TRPV4 channels promote vascular permeability in retinal vascular disease.

This study aimed to determine the role of transient receptor potential vanilloid 4 (TRPV4), a calcium (Ca2+)-permeable cation channel, in the pathophysiology of retinal vascular disease. The retinal vein occlusion (RVO) murine model was created by irradiating retinal veins using lasers. TRPV4 expression and localization were evaluated in RVO mice retinas. In addition, we examined the effects of TRPV4 antagonists (RQ-00317310, HC-067047, GSK2193874, and GSK2798745) on retinal edema, blood flow, and ischemic areas in RVO mice. Furthermore, changes in the retinal expression of tumor necrosis factor (TNF)-α and aquaporin4 (AQP4) by RQ-00317310 were analyzed using Western blot. We also assessed the barrier integrity of epithelial cell monolayers using trans-endothelial electrical resistance (TEER) in Human Retinal Microvascular Endothelial Cells (HRMECs). The expression of TRPV4 was significantly increased and co-localized with glutamine synthetase (GS), a Müller glial marker, in the ganglion cell layer (GCL) of the RVO mice. Moreover, RQ-00317310 administration ameliorated the development of retinal edema and ischemia in RVO mice. In addition, the up regulation of TNF-α and down-regulation of AQP4 were lessened by the treatment with RQ-00317310. Treatment with GSK1016790A, a TRPV4 agonist, increased vascular permeability, while RQ-00317310 treatment decreased vascular endothelial growth factor (VEGF)- or TRPV4-induced retinal vascular hyperpermeability in HRMECs. These findings suggest that TRPV4 plays a role in the development of retinal edema and ischemia. Thus, TRPV4 could be a new therapeutic target against the pathological symptoms of retinal vascular diseases.

Mechanochemistry of Group 4 Element-Based Metal-Organic Frameworks.

Mechanochemical synthesis is emerging as an environmentally friendly yet efficient approach to preparing metal-organic frameworks (MOFs). Herein, we report our systematic investigation on the mechanochemical syntheses of Group 4 element-based MOFs. The developed mechanochemistry allows us to synthesize a family of Hf4O4(OH)4(OOC)12-based MOFs. Integrating [Zr6O4(OH)4(OAc)12]2 and [Hf6O4(OH)4(OAc)12]2 under the mechanochemical conditions leads to a unique family of cluster-precise multimetallic MOFs that cannot be accessed by the conventional solvothermal synthesis. Extensive efforts have not yielded an effective pathway for preparing TiIV-derived MOFs, tentatively because of the relatively low Ti-O bond dissociation energy.

Evaluation of a simultaneous adsorption device for cytokines and platelet-neutrophil complexes in vitro and in a rabbit acute lung injury model.

BACKGROUND: Platelet-neutrophil complexes (PNCs) readily migrate into tissues and induce tissue damage via cytokine or other pathogenic factors release. These actions are involved in onset and progression of acute respiratory distress syndrome (ARDS). Thus, simultaneous removal of cytokines and activated neutrophils, including PNCs by blood purification may prevent development of ARDS and enhance drug effects. The goal of this study was to examine the effect of a newly developed adsorption column (NOA-001) that eliminates cytokines and activated neutrophils in a lung injury model. RESULTS: Adsorption of cytokines, such as IL-8, IL-6 and HMGB-1, and PNCs was first measured in vitro. Lung injury was induced by HCl and lipopolysaccharide intratracheal infusion in rabbits ventilated at a low tidal volume (7-8 mL/kg) and PEEP (2.5 cmH2O) for lung protection. Arterial blood gas, hematologic values, plasma IL-8, blood pressure and heart rate were measured, and lung damage was evaluated histopathologically in animals treated with 8-h direct hemoperfusion with or without use of NOA-001. The in vitro adsorption rates for IL-8, IL-6, HMGB-1, activated granulocytes and PNCs were 99.5 (99.4-99.5)%, 63.9 (63.4-63.9)%, 57.6 (57.4-62.1)%, 9.9 (-4.4-21.3)% and 60.9 (49.0-67.6)%, respectively. Absorption of PNCs onto fibers was confirmed microscopically. These adsorption effects were associated with several improvements in the rabbit model. In respiratory function, the PaO2/FIO2 ratios at 8 h were 314 ± 55 mmHg in the NOA-001 group and 134 ± 41 mmHg in the sham group. The oxygenation index and PaCO2 at 8 h were 9.6 ± 3.1 and 57.0 ± 9.6 mmHg in the sham group and 3.0 ± 0.8 and 40.4 ± 4.5 mmHg in the NOA-001 group, respectively (p < 0.05). Blood pH at 8 h reached 7.18 ± 0.06 in the sham group, but was maintained at 7.36 ± 0.03 (within the normal range) in the NOA-001 group (p < 0.05). In lung histopathology, fewer hyaline membrane and inflammatory cells were observed in the NOA-001 group. CONCLUSION: A column for simultaneous removal of cytokines and PNCs showed efficacy for improvement of pulmonary function in an animal model. This column may be effective in support of treatment of ARDS.

