Biomedical subjects

Y Kawashima

Publications and source records attributed to Y Kawashima.

At least 37 records · Page 2Linked to original sources

PubMed2001

The effect of cyclooxygenase-2 inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model.

BACKGROUND: Liver grafts from non-heart-beating donors inevitably suffer from warm ischemic injury. In these grafts, large quantities of inflammatory cytokines and arachidonic acid metabolites are induced, further aggravating injury. Cyclooxygenase (COX) is an intracellular enzyme that converts arachidonic acid into prostaglandin (PG)G2 and PGH2. COX has two isoforms: constitutive COX-1 and inducible COX-2. The aim of this study was to evaluate the effects of COX-2 inhibition by FK3311 (FK) on warm ischemic injury in a canine total hepatic vascular exclusion (THVE) model. STUDY DESIGN: Sixteen mongrel adult dogs were studied. The portal triad of the hilum and the inferior vena cava above and below the liver was clamped for 1 hour. Splanchnic decompression was achieved by active splenofemorojugular bypass. The animals were divided into two groups. FK (1 mg/kg) was administered in the FK group (n = 8), and saline was administered in the control group (n = 8). Hepatic venous blood was collected to measure serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and hyaluronic acid levels. Serum thromboxane (Tx)B2 and 6-keto-PGF1alpha levels were also measured. Hepatic tissue blood flow was estimated simultaneously. Liver specimens were harvested for histologic study and polymorphonuclear neutrophils were counted. RESULTS: Alanine aminotransferase, aspartate aminotransferase, and hyaluronic acid 2 and 6 hours after reperfusion and LDH 30 minutes and 2 and 6 hours after reperfusion were significantly (p < 0.05) lower in the FK group than in the control group. Hepatic tissue blood flow remained significantly (p < 0.05) higher in the FK group than in the control group 1, 2, and 6 hours after reperfusion. Histologic tissue damage was mild and polymorphonuclear neutrophil infiltration was significantly lower (p < 0.05) in the FK group than in the control group 1 and 6 hours after reperfusion. Thirty minutes after reperfusion, TxB2 was significantly reduced (p < 0.05) in the FK group, and 6-keto-PGF1alpha was not significantly lower. CONCLUSIONS: FK protected against hepatic warm ischemia-reperfusion injury by marked inhibition of TxA2.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Novel nitric oxide donor (FK409) ameliorates liver damage during extended liver resection with warm ischemia in dogs.

BACKGROUND: Nitric oxide attenuates ischemia-reperfusion injury by maintaining organ circulation through its actions as a vasoregulator, an inhibitor of platelet aggregation, and an attenuator of leukocyte adhesion. Otherwise, the harmful effects of enhanced nitric oxide production induced by inducible nitric oxide synthase mediate ischemia-reperfusion injury. FK409 has been characterized as a spontaneous nitric oxide donor. The aim of this study was to evaluate the effects of FK409 on extended liver resection with ischemia using a canine model. STUDY DESIGN: Adult mongrel dogs were subjected to 60 minutes of warm ischemia by partial inflow occlusion. After reperfusion the nonischemic lobes were resected and the remnant liver function was evaluated. The dogs were divided into two groups: the control group (n = 7) and the FK409 group (n = 6), which was given FK409 through the portal vein. RESULTS: The hepatic tissue blood flow, serum liver enzymes levels, and serum endothelin-1 level after reperfusion were significantly better in the FK409 group than in the control group. Electron microscopy demonstrated that endothelial cells and Ito cells were well-preserved in the FK409 group. The 3-day survival rate was statistically better in the FK409 group (67%) than in the control group (14%). CONCLUSIONS: FK409 appears to have protective effects during extended liver resection with ischemia.

Animals↗

PubMed2001

Lactulose-L-rhamnose intestinal permeability test in patients with liver cirrhosis.

A lactulose-L-rhamnose intestinal permeability test was conducted on 35 patients with liver cirrhosis and six normal controls. Gas chromatography was used to measure lactulose and L-rhamnose concentrations in blood and urine specimens. The excretion of each molecule was expressed as the percentage of the orally administrated dose and the lactulose-L-rhamnose ratio as the ratio of the percentage of each probe molecule excreted. The mean 8-h lactulose excretion ratios were 0.56 and 0.16% in patients with liver cirrhosis and the control subjects, respectively (P<0.05), whereas the corresponding excretion ratios for L-rhamnose were 4.40 and 3.49%. The mean lactulose-L-rhamnose excretion ratios in patients with liver cirrhosis and the control subjects were 0.124 and 0.049, respectively (P<0.05). The lactulose-L-rhamnose excretion ratio increased in patients with liver cirrhosis complicated by large intestinal vascular ectasia of the large intestine or rectal varices, which were used as parameters for evaluating the effects of portal hypertension on the lower digestive tract. These results suggest that an increase in lactulose intestinal permeability in patients with liver cirrhosis proves the effects of portal hypertension extending to the lower digestive tract.

