(1/150) Effects on the ciliated epithelium of protein D-producing and -nonproducing nontypeable Haemophilus influenzae in nasopharyngeal tissue cultures.

A pair of isogenic, nontypeable Haemophilus influenzae strains, one expressing protein D and the other protein D-negative, was compared in their ability to cause damage in a human nasopharyngeal tissue culture model. Damage was assessed by measuring the ciliary beat frequency (CBF) of tissue specimens at 12 h intervals. Cultures inoculated with H. influenzae manifested a decrease in CBF beginning after 12 h, with a maximum decrease after 36 h. The impairment of ciliary function by the protein D-expressing strain was significantly greater than that caused by the protein D-negative mutant (P<.01). Tissue specimens examined by scanning and transmission electron microscopy after 24 h appeared normal. After 48 h of incubation, the protein D-expressing strain caused a significant loss of cilia. These findings suggest that protein D is involved in the pathogenesis of upper respiratory tract infections due to nontypeable H. influenzae, probably by enhancing functional and morphological damage to cilia.  (+info)

(2/150) Residual low-level viral replication could explain discrepancies between viral load and CD4+ cell response in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

We report the evolution of chronic infection with human immunodeficiency virus type 1 (HIV-1) in a patient treated with stavudine plus didanosine, whose CD4+ lymphocyte count progressively decreased, despite a sustained plasma viral load <20 copies/mL. After 12 months of therapy, treatment was switched to zidovudine plus lamivudine plus nelfinavir. CD4+ T cell count decreased from 559 x 10(6)/L at month 0 to 259 x 10(6)/L at month 12. Plasma viral load decreased from 21,665 HIV-1 RNA copies/mL at baseline (month 0) to <20 copies/mL after 1 month of therapy with stavudine plus didanosine, and remained below 20 copies/mL until month 12, but always >5 copies/mL. Viral load in tonsilar tissue at month 12 was 125,000 copies/mg of tissue. After the change to triple-drug therapy, the plasma viral load decreased to 5 copies/mL, the CD4+ T cell count increased to 705 x 10(6)/L, and the viral load in tonsilar tissue decreased to <40 copies/mg of tissue at month 24. A low level of HIV-1 replication could explain the lack of immunologic response in patients with apparent virological response.  (+info)

(3/150) Amoxicillin for fever and sore throat due to non-exudative pharyngotonsillitis: beneficial or harmful?

OBJECTIVES: To determine duration of signs and symptoms and adverse reactions after treatment with amoxicillin of patients with fever and sore throat due to non-exudative pharyngotonsillitis. DESIGN: This was a randomized, double-blinded, placebo-controlled trial. Outpatients at four medical centers were enrolled. Patients over 5 years of age presented with fever and sore throat for less than 10 days due to non-exudative pharyngotonsillitis. Cases with any of the following symptoms or illness were excluded: earache, nasal discharge with foul smell, rheumatic fever, valvular heart disease, renal disease, and penicillin hypersensitivity. Amoxicillin or identical placebo at the dosage of 50 mg/ kg per day was given three or four times daily for 7 days. RESULTS: There were 1217 patients enrolled in this study. Some were lost to follow-up, which is the reason for the variability in number of cases in these analyses. After therapy, duration of fever was 2.46 and 2.48 days (P = 0.78) and of sore throat 3.01 and 3.04 days (P = 0.80) in amoxicillin (n = 431) and placebo (n = 436) groups, respectively. Complications were clinically documented in 13 (2.5%) and 16 (3.0%) cases in amoxicillin (n = 527) and placebo (n = 524) groups (P = 0.56). Two cases (0.46% and 0.46%) from each group (n= 433 and 431) were positive by antistreptolysin O antibody determination. The history of carditis and abnormal urinalysis after treatment were not obtained. CONCLUSIONS: Amoxicillin therapy for non-exudative pharyngotonsillitis conferred no beneficial or harmful effect.  (+info)

(4/150) Comparison of short-course (5 day) cefuroxime axetil with a standard 10 day oral penicillin V regimen in the treatment of tonsillopharyngitis.

Oral penicillin V given three times daily in doses of 50,000-100,000 IU daily has been the standard treatment for tonsillopharyngitis for the last few decades. These regimens, initially recommended by the American Heart Association, were extrapolated from i.v. dosing with long-acting forms of penicillin which had been shown to prevent post-streptococcal sequelae. More recently, several antibiotics, including cefuroxime axetil, have been shown to be at least as effective as penicillin G in eradicating group A beta-haemolytic streptococci (GABHS) but their influence on post-streptococcal sequelae has never been assessed in a large-scale trial. The German Society for Pediatric Infectious Diseases (DGPI) undertook a large study of culture-proven tonsillopharyngitis involving several agents and included a 1 year follow-up to establish the effect on sequelae. In one arm of this study, cefuroxime 250 mg bid was compared with 50,000 IU penicillin V given in three divided doses. Cefuroxime axetil was more effective than oral penicillin V in eradicating GABHS at the assessment 2-4 days post-treatment (441/490 (90%) patients versus 1196/1422 (84%) patients; P = 0.001). Clinically, the two agents were equivalent in efficacy, and carriage rates were similar (11.1% and 13.8%, respectively) in patients receiving cefuroxime axetil and penicillin V, 7-8 weeks post-treatment. One case of glomerular nephritis occurred in a patient given penicillin V. There were no post-streptococcal sequelae confirmed for patients treated with cefuroxime axetil. The findings confirm the previously reported efficacy of short-course (4-5 day) treatments with cefuroxime axetil and indicate that short-course treatment is comparable to the standard oral penicillin V regimen in preventing post-streptococcal sequelae.  (+info)

(5/150) Interaction of Bordetella pertussis with human respiratory mucosa in vitro.

