Effects of a psychosocial intervention programme combined with exercise in community-dwelling older adults with chronic pain: A randomized controlled trial.

BACKGROUND: Although researchers have recommended exercise training and psychosocial intervention to manage chronic pain, an effective intervention for Japanese community-dwelling older adults with chronic pain has not been established. This randomized controlled trial examined whether exercise training combined with psychosocial intervention more effectively improves pain, psychological status and physical activity than does exercise training alone in this population. METHODS: We randomized 128 older adults with chronic pain to either an intervention group (n = 64) involving exercise training combined with psychosocial intervention, or a control group (n = 64) involving only exercise training. Exercise training comprised weekly 60-min sessions for 12 weeks. Psychosocial intervention involved changing participants' focus on pain using self-management education and cognitive behavioural therapy, and participants recorded their daily pain intensity and step counts. Pain intensity, psychological status and physical activity were assessed before and 12 weeks after the intervention. RESULTS: A time-by-group interaction emerged for psychological status (p = 0.003) and physical activity (p < 0.001), both favouring the intervention group. The intervention group also showed greater improvement in pain intensity at 12 weeks than did the control group (p = 0.007). CONCLUSIONS: Exercise training combined with psychosocial intervention improves key outcome indicators more effectively than does exercise training alone in older adults with chronic pain. SIGNIFICANCE: Although research has shown that combined exercise and psychosocial intervention is optimal for managing chronic pain, our study is the first, to the best of our knowledge, to test a specific intervention of this type in community-dwelling older adults with chronic pain in Japan.

Clinicopathological significance of laminin-5γ2 chain expression in superficial esophageal cancer.

The glycoprotein laminin 5γ2 chain (LN-5γ2) has recently become a focus of increased interest and investigation as a marker of invasion in gastrointestinal malignancies. We investigated the significance of LN-5γ2 expression as a prognostic factor in superficial esophageal cancer. The study population consisted of 87 patients who had undergone a transthoracic esophagectomy and three-field lymphadenectomy for the treatment of superficial esophageal cancer at Tokai University Hospital. Formalin-fixed, paraffin-embedded sections of the resected specimens were examined using immunohistochemical staining and hematoxylin and eosin staining to assess the correlations between the LN-5γ2 expression pattern and the clinicopathological factors (age, sex, T-factor, N-factor, ly-factor, v-factor, degree of differentiation, infiltrative growth pattern, tumor node metastasis classification of malignant tumors [TNM] stage, etc.) and the patient outcome. The expression pattern of LN-5γ2 was classified into an extracellular type (E type), characterized by the staining of extracellular matrix such as the basement membrane and the stroma (31 cases, 35.6%), and a cytoplasmic type (C type), characterized by the staining of the cytoplasm in the cancer cells (56 cases, 64.6%). The expression pattern was not correlated with any of the clinicopathological factors that were assessed. However, univariate analyses of the survival analysis data showed that the N-factor (P = 0.011), TNM stage (P = 0.011), and LN-5γ2 C type (P = 0.017) were prognostic factors. A multivariate analysis revealed that the N-factor (P = 0.049) and LN-5γ2 C type (P = 0.048) were prognostic factors. In the survival analysis, a univariate analysis of the 75 T1b cases also showed that the N-factor (P = 0.048), TNM stage (P = 0.048), and LN-5γ2 C type (P = 0.029) were prognostic factors, while a multivariate analysis showed that the LN-5γ2 C type (P = 0.035) was a prognostic factor. The C type expression of LN-5γ2, i.e. confined to the cytoplasm, was correlated with an unfavorable outcome among the patients with superficial esophageal cancer in the present series. Observation of the LN-5γ2 expression pattern may be useful for the diagnosis of highly malignant tumors.

Supramolecular ferric porphyrins and a cyclodextrin dimer as antidotes for cyanide poisoning.

