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Purpose: We describe the epidemiology of invasive Haemophilus influenzae disease (IHD) among adults in Japan. Methods: Data for 200 adult IHD patients in 2014–2018 were analyzed. The capsular type of H. influenzae was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable Haemophilus influenzae (NTHi) was identified by PCR. Results: The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15–64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5% were aged ≥ 65 years. About one-fourth of patients were associated with immunocompromising condition. The major presentations were pneumonia, followed by bacteremia, meningitis and other than pneumonia or meningitis (other diseases). The case fatality rate (CFR) was 21.2% for all cases, and was significantly higher in the ≥ 65-year group (26.1%) than in the 15–64-year group (7.5%) (p = 0.013). The percentage of cases with pneumonia was significantly higher in the ≥ 65-year group than in the 15–64-year group (p < 0.001). The percentage of cases with bacteremia was significantly higher in the 15–64-year group than in the ≥ 65-year group (p = 0.027). Of 200 isolates, 190 (95.0%) were NTHi strains, and the other strains were encapsulated strains. 71 (35.5%) were resistant to ampicillin, but all were susceptible to ceftriaxone. Conclusion: The clinical presentations of adult IHD patients varied widely; about three-fourths of patients were age ≥ 65 years and their CFR was high. Our findings support preventing strategies for IHD among older adults, including the development of NTHi vaccine. [ABSTRACT FROM AUTHOR]

Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody that exhibits significant efficacy in treating melanoma and other malignancies. However, various nivolumab-induced immune-related adverse events (irAEs) have been reported, and differentiating irAEs from tumor progression is sometimes difficult. Here, we report a case of reactive lymphadenopathy occurring after treatment with nivolumab. A 56-year-old man with stage IIIC melanoma received adjuvant therapy with nivolumab after wide local excision. He developed systemic lymphadenopathy and autoimmune hemolytic anemia 1 month after receiving seven cycles of nivolumab. Pathological analysis of a cervical lymph node biopsy specimen revealed no metastatic lesion or any other malignancy, including lymphoma. Thus, the patient was diagnosed with nivolumab-induced reactive lymphadenopathy. Systemic corticosteroids were administered to reduce hemolysis, which led to the resolution of lymphadenopathy. When progressive lymphadenopathy is observed in a patient who received immune checkpoint inhibitor therapy, reactive lymphadenopathy should be carefully distinguished from progression to lymphoid metastasis, and biopsy should be performed if needed. [ABSTRACT FROM AUTHOR]

Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbβ3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT. [ABSTRACT FROM AUTHOR]

We assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014–2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016–2018 was 0.20–0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27–4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10–5.06) or 23A (aOR 3.91, 95% CI 2.47–6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44–0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65). [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (Group B Streptococcus, GBS) is an invasive pathogen that causes sepsis and meningitis among infants, elderly adults, and immunosuppressed patients. Generally, GBS is susceptible to penicillin; however, GBS with reduced penicillin susceptibility (PRGBS) has been reported. PRGBS are commonly isolated from respiratory specimens, but clinical features of patients with PRGBS remain unclear. In this case–control study, clinical features of patients with PRGBS and bacterial characteristics of these isolates from respiratory specimens were investigated. Patients with GBS at the University of the Ryukyus Hospital between January 2017 and June 2018 were retrospectively investigated. GBS were further classified into penicillin-susceptible GBS (PSGBS) and PRGBS using a drug susceptibility test. Moreover, serotypes, genotypes, and drug resistance genes of PRGBS isolates were determined. In total, 362 GBS were isolated, of which 46 were collected from respiratory specimens, which had the highest rate of PRGBS (24%). Compared to patients with PSGBS, those with PRGBS were more likely to have neuromuscular disease, poor performance status, risk of multidrug-resistant pathogen infection, prior pneumonia history within 1 year, and prior penicillin use within 1 year. Among eight PRGBS isolates, multilocus sequence typing revealed that five isolates were sequence type (ST) 358, two were ST3 and ST10, respectively, and one isolate was ST1404. All PRGBS isolates belonged to the ST1/ST19/ST10 group. This study reveals clinical characteristics of patients with PRGBS from respiratory specimens. Because invasive GBS infection cases are increasing, especially in the elderly, more attention should be paid to this infection. [ABSTRACT FROM AUTHOR]

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein-Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence. [ABSTRACT FROM AUTHOR]

Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report on a patient who developed encephalitis associated with antibodies against N-methyl-d-aspartate (NMDA)-type glutamate receptor (GluR) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against NMDA-type GluR in post-transplantation encephalitis. Autoimmunity to NMDA-type GluR may have contributed to neurological complications after transplantation in unresolved cases. [ABSTRACT FROM AUTHOR]