Journal Article↗

PubMed2001

False positive reaction in ELISA for IgM class anti-M2 antibody and its prevention.

Anti-M2 of anti-mitochondrial antibodies is recognized as the specific autoantibody detected in sera from patients with primary biliary cirrhosis (PBC). The IgG class and IgM class of this antibody can be separately measured using each ELISA. In the present study, false positive reactions were found in some sera from non-PBC patients such as acute hepatitis A, syphilis and rheumatoid arthritis using the IgM anti-M2 ELISA. They showed an increase of polyclonal IgM, and positivity for IgM anti-cardiolipin or rheumatoid factors, respectively. So, we developed a means to prevent these false positive reactions. First, dilutions of test sera at 1:1000-fold were carried out in addition to the original method at 1:100-fold. Secondly, some blocking reagents were added into the buffer system. By serum dilution, non-specific bindings disappeared in most samples other than showing an increase in polyclonal IgM. Moreover, the addition of suitable blocking reagents such as fetal bovine serum (FBS) and skimmed milk into the buffer system could prevent these non-specific bindings. From these findings, the procedure of optical serum dilution and the addition of suitable blocking reagents successfully prevented false positive reactions in this IgM anti-M2 ELISA.

Journal Article↗

PubMed2001

Effects of a dual inhibitor of tumor necrosis factor-alpha and interleukin-1 on lipopolysaccharide-induced lung injury in rats: involvement of the p38 mitogen-activated protein kinase pathway.

OBJECTIVE: Sepsis is a major cause of adult respiratory distress syndrome. In this study, we evaluated the effect of FR167653, which is a potent suppressant of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 production, on lipopolysaccharide (LPS)-induced lung injury and lethality in rats, and we examined the involvement of p38 mitogen-activated protein (MAP) kinase in the action of FR167653. DESIGN: Prospective, randomized study. SETTING: Animal research facility in a university. SUBJECTS: Male Sprague-Dawley rats weighing 200-270 g. INTERVENTIONS: All the animals were assigned to one of the following four groups: control group, FR-only group, LPS-only group, and LPS/FR group. Animals in the LPS-only and LPS/FR groups received 6 mg/kg of LPS intravenously. The animals in the FR-only and LPS/FR groups also received an infusion of FR167653 at 0.2 mg x kg(-1) x hr(-1), commencing 30 mins before the LPS (or vehicle) injection and continuing for 5.5 hrs. MEASUREMENTS AND MAIN RESULTS: LPS significantly induced the accumulation of pulmonary neutrophils and lung edema, both of which were significantly attenuated by treatment with FR167653. FR167653 also significantly decreased the LPS-induced lethality. Histologically, tissue damage was milder in the LPS/FR group than in the LPS-only group. Serum concentrations of TNF-alpha and IL-1beta and plasma concentrations of thromboxane B2 were all suppressed in the LPS/FR group compared with the LPS-only group. Western blot analysis revealed that FR167653 inhibited the phosphorylation of p38 MAP kinase in lung tissues. CONCLUSIONS: FR167653 administration decreased serum TNF-alpha and IL-1beta concentrations, which was associated with decreased lung injury and lethality. The mechanism responsible for the decreased TNF-alpha and IL-1 may be related to the inhibitory effect of FR167653 on p38 MAP kinase activation.

Animals↗

PubMed2001

Passive targeting of doxorubicin with polymer coated liposomes in tumor bearing rats.

