Fosfomycin nebulizer therapy to chronic sinusitis.

OBJECTIVE: effects of Fosfomycin (FOM) nebulizer therapy were studied in patients with chronic sinusitis. METHODS: about 28 patients with chronic sinusitis were administered 2 ml of FOM sodium (3% w/v) by nebulizer three times per week for 4 weeks. Levels of IL-1 beta, IL-6, IL-8, and TNF-alpha in nasal lavage were also measured before and at the end of treatment. RESULTS: the overall efficacy of this treatment on the basis of both subjective and objective symptoms, was 'excellent' for 28.6%, 'good' for 10.7%, 'fair' for 39.4%, and yield 'no change' for 21.4% of the patients. Both IL-1 beta and IL-6 concentrations were significantly decreased after treatment. Although the IL-8 level did not significantly decrease, it seems to be related to the overall efficacy. TNF-alpha was not detected in all of the samples. CONCLUSION: FOM nebulization therapy is highly effective in treatment for chronic sinusitis, and efficacy may be due to an immunomodulatory mechanism, as well as its bactericidal effect.

The effects of long-acting nitrates on 5-year cardiac events of patients with coronary thrombolytic therapy for acute myocardial infarction.

OBJECTIVE: A retrospective study was performed to evaluate the effects of using long-term long acting nitrates without a dose-free interval in treating patients undergoing thrombolytic therapy for acute myocardial infarction (MI). PATIENTS AND METHODS: A total of 297 patients taking prescribed medication for secondary prevention of the MI were selected for the study. They were divided into a nitrate group consisting of 222 patients who had continuously received long-acting nitrates without a dose-free interval, and a control group consisting of 75 patients who were not able to use the long-acting nitrates because of adverse effects. The primary endpoint was cardiac events, either cardiac death or a nonfatal MI, in five years. RESULTS: The incidence of primary endpoint in five years was 13.4 percent in the nitrate group and 6.2 percent in the control group, a 2.2-fold increase in risk. However, the difference was not significant. After adjustment for age, there was no statistically significant difference between the incidence of primary endpoint in the nitrate group (9.8%) and that in the control group (5.7%). A Cox proportional-hazards regression analysis revealed that the long-acting nitrates were not related to the incidence of primary endpoint (p=0.23). CONCLUSION: The administration of long-term long-acting nitrates without a dose-free interval had no benefit of reducing the incidence of cardiac events of patients undergoing thrombolytic therapy for acute MI.

Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of an alternative cardiopulmonary cerebral resuscitation (CPCR) using emergency cardiopulmonary bypass (CPB), coronary reperfusion therapy and mild hypothermia. BACKGROUND: Good recovery of patients with out-of-hospital cardiac arrest is still inadequate. An alternative therapeutic method for patients who do not respond to conventional CPCR is required. METHODS: A prospective preliminary study was performed in 50 patients with out-of-hospital cardiac arrest meeting the inclusion criteria. Patients were treated with standard CPCR and, if there was no response, by emergency CPB plus intra-aortic balloon pumping. Immediate coronary angiography for coronary reperfusion therapy was performed in patients with suspected acute coronary syndrome. Subsequently, in patients with systolic blood pressure above 90 mm Hg and Glasgow coma scale score of 3 to 5, mild hypothermia (34 C for at least two days) was induced by coil cooling. Neurologic outcome was assessed by cerebral performance categories at hospital discharge. RESULTS: Thirty-six of the 50 patients were treated with emergency CPB, and 30 of 39 patients who underwent angiography suffered acute coronary artery occlusion. Return of spontaneous circulation and successful coronary reperfusion were achieved in 92% and 87%, respectively. Mild hypothermia could be induced in 23 patients, and 12 (52%) of them showed good recovery. Factors related to a good recovery were cardiac index in hypothermia and the presence of serious complications with hypothermia or CPB. CONCLUSIONS: The alternative CPCR demonstrated an improvement in the incidence of good recovery. Based upon these findings, randomized studies of this hypothermia are needed.

Effects of combined emergency percutaneous cardiopulmonary support and reperfusion treatment in patients with refractory ventricular fibrillation complicating acute myocardial infarction.