A conditioning regimen with fludarabine and myeloablative dose of busulfan (FLU/BU4) has been commonly used in allogeneic hematopoietic cell transplantation (allo-HCT). However, there are two major problems with this regimen: insufficient anti-leukemic effect, especially in advanced cases, and slow time to complete donor-type chimerism, especially T-cell chimerism. To overcome these issues, we designed a combination regimen with FLU (150 mg/m2), intravenous BU (12.8 mg/kg), and melphalan (100 mg/m2) (FLU/BU4/MEL) and conducted retrospective analyses of treatment outcomes at our institute. Forty-two patients with myeloid malignancies received allogeneic bone-marrow transplantation or peripheral blood stem-cell transplantation (allo-BMT/PBSCT) with FLU/BU4/MEL regimen. The median age of patients was 46.5 years (20-63 years). Thirteen patients (31%) did not achieve complete hematological remission at transplantation. All patients examined achieved complete whole and T-cell chimerism within 1 month after allo-HCT. The 4-year overall survival and disease-free survival rates were 66.0% [95% confidence interval (CI) 49.4-78.3%] and 59.5% (95% CI 43.2-72.6%) in all patients, and 49.4% (95% CI 19.7-73.6%) and 38.5% (95% CI 14.1-62.8%) in patients who were not in remission. In conclusion, FLU/BU4/MEL showed curative potential, even in patients with advanced myeloid malignancies, accompanied by achievement of rapid complete chimerism after allo-BMT/PBSCT. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation is a feature of lung injury and plays a critical role in pulmonary vascular remodeling. Bone marrow-derived cells (BMCs) have anti-inflammatory properties and favor macrophage differentiation into an alternatively activated regulatory M2 profile. We investigated the effect of autologous BMCs on monocrotaline-induced pulmonary vessel remodeling and lung inflammation in rats, by direct administration into lungs via the airway.Methods: BMCs were isolated and plastic-adherent cells were cultured for 3 weeks. 1 week following monocrotaline (60 mg/kg) treatment, fluorescently labeled autologous BMCs (1 × 106 cells) or vehicle were administered intratracheally to male Sprague-Dawley rats. 4 weeks following monocrotaline treatment, lung pathology was evaluated.Results: Monocrotaline increased pulmonary vessel wall thickness, perivascular infiltration, alveolar septal thickening, and inflammatory cell infiltration including T lymphocytes and monocytes/macrophages in alveolar areas, and also increased mRNA expression of inflammatory-related cytokines including IL-10 in the lung. Intratracheal administration of autologous BMCs prevented pulmonary vessel wall thickening and perivascular infiltration, and increased CD163-positive M2-like macrophages in perivascular areas. BMC administration inhibited the thickening of alveolar septa and reduced monocrotaline-induced inflammatory cell infiltration in lung parenchyma compared with monocrotaline-vehicle-treated-rats. Furthermore, BMCs administration increased expression of CD163-positive cells in perivascular areas and maintained the increased mRNA expression of IL-10.Conclusions: Intratracheal administration of autologous BMCs prevented monocrotaline-induced pulmonary vessel remodeling and lung inflammation, at least in part, through induction of alternatively activated macrophages and regulation of the local lung environment toward resolving inflammation. [ABSTRACT FROM AUTHOR]

We consecutively examined the utility of measurements of percentage of immature platelet fraction (IPF%) and absolute IPF number (A-IPF) in predicting thrombopoietic recovery in 15 adult patients who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT). Four patients were excluded from the evaluation due to insufficient data. Platelet count and IPF were measured by Sysmex XN-1000 (XN), a newer generation analyzer. First, we confirmed that platelet count measured by XN was more accurate than by XE-2100 (XE). IPF measurement was effective to predict the recovery in 7 of the 11 patients examined. Moreover, IPF measurement, especially IPF% measurement, suggested accelerated platelet turnover in two patients who failed to achieve platelet recovery by day 60. In addition to IPF%, A-IPF showed a complementary role on the prediction of thrombopoietic recovery. The increase in IPF% was only transient, while A-IPF values showed lasting increase during platelet recovery. In two patients (cases 6 and 7) an increase in A-IPF, but not in IPF%, was observed during platelet recovery. Our data suggest that IPF% and A-IPF measured by XN are useful for the prediction of thrombopoietic recovery and the assessment of pathogenesis of thrombocytopenia in patients after allo-SCT. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 ( TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago. Our association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. We found that the recessive model was supported to fit the observed genotype frequency of risk alleles slightly better than the additive model, defining the genetic effect on CD if a pair of the chromosomes in an individual consists of all risk alleles. The combined analysis of haplotypes and salivary microbiome from a small set of samples showed a significant association of the genetic effect with the increase of Prevotella, which led to a significant increase of CD risk. However, the genetic effect on CD disappeared if the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent given a fixed amount of Prevotella. Although our statistical power is limited due to the small sample size, these results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella. [ABSTRACT FROM AUTHOR]