The human respiratory tract pathogen Bordetella pertussis is the major cause of whooping cough in infants and young children, and also causes chronic cough in adults. B. pertussis infection damages ciliated epithelium in the respiratory tract. However, the interaction of the bacterium with the respiratory mucosa is poorly understood, and previous studies have either utilized animal tissue which may not be appropriate, or isolated cell systems which lack the complexity of the respiratory mucosa. We have studied the interaction of B. pertussis strain BP536 with human nasal turbinate tissue in an air-interface organ culture over 5 days. We have also compared infection by BP536 with two other strains, Tohama I and CN2992, to determine whether the interactions observed with BP536 are consistent, and, in both nasal turbinate and adenoid organ cultures at 24 h, to determine whether there were differences between tissue from different parts of the respiratory tract. BP536 adhered to cilia, most commonly at their base, and disorganized their spatial arrangement, they also adhered to damaged tissue and mucus, but very rarely to unciliated cells. Within the first 24 h there was a five-fold increase in bacterial density on ciliated cells, and the total number of adherent bacteria increased up to 96 h. Infection caused increased mucus at 24h and an increase in damaged epithelium from 72 h which involved both ciliated and unciliated cells. The number of residual ciliated cells did not decrease after 72 h. The three different strains of B. pertussis exhibited similar interactions with the mucosa, and there was no tissue specificity for adenoid or turbinate tissue. We conclude that B. pertussis adhered to multiple sites on the mucosa and caused hypersecretion and epithelial damage which are the pathological changes described in vivo.  (+info)

(6/150) Adenoids provide a microenvironment for the generation of CD4(+), CD45RO(+), L-selectin(-), CXCR4(+), CCR5(+) T lymphocytes, a lymphocyte phenotype found in the middle ear effusion.

Adenoidectomy in children with otitis media with effusion reduces inflammation in the middle ear by an unknown mechanism. Potentially, the adenoids of these children may serve as a site for the differentiation of lymphocytes, which after entering blood circulation eventually extravasate in the middle ear mucosa and thereby contribute to excessive inflammation. During lymphocyte extravasation various adhesion molecules and chemokines play a crucial role. To evaluate possible connections between the adenoids and middle ear inflammation, the expression of the chemokine receptors CXCR4 and CCR5 and the lymphocyte homing receptor L-selectin were analyzed in adenoidal and middle ear lymphocytes. It was found that most CD4(+) T lymphocytes in the middle ear effusion express the memory phenotype marker CD45RO and the chemokine receptors CXCR4 and CCR5, but are negative for the lymphocyte homing receptor L-selectin. This cell phenotype was rare in peripheral blood but was found much more frequently in the adenoids. The results suggest that the adenoids provide a microenvironment for the generation for CD4(+), CD45RO(+), L-selectin(-), CXCR4(+) and CCR5(+) T lymphocytes. Further, these cells may include cells that have the capacity to home to the middle ear mucosa. As the adenoidal CD4(+) memory phenotype CD45RO(+) T cells expressed the activation antigen CD69 and included cells expressing the HIV co-receptors CXCR4 and CCR5 at a high level, they may be permissive for HIV infection.  (+info)

(7/150) Cytokeratin 17 is expressed in cells infected with respiratory syncytial virus via NF-kappaB activation and is associated with the formation of cytopathic syncytia.

We used differential display to detect enhanced expression of an mRNA fragment encoding cytokeratin 17 (Ck-17) in respiratory syncytial virus (RSV)-infected epithelial cells. Expression increased 12-fold by 96 h after infection but remained unchanged in cells challenged with virus in the presence of neutralizing anti-RSV fusion protein antibody. Immunoblots of RSV-infected cell lysates probed with an anti-keratin antibody demonstrated stable expression of total cytokeratins over time. When probed with an anti-Ck-17 monoclonal antibody, Ck-17 was first detected at 4 days after infection. In situ staining demonstrated that Ck-17 expression localized to regions of syncytia formation. Expression of Ck-17 mRNA also increased in response to intracellular RSV-F protein in the absence of active RSV infection. No increase in Ck-17 mRNA expression and no syncytia were observed in RSV-infected cells grown in the presence of the NF-kappaB inhibitor gliotoxin. These results suggest that RSV-induced transcriptional activation of the Ck-17 gene is dependent on an NF-kappaB-associated signaling pathway.  (+info)

(8/150) Human nasopharyngeal-associated lymphoreticular tissues. Functional analysis of subepithelial and intraepithelial B and T cells from adenoids and tonsils.

Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic immune responses. The distribution of T and B cell subsets, cytokine patterns, and antibody (Ab) isotype profiles were similar for adenoids and tonsils. Both tissues contained predominantly B cells ( approximately 65%), approximately 5% macrophages, and 30% CD3(+) T cells. The T cells were primarily of the CD4(+) subset ( approximately 80%). Tonsillar intraepithelial lymphocytes were also enriched in B cells. The analysis of dispersed cells revealed a higher frequency of cells secreting IgG than IgA and the predominant Ig subclass profiles were IgG1 > IgG3 and IgA1 > IgA2, respectively. In situ analysis also revealed higher numbers of IgG- than IgA-positive cells. These IgG-positive cells were present in the epithelium and in the subepithelial zones of both tonsils and adenoids. Mitogen-triggered T cells from tonsils and adenoids produced both Th1- and Th2-type cytokines, clearly exhibiting their pluripotentiality for support of cell-mediated and Ab responses. Interestingly, antigen-specific T cells produced interferon-gamma and lower levels of interleukin-5. These results suggest that adenoids and tonsils of the nasopharyngeal-associated lymphoreticular tissues represent a distinct component of the mucosal-associated lymphoreticular tissues with features of both systemic and mucosal compartments.  (+info)

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