Glatiramer acetate therapy for multiple sclerosis: a review

The past decade has witnessed a revolution in the treatment of multiple sclerosis (MS), the most common demyelinating disorder of the human CNS. After being considered as an untreatable disease for more than a century, six disease-modifying treatments have been approved between 1993 and 2006. Glatiramer acetate (GA) is a worldwide drug approved for the treatment of relapsing-remitting MS in 1996. The drug is a synthetic copolymer of four amino acids based on the composition of myelin basic protein, one of several putative autoantigens implicated in the pathogenesis of MS. Three separate double-blind, placebo-controlled trials have established its efficacy in relapsing-remitting MS. Observations from an ongoing study, the longest prospective study in MS therapeutics so far, suggest that the effect of GA in reducing the relapse rate and neurological disability is maintained over a 10-year period. Independent investigators have identified several putative immunological mechanisms of action of GA, with the unique observation of the generation of GA-reactive T-helper 2 (anti-inflammatory) polarised lymphocytes within days to weeks of initiating therapy and sustaining an anti-inflammatory milieu for years in the peripheral immune system and, presumably, in the CNS. Emerging data from immunological and imaging studies quantifying axonal injury in the brain point towards neuroprotective abilities of GA. Combined with its remarkable safety and tolerability, long-term efficacy and neuroprotective effect, GA presents it self as a first-line choice in relapsing-remitting MS, and holds immense promise in developing its potential as a combination therapy in MS, as well as extending its indications to other neurodegenerative diseases.     

Cutaneous Findings Mistaken for Physical Abuse: Present but Not Pervasive

Incorrect diagnoses during child abuse evaluations are serious. Because skin lesions are common in abuse, it is important to consider cutaneous mimics of physical abuse. The current study prospectively identified cutaneous mimics in a cohort of children evaluated for possible physical abuse. This is a secondary analysis of data from the Examining Siblings To Recognize Abuse research network's prospective, observational, cross‐sectional study involving 20 U.S. child abuse teams. Subjects were younger than 10 years old and were evaluated by child abuse physicians (CAPs) for concerns of physical abuse. CAPs prospectively documented whether mimics were identified during their physical abuse evaluations. Details of each patient with cutaneous mimics were evaluated to determine the types of mimics, which part of the evaluations identified mimics, and the perceived abuse likelihood. Of 2,890 children evaluated for physical abuse, 137 had at least one mimic identified and 69 had some cutaneous mimic components. Although 985 of 2,753 (39%) subjects without mimics had high levels of abuse concern, only 9 of 137 (6%) children with mimics had high levels of abuse concern (p < 0.001). Of 69 children with cutaneous mimics, 56 (81%) were diagnosed by history and physical examination. Cutaneous abuse mimics were identified in 2.4% of children evaluated for physical abuse. Although it was eventually determined that there was little or no concern for abuse in 84% of children with cutaneous mimics, a small number were physically abused. CAP evaluation may be valuable in recognizing children with cutaneous mimics who also were abused.     

Final report of a pilot trial of accelerated radiotherapy plus concurrent 96-hour infusional paclitaxel for locally advanced head and neck cancer

Recent data show that accelerated radiotherapy (XRT) improves local-regional control (LRC) over standard-fractionation XRT. Concurrent chemoradiotherapy improves LRC and survival over XRT alone. This study assesses the feasibility, toxicity, and preliminary efficacy of concurrent 96-hour paclitaxel infusion with accelerated XRT. Eligible patients had stage IV squamous cell carcinoma of the head and neck, exclusive of nasopharynx cancer. Tumor had to be considered technically unresectable after evaluation by our multidisciplinary head/neck tumor board. XRT was given continuous course using an accelerated regimen with twice a day fractionation for the cone down (70-72 Gy/6 weeks). Chemotherapy consisted of 2 cycles of paclitaxel via 96-hour infusion during weeks 1 and 5 of XRT. The first 10 patients received doses of 40-120 mg/m2/cycle, and the subsequent 13 patients received 100 mg/m2/cycle. Twenty-three patients were studied. Median follow-up was 20.4 months (44.4 months for the 10 long-term survivors). Most (19/23) patients had reversible grade 3 acute mucositis. Median treatment time was 44 days, and all but 1 patient received both cycles of paclitaxel at their planned dose. The 3- and 4-year actuarial survival was 37%. Three- and 4-year LRC was 50%. Four patients (18%) developed distant metastases. Two patients (9%) developed severe esophageal strictures requiring permanent gastrostomy/tracheostomy, and 2 patients developed other late grade 3+ toxicities. Accelerated XRT plus concurrent 96-hour infusional paclitaxel as given in this study has intense but acceptable toxicity and is feasible. LRC and survival compare favorably with other aggressive regimens for this poor-prognosis population. Further study of accelerated XRT with concurrent chemotherapy is indicated.