The impact of health problems on depression and activities in middle-aged and older adults: age and social interactions as moderators

In this study, we compared the impact of health problems (HPs) on everyday activities and depressive symptoms between middle-aged and older adults. We also examined what type and source of social interactions moderate the noxious effects of HPs. Longitudinal analyses of data with 1,802 Japanese community-dwelling adults indicated that HPs were significantly related to (a) an increase in depressive symptoms among middle-aged adults and (b) a decline in everyday activities among older adults. The former was buffered by emotional family support, whereas the latter (b) was buffered by instrumental family support and, surprisingly, by negative interactions with family. In contrast, social interactions with other friends and acquaintances did not show any moderating effect.     

Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells

Natural killer (NK) cells hold promise for improving the therapeutic potential of allogeneic hematopoietic transplantation, but their effectiveness is limited by inhibitory HLA types. We sought to overcome this intrinsic resistance by transducing CD56+CD3- NK cells with chimeric receptors directed against CD19, a molecule widely expressed by malignant B cells. An abundance of NK cells for transduction was secured by culturing peripheral blood mononuclear cells with K562 cells expressing the NK-stimulatory molecules 4-1BB ligand and interleukin 15, which yielded a median greater than 1000-fold expansion of CD56+CD3- cells at 3 weeks of culture, without T-lymphocyte expansion. Expression of anti-CD19 receptors linked to CD3zeta overcame NK resistance and markedly enhanced NK-cell-mediated killing of leukemic cells. This result was significantly improved by adding the 4-1BB costimulatory molecule to the chimeric anti-CD19-CD3zeta receptor; the cytotoxicity produced by NK cells expressing this construct uniformly exceeded that of NK cells whose signaling receptors lacked 4-1BB, even when natural cytotoxicity was apparent. Addition of 4-1BB was also associated with increased cell activation and production of interferon gamma and granulocyte-macrophage colony-stimulating factor. Our findings indicate that enforced expression of signaling receptors by NK cells might circumvent inhibitory signals, providing a novel means to enhance the effectiveness of allogeneic stem cell transplantation.     

Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy

BACKGROUND: To evaluate the efficacy of endoscopic variceal ligation (EVL) in prophylactic therapy for oesophageal varices, we performed a randomized prospective trial to compare the recurrence of oesophageal varices treated by EVL with those treated by endoscopic injection sclerotherapy. METHODS: Fifty patients with liver cirrhosis were divided into two groups at random, after informed consents were obtained, to receive prophylactic therapy for bleeding of oesophageal varices. Group 1 patients underwent sessions of sclerotherapy with 5% ethanolamine oleate used as the sclerosant. Group 2 patients underwent EVL followed by one or two sessions of sclerotherapy. RESULTS: During the 18 month follow-up period, both the recurrence rate in group 2 (56%) and the incidence of bleeding (20%) were significantly higher compared with group 1 (recurrence rate 16%, bleeding 0%). CONCLUSIONS: This result indicates that EVL is not effective for prophylactic therapy for oesophageal varices in liver cirrhosis.     

Chronic exposure to subtoxic levels of peroxidized lipids suppresses mucosal cell turnover in rat small intestine and reversal by glutathione

Oxidative challenge can compromise intestinal growth and death responses. This study examines the effect of chronic consumption of subtoxic levels of peroxidized lipids on intestinal redox balance and turnover and the effect of glutathione (GSH) supplementation. Male Sprague-Dawley rats were fed standard rat chow or 4% peroxidized menhaden oil chow (2–8 weeks). Intestinal GSH and glutathione disulfide (GSSG), GSH synthetic and redox enzymes as well as proliferative (ornithine decarboxylase, ODC) and apoptotic activities were evaluated. Chronic peroxide intake did not affect overall animal growth, but decreased intestinal GSH/GSSG ratio that directly correlated with decreased GSH and increased GSSG, and suppressed peak circadian ODC activities and postprandial mucosal apoptosis. Supplementation with GSH restored the mucosal GSH/GSSG ratio and abrogated the peroxide-induced suppression of intestinal cell turnover. Collectively, the results show that chronic lipid peroxide consumption induces intestinal GSH redox imbalance that interferes with regulation of enterocyte death and proliferation in vivo. These disruptive effects of lipid peroxides were reversed by GSH supplementation in accordance with the normalization of tissue GSH/GSSG redox balance.     

