The results of inspiratory muscle training on cardiac, respiratory, musculoskeletal, and psychological status in patients with stable angina: a randomized controlled trial.

PURPOSE: To determine the effect of inspiratory muscle training (IMT) on respiratory and peripheral muscle strength, functional exercise capacity, health-related quality of life (HRQoL), fatigue, depression, and cardiac functions in patients with stable angina. METHODS: A randomized, controlled, single-blinded study. Twenty patients (59.95 ± 7.35 y, LVEF = 58.77 ± 7.49) with stable angina received IMT at the lowest load (10 cmH2O), and 20 patients (55.85 ± 7.60 y, LVEF = 62.26 ± 7.75) received training at 30% of maximal inspiratory pressure (MIP) seven days/8 weeks. Respiratory muscle strength (MIP; maximal expiratory pressure, MEP), peripheral muscle strength, pulmonary functions, functional exercise capacity (6-min walking test; exercise test), fatigue, HRQoL, depression, and cardiac functions were evaluated before and after. RESULTS: A statistical difference was found between groups in terms of respiratory and peripheral muscle strength, pulmonary functions, functional exercise capacity (p < 0.05). The results of fatigue, depression, HRQoL, and cardiac functions were similar between the groups (p > 0.05). CONCLUSIONS: This study is the first to demonstrate the positive effects of IMT in patients with stable angina. IMT is a safe and effective method and is recommended to be added to cardiopulmonary rehabilitation programs and guidelines, as it results in increased peripheral muscle strength and functional exercise capacity in stable angina patients.Implications for rehabilitationInspiratory muscle training (IMT) is a safe and effective method for coronary artery disease (CAD) patients with stable angina.IMT improved respiratory and peripheral muscle strength, functional exercise capacity, pulmonary functions, and health-related quality of life in CAD patients with stable angina.Perception of depression and fatigue were decreased with IMT in CAD patients with stable angina.

Acinetobacter quorum sensing contributes to inflammation-induced inhibition of orthopaedic implant osseointegration.

Implant infection impairs osseointegration of orthopaedic implants by inducing inflammation. Acinetobacter spp. are increasingly prevalent multi-drug resistant bacteria that can cause osteomyelitis. Acinetobacter spp. can also cause inflammation and thereby inhibit osseointegration in mice. The purpose of the present study was to investigate the role of quorum sensing in this context. Therefore, wild-type bacteria were compared with an isogenic abaI mutant defective in quorum sensing in a murine osseointegration model. The abaI quorum- sensing mutant affected significantly less osseointegration and interleukin (IL) 1ß levels, without detectably altering other pro-inflammatory cytokines. Wild-type bacteria had fewer effects on IL1 receptor (IL1R)-/- mice. These results indicated that quorum sensing in Acinetobacter spp. contributed to IL1ß induction and the resultant inhibition of osseointegration in mice. Moreover, targeting the Gram-negative acyl-homoserine lactone quorum sensing may be particularly effective for patients with Acinetobacter spp. infections.

Characterization of a reproducible model of fracture healing in mice using an open femoral osteotomy.

PURPOSE: The classic fracture model, described by Bonnarens and Einhorn in 1984, enlists a blunt guillotine to generate a closed fracture in a pre-stabilized rodent femur. However, in less experienced hands, this technique yields considerable variability in fracture pattern and requires highly-specialized equipment. This study describes a reproducible and low-cost model of mouse fracture healing using an open femoral osteotomy. METHODS: Femur fractures were produced in skeletally mature male and female mice using an open femoral osteotomy after intramedullary stabilization. Mice were recovered for up to 28 days prior to analysis with microradiographs, histomorphometry, a novel µCT methodology, and biomechanical torsion testing at weekly intervals. RESULTS: Eight mice were excluded due to complications (8/193, 4.1%), including unacceptable fracture pattern (2/193, 1.0%). Microradiographs showed progression of the fracture site to mineralized callus by 14 days and remodelling 28 days after surgery. Histomorphometry from 14 to 28 days revealed decreased cartilage area and maintained bone area. µCT analysis demonstrated a reduction in mineral surface from 14 to 28 days, stable mineral volume, decreased strut number, and increased strut thickness. Torsion testing at 21 days showed that fractured femurs had 61% of the ultimate torque, 63% of the stiffness, and similar twist to failure when compared to unfractured contralateral femurs. CONCLUSIONS: The fracture model described herein, an open femoral osteotomy, demonstrated healing comparable to that reported using closed techniques. This simple model could be used in future research with improved reliability and reduced costs compared to the current options.