The purpose of this study was to reveal the effectiveness of the polymer coated liposomes as a carrier of the anticancer drug doxorubicin in intravenous administration. The size controlled doxorubicin-loaded liposomes (egg phosphatidylcholine : cholesterol = 1:1 in molar ratio) were coated with hydrophilic polymers (polyvinyl alcohol; PVA and hydroxypropylmethylcellulose; HPMC) having a hydrophobic moiety in the molecules (PVA-R, HPMC-R). The existence of a thick polymer layer on the surface of the polymer coated liposomes was confirmed by measuring the change in particle size and the amount of polymer on the liposomal surface. The polymer coating effects on the tumor accumulation of the drug encapsulated in the liposomes were evaluated in Walker rat carcinoma 256 cell bearing rats. The doxorubicin-loaded liposomes coated with PVA-R and HPMC-R showed higher drug accumulation into the tumor site by prolonging the systemic circulation in tumor-bearing rats. The targeting efficiency of the polymer coated liposomes calculated with the total and tumorous clearance of the drug was ca. 5 times larger than that of non-coated liposomes. We ascertained that polymers having a hydrophobic moiety in the molecule such as PVA-R and HPMC-R are suitable materials for modifying the surfaces of the doxorubicin-loaded liposome to improve its targeting properties.

Animals↗

PubMed2001

Formulation design of ointment base suitable for healing of lesions in treatment of bedsores.

We intended to develop a desired ointment base suitable for treatment of bedsores including the proliferation of granulation and epidermis. The main bedsore bacteria detected in our hospital were S. aureus in gram-positive coccus and P. aeruginosa in gram-negative bacillus. As the macrogol ointment (MO) was found to have bactericidal effects on these bacteria, MO was adopted as the base for the objective ointment. To improve the properties of the ointment base such as regulating the humidity of the exudation and controlling the release of antibiotics formulated in the ointment, co-formulating effects of various additives to MO were evaluated. The sustained release function of the ointment base was obtained by adding hydrophilic petrolatum (HP) to MO. However, the resultant ointment was found to have a poor humidity regulating property. On the other hand, MO containing 5% of hydroxypropyl cellulose (HPC) showed both the humidity regulating and the controlled drug releasing properties. It was considered that HPC particles dispersed in the ointment could be swelled by absorbing water to form a gel network. The curd tension meter tests for the ointments prepared with the various polymers showed that the MO-HPC base, which showed the highest sustained drug releasing property, was found to have the highest hardness. This result means that HPC formulated into the base forms the most rigid gel structure to resist the erosion of the ointment and to control the drug release.

Anti-Bacterial Agents↗

PubMed2001

[Preparation of a gel-forming ointment base applicable to the recovery stage of bedsore and clinical evaluation of a treatment method with different ointment bases suitable to each stage of bedsore].

A novel ointment base suitable for the treatment of bedsore at the recovery stage was developed by the use of hydroxypropyl methylcellulose (HM-HPMC) modified on the basis of the hydrophobicity. A considerable sustained release of drug (minocycline hydrochloride) formulated to the ointment (T50 of 170 min) was attained with a macrogol ointment (MO) mixed with the HM-HPMC and Carbopol (CP) of the formulating ratio of 3:7. It was also found that a change in the formulating ratio of HM-HPMC and CP lead to a change in the drug release rate. The water absorption property of the ointment base, required to absorb on exudative solution in applying to the bedsore treatment, was as high as that of an ointment base containing hydroxypropyl cellulose (HPC) and CP reported in our previous paper. We clinically evaluated the effectiveness of the bedsore treatment, in which different ointment bases were applied to patients at different stages of the bedsore. A total of 22 cases were divided into two categories for applying to the different treatments. One category comprised of 11 subjects was treated with a povidone-iodine sugargel, which was the conventional method in our hospital, while the other 11 subjects were treated by the use of the newly developed ointment bases in consideration for the different stages of the bedsore. In comparison of the clinical results with the healing index, we ascertained that the latter method was significantly more efficacious (p < 0.01-0.05) than the conventional one. The effectiveness was emphasized in treating the intractable bedsore classified into the grades IV and V. Therefore, we confirmed that the newly developed ointment base formulation is useful in treating bedsore at each stage.

Acrylic Resins↗

PubMed2001

Papillon-Lefèvre syndrome: serum immunoglobulin G (IgG) subclass antibody response to periodontopathic bacteria. A case report.