Brentuximab vedotin maintenance after autologous stem cell transplantation for refractory gray zone lymphoma with long-term remission.

Gray zone lymphoma (GZL) is a rare type of B-cell lymphoma characterized by features of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (cHL). The prognosis of GZL is poorer than that of cHL and mediastinal large B-cell lymphoma. However, an optimal treatment strategy for relapsed/refractory (R/R) GZL has not been established in the clinical setting. The current study reported an excellent clinical response in a patient with R/R CD30-positive GZL who received brentuximab vedotin (BV) maintenance after autologous stem cell transplantation (ASCT). Although the patient was resistant to prior treatments, BV maintenance after ASCT achieved long-term remission. Hence, BV was determined to be a safe and effective therapeutic option for CD30-positive R/R GZL.

Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation.

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.

Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.

Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.

Transformation Scoring System (TSS): A new assessment index for clinical transformation of follicular lymphoma.

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy-proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2-4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy.

Association between subjective well-being and presence of primary care dentists in community-dwelling elderly people: A cross-sectional study.

OBJECTIVE: The aim was to investigate the relationships between subjective well-being and the existence of primary care dentists in community-dwelling elderly people. BACKGROUND: Some studies have reported subjective well-being focusing on oral health, but no studies have examined the relationship between subjective well-being and primary care dentists. METHODS: This cross-sectional study used data from community-dwelling elderly people aged ≥70 years (n = 624). The Philadelphia Geriatric Center Morale Scale (PGCMS; range = 0 [low morale]-17) was used to assess subjective well-being. Additional information regarding age group, sex, medical consulting situation (ambulatory care/home care), primary care dentists, family structure, economic status, health status was collected via questionnaire. RESULTS: The average PGCMS score in ambulatory care patients (ACP) group who have primary care dentists was highest among community-dwelling elderly people. In a logistic regression model, a low PGCMS score (0-11) was independently correlated to 80-89 age group (OR = 1.70; 95% CI, 1.13-2.54; P = 0.008), ≥90 age group (OR = 3.86; 95% CI, 1.83-8.18; P < 0.001), unsatisfied for economic status (OR = 2.68; 95% CI, 1.59-4.53; P < 0.001), unsatisfied for health status (OR = 3.94; 95% CI, 2.60-5.98; P < 0.001) and having no primary care dentists (OR = 1.81; 95% CI, 1.09-3.01; P = 0.021) in ACP group. CONCLUSIONS: The subjective well-being of ACP who have primary care dentists was higher than in other people. Primary dentists contributed to the subjective well-being of elderly people.

Osseous changes of the mandibular condyle affect backward-rotation of the mandibular ramus in Angle Class II orthodontic patients with idiopathic condylar resorption of the temporomandibular joint.

Objective: To evaluate whether osseous changes of the temporomandibular joint (TMJ) condyle affect backward rotation of the mandibular ramus in Angle Class II orthodontic patients with idiopathic condylar resorption (ICR). Methods: Twenty Japanese women with Class II malocclusion with ICR (ICR group) and 24 women with Class II malocclusion without ICR (non-ICR group) were examined. Pre-treatment panoramic radiographs were used to measure condylar ratios. Pre-treatment lateral cephalograms were used to evaluate maxillofacial morphology. Results: The ICR group had a significantly smaller condylar ratio, greater backward rotation of the ramus, less labially inclined upper incisors, and a steeper occlusal plane. The increased backward rotation of the ramus in the ICR group was significantly associated with a smaller condylar ratio. Conclusion: Angle Class II patients with ICR had shorter condylar height attributable to osseous changes of the TMJ condyle, and the shorter condylar height may affect subsequent backward rotation of the ramus.

