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Biomedical subjects

A Sawada

Publications and source records attributed to A Sawada.

At least 19 recordsLinked to original sources
PubMed1998

Mutagenicity of isomeric alkanediazotates, precursors for ultimate alkylating species of carcinogenic N-nitroso compounds.

Alkanediazohydroxides are common key intermediates in carcinogenesis and mutagenesis of N-nitroso compounds, which are widely found in human environment. Mutagenicity of (E)- and (Z)-potassium alkanediazotates, as precursors of corresponding alkanediazohydroxides were evaluated to investigate the effect of geometric isomerism and also the effect of alkyl groups on their biological activity. Mutagenicity of N-nitroso-N-alkylureas which spontaneously produce alkanediazohydroxides after non-enzymatic hydrolysis were also tested in comparison to that of the corresponding diazotates and other activated chemical species of N-nitrosamines. When the mutagenicity was assayed in three microbial strains, Salmonella typhimurium TA1535, and Escherichia coli WP2 and WP2 uvrA, the order of mutagenic potency of the compounds with the same alkyl group was as follows; (E)-diazotates > (Z)-diazotates > nitrosoureas. The effect of alkyl groups on the mutagenic potency was different in Salmonella strain and in E. coli strains, and this result could be explained by the efficiency of O6-alkylguanine-DNA alkyltransferase. In each bacterial strain, this effect of alkyl groups was similar in mutagenicity induced by (E)- and (Z)-diazotates, N-nitroso-N-alkylureas and other activated N-nitrosodialkylamines such as alpha-hydroxy nitrosamines. The geometrical isomerism affected the mutagenicity of (E)- and (Z)-potassium alkanediazotates, and the result suggested that alkanediazohydroxides react through diazonium ions in a cage rather than through free alkyldiazonium ions which have no geometrical isomerism. Our results confirmed that (E)-potassium alkanediazotates, (Z)-potassium alkanediazotates and N-nitroso-N-alkylureas all decomposed through diazohydroxides, and that alkanediazohydroxides are the active alkylating species of N-nitroso compounds, and also that the geometrical isomerism is important for carcinogenic N-nitroso compounds to show their biological activity.

Alkylating Agents↗
PubMed1998

Favorable response to lymphoblastoid interferon-alpha in children with chronic hepatitis C.

BACKGROUND/AIMS: We investigated the efficacy of interferon therapy for the treatment of children with chronic hepatitis C virus infection. METHODS: Twenty-four out of 26 children completed the 6-month treatment with lymphoblastoid interferon-alpha and were followed for 12 months or longer. Response to interferon therapy was defined by assaying for circulating HCV-RNA, using a nested PCR, at 6-month intervals after the end of the therapy. RESULTS: At the end of treatment circulating HCV-RNA was undetectable in 18/24 patients and at 6 months in 12/24. Ten of these 12 primary responders have remained virus free for more than 2 years. One patient remained negative at 12 months. The remaining patient relapsed at 12 months. At 24 months 10 of 18 patients tested negative for HCV-RNA. Serum alanine aminotransferase was normal in 11/24 patients at the end of treatment, at 6 months 12/24 were normal, and at 12 months 11/12 were normal. In eight children with sustained response, repeated liver biopsies revealed a reduction in Knodell's scores for inflammation in the hepatic lobules and in the portal areas. In three of them neither plus nor minus strand of HCV-RNA was detectable in the liver tissue. Responders had a significantly lower level of viremia than non-responders. Side effects of interferon including fever, hair loss, neutropenia, and thrombocytopenia were not serious enough to warrant cessation of interferon treatment. CONCLUSIONS: Interferon therapy in children with chronic hepatitis C may be beneficial as evaluated by sustained loss of viremia as well as by primary response.

Adolescent↗
PubMed1998

Multifocal electroretinogram indicates visual field loss in acute zonal occult outer retinopathy.

PURPOSE: To report alterations of electrophysiologic tests, including the multifocal electroretinogram, in a case of acute zonal occult outer retinopathy. METHOD: We recorded photopic, scotopic, and single-flash electroretinograms and a multifocal electroretinogram in a 47-year-old woman with acute zonal occult outer retinopathy in the right eye. RESULTS: Her visual acuity was 20/20 in the right eye throughout the follow-up period. The electroretinograms indicated retinal impairment of the right eye, predominantly in the cones. The multifocal electroretinogram showed reduced responses corresponding to the visual field defect of the static perimetry. CONCLUSIONS: In acute zonal occult outer retinopathy, impairment of the retinal area results in a visual field defect. The multifocal electroretinogram can be useful in determining the location of the defect.

