Gene expression differences between ruptured anterior cruciate ligaments in young male and female subjects.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries is two to eightfold greater in female compared with male athletes. Anatomic, hormonal, and neuromuscular factors have been associated with this disparity. This study compared gene expression and structural features in ruptured but otherwise normal ACL tissue from young female and male athletes. METHODS: A biopsy sample of ruptured ACL tissue (which would normally have been discarded) was obtained intraoperatively from seven female and seven male athletes (12.7 to 22.6 years old). Each sample was divided into portions for histological and gene expression analyses. Specimens for gene analysis were frozen and ground, and RNA was extracted and purified. Microarray analysis was performed on RNA isolated from four female and three male study participants (13.9 to 18.5 years old) who had a noncontact injury. Genes with an expression level that differed significantly between these female and male athletes were grouped into functionally associated networks with use of IPA software (Qiagen). Three genes of interest were chosen for further validation by RT-qPCR (reverse transcription-quantitative polymerase chain reaction) analysis of the samples from all fourteen patients. Several statistical methods were used to examine sex-related differences. RESULTS: Microarray analysis of the RNA isolated from the ruptured ACL tissue from the female and male athletes identified thirty-two genes with significant differential expression. Fourteen of these genes were not linked to the X or Y chromosome. IPA analysis grouped these genes into pathways involving development and function of skeletal muscle and growth, maintenance, and proliferation of cells. RT-qPCR confirmed significant differences in expression of three selected genes: ACAN (aggrecan) and FMOD (fibromodulin) were upregulated in female compared with male study participants, and WISP2 (WNT1 inducible signaling pathway protein 2) was downregulated. No morphological differences among the ruptured tissue from the various participants were apparent on histological examination. CONCLUSIONS: The genes identified in this study as differing distinctly according to sex produce major molecules in the ACL extracellular matrix. Significant upregulation of ACAN and FMOD (which regulate the matrix) and downregulation of WISP2 (which is involved in collagen turnover and production) may account for the weaker ACLs in female compared with male individuals.

An unusual form of superficially disseminated glioma in children: report of 3 cases.

Three children, aged 4, 5, and 9 years, had an insidious onset of ataxia. Magnetic resonance imaging (MRI) showed hydrocephalus and countless foci of high T2 signal coating the cerebellum, basilar cisterns, brainstem, and fourth ventricle. Similar lesions were present in the spinal cord. Symptoms were relatively mild given the massive tumor burden. Biopsies were composed of superficially infiltrating cells with oligodendroglioma-like features (perinuclear halos and cytologic monotony) and microcysts. Classical cytogenetic analysis of 2 cases showed normal karyotypes. Chromosome fluorescence in situ hybridization revealed 1p36 deletion with intact 19q in 2 cases and no abnormality in one. A similar combination of clinical, MRI, and histopathologic findings has been reported previously in 10 other cases. The pathologic findings suggest a glioma with diffuse or multifocal superficial origin and do not correspond to a described entity in the current World Health Organization (WHO) classification of brain tumors.

"Smile" incision: an approach for open reduction and internal fixation of calcaneal fractures.

MATERIALS: A consecutive group of 73 patients (77 calcaneal fractures) treated with open reduction and internal fixation through a smile-shaped lateral approach to the hindfoot were reviewed retrospectively. Inclusion criteria were a closed displaced intra-articular fracture of the calcaneus, no compartment syndrome, and adequate followup. Followup ranged from 4 months to 4 years. RESULTS: One patient had a deep wound infection that required removal of hardware and intravenous antibiotics. No deep dehiscence or flap necrosis occurred. Superficial dehiscence occurred in three patients (4%) and superficial necrosis was seen in nine patients (12%); all resolved with continued casting to protect the wound. Six patients (8%) complained of numbness or pain in the sural nerve distribution. No symptomatic neuromas were seen. Reflex sympathetic dystrophy occurred in three patients (4%); all resolved with sympathetic blocks. Only one patient required an additional procedure for treatment of a wound-related problem or infection. CONCLUSION: The "smile" incision provides good fracture exposure for reduction without added morbidity.