Late-onset noninfectious pulmonary complication after allogenic hematopoietic stem cell transplantation is an important contributing factor associated with high rate morbidity and mortality. We report a case with pleuroparenchymal fibroelastosis (PPFE) occurred after allogenic bone marrow transplantation. The onset was infiltrative shadows in upper lobes, and the haziness spread gradually throughout the lungs with recurrent episodes of pneumothorax in both lungs. Progressive respiratory failure in course of adrenocortical steroid administration eventually caused death. Histological examination in general autopsy showed patchy subpleural fibrosis predominantly distributed in the upper lobes with substantial density rise of elastic fibers in the subpleural area, consistent with the diagnosis of PPFE. PPFE after allogenic transplantation has been seldom reported to date, but it is one of the most important histological components of late-onset noninfectious pulmonary complication after allogenic transplantation characterized by recurrent pneumothorax. Retrospective analysis in our case indicates early diagnosis may be possible by histological evaluation of elastic fibers in lung specimen when pneumothorax is treated surgically. This case suspects that it is important for hematologist and pathologist to aware this progressive disease along with information of histological characteristics, therefore, leading to the establishment of therapeutic strategies and the improvement of poor prognosis. [ABSTRACT FROM AUTHOR]

The switch from intravenous to oral antibiotic therapy is recommended for treating hospitalized patients with community-acquired pneumonia (CAP). We performed a multicenter, randomized study to assess the benefit of switching from intravenous sulbactam/ampicillin (SBT/ABPC) to oral garenoxacin (GRNX) in patients with CAP. Among adult CAP patients who must be hospitalized for intravenous antibiotic treatment, those with Pneumonia Patient Outcomes Research Team (PORT) scores of II–IV (mild to moderate) were initially treated with intravenous SBT/ABPC (6 g/day) for 3 days. A total of 108 patients who fulfilled the inclusion criteria (improved respiratory symptoms, CRP < 15 mg/dl, adequately improved oral intake, fever ≤ 38 °C for ≥ 12 h), were divided into two groups based on the antibiotic administered, the GRNX (switch to GRNX 400 mg/day) and SBT/ABPC groups (continuous administration of SBT/ABPC), for 4 days. Improvement in clinical symptoms, chest radiographic findings, and clinical effectiveness were evaluated by a central review board. Improvement in clinical symptoms was 96.3 and 90.2 % in the GRNX and SBT/ABPC groups, respectively. Improvement in chest radiographic findings was 94.4 and 90.2 % and clinical effectiveness was 94.4 and 90.2 % in the GRNX and SBT/ABPC groups, respectively. Microbiological efficacy was 90.9 and 69.2 % in the GRNX and SBT/ABPC groups, respectively. There were no significant differences between the groups. Converting to GRNX was as effective as continuous SBT/ABPC treatment in mild to moderate CAP patients in whom initial intravenous antibiotic treatment was successful. [ABSTRACT FROM AUTHOR]

We evaluated the clinical and bacteriological efficacy of oral sitafloxacin (STFX) in clinically diagnosed community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae. Additionally, we cultured these patient samples to test the minimal inhibitory concentrations (MICs) of levofloxacin (LVFX), moxifloxacin (MFLX), STFX, and penicillin G (PCG), as well as identified mutations in the quinolone resistance determinant regions (QRDRs) in LVFX-resistant strains. This study is a nested cohort from a prospective, multicenter clinical trial consisting of 139 patients with community-acquired pneumonia (CAP), from which 72 were included in this study. After diagnosis of CAP caused by S. pneumoniae, STFX (50 mg twice daily, or 100 mg once daily) was orally administered for 7 days. Sixty-five patient sputum samples were then cultured for MIC analysis. In a LVFX-resistant strain that was identified, mutations in the QRDRs of the gyrA, gyrB, parC, and parE genes were examined. Of 72 patients eligible for this study, S. pneumoniae was successfully cultured from the sputum of 65 patients, and only 7 patients were diagnosed by urinary antigen only. Clinical improvement of CAP was obtained in 65 of the 69 clinically evaluable patients (65/69, 94.2 %). Eradication of S. pneumoniae was observed in 62 patients of the 65 bacteriologically evaluable patients (62/65, 95.4 %). Additionally, STFX showed the lowest MIC distribution compared with LVFX, MFLX, and PCG, and no major adverse reactions were observed. STFX treatment in patients with CAP caused by S. pneumoniae was found to be highly effective both clinically (94.2 %) and bacteriologically (95.4 %). [ABSTRACT FROM AUTHOR]

The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily (50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. The clinical efficacy was 93.5 % in both groups. The pneumococci eradication rate was 98.2 % in the 100 mg qd group and 92.7 % in the 50 mg bid group. The mean of the free AUC divided by the minimum inhibitory concentration (MIC) ( fAUC/MIC) did not differ significantly between the 100 mg qd (103.24) and the 50 mg bid groups (105.25). The mean of the free C divided by the MIC ( fC/MIC) was higher in the 100 mg qd group (10.19) than in the 50 mg bid group (6.53). The pathogen eradication rate was 98.9 % (89/90) when the fAUC/MIC was greater than 30, and the eradication rate was 98.9 % (89/90) when the fC/MIC was greater than 2. The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered. [ABSTRACT FROM AUTHOR]