Acute Disease↗
PubMed1998

Effect of debridement of the retinal pigment epithelium in full-thickness macular hole surgery.

We assessed the efficacy of debridement of the retinal pigment epithelium (RPE) from the base of the macular hole during vitrectomy to treat 83 eyes of 75 patients with a stage 2 (n=29), stage 3 (n=35) or stage 4 (n=19) macular hole. Patients ranged in age from 51 to 77 years (mean, 67.6 years). Duration of symptoms preoperatively ranged from 1 to 120 months (average, 19.2 months). During vitrectomy for macular hole, the RPE at the base of the hole was gently aspirated with either a silicone-tipped extrusion needle or a blunt-tipped 27-gauge needle. Follow-up averaged 13.0 months (range, 3 to 36 months). The holes resolved in 73 (88%) of the 83 eyes after one surgical procedure. In 73 eyes with a follow-up period of 6 months or more, sixty-five (89%) showed improved VA of at least two lines of Snellen equivalent. Fifty-five (75%) eyes had a visual acuity (VA) of > or = 20/40. Our preliminary results suggest that RPE debridement from the base of the hole is a useful adjunct to vitrectomy for treating full-thickness macular holes.

Aged↗
PubMed1998

Peripheral blood stem cell autografts for the treatment of children over 1 year old with stage IV neuroblastoma: a long-term follow-up.

This is the first report of the long-term therapeutic results in 22 children more than 1 year old with stage IV neuroblastoma who were treated with autologous peripheral blood stem cell transplantation (PBSCT). The median age of the patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who were evaluated for N-myc amplification were positive. PBSC were collected by a median of four aphereses per patient. The patients underwent PBSCT from 6 to 21 months after the start of therapy (median 10.5 months) at which time 13 patients were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16 (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the primary cytoreductive regimen. The median number of infused MNC and CFU-GM was, respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died of regimen-related toxicities and one patient who was transplanted with refractory disease died of disease progression without any benefit from transplantation. Hematological recovery was evaluated in 21 patients, excluding one early death. The median number of days required to achieve an AGC of >0.5 x 10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13 who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84 months. Although the retrospective nature of this study and several variables prevent a meaningful analysis, the overall results still support the feasibility of developing a prospective study of PBSCT with a larger number of children with high-risk neuroblastoma.

Child↗
PubMed1998

Effects of nitric oxide synthase inhibitor on intraocular pressure and ocular inflammation following laser irradiation in rabbits.

PURPOSE: To examine the effects of nitric oxide synthase (NOS) inhibitors on intraocular pressure (IOP) and ocular inflammation following laser irradiation of the rabbit iris, and to investigate the involvement of nitric oxide (NO). METHODS: Thirty min after the intravenous administration of a nonselective inhibitor of NOS, N omega-nitro-L-arginine methyl ester (L-NAME, 1-100 mg/kg), or a selective inhibitor of iNOS, aminoguanidine (AG, 100 mg/kg), Q-switched Nd:YAG laser irradiation was applied to the iris of albino rabbits at an energy level of 48 mJ. IOP was measured prior to and for 24 h after irradiation. In separate groups of rabbits, aqueous humor was withdrawn 30 min after irradiation to determine protein and prostaglandin (PG) E2 concentrations. RESULTS: Intravenously administered L-NAME dose-dependently inhibited the acute increase in IOP, the peak of which was observed at 30 min, following laser irradiation. The IOP increase was completely abolished by 100 mg/kg of L-NAME. This dose of L-NAME significantly reduced the elevation of protein concentration in aqueous humor following irradiation; however, this dose failed to affect the increase in PGE2 concentration On the other hand, the inhibitory effects of AG (100 mg/kg) on the increase in IOP and aqueous protein following laser irradiation were not significant. CONCLUSIONS: Intravenous administration of L-NAME significantly inhibits the IOP rise and the increase in protein concentration in aqueous humor following laser irradiation, but AG does not, suggest the involvement of cNOS in these ocular responses to laser irradiation.

Animals↗
PubMed1998

Effects of hypoxia and post-hypoxic recovery on chick retinal pigment epithelium potentials and light-evoked responses in vitro.