A typical case of giant cell arteritis with vision loss due to delayed diagnosis.

A 75-year-old woman lost vision because of delayed recognition of GCA. Early diagnosis and treatment of GCA are important for preventing visual complications. Physicians must remember to evaluate the entire body, not just a single organ/system.

Hemoadsorption of high-mobility-group box 1 using a porous polymethylmethacrylate fiber in a swine acute liver failure model.

BACKGROUND: High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber. MATERIALS AND METHODS: First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model. RESULTS: Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column. CONCLUSION: The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.

A retrospective study of the safety and efficacy of paclitaxel plus ramucirumab in patients with advanced or recurrent gastric cancer with ascites.

BACKGROUND: Ramucirumab has recently proved to be effective for advanced or recurrent gastric cancer (AGC). Ascites and peritoneal metastasis are among the most common complications of AGC. However, there are few data on the safety and efficacy of paclitaxel plus ramucirumab in patients with AGC with ascites. The purpose of this retrospective study was to evaluate the safety and efficacy of paclitaxel plus ramucirumab in patients with AGC with ascites. METHODS: We retrospectively evaluated the safety and efficacy of paclitaxel plus ramucirumab in patients with AGC with ascites in comparison with patients without ascites in a single institution from June 2015 to May 2016. The median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and differences evaluated using the Log-lank test. The differences in baseline characteristics and response rates of each ascites group were calculated for homogeneity by chi-square tests and for trends by Fisher's exact test. RESULTS: Eighty-three patients were analyzed in this study. Ascites was detected in 40 patients, 26 patients (31%) had small to moderate ascites and 14 (17%) had massive ascites. The proportion of patients who started with a reduced dose of paclitaxel was higher for patients with massive ascites than others. The frequencies of any grade 3 or 4 hematological toxicity were 51% in patients without ascites, 77% in patients with small to moderate ascites, and 71% in patients with massive ascites. The frequencies of common ramucirumab-related adverse events were also not significantly different among ascites groups, however one patient had a tumor hemorrhage, and one patient had a gastrointestinal perforation. PFS and OS were shorter in patients with massive ascites than in patients with small or moderate ascites or patients without ascites. CONCLUSIONS: The use of paclitaxel and ramucirumab in patients with AGC with large amounts of ascites was tolerable with adequate dose modification. However, we should pay attention to the risks of ramucirumab-related toxicity in patients with bleeding tumors or intestinal stenosis.

Association between secondhand smoke exposure and early eruption of deciduous teeth: A cross-sectional study.

INTRODUCTION: Secondhand smoke (SHS) exposure is a risk factor for early childhood caries. Here we examined the association between SHS exposure and early tooth eruption (ETE) to clarify the additional etiology of an increased chance of contact between the tooth's surface and acid produced by fermenting oral bacteria. METHODS: Data of 388 child-mother pairs who attended health checkups at public health centers were assessed for children aged ≥18 months. SHS exposure was reported as maternal smoking during pregnancy and household smoking after birth. Associations between SHS exposure and ETE (≥3 canines in the oral cavity) were tested using multivariable analyses of the dose-response relationship. Subgroup and sensitivity analyses were performed for birth-weight subgroups and SHS exposure variables, respectively. RESULTS: ETE prevalence was 65.5%, 68.1%, and 76.9% in the no, medium-dose (ceased partway and sometimes), and highest-dose (every day) exposure groups, respectively, during pregnancy, and 61.5%, 75.0%, and 75.5%, respectively, after birth. The association between the highest dose exposure during pregnancy and ETE was not significant (OR=1.42, 95% CI: 0.34-5.96, p=0.631), whereas that between highest dose exposure after birth and ETE was significant (OR=2.13, 95% CI: 1.06-4.31, p=0.034); this association was distinct in the subgroup of children with smaller birth weights (<3000 g) (OR=3.19, 95% CI: 1.08-9.44, p=0.036). The dose-response relationship was consistently significant for exposure after birth (p<0.05). The sensitivity analysis that employed no SHS exposure, as a reference, revealed that exposure after birth but no exposure during pregnancy was significantly associated with ETE (OR=2.29, 95% CI: 1.19-4.40, p=0.013). However, the association between exposure during pregnancy and ETE was consistently non-significant (p>0.05). CONCLUSIONS: When controlling for variables of birth weight and exposure type, SHS exposure after birth was independently associated with the early eruption of deciduous canines. Further studies are warranted to examine the trajectory of SHS exposure after birth, ETE, and early childhood caries incidence. ABBREVIATIONS: ETE: Early tooth eruption, SHS: Secondhand smoke.