BACKGROUND: Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder which is characterized by palmar-plantar hyperkeratosis and rapid periodontal destruction of both primary and permanent dentitions. In this case report, we present clinical features, and microbiological and immunological findings of 40 month-old Thai male PLS patient. METHODS: Microbiological examinations consisted of bacterial culture methods utilizing selective media, morphological identification, and biochemical tests. In addition, the specific serum IgG subclass antibody titers reactive with etiologic periodontal bacteria were determined by the dot-blot immunological analysis and enzyme linked immunosorbent assay (ELISA). RESULTS: The examinations revealed that the patient harbored 3 major suspected periodontopathic microorganisms, A. actinomycetemcomitans, P. gingivalis, and P. intermedia. The patient's serum IgG1, IgG2, and IgG3, but not IgG4, titers against A. actinomycetemcomitans were dramatically increased. The predominant IgG subclass was IgG1. In contrast, the IgG titers against other tested bacteria, P. gingivalis, P. intermedia, and F. nucleatum, appeared to be similar to those of a healthy control. CONCLUSIONS: A. actinomycetemcomitans seems to play a pivotal role in the bacteria-host interaction in PLS periodontal pathogenesis. Response of the specific serum IgG subclass antibody titers against the A. actinomycetemcomitans antigen has been demonstrated. This association warrants further investigation.

Actinobacillus Infections↗

PubMed2001

[Perioperative mortality and morbidity for the year of 1999 in 466 Japanese Certified Anesthesia-training Hospitals: with special reference to ASA-physical status--report of Committee on Operating Room Safety of Japan Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan for the year 1999 were studied retrospectively. Committee on Operating Room Safety of the Japan Society of Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified Training Hospitals of JSA and received answers from 60.2% of the hospitals. We analyzed their answers with special reference to ASA physical status (ASA-PS). The total number of anesthetics analyzed was 655, 644. Mortality and morbidity due to all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and operation were as follows. The incidence of cardiac arrest (per 10,000 anesthetics) was 0.68, 3.76, 14.37, 67.03, 0.36, 4.68, 27.96, 206.30 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 8.93, 26.99, 71.30, 188.52, 8.68, 31.27, 136.16, and 790.92 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates (death during anesthesia and within 7th postoperative day) after cardiac arrest were 0.16, 0.94, 5.71, 33.51, 0.00, 1.46, 16.41 and 167.76 per 10,000 anesthetics in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality rates were 0.24, 1.66, 12.16, 67.03, 0.00, 3.51, 34.65 and 417.14 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. Overall mortality and morbidity were higher in emergency anesthetics than in elective anesthetics. ASA-PS correlated well with overall mortality and with morbidity, regardless of etiology. The incidences of cardiac arrest totally attributable to anesthesia were 0.24, 0.45, 1.47, 8.38, 0.36, 1.75, 2.43 and 11.34 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of all critical events totally attributable to anesthesia were 4.92, 8.81, 14.74, 20.95, 4.34, 11.40, 15.80 and 22.67 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates after cardiac arrest totally attributable to anesthesia were 0.00, 0.00, 0.61 and 4.53 in patients with ASA-PS of I-IV, I E-II E, III E, and IV E, respectively. The overall mortality rates totally attributable to anesthesia were 0.00, 0.04, 0.18, 0.00, 0.00, 0.61 and 4.53 in patients classified to ASA-PS of I, II, III, IV, I E-II E, III E, and IV E, respectively. Only one death, due to overdose of anesthetics, was reported among patients with good physical status (ASA-PS of I, II, II E and II E). Anesthetic management was mainly responsible for critical events in patients with good physical status, while co-existing diseases were in those with poor physical status. The major co-existing diseases or conditions leading to critical events were heart diseases in elective anesthetics, and hemorrhagic shock in emergency anesthetics. We reconfirmed that ASA-PS is beneficial to predict perioperative mortality and morbidity. It also seems likely that we should make much more efforts to reduce anesthetic morbidity in patients with good physical status, and to improve preanesthetic assessment and preparation of cardiovascular conditions in those with poor physical status.