PURPOSE: To determine the cellular mechanisms involved in the hypoxia-induced alteration of the retinal pigment epithelium (RPE) potentials and the light-evoked responses of the RPE in chicks. In addition, to determine the mechanisms involved in the recovery of the RPE during the post-hypoxic period. METHODS: In vitro preparations of chick retina-RPE-choroid were studied by potassium-selective microelectrodes placed in the subretinal space. In addition, single-barrel microelectrodes were used to obtain intracellular recordings from the RPE cells. The perfusate was bubbled continuously with 95% oxygen and 5% carbon dioxide for the control condition and replaced by 95% nitrogen and 5% carbon dioxide to induce hypoxia. RESULTS: Hypoxia induced a significant reduction of the trans-tissue potential which was found to result from the depolarization of the apical membrane of the RPE. This depolarization was induced by an increase of subretinal [K+]o. The c-wave was also markedly decreased or abolished during hypoxia. There were two phases of post-hypoxic recovery: an initial small increase in the trans-tissue potential resulting from a basal membrane depolarization followed by an apical membrane hyperpolarization. The trans-tissue potential and the c-wave also were supernormal in two phases during this post-hypoxic period. The c-wave amplitude was temporarily elevated (263.7 +/- 77.4% of pre-hypoxic control) because of the enhanced trans-epithelial c-wave and without a light-evoked decrease in subretinal [K+]o. CONCLUSIONS: The trans-tissue potential and the c-wave were markedly decreased during hypoxia. During the post-hypoxic period, both potential recovered with transient supernormalities in two phases. The results suggested that the hypoxic changes resulted directly from changes of the RPE membranes and indirectly from a change in the subretinal [K+]o but were not mediated by the light-evoked decrease in subretinal [K+]o.

Animals↗
PubMed1998

Three paediatric cases of primary sclerosing cholangitis treated with ursodeoxycholic acid and sulphasalazine.

We present here three paediatric patients with primary sclerosing cholangitis. In case 1, the serum gamma-glutamyl transpeptidase was decreased only temporarily by ursodeoxycholic acid (UDCA) treatment and 34 months later, sulphasalazine was added because of microscopic colitis. The enzyme level decreased with dual therapy. Similarly, in case 3, first diagnosed as autoimmune hepatitis, the transpeptidase levels remained elevated for 18 months during treatment with UDCA, prednisolone and mizoribin. The enzyme decreased only after a diagnosis of primary sclerosing cholangitis complicated with ulcerative colitis was established and sulphasalazine was introduced. Case 2 also had Crohn's colitis and was put on UDCA and sulphasalazine from the start. The enzyme level was normalized within 1 month and has remained normal for the following 5 years. Liver biopsies were analysed repeatedly in these three patients. In case 1, periductal fibrosis remained unchanged while being treated by UDCA. There appeared to be no progression in liver cirrhosis in case 3 while being treated by UDCA, prednisolone, and mizoribin. In case 2, who has been treated with both UDCA and sulphasalazine from the start, periductal fibrosis and portal fibrosis were remarkably improved 45 months later. We suggest that sulphasalazine in addition to UDCA might be a viable treatment for children with primary sclerosing cholangitis.

Adolescent↗
PubMed1998

An image analysis study of cataract development after trabeculectomy with mitomycin C.

We prospectively measured quantitative changes in the crystalline lens after trabeculectomy with mitomycin C. Twenty-four eyes in 24 trabeculectomy cases were consecutively enrolled in the study. The enrollment criteria consisted of: phakic eye, no history of intraocular surgeries and no corneal opacification. The transparency of the lens was measured and analyzed by EAS-1000 preoperatively, then 1 and 3 months postoperatively. Changes occurred primarily in the anterior part of the lens, especially in the anterior subcapsular region. The multivariate regression analysis demonstrated an association of cataract development with age, myopic refraction, difference in preoperative and postoperative IOP and systemic hypertension.

Adult↗
PubMed1998

Vibration acceleration magnitudes of hand-held tools and workpieces.

The magnitudes of the hand-transmitted vibration, 297 hand-held tools and workpieces were measured at workplaces. The tools were used mainly in construction and manufacturing industries. The current standard for the measurement of hand-transmitted vibration has been based on the frequency-weighted acceleration of dominant axis method. According to the proposal of ISO/CD5349-1, the results of measurements (462 points) were recalculated by the method of the frequency-weighted acceleration sum. There is 32% of difference in average value between the acceleration sum and the dominant axis method.

Acceleration↗
PubMed1997

Role of screening for hepatitis C virus in children with malignant disease and who undergo bone marrow transplantation.

