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The present paper concerns the assessment of phasic work stress using autonomic indices such as skin temperature, respiratory measures, and heart rate, blood pressure, and their variabilities. A physiological model of the autonomic regulation of the cardiovascular and respiratory systems is also introduced in order to simulate and interpret the changes in these indices. Two experiments were conducted to investigate high tension and monotony as two types of mental work stress. A tracking task was used to induce high-tension work stress with and without an instruction intended to induce additional emotional stress. The same tracking task was repeated 12 times to simulate monotonous work stress. Fifty healthy adults participated in each experiment. Many physiological measures showed task-dependent changes in the high-tension experiment and at the beginning of the monotonous stress condition. These changes were explained by sympathetic activation, parasympathetic withdrawal, and respiratory rate activation. An additional drop in skin temperature and an additional HR increase were caused by the stressful instruction, which may reflect an emotional strain and can be explained by sympathetic activation. Furthermore, the mid-frequency component (approx. 0.1 Hz) of respiration and respiratory instability showed an obvious increase during the course of the monotonous stress experiment, which may reflect boredom and disgust. It was concluded that multidimensional recordings of autonomic measures that can be obtained during work without extra load on the worker would be helpful to assess different types of phasic work stress. The proposed model was further shown to be able to detect periods of stress in a complex work environment.

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A simple and highly sensitive method is described for the HPLC determination of 4-nonylphenol (NP), 4-nonylphenol mono- (NP1EO) and diethoxylates (NP2EO) in fish and shellfish together with bisphenol A (BPA), 4-tert.-butylphenol (BP) and 4-tert.-octylphenol (OP). The NP, NP1EO, NP2EO and other alkylphenols in the samples are extracted with acetonitrile and the lipid in the sample extract is eliminated by partitioning between hexane and acetonitrile. After Florisil PR clean-up the sample extract is analyzed by HPLC with a fluorescence detection. Recoveries in Japanese smelt, carp and corbicura are 81.8-84.3% for NP, 83.5-84.3% for NP1EO, 90.5-96.2% for NP2EO, 70.7-72.9% for BPA, 71.0-73.4% for BP and 77.1-83.2% for OP spiked at 0.5 microg each chemical per 5 g of the fish and shellfish samples. The detection limits are 2 ng/g for NP, NP1EO and NP2EO, and 1ng/g for BPA, BP and OP.

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BACKGROUND AND AIM: Although mucosal alpha- and beta-chemokines are considered to be involved in the pathogenesis of Helicobacter pylori-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without H. pylori infection. METHODS: Levels of IL-8 and MIP-1alpha secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections. RESULTS: The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with H. pylori-positive GU showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with H. pylori-negative GU or the antral mucosal tissues from H. pylori-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1alpha and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with H. pylori-positive GU. CONCLUSION: Mucosal alpha- and beta-chemokines may be important to the ulcerogenesis in H. pylori-associated GU disease.

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Helicobacter pylori persists in the human stomach despite eliciting both cellular and humoral immune responses and inducing proinflammatory cytokines. To determine whether local humoral and cytokine responses are related to each other and to histologic responses, we studied 66 Japanese patients who underwent gastroscopy. Using specific enzyme-linked immunosorbent assays, we examined gastric antral mucosal-organ biopsy culture supernatants to assess interleukin-6 (IL-6) and interleukin-8 (IL-8) levels and antibody responses to H. pylori whole-cell antigens CagA, HspA, and HspB. Of the patients studied, 11 were H. pylori negative and 55 were H. pylori positive; by PCR, all strains were cagA(+). As expected, compared to H. pylori-negative patients, H. pylori-positive patients had significantly higher humoral responses to all H. pylori antigens and had higher IL-8 (47.8+/-3.5 versus 10.1+/-4.3 ng/mg of biopsy protein; P<0.001) and IL-6 levels (2.8+/-0.3 versus 0.26+/-0.2 ng/mg of protein; P<0.001). Among the H. pylori-positive patients, supernatant anti-CagA immunoglobulin G (IgG) levels were significantly associated with H. pylori density (P<0.005) and neutrophil infiltration (P<0.005) scores. Anti-CagA immunoglobulin A levels were correlated with intestinal metaplasia (P<0.05). Mononuclear cell infiltration scores were significantly associated with supernatant IL-6 levels (P<0.005) and with IgG responses to whole-cell antigens (P<0.05). Supernatant IL-8 levels were significantly associated with anti-CagA IgG (r = 0.75, P<0.001). Anti-CagA responses correlated with neutrophil infiltration, intestinal metaplasia, H. pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts.

