Pandemic and seasonal vaccine coverage and effectiveness during the 2009–2010 pandemic influenza in an Italian adult population

Objectives

To evaluate the response to pandemic vaccination and seasonal and pandemic vaccine effectiveness (VE) in an Italian adult population, during the 2009?C2010 influenza season.

Methods

Data were recorded by interviewing 19,275 subjects (??35?years), randomly recruited from the general population of the Moli-sani project. Events [influenza-like illness (ILI), hospitalization and death], which had occurred between 1 November 2009 and 31 January 2010 were considered. VE was analyzed by multivariable Poisson regression analysis.

Results

Pandemic vaccine coverage was very low (2.4%) in subjects at high-flu risk, aged 35?C65?years (N?=?8,048); there was no significant preventive effect of vaccine against ILI. Seasonal vaccine coverage was 26.6% in the whole population (63% in elderly and 21.9% in middle-aged subjects at high-flu risk). There was a higher risk to develop ILI in middle-age [VE: ?17% (95% CI: ?35,?1)] or at high flu-risk [VE: ?17% (95% CI: ?39, 2)] vaccinated groups.

Conclusions

Coverage of pandemic vaccine was very low in a Southern Italy population, with no protective effect against ILI.     

Antitumor agents. 2. Synthesis,structure-activity relationships,and biological evaluation of substituted 5H-pyridophenoxazin-5-ones with potent antiproliferative activity

New antiproliferative compounds, 5H-pyrido[3,2-a]phenoxazin-5-ones (1-10), 5H-benzophenoxazin-5-one (11), 5H-pyrido[2,3-a]phenoxazin-5-one (12), 5H-pyrido[3,4-a]phenoxazin-5-one (13), and 5H-pyrido[4,3-a]phenoxazin-5-one (14), were synthesized and evaluated against representative human neoplastic cell lines. The excellent cytotoxic activity of these polycyclic phenoxazinones, structurally related to the actinomycin chromophore, is discussed in terms of structural changes made to rings A and D (Chart 1). Electron-withdrawing or electron-donating substituents were introduced at different positions of ring A to probe the electronic and positional effects of the substitution. A nitro group in R(2) or in R(1) increases the cytotoxic activity, whereas electron-donating methyl groups in any position lead to 10- to 100-fold decreasing of the activity. The low antiproliferative activity of benzophenoxazinone 11 and pyridophenoxazinones 13 and 14 confirms the crucial role of pyridine nitrogen in the W position of ring D in DNA binding. The unexpected high activity exhibited by 12, which has the nitrogen in the X position, could be ascribed to a different mechanism of action, which needs further investigation.     

A case of bat rabies in a cat in the province of Buenos Aires, Argentina

In the Central Laboratory of Public Health in Buenos Aires, rabies was detected in a cat that was brought in for diagnosis by its owners. The animal, which was displaying symptoms of the furious form of the disease, had attacked three people in the rural area of Chascomús, near the Rio de la Plata. All three of the people who had been bitten received the necessary treatment. The diagnosis was made using the fluorescent antibody test and the inoculation of mice and the results were communicated to the Zoonoses Division of the Ministry of Health. The virus was then typed at the Institute Pasteur of Buenos Aires using monoclonal antibodies, where it was found to be antigenic variant 4 of serotype 1, i.e., the type of virus usually found in insectivorous bats. This area has been free of the canine variant since 1984. This is the first known case in the province of Buenos Aires of a cat becoming infected with this type of virus. It confirms that there is a link between the air and terrestrial cycles of rabies in this area.     

Folate-mediated targeting of polymeric conjugates of gemcitabine

The synthesis of two new macromolecular prodrugs for active tumor targeting was set up. Gemcitabine (2'-deoxy-2',2'-difluorocytidine) was conjugated to alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) through succinyl or diglycolyl hydrolysable spacers. The targeting agent folic acid was attached to the macromolecular backbone through the aminocaproic spacer. The two conjugates [PHEA-(5'-succinylgemcitabine)-1'-carboxypentyl-folamide and PHEA-(5'-diglycolyl-gemcitabine)-1'-carboxypentyl-folamide], were purified and extensively characterised by spectroscopic (UV, IR and NMR) and chromatographic analyses to determine the correct chemical structure, the purity degree and the reaction yield. In vitro studies demonstrated that the drug release depends on the spacer arm (diglycolyil or succinyl) and incubation pH. After 30 h incubation at pH 7.4, mimicking the plasma and extracellular compartments, the gemcitabine release from the succinyl and diglycolyl derivatives was 28 and 31%, respectively. After 30 h incubation at pH 5.5, mimicking the lisosomial compartment, the drug released from both bioconjugates was lower than 13%. In plasma, the polymer conjugation increased the drug stability and provided for a sustained drug release. In vitro citotoxicity studies performed using human nasopharyngeal epidermal carcinoma KB cells demonstrated that PHEA-(5'-succinylgemcitabine)-1'-carboxypentyl-folamide displays an higher dose dependent cytotoxic effect with respect to PHEA-(5'-diglycolyl-gemcitabine)-1'-carboxypentyl-folamide.     

