Serum cortisol level and depth of propofol-induced sedation.
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Biomedical subjects
Publications and source records attributed to M Shimada.
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BACKGROUND: The poor quality of oral health care for people with intellectual disability (ID) has been recognized, and the strong fears about dental treatment suggested as a major reason for disturbances of visits to dentists by such patients. Intravenous sedation is a useful method for relieving the anxiety and fear of such patients about dental treatment, and is frequently essential for ID patients undergoing dental treatment. However, decision regarding the dose of sedative required to be administered for an adequate level of sedation is difficult because the effect of sedation cannot be adequately assessed in patients with severe ID. As an appropriate sedative dose for dental patients with ID has not been fully established, we investigated sedative doses required and the effect of sedation in patients with ID, compared with other dental patients. METHODS: We reviewed the anaesthetic records of dental patients with ID (73 cases) and other dental patients (19 cases) aged between 20 and 29 years who had undergone intravenous sedation with midazolam and propofol in Okayama University Dental Hospital, from January 2000 to December 2000. Intravenous sedation was induced with a bolus intravenous administration of midazolam (2-3 mg) and maintained with a continuous infusion of propofol. The dose of propofol was titrated to achieve an adequate level of sedation: asleep but responding to painful stimulation. The efficacy of sedation, the required doses of propofol, and the wake-up times were investigated for all subjects. The efficacy of sedation was evaluated by judging whether the patient became cooperative and allowed the dental treatment to be carried out or not. The complications induced by intravenous sedation were also evaluated in each subject. Differences in variables between subjects with ID and other subjects were analysed using the Mann-Whitney U-test. RESULTS: Intravenous sedation was effective for dental treatment in all subjects with or without ID. The required dose of propofol in subjects with ID was 4.74 mg/kg/h (2.63-10.33 mg/kg/h), significantly higher than that required for other subjects (3.31, 1.72-4.80 mg/kg/h). Wake-up times of subjects with ID were similar to those of the other subjects. Severe complications were not seen during or after intravenous sedation. CONCLUSION: The results of this study show that intravenous sedation is a useful method for dental patients with ID as well as for other dental patients, but indicate that dental patients with ID need higher doses of sedative to obtain an adequate level of sedation.
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The TBP-like protein (TLP/TRF2/TLF), which belongs to the TBP family of proteins, is present in all metazoan organisms. Although the human TLP has been reported to interfere with transcription from TATA-containing promoters, the transcription activation potential of TLP in higher animals is obscure. We previously demonstrated that artificially promoter-recruited TLP behaves like an unconventional transcriptional activator. In this study, we investigated the effects of TLP on TATA-less promoters of mouse and human terminal deoxynucleotidyl transferase (TdT) genes by transient reporter assays. As expected, TLP repressed both basal and activator-augmented transcription from the TATA-containing adenovirus major late promoter (MLP) and E1B promoter. On the other hand, however, TLP significantly stimulated both basal and activated transcription from TdT promoters. We investigated the strength of the promoters in chicken DT40 cells that lack the TLP gene. The MLP showed higher activity but the TdT promoter showed lower activity in TLP-null cells than in the wild-type cells. Moreover, ectopic expression of mouse TLP in the TLP-null cells considerably stimulated the TdT promoter. Insertion of a TATA element upstream from the TdT core promoter resulted in a loss of TLP-mediated activation. The mouse TLP was demonstrated to bind specifically to TFIIA with greater strength than TBP. We constructed mutated TLPs having amino acid substitutions that impair TFIIA binding. A representative TLP mutant lacking TFIIA-binding ability could not stimulate transcription from the TdT promoter, whereas that mutation suppressed TLP-mediated transcription repression of TATA promoters. The results of the present study suggest that the vertebrate TLP potentiates exogenous TATA-less promoters and that TFIIA plays an important role in the TLP function.
We constructed a sex allocation model for local mate competition considering the asymmetry of competitive abilities among sons. This model assumes two females of a parasitoid wasp oviposit on the same host in sequential order. The evolutionarily stable strategy will be in either Stackelberg or Nash equilibrium, depending on whether the females can recognize their opponent's sex ratio or not, respectively. The Nash equilibrium predicts the second female produce more males than the first. If the second female is able to know and respond to the strategy of the first (a Stackelberg equilibrium), the first will decide an optimal sex ratio assuming that the second reply to it. Under such an assumption, our model predicts that not producing sons is adaptive for the second female when the sons she produces have low competitive ability. Males of parasitoid wasps Melittobia spp. are engaged in lethal male-male combat, indicating large asymmetry in mating success among sons. If females have the ability to recognize their opponent's sex ratio, our model suggests that the severe lethal male-male combat may be one factor explaining their extremely female-biased sex ratio that is unexplainable by pre-existent models.