OBJECT: We conducted a prospective study to determine whether or not combined emergency percutaneous cardiopulmonary support (PCPS) and coronary reperfusion treatment are useful for acute myocardial infarction (MI) patients with unsynchronized electric shock-resistive ventricular fibrillation (VF). PATIENTS AND METHODS: Thirty-two acute MI patients who lapsed into the refractory VF were entered into the study. Group 1 consisted of 19 patients with VF outside the hospital, and Group 2 consisted of 13 patients with VF immediately after arrival at the hospital. The primary endpoint was successful reperfusion, return of spontaneous circulation and good recovery without neurologic disability. RESULTS: The infarct-related arteries showed a significant difference between Groups 1 and 2. However, the two groups had similar rates of successful reperfusion (84.6% vs 94.7%, respectively) and return of spontaneous circulation (89.5% vs 84.6%, respectively). The rates of good recovery were similarly low in both groups (5.3% vs 15.4%, respectively). CONCLUSION: Combined emergency PCPS and reperfusion treatment produced high return of spontaneous circulation, however the neurologic outcome was low.

Interaction between oral alpha-streptococci and group A streptococci in patients with tonsillitis.

The incidence of oral alpha-streptococci with inhibitory activity against group A streptococci, as a defense mechanism against bacterial infection in the oral cavity, was investigated in 141 patients with streptococcal tonsillitis. The study population included both children (n = 79) and adults (n = 62). Infection by group A streptococci appeared to be more common in children than in adults, as the detection rates of inhibitory alpha-streptococci in healthy children (29.7%), as well as pediatric patients with tonsillitis (14.9%), were lower than those in adults (63.0%; p < .01). It is possible to consider oral alpha-streptococci with inhibitory activity to be among the indications for tonsillectomy in patients with streptococcal tonsillitis, since the detection rate of inhibitory alpha-streptococci in surgical cases (10.9%) was significantly lower than that in nonsurgical cases (31.1%; p < .01). The high detection rate of these strains during the postoperative state supported the observation that the incidence of group A streptococcal infection was decreased postoperatively. Accordingly, it is useful to investigate bacterial interference between oral alpha-streptococci and group A streptococci in patients scheduled for tonsillectomy.

Analysis of defense mechanisms against bacterial infection by oral streptococcus in normal flora.

The incidence of oral alpha-streptococci with inhibitory activity against pathogens as a defense mechanism in the oral cavity was investigated in healthy individuals. Inhibitory strains were isolated from tonsil, tongue, cheek, saliva and dental plaque, and the detection rate of these strains isolated from tonsil was the highest. These results suggested that tonsillar flora is most important as a defense mechanism of the oral cavity. With respect to the effects of antibiotics against inhibitory alpha-streptococci, minimal inhibitory concentration of 90% of cells (MIC90) of PCG, ABPC, CCL, CFIX and EM against inhibitory alpha-streptococci, and relative detection rates of inhibitory alpha-streptococci before and after antimicrobial therapy were investigated. MIC90s of all antibiotics against these strains were low and sensitive to antibiotics tested. However, in vivo, detection rates of these strains before and after therapy did not differ significantly. Therefore, inhibitory strains were not affected by antibiotics as their MIC90 were low during short term medication.

Investigation of the nasopharyngeal bacterial flora in children with otitis media with effusion.

A study was undertaken to evaluate the incidence of alpha-streptococci with inhibitory activity against pathogens, a defense mechanism of the normal flora against bacterial infection, in the nasopharynx and tonsils of 37 children with otitis media with effusion (OME). In the patients with OME, the detection rates of alpha-streptococci with inhibitory activity against Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and group A streptococci in the nasopharynx were significantly lower than those of alpha-streptococci isolated from the tonsils. Furthermore, the detection rates of nasopharyngeal alpha-streptococci with inhibitory activity against H. influenzae and S. pneumoniae in OME patients were lower than those in patients with tonsillitis. In conclusion, low nasopharyngeal levels of alpha-streptococci with inhibitory activity against pathogens appear to render children susceptible to attacks of OME. We suggest that it is important to investigate the relationships between the prevalence of pathogens and the inhibitory activity of alpha-streptococci against them in the nasopharynx.

Effects of platelet activating factor on mucociliary clearance of the eustachian tube.

