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Biomedical subjects

R Komatsu

Publications and source records attributed to R Komatsu.

At least 19 recordsLinked to original sources

Ondansetron does not reduce the shivering threshold in healthy volunteers.

BACKGROUND: Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans. METHODS: Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant. RESULTS: Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximately 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4) degrees C, ondansetron 37.6 (0.3) degrees C, P=0.16), vasoconstriction (37.0 (0.5) degrees C vs 37.1 (0.3) degrees C; P=0.70), or shivering threshold (36.3 (0.5) degrees C vs 36.3 (0.6) degrees C; P=0.76). No sedation was observed on either study day. CONCLUSIONS: /b>. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.

Adult↗

Intravenous myocardial contrast echocardiography predicts regional and global left ventricular remodelling after acute myocardial infarction: comparison with low dose dobutamine stress echocardiography.

OBJECTIVE: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE). METHODS: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2-4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months' follow up. Percentage increase in LV end diastolic volume (%DeltaEDV) was also calculated. RESULTS: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %DeltaEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%DeltaEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72). CONCLUSION: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling.

Aged↗

Comparison of the intubating laryngeal mask airway and laryngeal tube placement during manual in-line stabilisation of the neck.

We compared the placement of the laryngeal tube (LT) with the intubating laryngeal mask airway (ILMA) in 51 patients whose necks were stabilised by manual in-line traction. Following induction of anaesthesia and neuromuscular blockade, the LT and ILMA were inserted consecutively in a randomised, crossover design. Using pressure-controlled ventilation (20 cmH(2)O inspiratory pressure), we measured insertion attempts, time to establish positive-pressure ventilation, tidal volume, gastric insufflation, and minimum airway pressure at which gas leaked around the cuff. Data were compared using Wilcoxon signed-rank tests; p < 0.05 was considered significant. Insertion was found to be more difficult with the LT (successful at first attempt in 16 patients) than with the ILMA (successful at first attempt in 42 patients, p < 0.0001). Time required for insertion was longer for the LT (28 [23-35] s, median [interquartile range]) than for the ILMA (20 [15-25] s, p = 0.0009). Tidal volume was less for the LT (440 [290-670] ml) than for the ILMA (630 [440-750] ml, p = 0.013). Minimum airway pressure at which gas leak occurred and incidence of gastric insufflation were similar with two devices. In patients whose necks were stabilised with manual in-line traction, insertion of the ILMA was easier and quicker than insertion of the LT and tidal volume was greater with the ILMA than the LT.

Adult↗

Intubating laryngeal mask airway allows tracheal intubation when the cervical spine is immobilized by a rigid collar.

BACKGROUND: An intubating laryngeal mask airway (ILMA) facilitates tracheal intubation with the neck in neutral position, which is similar to the neck position maintained by a rigid cervical collar. However, a cervical collar virtually obliterates neck movement, even small movements that normally facilitate airway insertion. We therefore tested the hypothesis that the ILMA will allow tracheal intubation even in patients wearing a rigid cervical collar. METHODS: We performed blind tracheal intubation via an ILMA under general anaesthesia in 50 patients with a rigid Philadelphia collar in place undergoing cervical spine surgery and 50 general surgical patients. Time required for intubation, intubation success rate, and numbers and type of adjusting manoeuvres used were recorded. RESULTS: Inter-incisor distance was significantly smaller (4.1 (0.8) vs 4.6 (0.7) cm, mean (sd), P<0.01) and Mallampati scores were significantly greater (P<0.001) in the patients with collars. ILMA insertion took longer (30 (25) vs 22 (6) s), more patients required two insertion attempts (15 vs 3; P<0.005), and ventilation adequacy with ILMA was worse (P<0.05) in collared patients. However, there were no significant differences between the collars and control patients in terms of total time required for intubation (60 (41) vs 50 (30) s), number of intubation attempts, overall intubation success rate (96 vs 98%), or the incidence of intubation complications. CONCLUSIONS: Blind intubation through an ILMA is thus a reasonable strategy for controlling the airway in patients who are immobilized with a rigid cervical collar.

Adolescent↗

Short-term effect of buformin, a biguanide, on insulin sensitivity, soluble fraction of tumor necrosis factor receptor and serum lipids in overweight patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) showed that biguanide therapy in overweight patients reduced the risk for any diabetes-related endpoint and all-cause mortality. Biguanides lower the blood glucose values without stimulation of insulin release. We have investigated the short-term effect of buformin on insulin sensitivity, solved tumor necrosis factor receptors (sTNFRs), and serum lipids in overweight subjects with type 2 diabetes mellitus (DM). METHOD: Thirteen overweight subjects with type 2 DM were examined. The subjects who were fed 20 kcal/kg body weight were divided into two subgroups according to whether they were treated by buformin (Buformin group), or dietary therapy alone (Diet group). Six patients were in Buformin group and seven patients were in Diet group. We calculated insulin-mediated glucose uptake by the liver and peripheral tissues using euglycemic hyperinsulinemic clamp combined with an oral glucose load before and after buformin treatment or diet therapy for 2 weeks. RESULTS: Fasting plasma glucose, total cholesterol (T-chol), LDL-cholesterol (LDL-chol), and sTNFR2 were significantly decreased, and hepatic glucose uptake significantly increased from 32 +/- 7 to 42 +/- 7% (P < 0.05) in Buformin group but did not changed significantly in Diet group. However, the glucose infusion rate thought to express insulin sensitivity in peripheral tissue, TNF-alpha, sTNFR1, fasting plasma insulin, C-peptide, and NEFA levels did not change significantly in both the groups after treatment. CONCLUSION/INTERPRETATION: Buformin improved insulin sensitivity in the liver and decreased T-chol, LDL-chol, and sTNFR2. The mechanism of action for buformin likely involves inhibition of TNF-alpha. Buformin lowers insulin resistance and risk factors for cardiovascular disease including serum lipid and will therefore, be useful in management of overweight type 2 DM patients.

Buformin↗

Spectroscopic studies of a LiRbB4O7:Cu(II) crystal grown by the Czochralski technique.

A copper-doped LiRbB4O7 crystal was grown by the Czochralski technique. Powder X-ray, EPR and optical absorption studies were carried out. The results and discussion of the copper doped LiRbB4O7 crystal indicate that the copper ions enter the host lattice by replacing Li ions. The Cu(II) ion spectrum is characteristic of a tetragonally elongated octahedral site. Lattice and spin-Hamiltonian parameters were evaluated. The bonding parameters indicate that the bonding between copper and the ligands is partly covalent.

Boron Compounds↗

AIDS, HIV and STD among Japanese and Japanese-Americans in San Francisco, California, USA.

In affluent countries, some people may go abroad specifically for HIV testing or care for greater anonymity, better treatment, and less discrimination. A secondary analysis of data from the San Francisco Department of Public Health was conducted to characterize trends in AIDS incidence, AIDS care, sexually transmitted disease (STD) incidence, and HIV counselling and testing among Japanese in San Francisco. A total of 96 AIDS cases were diagnosed among ethnic Japanese, of whom 32 were born in Japan. From 1985 to 2000, 144 gonorrhoea and chlamydia cases were identified among Japanese. Of 368 self-identified Japanese seeking HIV counselling from 1995 to 1997, three (0.9%) were HIV-positive. The HIV/AIDS and STD epidemics among Japanese in San Francisco temporally parallels, but lags behind in magnitude, the epidemics for San Francisco's population as a whole. Some persons from Japan actively seek HIV/STD services while abroad. Our study points to several areas needing further research and improvements.

Acquired Immunodeficiency Syndrome↗

Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.

BACKGROUND: There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. METHODS AND RESULTS: Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP (P<0.0005) or SAP (P<0.0001) or in controls (P<0.0001) (AMI, 1.95+/-1.42 ng/5 microgram LDL protein; UAP, 1.19+/-0.74 ng/5 microgram LDL protein; SAP, 0.89+/-0.48 ng/5 microgram LDL protein; control, 0.58+/-0.23 ng/5 microgram LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL-positive macrophages was significantly higher in patients with UAP than in those with SAP (P<0.0001). CONCLUSIONS: This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL-positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.

Angina Pectoris↗

Vascular smooth muscle cell phenotypes in primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is associated with specific structural alterations, including cellular intimal thickening, intimal fibrosis, and plexiform lesions. To determine the phenotypes of smooth muscle cells (SMCs) in such lesions, the authors conducted an immunohistochemical analysis of lung tissues from two patients with PPH, using two antimuscle actin antibodies, HHF35 and CGA7, and two anti-SMC myosin heavy chain markers, anti-SM1 and anti-SM2 antibodies and related antibodies. Cells that stained positive (+) with HHF35, CGA7, anti-SM1, and anti-SM2 were considered to be SMCs of a mature state. Conversely, those that stained positive with HHF35 and anti-SM1, but weakly positive (+/-) or negative (-) with CGA7 and anti-SM2, were considered to be SMCs exhibiting an immature state. Cellular intimal thickening was composed of SMCs of an immature phenotype (HHF35+, CGA7+/-, SM1+, SM2+/-), accompanied by the expression of fibronectin and the presence of macrophages; intimal fibrosis contained mature SMCs (HHF35+, CGA7+, SM1+, SM2+); and plexiform lesion consisted of proliferative endothelial cells (von Willebrand factor-positive cells, proliferating cell nuclear antigen-positive cells) and underlying immature SMCs (HHF35+, CGA7-, SM1+, SM2-) associated with fibronectin expression and macrophage infiltration. These findings suggest that smooth muscle cells with specific phenotypes may contribute to the development of specific vascular lesions in primary pulmonary hypertension.