AIM: Angiopoietin 1 (Ang-1) and its antagonist, angiopoietin 2 (Ang-2), are novel ligands that regulate the Tie2 receptor. The Ang-2 gene is upregulated in the hypervascular type of human hepatocellular carcinoma (HCC). To gain a better understanding of the role of the Ang-Tie2 system in HCC the expression of these genes was investigated in a series of human HCCs. METHODS: The expression of the angiopoietin and Tie2 proteins was investigated in nine normal liver tissues and 52 surgically resected HCCs. In addition, the effects of hypoxic stimuli on Ang-1, Ang-2, vascular endothelial growth factor (VEGF), and erythropoietin (EPO) expression was investigated in Hep3B cells. RESULTS: Ang-1, rather than Ang-2, was more frequently expressed in the normal liver. Ang-1 was expressed in 68% of HCCs, whereas Ang-2 was expressed in 81%, and was significantly higher in poorly differentiated HCCs characterised by high vascularity (p = 0.02), and in tumours with a peliotic change (p = 0.02). Strong expression of Tie2 was seen in tumour vessels in accordance with Ang-2 expression. In Hep3B cells, hypoxic stimuli upregulated VEGF and EPO, but not Ang-1 or Ang-2. CONCLUSIONS: These data support the evidence that the reversal of Ang-1 and Ang-2 expression plays an important role in the angiogenic and dedifferentiation processes in HCC. The hypoxic stimuli were not responsible for Ang-2 upregulation, unlike that of VEGF, in human HCC cells.
In this study, we investigated the mechanisms of protein kinase B (PKB) activation and its role in cumulus cells during in vitro meiotic resumption of porcine oocytes. PKB activity in cumulus cells was significantly decreased by 12 h cultivation of cumulus-oocyte complexes (COCs) in basic medium. However, the addition of phosphodiesterase inhibitors, hypoxanthine or 3-isobutyl-1-methylxanthine, maintained the level of PKB activity in cumulus cells at comparable with that in cumulus cells just after collection from their follicles. When COCs were cultured with phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, PKB activity was significantly decreased, and both caspase 3 activity and the proportion of apoptotic cells were significantly increased as compared with those in cumulus cells just after collection from their follicles. Moreover, the inhibitory effect of hypoxanthine on spontaneous meiotic resumption was overcome by addition of LY294002. On the other hand, markedly high activity of PKB and high intensity of the phosphorylated PKB band were observed in cumulus cells of COCs which were cultured with FSH. The addition of 20 microM LY294002 to FSH-containing medium induced an apoptosis of cumulus cells, whereas little apoptotic-positive signal was detected in COCs cultured with 5 microM LY294002 and FSH. However, the inhibitory effects of LY294002 on progesterone production by cumulus cells and germinal vesicle breakdown in oocytes reached a maximum at 5 microM. Thus, high activity of the PI 3-kinase-PKB pathway in cumulus cells plays an important role in FSH regulation of cell function. Judging from these results, it is estimated that PI 3-kinase in cumulus cells is required for both the suppression of spontaneous meiotic resumption and the induction of gonadotropin-stimulated meiotic resumption.
We invesigated the availability of human hepatoblastoma cell line (Hep G2), compared with human primary hepatocytes (HH) and porcine primary hepatocytes (PH), as a cell source for the hybrid artificial liver support system (HALSS) by using polyurethane foam (PUF). All three kinds of hepatocytes spontaneously formed spherical multicellular aggregates (spheroids) of 100-200 microm diameter in the pores of PUF within 3 days of culture. In a PUF stationary culture, Hep G2 spheroids recovered the ammonia removal activity that was lost in monolayer culture, although the removal for each unit cell number was about one tenth that of HH spheroids and about one eighth of PH spheroids. The synthesis activities of albumin and fibrinogen of each unit cell number of Hep G2 were also upregulated by PUF spheroid culture, and were about twice as high as in monolayer culture. The albumin secretion activity of Hep G2 spheroids was almost the same as that of PH spheroids. HH scarcely secreted these proteins in this experiment, probably because they were cultured in a serum-free medium. In the PUF module in a circulation culture, HH had high ammonia removal and low synthesis activities similar to stationary culture. Hep G2 proliferated to a high cell density, such as about 4.8 x 10(7) cells/cm3-module at 10 days of culture. Although Hep G2 spheroids had low ammonia removal activity in each cell, the removal rate in the PUF module was almost the same as for PH at 7 days of culture because of the high cell density culture by cell proliferation. The albumin secretion rate by Hep G2 in the PUF module also increased with cell proliferation and was about 10 times higher than the initial for the rate for PH at 7 days of culture. These results suggest that Hep G2 is a potential cell source PUF-HALSS.
