Noninvasive genomic detection of melanoma.

BACKGROUND: Early detection and treatment of melanoma is important for optimal clinical outcome, leading to biopsy of pigmented lesions deemed suspicious for the disease. The vast majority of such lesions are benign. Thus, a more objective and accurate means for detection of melanoma is needed to identify lesions for excision. OBJECTIVES: To provide proof-of-principle that epidermal genetic information retrieval (EGIR™; DermTech International, La Jolla, CA, U.S.A.), a method that noninvasively samples cells from stratum corneum by means of adhesive tape stripping, can be used to discern melanomas from naevi. METHODS: Skin overlying pigmented lesions clinically suspicious for melanoma was harvested using EGIR. RNA isolated from the tapes was amplified and gene expression profiled. All lesions were removed for histopathological evaluation. RESULTS: Supervised analysis of the microarray data identified 312 genes differentially expressed between melanomas, naevi and normal skin specimens (P<0·001, false discovery rate q<0·05). Surprisingly, many of these genes are known to have a role in melanocyte development and physiology, melanoma, cancer, and cell growth control. Subsequent class prediction modelling of a training dataset, consisting of 37 melanomas and 37 naevi, discovered a 17-gene classifier that discriminates these skin lesions. Upon testing with an independent dataset, this classifier discerned in situ and invasive melanomas from naevi with 100% sensitivity and 88% specificity, with an area under the curve for the receiver operating characteristic of 0·955. CONCLUSIONS: These results demonstrate that EGIR-harvested specimens can be used to detect melanoma accurately by means of a 17-gene genomic biomarker.

Fibrillar collagen-biphasic calcium phosphate composite as a bone graft substitute for spinal fusion.

The osteoconductive capacity of fibrillar collagen-biphasic calcium phosphate composition was compared to autogenous bone in a canine spinal fusion model. All animals underwent a standard intervertebral body fusion (L2-L4) with rigid internal fixation and received either autogenous bone alone or a mixture of the ceramic and autogenous bone (3:1) as the graft material. Animals were followed for 12 months and the quality of fusion in each animal assessed by biomechanical testing and histological analysis. The fused L2-L4 segment of each dog was embedded in bone cement and mounted in a specially designed mechanical tester for testing in flexion, extension, and side bending. Overall, the mean rigidity of the fusion mass was not significantly different between the two groups [10.5 +/- 4.1 (SD) for autogenous bone vs. 11.3 +/- 1.7 for the ceramic plus autogenous bone, p greater than 0.05]. Similar findings were obtained for mean bending moment, compressive load, angular deformation, and energy absorbed for the two groups. Histological analysis was performed on transverse nondecalcified specimens. Quantitation of bone ingrowth using back-scattered electron imaging disclosed no significant differences in the amount of new bone formed at the graft site between autogenous bone and the ceramic plus autogenous bone recipients (23.4 +/- 10% vs. 25.8 +/- 8.8%) when correction for the autogenous bone volumes was performed. Light microscopic analysis of toluidine blue-stained transverse sections demonstrated new bone growth around and through the ceramic bone graft material. These results suggest that use of a collagen-biphasic calcium phosphate ceramic and autogenous bone mixture (3:1) provides a suitable osteoconductive alternative to the use of autogenous bone and results in the formation of a mechanically competent fusion mass not significantly different from that obtained with autogenous bone alone.

Porous ceramics as bone graft substitutes in long bone defects: a biomechanical, histological, and radiographic analysis.

Three porous ceramic bone graft materials were compared with regard to their ability to heal a 2.5 cm defect created surgically in a bilateral canine radius model. The ceramic materials were analyzed at 12 and 24 weeks after surgery and included tricalcium phosphate, hydroxyapatite, and collagen hydroxyapatite, which contained a mixture of 35% tricalcium phosphate and 65% hydroxyapatite with added collagen. Each material was evaluated alone and with added bone marrow aspirate. All the implants were compared with a graft of autogenous cancellous bone in the contralateral radius. Biomechanical testing and radiographic evaluation revealed that the addition of bone marrow aspirate was essential for tricalcium phosphate and hydroxyapatite to achieve results comparable with those of cancellous bone. Collagen hydroxyapatite performed well without the addition of bone marrow, although the addition of marrow did have a positive effect. Further qualitative radiographic and histological analysis demonstrated that tricalcium phosphate was the only ceramic that showed any sign of degradation at 24 weeks. This observed degradation proved to be an important factor in evaluating radiographs because the radiodensity of collagen hydroxyapatite and hydroxyapatite interfered with the determination of radiographic union. At 24 weeks, tricalcium phosphate with bone marrow was the material that performed most like cancellous bone. In this study, the biomechanical and radiographic parameters of tricalcium phosphate with bone marrow were roughly comparable with those of cancellous bone at 12 and 24 weeks. Tricalcium phosphate was the only implant that showed significant evidence of degradation at 24 weeks by both histological and radiographic evaluations, and this degradation took place only after a degree of mechanical competence necessary for weight-bearing was achieved.