Anesthesiology↗

PubMed2001

[Perioperative mortality and morbidity in 1999 with a special reference to age in 466 certified training hospitals of Japanese Society of Anesthesiologists--report of Committee on Operating Room Safety of Japanese Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan from Jan. 1 to Dec. 31, were studied retrospectively. Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified Training Hospitals of JSA and received answers from 60.2% of the hospitals. We analyzed their answers with a special reference to the age group. The total number of anesthetics available for this analysis was 732,788. All cases were divided in to 7 groups; group A(< 1 months), group B(< 12 months), group C(< 5 years), group D(< 18 years), group E (< 65 years), group F(< 85 years), and group G(> 85 years). The incidences of all critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 168.14, 47.86, 24.63, 14.65, 28.43, 50.4, and 43.68 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The overall mortality rate (death during anesthesia and within 7th postoperative day) were 74.10, 6.63, 3.30, 3.07, 4.82, 13.74, and 11.84 per 10,000 anesthetics in patients with group A, B, C, D, E, F, and G, respectively. The incidences of cardiac arrest were 54.15, 8.84, 5.08, 2.56, 4.84, 11.02, and 6.66 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The mortality rates after cardiac arrest were 42.75, 2.95, 2.54, 1.70, 2.00, 6.56, and 5.18 in patients with group A, B, C, D, E, F, and G, respectively. The incidences of all critical events, the incidence of cardiac arrest, and the overall mortality rate were much higher in group A than other groups and lower in group D. Mortality and morbidity due to all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and operation were as follows. The incidence of all critical events attributable to co-existing disease were the highest in these four groups, and 94.04, 15.46, 7.87, 6.13, 7.26, 17.38, and 16.29 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The incidences of all critical events attributable to anesthetic management were 31.35, 16.94, 4.60, 6.09, 10.77, and 14.07 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The incidence of cardiac arrest in group A was much more attributable to co-existing disease and operation than other causes. The incidences of cardiac arrest attributable to anesthetic management were 0.00, 1.47, 0.25, 0.34, 0.83, 0.92, and 0.22 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The mortality rates in these groups were 0.00, 0.00, 0.00, 0.17, 0.07, 0.05, and 1.48, and no death was found in cases under 5 years of age. The two cases of death in G group were due to too high anesthesia levels in spinal anesthesia. Other causes including overdose of anesthetics, toxic effect of local anesthetic, improper management of airway, and incompatible blood transfusion were preventable with the anesthesiologists' effort in protocol development and skilled assistance.

Adolescent↗

PubMed2001

[Annual report of perioperative mortality and morbidity for the year 1999 with a special reference to anesthetic methods at Certificated Training Hospitals of Japanese Society of Anesthesiologists].

The Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sends annually confidential questionnaires of perioperative mortality and morbidity to Certificated Training Hospitals of JSA. This report is on perioperative mortality and morbidity in 1999 with a special reference to anesthetic methods. Four hundred and sixty-seven hospitals reported the number of cases referred to anesthetic methods and total numbers of cases were 727,723. The incidences of cardiac arrest per 10,000 cases due to all etiology are estimated to be 6.77 cases in average, 5.33 cases in inhalation anesthesia, 34.26 cases in total intravenous anesthesia (TIVA), 5.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 5.29 cases in TIVA plus epidural or spinal or conduction block, 0.73 cases in spinal with continuous epidural block (CSEA), 2.85 cases in epidural anesthesia, 1.63 cases in spinal anesthesia, 2.53 cases in conduction block and 46.51 cases in other methods. However, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.78 case in average, 0.51 case in inhalation anesthesia, 1.35 cases in TIVA, 0.97 case in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, 0.73 case in CSEA, 1.71 cases in epidural anesthesia, 0.54 case in spinal anesthesia, 2.52 cases in conduction block and 1.08 cases in other methods. The incidences of severe hypotension per 10,000 cases due to all etiology are estimated to be 16.64 cases in average, 13.61 cases in inhalation anesthesia, 100.36 cases in TIVA, 13.32 cases in inhalation anesthesia plus epidural or spinal or conduction block, 9.07 cases in TIVA plus epidural or spinal or conduction block, 3.65 cases in CSEA, 6.26 cases in epidural anesthesia, 7.31 cases in spinal anesthesia, 2.52 cases in conduction block and 28.12 cases in other methods. On the other hand, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 2.40 cases in average, 1.65 cases in inhalation anesthesia, 0.81 cases in TIVA, 3.92 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, 3.42 cases in epidural anesthesia, 2.71 cases in spinal anesthesia, zero case in conduction block and zero case in other methods. The incidences of severe hypoxia per 10,000 cases due to all etiology are estimated to be 5.32 cases in average, 6.7 cases in inhalation anesthesia, 9.17 cases in TIVA, 5.16 cases in inhalation anesthesia plus epidural or spinal or conduction block, 4.53 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, zero case in epidural anesthesia, 1.08 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. On the other hand, the incidences of severe hypoxia per 10,000 cases totally attributable to anesthesia are estimated to be 2.39 cases in average, 3.22 cases in inhalation anesthesia, 2.43 cases in TIVA, 2.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, zero case in CSEA, zero case in epidural anesthesia, 0.54 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. The mortality rates of cardiac arrest per 10,000 cases due to all etiology are estimated to be 3.56 cases in average, 2.82 cases in inhalation anesthesia, 24.55 cases in TIVA, 1.4 cases in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, zero cases in CSEA, 0.57 cases in epidural anesthesia, 0.27 cases in spinal anesthesia, zero case in conduction block and 42.18 cases in other methods. On the other hand, the mortality rates of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.08 case in average, 0.09 case in inhalation anesthesia, 0.27 case in TIVA, 0.05 case in inhalation anesthesia plus epidural or spinal or conduction block, zero case in TIVA plus epidural or spinal or conduction block, zero case in CSEA, 0.57 case in epidural anesthesia, zero case in spinal anesthesia, conduction block and other methods. The outcomes of cardiac arrest totally attributable to anesthesia are 70.2% of full recovery without any sequelae, 10.5% of death within 7 days, 1.8% of vegetative state and 17.5% of unknown results while the outcome of critical events including severe hypotension and severe hypoxia totally attributable to anesthesia is 94.9% of full recovery without any sequelae, 0.4% of death within 7 days, 0.2% of vegetative state and 4.5% of unknown results. These results indicate that there are no differences in mortality and morbidity totally attributable to anesthesia among anesthetic methods in 1999 at Certificated Training Hospitals of Japan Society of Anesthesiologists.

