Decrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiency.

Common variable immunodeficiencies (CVID) are a heterogeneous group of antibody deficiency disorders complicated by autoimmune, lymphoproliferative and/or granulomatous manifestations, suggesting variations in immunoregulation. We sought to quantify regulatory CD4 T cells (T(reg) cells) in the blood of CVID patients and to correlate the frequency with clinical manifestations and classification subgroups. Blood samples from 99 CVID patients in Freiburg, London and Sydney, who had been phenotyped clinically and stratified according to their memory B cell phenotype (Freiburg and Paris classification schemes), were analysed for the proportion of T(reg) cells, defined either as CD25(+)/forkhead box P3 (FoxP3)(+), CD25(+)/CD127(low)/FoxP3(+) or CD25(+)/CD127(low) CD4(+) T cells, and results compared with 49 healthy controls. Irrespective of the phenotype used to define them, there was a significant decrease in the T(reg) cell proportion in patients with granulomatous disease and immune cytopenias. This allowed the definition of a subgroup of CVID patients with abnormally low T(reg) cells, which had a higher rate of these two manifestations as well as autoimmune disease in general. There was also a significant reduction in the proportion of T(reg) cells in the Freiburg group Ia compared with other CVID patients and controls, but there were no differences between the Paris groups. The reduction in T(reg) cells in subsets of CVID patients may be relevant to their clinical manifestations, and may contribute to our understanding of the pathogenesis of CVID complications.

Invariant natural killer (iNK) T cell deficiency in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a B cell immunodeficiency disorder characterized frequently by failure of memory B cell development and antibody secretion. A unifying cellular pathogenesis for CVID has not been forthcoming, but given the immunoregulatory role of invariant NK (iNK) T cells and their absence in several other immunodeficiencies, we quantified these cells in the blood of 58 CVID patients. There was a marked decrease in the proportion of iNK T cells in CVID patients compared with controls. This was particularly notable in those with low isotype-switched memory B cells, but subset analysis demonstrated no difference when stratified by specific clinical features. We propose that the decreased proportion of iNK T cells in CVID might be linked to the failure of memory B cell generation, which may contribute to reduced antibody production in these patients.

The role of the posterior bundle of the medial collateral ligament in posteromedial rotatory instability of the elbow.

Aims: The aim of this study was to evaluate two hypotheses. First, that disruption of posterior bundle of the medial collateral ligament (PMCL) has to occur for the elbow to subluxate in cases of posteromedial rotatory instability (PMRI) and second, that ulnohumeral contact pressures increase after disruption of the PMCL. Materials and Methods: Six human cadaveric elbows were prepared on a custom-designed apparatus which allowed muscle loading and passive elbow motion under gravitational varus. Joint contact pressures were measured sequentially in the intact elbow (INTACT), followed by an anteromedial subtype two coronoid fracture (COR), a lateral collateral ligament (LCL) tear (COR + LCL), and a PMCL tear (COR + LCL + PMCL). Results: There was no subluxation or joint incongruity in the INTACT, COR, and COR + LCL specimens. All specimens in the COR + LCL + PMCL group subluxated under gravity-varus loads. The mean articular contact pressure of the COR + LCL group was significantly higher than those in the INTACT and the COR groups. The mean articular contact pressure of the COR + LCL + PMCL group was significantly higher than that of the INTACT group, but not higher than that of the COR + LCL group. Conclusion: In the presence of an anteromedial fracture and disruption of the LCL, the posterior bundle of the MCL has to be disrupted for gross subluxation of the elbow to occur. However, elevated joint contact pressures are seen after an anteromedial fracture and LCL disruption even in the absence of such subluxation. Cite this article: Bone Joint J 2018;100-B:1060-5.

Intrinsic constraint of unlinked total elbow replacements--the ulnotrochlear joint.

