Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient's knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.

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Background: The ulnar collateral ligament (UCL) microstructural organization and collagen fiber realignment in response to load are unknown. Purpose/Hypothesis: The purpose was to describe the real-time microstructural collagen changes in the anterior bundle (AB) and posterior bundle (PB) of the UCL with tensile load. It was hypothesized that the UCL AB is stronger and stiffer with more highly aligned collagen during loading when compared with the UCL PB. Study Design: Descriptive laboratory study. Methods: The AB and PB from 34 fresh cadaveric specimens were longitudinally sectioned to allow uniform light passage for quantitative polarized light imaging. Specimens were secured to a tensile test machine and underwent cyclic preconditioning, a ramp-and-hold stress-relaxation test, and a quasi-static ramp to failure. A division-of-focal-plane polarization camera captured real-time pixelwise microstructural data of each sample during stress-relaxation and at the zero, transition, and linear points of the stress-strain curve. The SD of the angle of polarization determined the deviation of the average direction of collagen fibers in the tissue, while the average degree of linear polarization evaluated the strength of collagen alignment in those directions. Since the data were nonnormally distributed, the median 6 interquartile range are presented. Results: The AB has larger elastic moduli than the PB (P \ .0001) in the toe region (median, 2.73 MPa [interquartile range, 1.1-5.6 MPa] vs 0.65 MPa [0.44-1.5 MPa]) and the linear region (13.77 MPa [4.8-40.7 MPa] vs 1.96 MPa [0.58-9.3 MPa]). The AB demonstrated larger stress values, stronger collagen alignment, and more uniform collagen organization during stress-relaxation. PB collagen fibers were more disorganized than the AB during the zero (P = .046), transitional (P = .011), and linear (P = .007) regions of the stress-strain curve. Both UCL bundles exhibited very small changes in collagen alignment (SD of the angle of polarization) with load. Conclusion: The AB of the UCL is stiffer and stronger, with more strongly aligned and more uniformly oriented collagen fibers, than the PB. The small changes in collagen alignment indicate that the UCL response to load is due more to its static collagen organization than to dynamic changes in collagen alignment. Clinical Relevance: The UCL collagen organization may explain its susceptibility to injury with repetitive valgus loads.

MRI is a valuable, noninvasive method of elbow evaluation. This article updates orthopaedic surgeons on the various available MRI techniques and facilitates recognition of the MRI appearances of the most commonly seen pathologic elbow conditions.

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The role of ion channels in cell physiology is regulated by processes occurring after protein biosynthesis, which are critical for both channel function and targeting of channels to appropriate cell compartments. Here we apply biochemical and electrophysiological methods to investigate the role of the high-conductance, calcium-activated potassium (Maxi-K) channel C-terminal domain in channel tetramerization, association with the beta1 subunit, trafficking of the channel complex to the cell surface, and channel function. No evidence for channel tetramerization, cell surface expression, or function was observed with Maxi-K(1)(-)(323), a construct truncated three residues after the S(6) transmembrane domain. However, Maxi-K(1)(-)(343) and Maxi-K(1)(-)(441) are able to form tetramers and to associate with the beta1 subunit. Maxi-K(1)(-)(343)-beta1 and Maxi-K(1)(-)(441)-beta1 complexes are efficiently targeted to the cell surface and cannot be pharmacologically distinguished from full-length channels in binding experiments but do not form functional channels. Maxi-K(1)(-)(651) forms tetramers and associates with beta1; however, the complex is not present at the cell surface, but is retained intracellularly. Maxi-K(1)(-)(651) surface expression and channel function can be fully rescued after coexpression with its C-terminal complement, Maxi-K(652)(-)(1113). However coexpression of Maxi-K(1)(-)(343) and Maxi-K(1)(-)(441) with their respective C-terminal complements did not rescue channel function. Together, these data demonstrate that the domain(s) in the Maxi-K channel necessary for formation of tetramers, coassembly with the beta1 subunit, and cell surface expression resides within the S(0)-S(6) linker domain of the protein, and that structural constraints within the gating ring in the C-terminal region can regulate trafficking and function of constructs truncated in this region.

Some anesthetics attenuate expression of endotoxin-induced production of proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X) decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the effects of K/X on gut function and gene expression are unknown. The purpose of this study was to examine the effect of K/X on LPS-induced gastric fluid accumulation, and gastric tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase (COX)-2 expression, as well as serum TNF-alpha protein levels over time. We hypothesized that K/X would attenuate these LPS-induced endpoints. Rats were given either intraperitoneal saline or K (70 mg/kg) and X (6 mg/kg) 1 h before saline or LPS (20 mg/kg i.p.) treatment of 1, 3, or 5 h. Serum and gastric fluid and mucosa were collected and TNF-alpha, iNOS, and COX-2 expression were determined. LPS caused a significant increase in early serum and gastric mucosal TNF-alpha protein expression at 1 h, an effect that was significantly attenuated by K/X pretreatment. LPS caused significant gastric stasis and increased iNOS and COX-2 mRNA expression and iNOS protein expression in the stomach when compared with controls. K/X attenuated LPS-induced gastric fluid accumulation and upregulation of iNOS mRNA and protein, but not COX-2. These data indicate that K/X inhibits some proinflammatory genes and pathophysiologic responses in the serum and stomach during endotoxemia. The effects of K/X appear to inhibit transcriptional events in iNOS expression, which may be dependent on K/X-induced inhibition of early TNF-alpha expression. Furthermore, in rat models of endotoxemia, especially those evaluating the stomach, careful consideration needs to be given if anesthetic combinations with ketamine and/or xylazine are used, as they alter LPS-induced responses.

Loeys-Dietz syndrome is a recently recognized connective tissue disorder with widespread systemic involvement. Little is known about its skeletal phenotype. Our goal was to investigate the risk of fracture and incidence of low bone mineral density in patients with Loeys-Dietz syndrome. We performed a cross-sectional, descriptive, survey-based study with subsequent chart review from July 2011 to April 2012. Fifty-seven patients (26 men, 31 women) with Loeys-Dietz syndrome confirmed by genetic testing completed the survey (average age, 25.3 years; range, 0.9-79.6 years). There were a total of 51 fractures (33 patients): 35 fractures in the upper extremities, 14 in the lower extremities, and two in the spine. Fourteen patients (24.6%) reported two or more fractures. There was a 50% risk of fracture by age 14 years. The incidence of any fracture in this cohort was 3.86 per 100 person-years. Seventeen patients had dual-energy X-ray absorptiometry scans available for review, 11 (64.7%) of whom had at least one fracture. Thirteen included lumbar spine absorptiometry reports; eight (61.5%) indicated low or very low bone mineral density. In the left hip, ten of 14 participants (71.4%) had low or very low bone mineral density. In the left femoral neck, nine of 13 participants (69.2%) had low or very low bone mineral density. The lowest Z- and T-scores were not associated with an increased number of fractures. Patients with Loeys-Dietz syndrome have a high risk of fracture and a high incidence of low bone mineral density.