Anesthesia↗

PubMed2001

Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease.

The use of nanoparticles for targeted oral drug delivery to the inflamed gut tissue in inflammatory bowel disease was examined. Such a strategy of local drug delivery would be a distinct improvement compared with existing colon delivery devices for this disease. An experimental colitis was induced by trinitrobenzenesulfonic acid to male Wistar rats. Rolipram, an anti-inflammatory model drug, was incorporated within poly(lactic-coglycolic acid) nanoparticles, which were administered once a day orally for five consecutive days. A clinical activity score and myeloperoxidase activity were determined to assess the inflammation, whereas an adverse effect index reflected the remaining neurotropic effect of rolipram resulting from its systemic absorption. All nanoparticle formulations proved to be as efficient as the drug in solution in mitigating the experimental colitis. The clinical activity score and myeloperoxidase activity decreased significantly after the oral administration of rolipram nanoparticles or solution. During the next 5 days when animals were kept without drug treatment the drug solution group displayed a strong relapse, whereas the nanoparticle groups continued to show reduced inflammation levels. The rolipram solution group had a high adverse effect index, whereas the rolipram nanoparticle groups proved their potential to retain the drug from systemic absorption as evidenced by a significantly reduced index. This new delivery system enabled the drug to accumulate in the inflamed tissue with higher efficiency than when given as solution. The nanoparticle deposition in the inflamed tissue should be given particular consideration in the design of new carrier systems for the treatment of inflammatory bowel disease.

Animals↗

PubMed2001

[Perioperative mortality and morbidity for the year 1999 in 466 Japanese certified anesthesia-training hospitals: with special reference to operative regions--report of Committee on Operating Room Safety of Japanese Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan for the year 1999 were analyzed retrospectively with special reference to operative regions. The total number of analyzed cases was 701,940. The percentages for each operative region were as follows, craniotomy 4.5%, thoracotomy 3.3%, heart and great-vessels 3.9%, thoracotomy with laparotomy 0.8%, laparotomy except caeserian-section 31.7%, ceserian-section 3.2%, head-neck and otolarynx 14.5%, chest-abdomen-perineum 11.1%, spine 3.5%, extremity including peripheral-vessel 16.5%, and others 6.9%. The incidence of serious events, including cardiac arrest and severe hypotension and hypoxemia suggesting impending cardiac arrest was 34.58 per 10,000 cases in all operative regions. The events were observed more frequently in heart and great-vessels 247.26, thoracotomy with laparotomy 128.91 and thoracotomy 61.55, and less frequently in chest-abdomen-perineum 13.52 and extremity including peripheral-vessel 16.99. Regarding the prognosis of events, the cases with no sequela were 69.9% in all operative regions. While there were fewer cases with no sequela in craniotomy 50.4%, thoracotomy with laparotomy 54.3% and heart and great-vessels 58.6%, there were more cases in head-neck and oto-larynx 95.2% and chest-abdomen-perineum 90.5%. The incidence of serious events totally attributable to anesthetic management was 7.79 per 10,000 cases in all operative regions. The events were observed more frequently in thoracotomy 12.82, heart and great-vessels 12.29 and spine 11.06, and less frequently in extremity including peripheral-vessel 5.17 and chest-abdomen-perineum 6.05. Regarding the prognosis of events, the cases with no sequela were 93.1% in all operative regions. There were fewer cases with no sequela in thoracotomy with laparotomy 80.0% and craniotomy 81.8%. The main cause of events in thoracotomy and spine was the inadequate airway management, and in heart and great-vessels was the overdose or miss-selection of drugs. Although the incidence of serious events totally attributable to anesthetic management was one fourth of all events, most of them resulted from human factors. Thus, the more efforts are necessary to improve the outcomes. While the total deaths from 701,940 cases, including death on the operation day or within 7 days after it, were 528 cases (7.52 per 10,000 cases), the deaths totally attributable to anesthesia were 7 cases (0.10 per 10,000 cases).

