Faculty Bibliography

OBJECTIVES: To evaluate the variability of the ideal trochanteric starting point as a possible cause for malreduction of subtrochanteric fractures and to analyze the accuracy of contralateral templating to predict correct entry site. METHODS: Standardized anteroposterior pelvis radiographs of 50 patients were evaluated by two independent reviewers. Patients with advanced osteoarthritis, severe hip deformity, and radiographs with asymmetric hip rotation were excluded. Ideal nail entry site was established using a template for a trochanteric nail with a 6 degrees proximal bend. The distance from the greater trochanteric tip to the ideal nail entry site was measured. Additionally, offset of the greater trochanter tip from the femoral longitudinal axis was measured. Interobserver reliability and accuracy of contralateral templating were evaluated. RESULTS: The ideal entry point ranged from 16 mm medial to 8 mm lateral to the trochanteric tip (mean, 3 mm medial; standard deviation, 5 mm). In 70% of patients, the ideal entry point was medial to and in 23% lateral to the tip of the greater trochanter. Ideal entry points were located within 2 mm of the trochanteric tip in 29% and within 4 mm in 44% of patients. The location of the ideal entry point relative to the trochanteric tip had a weak correlation with patient height and neck shaft angle (r: -0.23 and r: -0.35, respectively). Interobserver reliability and agreement between left and right side measurements were strong (intraclass correlation coefficient: >0.94 and >0.88, P < 0.001, respectively). The mean measurement differences between sides was 0 mm (95% confidence interval: -1 to 1). Greater trochanter offset averaged 15 mm (range, 5-26 mm; standard deviation: 5) on the right and 15 mm (range, 5-25 mm; standard deviation: 5.1) on the left (P = 0.95). CONCLUSION: A high degree of variability exists for the ideal trochanteric entry site. The trochanteric tip represents the ideal starting point in only the minority of cases. Preoperative contralateral templating provides an accurate means for establishing a patient-specific entry point to minimize fracture malreduction.

BACKGROUND: The posterior interosseous nerve is at risk for iatrogenic injury during surgery involving the proximal aspect of the radius. Anatomic relationships of this nerve in skeletally intact cadavers have been defined, but variations associated with osseous and soft-tissue trauma have not been examined. This study quantifies the effect of a simulated diaphyseal fracture of the proximal aspect of the radius and of a radial neck fracture with an Essex-Lopresti injury on the posterior interosseous nerve. METHODS: In twenty unembalmed cadaveric upper extremities, the distance from the radiocapitellar joint to the point where the posterior interosseous nerve crosses the midpoint of the axis of the radius (Thompson approach) was recorded in three forearm positions (supination, neutral, and pronation). Specimens were then treated with either proximal diaphyseal osteotomy (n = 10) or radial head excision with simulated Essex-Lopresti injury (n = 10), and the position of the nerve in each forearm position was remeasured. We evaluated the effect of the simulated trauma on nerve position and correlated baseline measurements with radial length. RESULTS: In neutral rotation, the posterior interosseous nerve crossed the radius at a mean of 4.2 cm (range, 2.5 to 6.2 cm) distal to the radiocapitellar joint. In pronation, the distance increased to 5.6 cm (range, 3.1 to 7.4 cm) (p < 0.01). Supination decreased that distance to 3.2 cm (range, 1.7 to 4.5 cm) (p < 0.01). Radial length correlated with each of these measurements (r > 0.50, p = 0.01). Diaphyseal osteotomy of the radius markedly decreased the effect of forearm rotation, as the change in nerve position from supination to pronation decreased from 2.13 +/- 0.8 cm to 0.24 +/- 0.2 cm (p = 0.001). Proximal migration of the radius following radial head excision was accompanied by similar magnitudes of proximal nerve migration in all forearm positions. CONCLUSIONS: Forearm pronation has minimal effect on posterior interosseous nerve position within the surgical window following a displaced diaphyseal osteotomy of the proximal aspect of the radius. The nerve migrates proximally toward the capitellum with proximal migration of the radius in all forearm positions following a simulated Essex-Lopresti lesion. Visualization and protection of the posterior interosseous nerve is recommended when operatively exposing the traumatized proximal aspect of the radius.

Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-naive adult South Africans. These individuals ranged in disease severity from early (CD4 count >500) to advanced HIV-1 disease (CD4 count <50). We found that the frequency of NK cells expressing KIR2DL1, an inhibitory receptor, and/or KIR2DS1, an activating receptor, tended to decrease with increasing HIV-1 viral load. We also discovered a significant increase (p < 0.05) in overall NK cell degranulation with disease progression. We found that acutely activated NK cells (CD69(pos)) were deficient in NKp46 expression ex vivo. In conclusion, we observed that with viremia and advanced HIV-1 disease, activated NK cells lack NKp46 expression, and KIR2DS1(pos) and/ or KIR2DL1(pos) NK cells are reduced in frequency. These findings suggest that modulation of receptor expression on NK cells may play a role in HIV-1 pathogenesis, and provide new insights on immunological changes in advanced HIV-1 disease.

The exceptional value of gene targeting technology to generate mouse models of human disease exists under the shadow of potential genetic errors. We previously observed an unexpected brain-behavior phenotype that resulted from a gene-targeting experiment designed to delete the Zfa gene. Given that the transcription of Zfa is restricted to the germ cell lineage of adult testis, it was both a surprise and a concern when the resulting mice had a phenotype present in both sexes that included abnormal brains and violent behavior. We hypothesized that an unrelated mutation may have been responsible for the unexpected phenotype. Here we show that the single gene mutation, Nr2e1(frc) (fierce), which was responsible for the brain-behavior phenotype, existed in the embryonic stem (ES) cell even before the derivation of the Zfa knockout mice. Our work thus highlights a concern in gene targeting, namely, that ES cells can harbor unexpected mutations, which can lead to genotype-phenotype misattribution. Based on our findings, we caution the gene-targeting community to use low-passage ES cells, to characterize mice derived from more than one independently targeted ES cell clone, and to backcross mice to allow for segregation of distant but linked mutations.