Bacteriological activity of trovafloxacin, a new quinolone, against respiratory tract pathogens

BACKGROUND: Corpus callosum (CC) morphology has recently been investigated in schizophrenia using refined imaging and analytic techniques; however, methodological problems and small sample sizes have led to inconsistent findings. METHODS: This study used a large sample of male schizophrenics (n = 79) and male controls (n = 65) to investigate size and shape of the CC on midsagittal magnetic resonance images. Size was determined by tracing the area of the CC, and shape was determined using a landmark-based analysis. In addition, the relationship between CC morphology and phenomenologic variables such as age of onset, length of illness, exposure to medications, and symptom severity was explored. RESULTS: After controlling for age, height, and parental socioeconomic status, there was a main effect of diagnosis on CC size (F = 5.05, df = 1,139, p < .03), with patients' CCs being significantly smaller. No difference was found between patients and controls in CC shape (F = 1.07, df = 18,125, p > .38) or orientation (F = 0.79, df = 18,125, p > .70), using a landmark-based technique. Finally, there was a significant inverse correlation between size of CC and severity of negative symptoms. CONCLUSIONS: These findings support previous studies that have found a decrease in size of the CC in patients with schizophrenia. Moreover, the decrement in volume is generalized, not regional, and is related to the severity of negative symptoms.     

Activity of four fluoroquinolones against 346 strains of enteric pathogens

Several surgical approaches have been reported for operative correction of complex or recurrent form of aortic coarctation. In this study we report our experience with extra-anatomic ascending-supraceliac abdominal bypass grafting for complicated form of aortic coarctation in 12 patients. All patients survived the operations, without late mortality. This type of surgical correction of complex or recurrent form of coarctation is a safe and effective procedure.     

Bacterial flora of the respiratory tract in patients with long term tracheostomy--colonization of the lower respiratory tract by Pseudomonas aeruginosa

Throat secretions (TS) and bronchial secretions aspirated from tracheostomy sites (TSTA) from six subjects with long term tracheostomy were simultaneously collected and then cultured every two weeks from January, 1990, to December, 1992. Isolated bacteria were mainly alpha-streptococci (96.2%) and Neisseria (69.6%) in TS, and Pseudomonas aeruginosa (75.7%) in TSTA. In all cases, P. aeruginosa was isolated from and colonization of the lower respiratory tract by this organism was apparent 24.4 months, on average, after tracheostomy. There were ten episodes of respiratory infection in five cases, eight of which occurred after colonization. P. aeruginosa was the causative organism in seven of these episodes. Findings in patients with long term tracheostomy indicated separate colonization of the upper and lower respiratory tracts and that P. aeruginosa colonized the lower respiratory tract. The colonization of the lower respiratory tract by P. aeruginosa would thus appear to be an important factor inducing respiratory infection.     

Grain dust-induced airflow obstruction and inflammation of the lower respiratory tract

To investigate the relationship between the physiologic and biologic effects of grain dust inhalation, we exposed 15 nonsmoking, nonasthmatic, nonatopic male grain handlers to buffered saline and aqueous corn dust extract by inhalation challenge in a crossover study. The inhalation challenges to buffered saline and corn dust extract were separated by at least 14 d. Compared with buffered saline, inhalation of corn dust extract resulted in significant airflow obstruction, which was observed within 30 min of exposure and persisted for 5 h. Inhalation of corn dust extract resulted in an acute inflammatory response characterized by higher concentrations of neutrophils (p = 0.001), IL-1 beta (p = 0.001), IL-1RA (p = 0.001), IL-6 (p = 0.001), IL-8 (p = 0.001), and TNF-alpha (p = 0.04) in bronchoalveolar lavage (BAL) fluid. mRNA levels specific for IL-1 beta, IL-1RA, IL-6, and IL-8 from cells present in the BAL fluid were significantly greater after challenge with corn dust extract than after challenge with buffered saline. Importantly, no significant differences were observed in the concentration of lymphocytes or eosinophils in the BAL fluid following inhalation of corn dust extract, and the concentrations of histamine and 15-HETE were similar in BAL fluid after the two challenges. The maximal percentage decrease in FEV1 was significantly associated with the absolute neutrophil concentration in the BAL fluid (p = 0.001), as well as the concentration of TNF-alpha (p = 0.03), IL-1 beta (p = 0.005), IL-1RA (p = 0.001), IL-6 (p = 0.001), and IL-8 (p = 0.001) in the BAL fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breastfeeding, maternal smoking and lower respiratory tract infections

