Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults.

An open-label, multicenter study was performed to assess bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Seventy aerobic (52.2%) and 64 anaerobic (47.8%) pathogens were recovered from clinically evaluable patients at baseline (before therapy). The most commonly isolated anaerobes were Prevotella species (31.1%), anaerobic streptococci (21.9%), and Fusobacterium species (15.6%). The aerobes most frequently recovered included Streptococcus species (21.4%), Haemophilus influenzae (15.7%), Pseudomonas aeruginosa (15.7%), and Staphylococcus aureus and Moraxella catarrhalis (10.0% each). Recurrences of signs or symptoms of bacterial maxillary sinusitis associated with anaerobes were twice as frequent as were those associated with aerobes when counts of anaerobes were > or =10(3) cfu/mL. A pathogenic role for Granulicatella species in cases of chronic sinusitis was documented for the first time.

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.

Response of human ovarian carcinoma cell lines to antiprogestin mifepristone.

The effects of antiprogestin mifepristone (MF) on the growth, progesterone receptor expression and cell cycle kinetics of several human ovarian epithelial carcinoma (OEC) cell lines were evaluated. MF, a synthetic antiprogestin, has been shown to have some antiproliferative activity in breast tumors and in the endometrium, but its efficacy in ovarian carcinomas has not been explored previously. Continuous exposure of OEC cells to MF resulted in a dose- and time-dependent growth inhibition, as determined by MTT assay. Growth inhibition was apparent by day three following addition of MF to cultures in vitro. All cell lines used in this study expressed a progesterone receptor (PR). MF down regulated PR expression on these cells. Changes in the cell cycle kinetics of OEC cells exposed to MF correlated with the observed antiproliferative effects. MF blocked cells in a G0/G1 phase of the cell cycle and thus reduced the number of cells in the S phase. The efficacy of MF was compared with that of taxol and tamoxifen in the same human OEC cell lines. Continuous exposure of OEC cells to tamoxifen resulted in a varied cytostatic response and a transient change in the cell cycle. Taxol inhibited growth of some but not all of the cell lines. These results indicate that PR-positive human OEC cells are sensitive to MF in vitro and that MF may be an active agent against ovarian epithelial tumors.

Expression of quinone reductase activity in embryonal and adult porcine tissues.

Quinone reductase (QR; EC 1.6.99.2) is recognized as a major antimutagenic/anticarcinogenic enzyme in the organism. Our recent studies demonstrated the presence of significant QR activity in the early human placenta; whether this enzyme is expressed by the mammalian embryo is not known at present. In the investigation reported here, we sought to determine whether or not QR activity is detected in porcine embryonal tissues and if so, how early this expression takes place. In addition, the enzyme activity in the embryo was compared to that present in adult porcine tissue. Enzyme activity was determined by a colorimetric method with menadione as substrate in the presence of tetrazolium salt (MTT). NADH was a preferable cofactor in the embryo, whereas in the adult tissues NADPH was a better cofactor. Results show that the enzyme is present in all the embryonal organs tested from a very early age (30 days of gestation). Among the organs tested, activity was highest in the porcine embryo liver, and the specific activity remained unchanged until Day 70. Activity in the embryonal kidney increased with advancing gestation. The enzyme activity in embryonal tissues was much lower than that measured in the adult liver (30-40-fold). These findings suggest that the embryo has the potential for inactivating carcinogens/mutagens that will subsequently be eliminated by the maternal organism, thus protecting against adverse environmental impacts during the most critical period of development.

The acute effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence in normal subjects.

This study examined the effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence. Trazodone is a sedating antidepressant without anticholinergic properties. Nefazodone is a new antidepressant that is a structural analogue of trazodone but is less sedating. Buspirone is a nonsedating, nonbenzodiazepine anxiolytic with antidepressant properties. Nefazodone was compared to trazodone and buspirone in a double-blind, placebo-controlled crossover study in 12 normal healthy males. Nefazodone increased rapid eye movement (REM) sleep, whereas trazodone and buspirone suppressed REM sleep. The drugs only minimally affected other sleep stages. Trazodone increased total tumescence time by delaying the onset of detumescence; nefazodone increased total tumescence time only insofar as it increased REM sleep; buspirone did not change total tumescence time when compared to placebo. The results support a growing body of data indicating that not all antidepressants suppress REM sleep. The results also are consistent with the interpretation of an earlier study showing that trazodone prolongs penile tumescence during sleep as a result of its alpha-adrenergic blocking properties that suppress detumescence. Nefazodone, with less alpha-adrenergic blocking activity, did not abnormally penile tumescence beyond REM sleep.

Abrogation of IL-2 dependence by recombinant murine retrovirus containing v-myb.

Biological consequences of expression of v-myb gene in murine long-term T cell lines (CTLL-2 and HT-2) were studied using murine retroviral vectors. Expression of high levels of v-myb altered responses to interleukin (IL)-2, expression of surface markers, and growth characteristics of these cells. Interestingly, v-myb oncogene brings about growth-factor independence in IL-2-dependent T cell lines with concomitant induction of IL-2 mRNA and downregulation of IL-2 receptor synthesis. These results suggest a role for myb gene products in IL-2 gene expression.