Raman spectroscopy-based water content is a negative predictor of articular human cartilage mechanical function.

OBJECTIVE: Probing the change in water content is an emerging approach to assess early diagnosis of osteoarthritis (OA). We herein developed a new method to assess hydration status of cartilage nondestructively using Raman spectroscopy (RS), and showed association of Raman-based water and organic content measurement with mechanical properties of cartilage. We further compared Raman-based water measurement to gravimetric and magnetic resonance imaging (MRI)-based water measurement. DESIGN: Eighteen cadaveric human articular cartilage plugs from 6 donors were evenly divided into two age groups: young (n = 9, mean age: 29.3 ± 6.6) and old (n = 9, mean age: 64.0 ± 1.5). Water content in cartilage was measured using RS, gravimetric, and MRI-based techniques. Using confined compression creep test, permeability and aggregate modulus were calculated. Regression analyses were performed among RS parameters, MRI parameter, permeability, aggregate modulus and gravimetrically measured water content. RESULTS: Regardless of the method used to calculate water content (gravimetric, RS and MRI), older cartilage group consistently had higher water content compared to younger group. There was a stronger association between gravimetric and RS-based water measurement (Rg2 = 0.912) than between gravimetric and MRI-based water measurement (Rc2 = 0.530). Gravimetric and RS-based water contents were significantly correlated with permeability and aggregate modulus whereas MRI-based water measurement was not. CONCLUSION: RS allows for quantification of different water compartments in cartilage nondestructively, and estimation of up to 82% of the variation observed in the permeability and aggregate modulus of articular cartilage. RS has the potential to be used clinically to monitor cartilage quality noninvasively or minimally invasively with Raman probe during arthroscopy procedures.

Effects of different lasers on organic/inorganic ratio of radicular dentin.

The aim of this study was to evaluate the chemical stability of endodontic-treated root dentin after different laser irradiations through Raman spectroscopy. Fifty maxillary canines were selected and prepared with K3 system. Roots were randomly distributed into five groups (n = 10) according to the surface treatment: GI (water), GII (NaOCl + EDTA), GIII (NaOCl + EDTA + 980 nm Diode laser), GIV (NaOCl + EDTA+ 1064 nm Nd: YAG laser) and GV (NaOCl + EDTA+ 2780 nm Er,Cr: YSGG laser). Lasers were applied for 20 s. Samples were bisected, and the organic and inorganic content of dentin was analyzed by Raman spectroscopy. Data were submitted to ANOVA and Tukey tests (p < 0.05). None of the surface treatments alter the inorganic content (cts) (p = 0.183). Roots irradiated with Er,Cr: YSGG laser had a reduced collagen content (GV-290.7 ± 41.7) compared with the water-treated roots (GI-328.3 ± 63.5) and those treated with NaOCl + EDTA (GII-333.9 ± 55.8). Roots irradiated with Er,Cr: YSGG laser also showed a higher inorganic/organic ratio (GV-9.5 ± 1.1) than roots treated with water (GI-7.7 ± 1.5), NaOCl + EDTA (GII-8.0 ± 1.4) and diode laser (GIII-8.2 ± 1.6). Both organic and inorganic contents increased from cervical to apical thirds in all groups. None of the surface treatments were able to promote changes in the inorganic content of the root dentin; treatment with NaOCl + EDTA combined with Er,Cr: YSGG altered collagen.