BACKGROUND: Many unlinked total elbow replacement designs with radically differing articular geometries exist, suggesting that there is no consensus regarding an optimal design. A feature inherent to the articular design is the intrinsic constraint afforded to the joint by the implant. Our aim was to compare the intrinsic constraints of unlinked implants with that of the normal ulnotrochlear joint. METHODS: We tested twelve cadaveric ulnotrochlear joints with a custom-made multiple-axis materials testing machine. With compressive loads ranging from 10 to 100 N, the joints were moved in either valgus or varus directions at 90 degrees of flexion. The ulnotrochlear components from a single example of five medium-sized unlinked elbow replacements (Ewald, Kudo, Pritchard ERS, Sorbie-Questor, and Souter-Strathclyde) were also tested. The recorded measurements included the torques and forces, angular displacement, and axial displacement of the humerus relative to the ulna. RESULTS: In general, the peak torque and the constraint ratio significantly increased with increasing compressive load for the implants as well as for the normal elbow. In valgus displacement, the Souter-Strathclyde implant had the highest and the Sorbie-Questor had the smallest peak torque and the Souter-Strathclyde had the highest and the Ewald had the smallest constraint ratio. In varus displacement, the Kudo had the highest and the Ewald had the smallest peak torque and constraint ratio. CONCLUSIONS: The constraint ratio is a characteristic that is useful for describing elbow joint behavior and for comparing the behavior of implants with that of the human elbow. Of the unlinked implants tested, the Souter-Strathclyde and Kudo prostheses most closely approximated the behavior of the human elbow joint. Implants that resemble the human elbow in appearance do not replicate normal behavior consistently, whereas other implants that do not resemble the human elbow closely do not deviate markedly from human behavior. Thus, much basic information about elbow form and function is needed to improve the performance of total elbow prostheses.

Superior-inferior stability of the shoulder: role of the coracohumeral ligament and the rotator interval capsule.

OBJECTIVE: To study the superior-inferior stabilizing functions of the coracohumeral ligament (CHL) and the rotator interval capsule (RIC) with use of a material testing machine. MATERIAL AND METHODS: The axial translations of the humerus with the superior-inferior translation force of 30 N applied were recorded under the following joint capsule conditions: (1) intact, (2) vented, (3) the CHL sectioned, and (4) the RIC incised in six cadaver shoulders. The order of sectioning was changed for conditions 3 and 4 in six other cadaver shoulders. RESULTS: With the arm in internal and neutral rotations, venting the capsule significantly increased the superior-inferior translation, which was unaffected by further sectioning of the CHL and the RIC. With the arm in external rotation, only the CHL contributed significantly to inferior stability, whereas both this ligament and the RIC contributed to superior stability to a lesser degree. CONCLUSION: The CHL is a stabilizer in superior inferior directions with the arm in external rotation, and the intra-articular pressure that is maintained by the intact RIC is a stabilizer in superior-inferior directions with the arm in internal and neutral rotations. These findings may provide a scientific background to support closure of the interval space to stabilize the shoulder and may explain part of the superior instability observed in shoulders with rotator cuff tears.

Dynamic pressure transmission through agarose gels.

In biomedical research, agarose gel is widely used in tissue culture systems because it permits growing cells and tissues in a three-dimensional suspension. This is especially important in the application of tissue engineering concepts to cartilage repair because it supports the cartilage phenotype. Mechanical loading, especially compression, plays a fundamental role in the development and repair of cartilage. It would be advantageous to develop a system where cells and tissues could be subjected to compression so that their responses can be studied. There is currently no information on the pressure response of agarose gel when pressure is applied to the gas phase of a culture system. To understand the transmission of pressure through the gel, we set up an apparatus that would mimic an agarose suspension tissue culture system. This consisted of a sealed metal cylinder containing air as well as a layer of agarose submerged in culture medium. Pressure responses were recorded in the air, fluid, gel center, and gel periphery using various frequencies, pressures, gel volumes, and viscosities. Regression analyses show an almost perfect linear relation between gas and gel pressures (r(2) = 0.99987, p < 0.0001, f(x) = 0.9982 x - 0.0286). The pressure transmission was complete and immediate, throughout the range of the applied pressures, frequencies, volumes, and viscosities tested. Applying dynamic pressure to the gas phase results in reproducible pressure in the agarose and, therefore, validates the use of agarose tissue culture systems in studies employing dynamic pressurization in cartilage tissue engineering.