Secondary intratracheal infection of mice with Mycoplasma pulmonis generates IgG1 memory B cells.

Mycoplasma pulmonis, a rodent respiratory pathogen, was used to study the immune response in the bronchus-associated lymphoid tissue (BALT) and other lymphoid tissues. Infection of BALB/c mice intratracheally (i.t.) with M. pulmonis results in an increased frequency of antigen-sensitive B cells at the site of priming. Upon secondary i.t. challenge, the frequency of antigen-specific B cells rises significantly in BALT, in peripheral blood and, to a lesser extent, in lymphoid tissues distal to the site of priming, i.e., spleen and Peyer's patches. The predominant isotype of anti-M. pulmonis antibody expressed by clones grown in thymus-dependent splenic fragment cultures from B cells taken from all tissues is IgG1. Elimination of accompanying T cells in inocula from euthymic BALB/c mice or lack of T cells at the time of in vivo priming of athymic mice does not change the isotype profile of clones grown from M. pulmonis-specific B cells. The splenic fragment cultures used to grow these clones do not distort the isotype display towards IgG1 expression, since clones grown from either primed or unprimed B cells of other specificities (i.e., trinitrophenyl--TNP) express any or all isotypes in a variety of combinations. The majority of M. pulmonis-specific clonal precursor B cells are sIgG1+/IgD-. All these findings suggest that the potential to give rise to predominantly IgG1-secreting clones in vitro is intrinsic to the M. pulmonis-specific memory B cells primed in vivo.

Isotype commitment of B cells and dissemination of the primed state after mucosal stimulation with Mycoplasma pulmonis.

Live Mycoplasma pulmonis organisms were used to examine the immune response in the bronchus-associated lymphoid tissue after primary and secondary challenge with M. pulmonis, to study the dissemination of the primed state to distal tissues (i.e., spleen, peripheral blood, and Peyer's patches), and to determine whether the chronic antigenic stimulation accompanying infection influences the isotype potential and commitment of the primed B cells recovered from the various tissues. We have shown that exposure to M. pulmonis by a variety of routes results in a generalized rise in frequency of T-dependent, antigen-sensitive B cells in all lymphoid tissues. The route of secondary exposure to M. pulmonis was found to markedly increase the frequency of M. pulmonis-specific B cells in the bronchus-associated lymphoid tissue relative to that in the Peyer's patches after intraduodenal but not intratracheal challenge. A substantial rise in the number of M. pulmonis-sensitive B cells in the peripheral blood suggests that the dissemination of the primed state, at least in part, is due to B-cell migration via lymph and blood from local sites exposed to M. pulmonis. The majority of T-dependent clones generated by M. pulmonis-specific B cells secrete exclusively immunoglobulin G1 (IgG1). We have demonstrated that the exaggerated IgG1 response was not due to the accompanying viable donor T cells in the inoculum. The predominance of IgG1 was also demonstrated in clones from the bronchus-associated lymphoid tissue of athymic BALB/c mice that were primed with M. pulmonis. Thus, we can infer that functional T cells are not required for the development of specific B cells with the potential for IgG1 expression at the time of in vivo priming. When anti-trinitrophenyl- and anti-M. pulmonis-specific clones were generated in the same splenic fragment cultures stimulated by trinitrophenylated M. pulmonis, only the M. pulmonis-specific clones showed exaggerated IgG1 expression. Therefore, we conclude that the exaggerated IgG1 response accompanying M. pulmonis infection of euthymic mice seems to be dependent, at least in part, on an intrinsic property of the B cells that develop during this antigenic stimulation.

Changes in specific B cells and the dissemination of the primed state in vivo following antigenic stimulation by different mucosal routes.

Immunologic dogma holds that the adaptive and long-term potential of the antibody response is fashioned by antigen-dependent, selective clonal proliferation of specific B cells and the retention of some which may undergo a second round of antigen-stimulated clonal expansion with antibody production. Apparently, the short-term, immediate consequences of an antibody response depend on the mix of isotypes displayed in vivo upon exposure to antigen. This latter seems to be clearly regulated by T cells, but it is also likely that the isotype potential of a B cell population and its future possible display of isotypes is linked to the initial, antigen-dependent proliferative phase in the development of an antibody response. In vitro analysis at limiting dilutions of specific B cells primed in vivo has led to the operational definition of IgA-committed cells. These B cells increase in frequency following chronic or acute antigenic stimulation of gut mucosa and have the potential to proliferate again in the presence of antigen and TH(Ag) cells to produce exclusively IgA. A general relationship exists between mucosal or parenteral priming of B cells and their potentials to express IgA and/or IgE--both isotypes appear to be likely products of secondary B cells and frequently both can be expressed by the same clone activated by a second-round of T-dependent antigenic stimulation. Cross priming--exposure of GALT or BALT leading to secondary B cells in the opposite mucosal lymphoid tissue--suggests an inherent antagonism between development of allergic (IgE) and putative allergy blocking (IgA) potentials.(ABSTRACT TRUNCATED AT 250 WORDS)