Insomnia and depression impair oral health-related quality of life in the old-old.

AIM: A previous study reported that the oral health-related quality of life (OHRQoL) of Japanese individuals dropped sharply as they reached old-old age. The aim of present study was to explore the risk factors of OHRQoL by investigating the association of OHRQoL with oral indices, lifestyle and psychological distress. METHODS: A questionnaire survey was carried out to assess the OHRQoL, oral indices, lifestyle, and psychological distress of patients who were of ≥75 years of age and who regularly visited a dental clinic for maintenance. OHRQoL and psychological distress were assessed using the General Oral Health Assessment Index (GOHAI) and the General Health Questionnaire, respectively. The relationships between the GOHAI score and related factors were examined by non-parametric bivariate and logistic regression analyses using a GOHAI cut-off score of 45.0. RESULTS: A total of 187 old-old patients with a mean age of 77.9 ± 3.0 years participated in the present study. The average GOHAI score was 50.8 ± 8.0. In the bivariate analyses, the average sleeping hours, use of sleep medication, Short Form 8-Item Health Survey (SF-8), General Health Questionnaire score, and the number of teeth present were significantly correlated with the GOHAI score. A logistic regression analysis showed that the number of teeth present, General Health Questionnaire and the use of sleep medication were associated with the GOHAI score. CONCLUSIONS: The present study found that the OHRQoL was strongly associated with insomnia and depression. It is therefore suggested that oral healthcare professionals take general background information, such as the presence of insomnia and depression, into consideration to improve OHRQoL when they treat old-old patients. Geriatr Gerontol Int 2017; 17: 893-897.

The role of tobacco use on dental care and oral disease severity within community dental clinics in Japan.

BACKGROUND: To examine facilitators of dental smoking intervention practices in Japan, where smokeless tobacco is rarely used, we evaluated the characteristics of dental care for smokers. METHODS: Community dentists volunteered to record the treated disease or encounter with patients that was principally responsible for their dental care on the survey day. Patients were classified into groups receiving gingival/periodontal treatment (GPT), caries/endodontic treatment (CET), prosthetic treatment (PRT), periodical check-up/orthodontic treatment (POT), or other encounters/treatments. Potential effect of dentist clustering was adjusted by incorporating the complex survey design into the analysis. RESULTS: Data of 2835 current smokers (CS) and 6850 non-smokers (NS) from 753 clinics were analysed. Distribution of treatments significantly differed between CS and NS (P = 0.001). In ad hoc multiple comparisons for each treatment, CS were significantly higher than NS for CET (47.1% vs. 43.6%, P = 0.002), and lower for POT (1.6% vs. 2.7%, P = 0.001), whereas GPT and PRT proportions were equivalent by smoking. When stage of disease progression was compared in the GPT subpopulation, CS were more likely received treatment for advanced stage disease than NS in the age groups of 40-59 years (24.9% vs. 15.3%, P = 0.001) and more than 60 years (40.8% vs. 22.1%, P < 0.001). However, the difference was less apparent in the entire population (9.7% vs. 6.0%), and CS were not predominant among patients receiving GPT for advanced stage disease (37.6%). CONCLUSIONS: The association of smoking with type of dental care of CET and GPT severity would warrant the need for dental professionals to engage their patients smoking within clinical practice. The detrimental effects of smoking in dental care for smokers, as evidenced by the distribution of treatment and encounter and stage of treated disease, may not be clearly realized by dental professionals, unless the smoking status of all patients is identified.