Biochemically discrete zones of canine flexor tendon: evaluation of properties with a new photographic method.

We describe a photographic method that we have found useful for studying small strain fields within a larger zone of interest. We have used this method to document differences in material properties which correlate with zones of different biochemical makeup in the canine flexor digitorum profundus tendon. This method may be useful in analysis of experimental injury and wound healing in this model and may have application in evaluating material properties of soft tissue in other models as well.

The enhancement of periosteal chondrogenesis in organ culture by dynamic fluid pressure.

Cartilage repair by autologous periosteal arthroplasty is enhanced by continuous passive motion (CPM) of the joint after transplantation of the periosteal graft. However, the mechanisms by which CPM stimulate chondrogenesis are unknown. Based on the observation that an oscillating intra-synovial pressure fluctuation has been reported to occur during CPM (0.6-10 kPa), it was hypothesized that the oscillating pressure experienced by the periosteal graft as a result of CPM has a beneficial effect on the chondrogenic response of the graft. We have developed an in vitro model with which dynamic fluid pressures (DFP) that mimic those during CPM can be applied to periosteal explants while they are cultured in agarose gel suspension. In this study periosteal explants were treated with or without DFP during suspension culture in agarose, which is conducive to chondrogenesis. Different DFP application times (30 min, 4 h, 24 h/day) and pressure magnitudes (13, 103 kPa or stepwise 13 to 54 to 103 kPa) were compared for their effects on periosteal chondrogenesis. Low levels of DFP (13 kPa at 0.3 Hz) significantly enhanced chondrogenesis over controls (34 +/- 7% vs 14 +/- 5%; P < 0.05), while higher pressures (103 kPa at 0.3 Hz) completely inhibited chondrogenesis, as determined from the percentage of tissue that was determined to be cartilage by histomorphometry. Application of low levels of DFP to periosteal explants also resulted in significantly increased concentrations of Collagen Type II protein (43 +/- 8% vs 10 +/- 5%; P < 0.05). New proteoglycan synthesis, as measured by 35S-sulphate uptake was increased by 30% in periosteal explants stimulated with DFP (350 +/- 50 DPM vs 250 +/- 75 DPM of 35S-sulphate uptake/microg total protein), when compared to controls though this difference was not statistically significant. The DFP effect at low levels was dose-dependant for time of application as well, with 4 h/day stimulation causing significantly higher chondrogenesis than just 30 min/day (34 +/- 7 vs 12 +/- 4% cartilage; P < 0.05) and not significantly less than that obtained with 24 h/day of DFP (48 +/- 9% cartilage, P > 0.05). These observations may partially explain the beneficial effect on cartilage repair by CPM. They also validate an in vitro model permitting studies aimed at elucidating the mechanisms of action of mechanical factors regulating chondrogenesis. The fact that these tissues were successfully cultured in a mechanical environment for six weeks makes it possible to study the actions of mechanical factors on the entire chondrogenic pathway, from induction to maturation. Finally, these data support the theoretical predictions regarding the role of hydrostatic compression in fracture healing.

Gliding properties of the long head of the biceps brachii.

To elucidate the role of mechanical forces that resist motion of the long head of the biceps brachii, the gliding resistance of the tendon during abduction and adduction was measured. Nine human cadaveric glenohumeral joints were obtained (mean age 68 years, range 47-84). A testing device was developed to simulate glenohumeral abduction and adduction motion. Gliding resistance was calculated as the force differential on the proximal and distal ends of the biceps brachii at five glenohumeral angles (15 degrees, 30 degrees, 45 degrees, 60 degrees and 75 degrees ). The average gliding resistance in abduction at 15 degrees, 30 degrees, 45 degrees, 60 degrees and 75 degrees for a 4.9 N load was 0.41, 0.40, 0.36, 0.32 and 0.28 N, respectively. At these same angles, but during adduction motion, the force on the proximal tendon end was either identical or less than the distal tendon end (p>0.46) indicating a lack of resistance and even a phenomena of "negative" resistance in which some other force overcame the friction. The difference in gliding resistance between abduction and adduction was significant (p<0.05). The results indicate that forces opposing biceps tendon gliding are more complicated than simply due to friction. Tendon deformation inside the bicipital groove produces a direction-dependent effect due to a mechanism of elastic recoil. Understanding forces that are absorbed by the tendon during active motion may provide insight into pathological changes that develop inside and around the tendon.