Conduction characteristics in atrial fibrillation. Predictive value of tissue Doppler echocardiography.

BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmias observed in clinical practice. The frequency of AF is increased in patients with impaired interatrial conduction. We aimed to investigate whether tissue Doppler echocardiography could be used for the evaluation of atrial conduction characteristics instead of an electrophysiological study, and to examine the predictive accuracy of tissue Doppler echocardiography for the inducibility of sustained AF. METHODS: We enrolled 86 consecutive patients who underwent an electrophysiological study. We performed electrocardiographic P wave dispersion, M-mode, two-dimensional, Doppler, and tissue Doppler echocardiography as well as an electrophysiological study (EPS) to evaluate the intra- and interatrial conduction times. We tried to induce AF, and the patients were categorized according to the inducibility of sustained (> 120 s) AF. RESULTS: We found a good correlation between intra-left atrial conduction time detected by tissue Doppler echocardiography (ILCT-echo) and by EPS (ILCT-eps; r = 0.744, p < 0.001), and a weak correlation between interatrial conduction times (IACT-echo and IACT-eps, r = 0.396, p < 0.001). In patients with inducible sustained AF, P wave dispersion (46 ± 19 ms vs. 27 ± 18, p < 0.001), ILCT-echo (29 ± 10 ms vs. 17 ± 7 ms, p < 0.001), and IACT-eps (47 ± 11 ms vs. 36 ± 13 ms, p < 0.001) were found to be higher than those of the noninducible/nonsustained AF group. These three parameters were independent predictors of the inducibility of sustained AF. CONCLUSION: We demonstrated that ILCT-echo could be used instead of ILCT-eps for the evaluation of left atrial conduction characteristics. We also showed that ILCT-eps could be a valuable parameter for predicting the development of long-lasting AF.

A new diagnostic method for woven coronary artery: optical coherence tomography.

Woven coronary artery is an extremely rare and not clearly defined congenital malformation in which the epicardial coronary artery is divided into multiple thin channels. These multiple channels merge again into a normal conduit. This anomaly is a benign condition because there is normal blood flow after the anomalous segment of the abnormal coronary artery. We describe a woven coronary artery anomaly in the left anterior descending artery (LAD) and its first diagonal (DI) branch causing myocardial infarction that was confused with coronary dissection. The definitive diagnosis was made by optical coherence tomography (OCT). Although woven coronary is a benign anomaly, it may cause myocardial infarction. We used the novel method of OCT for the definitive diagnosis and appropriate treatment of this anomaly.

The morphological, material-level, and ash properties of turkey femurs from 3 different genetic strains during production.

Femoral fractures are observed in selective-bred commercial turkeys; however, the etiology of such fractures is unknown. The current study investigated the whole bone morphological, material-level mechanical, and bone ash properties to determine the effect of selective breeding on bone strength. Femora from 3 divergent strains of turkeys, a commercial line, a different selectively bred heavy line (F-line), and a lighter age or weight matched random-bred line (RBC2/R-EQ, respectively), were compared. Bone geometric properties were measured with micro-CT and bone mechanical properties were measured using 3-point bending tests. Whole bone ash quantities were also recorded. Statistics were run using a general linear model multivariate ANOVA (GLM ANOVA). Results showed that at similar ages, the faster growing birds (commercial and F-line) had femurs twice the size of the RBC2 line as measured by cross-sectional area as early as 8 wk into the study. The femurs of the commercial and F-lines also exhibited as much as 20% greater mechanical strength than femurs from the RBC2 line at 16 and 20 wk of age as measured by properties such as elastic modulus and ultimate tensile strength. However, at similar BW, the slower growing R-EQ line had higher mechanical properties than the other lines, with the elastic modulus being 40% greater and the ultimate tensile strength being 37% greater at weights equivalent to those of the commercial and F-lines at 12 wk of age. Moreover, it was observed that the morphological properties (i.e., cross-sectional area, moments of inertia) are largely governed by BW, as there is little difference in the amount gained per week of age across the different lines. Conversely, the mechanical properties, as well as the related ash content, appear to be governed at least in part by time. Therefore, whereas modulation of bone geometry is the key responder for changes in BW, sufficient time for matrix mineralization or maturation or both to occur is also essential for mechanical competence of bone.