BACKGROUND: Children with malignant disease who received multiple blood transfusions before the clinical definition of hepatitis C virus (HCV) require evaluation for HCV infection. STUDY DESIGN AND METHODS: The role of HCV infection in 54 children with primary malignant disease was evaluated in terms of the following aspects: prevalence of HCV infection, distribution of HCV subtype, the benefit of screening of blood donors, and the presence of chronic liver disease. The benefit of screening for HCV in a subset of patients who underwent bone marrow transplantation (BMT) was also evaluated. RESULTS: Seventeen patients (31.4%) of 54 tested were seropositive in a second-generation HCV antibody test. Thirteen patients (24.0%) were also positive for circulating HCV RNA. HCV subtype 1b and HCV subtype 2b were found in six and two patients, respectively. Multiple HCV genotypes were present in two patients. One of these two patients had relatively progressive liver disease. Before the introduction of blood screening with a second-generation HCV antibody test, 15 of 35 patients seroconverted, whereas none of 7 patients seroconverted after the screening was used (p = 0.032). For patients who underwent BMT, the screening drastically decreased the seroconversion rate, from 7 of 11 patients to 0 of 6 (p = 0.016). CONCLUSION: A considerable number of children with primary malignant disease who received multiple blood transfusions became infected by HCV before HCV screening was used. Patients who underwent BMT were at high risk for HCV infection. Screening with a second-generation HCV antibody test has proven to be remarkably beneficial in preventing HCV infection in these children.

Adolescent↗
PubMed1997

The nurse shortage problem in Japan.

This article discusses the serious problem of the shortage of about 50,000 nurses in Japan today. If efficient measures to solve it are not adopted by administrators, it is clear that the shortage will become still more alarming in the future, in a society with more people in advanced years and in which the numbers in the younger generation will decrease from now on. The main factors behind the Japanese nursing labour shortage are, among others: a rapid increase in the number of hospital beds between 1986 and 1989, poor working conditions; and nurses' low social position in their places of work. Behind these factors, there has always been a contempt for the art of nursing in our society. Why has Japanese society made light of nursing? Three points can be identified: traditional discrimination against women; our disregard for a religious mentality; and our short history of hospital nursing. To overcome these problems, we must first of all change fundamentally our sense of values, such as love for one another and compassion. We must now reconstruct a caring culture in our society.

Cultural Characteristics↗
PubMed1997

Progressive retinitis-encephalitis due to ganciclovir-resistant cytomegalovirus associated with aplastic anemia.

A 29-year-old woman with aplastic anemia who complained of visual disturbances and pain in the right eyeball was diagnosed as having cytomegalovirus (CMV) retinitis based upon the characteristic retinal changes and isolation of CMV. She received treatment with ganciclovir (GCV), and the retinitis initially responded for several months. However, the patient was found to have CMV lesions in the left eye followed by neurological symptoms. The CMV isolated just before her death was approximately 20 times more resistant to GCV than that isolated previously, suggesting that the GCV-resistant CMV had developed during the long-term treatment with GCV.

Adult↗
PubMed1997

Appositional angle closure in eyes with narrow angles: an ultrasound biomicroscopic study.

PURPOSE: To demonstrate appositional angle closure using ultrasound biomicroscopy under dark room conditions, to investigate patterns of appositional closure, and to correlate those patterns with the angle topology in eyes with narrow angles. METHODS: Forty-six eyes that met the study criteria, from 46 individuals, were examined by ultrasound biomicroscopy under dark room and illuminated conditions. RESULTS: In 40 of the 46 eyes (87.0%), appositional closure was identified by ultrasound biomicroscopy. Two distinct patterns of angle closure were seen: type B, in which closure starts from the bottom of the angle, and type S, in which closure starts in the vicinity of Schwalbe's line. In type B, the iris root was located closure to the chamber angle than in type S. CONCLUSIONS: Ultrasound biomicroscopy performed under dark room conditions is a useful technique for identifying appositional angle closure in eyes with narrow angles. The topology of the iris root is related to the pattern of the appositional angle closure.

Adult↗
PubMed1997

Use of antifibrosis agents and glaucoma drainage devices in the American and Japanese Glaucoma Societies.