Tensile properties of the supraspinatus tendon.

The tensile properties of the supraspinatus tendon were investigated in 11 shoulders from fresh cadavers. The tendon was divided into three longitudinal strips: anterior, middle, and posterior. Each specimen was mounted on a materials testing machine, with four fluorescent markers placed on both surfaces of the tendon strip. The positions of these markers were recorded during the test by two synchronized video cameras. Load-deformation and strain curves were determined, and the stress-strain curve, strength, and modulus of elasticity were calculated. The posterior strip was thinner in cross section than the others (p = 0.0355). The ultimate load and ultimate stress were significantly greater in the anterior strip (16.5 +/- 7.1 MPa) than in the middle (6.0 +/- 2.6 MPa) and posterior (4.1 +/- 1.3 MPa) strips (p < 0.0001). The modulus of elasticity also was significantly greater in the anterior strip (p < 0.0001), but there was no significant difference between the superficial and deep surfaces. It is concluded that the anterior portion of the supraspinatus tendon is mechanically stronger than the other portions, and it seems to perform the main functional role of the tendon.

Gliding resistance of extrasynovial and intrasynovial tendons through the A2 pulley.

The gliding ability of the flexor digitorum profundus tendon and of the palmaris longus tendon through the A2 pulley was compared, in terms of gliding resistance, with use of a system that we developed. Fourteen digits and the ipsilateral palmaris longus tendons from fourteen cadavera were used. The average gliding resistance at the interface between the palmaris longus tendon and the A2 pulley was found to be greater than that between the flexor digitorum profundus tendon and the A2 pulley under similar loading conditions. We concluded that the gliding ability of the palmaris longus tendon was inferior to that of the flexor digitorum profundus tendon in vitro.

The effect of a glenoid defect on anteroinferior stability of the shoulder after Bankart repair: a cadaveric study.

BACKGROUND: An osseous defect of the glenoid rim is sometimes caused by multiple recurrent dislocations of the shoulder. It is generally thought that a large defect should be treated with bone-grafting, but there is a lack of consensus with regard to how large a defect must be in order to necessitate this procedure. Some investigators have proposed that a defect must involve at least one-third of the glenoid surface in order to necessitate bone-grafting. However, it is difficult to determine (1) whether a defect involves one-third of the glenoid surface and (2) whether a defect of this size is critical to the stability of the shoulder after a Bankart repair. The purposes of the present study were (1) to create and quantify various sizes of osseous defects of the glenoid and (2) to determine the effect of such defects on the stability and motion of the shoulder after Bankart repair. METHODS: The glenoids from sixteen dried scapulae were photographed, and the images were scanned into a computer. The average shape of the glenoid was determined on the basis of the scans, and this information was used to design custom templates for the purpose of creating various sizes of osseous defects. Ten fresh-frozen cadaveric shoulders then were obtained from individuals who had been an average of seventy-nine years old at the time of death, and all muscles were removed to expose the joint capsule. With use of a custom multiaxis electromechanical testing machine with a six-degrees-of-freedom load-cell, the humeral head was translated ten millimeters in the anteroinferior direction with the arm in abduction and external rotation as well as in abduction and internal rotation. With a fifty-newton axial force constantly applied to the humerus in order to keep the humeral head centered in the glenoid fossa, the peak force that was needed to translate the humeral head a normalized distance was determined under eleven sequential conditions: (1) with the capsule intact, (2) after the creation of a simulated Bankart lesion, (3) after the capsule was repaired, (4) after the creation of an anteroinferior osseous defect with a width that was 9 percent of the glenoid length (average width, 2.8 millimeters), (5) after the capsule was repaired, (6) after the creation of an osseous defect with a width that was 21 percent of the glenoid length (average width, 6.8 millimeters), (7) after the capsule was repaired, (8) after the creation of an osseous defect with a width that was 34 percent of the glenoid length (average width, 10.8 millimeters), (9) after the capsule was repaired, (10) after the creation of an osseous defect with a width that was 46 percent of the glenoid length (average width, 14.8 millimeters), and (11) after the capsule was repaired. RESULTS: With the arm in abduction and external rotation, the stability of the shoulder after Bankart repair did not change significantly regardless of the size of the osseous defect (p = 0.106). With the arm in abduction and internal rotation, the stability decreased significantly as the size of the osseous defect increased (p<0.0001): the translation force in shoulders in which the width of the osseous defect was at least 21 percent of the glenoid length (average width, 6.8 millimeters) was significantly smaller than the force in shoulders without an osseous defect. The range of external rotation in shoulders in which the width of the osseous defect was at least 21 percent of the glenoid length was significantly less than that in shoulders without a defect (p<0.0001) because of the pretensioning of the capsule caused by closing the gap between the detached capsule and the glenoid rim. The average loss of external rotation was 25 degrees per centimeter of defect. CONCLUSIONS: An osseous defect with a width that is at least 21 percent of the glenoid length may cause instability and limit the range of motion of the shoulder after Bankart repair.