Association between perception of dentist oversupply and expectations of dentistry: a survey of dental graduates in Japan.

BACKGROUND: The perception that there is a surplus of dentists may be an opportunity to explore attractive career options in dentistry in Japan. METHODS: A self-administered questionnaire was mailed to 2,114 graduates of a private dental school in Japan. We asked about the perception of oversupply, rated by a visual analogue scale, work environment factors, potential areas of dentistry and necessary medical subjects for their dental practice. The association of a strong perception of dentist oversupply with work environment factors, dental areas and medical subjects was examined by multivariate logistic regression analyses. RESULTS: The response rate was 66%, and data from 1,203 community dentists were analysed. Most respondents (76%) perceived either a strong or very strong surplus of dentists. A very strong perception was significantly associated with work environment factors, including practising in large cities and earning the second lowest of four levels of annual income, but no further associations were found with either the number of patients treated or with the other two ranges of income. This perception was negatively associated with the number of necessary medical subjects, specifically otorhinolaryngology, but no significant association was seen with the number of potential areas of dentistry. CONCLUSIONS: The negative correlation between the aspiration to acquire medical knowledge and the perception of dentist oversupply under the circumstance of the possibly excessive perception among community dentists invites further research on the benefits of teaching oral medicine to graduate entry students to build future working satisfaction.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].

From October 2006 to September 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. The isolated bacteria were: Staphylococcus aureus 64, Streptococcus pneumoniae 96, Haemophilus influenzae 87, Pseudomonas aeruginosa (non-mucoid) 52, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 20, and Moraxella catarrhalis 44. Of 64 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 27 (42.2%) and 37 (57.8%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 microg/ml or less. Against MRSA, vancomycin and linezolid showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.125 and 0.5 microg/ml, respectively. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (45.8%) and clindamycin (20.8%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (50.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 49.2% and 28.1% of all the respiratory infections, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (29.2%), S. aureus (20.8%), and H. influenzae (12.9%). H. influenzae (25.0%) and P. aeruginosa (21.7%) also were frequently isolated from the patients with chronic bronchitis. Before the antibacterial agent administration, the bacteria frequently isolated from the patients were S. pneumoniae (27.5%) and H. influenzae (22.5%). The bacteria frequently isolated from the patients treated with macrolides was P. aeruginosa, and its isolation frequently was 39.4%.

Antimicrobial susceptibility of pathogens isolated from more than 10,000 patients with infectious respiratory diseases: a 25-year longitudinal study.

The Study Group on Antimicrobial Susceptibility of Pathogens Isolated from Respiratory Infections was established in 1981 in Japan to elucidate trends in such susceptibilities in patients with infectious respiratory diseases; the Group has conducted nationwide research in collaboration with 21 medical institutions. Examination of more than 10,000 patients by 2005 allowed a summary of study findings. Streptococcus pneumoniae started to become resistant to penicillin G in the 1990s, and the isolation rate of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP + PRSP) reached almost 60% in 2001. The proportion of PRSP also increased, reaching 19.4%. Thereafter, the rate of PISP + PRSP decreased somewhat to the mid-30% range. Macrolide resistance was also observed; in 2005, the prevalence of strains highly susceptible to erythromycin with MICs or= 128 microg/ml exceeded 40%. Among Staphylococcus aureus isolates, the proportion of methicillin-resistant S. aureus (MRSA) strains began to increase rapidly in 1986 and constituted around 60% of all S. aureus strains identified in 1990 and in the following years. In 1993, the prevalence of ampicillin-resistant isolates of Haemophilus influenzae had increased remarkably, presumably related to the outbreak of beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae strains, and the proportion of these strains among the isolates surpassed 30% in 2002 and thereafter. For Klebsiella pneumoniae, the antimicrobial activity of first- to fourth-generation cephems improved with each generation. The MIC distribution patterns of Pseudomonas aeruginosa shifted towards higher MICs when compared with the MICs for other pathogens. Broad patterns with no distinct peaks reflected the difficulty in treating P. aeruginosa infection. Regarding Moraxella catarrhalis, beta-lactamase-producing strains already constituted a majority of the isolates in 1990, and the proportion of strains highly susceptible to ampicillin, with MICs