Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case-Control Study.

Breast cancer (BC) has a high incidence rate among women worldwide, and the mechanisms and etiology of this disease are not yet fully understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that plays important roles in energy metabolism and cellular differentiation, is also suggested to be effective in cancer development. However, the results of studies investigating the cancer association with PPARgamma are inconsistent, creating a need for further investigation of the effects of this transcription factor on BC risk. We have examined the Pro12Ala-(rs1801282) and C161T-(rs3856806) polymorphisms of the PPARgamma gene in Turkish patients with BC in this case-control study. A total of 95 women diagnosed with BC as cases and 119 controls were genotyped for PPARgamma polymorphisms by polymerase chain reaction and restriction fragment length polymorphism techniques. The ProPro genotype and T161 allele were associated with an increased risk of BC comparing with the Ala12 allele and CC161 genotype, respectively (p < 0.001). The multivariate regression analysis confirmed that the ProPro genotype (p < 0.011), T161 allele (p < 0.001), smoking (p = 0.019), and advanced age (> 60 years) (p = 0.007) are risk factors for breast cancer. We also found that the PPARgamma Pro12Ala and C161T polymorphisms were in linkage disequilibrium (D':0.511, r2:0.099). It was determined that carrying ProPro-T161 risky PPARgamma haplotype was associated with a higher risk of BC compared to protective Ala12-CC161 haplotype (p < 0.01, OR:7.797, 95% CI:3.521-17.263). We concluded that PPARgamma Pro12Ala and C161T polymorphisms are associated with increased BC risk, and ProPro-T161 risky haplotype, which is in linkage disequilibrium, increases this effect.

Identification of candidate biomarkers in converting and non-converting clinically isolated syndrome by proteomics analysis of cerebrospinal fluid.

Multiple sclerosis (MS) often starts in the form of clinically isolated syndrome (CIS) and only some of the CIS patients progress to relapsing-remitting MS (RRMS). Biomarkers to predict conversion from CIS to MS are thus greatly needed for making correct treatment decisions. To identify a predictive cerebrospinal fluid (CSF) protein, we analyzed the first-attack CSF samples of CIS patients who converted (CIS-MS) (n = 23) and did not convert (CIS-CIS) (n = 19) to RRMS in a follow-up period of 5 years using proteomics analysis by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and verified by ELISA. Label-free differential proteomics analysis of CSF ensured that 637 proteins were identified and 132 of these proteins were found to be statistically significant. Further investigation with the ingenuity pathway analysis (IPA) software led to identification of three pathway networks mostly comprised proteins involved in inflammatory response, cellular growth and tissue proliferation. CSF levels of four of the most differentially expressed proteins belonging to the cellular proliferation network function, chitinase-3-like protein 1 (CHI3L1), tumor necrosis factor receptor superfamily member 21 (TNFRSF21), homeobox protein Hox-B3 (HOXB3) and iduronate 2-sulfatase (IDS), were measured by ELISA. CSF levels of HOXB3 were significantly increased in CIS-MS patients. Our results indicate that cell and tissue proliferation functions are dysregulated in MS as early as the first clinical episode. HOXB3 has emerged as a potential novel biomarker which might be used for prediction of CIS-MS conversion.

Z-plate instrumentation in thoracolumbar spinal fractures.

Anterior decompression enables direct access and good canal clearance of the injury level in thoracolumbar spinal fractures, and decompressing the neural elements is shown to be an important factor for neurologic improvement and pain relief in many cases. In this study, results with anterior decompression and Z-plate instrumentation in thoracolumbar spinal fractures are reviewed. Nineteen patients with old spinal fracture (average: 3 years) and neural compression, and 15 patients with fresh thoracolumbar fractures with neurologic deficit and/or major anterior spinal canal obstruction had anterior decompression and Z-plate instrumentation with anterior fusion. Stabilization was protected with thoracolumbar thermoplastic braces for six months. Preoperative kyphotic deformity averaged 20.9 degrees (range: 7 degrees to 64 degrees), while it was an average of 8.0 degrees (range: -12 degrees to 35 degrees) postoperatively. Medullary canal compromise was 41% an average (range: 13% to 67%) and postoperatively it had an average value of 6% (range: 0% to 18%). Patients were followed up an average of 30 months (range: 25 to 36 months). The unchanged positions of bone grafts and statistically insignificant loss of correction in the sagittal plane are accepted as evidence for bony fusion in all patients. Z-plate instrumentation provides stable fixation. Additionally, the technique can be performed easily and has the added benefit of being MRI-compatible.

Spinal imbalance and decompensation problems in patients treated with Cotrel-Dubousset instrumentation.