Anesthesia↗

PubMed2001

[Annual study of perioperative mortality and morbidity for the year of 1999 in Japan: the outlines--report of the Japan Society of Anesthesiologists Committee on Operating Room Safety].

Anesthetic mortality and morbidity in Japan Society of Anesthesiologists (JSA) Certified Training Hospitals (CTH) for the year 1999 were reported as continuation of annual studies started in 1993. The JSA Committee on Operating Room Safety (CORS) sent confidential questionnaires to 774 CTH and received valid responses from 60.3% of hospitals. A total number of 793,840 anesthetics were documented. The respondents were asked to report all cases of cardiac arrests and other critical incidents (serious hypotension, serious hypoxemia and others), and their outcomes (death in operating room, death within 7 days, transfer to vegetative state and rescue without sequelae) as well as one principal cause for each incident from list of 52 items. They were also requested to submit the tabulation of patients by ASA physical status, age distribution, surgery sites and anesthetic methods. Analysis was made by total incidents under anesthesia/surgery, and also by incidents totally attributable to anesthetic management (AM), due to preoperative complications (PC), due to intraoperative pathological events (IP) and due to surgery (SG), with special reference to each of four tabulation groups and the whole group of patients. This paper focused analysis on all patients, as analyses with special reference to ASA physical status, age distribution, surgery sites and anesthetic methods were previously reported. Total incidence of cardiac arrest under anesthesia/surgery was 6.53 per 10,000 anesthetics. PC, IP and SG represented principal causes in 42.9%, 22.0% and 21.4% causes of total cardiac arrest cases, respectively. AM was noted as the principal cause in 12.0% of cases, with an incidence rate of 0.78 per 10,000. In 52 more detailed classification of principal causes, the most frequent cause of cardiac arrest was preoperative hemorrhagic shock, 20.3% of all cardiac arrests. The second cause was massive hemorrhage and/or hypovolemia due to surgical procedures (13.1%), and the third was intraoperative myocardial infarction/coronary ischemia/coronary spasm (9.5%). Prognoses of cardiac arrest cases declined due to PC: 71.1% of cardiac arrests died in the operating room or within 7 days after surgery and only 19.8% survived without sequelae. The best prognoses were found in cardiac arrest cases due to AM: 69.4% survived without sequelae and 12.9% died. The mortality rate post-cardiac arrest was 3.44 per 10,000 anesthetics, of those 0.10 due to AM, 0.57 due to IP, 1.99 due to PC and 0.76 due to SG. The mortality rate after critical incidents other than cardiac arrest such as severe hypotension and severe hypoxemia was 3.75, of those 0.03 due to AM, 0.28 due to IP, 2.31 due to PC and 1.13 due to SG. The final mortality rate attributable to anesthesia/surgery including deaths post-cardiac arrest and after other critical incidents was 7.19 per 10,000 anesthetics and very close to 7.18 [6.22, 8.13], that of mean [95% C.I.] in 1994-1998. The final mortality rate totally attributable to anesthesia was 0.13 per 10,000 anesthetics, which was significantly improved from 0.21 [0.15, 0.27], that of mean [95% C.I.] in 1994-1998. IP, PC and SG showed the final mortality rate of 0.84, 4.30 and 1.89, respectively. Five major causes of all critical incidents were massive hemorrhage due to surgical procedures (20.8%), preoperative hemorrhagic shock (10.7%), surgical technique (8.0%), inappropriate airway management (5.2%) and intraoperative myocardial infarction and coronary ischemia (4.5%). Drug overdose or selection error (3.9%) and overdose of main anesthetic (2.9%) as a result of human error occupied the 7th and 10th places. As far as anesthetic management to reduce mortality and morbidity related to anesthesia is concerned, we should increase vigilance to avoid human errors in addition to improving preanesthetic preparations and assessment of cardiovascular status as well as intraoperative management of cardiovascular events.