OBJECTIVES: This study aimed to evaluate the antidotal effect of a newly developed supramolecular complex, ferric porphyrins and a cyclodextrin dimer (Fe(III)PIm3CD), that possess a higher binding constant and quicker binding rate to cyanide ions than those of hydroxocobalamin (OHCbl) in the presence of serum protein. METHODS: First, in vitro cytochrome activity and cell viability were evaluated in murine fibroblast cells cultured with various doses of Fe(III)PIm3CD and potassium cyanide (KCN). Next, BALB/c mice were pretreated with intravenous OHCbl (0.23 mmol/kg), Fe(III)PIm3CD (0.23 mmol/kg), or saline and then received KCN (lethal dose 100% (LD100): 0.23 mmol/kg) through a stomach tube. Finally, as a resuscitation model, KCN-induced apnea was treated with a bolus injection of an equimolar dose of antidotes followed by a slow infusion of the same reagent. RESULTS: Fe(III)PIm3CD showed dose-dependent antidotal effects in vitro. Pretreatment with Fe(III) PIm3CD prevented KCN-induced apnea significantly better than OHCbl. Resuscitation with Fe(III)PIm3CD resulted in an earlier resumption of respiration than that seen with OHCbl. However, 24-h survival was similar among the treatments (Fe(III)PIm3CD, nine of nine mice; OHCbl, eight of nine mice). CONCLUSION: Fe(III)PIm3CD exerted significant antidotal effects on cyanide toxicity in vitro and in vivo, with a potency equal in the mortality of cyanide-poisoned mice or superior in the respiratory status during an acute phase to those of OHCbl.

Characteristics of adult scald burn patients-a single center study in western Kanagawa Prefecture.

Burns sustained in bathtubs are a social and medical problem in Japan, especially among the elderly. Between October 2003 and March 2009, 22 adult scald burn patients (men, 17; average age, 65.3 ± 21.2 years) were transferred to Tokai University. In this study, we investigated the characteristics of these patients, and compared clinical parameters among patients with burns sustained in a bathtub (n = 10) and those with burns sustained due to other causes (n = 12). The average percentage total body surface area (%TBSA), dermal and deep burn area, and abbreviated burn severity index (ABSI) were 27.6 ± 23.8, 19.9 ± 20.5%, 7.8 ± 13.1%, and 7.7 ± 3.1, respectively. All patients in the bathtub burn group were elderly, 6 developed internal diseases, 3 had alcohol-related burns, and 4 died. Additionally, their %TBSA and ABSI were higher than those of the non-bathtub burn group patients. Burns sustained in bathtubs were more severe than those sustained due to other causes. The bathtub-related burn patients were elderly, and their burns were extensive and deep; hence, they were at a higher risk of developing internal diseases. Thus, introduction of safer bathing styles and bath systems will decrease incidences of bathtub-related burns.

Three dimensional ultrastructure of transverse (Harris) lines in the long bone.

To investigate the occurrence of transverse lines in long bones of adults, we studied 27 cadavers (14 males and 13 females). After confirming the presence of a transverse line, a cross-sectional sample was examined macroscopically, and by soft X-ray and scanning electron microscopy. The following results were obtained: 1. According to roentgenograms, transverse (Harris') lines were observed in 40.7% of the distal half of the femur and in 29.6% of the proximal half of the tibia. 2. Macroscopic examination of the bone cross-sections at the level of the transverse line showed various membranous structures. 3. In scanning electron micrographs, no marked difference in structure was observed between the transverse line trabeculae and the compact bone.

Accumulation of p53 in esophageal squamous cell carcinoma.

p53 is one of the most important tumor suppressor genes. Mutation of the p53 gene can be detected immunohistochemically as over-expression of its protein in the nucleus. The p53 gene product is known to regulate cell growth and proliferation. Genetic alterations related to the carcinogenesis or progression of esophageal cancer are poorly understood. We examined accumulation of p53 protein in esophageal squamous cell carcinomas including early-stage cancers, and its clinicopathological significance. p53 immunoreactivity in the cancer tissues was found in 61 (79.2%) of 77 esophageal squamous cell carcinomas. Over-expression of p53 protein (diffusely and focally positive staining) was seen in 70.1% (54/77). p53 over-expression was detected not only in the cases of in situ or intramucosal carcinomas, but also in invasive carcinomas. No significant correlations were found between p53 over-expression and clinicopathological features such as depth of tumor invasion, lymph node metastasis or venous/lymphatic invasion. These results suggested that p53 mutations may be closely associated with the early-stage of pre-invasive esophageal carcinoma, and p53 gene mutations may play an important role in the carcinogenesis of human esophageal cancer.

Pancreatic acinar cell carcinoma with endocrine differentiation: immunohistochemical and ultrastructural analyses.

The majority of pancreatic malignant tumors are adenocarcinomas of the ductal type (ductal cell carcinomas) and combined tumors consisting of different tumor components are very rare. We present here a rare case of acinar cell carcinoma with apparent foci of endocrine differentiation. A 46-year-old man underwent pylorus-preserving pancreatoduodenectomy under the diagnosis of pancreatic tumor. The pancreatic tumor was mainly composed of typical acinar cell carcinoma, but some tumor cells were positive for both acinar and endocrine cell markers such as pancreatic amylase, trypsin, lipase and chromogranin A. At the electron-microscopic level, the tumor cells were seen to have numerous electron-dense neuroendocrine, as well as a few zymogen-like, granules. The tumor part positive for both acinar and endocrine cell markers originated from a subclone (dis-differentiated tumor cells) of the typical acinar cell carcinoma tissue of the pancreas.

