Cytokines as an adjuvant to tumor vaccines: Efficacy of local methods of delivery

Background: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy. Methods: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer. Results: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not. Conclusions: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer.     

Which way for housing and human settlements?

In order to clarify the housing and settlements component of the European health-for-all programme and to identify perceived priorities with a view to the preparation of training materials, members of WHO's Rural and Urban Development and Housing Network were invited to complete a questionnaire. The results are reported below. The questionnaire can be used in identifying local development priorities, comparing attitudes, and studying perceived needs. Intended as a tool for policy-makers, course organizers and public health professionals, it is available from the authors of the present article.     

Complement Killing of Yersinia enterocolitica and Retention of the Bacteria by Leucocyte Removal Filters

We report studies on the complement sensitivity of four strains of Yersinia enterocolitica , serotypes O:3, O:9, O:5,27, and O:20, isolated from blood units involved in transfusion fatalities. Complement in fresh CPD plasma killed Y. enterocolitica within 4 h at 22°C in 100% of the experiments. The bactericidal action was serotype and complement activation pathway dependent. Both classic and alternate pathways seemed to be active, but the latter to a lesser degree. When the classic pathway was blocked by chelation of Ca²⁺ no complete killing was obtained. Complement did not enhance or condition Yersinia for leucocyte filter retention. Direct removal of Yersinia by filtration was also related to serotype; all strains were reduced by filtration in heat-inactivated plasma, and all except serotype O:5,27 were reduced in Ca²⁺ -chelated plasma. Our findings may explain why plasma products and platelet concentrates are rarely involved in Yersinia sepsis related to transfusion.     

Expectant management of deep cerebral venous thrombosis with intraventricular hemorrhage

Limited randomized clinical trial data favor the use of anticoagulation in patients with cerebral venous thrombosis. We present a patient with deep cerebral venous thrombosis in whom anticoagulation was withheld because of coexistent intraventricular hemorrhage. She had a benign clinical course without anticoagulation, suggesting that close observation may be a management option in these patients.