The objective of the study was to assess the relationship between breastfeeding and lower respiratory tract infections (LRTIs) during the first year of life, with special reference to maternal smoking. A cohort of 3,754 children born in 1992-1993 in the City of Oslo, Norway was recruited and data were collected at birth, 6 and 12 months of age. Complete information was obtained from 3,238 children (follow-up rate 86%). The main outcome was an episode of a LRTI, such as pneumonia, bronchitis or bronchiolitis, based on a self-administered questionnaire addressed to parents when the child was 6 and 12 months old. The outcome was specified as physician-diagnosed. In logistic regression analysis adjusting for confounding, maternal smoking increased the risk of LRTIs in children breastfed for 0-6 months (odds ratio (AOR) 1.7; 95% confidence interval (95% CI) 1.2-2.4), but not essentially when the child was breastfed for more than 6 months (AOR 1.1; 95% CI 0.7-1.6). Short-term breastfeeding (0-6 months) and no maternal smoking was related to an adjusted AOR of LRTIs of 1.3 (95% CI 1.0-1.7), and short-term breastfeeding combined with maternal smoking was related to an adjusted AOR of 2.2 (95% CI 1.6-3.1), as compared with long-term breastfeeding and no maternal smoking. The present study indicates a protective effect of long-term breastfeeding on the risk of lower respiratory tract infection during the first year of life. The results suggest that the protective effect is strongest in children exposed to environmental tobacco smoke.     

New approaches to Pseudomonas aeruginosa lower respiratory tract infections

Since 1973, the occurrence of respiratory tract infections due to P. aeruginosa has increased associated with the development of broad-spectrum penicillins. A clinical entity, diffuse panbronchiolitis (DPB) is a representative disease of chronic P. aeruginosa infections in Japan. In this paper, recent advances of research on pathogenesis and treatments of chronic P. aeruginosa lower respiratory tract infections in our department are reported. We examined sputum from patients with chronic P. aeruginosa infections under the electron microscope. Mucoid type of microcolonies were observed with fibrous matrix of exopolysaccharide. Neutrophils were found to be partially surrounding the microcolony in an attempt to defense. Debris was formed mainly by the destruction of the neutrophils. Most neutrophils were found full of phagocytized debris. These data support that instead of phagocytizing bacteria, neutrophils phagocytized debris and bacteria were not completely eradicated. This might be a factor in the pathogenesis of persistent colonization of P. aeruginosa. In the airways of patients with chronic airway diseases (CAD), neutrophils enhance the recruitment of more neutrophils through the production of neutrophil chemotactic factors such as interleukin-8 (IL-8) and LTB4, perpetuating a cycle of inflammation in the lung. We demonstrated increased levels of IL-8, a chemotactic cytokine, in bronchoalveolar lavage (BAL) fluid from patients with CAD associated with P. aeruginosa infections. We also documented a significant correlation between neutrophil numbers and IL-8 levels or IL-1 beta levels or neutrophil elastase levels in BAL fluids from patients with CAD. By immunohistochemical studies and in vitro data, three major sources of IL-8 in the airways of CAD patients were found to be alveolar macrophages, bronchial epithelial cells, and migrated neutrophils. In Japan, the clinical effectiveness of oral erythromycin (EM) for CAD, including DPB seems to be established, but its pharmacological mechanism remains unclear. In addition, we found a marked decrease of IL-8 levels in BAL fluid from two patients with CAD after treatment with EM. Therefore, we postulated that EM inhibited IL-8 production by stimulated respiratory cells. EM and Roxythromycin, suppressed IL-8 production in Pseudomonas-stimulated neutrophils in a dose-dependent manner. 1 alpha, 25-dihydroxy vitamin D3 also inhibited neutrophil-derived IL-8. Our data encourage the development of new anti-IL-8 agents against persistent P. aeruginosa lower respiratory tract infections.     

The problem of lower respiratory tract foreign bodies in children

The authors treat the problem of lower respiratory tract foreign bodies in children on the basis of their own longterm experience. In the years 1972-1991 in the Pediatric E.N.T. Clinic of the Pediatric Institute, Academy of Medicine in Poznań, 147 foreign bodies were removed. A positive history of foreign body aspiration was obtained in 45.7% of the cases. 44.7% of the foreign bodies were removed during the first 24 hours after their aspiration. Broncho-pulmonary complications occurred in 59.1% of the cases.     