Usually intrahepatic cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis. As a treatment for intrahepatic cholangiocarcinoma, dissection of lymph nodes alone does not seem to offer any significant advantages. The laparoscopic hepatectomy procedure, however, is a minimally invasive liver surgery. We recently had the case of a patient who underwent successful laparoscopic hepatectomy and dissection of lymph nodes for intrahepatic cholangiocarcinoma in the left lateral segment of the liver. The patient had intrahepatic cholangiocarcinoma with distant lymph node metastasis around the common hepatic artery determined to stage IVb according to TNM classification. The operation time was 335 min, and the total blood loss was only 225 ml. A left lateral hepatectomy and complete lymph node dissection around the hepatoduodenal ligament and celiac trunk was performed. In this case, a laparoscopic procedure enabled the patient to have an early discharge, and there was no recurrence for 14 months. Another advantage for this patient was that the hospital stay lasted only 10 days. As compared with conventional surgery, laparoscopic surgery reduces blood loss and shortens the hospital stay. In conclusion, laparoscopic surgery for intrahepatic cholangiocarcinoma is a good treatment for advanced intrahepatic cholangiocarcinoma because it allows a positive early postoperative outcome and possibly a better result over the long term.
Hemostasis of a resected stump of liver is extremely difficult in laparoscopic hepatectomy. Although Pringle's maneuver, which is a total clamping of the hepatoduodenal ligament, is a useful technique, it is often difficult in laparoscopic circumstances. Moreover, total inflow occlusion leads to postoperative liver damage. Therefore, the local bleeding method is ideal. The Endoclose, a device for port site closure, is formed from an outer sheath and an inner needle with a notch to load the suture. The Endoclose is loaded with a suture and passed through the liver. The suture is left under the liver, and the device is removed. Next, the suture carrier is passed through the liver at an appropriate distance, and the suture is regrasped by this suture carrier and brought out of the liver. Herein we report a case in which a new bleeding control method using Endoclose was introduced for laparoscopy-assisted hepatectomy.
We performed a variety of complete total endoscopic general surgical procedures, including colon resection, distal gastrectomy, and splenectomy, successfully with the assistance of the da Vinci computer-enhanced surgical system. The robotic system allowed us to manipulate the endoscopic instruments as effectively as during open surgery. It enhanced visualization of both the operative field and precision of the necessary techniques, as well as being less stressful for the endoscopic operating team. This technological innovation can therefore help surgeons overcome many of the difficulties associated with the endoscopic approach and thus has the potential to enable more precise, safer, and more minimally invasive surgery in the future.
The colour of tattooed skin has been predicted by a Monte Carlo method based on the optical coefficient spectra of the skin and tattoo dyes. Slices of pig skin, a tattoo phantom and skin phantoms with different thickness were prepared, and their reflectance and transmittance spectra were measured using an integrating sphere at wavelengths varying from 400nm to 700nm. The absorption and scattering coefficient spectra of skin phantoms, pig skins and the tattoo phantom were each calculated using the inverse Monte Carlo method. The skin phantoms and pig skins were overlaid on the tattoo phantom, and the reflectance spectra of the two-layered structures were measured. The reflectance spectra of the two-layered structures were calculated from the optical coefficient spectra using the Monte Carlo method. They agreed well with the measured spectra. The colour differences between the calculated and measured spectra were also evaluated by the L*a*b* colour space distances and showed good agreement, with 3.49 for the skin phantoms and 8.27 for the pig skins.
