Laparoscopic repair for internal hernia associated with colostomy: a case report.

A 63-year-old woman was admitted with abdominal pain two months after laparoscopic abdominoperineal resection for rectal cancer. Computed tomography revealed dilated small intestine had passed through a defect between the lifted sigmoid colon and abdominal wall. She was diagnosed with small bowel obstruction without strangulation due to internal hernia and managed nonoperatively based on her wish. Recurrence of intestinal obstruction occurred for which curative surgery was performed laparoscopically. The herniated intestine was restored to the normal position, and the hernia orifice was closed using barbed suture, on laparoscopic management. Internal hernia is a rare complication after colostomy that requires surgical management. Although laparoscopic approach on re-operation is difficult, laparoscopic surgery may be suitable for patients with IHAC in terms of required less use of adhesiolysis.

Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice.

BACKGROUND: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been clarified. We previously demonstrated DNA damage in murine bronchioles in the early stages of bleomycin-induced pulmonary fibrosis that subsequently extended to alveolar cells at the advanced stages of the disease. Club cells are progenitor cells for bronchioles and are known to play protective roles against lung inflammation and damage. The aim of the present study was to elucidate the role of club cells in the development of pulmonary fibrosis. METHODS: C57BL/6 J mice received naphthalene intraperitoneally on day -2 to deplete club cells and were given intratracheal bleomycin or a vehicle on day 0. Lung tissues were obtained on days 1, 7, and 14, and bronchoalveolar lavage was performed on day 14. Bronchiolar epithelial cells sampled by laser capture microdissection were analyzed by gene expression microarray analysis on day 14. RESULTS: Club cell depletion induced by naphthalene protected mice from bleomycin-induced lung injury and fibrosis. Bleomycin-triggered bronchiolar TGF-ß1 expression was reduced. Gene expression microarray analysis revealed that genes associated with inflammatory response and chemokine activity were downregulated in the bleomycin-injured bronchiolar epithelium with club cell injury compared to that in bronchiolar epithelium without cell injury. CONCLUSIONS: Club cells are involved in the development of lung injury and fibrosis.

Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice.

Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice. C57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/kg) was orally administered to mice from day -1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14. Sivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.

Amphiregulin suppresses epithelial cell apoptosis in lipopolysaccharide-induced lung injury in mice.

BACKGROUND AND OBJECTIVE: As a member of the epidermal growth factor family, amphiregulin contributes to the regulation of cell proliferation. Amphiregulin was reported to be upregulated in damaged lung tissues in patients with chronic obstructive pulmonary disease and asthma and in lung epithelial cells in a ventilator-associated lung injury model. In this study, we investigated the effect of amphiregulin on lipopolysaccharide (LPS)-induced acute lung injury in mice. METHODS: Acute lung injury was induced by intranasal instillation of LPS in female C57BL/6 mice, and the mice were given intraperitoneal injections of recombinant amphiregulin or phosphate-buffered saline 6 and 0.5 h before and 3 h after LPS instillation. The effect of amphiregulin on apoptosis and apoptotic pathways in a murine lung alveolar type II epithelial cell line (LA-4 cells) were examined using flow cytometry and western blotting, respectively. RESULTS: Recombinant amphiregulin suppressed epithelial cell apoptosis in LPS-induced lung injury in mice. Western blotting revealed that amphiregulin suppressed epithelial cell apoptosis by inhibiting caspase-8 activity. CONCLUSION: Amphiregulin signaling may be a therapeutic target for LPS-induced lung injury treatment through its prevention of epithelial cell apoptosis.

[Effects of parental parenting attitudes on adolescents' socialization via adolescents' perceived parenting].

The domain-specific approach to socialization has classified socialization mechanisms into several domains, including the protection and control domains, and postulates that parent­child interactions that promote socialization in each domain are different. However, there are few empirical investigations of the domain­specific approach. This study examined whether parental parenting attitudes affected early adolescents' empathy, including empathic concern and perspective taking, and social cognitive biases, including cognitive distortion and general beliefs about aggression, through the mediation of adolescents' perceptions. Junior high school students and their parents (N = 448) completed a questionnaire. Results of structural equation modeling indicated (a) parental acceptance and control increased empathy via adolescents' perceived acceptance and control, (b) parental acceptance and control decreased social cognitive biases via adolescents' perceived acceptance and control, and (c) parental control directly increased empathy. In addition, multiple group analyses indicated the validity of gender- and age-invariant models. These findings suggest that parental parenting attitudes are essential for appropriate socialization during early adolescence.

Retrospective analysis of nursing and healthcare-associated pneumonia: analysis of adverse prognostic factors and validity of the selection criteria.