Pharmacologic management of common lower respiratory tract disorders in women

In a primary care setting, nurse-midwives will collaboratively manage common lower respiratory conditions that require pharmacologic therapy. As such, they must maintain up-to-date knowledge about the indications, use, and potential side effects of these medications. This article reviews the drugs most commonly used for the out-patient treatment of pneumonia, asthma, tuberculosis, and bronchitis (both acute and chronic). Differences among common oral antibiotics recommended by the American Thoracic Society are described. Inhaled bronchodilator and anti-inflammatory medications are covered, as well as systemic corticosteroids. The use of isoniazid preventive therapy for latent tuberculous infection is described in detail, with brief mention made of other drugs used for active tuberculosis. Adjunct treatments including immunotherapy, vaccines, oxygen supplementation, and nicotine replacement for smoking cessation also are discussed.     

Role of the microbiology laboratory in the diagnosis of lower respiratory tract infections

A randomized, double-blind trial was undertaken to measure the effects of zinc supplementation on catch-up growth in severe protein-energy malnutrition, with particular reference to linear growth. One hundred forty-one children between the ages of 6 mo and 3 y were enrolled after admission to a nutritional rehabilitation unit in Dhaka, Bangladesh, and randomly assigned to receive elemental zinc by mouth, 1.5 mg/kg for 15 d, 6.0 mg/kg for 15 d, or 6.0 mg/kg for 30 d, and thereafter they were followed for a total of 90 d. Anthropometric outcome measures included change in knee-heel length, midupper arm circumference, subscapular and triceps skinfold thicknesses, and change in height-for-age, weight-for-age, and weight-for-height z scores. Higher zinc doses were not associated with significant change in any anthropometric measurement, but mortality was significantly greater in children who received high-dose zinc (6.0 mg/kg) initially as opposed to those who received low-dose zinc supplementation (1.5 mg/kg) (Yates-corrected chi-square P value of 0.033 and a risk ratio of 4.53; 95% CI: 1.09 < risk ratio < 18.8). We conclude that there is no benefit to using high-dose zinc supplementation regimens and that they could contribute to increased mortality in severely malnourished children.     

Antibiotic sensitivity of important pathogens of bacterial respiratory tract infections in Northeast Germany

BACKGROUND: There is still a lack of comprehensive study results about resistance of bacterial respiratory pathogens from the east of the Federal Republic of Germany. METHODS: In Greifswald we isolated in 1995 and 1996 320 strains of typical pathogens and tested their susceptibility to 14 antibiotics, using the microbouillon dilution method. RESULTS: Pneumococci and beta-haemolytic streptococci were completely susceptible to penicillin and all other beta-lactam-antibiotics, clindamycin and vancomycin. 4.8% of pneumococci and 10.0% of Streptococcus pyogenes isolates were resistant to erythromycin. This should lead to a more differentiated use of macrolides as concerns these pathogens, especially as penicillin still has high efficacy in these cases. Pneumococci had resistance rates of 4.8%, 9.5% and 6.7% to cotrimoxazole, tetracycline and ofloxacin, respectively. No strain of Haemophilus influenzae produced a beta-lactamase, 2.6% of strains were relatively resistant to ampicillin, even in combination with sulbactam. Cefaclor, erythromycin and tetracycline had restricted efficacy of 16.7%, 14.1% and 53.8%, respectively. Cefuroxime, cefixime, cefepime, imipenem and ofloxacin all had complete efficacy. 77.8% of Moraxella catarrhalis isolates were beta-lactamase positive. Strains were susceptible to erythromycin, ofloxacin and all tested beta-lactam-antibiotics except ampicillin and cefaclor. There was a relative resistance to clindamycin and tetracyclin of 22.2% and 2.2%, respectively. DISCUSSION: We present our results in national and international comparison, describe tendencies of resistance, give reasons for the low incidence of penicillin resistance in pneumococci in Germany and draw conclusions for empirical chemotherapy.     

Newer oral antimicrobials for resistant respiratory tract pathogens. Which show the most promise?

As antimicrobial resistance to tried-and-true drugs continues to build, an arsenal of new drugs aimed at resistant respiratory tract pathogens is needed. Penicillin is now ineffective against several common pathogens, including many pneumococcal organisms. Newer antimicrobials, including macrolides, cephalosporins, and fluoroquinolones, have been developed to take its place. The authors of this article present a progress report of the fight against respiratory tract infection and an assessment of the most promising newer agents for use against multidrug-resistant pathogens.     

