Mucosal vaccines and technology.

There is an urgent and unmet need to develop effective vaccines to reduce the global burden of infectious disease in both animals and humans, and in particular for the majority of pathogens that infect via mucosal sites. Here we summarise the impediments to developing mucosal vaccines and review the new and emerging technologies aimed at overcoming the lack of effective vaccine delivery systems that is the major obstacle to developing new mucosal vaccines.

Use of bioengineered human commensal gut bacteria-derived microvesicles for mucosal plague vaccine delivery and immunization.

Plague caused by the Gram-negative bacterium, Yersinia pestis, is still endemic in parts of the world today. Protection against pneumonic plague is essential to prevent the development and spread of epidemics. Despite this, there are currently no licensed plague vaccines in the western world. Here we describe the means of delivering biologically active plague vaccine antigens directly to mucosal sites of plague infection using highly stable microvesicles (outer membrane vesicles; OMVs) that are naturally produced by the abundant and harmless human commensal gut bacterium Bacteroides thetaiotaomicron (Bt). Bt was engineered to express major plague protective antigens in its OMVs, specifically Fraction 1 (F1) in the outer membrane and LcrV (V antigen) in the lumen, for targeted delivery to the gastrointestinal (GI) and respiratory tracts in a non-human primate (NHP) host. Our key findings were that Bt OMVs stably expresses F1 and V plague antigens, particularly the V antigen, in the correct, immunogenic form. When delivered intranasally V-OMVs elicited substantive and specific immune and antibody responses, both in the serum [immunoglobulin (Ig)G] and in the upper and lower respiratory tract (IgA); this included the generation of serum antibodies able to kill plague bacteria. Our results also showed that Bt OMV-based vaccines had many desirable characteristics, including: biosafety and an absence of any adverse effects, pathology or gross alteration of resident microbial communities (microbiotas); high stability and thermo-tolerance; needle-free delivery; intrinsic adjuvanticity; the ability to stimulate both humoral and cell-mediated immune responses; and targeting of primary sites of plague infection.

[A bibliometric analysis of the Farmacia Hospitalaria journal (2001-2006)]. / Análisis bibliométrico de la revista Farmacia Hospitalaria (2001-2006).

OBJECTIVE: To carry out a bibliometric analysis of the Farmacia Hospitalaria journal from 2001 to 2006. METHOD: A retrospective analysis of all of the articles published in Farmacia Hospitalaria from 2001-2006 was performed and the main bibliometric indicators for production, circulation, distribution and sales were calculated. RESULTS: 416 articles by 1,515 authors were analysed. Original articles were the most predominant with a growth of 30%. There were 4.6 +/- 2.3 authors per article. The Community of Valencia, Catalonia, Madrid and Andalusia were the autonomous communities with the highest levels of production. Four authors had a productivity index of > 1, with one group of 15 authors having an index of > 0.75. Only 14% of articles were included in presentations to congresses and 17% had funding. The subject matters of drug treatment and safety had the highest production levels. The publication delay remained constant. There was a circulation index of 0.74 in Medline. CONCLUSIONS: Farmacia Hospitalaria maintained or improved their bibliometric indicators between 2001 and 2006. There has been an increase in the publication of original articles and letters to the editor over recent years and this increase was in line with the journal s strategies. There has also been a decrease in literature reviews. There were some generational changes among the authors although the main authors remained the same. The subject matters and geographical origin of the authors corresponded to areas with the largest development of the specialty in Spain.

Description of controlled trials published in Methods and Findings, 1979-2002.

It is thought that the controlled trial (CT) is the most adequate research method to assess a therapeutic intervention in terms of efficacy, and it also constitutes the basis for the development of systematic reviews on health interventions. To identify and obtain the majority of published CTs is not an easy task, mainly because of limitations concerning the currently available electronic sources. The aim of the present work was to identify, describe, and assess the quality of CTs published in the journal Methods and Findings in Experimental and Clinical Pharmacology (M&F). Additionally, to assess the retrievability of both methods, a search was performed in Medline (PubMed access) through the use of an optimal search strategy for CTs. A total of 189 original studies out of a total of 2796 reviewed articles met the CT criteria according to the Jadad scale score, we could hold that only 58% of the CTs were of good quality. The present work confirms, once again, the limitations of a CT search performed exclusively through Medline (sensitivity 64% and specificity 98%). In conclusion, we suggest that the journal M&F explicitly joins the International CONSORT Statement.

Mouth-washings with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) do not improve grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Results of a randomized double-blind placebo-controlled study.

We investigated whether daily oral washings with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) solution improved grade III-IV oropharyngeal mucositis (OM) in patients with hematological malignancies undergoing stem cell transplantation. Forty-one consecutive patients (21 males and 20 females, median age (range) 44 (16-69) years) were prospectively randomized to perform daily mouth-washes with either a 400 microg rhGM- CSF (Molgramostin, Schering-Plough) solution (group A, n = 18) or with a saline solution (group B, n = 23). Primary end-points were the intensity of OM, night rest quality and characteristics of food intake. Secondary end-points were need for and duration of parenteral nutrition, oral and intravenous analgesic requirements, incidence of viral or fungal oral infections and development of neutropenic fever. No differences were found between the placebo and rhGM-CSF-treated groups regarding overall duration of OM, maximum grade, reduction in at least one grade of OM (nine patients (56%) in group A vs 13 patients (68%) in group B), reduction of spontaneous or swallowing-induced pain, improvement in oral food intake, use of parenteral nutrition or use of systemic analgesics. In conclusion, mouth-washings with a 400 microg of rhGM-CSF solution do not improve severe OM in hematological patients undergoing stem cell transplantation.

[Hematopoietic allogeneic transplantation with attenuated conditioning regimen on an outpatient basis. First experience in Spain]. / Trasplante alogénico de progenitores hematopoyéticos con acondicionamiento no mieloablativo en régimen ambulatorio. Primera experiencia en España.

BACKGROUND: Allogeneic hematopoietic transplantation using attenuated conditioning regimens seems promising. This procedure associates to relatively low morbidity and mortality. In consequence, an outpatient management of this transplantation modality may be considered, even in elderly patients. CLINICAL REPORT AND RESULTS: This approach was considered in a 62 years-old female suffering from chronic myeloid leukemia in chronic phase. The conditioning regimen included fludarabine and 200 cGy of total body irradiation. Cyclosporine A and mycophenolate mofetil were used as immunosuppression. Conditioning, peripheral-blood stem-cell infusion, and postransplant follow-up was managed in the outpatient setting. Two short admissions were required. Eight months after transplant, the patient remains in sustained haematological remission with complete donor chimerism,has a 100% Karnofsky score and continues being managed on an outpatient basis. CONCLUSIONS: Allogeneic stem-cell transplantation can be performed safely on an outpatient basis,even in elderly patients.

Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosage.

BACKGROUND: Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. PATIENTS AND METHODS: Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. RESULTS: Mean BU exposure (AUCss) (+/-DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade > or = II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. CONCLUSIONS: The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD.