Recurrent aspiration pneumonia precipitated by obstructive sleep apnea

ObjectiveThe clearance of the pharynx by deglutition and the respiratory phase patterns associated with deglutition are important in protecting airways and lungs against aspiration. The deglutition and respiratory phase patterns during sleep in patients (without swallowing disorders while awake) with obstructive sleep apnea (OSA) precipitating recurrent intractable aspiration pneumonia were investigated.MethodsAfter videoendoscopic and videofluorographic examinations of swallowing showed subjects had no swallowing disorders while awake, two adults with recurrent intractable aspiration pneumonia precipitated by severe OSA were examined via time-matched digital recordings of polysomnography and surface electromyography of the muscles (thyrohyoid and suprahyoid muscles) related to swallowing and compared with the same patients before and under CPAP therapy.ResultsCPAP therapy cured recurrent intractable aspiration pneumonia. Swallows following and/or followed by inspiration (uncoordinated deglutition with respiration), which were frequently observed before CPAP therapy, were markedly reduced under CPAP therapy. On the other hand, swallows following and/or followed by expiration (coordinated deglutition with respiration) markedly increased under CPAP therapy. Deglutition was related to the sleep stage. The deeper the sleep stage, the lower the deglutition frequency. Before and under CPAP therapy, swallowing was infrequent and absent for long periods. However, respiratory phase patterns associated with sleep-related deglutition in patients with OSA under CPAP therapy markedly improved.ConclusionsIn patients (without swallowing disorders while awake) with OSA precipitating recurrent intractable aspiration pneumonia, the high rate of uncoordinated deglutition with respiration (swallows following and/or followed by inspiration) during sleep were markedly reduced and the rate of coordinated deglutition with respiration (swallows following and/or followed by expiration) was markedly increased under CPAP therapy.Sleep-related deglutition and respiratory phase patterns are likely to adversely influence aspiration pneumonia in patients with OSA. CPAP therapy improved not only apnea-hypopnea during sleep and sleep quality but also sleep-related deglutition, especially respiratory phase patterns associated with deglutition in patients with OSA. CPAP therapy may decrease the risk of aspiration and greatly improve aspiration-related diseases such as aspiration pneumonia.     

Analysis of systemic and airway inflammation in obstructive sleep apnea

Purpose

The presence of both systemic and airway inflammation has been suggested in obstructive sleep apnea (OSA) by increased levels of inflammatory biomarkers in the circulation and respiratory specimens. We aimed to investigate the relationship between systemic and airway inflammation in OSA.

Methods

This study was conducted by simultaneously measuring various biomarkers both in serum and induced sputum of 43 patients. We compared the relationships of these biomarker levels with polysomnographic data and obesity measurements and also investigated their interrelationships between systemic and local compartments. We also assessed the relation of inflammatory markers with proximal airway resistance measured by impulse oscillometry.

Results

In multiple regression analyses, each measured serum biomarker [leptin, interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)] significantly correlated with waist circumference or fat area determined by computed tomography. In contrast, regarding airway inflammation, sputum IL-6, IL-8, TNF-α, and VEGF significantly correlated with OSA severity as indicated by the respiratory disturbance index or oxygen desaturation indices. Sputum IL-6, IL-8, TNF-α, and VEGF were significantly related to sputum neutrophil number, and sputum IL-8 and TNF-α were related to proximal airway resistance independently of body mass index. There were no significant interrelationships between the same biomarkers in serum and induced sputum.

Conclusions

Systemic and airway inflammation in OSA might be differently regulated by OSA itself and comorbid obesity, depending on the type of cytokine. Although we did not find apparent interrelationships between systemic and local compartments, further studies are needed to clarify this concept.     

Bladder-Sparing Extended Resection of Locally Advanced Rectal Cancer Involving the Prostate and Seminal Vesicles

Purpose Total pelvic exenteration (TPE) is the standard procedure for locally advanced rectal cancer involving the prostate and seminal vesicles. We evaluated the feasibility of bladder-sparing surgery as an alternative to TPE. Methods Eleven patients with advanced primary or recurrent rectal cancer involving the prostate or seminal vesicles, or both, underwent bladder-sparing extended colorectal resection with radical prostatectomy. The procedures performed were abdominoperineal resection (APR) with prostatectomy (n = 6), colorectal resection using intersphincteric resection combined with prostatectomy (n = 4), and abdominoperineal tumor resection with prostatectomy (n = 1). Local control and urinary and anal function were evaluated postoperatively. Results Cysto-urethral anastomosis (CUA) was performed in seven patients and catheter-cystostomy was performed in four patients. Coloanal or colo-anal canal anastomosis was also performed in four patients. There was no mortality, and the morbidity rate was 38%. All patients underwent complete resection with negative surgical margins. After a median follow-up period of 26 months there was no sign of local recurrence, and ten patients were alive without disease, although distant metastases were found in three patients. Five patients had satisfactory voiding function after CUA, and three had satisfactory evacuation after intersphincteric resection (ISR). Conclusion These bladder-sparing procedures allow conservative surgery to be performed in selected patients with advanced rectal cancer involving the prostate or seminal vesicles, without compromising local control.     

Effect of FTY720 in rat small bowel transplantation: apoptosis of crypt cells and lymphocytes in gut-associated lymphoid tissues

AIM: We investigated the extent of apoptosis in crypt cells and Peyer's patches (PPs) during small bowel allograft rejection in rats to examine the effect of FTY720 during rejection. METHODS: Orthotopic small bowel transplantations (SBTs) were performed from BN to LEW rats. Isografted animals served as controls. Three groups of SBT animals were studied on days 3, 5, and 7 after operation: isograft, untreated allograft, allograft with FTY720. FTY720 was orally administered by gavage (1 mg/kg/d) to allograft recipients on 7 consecutive days. Cryostat sections were prepared from grafts, including PPs. An in situ end-labeling (ISEL) technique was used to detect apoptotic cells. Indirect immunoperoxidase staining was also performed using monoclonal antibodies against rat Fas/Fas-L. RESULTS: Graft survival was prolonged in the FTY720-treated group. The number of ISEL-positive enterocytes in the allografts increased significantly on days 3, 5, and 7 compared with the isograft group. In the FTY720-treated group, the number of ISEL-positive enterocytes in the allografts was down-regulated significantly on days 3, 5, and 7 compared with untreated allograft group. In the PPs, the number of ISEL-positive mononuclear cells increased significantly in the allografts compared with the isograft group. In the FTY720-treated groups, the number of ISEL-positive mononuclear cells were down-regulated significantly in the allografts compared with the untreated allograft group. The number of Fas/FasL-positive enterocytes were increased significantly in allografts compared with isograft group. In FTY720-treated groups, the number of Fas/FasL-positive enterocytes were down-regulated significantly on day 7 compared with the untreated allograft group. In the PPs, Fas/FasL-positive mononuclear cells also increased significantly on day 7 in the allografts compared with isografts. In the FTY720-treated groups, Fas/FasL-positive mononuclear cells were down-regulated significantly in the allografts compared with the untreated allograft group. CONCLUSIONS: The number of apoptotic enterocytes, lymphocytes, and Fas/FasL-positive lymphocytes increased during small bowel graft rejection. FTY720 prevented up-regulation of the number of apoptotic enterocytes, lymphocytes, and Fas/FasL-positive lymphocytes while also prolonging small bowel allograft survival.     

Diverse biological activities of fermented pine seed shell extract

Intraperitoneal administration of fermented pine seed shell extract (PSSE) (up to 2 g/kg) induced no apparent acute toxicity to mice. Pretreatment of mice with PSSE protected them from the lethality of Escherichia coli infection. PSSE showed a very weak cytotoxic activity against both normal and tumor cells and no anti-HIV activity, but stimulated the mouse macrophage-like Raw 264.7 cells to produce nitric oxide (NO) and citrulline. ESR spectroscopy showed that PSSE produced no detectable radicals, but effectively scavenged O2- (generated by the hypoxanthine-xanthine oxidase reaction), hydroxyl radical (generated by the Fenton reaction) and NO (generated by NOC-7). Comparison of PSSE with other natural products, such as polyphenols and vitamins, further confirmed the close association between radical intensity and radical scavenging activity, suggesting the bimodal action of natural products. Although the biological activities of PSSE were relatively lower than those of other natural products, the present study suggests the possible medicinal efficacy of PSSE.     

An 80-year-old woman with non-resectable pulmonary adenocarcinoma that responded to concomitant use of gemcitabine and vinorelbine

An 80-year-old female with non-resectable pulmonary adenocarcinoma was treated with five courses of chemotherapy consisting of gemcitabine (GEM) 1,000 mg/m2 plus vinorelbine (VNR) 25 mg/m2 (days 1 and 8, every 4 weeks). A partial response (PR) was achieved, and her complaints abated and quality of life (QOL) improved. Although gastro-intestinal symptoms and bone marrow suppression were observed as side effects, they were within a tolerable range and did not interfere with the therapy. Anti-cancer chemotherapy for non-resectable lung cancer might be worth consideration even for elderly patients more than 80 years of age.     

