RATING: A-1b.

Adult↗

Impact of electrode insertion depth on intracochlear trauma.

OBJECTIVE: To assess the effect of cochlear implant (CI) insertion depth and surgical technique on intracochlear trauma. STUDY DESIGN AND SETTING: Twenty-one fresh human temporal bones were implanted with CI electrodes and underwent histologic processing and evaluation. Specimens were grouped into 3 categories: 1) soft implantation technique and standard electrode; 2) soft implantation technique and flexible prototype array; 3) forceful implantations and standard electrode. Based on the grading system (1 to 4), 2 numeric values were calculated indicating the overall severity of cochlear damage (trauma indices). RESULTS: Mean trauma index values were 13.8, 36.3, and 59.2 for group 1, 2, and 3, respectively. Differences in cochlear trauma (trauma index) were nonsignificant between specimens in groups 1 and 2 but were significant between groups 1 and 3. CONCLUSION: This study gives evidence that intracochlear trauma increases with deep insertions. Thus, in cases where cochlear integrity might be important, limited insertions should be achieved.

Alloys↗

Popliteal angle of low birth weight infants during the first year of life.

The aim of this study is to clarify the evolutional changes of the popliteal angle in low birth weight infants during the first year of life. The popliteal angle was measured at 1, 4, 8, and 12 months of corrected age on routine physical examination of 204 appropriate-for-date infants who had achieved normal psychomotor development. The popliteal angle was visually determined and categorized into two groups; tight, when it was 120 degrees or less, and wide, when it was more than 120 degrees. The infants were divided into five groups according to their birth weights; Group E, birth weight or=2500 gm. At 4 months of corrected age, the rate of a tight popliteal angle was significantly higher in Groups E + V + L1 than in Groups L2 + N. A tight popliteal angle was rare in all groups at 8 or 12 months of age. The results of this study indicate that the physiologic muscle tone of lower extremities is higher in infants with birth weights of <2000 gm at 4 months of corrected age. One should carefully interpret a tight popliteal angle in low birth weight infants during early infancy. Serial assessment of the popliteal angle is necessary before judging that a low birth weight infant has spastic cerebral palsy.

Biological Evolution↗

The influence of the veneering porcelain and different surface treatments on the biaxial flexural strength of a heat-pressed ceramic.

STATEMENT OF PROBLEM: The strength of all-ceramic restorations can be adversely affected by surface defects, leading to restoration failures. Additionally, when a 2-layer all-ceramic restoration is required for esthetic purposes, part of the stronger ceramic core material is replaced by veneering porcelain. PURPOSE: This study evaluated the effect of different surface treatments on the strength of a ceramic core material and veneering porcelain, as well as the influence of veneering porcelain on the strength of a 2-layer ceramic structure. MATERIAL AND METHODS: Fifty heat-pressed ceramic cores and 30 veneering porcelain discs (17 mm diameter x 2 mm) were made. From the ceramic core group, 20 discs were selected and reduced to a thickness of 1 mm and veneered with 1 mm of porcelain. These specimens were divided into 2 groups of 10 each. The remaining 30 ceramic core and the 30 veneering porcelain discs were divided into 2 sets of 3 equal sized groups (n=10). Ceramic core groups were prepared for testing having the following surfaces: airborne-particle abrasion, ground, and overglazed. Veneering porcelain groups were tested: as fired (no additional treatment), ground, and overglazed. Biaxial flexural strength was measured using the ball-on-ring test method. All specimens were loaded to fracture. One and 2-way analysis of variance were used to analyze the data (alpha=.05). RESULTS: The ceramic core discs were significantly (P=.001) stronger than the veneering porcelain discs for the airborne-particle abrasion, as-fired, and ground surface treatments (82 +/- 11 MPa vs 51 +/- 8 MPa and 93 +/- 14 MPa vs 60 +/- 6 MPa, respectively). For the overglazed treatment, there was not a significant difference between the core (115 +/- 1 4 MPa) and the veneer materials (107 +/- 14 MPa). The ground 1-layer core was significantly (P=.015) stronger (93 +/- 14 MPa) than the 2-layer with the core tested in tension (72 +/- 19 MPa). There was no significant difference between 1-layer veneer overglazed (107 +/- 14 MPa) and 2-layer discs when tested with the veneer in tension (105 +/- 16 MPa). CONCLUSION: The overglazed surface treatment significantly improved the strength of the materials tested, as well as the strength of 2-layer discs with the veneer in tension. The veneering porcelain influenced the strength of 2-layer specimens only when tested with the ground ceramic core surface in tension.

Analysis of Variance↗