Longitudinal Tears of Both Peroneal Tendons Associated With Tophaceous Gouty Infiltration. A Case Report

The authors report a case of longitudinal tendon tears of the peroneus longus and brevis in the presence of tophaceous gouty infiltration. There are a limited number of reports discussing similar processes affecting various tendons throughout the body. There has been 1 prior case of peroneal tendon involvement affecting only the peroneus brevis. A 35-year-old man presented with a 4-year history of left-sided lateral ankle pain, redness, and swelling. The patient described the "attacks" as occurring off and on, with a recent increase in frequency. The symptoms were relieved with indomethacin, colchicine, and narcotic analgesics. Upon clinical evaluation, there was a cavus foot type with moderate calcaneal varus. Peroneal subluxation was elicited with resisted eversion. An MRI evaluation revealed longitudinal tears of both peroneal tendons. During surgical repair, a chalky-white substance resembling gouty tophi was present within both tendon tears. The tendons were remodeled and repaired. The patient had an uneventful postoperative course with nearly completed resolution of his symptoms at 1-year follow-up. The patient was referred to his primary care physician for further evaluation and long-term control of elevated uric acid levels.     

Antibiotics in the management of hepatic encephalopathy: an evidence-based review

Hepatic encephalopathy (HE) is an increasingly prevalent and debilitating condition that occurs in functional hepatic insufficiency. It is marked by fluctuating neuropsychiatric and cognitive impairment, which can be severe and life threatening. Hepatic encephalopathy is a diagnosis of exclusion; thus, it is challenging to diagnose definitively and to investigate in clinical trials. High response rates in the placebo arms of well-conducted studies demonstrate that the most effective treatment for HE is the correction of known precipitating triggers. However, pharmacological therapies may also be helpful. Although the precise pathogenesis remains unknown, bacterially derived neurotoxins from enteric flora likely play an important role. Based on this hypothesis and on accumulating clinical experience documented in randomized trials, oral antibiotics have emerged as an important treatment adjunct. This article addresses the qualities of an ideal antibiotic and reviews the literature on 4 antibiotics used to treat HE: neomycin, metronidazole, vancomycin, and rifaximin, with the most promising of these drugs appearing to be rifaximin. Unfortunately, most studies of the treatment of HE are difficult to interpret due to small sample sizes, methodological flaws, vulnerability to bias, and the intrinsic challenges of studying HE. Many studies have erroneously concluded that treatments are equivalent simply because no significant difference between treatment arms was detected. Consequently, the literature generally lacks definitive data from large, randomized, placebo-controlled trials. Nevertheless, the data suggest that minimally absorbed antibiotics are emerging as a safe and effective approach for the treatment of HE.     

Phase II trial of vinorelbine for relapsed ovarian cancer: a Southwest Oncology Group study

OBJECTIVES: To assess the activity of vinorelbine in women with recurrent or resistant epithelial ovarian cancer following treatment with platinum and paclitaxel in terms of survival rate at 6 months, objective response rate (in the subset of patients with bidimensionally measurable disease), and health-related quality of life. METHODS: Seventy-nine evaluable patients with progressive ovarian cancer following platinum and taxane therapy received vinorelbine 30 mg/m(2) days 1 and 8 of a 21-day treatment cycle. RESULTS: Six-month survival rate for the entire group was 65% (95% CI: 54-75%) and median survival was 10.1 months (95% CI: 7.7-13.6 months). In the 71 women with measurable disease, 0 complete and 2 partial responses were observed (RR = 3%) (95% CI: 0.3-10%). Patients reported substantial symptom-related distress at baseline, which persisted, but did not worsen, during treatment. Patients also had impaired physical functioning at baseline and this continued to decline during treatment. CONCLUSIONS: The 6-month survival rate achieved with salvage vinorelbine is comparable to the results obtained with other salvage therapies in patients with relapsed ovarian cancer. During the initial 10 weeks of treatment, vinorelbine did not appear to be effective in alleviating the symptom-related distress or progressive impairment of physical functioning associated with this disease.     

The clinical development of new mitotic inhibitors that stabilize the microtubule

Microtubule-stabilizing agents are increasingly studied for cancer treatment based largely on the prior success of paclitaxel and docetaxel. In this review, we focus on the clinical development of epothilones and discodermolide, and we discuss salient preclinical and clinical highlights of these two novel natural products. These agents are distinguished by their biochemical features making them poor P-glycoprotein substrates and capable of inducing cytotoxicity in cell lines or in vivo tumor models harboring mutations in tubulin. There is now considerable data regarding the efficacy of the epothilones in human beings and discodermolide holds such promise, as well.     

T-lineage specification and commitment: a gene regulation perspective

T lymphocytes originate from pluripotent precursors and undergo lasting commitment to the T cell developmental fate during their processing in the thymus. Commitment includes both the acquisition of essential T cell characteristics and the foreclosing of other developmental options. Gain of T cell characteristics is probably mediated by separate mechanisms, at least in detail, from loss of alternative developmental potentials. Programmed shifts in survival requirements make changes irreversible. Here we review the current evidence identifying the regulatory components of this commitment pathway, and the first hints of how they work together. Roles for PU.1, GATA-3, and their target genes are highlighted.