Improved PCR based methods for detecting C9orf72 hexanucleotide repeat expansions.

Due to the GC-rich, repetitive nature of C9orf72 hexanucleotide repeat expansions, PCR based detection methods are challenging. Several limitations of PCR have been reported and overcoming these could help to define the pathogenic range. There is also a need to develop improved repeat-primed PCR assays which allow detection even in the presence of genomic variation around the repeat region. We have optimised PCR conditions for the C9orf72 hexanucleotide repeat expansion, using betaine as a co-solvent and specific cycling conditions, including slow ramping and a high denaturation temperature. We have developed a flanking assay, and repeat-primed PCR assays for both 3' and 5' ends of the repeat expansion, which when used together provide a robust strategy for detecting the presence or absence of expansions greater than ∼100 repeats, even in the presence of genomic variability at the 3' end of the repeat. Using our assays, we have detected repeat expansions in 47/442 Scottish ALS patients. Furthermore, we recommend the combined use of these assays in a clinical diagnostic setting.

A comparison of the lateral decubitus and beach-chair positions for shoulder surgery: advantages and complications.

Arthroscopic or open shoulder surgery can be performed using the lateral decubitus or beach-chair position. Advantages of the lateral decubitus position include better visualization and instrument access for certain procedures and decreased risk for cerebral hypoperfusion. Complications associated with this position include traction injuries, resulting in neurapraxia, thromboembolic events, difficulty with airway management, and the potential need to convert to an anterior open approach. One advantage of the beach-chair position is easier setup from a supine to upright position, which allows the surgeon the option to convert to an open procedure if necessary. Although rare, patients in this position may experience cerebral hypoperfusion and complications that range from cranial nerve injury to infarction. Other complications related to this position include cervical traction neurapraxia, blindness, and cardiac and embolic events. The surgeon must be cognizant of the complications associated with both positions and take extra care in the initial patient setup and coordination with the anesthesiologist to minimize the risk of complications and morbidity.

In-vivo glenohumeral translation and ligament elongation during abduction and abduction with internal and external rotation.

STUDY DESIGN: Basic Science. To investigate humeral head translations and glenohumeral ligament elongation with a dual fluoroscopic imaging system. BACKGROUND: The glenohumeral ligaments are partially responsible for restraining the humeral head during the extremes of shoulder motion. However, in-vivo glenohumeral ligaments elongation patterns have yet to be determined. Therefore, the objectives of this study were to 1) quantify the in-vivo humeral head translations and glenohumeral ligament elongations during functional shoulder positions, 2) compare the inferred glenohumeral ligament functions with previous literature and 3) create a baseline data of healthy adult shoulder glenohumeral ligament lengths as controls for future studies. METHODS: Five healthy adult shoulders were studied with a validated dual fluoroscopic imaging system (DFIS) and MR imaging technique. Humeral head translations and the superior, middle and inferior glenohumeral ligaments (SGHL, MGHL, IGHL) elongations were determined. RESULTS: The humeral head center on average translated in a range of 6.0mm in the anterior-posterior direction and 2.5mm in the superior-inferior direction. The MGHL showed greater elongation over a broader range of shoulder motion than the SGHL. The anterior-band (AB)-IGHL showed maximum elongation at 90° abduction with maximum external rotation. The posterior-band (PB)-IGHL showed maximum elongation at 90° abduction with maximum internal rotation. DISCUSSION: The results demonstrated that the humeral head translated statistically more in the anterior-posterior direction than the superior-inferior direction (p = 0.01), which supports the concept that glenohumeral kinematics are not ball-in-socket mechanics. The AB-IGHL elongation pattern makes it an important static structure to restrain anterior subluxation of the humeral head during the externally rotated cocking phase of throwing motion. These data suggest that in healthy adult shoulders the ligamentous structures of the glenohumeral joint are not fully elongated in many shoulder positions, but function as restraints at the extremes of glenohumeral motion. Clinically, these results may be helpful in restoring ligament anatomy during the treatment of anterior instability of the shoulder.

Glenohumeral contact kinematics in patients after total shoulder arthroplasty.

BACKGROUND: Knowledge of in vivo glenohumeral joint contact mechanics after total shoulder arthroplasty may provide insight for the improvement of patient function, implant longevity, and surgical technique. The objective of this study was to determine the in vivo glenohumeral joint contact locations in patients after total shoulder arthroplasty. We hypothesized that the glenohumeral joint articular contact would be centered on the glenoid surface because of the ball-in-socket geometric features of the implants. METHODS: Dual-plane fluoroscopic images and computer-aided design models were used to quantify patient-specific glenohumeral articular contact in thirteen shoulders following total shoulder arthroplasty. The reconstructed shoulder was imaged at arm positions of 0 degrees, 45 degrees, and 90 degrees of abduction (in the coronal plane) and neutral rotation and at 90 degrees of abduction with maximum internal and external rotation. The patients were individually investigated, and their glenohumeral joint contact centroids were reported with use of contact frequency. RESULTS: In all positions, the glenohumeral joint contact centroids were not found at the center of the glenoid surface but at an average distance (and standard deviation) of 11.0 +/- 4.3 mm from the glenoid center. Forty (62%) of the sixty-five total contact occurrences were found on the superior-posterior quadrant of the glenoid surface. The position of 0 degrees of abduction in neutral rotation exhibited the greatest variation of quadrant contact location; however, no contact was found on the superior-anterior quadrant of the glenoid surface in this position. CONCLUSIONS: In vivo, glenohumeral joint contact after total shoulder arthroplasty is not centered on the glenoid surface, suggesting that kinematics after shoulder arthroplasty may not be governed by ball-in-socket mechanics as traditionally thought. Although contact locations as a function of arm position vary among patients, the superior-posterior quadrant seems to experience the most articular contact in the shoulder positions tested.

In vivo articular cartilage contact at the glenohumeral joint: preliminary report.

BACKGROUND: Little is known about normal in vivo mechanics of the glenohumeral joint. Such an understanding would have significant implications for treating disease conditions that disrupt shoulder function. The objective of this study was to determine articular contact locations between the glenoid and humeral articular surfaces in normal subjects during shoulder abduction with neutral, internal, and external rotations. We hypothesized that glenohumeral articular contact is not perfectly centered and is variable in normal subjects tested under physiological loading conditions. METHODS: Orthogonal fluoroscopic images and magnetic resonance image-based computer models were used to characterize the centroids of articular cartilage contact of the glenohumeral joint at various static, actively stabilized abduction and rotation positions in five healthy shoulders. The shoulder was investigated at 0 degrees , 45 degrees , and 90 degrees abduction with neutral rotation and then at 90 degrees abduction combined with active maximal external rotation and active maximal internal rotation. RESULTS: For all the investigated positions, the centroid of contact on the glenoid surface for each individual, on average, was more than 5 mm away from the geometric center of the glenoid articular surface. Intersubject variation of the centroid of articular contact on the glenoid surface was observed with each investigated position, and 90 degrees abduction with maximal internal rotation showed the least variability. On the humeral head surface, the centroids of contact were located at the superomedial quarter for all investigated positions, except in two subjects' positions at 0 degrees abduction, neutral rotation. CONCLUSIONS: The data showed that the in vivo glenohumeral contact locations were variable among subjects, but in all individuals they were not at the center of the glenoid and humeral head surfaces. This confirms that "ball-in-socket" kinematics do not govern normal shoulder function. These insights into glenohumeral articular contact may be relevant to an appreciation of the consequences of pathology such as rotator cuff disease and instability.