Application of a magnetic tracking device to kinesiologic studies.

A magnetic position and orientation tracking system is currently available for the determination of the position and orientation of a sensor relative to a source by utilizing the principle of low-frequency magnetic field technology. The application of this system for biomechanical analysis of human movement is examined in this study. Studies of both planar particle motion and spatial rigid body motion based on Eulerian angle description and screw displacement axis description have been performed. The system has been found to be quite accurate and easy to use, and it would be a useful tool in kinesiologic research.

A dynamic simulator to evaluate distal radio-ulnar joint kinematics.

In order to perform cadaveric biomechanical studies of the human forearm and distal radio-ulnar joint, a dynamic simulator has been constructed. The device is based upon a Plexiglas frame, to which the ulna is secured in a vertical orientation and the humerus in a horizontal orientation. The hand is secured in a sliding bar linkage to a stepper-motor that is used to rotate the forearm. The tendons to be loaded are connected to pneumatic actuators that provide agonist and antagonist muscle loading resulting in torque along the forearm axis. The muscle loading profiles and magnitudes are programmable as a function of the pronation-supination position and direction. A magnetic tracking system is used to collect three-dimensional kinematics data of up to four segments, in conjunction with the muscle tendon loads, forearm torque and other prescribed experimental measures. All functions are under PC control using custom software written with LabVIEW (National Instruments, Austin, TX). For the DRUJ testing, the validity of the tendon loading protocol to produce physiologic torque/rotation patterns was verified using in vivo data. The relationship of individual muscle forces to forearm torque was determined by a cadaveric study.

Accuracy of a video strain measurement system.

The purpose of this study was to determine the accuracy of a video system which our laboratory has been using to measure soft tissue strain. Both static and dynamic error analyses were performed to assess the accuracy of our video system. Static error was defined as the amount of movement reported by the video system for markers that were stationary. Dynamic error was defined as the difference between the motion of the markers as reported by the video system and their actual motion. Two sets of fluorescent markers were attached to a servo-hydraulic materials test machine. One marker set was attached to the hydraulic actuator (moving markers) and the other set was attached to the base of the machine (stationary markers). Five different marker sizes, five camera distances, and seven different loading rates were studied. Results indicated that the static error was independent of marker size, and that the dynamic error was independent of the loading rate and marker size for loading rates of 50% of the camera field of view (CFV) per second or slower. For loading rates greater than 50 percent of CFV per second, the marker size did have an affect on the dynamic error. The mean static error was found to be 0.026 percent of CFV and the mean dynamic error was found to be 0.062 percent of CFV.