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BACKGROUND: The bedside wellness system (BSW) is effective for decreasing stress and improving mental well-being and should help relieve the side effects and mental disorders of patients during cancer chemotherapy. METHODS: The study was a randomized clinical trial. After giving informed consent, patients were randomly assigned to the BSW intervention or control groups. The patients were given the Hospital Anxiety and Depression Scale (HADS) test before the trial to evaluate their emotional baseline. The Cancer Fatigue Scale, which was developed at our institute, and face visual analog scale were used to measure the emotional state and subjective feelings before and after the trial. The degree of emesis was measured using a visual analogue scale after the experience. We set up the system in a room in the outpatient clinic of the National Cancer Center New Hospital Building. RESULTS: The decreases in the fatigue score and emesis score 3-5 days after chemotherapy were statistically significant (both p < 0.05) and carry-over effects were detected. CONCLUSIONS: BSW intervention therapy is an effective way to treat fatigue and emesis. This virtual reality system is a new therapeutic method that can be used in palliative medicine.

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BACKGROUND: Enhanced gastric mucosal chemokine activity has been demonstrated in patients with Helicobacter pylori infection. However, little is known about the mechanisms involved in this phenomenon. AIM: To examine whether in vivo chemokine activity is similar to in vitro response of gastric epithelial cells infected by H. pylori. PATIENTS AND METHODS: Antral biopsy specimens were obtained from patients with H. pylori infection for organ culture, isolation of H. pylori and histological examination. RESULTS: In organ cultures of mucosal tissues, the levels of interleukin-8 and growth-related gene product a were elevated in patients with peptic ulcer disease compared with those with erosive gastritis or endoscopically normal mucosa. However, there were no significant differences in in vitro cultures of MKN45 or KATO III cells that were infected with H. pylori isolated from these same patients. These in vivo and in vitro alpha-chemokine levels showed no significant association with the presence of cagA gene and CagA protein, ureB genotype, or binding capacity to MKN45 or KATO III cells in individual H. pylori isolates. In contrast, in vivo mucosal alpha-chemokine activity correlated with H. pylori colonization density. CONCLUSION: Mucosal chemokine profiles and inflammatory responses in H. pylori infection may be associated more closely with host factors, including those determining bacterial adhesiveness, than with differences in H. pylori strains.

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BACKGROUND: Interleukin-6 (IL-6) has multiple immunological effects on a wide variety of cells and tissues. The expression of IL-6 and IL-6 receptor (IL-6R) may be important to the pathogenesis of inflammatory bowel disease (IBD). METHODS: In the present study, we examined whether mucosal IL-6 and soluble IL-6R were associated with the pathophysiology of IBD using the colonic mucosal specimens obtained from patients with IBD. Enzyme-linked immunosorbent assay was used to measure the levels of IL-6 and sIL-6R in organ cultures of mucosal tissues and in cell cultures of fractionated mucosal cells as well as in the serum. Expression of IL-6 and IL-6R was analysed by reverse transcription-polymerase chain reaction analysis using freshly isolated lamina propria mononuclear cells (LPMC). RESULTS: The levels of IL-6 and sIL-6R in organ cultures were substantially elevated in patients with IBD, especially in those with histologically active inflammation. In contrast, considerably higher levels of sIL-6R were detected in patients with other types of colonic inflammation who were included as inflammatory controls, but elevation of IL-6 was less prominent in such patients. The positivity for expression of IL-6 and IL-6R mRNA in LPMC was in parallel with the results obtained in organ cultures. In cell cultures, mucosal macrophages were the main cell type producing both IL-6 and sIL-6R on a per cell basis and other cell fractions including colonic epithelial cells and lymphocytes produced substantially lower amounts of these molecules. The levels of IL-6 and sIL-6R in organ cultures, but not those in the serum, showed a significantly positive correlation with the degree of clinical disease activity in patients with IBD. CONCLUSIONS: Enhanced IL-6/sIL-6R-mediated immune and inflammatory responses may be implicated, at least partly, in the continuation of intestinal inflammation in patients with IBD.