The virulence factor known as the macrophage infectivity potentiator ( mip) is responsible for the intracellular survival of Legionella species. In this study, we investigated the potential of the mip gene sequence to differentiate isolates of different species of Legionella and different serogroups of Legionella pneumophila. We used 35 clinical L. pneumophila isolates and one clinical isolate each of Legionella micdadei, Legionella longbeachae, and Legionella dumoffii (collected from hospitals all over Japan between 1980 and 2007). We used 19 environmental Legionella anisa isolates (collected in the Okinawa, Nara, Osaka, and Hyogo prefectures between 1987 and 2007) and two Legionella type strains. We extracted bacterial genomic DNA and amplified out the mip gene by PCR. PCR products were purified by agarose gel electrophoresis and the mip gene was then sequenced. The L. pneumophila isolates could be divided into two groups: one group was very similar to the type strain and was composed of serogroup (SG) 1 isolates only; the second group had more sequence variations and was composed of SG1 isolates as well as SG2, SG3, SG5, and SG10 isolates. Phylogenetic analysis displayed one cluster for L. anisa isolates, while other Legionella species were present at discrete levels. Our findings show that mip gene sequencing is an effective technique for differentiating L. pneumophila strains from other Legionella species. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess pulmonary vascular resistance (PVR) in patients with pulmonary fibrosis (PF) by phase-contrast magnetic resonance imaging (MRI).Materials and Methods: Subjects were 11 healthy volunteers and 11 patients with PF. Using phase-contrast MRI, we measured pulmonary arterial blood flow and calculated the parameters of PVR. Parameters were compared between volunteers and patients using unpaired t-tests. The diagnostic capability of the parameters was evaluated by receiver operating characteristic (ROC) curve analysis. Patients underwent respiratory function tests (RFTs) and chest computed tomography (CT), and they were correlated with MRI parameters.Results: Most MRI parameters were significantly different between volunteers and patients (t-test P values were <0.05 in 9 of 10 parameters). Regarding the RFT and CT visual score, only the %DLco/VA and acceleration time and the CT visual score and average flow volume had significant correlation [r = -0.667 (P = 0.024) and r = -0.6 (P = 0.031)], respectively.Conclusion: Our findings suggest that PVR derived from phase-contrast MRI is significantly higher in patients with PF than in volunteers. However, all but two of these parameters may not correlate with the severity of PF. [ABSTRACT FROM AUTHOR]

The main aim of this study was to describe the appearance of the CT pattern of organizing pneumonia in Legionella-infected patients. Serial CT scans obtained from five sporadic cases of Legionella pneumophila pneumonia were retrospectively reviewed. The mean time of follow-up was 14 days. Chest CT was analyzed with regard to frequency and appearance of CT patterns of pulmonary abnormalities. Consolidation and ground-glass opacities, with or without an air bronchogram, were the most common abnormalities detected in CT scans during follow-up patients with L. pneumophila pneumonia. Two patterns were observed: subpleural and peribronchovascular. The subpleural pattern was seen in four patients and the peribronchovascular pattern in one. Interlobular septal thickening was seen in one patient. Pleural effusion was seen in one patient. The CT pattern of organizing pneumonia, a subpleural pattern, was frequently observed after treatment of L. pneumophila pneumonia. [ABSTRACT FROM AUTHOR]

In this study, we report three cases diagnosed with human T-cell lymphotropic virus type 1 (HTLV-1) and Sjögren’s syndrome (SS) who developed pulmonary complications. Radiologic and pathologic findings were evaluated. Although the histologic diagnosis was considered to be hypersensitivity pneumonitis in case 1, and discordant usual interstitial pneumonia (UIP) in cases 2 and 3, lymphocytic alveolitis was observed in all cases. We also did a literature review and concluded that, although the pathologic diagnosis of pulmonary complications in HTLV-1 carriers with SS may vary, lymphocytic infiltrations are commonly observed. [ABSTRACT FROM AUTHOR]

