Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats

Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.     

Lymphoepithelioma-like carcinoma of the bladder: three cases with clinicopathological and p53 protein expression study

Lymphoepithelioma-like carcinoma of the bladder is an uncommon neoplasm, of which 49 cases have been described in the English literature, none of which has been studied for p53 protein expression. We studied three muscle-infiltrating cases of this tumor using immunohistochemical, in situ hybridization and polymerase chain reaction (PCR) methods. The three cases were positive for epithelial markers and negative for lymphoid antigens in the tumoral syncytial areas. The intensive infiltrate of small cells was negative for epithelial and positive for lymphoid markers. This population was mainly made up of cytotoxic T-lymphocytes, positive for TIA-1. p53 protein was intensely positive in more than 90% of the epithelial component nuclei, being negative in the lymphoid cells. PCR study did not show mutations on p53. Both lymphocytes and epithelium were negative for Epstein–Barr virus markers, such as the latent membrane protein and EBER (Epstein–Barr-encoded RNA). The prognosis was very good after radiotherapy and chemotherapy treatment, preserving the bladder despite the muscle infiltration. The presence of an intense cytotoxic T-lymphocyte population may be related to this good prognosis. Both aspects, p53 protein status and T-lymphoid population, had never been studied before in bladder lymphoepithelioma-like carcinoma.     

Evolution of foot-and-mouth disease virus

Foot-and-mouth disease virus evolution is strongly influenced by high mutation rates and a quasispecies dynamics. Mutant swarms are subjected to positive selection, negative selection and random drift of genomes. Adaptation is the result of selective amplification of subpopulations of genomes. The extent of adaptation to a given environment is quantified by a relative fitness value. Fitness values depend on the virus and its physical and biological environment. Generally, infections involving large population passages result in fitness gain and population bottlenecks lead to fitness loss. Very different types of mutations tend to accumulate in the foot-and-mouth disease virus (FMDV) genome depending on the virus population size during replication. Quasispecies dynamics predict higher probability of success of antiviral strategies based on multivalent vaccines and combination therapy, and this has been supported by clinical and veterinary practice. Quasispecies suggest also new antiviral strategies based on virus entry into error catastrophe, and such procedures are under investigation. Studies with FMDV have contributed to the understanding of quasispecies dynamics and some of its biological implications.     

Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite

The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function.     

Molecular genetic methods in the diagnosis of hematologic neoplasms

Leukemias and lymphomas are monoclonal neoplasms that arise as a result of molecular abnormalities. These abnormalites are diverse but can be grouped into two general categories, chromosomal translocations that usually result in oncogene activation and inactivation of tumor suppressor genes. Recent advances in our understanding of chromosomal translocations have led to improved classification of leukemias and lymphomas. For example, the t(9;22)(q34;q11) is now considered a defining feature of chronic myeloid leukemia, and the t(2;5)(p23;q35) defines a clinically and biologically unique subset of anaplastic large cell lymphomas. In this review, we focus on chromosomal translocations in hematologic neoplasms and the techniques used for their detection. We also briefly discuss tumor suppressor genes and assessment of clonality in lymphoid neoplasms.     

The association of access to medical care with regular source of care and sociodemographic characteristics in patients with HIV and tuberculosis

PURPOSE: To examine satisfaction with access to health care in two populations, one with HIV and one with TB, and examine the effect of having a regular doctor and sociodemographic characteristics. DESIGN: Cross-Sectional survey. PATIENTS: A sample of HIV inpatients hospitalized at seven Los Angeles sites (N = 217) and TB outpatients chosen randomly from the Los Angeles County TB Registry Census (N = 313). ANALYSIS: We performed bivariate and multivariate regression analyses of satisfaction with access to care on gender, race/ethnicity, age, education, income, insurance, and having a regular doctor. MAIN OUTCOME MEASURES: A six-item scale of satisfaction with access to care (range 0-100; Cronbach's alpha 0.87). RESULTS: The mean satisfaction with access score for the HIV sample was significantly lower than the TB sample (53.5 vs. 61.2, p<0.001). The HIV sample multivariate analysis (including all the variables) showed that increasing age (p<0.021 and having a regular doctor (p<0.002) were associated with better access, and that low income (p<0.005) was associated with poor access. In the TB sample analysis, only increasing age was associated with better satisfaction with access to care (p< 0.01). CONCLUSION: HIV patients receiving care in the private sector reported less satisfaction with access to care compared to TB patients receiving care in the public health sector. The traditional factors of socio-economic status and having a regular doctor were associated with satisfaction with access-to-care in the HIV sample but not the TB sample. Our findings suggest that certain characteristics of the TB public health programs may explain these differences and suggests that, perhaps, the existence of a similar public health program for vulnerable low-income populations with HIV would improve their satisfaction with access, as well.