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Mucosal chemokines are considered to be important in the pathogenesis of Helicobacter pylori-associated gastritis. The aims of this study are to examine the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures, the expression of MIP-1alpha mRNA and the cellular source of MIP-1alpha, using the antral mucosal specimens obtained from H. pylori-positive and -negative patients. Enzyme-linked immunosorbent assay was used to measure the levels of MIP-1alpha in organ cultures of mucosal tissues and cell cultures of fractionated mucosal cells. The expression of MIP-1alpha mRNA and protein was analysed in fresh biopsy tissues with reverse transcriptase-polymerase chain reaction (RT-PCR) and double immunofluorescence microscopy, respectively. The mucosal specimens obtained from H. pylori-positive patients exhibited significantly higher values of MIP-1alpha activity in organ cultures with increased numbers of CD68+ macrophages, myeloperoxidase+ neutrophils and mononuclear cells in the lamina propria compared with those from H. pylori-negative patients. The RT-PCR analysis detected MIP-1alpha mRNA in more than 50% of the specimens with H. pylori infection, but not in those without infection. In cell cultures, the macrophage fraction contained substantially higher amounts of MIP-1alpha on a per cell basis than the lymphocyte fraction and MIP-1alpha activity was not detected in cultures of gastric epithelial cells. This observation was also confirmed by a double immunofluorescence microscopic study in which most (>90%) MIP-1alpha-positive infiltrating cells were CD68+ macrophages. This study indicates that synthesis and secretion of MIP-1alpha are increased in H. pylori-infected antral mucosa and that mucosal macrophages are the main cell type responsible for this phenomenon.

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Tissue accumulation of polymorphonuclear neutrophils (PMN) in Inflammatory Bowel disease (IBD) might be, in part, due to a delay in apoptotic processes associated with the effects of their specific growth factors and inflammatory cytokines. We addressed this hypothesis by examining the activity of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) in the organ culture supernatants of colonic mucosal specimens and their regulatory effects on PMN apoptosis in patients with IBD. The contents of G-CSF and GM-CSF in the supernatants were measured by the enzyme-linked immunosorbent assays and PMN apoptosis was evaluated by acridine orange/ethidium bromide staining, respectively. Mucosal specimens obtained from patients with active IBD exhibited higher levels of G-CSF and GM-CSF activity than controls. Notably, the levels of G-CSF activity were approximately 1000-fold higher than those of GM-CSF activity. Freshly isolated PMN showed a time-related increase in the proportion of cells with characteristic features of apoptosis when they were incubated with the culture medium alone and exposure of PMN to recombinant G-CSF and GM-CSF caused a concentration-dependent inhibition of apoptosis. Incubation of PMN with the supernatants from patients with active IBD induced an inhibitory effect on PMN apoptosis; this effect was abrogated to a significant degree by pre-incubation of the supernatants with anti-G-CSF serum. This study suggests that PMN apoptosis may be delayed under the influence of soluble mediators, especially G-CSF, in the microenvironment of IBD-affected mucosa, thus providing possible mechanisms for tissue accumulation of PMN in IBD.

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This article describes how a virtual forest walk system (a bedside Wellness system) is expected to help cancer patients to relax and become more positive emotionally. It is also expected that the beautiful scenery (with wind, scents, and sounds) will refresh patients and that the evoked changes in the natural world will relax them. We have demonstrated the possible uses of virtual reality (VR) technology in the care of patients' mental health; however, we still have to improve the VR technology itself and investigate how to utilize it most effectively. It is essential that VR technology may be able to construct virtual, but realistic, environments that patients can enjoy without being caused additional stress or fatigue. This type of medical VR system may be effective in improving the quality of life of not only cancer patients, but also of the elderly.

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There is differential resolution of mucosal infiltration with neutrophils and mononuclear cells following successful Helicobacter pylori eradication. We investigated the effects of H. pylori eradication on mucosal interleukin-8 (IL-8) and IL-6 activity in relation to the resolution of H. pylori-associated gastritis. Eighty-one duodenal ulcer patients with H. pylori infection received dual- or triple-treatment eradication therapy, and mucosal biopsy specimens obtained at the initial and follow-up endoscopic examinations were cultured in vitro for 24 h. The levels of IL-8 and IL-6 were measured by enzyme-linked immunosorbent assays. In the 42 patients in whom H. pylori eradication failed, there was little change in the numbers of neutrophils and mononuclear cells infiltrating the mucosa and in IL-8 and IL-6 activity. In the 39 patients in whom H. pylori was eradicated, there was normalization both in the numbers of infiltrating neutrophils and in mucosal IL-8 activity, which was evident within 1 month following therapy. In contrast, there was a gradual resolution of mononuclear cell infiltration over a 6-month period, accompanied by a gradual normalization in IL-6 levels. Addition of H. pylori to cultures of mucosal tissues induced a significant increase in IL-8 activity in both uninfected control subjects and patients from whom H. pylori was eradicated. However, this introduction yielded a significant increase in IL-6 activity only in the latter group. This study indicates a dichotomy in the changes of mucosal IL-8 and IL-6 activity after H. pylori eradication. The rapid normalization of IL-8 after H. pylori eradication and the ability of H. pylori cells to stimulate IL-8 in control tissues indicate that IL-8 induction is a part of the innate (nonimmune) responses to this organism. In contrast, the results of experiments analyzing IL-6 activity in cultured mucosal tissues suggest that the gradual resolution of mucosal IL-6 activity and mononuclear infiltration after successful eradication observed in vivo may reflect gradually diminishing residual immune responses against H. pylori.