Intrinsic stability of an unconstrained metacarpophalangeal joint implant.

OBJECTIVE: To compare the intrinsic stability of an unconstrained resurfacing metacarpophalangeal arthroplasty to that of a normal human cadaveric joint. DESIGN: Cadaveric joints and metacarpophalangeal prostheses were studied in a mechanical testing machine at different angles and axial loads to determine the stability ratio in eight directions of movement. BACKGROUND: An unconstrained resurfacing arthroplasty was designed to replicate the normal anatomy with the exception of the proximal component having a greater arc of curvature on its dorsal aspect. METHODS: Eight fresh-frozen cadaveric joints and five different sizes of the AVANTA metacarpophalangeal prosthesis were studied at 0 degrees, 45 degrees and 90 degrees angles of flexion and at eight different directions of motion with three different axial loads (0, 20, 40 N). A 6-component load cell measured the force needed to sublux the joint. The stability ratio was the measured outcome and is defined as ratio of the force of subluxation to the axial force. RESULTS AND CONCLUSIONS: The unconstrained resurfacing arthroplasty has more intrinsic stability than the cadaveric metacarpophalangeal joint in all eight directions tested. RELEVANCE: A major complication of metacarpophalangeal implants is ulnopalmar subluxation. The AVANTA implant is designed to decrease the risk of ulnopalmar subluxation by having a greater arc of curvature on the dorsal aspect of the proximal component. This study shows that the designed implant has greater stability due to the geometry of the implant compared to that of the anatomical joint.

Validation of F-Scan pressure sensor system: a technical note.

This study performed a quantitative validation on a recently developed pressure sensitive transducer system, the F-Scan sensor system. The results indicate that the sensor is adequate for determination of pressure distribution under contact conditions with soft materials. The linear response of the sensor was up to 1.7 MPa with good homogeneity throughout sensor cells. However, the sensor is sensitive to surface conditions, loading speeds, and temperature. Variations also exist from sensor to sensor. In order to have accurate measurement, calibration was recommended in actual clinical or experimental conditions prior to use, including surface contact conditions, loading speeds, and temperature environment. In addition, this sensor system is not suitable for hard surface contact such as plexiglas.

Healing of canine tendon in zones subjected to different mechanical forces.

The effect of external force environment on the healing of a partial thickness injury to canine flexor tendon was studied. A 50% laceration was made in either the fibrocartilaginous (compressive) zone or in the tendinous (tensile) zone of canine flexor digitorum profundus tendons. After three or six weeks, the tendons were harvested. An optical method for determining zone-specific material properties showed that, in response to injury, the structural stiffness decreased in the tensile zone of the tendon but increased in the compressive zone. The mechanical properties and failure mechanism of canine tendon and their changes in response to injury vary according to tendon zone, and differences in the healing process in mechanically specialised zones of the flexor tendon are discussed.

Flexor tendon-pulley interaction after tendon repair. A biomechanical study.

Ten normal ring fingers from ten donors were used to determine the effect of flexor tendon repair on the gliding resistance between the tendon and the A2 pulley. Gliding resistance was measured for the intact FDP tendon and for the same tendon after it was cut transversely and repaired with a 4/0 Ticron core suture and a 6/0 running epitendinous nylon suture. After repair, the gliding pattern of the tendon through the A2 pulley changed significantly. The resistance and the friction coefficient were approximately doubled (P < 0.005).

Material properties of the plantar aponeurosis.

Material properties of the plantar aponeurosis were determined by a two-dimensional video tracking method to simultaneously measure the aponeurosis deformation. Failure loads averaged 1189 +/- 244 N and were higher in men. Average stiffness of the intact fascia was 203.7 +/- 50.5 N/mm at a loading rate of 11.12 N/sec and it did not vary significantly for the loading rates of 11.12 to 1112 N/sec. The high tensile loads required for failure were consistent with clinical and biomechanical studies and indicated the importance of the aponeurosis in foot function and arch stability.