Actins↗

Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages: intracellular fate of oxidized low density lipoprotein.

Oxidized phosphatidylcholine (OxPC) formed in oxidized low density lipoprotein (OxLDL) is thought to be involved in the development of atherosclerosis. OxPC has been found in foam cells in atherosclerotic lesions and suggested to be the epitope for OxLDL recognition by macrophages. OxPC is present as a complex with apolipoprotein B (apoB) in OxLDL, since some OxPC can bind with proteins. In the current study, the intracellular fate of OxPC-apoB complexes after internalization of OxLDL by macrophages was investigated. Murine macrophage cell line J774.1 was incubated with either OxLDL or acetylated LDL for 24 h, then the cells were further incubated for up to 24 h in new medium without lipoprotein. Modified apoB in the cells was quantitated by sandwich ELISA using monoclonal antibodies against OxPC and apoB. Intracellular OxLDL decreased rapidly for the first 4 h to approx. 20% of that before medium change, with the apparent metabolism of OxPC-apoB complex ceasing. OxPC-apoB complexes that remained in the cells after 24 h chasing increased as the period of OxLDL loading in macrophages prolongs. Acetylated LDL in the cells decreased quickly and disappeared after 4 h of chasing. Subcellular fractionation using sucrose density gradient ultracentrifugation of macrophages, which had already accumulated OxPC-apoB complexes by 24 h of incubation with OxLDL and further 24 h chasing, showed that the complex was co-localized with endosomal and lysosomal markers. Immunohistochemical double staining studies demonstrated that OxPC and apoB co-localize in foam cells in early atherosclerotic lesions obtained from human coronary artery. These results suggest that OxPC-apoB complexes originating from OxLDL accumulate in foam cells in human atherosclerotic lesions as well as in macrophages in vitro.

Animals↗

Lithium potassium borate and lithium rubidium borate: new non-linear optical crystals

The title compounds, LiKB(4)O(7) and LiRbB(4)O(7), are newly developed non-linear optical crystals containing two kinds of anionic groups, namely (B(3)O(8))(7-) and (B(5)O(10))(5-). The (B(3)O(8))(7-) groups form infinite spiral chains parallel to the [100] direction, which are interconnected by sharing O atoms with (B(5)O(10))(5-) groups.

Journal Article↗

Adenosine-induced coronary flow reserve in Watanabe heritable hyperlipidemic rabbits.

The Watanabe heritable hyperlipidemic (WHHL) rabbit develops coronary atherosclerosis and hypercholesterolemia because of a genetic deficiency of low-density lipoprotein receptors and is therefore a good animal model for studying the relationships of coronary atherosclerosis, hypercholesterolemia and coronary flow reserve. The aim of the present study was to assess myocardial perfusion at baseline and during adenosine infusion (0.2 mg x kg(-1) x min(-1)) in 8 WHHL rabbits (13.8+/-0.5 months) with 13N-ammonia, small-animal positron emission tomography (PET) and colored microspheres. Results were compared with those from 6 age-matched Japanese white rabbits. Plaque distribution was also examined in the extramural coronary arteries. All 8 WHHL rabbits had coronary plaques, with 6 showing multiple plaques. Mean global myocardial blood flow (ml x min(-1) x g(-1)) did not differ significantly between control and WHHL groups both at baseline (3.67+/-0.72 vs 4.26+/-1.12 ml x min(-1) x g(-1), p=NS) and with adenosine (7.92+/-2.00 vs 9.27+/-2.91 ml x min(-1) x g(-1), p=NS), nor did coronary flow reserve (2.16+/-0.37 vs 2.18+/-0.41, p=NS). None showed evidence of regional perfusion abnormalities by visual and semiquantitative analyses of PET images. It was concluded that WHHL rabbits preserve adenosine-induced coronary flow reserve despite coronary atherosclerosis and hypercholesterolemia, suggesting that a compensatory mechanism develops in this animal model.

Adenosine↗

Increased JNK, AP-1 and NF-kappa B DNA binding activities in isoproterenol-induced cardiac remodeling.