Study of the viral etiology of lower respiratory tract infections in a neonatal unit

OBJECTIVE: To study the possible viral etiology in 139 infants with lower respiratory tract infection who required hospitalization in the Infant Unit of our hospital, from October 1994 to June 1995. PATIENTS AND METHODS: 139 patients were admitted, aged from 13 days to 14 months, during this period. The etiological agent was detected by direct immunofluorescence from nasopharyngeal secretions. Monoclonal antibodies were used against Respiratory Syncitial Virus, Influenza A Virus, Influenza B Virus, Adenovirus and Parainfluenza 3 Virus. Antibody detection against these viruses by Complement Fixation Test was done on 29 of these patients, with paired sera (acute and convalescent phase). RESULTS: In 82 patients (59%) we found at least one viral agents from the nasopharyngeal specimens, but in 64 of these only one was detected, in the remaining 18, there were more than one. Significant levels of antibodies were detected in only six of the 29 patients tested. Serology was negative in the remaining 23 patients. CONCLUSIONS: Syncitial Respiratory Virus is the first virus responsible for the lower respiratory tract infection in this age group (49%). There was no correlation between serological diagnosis and antigen detection.     

Bacteriology of the lower respiratory tract as determined by fiber-optic bronchoscopy and transtracheal aspiration

For assessment of the validity of cultures of tracheobronchial secretions and exudates (TBSE) obtained by fiber-optic bronchoscopy, the aerobic and anaerobic flora of expectorated saliva and TBSE obtained by fiber-optic bronchoscopy from nine healthy volunteers and eight patients were compared with those obtained by fiber-optic bronchoscopy as well). Normal volunteers yielded both aerobic and anaerobic bacteria in amounts usually less than 104.5 colony-forming units (cfu)/ml in TBSE obtained by fiberoptic bronchoscopy. In patients with chronic bronchitis, 42 isolates of aerobic bacteria (104-105.5 cfu/ml) and only 10 isolates of anaerobes (usually less than 104 cfu/ml) were reovered from 15 samples obtained by trantracheal aspiration. The data lead to the conclusion that low-level contamination (less than or equal to 104 cfu/ml) with oral flora is common in TBSE obtained by fiber-optic bronchoscopy. A single potential pathogen in numbers of greater than or equal to 105 cfu/ml may be of etiologic significance, particularly if recovered from purulent drainage material from a localized portion of the lung. Under circumstances in which quantitative bacteriology cannot be done, TBSE obtained by transtracheal aspiration will most reliably reflect the bacterial flora present in the lung.     

Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract

Mutations of the p53 tumor suppressor gene are the most common genetic alterations associated with human cancer. Tumor-associated p53 mutations often show characteristic tissue-specific profiles which may infer environmentally induced mutational mechanisms. The p53 mutational frequency and spectrum were determined for 95 carcinomas of the upper and lower respiratory tract (32 lung and 63 upper respiratory tract). Mutations were identified at a frequency of 30% in upper respiratory tract (URT) tumors and 31% in lung tumors. All 29 identified mutations were single-base substitutions. Comparison of the frequency of specific base substitutions between lung and URT showed a striking difference. Transitions occurred at a frequency of 68% in URT, but only 30% in lung. Mutations involving G:C-->A:T transitions, which are commonly reported in gastric and esophageal tumors, were the most frequently identified alteration in URT (11/19). Mutations involving G:C-->T:A transversions, which were relatively common in lung tumors (3/10) and are representative of tobacco smoke-induced mutations were rare in URT tumors (1/19). Interestingly, G:C-->A:T mutations at CpG sites, which are characteristic of endogenous processes, were observed frequently in URT tumors (9/19) but only rarely in lung tumors (1/10), suggesting that both endogenous and exogenous factors are responsible for the observed differences in mutational spectra between the upper and lower respiratory systems.     

可吸入颗粒污染物在下呼吸道运动和沉积规律的数值模拟

为研究受慢性阻塞性肺病影响的呼吸道内气固流动特性,建立了基于Weibel模型的5～8级三维肺部模型.气相采用标准k-ε湍流模型,颗粒相采用离散颗粒模型.三级呼吸道内模拟的气固流动特性与实验结果进行了对比验证.在呼吸强度为30,60和90 L/min条件下,模拟了稳态、非稳态吸气时第7级内侧呼吸道受慢性阻塞性肺病影响收缩和非稳态正常呼吸道内的气固流动特性,分析了颗粒沉积形式和沉积率.通过对比发现:呼吸道内变形使前后级沉积范围缩小,对侧沉积范围扩大;使前级同侧和后级的沉积率下降,对侧和同级外侧的沉积率增加;并使更多的颗粒在收缩处产生沉积,使原本阻塞的呼吸道愈发狭窄.