Citations

Background We have recently reported that interpositional synovium grafts from tendon sheath have a potential to accelerate tendon healing when implanted at the repair site. The purpose of this study was to investigate the effect of orientation of the synovium after synovium graft transplantation, by comparing the ability of cells from the visceral and parietal surfaces to migrate into the tendon in a canine tissue culture model. Methods The synovium graft was placed within a complete tendon laceration, with either the visceral or parietal surface facing the proximal end of the lacerated tendon. The number of migrating cells was quantified by a cell migration assay. Qualitative immunohistochemistry and confocal laser microscopy were also used at day 10. Results Many labeled synovial cells were observed within the tendon to which the visceral surface of the synovium graft was facing. Migrated cells were also observed on the parietal side, but there were fewer cells compared to visceral surface cells. Migrating cells all expressed α-smooth muscle actin. Conclusion We found that graft orientation affected cell migration. Whether this finding has clinical significance awaits in vivo study.

Abstract Purpose: Glioblastoma (GBM), the most common primary brain tumor in adults, presents a high frequency of alteration in the PI3K pathway. Our objectives were to identify a dual PI3K/mTOR inhibitor optimized to cross the blood–brain barrier (BBB) and characterize its brain penetration, pathway modulation in the brain and efficacy in orthotopic xenograft models of GBM. Experimental Design: Physicochemical properties of PI3K inhibitors were optimized using in silico tools, leading to the identification of GNE-317. This compound was tested in cells overexpressing P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP). Following administration to mice, GNE-317 plasma and brain concentrations were determined, and phosphorylated biomarkers (pAkt, p4EBP1, and pS6) were measured to assess PI3K pathway suppression in the brain. GNE-317 efficacy was evaluated in the U87, GS2, and GBM10 orthotopic models of GBM. Results: GNE-317 was identified as having physicochemical properties predictive of low efflux by P-gp and BCRP. Studies in transfected MDCK cells showed that GNE-317 was not a substrate of either transporter. GNE-317 markedly inhibited the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 was efficacious in the U87, GS2, and GBM10 orthotopic models, achieving tumor growth inhibition of 90% and 50%, and survival benefit, respectively. Conclusions: These results indicated that specific optimization of PI3K inhibitors to cross the BBB led to potent suppression of the PI3K pathway in healthy brain. The efficacy of GNE-317 in 3 intracranial models of GBM suggested that this compound could be effective in the treatment of GBM. Clin Cancer Res; 18(22); 6239–48. ©2012 AACR.

Physiologic observations were made on eight patients following repair of atrial septal defect or total anomalous pulmonary venous connection. A pattern of changes in cardiac output and atrial pressures during the first 3 postoperative days was noted. Cardiac output was abnormally low in some patients with obstructive pulmonary vascular disease or low atrial pressures. Transfusion of whole blood was effective in elevating cardiac output in the operating room and after operation. Left atrial pressure was higher than right atrial pressure in the operating room. Postoperatively left and right atrial pressures tended to become equal in some patients, and the levels were slightly elevated. Heart rate did not seem to be directly related to cardiac output. Ventilation was adequate with regard to elimination of carbon dioxide. Arterial oxygen saturation was maintained at 93 per cent or more by the use of oxygen-enriched mixtures. The difference in arteriovenous oxygen content was inversely related to cardiac output. Acidemia was present 2 to 4 hours after operation, but in general the pH of arterial blood had returned to normal by day 2. Some mechanisms possibly related to the observations are discussed.

When 24 normal subjects under basal conditions smoked two thirds of 2 cigarettes, there was no appreciable rise in the levels of the fasting blood sugar and the epinephrine-like substances of the systemic venous blood. However, the smoking of two thirds of 2 cigarettes significantly raised the blood pressure and pulse rate, and decreased the skin temperature of fingers and toes.

The purpose of this study was to compare two different methods of joining tendons of similar and dissimilar sizes between recipient and donor tendons for flexor tendon grafts. Flexor digitorum profundus (FDP) and peroneus longus (PL) canine tendons were harvested and divided into four groups. The repair technique we compared was a step-cut (SC) suture and a Pulvertaft weave (PW). FDP tendons were significantly larger in diameter than PL tendons ( p < 0.05). The volume of the SC repairs using either FDP or PL tendon as a graft was significantly smaller than PW repairs ( p < 0.05). The ultimate load to failure and repair stiffness in FDP graft tendons significantly increased compared with the PL graft tendons ( p < 0.05). The SC suture can be used as an alternative to the PW, with similar strength and less bulk for repairs using graft tendons of similar diameter. Surgeons should be aware of the effect of graft tendon size and repair method on strength and bulk when performing flexor tendon grafts.

