Evaluation of in vitro antifungal activity of LY121019

LY121019 is a new semisynthetic lipoeptide antifungal agent with potent in vitro fungicidal activity against multiple clinical strains ofCandida albicans andCandida tropicalis but is 10–100 fold less active againstTorulopsis glabrata andCandida parapsilosis. Its in vitro activity againstCandida albicans andCandida tropicalis is comparable to that of amphotericin B. The in vitro fungicidal activity of this new agent supports further investigations into its use in treatment ofCandida infections.     

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

BACKGROUND: Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. AIM: To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). METHOD: All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. RESULTS: Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. CONCLUSION: Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.     

The production of hybridomas from the gut associated lymphoid tissue of tumour bearing rats. II. Peripheral intestinal lymph as a source of IgA producing cells.

Peripheral intestinal lymph afferent to the mesenteric nodes has been collected from rats bearing syngeneic sarcomata in their Peyer's patches and the B cells used to produce rat X rat hybridomas. Analysis of the hybridoma supernatants by radioimmunoassay for the presence of immunoglobulins, showed that hybridomas secreting IgA predominated. Eleven out of the 15 hybridomas selected for antibody binding to cells of the immunising tumour secreted IgA antibodies, and six of these were tumour specific. Efferent mesenteric lymph (i.e. normal thoracic duct lymph), on the other hand, was found to be a poor source of B cells for hybridoma production and no specific IgA secreting hybridomas were obtained. The high yield of IgA secreting hybridomas obtained shows that peripheral intestinal lymph is a better source of IgA committed B cells than are the mesenteric nodes or thoracic duct lymph. We conclude that the IgA producing cells in the latter tissues are too far along the differentiation pathway to plasma cells to undergo successful somatic cell fusion.     

Tyrosine Kinase Inhibitors in the Treatment of Chronic-Phase CML: Strategies for Frontline Decision-making

Purpose of Review

Over the past two decades, the introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). With four agents currently approved for frontline use in chronic-phase (CP) disease, it follows that treatment decision-making has been rendered more challenging. Here we will review recent advances that help inform the selection of a first-line TKI.

Recent Findings

Extended follow-up of the seminal CML trials has demonstrated the long-term efficacy of TKIs, while also highlighting significant differences in their respective toxicity profiles and potency. Dasatinib and nilotinib generate deeper molecular responses than imatinib, particularly among patients with higher risk disease, but this has not translated into a significant survival advantage. Similar results have been obtained at 1 year with bosutinib; its efficacy and toxicity were well balanced at a dose of 400 mg daily, prompting its recent approval for this indication. Lastly, multiple studies have demonstrated that TKIs can be safely discontinued in select individuals who have maintained deep responses for extended periods, establishing treatment-free remission as a novel goal in CP CML.

Summary

The careful consideration of parameters such as disease risk, the potency, and toxicity profile of each TKI, as well as each patient’s unique comorbidities and preferences, enables truly individualized therapeutic decision-making in CP CML, with the goal of ensuring that a high quality of life accompanies the survival advantage conferred by these agents.

     

Giant Caudate Lobe Hemangioma

Journal of Gastrointestinal Surgery - Liver hemangiomas are the most common benign liver mass and typically asymptomatic and incidentally found. Giant liver hemangiomas are defined as having an...     

In vivo trafficking of adoptively transferred interleukin-2 expanded tumor-infiltrating lymphocytes and peripheral blood lymphocytes. Results of a double gene marking trial.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and IL-2 appears to produce dramatic regressions in patients with metastatic melanoma and renal cancer. However, the in vivo mechanism of TIL function is not known. We conducted an UCLA Human Subject Protection Committee, Recombinant DNA Advisory Committee, and FDA-approved clinical trial using genetically-marked TIL to test the hypothesis that these cells have unique, tumor-specific in vivo trafficking patterns. TIL and PBL (as a control effector cell population) were isolated and expanded in parallel in vitro in IL-2-containing medium for 4-6 wk. During the expansion, TIL and PBL were separately transduced with the amphotropic retroviral vectors LNL6 and G1Na. Transduced TIL and PBL were coinfused into patients and their respective numbers measured in tumor, peripheral blood, and normal tissues; integrated provirus could be quantitated and distinguished by DNA PCR. Nine patients were treated (six melanoma, three renal) and received between 4.5 x 10(8) and 1.24 x 10(10) total cells. Both "marked" TIL and PBL could be detected circulating in the peripheral blood, in some patients for up to 99 d after infusion. Marked TIL and/or PBL could be detected in tumor biopsies in six of nine patients as early as day 6 and as late as day 99 after infusion. No convincing pattern of preferential trafficking of TIL vs. PBL to tumor was noted. Moreover, concurrent biopsies of muscle, fat, and skin demonstrated the presence of TIL/PBL in comparable or greater numbers than in tumor in five patients. The results of this double gene marking trial provide interesting insights into the life span and trafficking of adoptively transferred lymphocytes, but do not support the hypothesis that TIL specifically traffic to tumor deposits.