BACKGROUND: Nursing and healthcare-associated pneumonia (NHCAP) is a relatively new condition that was recently defined by the Japanese Respiratory Society. Previous reports and guidelines have not thoroughly investigated the adverse prognostic factors and validity of the selection criteria for NHCAP. The purpose of this research was to clarify the adverse prognostic factors of NHCAP and investigate the validity of the selection criteria with respect to patient deaths. METHODS: We retrospectively analyzed 418 patients with pneumonia who were admitted to our hospital between January 2009 and December 2011. RESULTS: We analyzed 215 (51.4%) cases of community-acquired pneumonia (CAP) and 203 (48.6%) cases of NHCAP. NHCAP patients were generally older and had poorer performance status (PS), more complications, and higher levels of mortality than CAP patients. In both groups, the most common causative pathogen was Streptococcus pneumoniae. A multivariate analysis of NHCAP revealed that age ≥ 80 years, oxygen saturation (SpO2) ≤ 90%, and methicillin-resistant Staphylococcus aureus (MRSA) infection to be independent factors associated with mortality. Of the NHCAP selection criteria, a PS ≥ 3 and a hospitalization history within the past 90 days were adverse prognostic factors in the broad community-acquired pneumonia category (CAP+NHCAP), according to a multivariate analysis. Univariate analysis revealed that admission to an extended care facility or nursing home was associated with death. CONCLUSIONS: Our results demonstrated that age ≥ 80 years, SpO2 ≤ 90%, and MRSA infection were adverse prognostic factors for NHCAP patients. Furthermore, we confirmed the validity of the NHCAP selection criteria.

[The attempts and current status of cancer rehabilitation at Osaka Medical College Hospital].

We introduced an attempt at cancer rehabilitation at Osaka Medical College Hospital. We also reported trends in the clinical department that ordered the cancer rehabilitation, and the days needed to consult the rehabilitation department after hospitalization for 1,028 patients who needed rehabilitation from January to June 2012. The number of rehabilitation orders for cancer patients has increased in comparison with the same period during 2009, and the percentage of cancer rehabilitation orders has also increased, both in total and in each clinical department consulted. In addition, clinical departments that introduced a rehabilitation schedule along with their treatments ordered cancer rehabilitations much earlier than those departments without such a schedule. In future, to start cancer rehabilitation at an earlier stage, we should endeavor to create awareness of the importance of cancer rehabilitation and the introduction of a rehabilitation schedule along with cancer treatments.

A Case of Follicular Bronchiolitis as the Histological Counterpart to Nodular Opacities in Bronchiectatic Mycobacterium avium Complex Disease.

Here we report the case of a 72-year-old woman with nodular bronchiectatic Mycobacterium avium complex (MAC) disease. Chest computed tomography on admission revealed multiple micronodular and branching opacities in both lobes with segmental distribution; bronchiectasis and bronchial wall thickening were observed in the middle lobe and lingula. The patient consented to and underwent thoracoscopic lung biopsy; epithelioid granulomas were occasionally observed, but follicular bronchiolitis was widespread. While bronchial lesions from nontuberculous mycobacterial infection generally present as epitheliod granulomas, the present case suggests that follicular bronchiolitis can also be a histological counterpart to nodular opacities in nodular bronchiectatic MAC disease.

Congenital cystic adenomatoid malformation in adulthood complicated by Mycobacterium celatum infection.

A 25-year-old woman with no underlying disease presented with a large fluid-filled cavitary lesion in the right lung. Mycobacterium celatum was isolated from the cavitary fluid, and treatment with ethambutol, rifampicin, and clarithromycin was initiated. After 4 months of treatment, right lower pulmonary lobectomy was performed. Histological examination confirmed M. celatum infection as well as concurrent congenital cystic adenomatoid malformation (CCAM). M. celatum has been implicated in opportunistic infections. This infection, however, was related to underlying CCAM, which resulted in a large cavitary lesion. CCAM diagnosed in adulthood is rare, and is made more challenging by an infectious complication.

EGFR tyrosine kinase inhibition worsens acute lung injury in mice with repairing airway epithelium.

RATIONALE: Epidermal growth factor receptor (EGFR) and its ligands play important roles in the regeneration of damaged epithelium and proliferation of various epithelial tumors. Although the EGFR-tyrosine kinase inhibitor gefitinib is effective against advanced non-small cell lung cancer with EGFR mutations, some patients treated with this agent develop severe acute interstitial pneumonia. Characteristics of patients who develop interstitial pneumonia include older age, smoking history, and preexisting interstitial pneumonia suggesting a connection between airway injury and alveolar dysfunction. OBJECTIVES: The purpose of this study was to investigate the effects of gefitinib on airway repair after injury. METHODS: C57BL/6J mice received intraperitoneally naphthalene at Day 0. Gefitinib (20, 90, or 200 mg/kg) was given daily at Days--1 to 13 after naphthalene administration. Bronchoalveolar lavage fluid and lung tissue were obtained at Days 7 and 14. Terminal bronchial epithelial cells from Days 7 and 14 were retrieved with laser capture microdissection, and gene expression analyzed using microarray. MEASUREMENTS AND MAIN RESULTS: Gefitinib treatment after naphthalene prolonged neutrophil sequestration and worsened acute lung injury. We found 17 genes with more than a threefold increase in bronchiolar epithelial cells from mice treated with 200 mg/kg of gefitinib after naphthalene at Day 14 compared with those treated with naphthalene alone. Up-regulated genes included S100A8, S100A6, and StefinA3. These genes are known to participate in neutrophil sequestration, acute inflammation, and airway remodeling. CONCLUSIONS: EGFR inhibition in repairing airway epithelial cells modulated significant expression of genes involved in the airway microenvironment, prolonged inflammation, and potentiated acute lung injury.