PURPOSE: To investigate practice patterns among glaucoma subspecialists in the American Glaucoma Society (AGS) and the Japanese Glaucoma Society (JGS), regarding use of antifibrosis agents and glaucoma drainage devices. METHODS: An anonymous survey incorporating 10 clinical situations was mailed to all AGS and JGS members in December 1995. RESULTS: Half of the AGS (105 of 210), and JGS (25 of 50) members returned surveys. Most respondents (51-87%) preferred trabeculectomy with adjunctive mitomycin for all 10 clinical situations. Mitomycin concentrations varied from 0.1 to 0.8 mg/ml (range of means for 10 situations 0.31-0.39 mg/ml) and intraoperative application times ranged from 5 s to 7 min (range of means for 10 situations 2.5-4.6 min). Preferences for either no antifibrosis agent (up to 39%) or 5-fluorouracil (up to 29%) were highest in primary trabeculectomy. Thirty-seven percent to 64% of AGS members used glaucoma drainage devices, especially after complicated postsurgical glaucomas (after penetrating keratoplasty, scleral buckling, or pars plana vitrectomy) and in neovascular glaucoma, but few JGS members used them. Large differences between university- and private practice-based AGS members were found only in mitomycin use for primary trabeculectomy (33% vs. 52%, respectively; p = 0.07) and for complicated postsurgical glaucomas (46% vs. 70%, respectively; p = 0.03). CONCLUSIONS: Trabeculectomy with mitomycin was the preferred surgical procedure among AGS and JGS members in the clinical situations surveyed. Mitomycin concentration and time of application varied widely. Many respondents used 5-fluorouracil or no antimetabolite in primary trabeculectomy. Glaucoma drainage devices were widely used for complicated glaucomas in the United States.

Chemotherapy, Adjuvant↗
PubMed1997

Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway in cholinergic and tachykinergic contractions of the rabbit iris sphincter muscle.

PURPOSE: In the rabbit iris sphincter muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachykinergic muscular contractions, and to examine whether the mechanism for NO-induced inhibition of cholinergic muscular contraction is operative in vivo. METHODS: Iris sphincter muscle was dissected from the rabbit eye pretreated with or without endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine monophosphate (cGMP) content in the iris sphincter muscle was determined by radioimmunoassay. The motor activity of the ring-shaped iris sphincter muscle was measured isometrically. Sodium nitroprusside, carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO radicals), and 8-bromo cGMP (a permeable cGMP analogue) were administered between the first and second administrations of carbachol and neurokinin A, both of which had caused sustained contraction in the iris sphincter muscle. RESULTS: Sodium nitroprusside inhibited the contraction of the iris sphincter muscle caused by carbachol but had no effect on the contraction caused by neurokinin A. Application of C-PTIO significantly reduced SNP-induced cGMP accumulation in the muscle, as well as the SNP-induced inhibition of muscular contraction caused by carbachol. Neither carbachol nor neurokinin A influenced SNP-induced cGMP accumulation in the muscle. Induction of 8-bromo-cGMP significantly diminished the muscular contraction caused by carbachol but not that caused by neurokinin A. In vivo pretreatment of the eye with LPS increased, in a time-dependent manner, the cGMP accumulation in the iris sphincter muscle, which was significantly inhibited by pretreatment of NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis) in vivo. CONCLUSIONS: These results demonstrate that in rabbits the increase in cGMP accumulation induced by NO in the iris sphincter muscle is involved in the cholinergic contraction but not in the tachykinergic contraction, suggesting that different sensitivities to cGMP are essential for the different responsiveness to NO. Furthermore, the results of this study showed that the NO-cGMP pathway is operative in vivo and regulates iris sphincter muscle tone, at least when the eyes are infected with bacteria.

Animals↗
PubMed1997

Appositional angle closure in eyes with narrow angles: comparison between the fellow eyes of acute angle-closure glaucoma and normotensive cases.

PURPOSE: To identify topologic features of eyes with acute primary angle-closure glaucoma before an attack as compared with those features in normotensive cases, assuming that untreated fellow eyes of acute primary angle-closure glaucoma are candidates for an acute attack. METHODS: A total of 50 eyes (12 fellow eyes of acute primary angle-closure glaucoma and 38 normotensive cases with a closure-possible narrow angle) were prospectively examined by ultrasound biomicroscopy under dark-room conditions. All eyes were examined before surgical or laser intervention and had normal pupillary reaction without any topical drugs. Four predetermined angle locations per eye were examined. Parameters regarding the chamber angle configuration were measured and compared between the two groups. RESULTS: Appositional angle closures were observed in 27 locations in fellow eyes and in 48 locations in normotensive eyes with a closure-possible narrow angle. The incidence was statistically different between the two groups (69.2% in the fellow eyes and 48% in the normotensive eyes). Appositional angle closures beginning at the entrance of the angle were more frequently detected in the fellow eye group. The distance between the iris root and the bottom of the angle was significantly different between the two groups. CONCLUSION: The fellow eyes of acute primary angle-closure glaucoma have different topologic features from normotensive narrow-angled eyes and a higher incidence of appositional closure that may predispose these eyes to an imminent acute attack.

Acute Disease↗