Long and Short Sleep Duration and Physical Frailty in Community-Dwelling Older Adults.

OBJECTIVE: The objective of this study was to investigate whether older adults who have a particularly long sleep duration are likely to exhibit physical frailty, similar to those with a particularly short sleep duration. DESIGN: Cross-sectional study. SETTING: The National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes. PARTICIPANTS: A total of 9,824 older adults (mean age: 73.6 ± 5.5 years, 4,812 men and 5,012 women) met the entry criteria for this study. MEASUREMENTS: We divided the participants into three groups according to self-reported sleep duration (Short: ≤6 h, Mid: 6.1-8.9 h (control), Long: ≥ 9 h). Physical frailty was characterized based on the criteria from the Cardiovascular Health Study. Multinomial logistic regression analysis was performed to evaluate the effect of sleep duration on physical frailty by sex. RESULTS: Among all participants, the prevalence of physical frailty was higher in the Short (10.5%) and Long (17.9%) groups than in the Mid (7.4%) group (p < 0.001). Multinomial logistic regression analysis showed that both Short and Long groups had a significantly higher odds ratio (OR) for physical frailty than the Mid group [Short: OR 1.53, 95% confidence interval (CI) 1.26-1.87; Long: OR 2.39, 95% CI 1.90-3.00], even after adjusting for age, educational level, number of medications, body mass index, Mini Mental State Examination score, current smoking and alcohol habits, self-perceived health, and medical history. CONCLUSION: Both long and short sleep durations were associated with physical frailty. Further studies are required to confirm the effect of sleep duration on the incidence or worsening of physical frailty in older adults.

Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease.

BACKGROUND: Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. METHODS: ENSCs isolated from the ganglionic intestine of Ednrb(-/-) mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb(-/-) colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb(-/-) rectum in vivo. KEY RESULTS: HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb(-/-) aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb(-/-) HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. CONCLUSIONS & INFERENCES: ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies.

Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease.

BACKGROUND: Transplantation of enteric neural stem cells (ENSC) holds promise as a potential therapy for enteric neuropathies, including Hirschsprung disease. Delivery of transplantable cells via laparotomy has been described, but we propose a novel, minimally invasive endoscopic method of cell delivery. METHODS: Enteric neural stem cells for transplantation were cultured from dissociated gut of postnatal donor mice. Twelve recipient mice, including Ednrb(-/-) mice with distal colonic aganglionosis, underwent colonoscopic injection of ENSC under direct vision using a 30-gauge Hamilton needle passed through a rigid cystoureteroscope. Cell engraftment, survival, and neuroglial differentiation were studied 1-4 weeks after the procedure. KEY RESULTS: All recipient mice tolerated the procedure without complications and survived to sacrifice. Transplanted cells were found within the colonic wall in 9 of 12 recipient mice with differentiation into enteric neurons and glia. CONCLUSIONS & INFERENCES: Endoscopic injection of ENSC is a safe and reliable method for cell delivery, and can be used to deliver a large number of cells to a specific area of disease. This minimally invasive endoscopic approach may prove beneficial to future human applications of cell therapy for neurointestinal disease.

Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies.

BACKGROUND Most enteric neurones arise from neural crest cells that originate in the post-otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung's disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin-3 (Et-3). METHODS Co-cultures were used to examine the ability of enteric neural crest-derived cells (ENCCs) from E11.5 mouse gut to colonize a variety of recipient hindguts. KEY RESULTS Enteric neural crest-derived cells migrated and gave rise to neurones in E14.5 and E16.5 aneural colon in which the external muscle layers had differentiated, but they did not migrate as far as in younger colon. There was no evidence of altered ENCC proliferation, cell death or neuronal differentiation in older recipient explants. Enteric neural crest-derived cells failed to enter most recipient E14.5 and E16.5 colon explants already containing enteric neurones, and the few that did showed very limited migration. Finally, ENCCs migrated a shorter distance and a higher proportion expressed the pan-neuronal marker, Hu, in recipient E11.5 Et-3(-/-) colon compared to wild-type recipient colon. CONCLUSIONS & INFERENCES Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration.

[Right lung cancer with right aortic arch].

An abnormal shadow was detected on chest X-ray mass screening in an asymptomatic 63-year-old man. The further examinations revealed the shadow to be primary lung cancer (Rt. S6. adenocarcinoma, cT2N0M0, c-stage IB) with right aortic arch. We used 3 dimentional-computed tomography (3D-CT) to assess an anatomical feature of vessels in detail. The right lower lobectomy and the dissection of medi astinal lymph nodes was performed. We confirmed no abnormal anatomy of pulmonary artery and vein at surgery, and it was possible to perform right lower lobectomy with the common procedure. Since lymph node was found by intraopetrative pathological examination, since no metastasis from interlobar to subcarinal lymph node was found, we did not perform dissection of upper mediastinal dissection, which was equivalent to ND2a lymph nodes dissection of the left lung cancer in General Rule for Clinical and Pathological Record of Lung Cancer. The patient with right aortic arch is known to have variant anatomy of other intrathoracic vessels occasionally. 3D-CT was quite useful in assessing anatomical feature, and enabled us to perform safe operation.

Usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastasis from lung cancer.

Ninety-one lung cancer patients were evaluated to determine the usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastases and also to investigate their clinical usefulness as an adjunct to bone scintigraphy. Both bone resorption markers, ICTP and fDPD, and bone formation markers, Al-p, BAL, PICP and BGP, were evaluated in 47 patients with and 44 without bone metastasis. The patients with bone metastasis were classified according to the bone metastatic burden, and they were also separately classified into groups according to the course of the bone metastasis. ICTP, fDPD, Al-p and BAL were significantly elevated (P < 0.001) in patients with bone metastasis, but PICP and BGP were not. Receiver-operating characteristic (ROC) curves of these markers revealed that ICTP was most highly correlated with the diagnosis of bone metastasis. The sensitivity of ICTP (71.4%) and fDPD (61.0%) were good with high specificity. T scores of ICTP, fDPD and BAL tended to be higher at higher grades of bone metastasis. T-scores of ICTP, fDPD and BAL were elevated in the newly diagnosed cases and progressed cases, but the T-scores of ICTP and fDPD in those cases were higher than that of BAL. In the follow-up study, ICTP was well correlated with uncontrolled or controlled bone metastasis. Thus, bone resorption markers, especially ICTP, could be a good indicator of the progression and multiplicity of disease, and it could help in the follow-up and in the monitoring of therapy for bone metastasis from lung cancer.

[Perioperative management of patients with Meigs syndrome].

We report our perioperative management of three cases of Meigs syndrome. The major pre-operative problems in Meigs syndrome are physical trouble caused by giant mass in peritoneal space, respiratory distress, and poor nutrition. These problems must be settled before the operation. The important points in the pre-operative management are 1) respiratory care employing the intermittent positive pressure breathing (IPPB) and the pleural effusion drainage, and 2) the correction of intravascular volume and the concentration of albumin and hemoglobin by transfusion of massive lactated Ringer solution and albumin solution and/or whole blood when they are necessary. During the operation, the epidural anesthesia under spontaneous breathing is the best method of anesthesia. According to circumstances, we adopt the intra-tracheal intubation with continuous positive airway pressure breathing (CPAP). We can generally deal with excessive bleeding by transfusion of lactated Ringer solution and plasma expander, during the first half of operation. By the end of the operation, however, the correction of the concentration of albumin and hemoglobin must be made by the fresh frozen plasma and blood transfusion. After the operation, we use epidural analgesia to control the postoperative pain. We have succeeded in the treatment of three cases of Meigs syndrome owing to our perioperative management as described above.

Effects of progesterone and estradiol on aminopeptidase A (AAP) and leucine aminopeptidase (LAP) activities in the pregnancy serum and placenta of the rat.

We investigated the effects of estradiol and progesterone on placental aminopeptidase A and leucine aminopeptidase activities in pregnant rats. Estradiol (0.5, 1.0 and 2 mg/day) plus progesterone (5, 10 and 20 mg/day) was given for five days starting from the 16th day. Changes in both enzyme activities in the serum, placental cytosol and microsome caused by the steroids were analyzed. Aminopeptidase A activities in all three compartments and leucine aminopeptidase activities in the serum and cytosol were stimulated by estradiol (1.0 mg/day) plus progesterone (10 mg/day). Since we previously found that the placental aminopeptidases degrade peptide hormones, our present study suggests that steroids effect the metabolism of peptide hormones of fetal and/or maternal origin.