Ureaplasma in lung. 2. Association with bronchopulmonary dysplasia in premature newborns

Infants with Ureaplasma urealyticum in the lower respiratory tract are at risk for chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) but causality has been difficult to prove. The goal of this study was to identify ureaplasma in human neonatal lung tissue using the in situ hybridization (ISH) procedure described in Part 1 (Exp. Mol. Pathol., in press) of this report. By correlating their presence with the histopathologic findings, it may be possible to provide further evidence of the pathogenicity of ureaplasmas and their association with BPD. Lung autopsy tissue from seven infants with positive cultures and seven infants with negative cultures for ureaplasma were included in the study. All culture-positive infants were positive for ureaplasma on ISH and all had histopathologic evidence of BPD. Two of the seven infants with negative cultures were positive for ureaplasma with ISH. Of interest, these two infants were also found to have BPD at autopsy. The other five infants with negative cultures were also negative for ureaplasma on ISH and had no evidence of BPD. This study correlates the presence of U. urealyticum by ISH with the finding of BPD on histopathologic evaluation and provides evidence that it has a role in the development of CLD.     

Detection of Serum Antibodies to Ovine Progressive Pneumonia Virus in Sheep by Using a Caprine Arthritis-Encephalitis Virus Competitive-Inhibition Enzyme-Linked Immunosorbent Assay

A competitive-inhibition enzyme-linked immunosorbent assay (cELISA) for detection of antibodies to the surface envelope (SU) of caprine arthritis-encephalitis virus (CAEV) was recently reported (L. M. Herrmann, W. P. Cheevers, T. C. McGuire, D. Scott Adams, M. M. Hutton, W. G. Gavin, and D. P. Knowles, Clin. Diagn. Lab. Immunol. 10:267-271, 2003). The cELISA utilizes CAEV-63 SU captured on microtiter plates using the monoclonal antibody (MAb) F7-299 and measures competitive displacement of binding of the anti-CAEV MAb GPB 74A by goat serum. The present study evaluated the CAEV cELISA for detection of antibodies to ovine progressive pneumonia virus (OPPV) in sheep. Three hundred thirty-two sera were randomly selected from 21,373 sheep sera collected throughout the United States to determine the sensitivity and specificity of cELISA and agar gel immunodiffusion (AGID) based on immunoprecipitation (IP) of [³⁵S]methionine-labeled OPPV antigens as a standard of comparison. A positive cELISA test was defined as >20.9 percent inhibition (% I) of MAb 74A binding based on two standard deviations above the mean % I of 191 IP-negative sheep sera. At this cutoff, there were 2 of 141 false-negative sera (98.6% sensitivity) and 6 of 191 false-positive sera (96.9% specificity). Sensitivity and specificity values for IP-monitored AGID were comparable to those for cELISA for 314 of 332 sera with unambiguous AGID results. Concordant results by cELISA and IP resolved 16 of the 18 sera that were indeterminate by AGID. Additional studies evaluated cELISA by using 539 sera from a single OPPV-positive flock. Based on IP of 36 of these sera, there was one false-negative by cELISA among 21 IP-positive sera (95.5% sensitivity) and 0 of 15 false-positives (100% specificity). We conclude that the CAEV cELISA can be applied to detection of OPPV antibodies in sheep with high sensitivity and specificity.     

Multicenter evaluation of the performance characteristics of the NucliSens HIV-1 QT assay used for quantitation of human immunodeficiency virus type 1 RNA

The analytical performance of the NucliSens HIV-1 QT assay, a highly sensitive test based on nucleic acid sequence-based amplification technology, was evaluated in a multicenter trial. Assay specificity was evaluated with 502 plasma (EDTA) specimens from human immunodeficiency virus type 1 (HIV-1)-seronegative volunteer donors. No HIV-1 RNA was reported in any of the donor specimens. Analytical sensitivity and reproducibility were estimated with panels prepared from a high-titer well-characterized HIV-1 RNA stock (5.84 x 10(8) RNA copies/ml). The assay's dynamic range was linear from 10(6) to 10(1) HIV-1 RNA copies, with a lower detectable limit of 25 copies/ml and a 95% detection rate of 176 copies/ml. Sensitivity of the assay to detect HIV-1 RNA in clinical specimens from patients (n = 101) and in commercially available or prepared panels (n = 24) was compared with NASBA HIV-1 RNA QT (an earlier version of NucliSens HIV-1 QT) and with the Food and Drug Administration-approved standard and ultrasensitive AMPLICOR HIV-1 MONITOR, version 1.0, assays. Detection of HIV-1 RNA was reproducible over a 5-log range (mean standard deviation = 0.15 log). The NucliSens and the standard AMPLICOR assays were equivalent in detection of HIV-1 RNA (concentration, 10(3) to 10(5) copies/ml) in 57 clinical specimens. The NucliSens assay was more sensitive in detecting HIV-1 RNA at lower concentrations (相似文献   

A classification of diabetic foot infections using ICD-9-CM codes: application to a large computerized medical database

Background  

Diabetic foot infections are common, serious, and varied. Diagnostic and treatment strategies are correspondingly diverse. It is unclear how patients are managed in actual practice and how outcomes might be improved. Clarification will require study of large numbers of patients, such as are available in medical databases. We have developed and evaluated a system for identifying and classifying diabetic foot infections that can be used for this purpose.     