Local variations in the micromechanical properties of mouse femur: the involvement of collagen fiber orientation and mineralization.

In this study we sought to understand the material level basis for local variations in the uniaxial micromechanical properties of mouse cortical bone. It was hypothesized that the opposing anterior and posterior quadrants will significantly differ in terms of their mechanical function, such that, the anterior portion will be stronger in tension whereas the posterior quadrant will be stronger in compression. Mechanical properties were assessed via microtensile and microcompressive tests of standardized coupon-shaped specimens from femurs of Swiss Webster mice (9 weeks). The mineralization and mineral quality was assessed via Raman spectroscopy and the overall collagen orientation was investigated with quantitative polarized imaging. Micromechanical tests demonstrated that the modulus, yield stress, maximum stress and fracture energy of the posterior quadrant was 66%, 53%, 42% and 31% of anterior quadrant; however, the compressive properties did not differ between the two quadrants. Raman microspectroscopic analysis indicated that the mineral matrix ratio, mineral crystallinity and carbonation did not vary between the quadrants. However, the collagen fibers in the anterior quadrant were significantly (p<0.05) more oriented along the longer axis of the diaphyseal shaft than the collagen fibers of the posterior quadrant. Therefore, we concluded that the orientation of collagen fibers with respect to the anatomical loading axis has a profound effect on the uniaxial mechanical function of murine bone. It will be a matter of further research to reveal the role of local variations in the mode of stress on this material level dichotomy in tissue organization and mechanical function.

Effect of fixation and embedding on Raman spectroscopic analysis of bone tissue.

Raman spectroscopy provides valuable information on the physicochemical properties of hard tissues. While the technique can analyze tissues in their native state, analysis of fixed, embedded, and sectioned specimens may be necessary on certain occasions. The information on the effects of fixatives and embedding media on Raman spectral properties is limited. We examined the effect of ethanol and glycerol as fixatives and a variety of embedding media (Araldite, Eponate, Technovit, glycol methacrylate, polymethyl methacrylate, and LR white) on Raman spectral properties (mineralization, crystallinity, and carbonation) measured from the cortical bone of mouse humeri. Humeri were fixed in ethanol or glycerol, followed by embedding in one of the media. Nonfixed, freeze-dried, and fixed but not embedded sections were also examined. Periosteal, endosteal, and midosteal regions of the intracortical envelope were analyzed. Raman spectra of fixative solutions and embedding media were also recorded separately in order to examine the specifics of overlap between spectra. We found significant effects of fixation, embedding, and anatomical location on Raman spectral properties. The interference of ethanol with tissue seemed to be relatively less pronounced than that of glycerol. However, there was no single combination of fixation and embedding that left Raman spectral parameters unaltered. We conclude that careful selection of a fixation and embedding combination should be made based on the parameter of interest and the type of tissue. It may be necessary to process multiple samples from the tissue, each using a combination appropriate for the Raman parameter in question.

Fracture resistance of gamma radiation sterilized cortical bone allografts.