There is very little data addressing cartilage response to tensile forces, and no literature attempts to correlate compressive with tensile modalities. Our hypothesis was that the cyclic compression and tension modulate chondrocyte matrix proteoglycan synthetic response differently. Porcine chondrocytes cultured to confluence on a flexible membrane were subjected to cyclic compression (Group A: 13 KPa at 1 Hz) or tension (Group C: 10% strain at 1 Hz) for 16 or 32 h; while controls not subjected to any force were kept (Group B). The chondrocytes were then stained with alcian blue and stained areas quantified with confocal microscopy and image processing software. Two-factor ANOVA with post-hoc tests (Scheffe and Bonferroni) statistical analysis were used. Proteoglycan staining covered 46% (range 28%–61%) and 39% (range 26%–49%) of the surface area following 32 and 16 h of compression respectively, 23% (range 15%–49%) for control, and 19% (range 10%–29%) and 16% (range 9%–25%) following 16 and 32 h tension respectively. Proteoglycan content following all compressions was significantly greater than with cyclic tension or control (p < 0.0001). Our data demonstrate that chondrocytes cultured in vitro respond to compression distinctly different from tension and that it is highly sensitive to mechanical loading, with rapid adaptation to its mechanical environment. These results imply that cartilage grown in culture, with the intention of transplantation, may structurally benefit from an environment of cyclic loading at higher frequencies.

We undertook this study to determine the minimum amount of coronoid necessary to stabilise an otherwise intact elbow joint. Regan–Morrey types II and III, plus medial and lateral oblique coronoid fractures, collectively termed type IV fractures, were simulated in nine fresh cadavers. An electromagnetic tracking system defined the three-dimensional stability of the ulna relative to the humerus. The coronoid surface area accounts for 59% of the anterior articulation. Alteration in valgus, internal and external rotation occurred only with a type III coronoid fracture, accounting for 68% of the coronoid and 40% of the entire articular surface. A type II fracture removed 42% of the coronoid articulation and 25% of the entire articular surface but was associated with valgus and external rotational changes only when the radial head was removed, thereby removing 67% of the articular surface. We conclude that all type III fractures, as defined here, are unstable, even with intact ligaments and a radial head. However, a type II deficiency is stable unless the radial head is removed. Our study suggests that isolated medial-oblique or lateral-oblique fractures, and even a type II fracture with intact ligaments and a functional radial head, can be clinically stable, which is consistent with clinical observation.

The purpose of this study was to describe a modification of the Massachusetts General Hospital (MMGH) tendon repair and to compare it with three other suture techniques. Twenty human flexor digitorum profundus (FDP) tendons were randomly assigned to the modified Pennington (MP) suture and the MMGH suture. These were compared to the modified Kessler (MK) and Massachusetts General Hospital (MGH) sutures, using data from a previous study. All tendons were repaired with a similar epitendinous stitch and core sutures of 4-0 FiberWire. There was no significant difference in the normalized gliding resistance within the two-strand or four-strand core repair groups. The MP suture had significantly higher 2 mm gap force and ultimate load to failure than the MK suture. The MMGH suture had significantly higher 2 mm gap force and maximum failure ultimate load than the MGH suture. All repairs failed by knot unravelling.

Background The etiology of carpal tunnel syndrome (CTS) remains idiopathic in many cases. Noninflammatory fibrosis of the subsynovial connective tissue (SSCT) within the carpal tunnel is common in CTS, and some clinicians have hypothesized that this fibrosis might be a cause rather than an effect of CTS. An animal model in which to test this hypothesis would be useful. The principal objective of this study was to investigate the effect of a surgical injury on SSCT fibrosis and median nerve function within the carpal tunnel in an in vivo rabbit model. Methods Rabbits were sacrificed 12 weeks after surgery and were evaluated by mechanical testing, histology, transmission and scanning electron microscopy, and electrophysiology. Results SSCT fibroblast density ( p<0.0001) and collagen fiber size ( p=0.0004) were significantly higher, and the median nerve distal motor amplitude was significantly lower ( p=0.0018), in the tendon injury group SSCT than in either the sham or control groups. Conclusions Our findings are similar to those seen in patients with carpal tunnel syndrome and suggest that the tendon injury procedure may be the basis of a new animal model of SSCT injury and, possibly, CTS.