Natural history of human prostate gland: Morphometric and histopathological analysis of Japanese men

BACKGROUND: To clarify the pathology of the development of prostatic disorders such as inflammation, cancer, and hyperplasia, we compared histopathological findings of the prostate according to age group. METHODS: Whole-mount sections of prostates were used to assess the relationship between age and prostate weight (n=962), prostate histological composition in the transition zone (TZ) and in the peripheral zone (PZ) (n=68), prostate histopathological findings by zone (n=102), and comparison of latent tumor development by age group (n=1,815). RESULTS: A rapid increase in prostate weight from birth to the 20s was followed by a slow rise thereafter. Volume increases (P<0.01) were observed in all components of glandular epithelium, glandular lumen, and stroma in the TZ from the 40s to 70s inclusive. In the PZ, the epithelial and stromal volumes tended to decrease in an age-dependent manner (P<0.05). Calculi and lymphocyte infiltration were detected at a relatively early age, with a tendency towards an age-dependent increase. Glandular dilation and nodular hyperplasia were noted first in the 30s group, also with a tendency towards age-dependent increase. Latent tumors were first detected in the 30s group (5.6%), and slowly increased thereafter. CONCLUSIONS: There was an age-dependent trend towards prostate glandular dilation and prostate enlargement with inflammation. It was demonstrated that tumor and hyperplasia have a long natural history, usually starting in the fourth decade of life, accompanied by dynamic changes with age in glandular tissue composition as well as cell proliferation activity.     

Rectovaginal fistulas after rectal cancer surgery: Incidence and operative repair by gluteal-fold flap repair

BACKGROUND: We investigated the correlation between operative procedures for rectal carcinoma and postoperative rectovaginal fistulas (RVF), and treatment for RVF. METHODS: The medical records of 161 female patients with rectal carcinoma were examined retrospectively with respect to the cause, incidence, and methods of treatment for RVF occurring after rectal cancer operations, and to the outcomes of gluteal-fold flap repairs for RVF. RESULTS: Of the 161 patients, 16 developed RVF clinically. The incidence of RVF was significantly higher in patients who were anastomosed by the double stapling technique (DST) and had concomitant resection of the vaginal wall. No statistical difference was found between the established diverting ostomy group and the no-stoma group. Six patients recovered by the establishment of a diverting ostomy only. The gluteal-fold flap technique was performed for 5 patients. No RVF recurrences were noted in these 5 patients. CONCLUSIONS: The incidence of RVF was higher in the patients who were anastomosed by DST or had concomitant resection of the vaginal wall. Although some RVFs heal with only fecal diversion, for patients in whom RVF is caused by involvement of the vaginal wall in the circular staple or intersphincteric resection, good results are obtained with the gluteal-fold flap repair technique.     

The Effect of a Novel Immunosuppressant, FTY720, in Mice Without Secondary Lymphoid Organs

Purpose FTY720 is a novel immunosuppressive agent that is thought to reduce the number of peripheral blood lymphocytes (PBL) by directing them toward secondary lymphoid organs such as the lymph nodes and Peyer’s patches. We studied the effects of FTY720 on aly/aly mice that do not have either lymph nodes or Peyer’s patches, as well as on splenectomized aly/aly mice.Methods FTY720 was orally administered by gavage (1 mg/kg) to aly/aly mice as well as to aly/+ mice with and without a splenectomy on 14 consecutive days. The number of lymphocytes was then counted using True Cell beads and flow cytometry. The number of B220-, CD3-, and CD4-positive cells was also determined. In addition, skin grafts from C3H donor mice were performed on these mice.Results FTY720 was effective in significantly reducing the total lymphocyte count as well as the B220-, CD3-, and CD4-positive subtypes in the peripheral blood of aly/+ mice as well as in aly/aly mice with and without a splenectomy. While we did observe allograft skin graft rejection in both the aly/+ mice as well as the aly/aly mice recipients and splenectomized aly/aly mice, the graft survival was prolonged in all groups. The skin allografts treated by FTY720 thus demonstrated fewer lymphocytic cells and less infiltration of CD4-positive cells.Conclusions The administration of FTY720 to mice without lymph nodes, Peyer’s patches, or spleens still results in peripheral lymphopenia. In all groups, FTY720 was found to prevent the infiltration of CD4-positive cells in skin allografts while also prolonging skin allograft survival. The fate of these lymphocytes, however, is unclear.