Comprehensive short-term outcome assessment of selective dorsal rhizotomy

This study retrospectively evaluated the safety and efficacy of selective dorsal rhizotomy (SDR) in participants who underwent a rigorous selection process, uniform surgical procedure, and a standardized postoperative rehabilitation process. Outcome measures assessed were the Ashworth scale for spasticity, the Gillette Gait Index (GGI) for overall gait pathology, oxygen cost for gait efficiency, and the Gillette Functional Assessment Questionnaire (functional walking ability scale; [FAQ]) for functional mobility. Outcomes were evaluated for 136 children (81 males, 55 females; mean age 7y 3mo [SD 2y 1mo], range 3y 5mo-18y 9mo) for an average of 18.3 months (SD 4.4mo) postoperatively. All participants had a diagnosis of cerebral palsy (CP): 10 quadriplegia, 19 triplegia, and 107 diplegia. Preoperative Gross Motor Function Classification System levels were: Level I n=6; Level II n=64; Level III n=59, and Level IV n=7. All outcome measures improved for the group as a whole. Spasticity improved with 66 to 92% of possible gain in Ashworth scores; GGI was 7.5 times more likely to have a good as opposed to a poor outcome; energy efficiency improved in over half of the participants, and the FAQ demonstrated a statistically significant improvement of 0.9 levels (p<0.001). The rate of complications was low, with peri- and postoperative complications resolved by time of discharge.     

Metallosis after metal-on-polyethylene total hip arthroplasty

Metal debris should not be generated in a well-fixed, well-functioning metal-on-polyethylene total hip arthroplasty. However, surgeons sometimes encounter periprosthetic metallosis during revision hip surgery. Insert wear, fracture, or dislodgment in modular components may lead to articulation of the prosthetic head with the metallic shell and subsequent metallosis. Metallosis may occur with loose acetabular components as a consequence of fretting of the screws and shell screw holes or shedding of the ingrowth surface of the component. The femoral component can also be a source of metallosis: Wear of a titanium femoral head, loosening of rough surface finish from the femoral stem, and stem fracture all may result in metallic particles being deposited in periarticular tissues. Specific clinical and radiographic findings can help in differentiating these forms of failure and in planning surgery. When metallic debris-induced bone loss is recognized early, surgical intervention may limit its progression.     

Moving on time: brain network for auditory-motor synchronization is modulated by rhythm complexity and musical training

Much is known about the motor system and its role in simple movement execution. However, little is understood about the neural systems underlying auditory-motor integration in the context of musical rhythm, or the enhanced ability of musicians to execute precisely timed sequences. Using functional magnetic resonance imaging, we investigated how performance and neural activity were modulated as musicians and nonmusicians tapped in synchrony with progressively more complex and less metrically structured auditory rhythms. A functionally connected network was implicated in extracting higher-order features of a rhythm's temporal structure, with the dorsal premotor cortex mediating these auditory-motor interactions. In contrast to past studies, musicians recruited the prefrontal cortex to a greater degree than nonmusicians, whereas secondary motor regions were recruited to the same extent. We argue that the superior ability of musicians to deconstruct and organize a rhythm's temporal structure relates to the greater involvement of the prefrontal cortex mediating working memory.     

A randomized crossover trial of a wedged insole for treatment of knee osteoarthritis

OBJECTIVE: In uncontrolled studies, a lateral-wedge insole has reduced knee pain in patients with medial knee osteoarthritis (OA). The aim of this study was to test the efficacy of this simple, low-cost intervention for pain in patients with medial knee OA. METHODS: We conducted a double-blind, randomized, crossover trial designed to detect a small effect of treatment. Participants were at least 50 years of age and had medial joint space narrowing on posteroanterior semiflexed radiographs and scores indicating moderate pain for 2 of the 5 items on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale. Participants were randomized to receive a 5 degrees lateral-wedge insole or a neutral insole for 6 weeks. Following a 4-week washout period, participants crossed over to the other treatment for 6 weeks. Knee pain, the primary outcome, was assessed by the WOMAC pain scale (visual analog scale version). Secondary outcomes included the WOMAC disability subscale, overall knee pain, 50-feet walk time, chair-stand time, and use of medications for knee pain. RESULTS: Ninety patients were randomized. The mean difference in pain between the 2 treatments was 13.8 points on the WOMAC pain scale (95% confidence interval -3.9, 31.4 [P=0.13]). We observed similar small effects for the secondary outcomes. CONCLUSION: The effect of treatment with a lateral-wedge insole for knee OA was neither statistically significant nor clinically important.     