Amphiregulin attenuates bleomycin-induced pneumopathy in mice.

Amphiregulin, an EGF receptor (EGFR) ligand, is essential for epithelial development in various organs. A recent report suggested that amphiregulin acts as a protective factor in a liver injury model. Little is known about the roles of amphiregulin in lung injury and pulmonary fibrosis. The purpose of the present study was to investigate the role of amphiregulin in an experimental model of bleomycin-induced pneumopathy in mice. C57BL/6 mice were administered a bleomycin hydrochloride solution intratracheally. Recombinant human amphiregulin was injected intraperitoneally at 6, 8, 10, and 12 days after the bleomycin instillation. The grades of inflammation and fibrosis were assessed histologically and biochemically, and the numbers of apoptotic cells were counted after TdT-mediated dUTP nick end labeling (TUNEL) staining in the lung tissues. We also examined downstream survival signals of EGFR, namely phosphorylated Akt and phosphorylated Erk, in lung tissues by Western blotting analysis and immunohistochemistry. Expression of intrinsic amphiregulin was increased in murine lung tissues after bleomycin instillation. Administration of recombinant amphiregulin improved the survival rate and suppressed the degrees of inflammation and fibrosis and the number of TUNEL-positive cells in lung tissues. Amphiregulin treatment enhanced the activation of Akt and Erk in lung epithelial cells. Amphiregulin may play a protective role in bleomycin-induced pneumopathy in mice, probably through the activation of survival signals. Administration of amphiregulin may be a novel therapeutic strategy against lung injury and fibrosis.

[Effects of neighborhood collective efficacy and violence on antisocial behavior: dual mediation of socialization and routine activities].

The authors examined the effects of neighborhood collective efficacy and violence on adolescents' antisocial behavior tendencies by means of the dual mediation of socialization indices (i.e., social information-processing and self regulation) and routine activities. Collective efficacy and violence exposure were assessed by neighborhood "informal social control" and "social cohesion and trust" during the elementary and junior high school years, and the frequency of violence in the community during junior high and high school years. Normative beliefs about aggression, cognitive distortions, social rule appropriateness and self regulation were used to assess both the positive and negative indices of socialization. Routine activities were assessed by the experience in unstructured socializing activities. Antisocial tendencies were assessed by evaluations of the seriousness and past experience of delinquent behaviors. The results of structural equation modeling revealed that the effect of collective efficacy on antisocial tendencies was perfectly mediated by the socialization indices, whereas experienced violence was partly mediated by routine activities. Possible improvements of this dual mediation model were discussed.

Involvement of mast cells in the regulation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteases-1 in 12-O-tetradecanoylphorbolacetate-induced inflammation in mice.

In this study, we investigated the involvement of mast cells in the regulation of matrix metalloproteinase-9 (MMP-9) in 12-O-tetradecanoylphorbolacetate (TPA)-induced inflammation, using mast cell-deficient (W/W(v)) mice and control (+/+) mice. Topical application of TPA to the ears induced acute inflammation, accompanied by mast cell degranulation in +/+ mice, which peaked at 6-12 h. There was no significant difference in ear thickness between the groups until 12 h, but the swelling was greater in W/W(v) mice than +/+ mice at 24-36 h. Western blot analysis revealed that TPA-induced marked increases in levels of proMMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1), which existed as complexes with proMMP-9. The amount of proMMP-9-TIMP-1 complex was markedly smaller in +/+ mice than W/W(v) mice at 6 and 24 h, but had almost returned to control levels in both groups at 48 h. The free form of proMMP-9 was also slightly less abundant in +/+ mice than W/W(v) mice at 6, 24, and 48 h. Gelatin zymographic analysis revealed that levels of the active species of MMP-9 (approximately 74 and 83 kD), as well as free form of proMMP-9, increased time-dependently after the application of TPA and peaked at 24 h in +/+ mice. The 74-kD band was detected only in +/+ mice at 6 h. Our results therefore suggested that during inflammation degranulation of mast cells results in a reduction of the proMMP-9-TIMP-1 complex levels, together with a fall in the amount of free proMMP-9.