Phylogenetics and pathogenesis of early avian influenza viruses (H5N1), Nigeria

Three highly pathogenic avian influenza subtype H5N1 and 4 Newcastle disease viruses were isolated from sick or dead chickens in southwestern Nigeria. Sequencing and phylogenetic analysis placed them within H5N1 subclade 2.2.2. Intravenous and intranasal pathogenicity tests produced systemic disease with vascular endothelial cell tropism in chickens.     

Marginal structural models might overcome confounding when analyzing multiple treatment effects in observational studies

OBJECTIVE: We review marginal structural models (MSMs) and show how they are useful when comparing the effects of multiple treatments on outcomes in observational studies. Until now, MSMs have not been used to compare the effects of more than two treatments. STUDY DESIGN AND SETTING: To illustrate the application of MSMs when patients may receive several treatments, we have reanalyzed the effects of antipsychotic medication on achieving remission in schizophrenia using data from the SOHO study, a 3-year observational study of health outcomes associated with the treatment of schizophrenia. RESULTS: The MSM results were, in general, consistent with but less statistically significant than those obtained using conventional methods. The MSM also showed qualitative differences in some comparisons in which the conventional analysis obtained results that were not consistent with previous knowledge. CONCLUSION: MSMs can be used to analyze multiple treatment effects. MSMs, by using inverse-probability of treatment weights, might provide a better control for confounding than conventional methods by improving the adjustment for treatment group differences in observational studies, which may approximate their results to those of randomized controlled trials.     

Granuloma annulare of the penis: a uncommon location for an usual disease

The subcutaneous clinical variant of granuloma annulare (GA) is rare and tends to present more frequently in children, in locations unusual for conventional GA. Involvement of the penis is exceptional and has been rarely reported. Most cases are located in the shaft of the penis and tend to persist without spontaneous remission. Diagnosis is done only after biopsy, and surgical resection of the lesions is not unusual. We report a new case of subcutaneous GA of the penis in a 13-year-old boy with lesions persistent for the past year. Surgical excision of one of them allowed the correct diagnosis. No further treatment was done, and the condition has not remitted 1 year later. We stress the importance of clinical recognition of unusual presentations of GA to avoid overtreatment of lesions that do not need an aggressive approach.     

Epizooty caused by high-virulent influenza virus A/H5N1 of genotype 2.2 (Qinghai-Siberian) among wild and domestic birds on the paths of fall migrations to the north-western part of the Azov Sea basin (Krasnodar Territory)

Isolation, followed by the sequencing the full-size genome of strains of A/chicken/Krasnodarl300/07 and A/Cygnus cygnus/Krasnodar/329/07, has shown that they belong to genotype 2.2 (Qinghai-Siberian). The strains were deposited at the State Virus Collection of the Russian Federation and nucleotide consequences were at the International databank GenBank. The strains contained 10 unique amino acid replacements in reference to the consensus of the Qinghai-Siberian genotype in the PB2, PA, HA, NA, and NS1, which suggests that regional variants may form in different parts of an area.     

Mechanical, tribological, and biocompatibility properties of ZrN-Ag nanocomposite films

Nanocomposite films of ZrN-Ag were produced by reactive unbalanced magnetron sputtering, and their structural, chemical, mechanical, tribological, haemocompatibility, and antibacterial properties were studied as a function of film composition. The films formed a dense and homogeneous microstructure whereby nanocrystals of Ag are distributed evenly throughout the ZrN matrix. For small additions of silver, the hardness was found to increase, whereas the elastic modulus was found to decrease drastically. In the process of optimizing the deposition conditions, three kinds of coatings were prepared on 316 L surgical steel and tested by accelerated electrochemical polarization tests in order to detect the influence of Ag and the value of the bias potential on the corrosion performance of the system. Films produced under the optimum deposition conditions were, subsequently, deposited on medical grade Ti-Al-V and worn against ball-bearing steel using a ball-on-disk tribotester in bovine serum and were found to have superior tribological properties compared with single-phase ZrN coatings. The haemocompatibility of the films was assessed by investigating the adsorption of human serum albumin and fibrinogen on samples with different phase compositions. Quantification of the protein adsorption was carried out using spectroscopic ellipsometry, which confirmed the haemocompatibility of the films. Antibiotic activity of the films was quantified by incubating the films in bacterial cultures, namely, Staphylococcus epidermis, Staphylococcus aureus, and Escherichia coli. Films with a silver content > 10% exhibited superior antibacterial activity compared with the uncoated samples.     