Human β‐defensin 3 increases the TLR9‐dependent response to bacterial DNA

Human β‐defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self‐DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt‐3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E. coli and self‐DNA in mouse FLDCs, only the response to bacterial DNA is enhanced. Liposome transfection also increases uptake of bacterial DNA and amplifies the TLR9‐dependent response. In contrast to hBD3, lipofection of self‐DNA enhances inflammatory signaling, but the response is predominantly TLR9‐independent. Together, these data show that hBD3 has a role in the innate immune‐mediated response to pathogen DNA, increasing inflammatory signaling and promoting activation of the adaptive immune system via antigen presenting cells including dendritic cells. Therefore, our data identify an additional immunomodulatory role for this copy‐number variable defensin, of relevance to host defence against infection and indicate a potential for the inclusion of HBD3 in pathogen DNA‐based vaccines.     

Nonparametric simulation-based statistical analyses for bipolar affective disorder locus on chromosome 21q22.3

Straub et al. [1994: Nat Genet 8:291-296] reported a candidate bipolar affective disorder (BAD) locus on chromosome 21q22.3. As a replication study, we analyzed 12 Australian BAD pedigrees for the presence of excess allele sharing and cosegregation with the putative chromosome 21q22.3 BAD locus, using six microsatellite markers. The nonparametric simulation-based statistic SimAPM produced positive results for the marker PFKL (P < 0.001) and D21S198 (P = 0.007). PFKL also demonstrated linkage (P < 0.001) when analyzed using the more conservative statistic, SimIBD. Comparable results were obtained when using the original APM statistic (P = 0.02 for D21S198). However, other nonparametric analyses such as GENEHUNTER and model-free linkage (MFLINK) analysis did not yield significant results. Combined LOD scores for the 12 families were strongly negative for all six markers under six genetic models. Two-point and multipoint analyses of individual families revealed one family, family 17, with maximal LOD scores greater than 1.41 for the 10.5-cM region between PFKL and D21S198. This report provides additional support for the suggestive linkage of a susceptibility locus for BAD on chromosome 21q22.3.     

Mastitis and Immunological Factors in Breast Milk of Lactating Women in Malawi

Although an elevated sodium concentration in human milk is suggested to be an indicator of mastitis, it is unclear whether elevated sodium concentrations are associated with immunological and inflammatory mediators in human milk. We conducted a cross-sectional study to evaluate the relationships between elevated breast milk sodium concentrations and levels of lactoferrin, lysozyme, secretory leukocyte protease inhibitor (SLPI), interleukin-8 (IL-8), and RANTES (regulated on activation normal T cell expressed and secreted) in human milk at 6 weeks postpartum in 96 lactating women in Blantyre, Malawi. Mastitis, as indicated by an elevated breast milk sodium concentration, was present in 15.6% of the women. Women with and without mastitis had respective median levels of other factors as follows: lactoferrin, 1,230 versus 565 mg/liter (P < 0.0007); lysozyme, 266 versus 274 mg/liter (P = 0.55); SLPI, 76 versus 15 μg/liter, (P < 0.0002); IL-8, 339 versus 25 ng/liter (P < 0.0001); and RANTES, 82 versus 3 ng/liter (P < 0.0001). Elevated sodium concentrations in breast milk are associated with an increase in levels of some immunological and inflammatory factors in breast milk.     

The search for a vaccine against schistosomiasis - a difficult path hut an achievable goal

Summary: The search for an effective vaccine against schistosomiasis, a parasitic disease currently affecting over 200 million people, remains a desirable but as yet challenging and elusive goal. Progress in the area has been relatively slow but research demonstrating the ability of humans to acquire natural immunity to schistosome infection, together with the successful use in animals of attenuated vaccines, supplemented with encouraging results obtained with defined antigens, suggests that development of a vaccine is achievable. Noteworthy also are recent immune correlate findings which shed light on the complex, putatively protective immune responses in buinans, which have improved the prospects of success. With the first human clinical trial having been completed with a schistosome vaccine candidate, this review examines current progress aimed at achieving the objective of a safe and effective vaccine for widespread use against schistosomiasis. The review emphasises work undertaken in the author's laboratory and those of his chief collaborators in the search for a vaccine against schistosomiasis japonica, a disease of major public health significance in The People's Republic of China and The Philippines. Schistosomiasis vaccines should not be considered as the panacea for schistosomiasis control as, when available, it is generally envisaged that they would be used as one component of an integrated strategy complementing currently available and effective tools such as chemotherapy, improvements to sanitation, piped water supply, effective sewage draining and health education.     

Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.