Abstract  A 49-year-old woman with poorly controlled type 2 diabetes mellitus was admitted to hospital complaining of fever, vomiting, and lower abdominal pain. Laboratory investigation revealed leukocytopenia, high blood sugar, and pyuria. Pyelonephritis was then diagnosed. Escherichia coli was isolated from blood and urinary cultures. In spite of antimicrobial therapy, the patient’s condition deteriorated. A computed tomography scan of the abdomen on the second day of hospitalization revealed the presence of air in the collecting system of the left kidney. Emphysematous pyelonephritis was diagnosed, and a renoureteral catheter was promptly inserted via the left ureter into the affected pelvis of the left kidney. Imipenem, cefotiam, and levofloxacin were administered during the clinical course. This early intervention and the appropriate antimicrobial therapy were effective in resolving the infection. Urinary tract infections should be carefully managed in patients with poorly controlled diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background/Aim: Cytokeratin 8 (CK8) is a type II intermediate filament protein that is persistently expressed in most epithelial malignancies. Circulating CK-related polypeptides have commonly been used as tumor markers. While apoptosis is a mechanism of CK release, the molecular nature of circulating CKs is poorly understood. The aim is to clarify the dynamics of CK8 during apoptosis in vitro and the nature of circulating CK8 in patients with lung cancer. Methods: Extracellular release of CK8 was examined using A549 human non-small cell lung cancer (NSCLC) cells after apoptosis induction by etoposide. Serum samples from NSCLC patients were examined for circulating CK8 by ELISA (n = 60) and by immunoprecipitation (n = 9). Results: CK8 is released predominantly in full length from A549 cells undergoing apoptosis and is resistant to intracellular cleavage by caspases, unlike type I CK18, which is readily cleaved during apoptosis. Full-length CK8 is shown to constitute a considerable fraction of circulating CK8 in the serum of lung cancer patients. Conclusion: Apoptosis causes extracellular release of full-length CK8 in NSCLC cells. CK8 circulates predominantly in full length in patients with NSCLC, illustrating the fundamental differences in protein processing between type I and type II CKs. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To clarify the localization of KL-6 and epithelial membrane antigen (EMA) in human lungs, immune reactions to antibodies to these factors were examined in detail at light and electron microscopic levels. Immunohistochemical investigation was performed in 17 cases of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), hypersensitivity pneumonitis (HP), collagen vascular disease-associated interstitial pneumonias (CVD-IP), viral pneumonia, and bronchobronchioloectasis, as well as in 10 cases of presumably normal pulmonary tissue resected as a result of spontaneous pneumothorax. Immunohistochemical study revealed similar discontinuous linear or dome-shaped positive patterns restricted to type II alveolar cells in presumably normal tissue and only some regions of interstitial pneumonia. In sharp contrast, immune reactions with each of the two antibodies yielded a continuous linear pattern surrounding damaged areas in most regions of interstitial pneumonias and some normal areas as well. Staining for EMA antibody was negative in some regenerating alveolar and bronchial cells in regenerating foci in interstitial pneumonias, although staining for KL-6 antibody was always positive in these cells. Immunoelectron microscopic studies demonstrated similar positive reactions with both antibodies on the surface of alveolar epithelial cells in three of the cases examined, with surface positive granules 100–200 nm in diameter. Thus, although staining for both KL-6 and EMA antibodies exhibited discontinuous positivity restricted to type II alveolar cells in nondamaged regions, immune reactions were continuous and linear in pattern in or around damaged areas of the lungs at both light and electron microscopic levels, probably as a consequence of cell-surface barrier function. These findings in pulmonary tissue might be evidence of defense functions. [ABSTRACT FROM AUTHOR]

The immunohistochemical distribution of SP-D was compared with that of SP-A and KL-6 using a monoclonal antibody in lung tissues of 15 cases of collagen vascular disease-associated interstitial pneumonia (CVD-IP), 4 cases of hypersensitivity pneumonitis (CHP), and 6 cases of other diseases to determine their differences in distribution. In this study, the main targets were alveolar epithelial cells, especially those in the regenerating stage, as well as lymph vessels and stroma. The cytoplasm of type II alveolar epithelial cells and Clara cells was positive for SP-D, with sharp margins; interestingly, however, during the process of regeneration large positive cells were intermingled with relatively small negative cells, even in the same row of cells. In sharp contrast, staining for SP-A and KL-6 was positive in the cytoplasm of all the regenerating alveolar epithelial cells, as well as Clara cells. Staining for KL-6 was usually positive in the surface of air spaces in linear fashion. Staining for SP-A was also positive in elastic fibers in vascular walls. In areas of destruction of pulmonary structures, loose stroma and the endothelial cells of lymph vessels as well as their contents were distinctly positive for SP-A and/or KL-6 but not SP-D. Judging from these results in pulmonary tissues of CVD-IP and HP, SP-D might be a marker for maturity of regenerating epithelial cells. Both SP-A and KL-6 were detected in intimate relationship to the stage of regeneration of alveolar epithelial cells and were expressed before SP-D. In addition, the lymph vessels play a very important role in transfer of KL-6 into the bloodstream. [ABSTRACT FROM AUTHOR]

Although rates of emphysematous change in smokers have previously been reported, the precise effects of smoking on emphysematous change have yet to be established because the study subjects of previous reports were heterogeneous in background, and particularly in their professions. This study was prospectively designed to determine the incidence of emphysematous change identified by low-dose multislice computed tomography (LMCT) as well as high-resolution CT (HRCT) imaging in public school teachers. We prospectively examined a series of 859 public school teachers (all males, age = 31–61 years) who had undergone LMCT and HRCT scanning during healthcare examinations. In addition, the subjects’ replies to a questionnaire concerning smoking were also collected. Furthermore, most underwent a pulmonary function test. Of the 859 subjects, emphysematous change was found by LMCT imaging in 54 subjects and by HRCT in 75 subjects. All of these subjects were smokers. The FEV1/FVC and FEV1% predicted were significantly lower for subjects with PE compared with those for subjects without PE. Our study clearly demonstrated the incidence of emphysematous change in smokers in accordance with age. [ABSTRACT FROM AUTHOR]