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BACKGROUND & AIMS: Interleukin (IL)-15 has been found to share many immunoregulatory activities in lymphocytes with IL-2. The aim of this study was to investigate IL-15 activity in organ cultures, localization of IL-15 messenger RNA (mRNA), and proliferation of lamina propria mononuclear cells (LPMCs) in response to recombinant IL-15 using the mucosal tissues obtained from patients with inflammatory bowel disease (IBD). METHODS: The contents of IL-15, tumor necrosis factor alpha, and IL-2 in the culture supernatant of the rectal mucosal tissues were determined by an enzyme-linked immunosorbent assay. Expression of IL-15 mRNA was analyzed by in situ hybridization, and proliferative response of LPMCs to recombinant IL-15 was determined by [3H]thymidine incorporation into DNA. RESULTS: Significantly greater IL-15 activity was detected in active IBD, and this elevation was also observed in inactive ulcerative colitis. In contrast, greater tumor necrosis factor alpha activity was observed only in active IBD, and IL-2 was not detected in organ cultures. In situ hybridization showed IL-15 mRNA in macrophages and epithelial cells in active IBD specimens, and recombinant IL-15 induced a dose-dependent proliferative response in LPMCs. CONCLUSIONS: Mucosal IL-15 may be involved in the pathogenesis of IBD as one of the important mediators in activation of mucosal immune cells.

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The present study aims at the development of a new concept system that will contribute toward improving the quality of life for bedridden patients and the elderly. The results of a basic study showed the possibility of a virtual reality system reducing stress and pain, provided VR sickness does not occur. A Bedside Wellness System which lets a person experience a virtual forest walk and provides a facility of rehabilitation was proposed based on the basic study and developed. An experiment to assess the developed system using healthy subjects was executed. The data suggested the positive effects of the system; however, some points to be improved were also extracted. After a few improvements, the system will be available for clinical use.

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We examined the relationship between the levels of macrophage inflammatory protein 1alpha (MIP-1alpha) and interleukin-8 (IL-8) in organ cultures of antral mucosal tissues, background gastroduodenal diseases, and grades of histologic gastritis. Significantly higher levels of MIP-1alpha and IL-8 were detected in patients with H. pylori infection than in those without infection. In H. pylori-positive patients, mucosal specimens from patients with peptic ulcer disease showed higher levels of MIP-1alpha and IL-8 than the specimens obtained from patients with erosive gastritis or those from endoscopically normal mucosa, and this was particularly pronounced in patients with duodenal ulcer. There were positive correlations between MIP-1alpha and IL-8 levels and histologic grades of activity, inflammation, and H. pylori density as defined by the Sydney system. However, the degree of association with the inflammatory cell count was different between these two chemokines. MIP-1alpha levels had a stronger association with mononuclear cells than with neutrophils, whereas IL-8 levels showed an association with neutrophils and mononuclear cells to an almost equal degree. These results suggest that MIP-1alpha and IL-8 may play important roles as inflammatory mediators in the pathogenesis of histologically proven H. pylori-associated gastritis.

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The possibility of applying Virtual Reality (VR) techniques to the mental care of patients is discussed in this chapter. VR technology holds much promise for providing supportive activities and promoting cooperation among caregivers. Interactivity with media may give the feeling of control to patients and thus provide a greater joy than passively watching television. Immersion in VR is expected to reduce pain and relieve anxieties for a while. Some kinds of VR content would make patients relaxed or encourage them in their fight against disease. Moreover, networked VR could offer a virtual space where patients meet, communicate, organize activities, and share experiences with other people--other patients, friends, family members, medical doctors, social workers, and so on. A basic study and trials to evaluate our developed VR system, called the 'Bedside Wellness System,' provide evidence for the effectiveness of this approach. Future research tasks are also discussed.