Understanding the private worlds of physicians, nurses, and parents: a study of life-sustaining treatment decisions in Italian paediatric critical care

This study's aim was to describe: (a) How life-sustaining treatment (LST) decisions are made for critically ill children in Italy; and (b) How these decisional processes are experienced by physicians, nurses and parents. Focus groups with 16 physicians and 26 nurses, and individual interviews with 9 parents were conducted. Findings uncovered the 'private worlds' of paediatric intensive care unit (PICU) physicians, nurses and parents; they all suffer tremendously and privately. Physicians struggle with the weight of responsibility and solitude in making LST decisions. Nurses struggle with feelings of exclusion from decisions regarding patients and families that they care for. Physicians and nurses are distressed by legal barriers to LST withdrawal. Parents struggle with their dependence on physicians and nurses to provide care for their child and strive to understand what is happening to their child. Features of helpful and unhelpful communication with parents are highlighted, which should be considered in educational and practice changes.     

Microvessel density,mast cell density and thymidine phosphorylase expression in oral squamous carcinoma

To elucidate the role of angiogenesis in the carcinogenesis and progression of oral cancer, we investigated microvessel density (mVd), mast cell density (mCd) and thymidine phosphorylase (TP) expression in a series of 50 patients with T1-3 N0-1 M0 oral squamous carcinoma (OSC) and 21 patients with non-dysplastic oral leukoplakia (NDOLP). Paraffin-embedded pathological tissue was utilised for the immunohistochemical analysis of mVd and TP expression. Toluidine blue histochemical method was employed for mast cell identification. OSC and NDOLP were not significantly different with respect to mVd (mVd mean value +/- SD: 30+/-17 and 27+/-18, respectively) and mCd characteristics (mCd mean value +/- SD: 8+/-6 and 7+/-6 units, respectively). Conversely, tumour epithelia showed some degree of TP immunostaining in 100% of cases compared with 76% in NDOLP samples (p< or =0.001 by Fisher's test). A good correlation was found between mVd and mCd in both NDOLP (c.c. 0.632; p=0.002) and OSC (c.c. 0.496; p=0.000) tissue, whereas no association between TP expression and mVd or between mCd and TP status was evident. At a median follow-up of 18 months, patients with high mVd tumours showed a greater probability of survival than those with low mVd (75 and 40%, respectively; p=0.04 log-rank test). Our results suggest that the development of oral cancer epithelia is associated with a significant increase in TP expression. Conversely, the clinical outcome of OSC seems inversely related specifically to mVd.     

CD40 activation as potential tool in malignant neoplasms

BACKGROUND: CD40, a cell surface molecule, is expressed on B-cell malignancies and many different solid tumors. It is capable of mediating diverse biological phenomena such as the induction of apoptosis in tumors and stimulation of the immune response. It has thus been studied as a possible target for antitumor therapy. The general aim of this review is to focus the attention of clinical oncologists on the involvement of CD40 in tumors and the rationale of CD40-activation-based therapies in new, biologically oriented antitumor protocols. METHODS: A Medline review of published papers about the role of CD40 activation in cancer therapy. RESULTS: Many authors have shown that CD40 activation promotes apoptotic death of tumor cells and that the presence of the molecule on the surface of carcinoma lines is an important factor in the generation of tumor-specific T-cell responses that contribute to tumor cell elimination. The CD40 ligand (CD40L) is the natural ligand for CD40; it is expressed primarily on the surface of activated T lymphocytes. Preclinical studies suggest that CD40-CD40L interaction could be useful for cytotoxicity against CD40-expressing tumors and for immune stimulation. Tumor inhibition was observed when tumor cells were treated with agonistic anti-CD40 monoclonal antibodies or with the soluble form of CD40L. The results of the first phase I clinical trial to treat cancer patients with subcutaneous injection of recombinant human CD40L have been recently reported. Immunohistochemical studies have revealed that detection of CD40 in primary cutaneous malignant melanoma and lung cancer may have a negative prognostic value. Interestingly, up-regulation of CD40 was observed in the tumor vessels of renal carcinomas and Kaposi's sarcoma, suggesting possible involvement of CD40 in tumor angiogenesis. Recently, it has also been shown that CD40 engagement on endothelial cells induces in vitro tubule formation and expression of matrix metalloproteinases, two processes involved in the neovascularization and progression of tumors. CONCLUSIONS: CD40 activation represents an exciting target for hematological malignancies and solid tumors expressing the molecule, but its functional role in cancer development still remains unclear and controversial.     

Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma.

PURPOSE: The quest for prognostic molecular markers in prostatic carcinoma is still in progress. Many proteins have already been screened by immunohistochemistry with the aim to find the most reliable indicator of progressive disease. In this study, we evaluated the expression of pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) by immunohistochemistry in 24 prostate carcinomas compared with the paired expression of normal prostates. EXPERIMENTAL DESIGN: Expression of the different proteins in normal and pathological specimens was evaluated by the Wilcoxon test. A matrix of correlation (Spearman coefficient) was used to evaluate the possible association in expression among the different proteins. Logistic regression analysis was used to test the multivariable prognostic value of the levels of protein expression for the probability of disease development. RESULTS: p53 and Ki-67 (MIB-1) showed a higher expression in cancer than in normal tissue (P = 0.006 and <0.001, respectively). pRb2/p130, p107, and p27(kip1) showed an overall lower expression in cancer, but the difference between cytoplasmic and nuclear expression was always higher for cancer (Ps, from <0.001 to 0.016). mdm-2 expression was lower in cancer, but the difference between cytoplasmic and nuclear expression was not significant (P = 0.571) when compared with that in normal tissue. A positive correlation between p27 and pRb2/p130 levels expressed, in normal and cancer counterparts in the same sample, as the difference between cytoplasmic and nuclear protein concentrations (P = 0.045) was found. Additionally, p107 expression showed an inverse correlation with Ki-67 (MIB-1) expression in the most aggressive tumors (P = 0.046). Logistic regression output showed that Ki-67 (MIB-1) and pRb2/p130 (expressed as differences between cytoplasmic and nuclear concentrations) were the variables associated with a higher risk of cancer. The highest value was reported for Ki-67 (MIB-1) (odds ratio, 2.11), followed by pRb2/p130 (odds ratio, 1.01). pRb2/p130 alone was associated with a sensitivity (rate of cases having a posterior probability of disease >/=0.5) of 61% with a false positive rate of 22%. Ki-67 (MIB-1) alone yielded a sensitivity of 69% and a false positive rate of 14%. The combined model (Ki-67 + pRb2/p130) yielded a sensitivity of 83% with a false positive rate of 17%. Interestingly, one specimen in which we also found a high-grade prostatic intraepithelial neoplasia showed the progressive loss of pRb2/p130 from normal prostatic cells to prostatic intraepithelial neoplasia cells, suggesting that in prostatic cancer, lack of expression of the tumor suppressor gene pRb2/p130 could be involved in the progression of the disease, from an early stage. CONCLUSIONS: This study showed that all of the proteins but mdm-2 were expressed at a different rate in normal and pathological prostate specimens. Multivariate analysis showed that pRb2/p130 and p107 may be involved in the pathogenesis and progression of prostate cancers, and that the expression of the retinoblastoma-related protein pRb2/p130 along with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear concentrations, could be considered new parameters to be evaluated in discriminating patients at a higher risk for prostate cancer.     

Idiopathic macular hole surgery with low-concentration infracyanine green-assisted peeling of the internal limiting membrane

PURPOSE: To evaluate the efficacy of pars plana vitrectomy with infracyanine green (IFCG)-assisted internal limiting membrane peeling for the treatment of idiopathic macular hole. DESIGN: Prospective, noncomparative interventional case series. METHODS: Thirty-eight consecutive eyes of 35 patients with idiopathic macular hole were included in the study. Patients underwent early treatment diabetic retinopathy (ETDRS) visual acuity examination, dilated ophthalmoscopy, and optical coherence tomography before treatment and during follow-up. Fluorescein angiography was done in selected cases. Patients underwent a three-port pars plana vitrectomy with complete posterior hyaloid and epiretinal membrane removal. The internal limiting membrane (ILM) was stained with 0.5 cc of IFCG (0.5 mg/ml, 308 mOsm) and peeled up to the vascular arcades. Perfluoropropane gas (C(3)F(8)) 10% was used as tamponade. RESULTS: Mean follow-up duration was 10 +/- 5 months (range, 3 to 24 months). Six eyes had stage 2 macular hole, 15 eyes stage 3, and 16 eyes stage 4. Overall, 37 of 38 macular holes closed after a single surgery. Median visual acuity was 20/100 (range, 20/400 to 20/50) before surgery and 20/50 (range, 20/640 to 20/25) after surgery. Visual acuity after surgery was 20/50 or better in 24 of 38 (63.1%) eyes. Twenty-five (65.8%) eyes improved by 2 or more lines, nine (23.7%) eyes were stable, and four (10.5%) eyes worsened by 2 or more lines. CONCLUSIONS: This study suggests that IFCG (0.05%) effectively stains the ILM with apparent safety, and that IFCG-assisted peeling of the ILM may be useful in the treatment of idiopathic macular hole.