To investigate the fine-structural nature of nuclear inclusions immunopositive for surfactant protein A (SP-A) antibody staining, a detailed ultrastructural study was performed, as well as immunohistochemical examination of pulmonary adenocarcinomas. Surgically resected tumor specimens from 31 patients were examined by immunohistochemistry focused on reactivity to SP-A and thyroid transcription factor 1 (TTF-1) antibodies. Only cases with >5% positive nuclear inclusions in cancer cells were considered positive, some of which were examined by electron microscopy. Immunohistochemically, 6 of 31 cases were doubly positive for SP-A and TTF-1 antibodies. On electron microscopy, SP-A-positive nuclei contained diffuse or globular fine granular substance as inclusions. Both types of globular and diffuse inclusions were sometimes connected to the inner nuclear membrane, in association with fragmented or stacked membranous structures. The findings of this study suggested that nuclear inclusions positive for SP-A antibody staining in adenocarcinomas of the lung were derived from accumulated content in the perinuclear cistern resembling pseudoinclusion processes and composed of proteins antigenically cross-reactive with SP-A. [ABSTRACT FROM AUTHOR]

Recently, we have experienced significant numbers of patients diagnosed with non-specific interstitial pneumonia (NSIP) by open lung biopsy or video-assisted thoracoscopic surgery. The purpose of this work was to describe the clinical features of patients with collagen vascular disorders (CVD) presenting NSIP in the absence of systemic involvement. This study also involved a retrospective review of patients with CVD presenting clinical and pathological evidence of NSIP in the absence of systemic manifestations of CVD. We found seven patients (six from our experience and one from literature review) with histologically proven NSIP who later developed typical CVD more than 6 months after the first presentation of NSIP. In these cases, it was difficult to speculate the development of CVD at the point of first presentation. Therefore, association of CVD should be considered in patients with NSIP even in the absence of classical systemic involvement. [ABSTRACT FROM AUTHOR]

Patients with primary Sjogren's syndrome (SS) occasionally develop interstitial pneumonia (SS-IP), the prognosis of which is less grave compared with that of idiopathic pulmonary fibrosis (IPF). We examined distribution of helper T-cell subsets in open lung biopsy specimens from seven patients with SS-IP and, for comparison, ten patients with IPF. The expression of CXCR3 and CCR4, chemokine receptors associated in vitro with Th1 and Th2 cells, respectively, was analyzed in the mononuclear infiltrate using immunohistochemistry. The expression of CD4, CD8, and CD20 in the infiltrate was similarly examined. The positive cells were semiquantified in fibrosing areas and lymphoid clusters of both SS-IP and IPF. In fibrosing areas, CXCR3-positive cells were dominant over CCR4-positive cells in all cases of SS-IP, whereas the two types of cells showed no such difference in cases of IPF. Each of the CXCR3/CD4 and CXCR3/CCR4 ratios was significantly higher in SS-IP than in IPF ( P<0.05 and P<0.05, respectively). The CCR4/CD4 ratio showed a significantly lower value in SS-IP than in IPF ( P<0.05). In lymphoid clusters, prominent in SS-IP and few and small in IPF, CXCR3-positive cells predominated over CCR4-positive cells in both lung lesions. There was no significant difference of CXCR3/CCR4 ratio in lymphoid clusters between SS-IP and IPF ( P=0.33). These findings in SS-IP are in accordance with those reported in previous studies of the salivary glands of SS patients, where most of the infiltrating lymphocytes expressed CXCR3, and the expression of interferon-gamma was upregulated. In contrast, the Th2 cell dominance was reported in IPF in the previous studies. The present findings suggest that the pathogenesis of interstitial pneumonia is different between SS-IP and IPF in regard to the roles of helper T-cell subsets. [ABSTRACT FROM AUTHOR]

We report a case of lung cancer arising from progressive massive fibrosis (PMF) associated with pneumoconiosis. In this case, fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) was able to clearly distinguish the lung cancer from PMF, suggesting a potential usefulness of FDG-PET in cancer screening in patients with pneumoconiosis. To our knowledge, this is the first description of an FDG-PET image of lung cancer arising from PMF. [ABSTRACT FROM AUTHOR]

We report a case of lung cancer arising from progressive massive fibrosis (PMF) associated with pneumoconiosis. In this case, fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) was able to clearly distinguish the lung cancer from PMF, suggesting a potential usefulness of FDG-PET in cancer screening in patients with pneumoconiosis. To our knowledge, this is the first description of an FDG-PET image of lung cancer arising from PMF. [ABSTRACT FROM AUTHOR]