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OBJECTIVE: The effects of aging and liver disease on the pharmacokinetics of nipradilol were studied after a single oral dose of 6mg. STUDY PARTICIPANTS: Nipradilol was administered to three groups of subjects: younger healthy volunteers with a mean age of 33.2 years (group I, n = 6), older subjects without hepatic dysfunction with a mean age of 55.5 years (group II, n = 6), and patients with histologically confirmed cirrhosis of the liver with a mean age of 55.4 years (group III, n = 8). RESULTS: When compared with younger subjects (group I), the older subjects (group II) had a significantly longer time to maximum concentration, a greater area under the plasma concentration-time curve (AUC), a greater bioavailability (F), and a greater 24-hour urinary excretion of nipradilol. There was also a tendency towards a longer half-life in group II compared with group I. Cirrhotic subjects (group III) showed the same differences relative to group I. In addition, F was significantly larger and the plasma clearance was significantly decreased in group III compared with group II. Nearly identical results were demonstrated for the pharmacokinetics of denitrated nipradilol, one of the major metabolites of the test drug. A significant correlation was demonstrated between the AUC of nipradilol and age when groups I and II were combined. CONCLUSION: It was concluded that the pharmacokinetics of nipradilol may be altered with aging and hepatic dysfunction, and that changes in metabolism are likely to be a major factor.

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OBJECTIVES: In this study, our purpose was to determine whether locally generated interleukin-8 (IL-8) is involved in neutrophil migration and binding to extracellular matrix, using the colonic mucosal specimens obtained from patients with inflammatory bowel disease (IBD). METHODS: Levels of IL-8 secreted in the organ cultures were measured by enzyme-linked immunosorbent assay. Chemotactic activity and binding capacity of neutrophils were induced by the organ culture supernatants. RESULTS: Significantly higher levels of IL-8 were secreted in patients with IBD, and its elevation was more prominent in patients with active ulcerative colitis. The organ culture supernatants induced higher chemotactic activity and binding capacity of neutrophils in patients with IBD, especially in those with active ulcerative colitis, compared with controls. These effects were inhibited significantly when the supernatants were submitted to preincubation with neutralizing anti-IL-8 antibody. CONCLUSIONS: Increased mucosal generation of IL-8 may attract neutrophils from the circulation into the inflammatory site and induce binding of neutrophils in the interstitial tissue, contributing to accumulation and activation of neutrophils in the affected mucosa with IBD.

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To enhance the portal hypotensive effect of nonselective beta-blockers, combinations of vasoactive agents with different mechanisms should be considered. The effect of carvedilol (CAS 72956-09-3, Artist), and alpha-/beta-blocking agent, on hepatic and systemic hemodynamics in 10 patients with portal hypertension was evaluated. After administration of carvedilol, the hepatic venous pressure gradient (HVPG) decreased from 15.9 +/- 3.2 mmHg to 13.3 +/- 4.0 mmHg (mean +/- SD) at 60 min (-15%) and to 12.9 +/- 3.0 mmHg at 90 min (-17%, p < 0.05). However, only 5 patients showed a decrease of HVPG by more than 20% at 60 or 90 min. The estimated hepatic blood flow (EHBF) was not significantly reduced. In contrast, heart rate (-8%, p < 0.05), mean arterial pressure (-10%, p < 0.01), and cardiac index (CI) (-8%, p < 0.05) were all reduced at 90 min, while total systemic vascular resistance was not altered. The reduction of HVPG was significantly correlated with the decrease of CI (r = 0.6415, p < 0.05). The portal hypotensive effect of carvedilol may mainly result from a reduction of CI. However, because of the greater reduction of HVPG than that of CI, other additive actions were suggested.

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We examined secretion, mRNA expression, and histologic localization of interleukin-8 (IL-*) and growth-related gene product-alpha (GRO alpha) in the Helicobacter pylori-infected gastric antral mucosa. Antral biopsies were obtained from an area of endoscopically intact mucosa. Significantly higher levels of IL-8 and GRO alpha were secreted in organ cultures from patients with H. pylori infection, and their elevation was prominent in patients with duodenal ulcer. There was a significant association between these alpha-chemokine levels and histologic grades of activity, inflammation, and H. pylori density. In fresh antral biopsies, IL-8 and GRO alpha mRNA expression was detected more frequently in H. pylori-infected patients compared with those without infection. Immunofluorescence microscopy showed localization of IL-8 and GRO alpha proteins in gastric epithelial cells and infiltrating CD68+ macrophages. In the chemotaxis assay, a significant positive correlation was found between neutrophil migration induced by the organ culture supernatants and their contents of IL-8 and GRO alpha. After H. pylori eradication, a significant decrease was observed in IL-8 and GRO alpha levels detected in organ cultures. In conclusion, mucosal alpha-chemokine activity correlates well with histologic severity of H. pylori-associated antral gastritis and can be used to predict the effects of H. pylori eradication therapy.

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