Clinical evaluation of three urine screening tests

Evaluations of screening tests for bacteriuria have traditionally compared the test results with those of quantitative urine cultures. However, many patients with symptomatic urinary tract infections can have less than 10(5) CFU/ml in their urine. Therefore, the results of urine culture and three screening tests (Bac-T-Screen, Chemstrip LN [which tests for leukocyte esterase and nitrate reductase], and Gram stain) were correlated with the clinical classification of urinary tract infection. The Bac-T-Screen test detected 98, 93, and 100% of the infections classified as probable, possible, and asymptomatic, respectively. In contrast, the Gram stain, leukocyte esterase, and nitrate reductase tests were all insensitive screening tests for infection. Additionally, only 45% of the patients with probable infections had greater than or equal to 10(5) CFU/ml. Thus, the majority of infected patients would not have been detected if quantitative urine cultures were used alone.     

Active and inactive influenza virus induction of tumor necrosis factor-alpha and nitric oxide in J774.1 murine macrophages: modulation by interferon-gamma and failure to induce apoptosis

Infection of J774.1 murine macrophages by influenza A virus (IAV) induces two major responses, production of host defense molecules and death by apoptosis. We investigated whether induction of two cytotoxic compounds, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), directly caused IAV-induced apoptosis, and whether induction could be modulated by interferon-gamma (IFN-gamma) or the replication competence of the virus. Live IAV potently induced production of both TNF-alpha and NO, but UV inactivated virus was a poor inducer of both molecules. When cells were pre-treated with IFN-gamma, inactive IAV became as effective an inducer of NO, but not TNF-alpha, as live IAV. Amantadine, which antagonizes viral entry and replication, partly inhibited TNF-alpha and NO production in unprimed cells, but did not inhibit NO in IFN-gamma primed cells. IAV-induced cytotoxicity was not due to the induction of TNF-alpha or NO. Cells were insensitive to either TNF-alpha-containing supernatants or to recombinant TNF-alpha. Anti-TNF-alpha antibody did not protect cells from IAV-induced cell death, and anti-oxidants that inhibited TNF-alpha production also failed to increase cell survival. Inhibitors of NO production did not protect from IAV-induced cell death, either alone or in combination with superoxide dismutase (SOD). We conclude that, even though IAV was a potent inducer of TNF-alpha and NO in macrophages, IAV-induced apoptosis was not mediated directly by them. Importantly, viral replication was not required for the induction of TNF-alpha or NO, and the action of inactive IAV could be potentiated by IFN-gamma.     

Optimizing vaccine design for cellular processing,MHC binding and TCR recognition

In this review we describe the methods and processes that our group have developed while aiming to test and design multiepitope vaccines for infectious diseases and cancer. Testing the performance of vaccines composed of epitopes restricted by human leukocyte antigen (HLA) molecules is accomplished by in vitro antigenicity assays, as well as in vivo immunogenicity assays in HLA transgenics. The efficiency by which multiepitope vaccines are processed is optimized by spacer residues, which are designed to facilitate generation by natural processing of the various class I- and class II-restricted epitopes. Methods and strategies to test and optimize HLA binding affinity, patient coverage from the vaccine construct, and TCR recognition of HLA/epitope complexes are also discussed.     

A String Matching Computer-Assisted System for Dolphin Photoidentification

This paper presents a syntactic/semantic string representation scheme as well as a string matching method as part of a computer-assisted system to identify dolphins from photographs of their dorsal fins. A low-level string representation is constructed from the curvature function of a dolphin's fin trailing edge, consisting of positive and negative curvature primitives. A high-level string representation is then built over the low-level string via merging appropriate groupings of primitives in order to have a less sensitive representation to curvature fluctuations or noise. A family of syntactic/semantic distance measures between two strings is introduced. A composite distance measure is then defined and used as a dissimilarity measure for database search, highlighting both the syntax (structure or sequence) and semantic (attribute or feature) differences. The syntax consists of an ordered sequence of significant protrusions and intrusions on the edge, while the semantics consist of seven attributes extracted from the edge and its curvature function. The matching results are reported for a database of 624 images corresponding to 164 individual dolphins. The identification results indicate that the developed string matching method performs better than the previous matching methods including dorsal ratio, curvature, and curve matching. The developed computer-assisted system can help marine mammalogists in their identification of dolphins, since it allows them to examine only a handful of candidate images instead of the currently used manual searching of the entire database. © 2000 Biomedical Engineering Society. PAC00: 8780Tq, 4230Sy, 0705Pj     

Myopathic alterations in extraocular muscle of rats subchronically fed pyridostigmine bromide