A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies

Malignancies associated with latent Epstein-Barr virus (EBV) are resistant to nucleoside-type antiviral agents because the viral enzyme target of these antiviral drugs, thymidine kinase (TK), is not expressed. Short-chain fatty acids, such as butyrate, induce EBV-TK expression in latently infected B cells. As butyrate has been shown to sensitize EBV(+) lymphoma cells in vitro to apoptosis induced by ganciclovir, arginine butyrate in combination with ganciclovir was administered in 15 patients with refractory EBV(+) lymphoid malignancies to evaluate the drug combination for toxicity, pharmacokinetics, and clinical responses. Ganciclovir was administered twice daily at standard doses, and arginine butyrate was administered by continuous infusion in an intrapatient dose escalation, from 500 mg/(kg/day) escalating to 2000 mg/(kg/day), as tolerated, for a 21-day cycle. The MTD for arginine butyrate in combination with ganciclovir was established as 1000 mg/(kg/day). Ten of 15 patients showed significant antitumor responses, with 4 CRs and 6 PRs within one treatment cycle. Complications from rapid tumor lysis occurred in 3 patients. Reversible somnolence or stupor occurred in 3 patients at arginine butyrate doses of greater than 1000 mg/(kg/day). The combination of arginine butyrate and ganciclovir was reasonably well-tolerated and appears to have significant biologic activity in vivo in EBV(+) lymphoid malignancies which are refractory to other regimens.     

Molecular mechanisms of resistance and toxicity associated with platinating agents

Platinating agents, including cisplatin, carboplatin, and oxaliplatin, have been used clinically for nearly 30years as part of the treatment of many types of cancers, including head and neck, testicular, ovarian, cervical, lung, colorectal and relapsed lymphoma. The cytotoxic lesion of platinating agents is thought to be the platinum intrastrand crosslink that forms on DNA, although treatment activates a number of signal transduction pathways. Treatment with these agents is characterized by resistance, both acquired and intrinsic. This resistance can be caused by a number of cellular adaptations, including reduced uptake, inactivation by glutathione and other anti-oxidants, and increased levels of DNA repair or DNA tolerance. Here we investigate the pathways that treatment with platinating agents activate, the mechanisms of resistance, potential candidate genes involved in the development of resistance, and associated clinical toxicities. Although the purpose of this review is to provide an overview of cisplatin, carboplatin, and oxaliplatin, we have focused primarily on preclinical data that has clinical relevance generated over the past five years.     

Cyclooxygenase-2 expression is critical for chronic UV-induced murine skin carcinogenesis

While it has been established that both the constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2, respectively) play important roles in chemical initiation-promotion protocols with phorbol ester tumor promoters, the contribution of these two enzymes to ultraviolet (UV) light-induced skin tumors has not been fully assessed. To better understand the contribution of COX-1 and COX-2 to UV carcinogenesis, we transferred the null allele for each isoform onto the SKH-1 hairless strain of mouse. Due to low viability on this background with complete knockout of COX-2, heterozygous mice were used in UV carcinogenesis experiments. While the lack of one allele of COX-1 had no effect on tumor outcome, the lack of one allele of COX-2 resulted in a 50-65% reduction in tumor multiplicity and a marked decrease in tumor size. Additionally, transgenic SKH-1 mice that overexpress COX-2 under the control of a keratin 14 promoter developed 70% more tumors than wild-type SKH-1 mice. The lack of one allele of either COX-1 or COX-2 reduced prostaglandin (PG) E2 levels in response to a single UV treatment. The proliferative response to UV was significantly reduced in COX-2, but not COX-1, heterozygous mice. UV-induced apoptosis, however, was greater in COX-2 heterozygous mice. Collectively, these results clearly establish the requirement for COX-2 in the development of skin tumors.