The medial temporal lobe, especially the hippocampus, is important for normal cognitive function. especially for memory, and is the region with the earliest and most extensive pathological changes in Alzheimer's disease (AD). We investigated the atrophic changes of the hippocampus over a 5-year period and its relation to cognitive screening test performances in normal elderly subjects, those with very mild AD, and patients with AD. Fifty-seven elderly subjects without a moderate or greater degree of cerebrovascular disease as shown by MRI were randomly selected from the town of Tajiri. Thirty-three subjects with a clinical dementia rating (CDR) of 0 (normal), 18 CDR-0.5 (very mild AD) subjects, and six CDR-1&2 (AD) subjects underwent MRI and the Mini Mental State Examination (MMSE) twice during the period. Retrospective changes in the hippocampal width and the MMSE scores were evaluated. There were significant CDR group effects for the changes in the mean bilateral hippocampal widths and the MMSE scores. Normal subjects did not show cognitive decline, although there was a slight tendency for hippocampal atrophy. A significant and meaningful Spearman's correlation was noted between left hippocampal atrophy and the MMSE scores over the 5-year period for the CDR-0.5 group. These CDR-0.5 subjects met the MCI (mild cognitive impairment) criteria as proposed by the consensus paper. Findings suggested that normal elderly subjects maintain a high level of cognitive functions for at least 5 years, although hippocampal atrophy might occur. Atrophic change of the left hippocampus might be a good marker of the very early stage of AD.
AIMS: The c-erbB-2 and c-Met proto-oncogenes are important for tumour invasiveness and metastasis in many types of malignant tumours. Previous studies have indicated that these proteins are associated with carcinogenesis in intrahepatic cholangiocarcinoma. In this study, we examined c-erbB-2 and c-Met expression by immunohistochemistry in hepatolithiasis, intrahepatic cholangiocarcinoma and metastatic lymph node, in order to clarify whether these proteins play a role in carcinogenesis and tumour metastasis in intrahepatic cholangiocarcinoma. METHODS AND RESULTS: In hepatolithiasis, the staining for c-erbB-2 was positive in 14 of the 23 (61%) cases, while staining for c-Met was positive in eight of the 23 (35%) cases. In intrahepatic cholangiocarcinoma, staining for c-erbB-2 was positive in 45 of the 81 (55%) cases, while staining for c-Met was positive in 28 (35%) cases. The positivity of c-Met staining in intrahepatic cholangiocarcinoma was significantly higher in the differentiated type of cholangiocarcinoma than in the undifferentiated type. In addition, c-Met-positive staining had an inverted correlation with tumour size, the presence of perineural invasion and the presence of lymph node metastasis. c-Met staining had a significantly higher positivity in cases at an early stage of intrahepatic cholangiocarcinoma. In contrast, the positivity of c-erbB-2 staining in intrahepatic cholangiocarcinoma was significantly higher in cases with lymph node metastasis than in cases without. In metastatic lymph nodes, the staining for c-erbB-2 was positive in 20 of the 25 (80%) cases, while staining for c-Met was positive in six of the 25 (24%) cases. There was no difference in survival between c-erbB-2-positive and negative patients. However, the patients with c-Met-positive tumours had a significantly longer survival than those with c-Met-negative tumours in the medium survival term. The multivariate analysis showed the presence of lymph node metastasis, lymphatic permeation and histological differentiation to be independent prognostic factors. CONCLUSION: These results indicate that increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma, while increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis.
BACKGROUND: Excessive upregulation of gastric epithelial cell apoptosis is speculated to be associated with ulcerogenesis in Helicobacter pylori-positive peptic ulcer disease. H. pylori may have an ulcerogenic effect through induction of gastric epithelial cell apoptosis mediated by infiltrating T cells and their soluble products. METHODS: The contents of soluble Fas ligand (sFasL) and interferon-gamma (IFN-gamma) in organ cultures and the degree of apoptosis and the expression of apoptosis-related proteins in the gastric epithelium were examined using the mucosal tissues obtained from the antrum and the ulcer site in patients with H. pylori-positive gastric ulcer (GU). The molecular mechanisms of gastric epithelial cell apoptosis induced by sFasL and IFN-gamma were analyzed using epithelial cell lines, MKN 45 and KATO III. RESULTS: The mucosal tissues of the ulcer site had substantially higher contents of sFasL and IFN-gamma in organ cultures regardless of its healing stage in association with increased numbers of apoptotic cells and enhanced expression of proapoptotic proteins Bak and Bax in the surface foveolar epithelium as compared with the antral tissues in patients with H. pylori-positive GU. The addition of sFasL caused increases in cytotoxic cell death and caspase-3 activation in MKN 45 and KATO III cells in which IFN-gamma treated cells had more prominent effects than untreated cells. The expression of Bak in MKN 45 cells increased when they were treated with IFN-gamma. CONCLUSIONS: Upregulation of mucosal sFasL and IFN-gamma may be involved in ulcerogenesis in patients with H. pylori-positive GU through induction of gastric epithelial cell apoptosis.