The basic principles of current idiopathic scoliosis treatment are three-dimensional correction and rigid fixation. Although it is accepted that Cotrel-Dubousset instrumentation (CDI) meets these goals, there is concern about the potential risk of trunk imbalance and spinal decompensation during the derotation manoeuvre. The results of 45 patients with idiopathic scoliosis treated with CDI between December 1988 and August 1992 were retrospectively analysed. Mean age was 14.3 years and mean follow-up period was 48.6 months. An average correction of 49.6% was achieved in the major curves. The best results were obtained in King type III curves, with a 69.4% correction. Spinal imbalance was evaluated by measuring lateral trunk shift (LT), shift of head (SH) and shift of stable vertebra (SS). Decompensation was measured by the increase in secondary curves. When all curve types were included, the average preoperative LT value of 1.96 vertebral units (VU) was brought down to 0.91 VU postoperatively, achieving a 55.9% correction. Fourteen patients had an SH value of zero preoperatively and remained balanced after instrumentation. Of the 41 remaining patients, 21 achieved an SH value of zero postoperatively. When all cases were included, the average preoperative SH value was 1.0 VU, which was corrected to 0.42 VU with CDI (69% correction). An average correction of SS of 75.5% was obtained, with the mean preoperative value of 0.73 VU being corrected to 0.19 VU. At the last follow-up visit, a secondary curve had formed above the major curve in one patient, and three patients had a junctional kyphosis. Loss of correction in the frontal plane correlated with loss of correction of LT. The rigid and semiflexible lumbar curves had a tendency to progress when they were not instrumented, especially in type II curves. Junctional kyphosis could be prevented when concave laminar claws were used in the thoraco-lumbar region. It was concluded that spinal decompensation and imbalance could be minimized with careful preoperative planning, avoidance of overcorrection and use of long instrumentation in double major curves.

Results of the AO spinal internal fixator in the surgical treatment of thoracolumbar burst fractures.

The potential for clinical instability following thoracolumbar fractures has evoked a progressive increase in interest in the surgical treatment of unstable thoracolumbar fractures. From September 1988 to October 1991, 44 thoracolumbar burst fractures were treated surgically by the AO Spinal Internal Fixator at the Orthopaedics and Traumatology Clinics of Ankara Social Security Hospital. Mean follow-up period was 28.8 (range 12-48) months. Fourteen (31.8%) of the patients were female, and 30 (68.2%) were male. Postoperatively, the mean anterior vertebral height loss and spinal canal compromise were corrected by 36.5% and 39.9%, respectively. Also, postoperatively 15.9% of improvement was obtained in the mean kyphosis angle. The mean compression angle, which was 19.5 degrees preoperatively, was corrected by 12.3 degrees and came to an average of 7.1 degrees postoperatively. In light of these data, it is suggested that the AO Spinal Internal Fixator effectively restores three-dimensional alignment of the spine and provides a rigid fixation.

Cotrel-Dubousset instrumentation in the treatment of unstable thoracic and lumbar spine fractures.

The use of computed tomography and developments in spinal biomechanics have led to a better understanding of vertebral fractures. The disappointing results achieved with conservative treatment have led to an increasing popularity of surgical treatment in the last 15 years. The results of 20 unstable thoracic or lumbar spine fractures treated surgically with Cotrel-Dubousset instrumentation at the First Clinic of Orthopaedics and Traumatology of the Ankara Social Security Hospital between December 1988 and June 1991 were evaluated in this study. The mean follow-up was 31.9 months. The mean sagittal index angle was 23.7 degrees +/- 6.8 degrees preoperatively and was corrected by 67.1 +/- 29.9%, and the thoracolumbar junction angle was brought within physiological limits in 65% of the cases. Postoperatively, the neurological status improved in 15% of the patients and remained unchanged in the rest. It was concluded that the Cotrel-Dubousset instrumentation established vertebral stability in unstable vertebral fractures by forming a rigid frame and restored physiological thoracic and lumbar postural contours due to its highly corrective effect in the sagittal plane.

Supracondylar fractures of the humerus in children: analysis of the results in 142 patients.

One hundred forty-two children who had supracondylar humerus fractures and who were treated either by open reduction and internal fixation or by closed methods were reviewed. There were 104 boys and 38 girls. Their ages ranged between 2 and 14 years, with an average age of 8 years. One hundred thirteen of the fractures were of the extension type and 29 were of the flexion type. Sixty-two patients were treated by manipulative reduction and immobilization in a plaster of Paris cast, and 20 were treated by overhead skeletal traction followed by the application of a plaster of Paris cast. The other 60 patients were treated by open reduction and internal fixation. The follow-up period ranged from 4 years to 11 years, with an average of 7.5 years. The results were evaluated based on the range of motion, the subsequent deformity, if any, and the carrying angle. In the overall series we had 72 (50.70%) excellent, 31 (21.83%) good, 13 (9.15%) fair, and 26 (18.30%) poor results.