Intrathecal baclofen pumps do not accelerate progression of scoliosis in quadriplegic spastic cerebral palsy.

PURPOSE: To compare scoliosis progression in quadriplegic spastic cerebral palsy with and without intrathecal baclofen (ITB) pumps. METHODS: A retrospective matched cohort study was conducted. Patients with quadriplegic spastic cerebral palsy, GMFCS level 5, treated with ITB pumps with follow-up >1 year were matched to comparable cases by age and baseline Cobb angle without ITB pumps. Annual and peak coronal curve progression, pelvic obliquity progression and need for spinal fusion were compared. RESULTS: ITB group: 25 patients (9 female), mean age at pump insertion 9.4 and Risser 0.9. Initial Cobb angle 25.6° and pelvic tilt 3.2°. Follow-up 4.3 (1.0-7.8) years. Cobb angle at follow-up 76.1° and pelvic tilt 18.9°. Non-ITB group: 25 patients (14 female), mean age at baseline 9.2 and Risser 1.0. Initial Cobb angle 29.7° and pelvic tilt 7.1°. Follow-up 3.5 (1.0-7.5) years. Cobb angle at follow-up 69.1° and pelvic tilt 21.0°. The two groups were statistically similar for baseline age, Cobb angle and Risser grade. Mean curve progression was 13.6°/year for the ITB group vs 12.6°/year for the non-ITB group (p = 0.39). Peak curve progression was similar between the groups. Pelvic tilt progression was comparable; ITB group 4.5°/year vs non-ITB 4.6°/year (p = 0.97). During follow-up 5 patients in the ITB group and 9 in the non-ITB group required spinal fusion surgery for curve progression (p = 0.35). CONCLUSIONS: Patients with quadriplegic spastic cerebral palsy with and without ITB pumps showed significant curve progression over time. ITB pumps do not appear to alter the natural history of curve progression in this population.

Combined selective dorsal rhizotomy and scoliosis correction procedure in patients with cerebral palsy.

UNLABELLED: Intrathecal baclofen (ITB) therapy for spasticity has been suggested to accelerate the development of scoliosis. We present the case of a 17-year-old female patient with cerebral palsy who had ITB therapy from the age of 11 years. During this period, she developed a severe scoliosis measuring 86° from T11 to L4, with pain due to costo-pelvic impingement. Her baclofen pump had reached its end of life and required replacement if ITB therapy was to continue. This coincided with plans for scoliosis corrective surgery. METHODS: We performed scoliosis correction along with removal of baclofen pump and selective dorsal rhizotomy (SDR), as a single combined procedure. SDR was performed instead of ITB pump replacement for management of spasticity. RESULTS: Following surgery, scoliosis improved to 24°. At 6 month follow-up, there was significant improvement in spasticity and quality of life. CONCLUSIONS: This report illustrates the feasibility of a combined procedure to correct scoliosis and manage spasticity with SDR. We present the case details, our management and review of the published literature regarding the factors influencing treatment of scoliosis and spasticity.

The effect of pomegranate fruit extract on testosterone-induced BPH in rats.

BACKGROUND: Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. METHODS: A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. RESULTS: PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. CONCLUSION: The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties.

Cervical implantation of intrathecal baclofen pump catheter in children with severe scoliosis.

OBJECT: Intrathecal baclofen (ITB) pump catheter placement is traditionally performed through entry into the spinal sac at the lumbar spine. A minority of children with cerebral palsy have severe concomitant neuromuscular scoliosis. In these children, whether surgically treated or not, access to the intradural space via the lumbar spine may prove technically challenging. The authors report on a series of children in whom, for various reasons, an ITB catheter was implanted using a posterior cervical spine approach. METHODS: The records of 20 children in whom a baclofen catheter had been placed were retrospectively reviewed to assess the demographic details, indications, and outcome of this procedure. RESULTS: This approach was successful in all but one of the children in whom the procedure was abandoned given the presence of significant extradural scar tissue. Of the 20 children, 7 had previously undergone lumbar ITB catheter implantation, although the catheter was subsequently, iatrogenically transected during scoliosis surgery. Nine children had had corrective scoliosis surgery, and the fusion mass obviated access to the lumbar spinal sac. Four children had untreated scoliosis and corrective surgery was being contemplated. Complications included infection requiring explantation (2 patients), catheter migration (1 patient), intolerance to ITB (1 patient), and failure of implantation (1 patient). All patients who tolerated the ITB experienced improvement in spasticity. No complications were associated with the spinal level of catheter insertion. CONCLUSIONS: Implantation of an ITB catheter via a cervical approach is safe and feasible and should be considered in children with severe corrected or uncorrected scoliosis, and thus avoiding the lumbar spinal sac.

Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome.

Post-translational histone modifications are known to be altered in cancer cells, and loss of selected histone acetylation and methylation marks has recently been shown to predict patient outcome in human carcinoma. Immunohistochemistry was used to detect a series of histone lysine acetylation (H3K9ac, H3K18ac, H4K12ac, and H4K16ac), lysine methylation (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) marks in a well-characterized series of human breast carcinomas (n = 880). Tissue staining intensities were assessed using blinded semiquantitative scoring. Validation studies were done using immunofluorescence staining and Western blotting. Our analyses revealed low or absent H4K16ac in the majority of breast cancer cases (78.9%), suggesting that this alteration may represent an early sign of breast cancer. There was a highly significant correlation between histone modifications status, tumor biomarker phenotype, and clinical outcome, where high relative levels of global histone acetylation and methylation were associated with a favorable prognosis and detected almost exclusively in luminal-like breast tumors (93%). Moderate to low levels of lysine acetylation (H3K9ac, H3K18ac, and H4K12ac), lysine (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) were observed in carcinomas of poorer prognostic subtypes, including basal carcinomas and HER-2-positive tumors. Clustering analysis identified three groups of histone displaying distinct pattern in breast cancer, which have distinct relationships to known prognostic factors and clinical outcome. This study identifies the presence of variations in global levels of histone marks in different grades, morphologic types, and phenotype classes of invasive breast cancer and shows that these differences have clinical significance.