Gamma radiation is widely used for sterilization of human cortical bone allografts. Previous studies have reported that cortical bone becomes brittle due to gamma radiation sterilization. This embrittlement raises concern about the performance of a radiation sterilized allograft in the presence of a stress concentration that might be surgically introduced or biologically induced. The purpose of this study was to investigate the effect of gamma radiation sterilization on the fracture resistance of human femoral cortical bone in the presence of a stress concentration. Fracture toughness tests of specimens sterilized at a dose of 27.5 kGy and control specimens were conducted transverse and longitudinal to the osteonal orientation of the bone tissue. The formation of damage was monitored with acoustic emission (AE) during testing and was histologically observed following testing. There was a significant decrease in fracture toughness due to irradiation in both crack growth directions. The work-to-fracture was also significantly reduced. It was observed that the ability of bone tissue to undergo damage in the form of microcracks and diffuse damage was significantly impaired due to radiation sterilization as evidenced by decreased AE activity and histological observations. The results of this study suggest that, for cortical bone irradiated at 27.5 kGy, it is easier to initiate and propagate a macrocrack from a stress concentration due to the inhibition of damage formation at and near the crack tip.

Cortical bone tissue resists fatigue fracture by deceleration and arrest of microcrack growth.

Knowledge of kinetics of fatigue crack growth of microcracks is important so as to understand the dynamics of bone adaptation, remodeling, and the etiology of fatigue-based failures of cortical bone tissue. In this respect, theoretical models (Taylor, J. Biomech., 31 (1998) 587-592; Taylor and Prendergast, Proc. Instn. Mech. Engrs. Part H 211 (1997) 369-375) of microcrack growth in cortical bone have predicted a decreasing microcrack growth rate with increasing microcrack length. However, these predictions have not been observed directly. This study investigated microcrack growth and arrest through observations of surface microcracks during cyclic loading (R=0.1, 50-80MPa) of human femoral cortical bone (male, n=4, age range: 37-40yr) utilizing a video microscopy system. The change in crack length and orientation of eight surface microcracks were measured with the number of fatigue cycles from four specimens. At the applied cyclic stresses, the microcracks propagated and arrested in generally less than 10,000 cycles. The fatigue crack growth rate of all microcracks decreased with increasing crack length following initial identification, consistent with theoretical predictions. The growth rate of the microcracks was observed to be in the range of 5x10(-5) to 5x10(-7)mmcycle(-1). In addition, many of the microcracks were observed not to grow beyond 150 microm and a cyclic stress intensity factor of 0.5MNm(-3/2). The results of this study suggest that cortical bone tissue may resist fracture at the microscale by deceleration of fatigue crack growth and arrest of microcracks.

Assessment of mineral density and atomic content of fracture callus by quantitative computerized tomography.

The mineral density and atomic numbers of elements in the periosteal callus and the cortex area of a healing fracture were measured by quantitative computerized tomography (QCT) to obtain accurate information on the mineralization process in rabbit tibia. The mineral density of the periosteal callus was highest on day 15 and decreased gradually throughout the experiment. This was initially detected by QCT, but not with conventional radiography. An apparent decrease in cortical bone density on days 28 and 42 after fracture was observed. Atomic numbers of elements in the cortex remained stable, indicating a possible homeostatic mechanism of mineral preservation at the fracture callus and involved cortical area. QCT may predict density alterations in the fracture callus more accurately than conventional X-ray. Further studies are essential to predict a relationship between mineral density, atomic numbers, and mechanical stability.

Relation between mechanical stiffness and vibration transmission of fracture callus: an experimental study on rabbit tibia.

It has been suggested that the vibration transmission across a fracture is affected by the stages of healing of the fracture callus. This study aims to correlate the change in vibration transmission with mechanical stiffness of the callus measured by three-point bending. The right tibiae of male, three-month old local albino rabbits were osteotomized and stabilized by intramedullary fixation following open reduction. The intramedullary rods were removed on the 15th, 28th, 42nd and 90th days postoperatively and the tibiae were excised for vibration, three-point bending and bone mineral density analysis by quantitative computerized tomography (QCT). Optimum time for clinical weight bearing was determined by checking the convergence of the vibration parameters of the fractured tibia to those of the unfractured contralateral. The conclusions obtained from curvature analysis, based on vibration experiments, were in considerable correlation (Spearman's rank correlation coefficient r = 0.93, p = 0.003) with the conclusions obtained from the three-point bending test data which reflected the mechanical condition of the bone by direct means. However, no correlation between bone mineral density change and vibration transmission was noted.