Comparison of the efficacy of granulocyte and monocyte/macrophage adsorptive apheresis and leukocytapheresis in active ulcerative colitis patients: a prospective randomized study

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurring inflammation of the colorectal mucosa. Recently, cytapheresis has emerged as a new treatment for patients with UC. Removal methods are mainly performed with beads [granulocyte and monocyte/macrophage adsorptive apheresis (GMCAP)] or filters [leukocytapheresis (LCAP)]. Both treatments have been reported to be effective for active UC. There have been few trials, however, comparing the efficacy of GMCAP and LCAP. In this study, we prospectively evaluated the efficacy of LCAP and GMCAP for the treatment of active UC. METHODS: Thirty-nine patients [18 male, 21 female; mean age 38.7 years; duration of disease 6 years; clinical activity index (CAI) >6 points] with moderate-to-severe active UC were randomly assigned to the LCAP (n=21) or GMCAP group (n=17). Adacolumn (cellulose acetate beads; Japan Immunoresearch Laboratories, Takasaki, Japan) for GMCAP and Cellsorba EX (polyethylene phthalate fibers; Asahi Medical Co. Ltd, Tokyo, Japan) for LCAP were used for leukocyte removal. Patients received two sessions of cytapheresis in the first week, followed by four weekly administrations. Steroid doses were tapered if patients achieved clinical improvement. When the CAI score had decreased by 5 points or more, the patient was considered to have improved. RESULTS: Thirteen patients in the GMCAP group and 14 in the LCAP group achieved clinical improvement. No significant difference was found in clinical response and clinical course between LCAP and GMCAP. Hemoglobin levels were significantly decreased immediately after one session of cytapheresis in the LCAP group. No severe adverse effects were observed in any of the patients. No significant differences were observed in any clinical parameters predictive of a response to either LCAP or GMCAP. But in all patients receiving cytapheresis, a high CAI score was a significant risk factor for treatment failure. All of the cytapheresis nonresponders had CAI scores >or=16. CONCLUSION: Both GMCAP and LCAP were effective treatments for active UC. Patients with severe UC and a high CAI score were, however, refractory to treatment.     

Recurrence of Helicobacter pylori infection and the long-term outcome of peptic ulcer after successful eradication in Japan.

Recurrence of peptic ulcer after successful eradication of Helicobacter pylori is closely associated with reinfection. The aim of this study was to examine the recurrence of peptic ulcer and reinfection with H. pylori after successful eradication. To eradicate H. pylori infection, patients with active peptic ulcer disease were assigned to two treatment groups depending on the year of their enrollment (AM group and OAMR group). Patients in the AM group received 400 mg of cimetidine twice per day, 300 mg of amoxicillin three times per day, and 250 mg of metronidazole three times per day for 2 weeks. Patients in the OAMR group received 20 mg of omeprazole once per day, 500 mg of amoxicillin granules three times per day, 250 mg of metronidazole three times per day, and 150 mg of roxithromycin twice per day for 1 week. After endoscopy verified ulcer scarring and successful eradication of H. pylori infection, study patients were followed up monthly and did not undergo acid-suppressive therapy. Endoscopy was performed at 6-month intervals for the 1st year. After the 1st year, follow-up endoscopies were performed annually. In total, 107 patients with peptic ulcer (duodenal ulcer [DU], 65; gastric ulcer [GU], 42) were followed up for a mean period of approximately 2 years. Recurrence of infection occurred in 10 (9.3%) of 107 patients (AM group, 9; OAMR group, 1) after 210 patient-years of follow-up; the recurrence rate was 4.8% per patient-year. Recurrence of H. pylori infection was significantly higher in the AM group (23.1%) than in the OAMR group (1.5%). H. pylori infection recurred in two patients 6 months after eradication therapy, in seven 1 year after, and in one 2 years after. Thereafter, no further cases of H. pylori recurrence were observed. During follow-up periods, seven cases of ulcer recurrence were observed (DU, 4; GU, 3). The rate of peptic ulcer recurrence within 2 years after eradication therapy was significantly higher than that after more than 2 years. Four cases of ulcer recurrence (DU, 3; GU, 1) also had recurrence of H. pylori infection. One recurrent case of DU without reinfection was associated with nonsteroidal anti-inflammatory drugs. The remaining two cases of GU recurred without H. pylori reinfection. In conclusion, peptic ulcer recurrence rarely occurred (3 [2.9%] of 103) in patients cured of H. pylori infection. Reinfection after apparent successful eradication was rarely noted when a powerful therapeutic regimen in eradication was used. Therefore, to eradicate H. pylori, a highly effective therapeutic regimen should always be used.     

Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.