The effects of platelet activating factor (PAF) on mucociliary clearance of the eustachian tube were investigated both in vitro and in vivo. Normal ciliated epithelium was obtained from the eustachian tube of guinea pigs and incubated with PAF at concentrations ranging from 10(-10) to 10(-6) mol/L. Ciliary activity was observed under an inverted microscope and quantified photoelectrically. The PAF dose-dependently inhibited ciliary activity. One milliliter each of 10(-5) mol/LPAF, 10(-5) mol/L prostaglandin E2 (PGE2), 10(-5) mol/LPAF and PGE2, or the control solution (0.1 v/v% methanol-phosphate-buffered saline) was directly injected into the tympanic bullae of anesthetized chinchillas. The middle ear was examined by otomicroscopy, tympanometry, and auditory brain stem response in relation to time. The PAF delayed middle ear clearance, and the PGE2 augmented its delay. These findings suggest that PAF inhibits mucociliary clearance of the eustachian tube from the middle ear, and that PGE2 plays an important role in the augmentation of inflammatory disorders.

The nasopharyngeal bacterial flora in children with otitis media with effusion.

A study was undertaken to evaluate the incidence of nasopharyngeal alpha-streptococci with inhibitory activity against pathogens, as a defense mechanism of the normal bacterial flora against infection. Cultures were taken from the nasopharynges of 43 children with otitis media with effusion (OME). The detection rates of alpha-streptococci with inhibitory activity against Haemophilus influenzae, Streptococcus pneumoniae, Staphylococus aureus and group A streptococci were significantly lower in the nasopharynx than those isolated from the tonsils of the same patients. Moreover, the detection rates of alpha-streptococci with inhibitory activity against all of these pathogens derived from the nasopharynx were lower than those in healthy children, streptococcal strains with activity against H. influenzae and Strep, pneumoniae were also lower than that in patients with tonsillitis. These findings suggest that low nasopharyngeal levels of alpha-streptococci with inhibitory activity against respiratory pathogens may render children susceptible to OME. Further studies are needed to investigate the relationships between the prevalence of pathogens in the nasopharynx and the inhibitory activities of alpha-streptococci against them in order to devise and select optimal treatment for patients with OME.

Investigation of oral alpha-streptococcus showing inhibitory activity against pathogens in children with tonsillitis.

The incidence of oral alpha-streptococcus with inhibitory activity against group A streptococcus, as a defense mechanism against bacterial infection in the oral cavity, was investigated in pediatric individuals with tonsillitis. Infection by group A streptococcus appeared to be common in children, because the detection rate of inhibitory alpha-streptococcus in healthy children as well as pediatric patients with tonsillitis was lower than in adults and elderly patients. In particular, the detection rate of these strains was predominantly low in patients with beta-streptococcus. Among pediatric patients scheduled for tonsillectomy, the detection rate of inhibitory alpha-streptococcus was low preoperatively. However, the rate was markedly increased after surgery. The high postoperative detection rate of these strains reflected the decreased incidence of group A streptococcal infection. The results of this investigation of bacterial interference between oral alpha-streptococcus and group A streptococcus suggested that surgical treatment is a more effective approach for improving the oral bacterial flora in children with recurrent tonsillitis.

[Participation in causing O.M.E. with nasopharyngeal alpha-Streptococcus].

The role of normal pharyngeal flora in the defense mechanism against infections in the upper respiratory tract was studied in 50 children with otitis media with effusion (O.M.E.). In the bacteriological study of the nasopharynx, the incidence of H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis and group A Streptococcus was about 46%, 24%, 20%, 12% and 8%, respectively. The incidence of these species in the cases with O.M.E. was higher than that in the cases with chronic tonsilitis or control cases. In 41 O.M.E. cases with alpha-streptococci (82%), the incidence of alpha-streptococci with inhibitory activity against 5 pathogens (H. influenzae, S. pneumoniae, S. aureus, M. catarrhalis, group A Streptococcus) was examined. The detection rate of alpha-streptococcal strains with inhibitory activity against 5 pathogens derived from the nasopharynx in the cases with O.M.E. was significantly lower than that of the strain in the chronic tonsilitis cases and the control cases. Moreover, the detection rate of inhibitory alpha-streptococci from the nasopharynx was lower than that of from the tonsil. These findings suggest that the decline of inhibitory activity against pathogens by normal flora in nasopharynx is one of the factors causing O.M.E.