The in vivo signal transduction pathway, responsible for isoproterenol-induced cardiac hypertrophy or remodeling, remains to be clarified. The purpose of this study was to examine c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), activator protein-1 (AP-1) and nuclear factor-kappa B (NK-kappa B) DNA binding activity, which seem to be important in a signal transduction cascade upstream of the increased level of mRNA expression observed in isoproterenol-induced cardiac remodeling. Rats were continuously infused with saline and isoproterenol by intravenous injection (a short period; 0.5 microgram/kg/min) and an osmotic minipump (a long period; 0.5 or 3 mg/kg/day). Cardiac morphology was measured by echocardiography. JNK and ERK were measured by in gel kinase assay. AP-1 and NF-kappa B DNA binding activity was determined using an electrophoretic mobility shift assay. Echocardiogram showed that the thickness of the left ventricular anterior wall (AW) and left ventricular posterior wall (PW) increased at day 1 in low doses, and at day 1 in high doses. Isoproterenol significantly increased ERK and JNK activity at 15 min after intravenous infusion of 0.5 microgram/kg/min isoproterenol. At late phase about JNK and ERK activity, only a high dose of isoproterenol increased JNK. AP-1 DNA binding activities spurred by low or high doses of isoproterenol administration increased at 12 h, reached their peak of 24.1- and 37.1-fold (P < 0.01), respectively, at 24 h, and thereafter decreased. Although low doses of isoproterenol did not change the level of NF-kappa B DNA binding activities, high doses increased it to 10.9-fold (P < 0.01) at day 2. This study showed increased JNK, ERK, AP-1 and NF-kappa B DNA binding activities in isoproterenol-induced cardiac remodeling. AP-1 may contribute to the isoproterenol-induced cardiac remodeling, and JNK or NF-kappa B may also play some roles in it.

Animals↗

Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important angiogenic factor reported to induce migration and proliferation of endothelial cells, enhance vascular permeability, and modulate thrombogenicity. VEGF expression in cultured cells (smooth muscle cells, macrophages, endothelial cells) is controlled by growth factors and cytokines. Hence, the question arises of whether VEGF could play a role in atherogenesis. METHODS AND RESULTS: Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal with diffuse intimal thickening, early atherosclerosis with hypercellularity, and advanced atherosclerosis (atheromatous plaques, fibrous plaques, and totally occlusive lesions). VEGF expression as well as the expression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immunohistochemical techniques in these samples at the different stages of human coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction. Normal arterial segments showed no substantial VEGF expression. Hypercellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunostaining for VEGF was observed in accumulated macrophages and endothelial cells of the microvessels. Furthermore, VEGF mRNA expression was detected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in aggregating macrophages in atherosclerotic lesions and also in endothelial cells of the microvessels in totally occlusive lesions. CONCLUSIONS: These results demonstrate distinct expression of VEGF and its receptors (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arteries. Considering the multipotent actions of VEGF documented experimentally in vivo and in vitro, our findings suggest that VEGF may have some role in the progression of human coronary atherosclerosis, as well as in recanalization processes in obstructive coronary diseases.

Adult↗

Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses.

BACKGROUND: Experimental animal studies have shown that coronary stenting induces neointimal proliferation. However, the histopathological events after coronary stenting in humans have not been studied systematically. METHODS AND RESULTS: We investigated 11 stented coronary arteries (9 Palmaz-Schatz stents, 1 Wiktor stent, and 1 ACS Multi-Link stent) obtained from 11 patients who had died 2 days to 21 months after stenting. We focused on gross, histological, and immunohistochemical aspects of the repair processes. Two patients developed symptoms of restenosis. Serial sections were stained with antibodies against smooth muscle cells (SMCs), macrophages, and endothelial cells. At 9 and 12 days after stenting, the stent sites showed thrombus formation with early formation of neointima composed of abundant macrophages and alpha-actin-negative spindle cells. From 64 days on, all sites with stenting showed a distinct layer of neointima, albeit to varying degrees. In nonrestenotic lesions, neointimal thickening was markedly less than in restenotic lesions but without qualitative differences; the neointima contained macrophages but was composed predominantly of alpha-actin-positive SMCs. CONCLUSIONS: These observations strongly support the concept that neointimal proliferation in humans is a process of staged redifferentiation of SMCs, which may cause in-stent stenosis. Moreover, the exuberant neointimal proliferation with accumulation of macrophages and extensive neovascularization at sites of stent restenosis suggests a role for organization of mural thrombus.

Actins↗

Efficacy and safety of early coronary stenting for unstable angina.

To determine the efficacy and safety of early coronary stenting for unstable angina, we studied 91 consecutive patients with unstable angina. Thirty-one patients underwent stenting 72 h or more after admission, and another 60 patients underwent stenting within 72 h of admission. The clinical and angiographic follow-up had been done for 6 mo. There were no differences between the baseline clinical and angiographic characteristics of both groups. The maximum balloon pressure was higher (14.1 +/- 1.2 vs. 12.6 +/- 0.9, P < 0.01) and the hospital stay was shorter (9.7 +/- 2.7 vs. 18.7 +/- 5.8 d, P < 0.0001) in the early stenting group. These two groups were similar in the clinical success rate (90.0% vs. 93.5%), without any abrupt closure, subacute thrombosis, death, myocardial infarction, or coronary bypass surgery. These findings indicate that early stenting can be useful in patients with unstable angina.

Aged↗