To determine if alterations in extraocular muscle morphology occur after subchronic oral administration of pyridostigmine bromide, rats were continuously fed 90 mg/kg in meal and examined at 1, 2, 4, 7, and 15 days. Within the first day, blood acetylcholinesterase activity was reduced by 87% and remained inhibited by 74-91% during the study. Light microscopy demonstrated that by day 1 approximately 3% of the extraocular myofibers were shrunken and invaded by inflammatory cells. The most severe degenerative changes consisting of vacuoles and inflammatory cell infiltration occurred at day 1 with progressively less severe changes at days 2 and 4. At days 7 and 15, 1.3-4.5% of the myofibers still exhibited damage. Ultrastructurally, all presynaptic areas were normal but the postsynaptic areas of affected myofibers at days 1, 2, and 4 showed myofilament and Z-band dissolution, mitochondrial inclusions, subneural fold and T-tubule/sarcoplasmic reticulum vacuolization and subneural fold depth reduction. By days 7 and 15, these changes were diminished in some cases and in others alterations appeared similar to day 1. We conclude that subchronic feeding of pyridostigmine bromide induces myopathic rather than neurogenic changes in rat extraocular muscle and that the myopathy is different in these muscles than in the diaphragm from the the same rats.     

Interorganizational exchanges as performance markers in a community cancer network.

OBJECTIVE. This study examines how "strategic partnerships" between community-based consortia of oncologists and hospitals (CCOPs) and clinical cooperative groups emerge, develop, and influence patient accruals (i.e., the number of patients enrolled in clinical trials) over time. DATA SOURCES AND STUDY SETTING. Study analyses are based on 65 pairwise relationships that 38 CCOPs established with eight clinical cooperative groups in September 1983 and maintained through February 1989. Data are drawn from grantee applications and progress reports. STUDY DESIGN. The study examines how different types of CCOP-cooperative group exchange relate to one another and to CCOP patient accruals over six time points. Key independent variables include resource dependence, information exchange (i.e., meeting attendance and committee membership), and protocol exchange (i.e., the number of different protocols used). DATA COLLECTION METHODS. Data extracted from secondary sources were entered in a data base. PRINCIPAL FINDINGS. The number of CCOP physicians and support staff who attend cooperative group meetings during the first two years of a clinical research partnership has a significant influence on meeting attendance and protocol use in later years. Two-thirds or more of the variance in patient accruals at each time point can be explained by the number of different protocols used and the number of CCOP representatives serving on cooperative group committees (or attending cooperative group meetings). CONCLUSIONS. The findings highlight the importance of historical relationships and anticipated resource dependence in shaping initial exchange patterns. They also suggest that strategic partnerships need to emphasize structures and processes that encourage early involvement in collaborative activities and that reward participants for maintaining high levels of interaction.     

Balancing the equation: The significance of professional and lay perceptions in the promotion of cervical screening amongst minority ethnic women

Studies of minority ethnic women and cancer screening have, in the past, suffered from many theoretical and methodological weaknesses. In addition, no attempts have been made to study the complexity of the issue involved in the intercultural context, or the possible contribution of women's experiences to low uptake rates. In order to further our understanding of the issues, an alternative approach, participatory action research (PAR), was adopted to identify factors that might have contributed to the persistently low participation of minority ethnic women in the cervical screening programme, and address them collaboratively. This paper presents the key findings of the ‘problem identification' phase of the project. Using mainly the focus-group method, it explores both smear takers' and minority ethnic women's perceptions and experiences of cervical screening. Data suggest that there was a divergence in perceptions held by these groups regarding cervical screening, which contributed to negative experiences for both groups. There is also clear evidence of dysfunctional clinical communication arising from these differing perceptions. Opportunistic screening at post-natal examination adopted by many general practices appeared to have perpetuated the perceptions that the majority of minority ethnic women held about the purpose of the smear test. Compounded by language differences, the majority of women who had undergone smear testing understood neither the purpose of screening programme nor the procedure of the test. This has clear implications for promoting regular uptake, and more importantly for informed consent and choice.     

Effects of imipramine treatment of separation-induced social disorders in rhesus monkeys.

Two groups of young rhesus monkeys were subjected to repetitive peer separations, a procedure that has been shown to produce depressivelike reactions in infant monkeys. Midway through the procedure one group was treated with the antidepressant imipramine hydrochloride, the other with a saline placebo. In comparison with placebo treatment, the imipramine treatment yielded significant behavioral improvement in a form and with a time course similar to that seen when the drug is given clinically to human depressives. We discuss the implications of the findings.