We evaluated the accumulation of 99mTc-MIBI in small cell lung cancer patients before chemotherapy and after unresponsive chemotherapy. The pre-chemotherapeutic group included 22 newly diagnosed patients. These patients underwent a 99mTc-MIBI SPECT study before starting chemotherapy. After chemotherapy, based on changes in tumor size, three different patterns of response (complete remission: CR, partial remission: PR and no change: NC) were defined. The post-chemotherapeutic group included 11 patients after chemotherapy who did not respond to chemotherapy. These patients underwent a 99mTc-MIBI SPECT study after completion of chemotherapy. SPECT images were acquired 15 min (early) and 2 hr (delayed) after injection of 99mTc-MIBI. With a region of interest technique, the early ratio, delayed ratio and retention index were calculated. Early and delayed ratios in pre-chemotherapeutic patients were significantly higher than those in post-chemotherapeutic patients. There were no significant differences between the pre-chemotherapeutic and post-chemotherapeutic patients in the retention index. In the pre-chemotherapeutic patients, early and delayed ratios for the CR and PR groups were significantly higher than those for the NC group. There were no significant differences in the retention index with respect to the tumor response. 99mTc-MIBI might be useful for evaluating the tumor chemosensitivity in patients with small cell lung cancer. [ABSTRACT FROM AUTHOR]

T cadherin is a unique cadherin cell adhesion molecule that is anchored to the surface membrane through a glycosyl phosphatidyl inositol (GPI) moiety. In the present study, we postulated that T cadherin could regulate surfactant protein (SP)-D gene expression in human bronchioloalveolar type-II cells. We transfected A549 cells (human lung cancer cell line with alveolar type-II cell characteristics) with the T-cadherin expression vector. Both original and control plasmid-transfected A549 cells expressed SP-D; however, neither human nor murine T-cadherin-transfected A549 cells expressed SP-D mRNA. The downregulation of SP-D production in human T-cadherin-expressed A549 cells was also demonstrated using Western immunoblotting techniques. Control vector-transfected A549 cells showed a positive band of SP-D but not of T cadherin. In contrast, T-cadherin-transfected A549 cells, which expressed T-cadherin protein, did not produce SP-D. We further examined the relationship of T cadherin and SP-D expression in secondary pulmonary alveolar proteinosis associated with hematolymphoid malignancies. SP-D was detected in bronchioloalveolar type-II cells in alveolar proteinosis. However, little or no T-cadherin expression was detected in alveolar type-II cells in these patients. To our knowledge, this is the first report describing an effect of cadherin on SP production in bronchioloalveolar cells. [ABSTRACT FROM AUTHOR]

Bronchial asthma is a clinical syndrome characterized by the reversibility of airway obstruction. Recently it has been suggested that remodeling of the airway causes irreversible airway obstruction which may be responsible for the patient's symptoms. With this background, the purpose of the present study was to assess patients with corticosteroid-dependent asthma by Tc-99m Technegas scintigraphy (Technegas) in both planar and SPECT images. Twelve patients (7 females and 5 males aged 36-72 years with a median age of 60 years: 4 smokers and 8 non-smokers) with oral corticosteroid-dependent asthma were enrolled in this study. Lung ventilation scanning with Technegas in both planar and SPECT images, high-resolution computed tomography, and pulmonary function tests were performed in all patients. The results of Technegas scanning were graded and correlations with other clinical parameters were evaluated. Significant abnormalities were detected by ventilation scintigraphy with Technegas in patients with corticosteroid-dependent bronchial asthma even during remission. Our data demonstrate that airflow obstruction took place in patients with corticosteroid-dependent asthma even during remission. Technegas scanning appears to be a useful radiopharmaceutical for demonstrating airflow obstruction in patients with bronchial asthma. [ABSTRACT FROM AUTHOR]

Twenty patients with bladder cancer (T1, 3 patients; T2, 6 patients; T3, 8 patients; T4a, 3 patients) were preoperatively treated with intra-arterial doxorubicin chemotherapy in combination with low-dose irradiation. The originally scheduled operations were as follows: total cystectomy in 16 patients (T1+cis, 1 patients; T2, 5 patients; T3, 7 patients; T4a, 3 patients), segmental cystectomy in 2 patients, and transurethral resection in 2 patients. The total dose of doxorubicin ranged from 120 to 540 mg (251.5±100.2 mg), and that of irradiation was from 4 to 36 Gy (24.4±7.3 Gy). Clinical and pathological effects were evaluated in all of the cases. Clinically, complete remission (CR) was observed in 14 cases (70.0%), partial remission (PR) was seen in 3 cases, a minor response (MR) occurred in 2 cases, and no response (NR) was seen in 1 patient; non patient showed progressive disease (PD). The pathological effects (according to the criteria of Shimosato et al.) were as follows: grade IV was seen in 10 cases, grade III in 3 cases, and less than grade II in 7 cases; however, viable tumor cells were not seen in 13 (65.0%) of the 20 cases. The bladder was preserved in 13 (81.3%) of the 16 cases for which total cystectomy had been recommended. All of the patients were followed up for periods ranging from 3 to 54 months (26.3±16.5 months), durng which time 6 patients (30.0%) died (3 with cancer, 1 without cancer, and 2 unknown causes). The actual survival rate according to the stage of disease was 100.0% at 50 months in T1-T2 and 40.9% at 54 months in T3-T4a. In T3-T4a, the actual survival rate in pathologically complete responders was 60% (relative rate 68.8%) at 54 months, and the actual survival rate in incomplete responders was 25.0% (relativ rate 27.1%) at 36 months. The results of our study are encouraging, especially in T1-T2 and T3-T4a cases, who showed a complete response. It is concluded that doxorubicin intra-arterial chemotherapy combined with low-dose irradiation could be the first treatment of choice for locally invasive bladder cancer. [ABSTRACT FROM AUTHOR]