Hyperplastic vascular smooth muscle cells of the intrarenal arteries in angiotensin II type 1a receptor null mutant mice.

BACKGROUND: Angiotensin II (Ang II), which contracts vascular smooth muscle cells (VSMCs), has been reported to regulate VSMC growth. Recently formed transgenic mice without angiotensinogen or Ang II receptors showed vascular alterations. However, it is still unclear how their VSMCs alter. We explored the role of Ang II via the Ang II type 1a receptor (AT1a) in VSMCs in vivo using AT1a null mutant mice. METHODS: We analyzed the ultrastructure of the intrarenal arteries in AT1a null mutant mice that were homozygous for a targeted disruption of AT1a receptor gene using light and electron microscopy. RESULTS: The structural changes of the intrarenal arteries in AT1a null mutant mice showed the wall thickening, which in the interlobar, arcuate, and proximal interlobular arteries consisted of two additional populations of VSMCs, on the luminal and abluminal sides of the media. The luminal overpopulation of smooth muscle cells (SMCs) was arranged in a longitudinal direction separated by increased interposed elastic laminae. The abluminal overpopulation of SMCs ran in circumferential directions separated from the main population. The cytological structure of VSMCs in AT1a null mutant mice was smaller in size, contained more organelles for protein synthesis and secretion than in control mice, and had poorly developed contractile apparatus. CONCLUSIONS: The lack of AT1a signaling causes structural abnormalities in the renal vascular system and transforms the phenotype of VSMCs into cell proliferation, induces the escape of VSMCs from the circular mechanical integrity, and results in increased synthesis of extracellular matrices.

Injection of CD4(+) and CD8(+) cells with donor or host accessory cells induces acute graft-vs-host disease in human skin in immunodeficient mice.

OBJECTIVE: We examined cell subsets with respect to cutaneous graft-vs-host disease by cell sorting selection of subsets of human mononuclear cells and injecting the subsets subcutaneously in a mouse model. MATERIALS AND METHODS: Cell suspensions containing cultured human epidermal cells and dermal fibroblasts from a single donor mixed with lymphoid cell subsets positively selected using the FACSVantage cell sorting instrument and/or MACS cell isolation kits from unrelated individuals were injected into immunodeficient mice. This model is known to generate human skin with histologic findings similar to human graft-vs-host disease. RESULTS: Donor T-cell subsets CD4(+) and CD8(+) plus either host or donor CD14(+) cells were necessary to cause acute cutaneous graft-vs-host disease. Although graft-vs-host disease can result from recognition of class I antigens expressed on human cutaneous cells by donor peripheral blood mononuclear cells, additional recognition of class II antigens expressed on host mononuclear cells resulted in more severe histologic manifestations. Dendritic cells that differentiated from donor and host monocytes also showed competent accessory cell function in this system. CONCLUSIONS: Based on this model, human cutaneous graft-vs-host disease was caused by donor CD4(+) cells and CD8(+) cells activated through recognition of host antigens, including class I and class II antigens presented by either donor or host CD14(+) cells or dendritic cells.

MUC1 and MUC2 expression in human gallbladder carcinoma: a clinicopathological study and relationship with prognosis.

Mucins are a group of high molecular weight glycoproteins consisting of a mucin core protein and O-linked carbohydrates. To date, nine apomucins (MUC1-8, and MUC5B) have been identified. Recent studies have demonstrated that MUC1 is expressed in tumors of various human organs, and may function as an anti-adhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis. MUC2 is a major secreted mucin of colon and is known to be expressed in cells showing intestinal metaplasia in the stomach and other organs. MUC2 expression in the mucosal epithelia is an apparently abnormal phenomenon related to the neoplastic process. In this study, we examined MUC1 and MUC2 expression in human gallbladder adenocarcinoma and its clinicopathological significance and relationship with the prognosis of the patients. MUC1 immunoreactivity was detected not only in the cancer cells but also in the cancer stroma. Cytoplasmic MUC1 expression was significantly relation to lymphatic invasion and lymph node metastasis (p < 0.001), and was associated with a poor outcome. In contrast, MUC2 was rarely expressed in gallbladder carcinomas, and its immunoreactivity was detected only in the cancer goblet cells. Overexpression of MUC2 was not significantly related to lymphatic invasion or lymph node metastasis, or prognosis of patients. These observations suggested that MUC1 expression plays a more important role than MUC2 expression in cancer cell growth and metastasis of human gallbladder adenocarcinomas.