Effect of ibudilast on ciliary activity of human paranasal sinus mucosa in vitro.

The effect of ibudilast (CAS 50847-11-5, 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine, KC-404), an anti-asthmatic drug, on ciliary beat frequency (CBF) of human paranasal sinus mucosa was examined in vitro. Ciliary activation was observed after a 10-min exposure to 4.6 x 10(-6) mol/l ibudilast. Ibudilast dose-dependently increase CBF at the concentrations ranging from 4.6 x 10(-7) mol/l to 4.6 x 10(-5) mol/l. Propranolol inhibited ciliary activity induced by ibudilast; however, neither indometacin nor verapamil affected the activation of ibudilast on CBF. Platelet activating factor (PAF) and Leukotriene D4 (LTD4) are chemical mediators inducing mucosal dysfunction and damage. Ibudilast prevented ciliary inhibition induced by PAF and LTD4. These findings indicated that ibudilast activates CBF and inhibits the effect of PAF and LTD4 on ciliated cells, and consequently improves the pathogenesis of allergic disorders such as the inhibited mucociliary transport system and airway hyperresponsiveness.

[Isolation of alpha-streptococci with inhibitory activity against pathogens, in the oral cavity and the effect of tobacco and gargling on oral flora].

We investigated the distribution of oral alpha-streptococci with inhibitory activity against pathogens, which compose an oral defense mechanism. Detection rate of alpha-streptococci with inhibitory activity against S. pyogenes and S. aureus derived from the tonsil was higher than in other portions, the tongue, cheek, gingiva, or saliva. It has suggested that tonsillar bacterial flora are mainly a defense mechanism. The oral flora in healthy smokers was compared with healthy non-smokers to investigate the influence of tobacco on oral bacterial flora. The results showed that the detection rate of S. aureus in smokers was higher while that of alpha-streptococci with inhibitory activity against S. aureus was lower. However, the detection rate of alpha-streptococci with inhibitory activity against S. pyogenes in smokers was as high as in non-smokers. It is suggested that it was easy for S. aureus to adhere to the oral mucosa in smokers, and was considered to influence the strain which produces beta-lactamase for medical treatment. We investigated the influence of gargling on oral bacterial flora by comparing the amount of bacteria before and after gargling with popidine-iodine gargle and saline solution. It was shown that alpha-streptococci, a main component of normal oral flora were decreased after gargling in both smokers and non-smokers. Furthermore, it was shown that group A Streptococcus was not decreased after gargling, and it was concluded that use of gargle medicinal mouth wash in bacillus carriers should be studied further.

Detection of soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 in the effusion of otitis media with effusion.

We measured sIL-2R, TNF-alpha and sICAM-1 in the sera and middle ear effusions (MEEs) of patients with otitis media with effusion (OME). Although there was no signmcant difference between the sIL-2R levels of the serous and mucoid MEEs, they were significantly higher than serum sIL-2R levels of OME patients and healthy controls. TNF-alpha levels of the mucoid MEEs were significantly higher than those of the serous type. However, TNF-alpha was rarely detected in the sera of OME patients or healthy controls. We observed significant differences between the serous and mucoid MEEs with respect to their sICAM-1 levels, which were also higher than serum slCAM-1 levels of OME patients and healthy controls. Our findings suggested that IL-2, TNF-alpha and ICAM-1 could be significantly involved in the pathogenesis of OME through the cytokine network.

[Effect of 14-member lactone ring macrolides on anti staphylococcal activity and swarming ability of Pseudomonas aeruginosa].

The purpose of this report is to examine the effect of Macrolides (Erythromycin and Roxythromycin) on swarming ability and antistaphylococcal activity of Pseudomonas aeruginosa. The standard strain (ATCC27854) and clinically isolated P. aeruginosa were used as test strains. The influence of Macrolides on antistaphylococcal activity and swarming ability were determined by the agar plate dilution method. The antistaphylococcal activity of P. aeruginosa was not affected at the concentration of 1.56 micrograms/ml of both Erythromycin and Roxythromycin. But the antistaphylococcal activity was not observed at the concentration over 100 micrograms/ml. The swarming ability was not affected at the concentration up to 12.5 micrograms/ml. It has been proved that Macrolides reveal inhibition of virulent factors of P. aeruginosa such as protease, elastase, piocianin and so on. Furthermore our data revealed that Macrolides inhibited swarming ability of P. aeruginosa, and did not affect the antistaphylococcal activity of P. aeruginosa under 1.56 micrograms/ml concentration. Consequently, these results suggest that Macrolides have exhibited a previously unknown pharmacological effect, and may be of interest in that there may be bacterial interaction between MRSA and P. aeruginosa.