Twenty patients with bladder cancer were treated by semiselective intra-arterial chemotherapy with Adriamycin. Ten of them were given the agent while the femoral arteries were compressed, to prevent loss of the agent into the external iliac arteries. The other ten were given Adriamycin without this compression. Clinical and pathological responses of tumor and the side-effects were examined in these two groups. The results of the comparative study led us to the conclusion that the compression technique is a simple and valuable means of decreasing the side-effects of Adriamycin and increasing tumor response. [ABSTRACT FROM AUTHOR]

This study was undertaken to compare axial images of99mTc-Technegas SPECT (Technegas) with those of133Xe gas dynamic SPECT in patients with pulmonary emphysema. There were 20 patients, 19 males and 1 female. All patients except one ex-smoker were heavy smokers with a mean age of 68.1 years. For Technegas scintigraphy, the patients inhaled 505 MBq99mTc-Technegas in several tidal volume breaths in the supine position without breath holding. For133Xe gas scintigraphy, the patients inhaled 370 MBq133Xe gas.133Xe gas dynamic SPECT was performed in the equilibrium phase for the last minute of the 3 minute inhalation in a closed circuit, and in the washout phase for 6 minutes of inhalation in a semi-closed circuit, by means of a gamma camera with dual detectors (Picker model Prism 2000). Abnormal findings included heterogeneity, defects and hot spots on Technegas images and on retention images taken 3 minutes after133Xe gas washout. In 2 of 20 patients, the degree of abnormal findings on Technegas images depended on the area of133Xe gas retention in the washout phase. In 3 patients, the degrees of abnormal findings on both Technegas SPECT and133Xe gas dynamic SPECT images were equivalent. In the remaining 15 patients, more detailed findings and a greater area were shown by Technegas SPECT than133Xe gas dynamic SPECT. We conclude that in patients with pulmonary emphysema Technegas SPECT can demonstrate ventilation impairment more easily than133Xe gas dynamic SPECT. [ABSTRACT FROM AUTHOR]

Pulmonary emphysema can be diagnosed easily by X-ray CT (CT) as a low attenuation area. Recently Tc-99m-Technegas (Technegas) has been used for ventilation scintigraphy. The present study was undertaken to assess the usefulness of planar and SPECT images by using Technegas scintigraphy in patients with pulmonary emphysema. Technegas scintigraphy, CT and pulmonary function tests were performed in 20 patients (males, age 32–78 years). We classified the findings of Technegas images into 4 grades. Comparing planar and SPECT images of Technegas, more detailed findings were shown by SPECT than by planar images in mild cases (6 cases, 30%). In more severe cases, findings of SPECT and planar images were equivalent (14 cases, 70%). The degree of abnormal findings obtained by SPECT was equivalent to that obtained by CT in severe cases (6 cases, 30%). SPECT should be excluded in advanced stages as indicated by planar images. [ABSTRACT FROM AUTHOR]

In this study, we report plasma hepatocyte growth factor (HGF) levels during cancer chemotherapy and the relationship between plasma HGF and pneumonia onset in 19 patients with primary lung cancer. These measurements are compared with patients plasma HGF levels prior to cancer chemotherapy, as well as with plasma HGF levels in 23 control patients with silicosis. Plasma HGF, as well as peripheral white blood cells and C-reactive protein, were measured every three days during cancer chemotherapy. In the eight patients who did not develop pneumonia, plasma HGF remained within normal limits. In the 11 patients who did develop pneumonia, however, HGF exceeded normal limits three days after the onset of infection. Further-more, the maximum HGF concentration was significantly higher in the 11 patients with pneumonia (0.62±0.12 ng/mL) than in the eight without complications (0.24±0.02, P<0.01), in the entire lung cancer group prior to chemotherapy (0.17±0.01, P<0.01), or in the 23 control patients with silicosis (0.22±0.01, P<0.01). This suggests that HGF may play a role in repairing lung damage due to pneumonia. [ABSTRACT FROM AUTHOR]

The article presents the case of a 44-year-old man who was diagnosed with distal ulcerative colitis (UC) when he had hematochezia at age 34. Colonoscopy revealed the appendiceal orifice inflammation (AOI) with reddish and friable mucosa and mucopus. Clinical evidence has shown the protective role of appendicectomy on UC.

The article presents the case of a 70-year-old man who was referred to an emergency unit for haematochezia of two weeks duration. It cites a result of the physical examination, showing a localized tenderness in the left lower quadrant without rebound. It adds that a plain abdominal radiography showed the sigmoid colon with foreshortening and a loss of haustra, indicating active ulcerative colitis.