BACKGROUND: Interleukin (IL)-17 is a newly identified T-cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of CD4+ T-cell-derived cytokines on chemokine secretion in human pancreatic periacinar myofibroblasts. METHODS: The secretion of IL-8 and monocyte chemoattractant protein (MCP)-1 was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analyzed by Northern blot and a binding assay using 125I-labeled IL-17. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). RESULTS: IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h. and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 secretion and additively enhanced MCP-1 secretion. IFN-gamma induced a weak increase in IL-17R mRNA abundance, but incubation with IFN-gamma for 24 h had no effects on 125I-labeled IL-17-binding, indicating that the co-stimulatory effects of IL-17 and IFN-gamma were not regulated by the modulation of IL-17R expression. Furthermore, IL-17 induced a rapid increase in NF-kappaB DNA-binding activity, and the combination of IL-17 and IFN-gamma further enhanced NF-kappaB DNA-binding activity. CONCLUSIONS: In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion in human pancreatic periacinar myofibroblasts. The combination of IL-17 with IFN-gamma further enhances chemokine secretion. These findings indicate a linkage between T-cell-mediated immunity and inflammatory responses in the pancreas.
We describe a preclinical study of our original hybrid artificial liver support system (HALSS) for a clinical trial. We designed a HALSS comprising a multi-capillary polyurethane foam packed-bed module (MC-PUF module) containing a total 200 g (2 x 10(10) cells) porcine hepatocytes, and an extracorporeal circulation device. Almost all porcine hepatocytes in the MC-PUF module formed many spherical multicellular aggregates (spheroids). This extracorporeal circulation device was improved to promote solute exchange between a living body and a MC-PUF module by including a plasma bypass line in the circulation loop. The efficacy of the HALSS was evaluated using a 25-kg pig with warm ischemic liver failure by portocaval shunt and ligation of hepatic artery (HALSS group, n=3). As a control experiment, the same system without hepatocytes in the module was used with the same kind of liver failure pig (Control group, n=3). The blood ammonia in the control group was 143 N-microg/dl at the start of circulation, and rapidly increased to 351 N-microg/dl at 2 hours and to 704 N-microg/dl at 6 hours. But the blood ammonia in the HALSS group was completely suppressed, and remained less than the hepatic coma level (over 200 N-microg/dl) during the circulation time. The blood glucose in the control group gradually decreased, and became less than 40 mg/dl within 6 hours of circulation. But the blood glucose in the HALSS group was maintained well, and remained the normal glucose level (50 - 105 mg/dl) for more than 20 hours of circulation. Improvement in blood creatinine and lactate, and the stabilization of vital signs and urinary excretion, were observed in the HALSS group. The survival time of the pigs in the HALSS group was 19.3 hours compared with 8.9 hours in the control group. In conclusion, our HALSS was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that our HALSS has a strong possibility to be used in treating liver failure patients. We have applied for approval of the clinical trial of our HALSS to our institutional ethics committee.
Steroid hormones, such as progesterone, oestrogen, androgen and meiosis activating sterols, are secreted from cumulus cells that are stimulated by gonadotrophins during maturation of oocytes in vitro. These steroid hormones may be absorbed by mineral oil or paraffin oil; however, in vitro maturation of pig oocytes is commonly performed using medium covered by oil. In this study, high concentrations of progesterone, oestradiol and testosterone were detected in the culture medium after pig cumulus-oocyte complexes (COCs) were cultured with FSH and LH for 44 h in medium without an oil overlay. However, high concentrations of these steroid hormones were not detected in medium when COCs were cultured with the mineral oil overlay. When high concentrations of these steroid hormones were secreted by COCs, germinal vesicle breakdown (GVBD) and the activation of p34(cdc2) kinase and mitogen-activated protein (MAP) kinase in oocytes occurred earlier in comparison with oocytes cultured in medium covered with mineral oil. Moreover, a decrease in p34(cdc2) kinase activity during meiotic progression beyond metaphase I was observed in oocytes cultured in conditions under which high concentrations of steroid hormones were secreted by COCs. In addition, the rate of development to the blastocyst stage after IVF was higher in oocytes matured in medium without an oil overlay. These adverse effects of oil may be explained by absorption by the oil of cumulus-secreted steroids or by the release of toxic compounds into the medium.