Early versus delayed stabilization of femoral fractures. A prospective randomized study.

A prospective randomized study comparing the results of early with delayed reduction and stabilization of acute femoral fractures in adults was performed over a two-year period in 178 patients. Only patients who were more than sixty-five years old and had a fracture of the hip were excluded. Arterial blood gases, injury-severity score at the time of admission, pulmonary function, days in the hospital, days in the intensive-care unit, and hospital costs were recorded for all patients. The patients were divided into two groups: those who had an isolated fracture of the femur and those who had multiple injuries. When stabilization of the fracture was delayed in the patients who had multiple injuries, the incidence of pulmonary complications (adult respiratory-distress syndrome, fat embolism, and pneumonia) was higher, the hospital stay was longer, and the number of days in the intensive-care unit was increased. The cost of hospital care showed a statistically significant increase for all patients who had delayed treatment of the fracture compared with those who had early stabilization.

Capitellocondylar total elbow arthroplasty.

Sixty-nine non-constrained capitellocondylar metal-to-plastic total elbow-replacement prostheses were implanted in sixty-four patients with rheumatoid arthritis. These patients were followed for an average of 3.5 years. Postoperative flexion and pronation were significantly improved, but no significant increase in postoperative extension or supination could be demonstrated. Based on a rating system evaluating pain and function, there were 87 per cent good or excellent results. The complication rate based on the total number of prostheses implanted was 39 per cent. Eight patients required revision of the arthroplasty: four for dislocation of the prosthesis, two for sepsis, one for loosening, and one for a fracture. Eight other asymptomatic patients showed minimum radiolucent lines adjacent to the ulnar component. No patient demonstrated radiolucent lines adjacent to the humeral component.

Severe open tibial fractures: a study protocol.

A prospective randomized study of severe open tibial fractures (Type II and III) was performed. Individual fractures were randomized to treatment groups according to initial antibiotic therapy: One consisted of a first-generation cephalosporin, and the other consisted of a third-generation cephalosporin. Initial antibiotic therapy was given in all patients for 48 h and then specific antibiotic treatment was used as indicated by culture. The purpose of this study was to determine whether or not additional gram-negative coverage had an effect on the overall infection rate or the type of infection in severe open tibial fractures. Additional factors, such as the timing of bone grafts and soft tissue coverage, were evaluated in this study as well. Although there was no statistical difference in the rate of infection with the use of a first- versus a third-generation cephalosporin, there was a trend toward a decreased infection rate as well as toward less morbid infections with the use of a third-generation cephalosporin. The study also confirms that early bone graft should not be performed prior to 6 weeks post injury or after successful soft tissue coverage has been achieved. On the other hand, soft tissue coverage procedures should be performed at the earliest possible date to decrease the overall infection rate.

Surgical anatomy of the axillary nerve.

Any surgical approach that splits the deltoid puts the axillary nerve at risk secondary to extension from traction or sharp dissection. Standard texts an anatomy and chapters on surgical approaches frequently state the axillary nerve comes to lie approximately 2 inches from the acromion. However, a large series of cadavers of varying sex and size on which these measurements had been obtained could not be found in an extensive literature search. Fifty-one embalmed cadaveric specimens representing 102 shoulders were dissected in the static portion of this study. In nearly 20% of cadavers the nerve at some point along its course around the humerus in the deltoid muscle was less than 5 cm from the palpable edge of the acromion. This was especially true of female cadavers with short arm spans; in one cadaver the nerve was 3.1 cm from the acromial edge. Abducting the shoulder to 9cr decreases the distance from the nerve to the palpable edge of the acromion nearly 30%. Five centimeters does not describe an absolute safe zone for the axillary nerve. Furthermore, abduction of the arm brings the nerve even closer to commonly used bony landmarks.

Degradative enzyme activity in isolated chondrocyte populations.

Chondrocytes from adult and immature articular cartilage were separated on the basis of size by rate-zonal centrifugation in a Ficoll density gradient. Lysozomal enzyme activity (acid phosphatase and beta-glucuronidase) was determined in gradient fractions containing chondrocytes of different sizes. Acid phosphatase and beta-glucuronidase activity in mature articular cartilage was greatly increased in small sized cells, located in the superficial tangential zone. In cells from immature calf articular cartilage, there were two peaks of increased activity, on in the superficial tangential zone, the other in the deep radial zone, close to the cartilage bone junction. It is speculated that the small surface cells, with thier high degradative enzyme levels, may explain why the osteoarthritis process starts at the surface.