Inhibition of neutrophil elastase reduces lung injury and bacterial count in hamsters

Neutrophil elastase (NE) has been recognized as a double-edge sword as it can be both host-defensive and pro-inflammatory depending on its tissue level and microenvironment. The present study was designed to examine whether inhibition of NE activity by sivelestat, a specific NE inhibitor with low cellular permeability, is beneficial for acute lung injury induced by Streptococcus pneumoniae in hamsters. Intratracheal inoculation of live S. pneumoniae (1.5 x 10(7) CFU/Lung) into hamsters caused acute lung injury characterized by an increase in lung alveolar permeability and leukocytes accumulation in the lungs. These pathophysiological changes, which were associated with elevation of NE activity in the bronchoalveolar lavage fluid (BALF), were transient but remained high 4-22 h post-bacterial inoculation. Intravenous infusion of sivelestat at 3mg/kg/h 0-22 h after bacterial inoculation reduced the increase in NE activity and lung alveolar permeability, as indicated by leakage of pre-injected human serum albumin into BALF, without affecting the number of leukocytes in BALF and lung interstitial tissue. Interestingly, the number of bacteria in BALF and lung interstitial tissue was also reduced by sivelestat to less than 10% of the control values. Furthermore, S. pneumoniae-induced decrease in the level of surfactant protein D (SP-D), a protein that protects against bacterial infection, was preserved by sivelestat treatment with a significant negative correlation between NE activity and SP-D content in BALF. These results suggest that sivelestat is beneficial in acute lung injury associated with lung bacterial infection and that this inhibitor rather decreases infection by preserving host defense system.     

ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1‐RUNX1T1 and associated with a better prognosis

ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0–17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1‐RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event‐free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild‐type (5‐year OS, 75% vs. 100% vs. 91% and 5‐year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously.     

Chronic obstructive pulmonary disease (COPD) burden in Japan--confronting COPD Japan survey

To grasp the burden and management status of COPD in Japan, a large telephone survey was conducted. In initial screening 400 individuals > or =45 years were identified as either having been given a diagnosis of COPD or fulfilling criteria for their respiratory-related symptoms and smoking history (baseline population) and they were recruited for a detailed investigation (interview sample). They were asked about demographic information, exacerbation, impact of COPD on daily life, and management and treatment. Of the 400 interview samples, 209 subjects (52%) had a diagnosis of COPD, and the remaining 191 ones (48%) were not, retrospectively. It was confirmed that proportions of a current smoker in the COPD (35.4%) and non-COPD (35.6%) groups were almost at the same level. The use of inhaled bronchodilators, recommended by guidelines in 157 treated subjects, was 16% or less, whereas respiratory conditions affected daily activities in 70% of all the subjects. In conclusion, COPD in Japanese subjects significantly affects daily life yet is undiagnosed; there is a need to improve COPD diagnosis and management by general practitioners through disseminating guidelines for diagnosis, management, and prevention of COPD in Japan.     

Effects of parity and gestational age on second-trimester induction-abortion interval in combination with osmotic dilators and gemeprost

BackgroundThe true prognostic factors for induced medical abortion are unknown. We sought to investigate the effects of a patient's obstetric parameters on the induction–abortion interval in second-trimester medical abortion.Study DesignWe studied 216 consecutive women. Pregnancy was terminated with cervical preparation using osmotic dilators followed by 1 mg vaginal gemeprost administered every 3 h for a maximum of five doses in the first 24 h. All variables are expressed in categorical form (parity, gestational age, maternal age and body mass index) and analyzed by the Cox proportional hazards model.ResultsParity ≥3 was associated with a shorter duration of the induction–abortion interval (adjusted hazards ratio 1.96; 95% confidence interval 1.13–3.40). A gestational age ≥16 weeks was associated with a longer duration of the induction–abortion interval (0.71; 0.52–0.98). No significant association was found in maternal age and body mass index.ConclusionsIn combination with osmotic dilators and gemeprost, gestational age and parity are independent factors that affected the induction to abortion interval of second-trimester medical abortion.     

A great Brunner's gland adenoma of the duodenal bulb

Summary The occurrence of Brunner's gland adenoma in the duodenum is infrequent. The authors report a case of great Brunner's gland adenoma of the duodenal bulb, which is of interest because of its great size (8.5×4.5 cm) and the negative result of the endoscopic biopsy. Endoscopy has improved the diagnosis of the duodenal tumors; however, traditional endoscopic pinching biopsy does not always make a histological diagnosis. In our case, the endoscopic biopsy was negative because the tumor was located completely in the submucosa and the biopsy forceps was unable to reach to the tumor tissue.     

Successful Low-Dose Chemotherapy Using Vinblastine and Methotrexate for the Treatment of an Ileoanal Pouch Mesenteric Desmoid Tumor: Report of a Case

The purpose of this report was to describe the first known case of ileoanal pouch salvage by a low-dose regimen of vinblastine and methotrexate chemotherapy for the treatment of desmoid tumor arising from the mesentery of the ileoanal pouch in a patient who had undergone ileal pouch-anal anastomosis for familial adenomatous polyposis. Mesenteric desmoid tumor involving the ileoanal pouch in a 28-year-old female was treated with vinblastine and methotrexate biweekly for 12 months and monthly for 12 months in an outpatient unit. The desmoid tumor response to the treatment was assessed at routine intervals by physical examination and magnetic resonance imaging. Desmoid tumor was successfully treated with a low-dose regimen of vinblastine and methotrexate chemotherapy without significant side effects, and function of the ileoanal pouch was fully preserved. Magnetic resonance imaging showed a decrease in desmoid tumor size and cellularity, and changes consistent with fibrosis. This is a unique case highlighting the possibility of ileoanal pouch salvage by low-dose combination chemotherapy using vinblastine and methotrexate in a familial adenomatous polyposis patient with mesenteric desmoid tumor.     

Clinical effectiveness of measurement of serum total human chorionic gonadotropin for diagnosis and management of testicular seminomatous germ cell tumor

Serum free-beta human chorionic gonadotropin (fbhCG) has been used for the diagnosis and management of testicular tumors for many years in Japan, while the measurement of serum hCG is widely used in the world. There have been reports of false-positive cases with serum fbhCG and due care must be taken in order not to take the wrong treatment strategy. Serum hCG is said to be more useful in the diagnosis and management of non-seminoma than serum fbhGC. Because of the false-positive issue with serum fbhCG, however, we consider it appropriate to use serum hCG for measurement even in seminoma. We simultaneously measured serum hCG and serum fbhCG in 25 cases of seminoma in order to evaluate the usefulness of hCG assay in the diagnosis and management of seminoma. In the measurements, we found 5 false-positive cases (20%) with serum fbhCG. The diagnostic sensitivity of the 20 cases with the exception of the 5 false-positive cases was 16 cases (80%) and 14 cases (70%) with serum hCG and serum fbhCG, respectively. We conclude that serum hCG is more reliable and is a useful assay in the diagnosis and management of seminoma, but serum fbhCG is not useful in the diagnosis and management of testicular tumor and its independent measurement should not be used to avoid misleading results.