Effect of ankle disk training combined with tactile stimulation to the leg and foot on functional instability of the ankle.

Twenty-two university students with unilateral functional instability of the ankle participated in this study. They were randomly assigned to one of two experimental groups. Subjects in both groups were trained to stand on the affected limb on an ankle disk. In group 1, two pieces of 1-cm wide nonelastic adhesive tape were applied to the skin around the lateral malleolus from the distal third of the lower leg to the sole of the foot before the training sessions. Subjects in group 2 participated in the training sessions without the application of the adhesive tape. Training was performed for 10 minutes a day, five times per week, for a period of 10 weeks. Subjects were tested for postural sway while standing on the affected limb before, during, and after the training period. In group 1, postural sway values decreased significantly after 4 weeks compared with the pretraining performance, and they were within the normal range after not more than 6 weeks of training. In group 2, the values did not improve significantly compared with the pretraining performance until after 6 weeks of training, and they were not within the normal range until after 8 weeks of training. The findings suggest that the 2-week earlier correction of postural sway in group 1 was due to an increased afferent input from skin receptors that were stimulated by the traction of the adhesive tape.

Effects of physical training and mental practice of in-clothes swimming: assessment by physiological parameters.

PURPOSE: This study examined whether a short-term physical or mental training reduces the physiological load and perceived exertion of the in-clothes swimming. METHODS: The study included 24 male inter-collegiate competitive swimmers with no previous experience of the in-clothes swimming. Prior to the training, the subjects performed 200-meter swimming with two styles of swimming, namely the crawl and elementary backstroke, and the degree of perceived exertion in the Borg scale, heart rate, and blood lactic acid level were determined. Following this baseline determination, the subjects were divided into 4 groups with 6 individuals each. These four groups were Group A "in-clothes training", Group B "image training", Group C "swimsuit training", and Group N "no training". Group A and C were lectured on the in-clothes swimming and practiced 7.5 min-long in-clothes swimming per day for a week with the two swimming styles, with Group A subjects wearing daily clothes and Group C subjects in swimsuits. Group B received 15 min of nonphysical mental practice primarily through viewing video recording of swimming performance everyday for a week. No training was given to Group N. At the completion of the training session, the subjects underwent the 2nd 200-meter swimming, and the physiological parameters were determined. RESULTS: The 1st in-clothes swimming load test showed that the elementary backstroke swimming resulted in significantly lower values of heart rate, blood lactic acid level, and perceived exertion than the crawl. For Group N, no difference was observed in the physiological parameters between the 1st and 2nd load test with either the elementary backstroke or crawl. Upon the 2nd in-clothes load test with the elementary backstroke, all three parameters were lower for Group A, B, and C than those seen for the 1st load test, and these differences were statistically significant, except for blood lactic acid in Group A. The 2nd in-clothes load test with the crawl showed that both heart rate and blood lactic acid were lower than those of the 1st load test for all three groups, with the differences in heart rate and blood lactic acid in Group A and that in blood lactic acid in Group B reaching the statistic significance. With respect to perceived exertion, the Borg score determined after the in-clothes load test with the crawl was significantly reduced for Group A, B, and C. The score after the in-clothes load test with the elementary backstroke was significantly reduced only for Group A. CONCLUSION: The elementary backstroke, when practiced in-clothes, imposes a relatively less physiological load. The present training methods can reduce physiological load and/or perceived exertion of the in-clothes swimming. Thus, both image training and swimsuit swimming are equally effective as a training method of the in-clothes swimming.

Analysis of inositol phospholipid turnover during lymphocyte activation.

Receptor-mediated activation of phospholipase C (PLC) leads to the hydrolysis of membrane inositol phospholipids, generating diacylglycerol (DAG) and water-soluble inositol phosphates. This signaling mechanism is used by antigen receptors on T and B cells that have been implicated as mediators of receptor-induced influx of extracellular Ca(2+). This unit provides protocols that describe the resolution of InsP by Dowex anion-exchange chromatography. This technique provides a reliable means of separating inositol monophosphate, inositol bisphosphate, and inositol trisphosphate, but does not resolve isomers of these. An Alternate Protocol describes the separation of inositol phosphates by anion-exchange HPLC. A protocol for resolution of inositol phospholipids by thin-layer chromatography (TLC) is also provided.

A patient with diabetes mellitus and severe arterial embolism.