[Further study of Schellong testing in 152 young females].

Orthostatic dysregulation (OD) generally implies a systemic condition indicating poor circulatory function resulting from autonomic imbalance, which usually appears in a rather young population at or around puberty, predominantly in females. This condition can be recognized from the results of a questionnaire which has been proposed and prepared by the Pediatric OD Study Group of Japan as diagnostic criteria for OD. Schellong testing has also been developed as a screening method to determine OD or orthostatic hypotension. We carried out a survey and analyzed data collected with the questionnaire and Schellong test results among 152 young normal females ranging in age from 18 to 21 years in order to obtain the actual prevalence of OD in these subjects. Among 152 young normal females, 39 (25.7%) were confirmed to have OD based on the questionnaire. Although orthostatic dizziness was relatively common in this series of young females, regardless of the presence or absence of OD (90/152, 59.2%), this symptom, which is listed as one of the 5 major items on the questionnaire, was much more prevalent in subjects with OD (37/39, 94.9%). Similar prevalence patterns for fatigability or unexplained tiredness were also found in subjects with OD (28/39, 71.8%) when compared with total subjects (55/152, 36.2%). As for the positive rate of the Schellong test, subjects with and without OD showed 33.3% and 31.3%, respectively, and this difference was not statistically significant. There was, however, a highly significant difference in the fall in systolic pressure during the Schellong test procedure between subjects without OD and 10 subjects with OD in whom orthostatic dizziness frequently occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of erythromycin on anti staphylococcal activity and dye production of Pseudomonas aeruginosa isolated from clinical materials].

Anti staphylococcal activity by Pseudomonas aeruginosa was investigated through the use of the reversed agar plate and the filter paper stamp methods. Investigation was also conducted on the dye production of different clinical isolates of Pseudomonas aeruginosa, the relationship between drug susceptibility and anti staphylococcal activity, and the influence of erythromycin on anti staphylococcal activity. Seventy four strains of Pseudomonas aeruginosa were prepared which included 20 strains from pus, 34 strains from sputum and 20 strains from urine. These were then inoculated with methicillin resistant Staphylococcus aureus (MRSA). They were then cultured for 48 hours by using the reversed agar plate and the filter paper stamp methods. Anti staphylococcal activity was observed in 16 strains from pus (80%), 19 strains from sputum (55.9%) and 8 strains from urine (40%). The Pseudomonas aeruginosa strains which have no pigment tended to show poor anti staphylococcal activity. Drug susceptibility was tested using PIPC, AMK, IPM, CFS and OFLX. The strains which showed resistance to OFLX tended to show poor anti staphylococcal activity. Erythromycin inhibited the dye production of Pseudomonas aeruginosa but exhibited no effect on anti staphylococcal activity. Consequently, these results suggest erythromycin has exhibited a previously unknown pharmacological effect, furthermore, anti staphylococcal activity was not caused by pigmentation only.

[Significance of normal oral flora, particularly group oral streptococci as defense mechanism against infection in healthy individuals (normal defense mechanism by oral Streptococcus group)].

The alpha-streptococci, consisted of normal oral flora mainly, with inhibitory activity against pathogenic microbes in healthy individuals was investigated by group A Streptococcus (indicator strain 6-22 nonmucoid T-12). Rate of alpha-streptococci with inhibitory activity against group A Streptococcus was increased as aging, and the rate in pre-school children was higher than that in school children. These results suggested that more than 90% of the tested alpha-streptococci with strong inhibitory activities (S. salivarius) against indicator strain had inhibitory activities against group A Streptococcus (mucoid T-6), H. influenzae, S. pneumoniae, group C Streptococcus, and from 40% to 70% of the tested strains had also inhibitory activities against other pathogens. As there were many strains of alpha-streptococci with inhibitory activities against pathogens, that usually detected in the upper respiratory infection, the problem on the strains in the future will explain significance of the defense mechanism against upper respiratory infection and this can be applied clinically.