L-Asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature

Background: Extranodal natural killer (NK)/T-cell lymphoma,nasal type, and aggressive NK-cell leukemia are highly aggressivediseases with a poor outcome. Patients and methods: We report a multicentric French retrospectivestudy of 15 patients with relapsed, refractory, or disseminateddisease, treated with L-asparaginase-containing regimens inseven French centers. Thirteen patients were in relapse and/orrefractory and 10 patients were at stage IV. Results: All but two of the patients had an objective responseto L-asparaginase-based treatment. Seven patients reached completeremission and only two relapsed. Conclusion: These data, although retrospective, confirm theexcellent activity of L-asparaginase-containing regimens inrefractory extranodal NK/T-cell lymphoma and aggressive NK-cellleukemia. Therefore, L-asparaginase-based regimen should beconsidered as a salvage treatment, especially for patients withdisseminated disease. First-line L-asparaginase combinationtherapy for extranodal NK/T-cell lymphoma and aggressive NK-cellleukemia should be tested in prospective trials. Key words: L-asparaginase, NK/T-cell lymphoma Received for publication July 2, 2008. Accepted for publication July 4, 2008.     

Type I (insulin dependent) diabetes mellitus

Summary A recent investigation of families containing two and three consecutive generations affected with Type I (insulin dependent) diabetes mellitus has led to speculation that there is a second susceptibility gene, not linked to the major histocompatibility complex. These families differ in important respects from families which have provided the strongest evidence for HLA linkage, namely, families with two or more affected siblings. Computer simulations were designed to test the hypothesis that these two types of families were drawn from the same population of insulin dependent patients. The results indicate that this hypothesis is tenable and that the consecutive generation families probably failed to yield strong evidence for an HLA linked susceptibility gene because of ascertainment bias combined with probable incorrect specifications of the mode of inheritance of insulin dependent diabetes.     

Interferon producing killer dendritic cells (IKDC): A matter of controversy

Division of labour among cells of the immune system is a prevailing theme in the orchestration of immune responses. Contrary to this paradigm, a particular leukocyte population in the mouse seems to be equipped with the ability to kill transformed and virally infected cells and with the capability to mediate antigen processing and presentation to T cells. Those two functions are classically ascribed separately to Natural Killer (NK) cells and Dendritic cells (DC). IKDC (interferon-producing killer dendritic cell) were defined in mice as cells expressing CD11c, although to a lesser extent than conventional DCs (cDCs), while coexpressing B220, NK1.1, CD49b (VLA-2) and MHC Class II molecules. Absence of CD3, CD19 and Gr1(Ly49c) expression also featured this minor subset upon multicolour FACS characterization. These cells kill a variety tumor cell lines in a TRAIL-dependent fashion. Furthermore, IKDC produce high amounts of Interferon (IFN) gamma (IFN-γ) and type I IFN upon activation by combined interleukins (IL-18, IL-2, IL-12 or IL-15), tumor cells, or TLR-9 nucleotide agonists. Importantly, these cells may present antigen to prime CD4 and CD8 T cells. The discovery of this subset in mice was reported in two back to back articles published in Nature Medicine in 2006, along with a comment that highlighted how such a cell may provide the ability to kill cells in an innate fashion while starting T-cell adaptive immunity by means of cross-presentation of antigens collected from the apoptotic remains of their victim cells. However, two years later three articles in a single issue of the Journal of Experimental Medicine contended that such a population did not exist and that IKDC were actually nothing more than activated NK cells. The arguments were based on the inability of IKDC to present antigen and prime T cells, and on their dependency on IL-15 for differentiation and survival. Later on, the groups that first described IKDC have provided evidence that such a subpopulation can mediate antigen presentation and have also stressed several characteristics that discriminate activated NK cells and IKDC. The reasons for some of these experimental discrepancies are obscure. Yet, the core of the controversy is to establish wether the hybrid abilities proposed for such minor leukocyte population are relevant to physiology, pathology or therapy. To date, no equivalent population has been described in human lymphoid tissues.