An 89-year-old man with diabetes mellitus was admitted to the hospital because of a low-grade fever and a disturbance in consciousness. He had been diagnosed as having diabetes mellitus at the age of 22 years and had been taking oral hypoglycemic drugs for 16 years at least. A few days before admission, a loss of appetite was noticed by his family; he developed a stupor on the day of admission. On physical examination, his lower extremities were pale and his skin temperature was low. Laboratory tests showed an increase in his white blood cell count and his blood culture was positive for Staphylococcus aureus. An MRI showed that the abdominal aorta was totally occluded beneath the renal arteries, and no significant collateral circulation was observed. He was given antibiotics and anticoagulants, but his general condition continued to worsen. Laboratory tests showed renal failure and liver dysfunction, indicating multi-organ failure. On the 24th day of admission, he died of respiratory and heart failure. An autopsy showed the aorta to be totally occluded beneath the renal arteries by an embolism; atherosclerotic changes were rather mild. Acute plaque change on the surface of the aorta may have induced the sudden development of emboli in the aorta.

Correlating the severity of paraquat poisoning with specific hemodynamic and oxygen metabolism variables.

OBJECTIVE: To investigate the hemodynamics and oxygen metabolism of patients with varying degrees of severity of paraquat poisoning. DESIGN: Prospective, observational, clinical study. SETTING: Intensive care unit in a university hospital. PATIENTS: Forty-three consecutive patients with paraquat and/or diquat poisoning were classified into three groups by the severity index of paraquat poisoning (SIPP; hr/mg/L). INTERVENTIONS: Standard treatments included specific respiratory management, fluid resuscitation, and aggressive circulatory support. MEASUREMENTS AND MAIN RESULTS: Serum paraquat and diquat levels were measured at arrival, and SIPP was calculated. The cardiac index (CI), left ventricular stroke work index (LVSWI), systemic vascular resistance index (SVRI), oxygen delivery index (DO2I), oxygen consumption index (VO2I), and oxygen extraction ratio (O2ER) were measured at 6, 12, 24, 36, 48, 72, and 96 hrs postadmission. A significant inverse correlation between SIPP and survival time was found in 31 fatal cases (r = .85; p < .001). In the SIPP 10-50 group, CI, DO2I, VO2I, and O2ER were maintained at higher levels than in the SIPP group of <10 (p < .05), whereas SVRI decreased significantly (p < .05). In the SIPP group of >50, CI, LVSWI, SVRI, DO2I, and VO2I decreased, whereas O2ER had a tendency to increase progressively. There was a significant correlation between SVRI and SIPP, O2ER and SIPP, and O2ER and SVRI 24 hrs after admission, respectively (p < .001). CONCLUSIONS: Paraquat poisoning is characterized by high oxygen consumption with high oxygen extraction, with the degree of derangement based on the severity index. The development of a marked imbalance between increased oxygen demand and decreased oxygen supply because of myocardial depression might be a possible cause of death in circulatory failure.

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

Study for verification testing of the helmet-mounted display in the Japanese Experimental Module.

Our purpose is to propose a research and development project in the field of telemedicine. The proposed Multimedia Telemedicine Experiment for Extra-Vehicular Activity will entail experiments designed to support astronaut health management during Extra-Vehicular Activity (EVA). Experiments will have relevant applications to the Japanese Experimental Module (JEM) operated by National Space Development Agency of Japan (NASDA) for the International Space Station (ISS). In essence, this is a proposal for verification testing of the Helmet-Mounted Display (HMD), which enables astronauts to verify their own blood pressures and electrocardiograms, and to view a display of instructions from the ground station and listings of work procedures. Specifically, HMD is a device designed to project images and data inside the astronaut's helmet. We consider this R&D proposal to be one of the most suitable projects under consideration in response to NASDA's open invitation calling for medical experiments to be conducted on JEM.

Clinical application of artificial ligament for ankle instability--long-term follow-up.

We have applied a reconstructive operation to patients with injury of the lateral ligament in the ankle joint using an artificial ligament made of polyester (Leeds-Keio) since 1985. The operation was performed on 451 feet of 436 patients. Average follow-up period was 5 years and 8 months. Talar tilt and anterior drawer translation before and after the operation were improved from 16 degrees to 4 degrees and from 11 mm to 4 mm, respectively. In this study, which has followed the same patients over an extended period, there were no cases with a decrease in the range of motion of the joint, with further development of osteoarthritis, or with a poorer result than those observed in our earlier study, which reported a short-term follow-up of the same patients. It may therefore be concluded that this reconstructive procedure of the lateral ligament of the ankle joint, using the artificial ligament, is also excellent after long-term follow-up.