Anesthesia↗

PubMed2000

Basic study for stabilization of w/o/w emulsion and its application to transcatheter arterial embolization therapy.

Stabilization of w/o/w emulsion and its application to transcatheter arterial embolization (TAE) therapy are reviewed. W/o/w emulsion was stabilized by making inner aqueous phase hypertonic, addition of chitosan in inner phase, and techniques of phase-inversion with porous membrane. Lipiodol w/o/w emulsion for TAE therapy was prepared by using a two-step pumping emulsification procedure. The procedure is so easy that the emulsion could be prepared even during the surgical operation. The deposition after hepatic arterial administration of the emulsion was detected by an X-ray CT scanner. The concentration of epirubicin hydrochloride (EPI) in liver was increased and its residence was prolonged by encapsulating it in the w/o/w emulsion. The toxic effects of EPI and lipiodol on the normal hepatic cells were reduced. The w/o/w emulsion prepared by us is a suitable formulation for the TAE therapy.

Animals↗

PubMed2000

Contribution of ecto-5'-nucleotidase to the inhibition of platelet aggregation by human endothelial cells.

We studied the role of adenosine (Ado), which is generated from adenine nucleotides via the activity of ecto-5'-nucleotidase (ecto-5'-NT), in the inhibition of platelet aggregation by endothelial cells (ECs). The enzymatic activity of nucleotidases on human umbilical vein endothelial cells (HUVECs) was examined with regard to (1) the inhibition of adenosine diphosphate (ADP)-induced platelet aggregation and (2) the liberation of inorganic phosphate from adenine nucleotides. Adenosine 5'-monophosphate (AMP) preincubated with HUVECs significantly inhibited ADP-induced platelet aggregation. This was completely blocked by the treatment of HUVECs with a specific inhibitor of ecto-5'-NT, 5'-[alphabeta-methylene] diphosphate (APCP), or by the addition of an A(2a) receptor antagonist. Neither nitric oxide nor prostacyclin was involved in this inhibitory activity, suggesting that Ado generated in the incubation medium by the activity of 5'-NT on HUVECs inhibited platelet aggregation. When ADP was incubated on HUVECs, it lost most of its agonistic activity for platelets. Pretreatment of HUVECs with APCP at a concentration that abolished ecto-5'-NT activity partially restored ADP-induced platelet aggregation. Ecto-5'-NT contributes to EC function by inhibiting platelet aggregation in cooperation with ATP diphosphohydrolase, which degrades ADP to AMP.

5'-Nucleotidase↗

PubMed2000

Polymer coating of liposomes with a modified polyvinyl alcohol and their systemic circulation and RES uptake in rats.

The objective of this study was to evaluate the in vivo characteristics of liposomes coated with a polyvinyl alcohol having a long alkyl chain at the end of the molecule (PVA-R) as an injectable drug carrier for passive targeting of drugs. A fluorescence marker, cholesteryl-anthracene-9-carboxylate, was incorporated into the liposomes to detect their concentration in the plasma and organs. The small unilamellar liposomes (100 nm in diameter) with various lipid compositions, such as the different cholesterol contents or the different charges, were prepared by the hydration method followed by sonication and coated with PVA or PVA-R by just mixing the resultant liposomal suspensions with the polymer solutions. The circulation and distribution of the liposomes were tested with their intravenous administration in rats. The PVA-R-coated liposomes showed significantly higher circulation compared to that of non-coated ones in any liposomal formulation tested. The prolonged circulation of PVA-R-coated liposomes was attributed to their fewer uptake in liver and spleen. The extent in improvement in the in vivo characteristics were well interpreted by the hydrophobicity of liposomes and their coating amount of PVA-R. It was also demonstrated that the liposomes having a positive and a negative charge, which showed the completely different circulating profiles, showed almost the same profile by coating with PVA-R. When the liposomes were coated with PVA the improvement in blood circulation was much less in any cases, although coating layer of PVA was detected. These results confirm that not only the hydrophilic property but the sterically stabilizing effect of the coating layer is important to prolong the circulation of the particulate drug carriers with less RES uptake, and the PVA-R having a hydrophobic moiety at the end of the molecule of PVA is a suitable material for the coating of liposomes.

Animals↗