Evaluation of A2 and A4 Hand Pulley Repair Using Tendon Graft Rings.

PURPOSE: To compare the mechanical characteristics of A2 and combined A2-A4 pulley repair in the intact and damaged flexor pulley system. METHODS: After control testing, we recorded tendon excursion and flexion of 11 cadaveric fingers after several interventions: (1) complete excision of A2 and A4, (2) repair of the A2 with one ring of tendon graft, (3) repair of the A2 with 2 rings of tendon graft, and (4) repair of the A2 with 2 rings combined with repair the A4 with one ring. RESULTS: At the proximal interphalangeal (PIP) joint, the maximum rotational angle decreased by an average of 30% after complete excision of the A2 and A4 pulleys. This angle was still decreased compared with the control by an average of 25% after one-ring repair at A2, 23% after 2-ring repair at A2, and 17% after 2-ring repair at A2 combined with one-ring repair at A4. At the metacarpophalangeal joint, the average maximum rotational angle decreased by an average of 17% after complete excision of the A2 and A4 pulleys. This angle was still decreased compared with the control by an average of 11% after one-ring repair at A2, 7% after 2-ring repair at A2, and 4% after 2-ring repair at A2 combined with one-ring repair at A4. Kinematic behavior at the PIP joint with an intact pulley system was most closely approximated by the 3-loop repair. The least similar behavior was with a 2-ring construct at A2. CONCLUSIONS: All repairs increased average flexion at the PIP and metacarpophalangeal joints compared with the unrepaired samples. The 3-ring configuration exhibited a higher recovery of PIP flexion compared with the other repairs. CLINICAL RELEVANCE: Although each repair restored flexion, clinical studies are necessary to evaluate the clinical relevance of the mechanical results of this study.

What Protects Certain Nerves from Stretch Injury?

The human tibial nerves is less prone to injury following joint arthroplasty compared with the peroneal nerves. Besides the anatomical distribution, other features may confer protection from stretch injury. We therefore examined the size, shape and connective tissue distribution for the two nerves. The tibial and peroneal nerves from each side of nine fresh human cadavers we reharvested mid-thigh. Proximal segments manually stretched 20%-25% were fixed in aldehyde, while the adjacent distal segments were fixed in their natural length. Paraffin sections stained by Masson's trichrome method for connective tissue were examined by light microscopy. Tibial nerves had 2X more fascicles compared with the peroneal, but the axonal content appeared similar. Analysis showed that neither nerve had a significant reduction in cross sectional area of the fascicles following stretch. However, fascicles from stretched tibial nerves become significantly more oval compared with those from unstretched controls and peroneal nerves. Tibial nerves had a greater proportion that was extrafascicular tissue (50-55%) compared with peroneal nerves (38%-42%). This epineurium was typically adipose tissue. Perineurial thickness in both nerves was directly related to fascicular size. Tibial nerves have several unique histological features associated with size, shape and tissue composition compared with the peroneal nerve. We suggest that more fascicles with their tightly bound perineurium and more robust epineurium afford protection against stretch injury. Mechanical studies should clarify how size and shape contribute to nerve protection and/or neurapraxia.

Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion.

Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, 18 of 191). Paxillin mutations (19 of 21) were clustered between LD motifs 1 and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, cell proliferation, and invasion. These results establish an important role for paxillin in lung cancer.