Synthesis and mechanical properties of interpenetrating networks of polyhydroxybutyrate-co-hydroxyvalerate and polyhydroxyethyl methacrylate.

Naturally occurring, biocompatible, and biodegradable polyhydroxybutyrate-co-hydroxyvalerate (PHBV), and synthetic, non-degrading polyhydroxyethylmethacrylate (PHEMA) membranes were prepared and their mechanical properties were studied. Their performances were compared with the interpenetrating networks (IPN) prepared by photopolymerization of HEMA in the presence of PHBV. The modulus of elasticity, failure stress and failure strain indicated that the IPNs are viscoelastic with properties closer to PHEMA but much stronger than PHEMA homopolymers. Incorporation of PHBV (7, 14 and 22% HV) affected the mechanical properties positively. Increasing the PHBV content increased the modulus of elasticity and failure stress nearly in all samples tested. PHBV (7, 14, and 22% HV, 300 mg) samples showed an approximately 17-30 fold increase in terms of modulus of elasticity and 7-10 fold increase in terms of failure stress. The scanning electron micrographs of the membranes showed that the PHEMA membranes are more porous than the PHBV membranes but the IPN structure displayed channels on the membrane surface indicating that HEMA polymerization was achieved by using the PHBV as a scaffold. With the use of the present technique, it is possible to synthesize supramolecular structures from molecules that are not compatible and miscible with each other.

Reduction of restrictive adhesions by local aprotinin application and primary sheath repair in surgically traumatized flexor tendons of the rabbit.

The effects of microsurgical and medical treatments on reduction of adhesions in surgically traumatized flexor tendons of rabbits are quantified in this study. The effects of the mentioned techniques were investigated for the following 4 groups: (1) neither primary sheath repair nor aprotinin application was done, (2) primary sheath repair was done but no aprotinin was used, (3) primary sheath repair was not done but local aprotinin (15,000 IU/kg) was applied, and (4) primary sheath repair was done and local aprotinin was applied. At the sixth and twelfth postoperative weeks, the flexor digitorum profundus tendons of the second and the third digits were subjected to biomechanical tests. Only the third digit was used in macroscopic and histopathologic evaluations. There were 6 digits included in each subgroup of biomechanical tests and 4 digits per subgroups in macroscopic and histopathologic evaluations. Work of flexion (WOF) values were obtained by calculating the area under the load-displacement curve. Percent resistive work of flexion (PRWOF) was obtained by calculating the difference between the WOF value for the repaired right digit and the WOF value for the contralateral corresponding nonrepaired digit. Combined primary sheath repair and medical treatment yielded the best results in reducing the restrictive adhesions in injured tendons. The differences between the PRWOF values of group 4 were 33.7% +/- 8.2% and 15.8% +/- 7.7% for the sixth and twelfth postoperative weeks, respectively. The corresponding values for group 1 were 95.7% +/- 13.8% and 51.75% +/- 10.25%.

Biomechanical analysis of the effects of single high-dose vitamin D3 on fracture healing in a healthy rabbit model.

In a previous ultrastructural study, the benefit of a single high dose of vitamin D3 on fracture healing in a healthy animal model was demonstrated. This study examined the biomechanical consequences of applying a single high dose of vitamin D3 in a healthy rabbit model subsequent to femoral fracture. The fracture load, the values of energy absorbed until fracture and the flexural rigidity values of the vitamin D group were significantly higher than the corresponding ones of the control group in the case of fracture. On the other hand, for intact bones, those values did not differ significantly between the two groups. It was concluded that single high-dose vitamin D3 application had positive effects on fracture healing in a healthy animal model, as far as the parameters related to mechanical strength are concerned.