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A Sawada

Publications and source records attributed to A Sawada.

At least 55 records · Page 3Linked to original sources
PubMed1999

Confirmation of the rat model of chronic, moderately elevated intraocular pressure.

We have confirmed the usefulness of the rat model of chronic, moderately elevated intraocular pressure (IOP) for studying loss of retinal ganglion cells, and as a model for pharmacological neuroprotection studies that may be relevant to treating human glaucoma. By unilaterally cauterizing three episcleral vessels, as described previously in the literature by another laboratory, we observed an approximately 1.6-fold increase in IOP compared to the contralateral eye (18.6 vs 11.5 mm Hg, respectively). Elevated IOP persisted for 6 months without re-treatment. Cupping of the optic disk was observable by examination, in vivo. In 6 months, there was an approximately 40% loss of retinal ganglion cells in the peripheral retina. This model provides a reproducible and quantitative model for pharmacological experiments using neuroprotective agents.

Animals↗
PubMed1999

Effects of bicarbonate ion on chick retinal pigment epithelium: membrane potentials and light-evoked responses.

The purpose of this study was to determine how changes in [HCO3-] alter the electrical properties of the retinal pigment epithelium (RPE). Experiments were conducted on the isolated chick retina-RPE-choroid preparation. The chamber holding the preparation allowed independent perfusion of the retinal and the choroidal surfaces. The light-evoked trans-tissue potential (TTP), the trans-epithelial potential (TEP), the trans-retinal potentials, and the intracellularly-recorded apical and basal membrane potentials were studied. Increasing the [HCO3-]0 in the choroidal bath from 25 to 40 mEq/1 led to an increase in the TTP and TEP. The same change in the retinal bath decreased the TTP because of a biphasic change of the RPE membrane potentials. There was also an increase in the amplitudes of the TEP, the c-wave and the slow PIII. The light-evoked subretinal K+ decrease was greater which is consistent with an increase in the photoreceptor light response. These observations indicated that the decrease of TTP resulted from a basal membrane hyperpolarization followed by an apical membrane depolarization induced by an increase in retinal [HCO3-]0. The relationship of these potential changes to the human bicarbonate responses is discussed.

Animals↗
PubMed1999

Synthesis and biological activity of 4-methyl-3,5-dioxane derivatives as thromboxane A2 receptor antagonists.

The synthesis and biological activity of novel 4-methyl-3,5-dioxane analogues are described. All compounds were produced through modification of the substituent formally corresponding to the omega-octenol side chain of thromboxane A2 (TXA2), in reference to the structure of SQ29548. Several compounds were found to be potent TXA2 receptor antagonists. Compound 8b was the most effective inhibitor of 9,11-epoxymethano PGH2 (U-46619)-induced human platelet aggregation (IC50 = 7.4 nM).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Pharmacokinetic drug interactions between ampiroxicam and sulfaphenazole in rats.

The aim of the present study was to determine the effect of sulfaphenazole (SP) on the pharmacokinetics of ampiroxicam (AM) which is metabolized by cytochrome P-450 (CYP) 2C9, since SP is a potent inhibitor of CYP 2C9, and so a dramatic pharmacokinetic drug interaction between both drugs is assumed after dosing. Single intravenous and oral administrations of AM (5 and 7.5 mg/kg piroxicam equivalent, respectively) and SP (80 and 120 mg/kg, respectively) to rats did not significantly alter the elimination kinetics of AM and piroxicam (PX) converted from AM. When SP was preloaded orally at 2 h before the dosing of AM, and when AM and SP were orally coadministered for 7 d, the elimination of PX from plasma was slightly retarded and the area under the plasma concentration-time curve (AUC) was increased 77 and 53%, respectively, but not significantly, compared with those after AM alone. On the other hand, a significantly decreased metabolic conversion of PX to 5'-hydroxyPX in plasma was observed by these treatments (p<0.05). In order to clarify the mechanism for the interaction, hepatic and intestinal metabolizing enzyme activities, CYP, uridine 5'-diphosphoglucuronyltransferase (UDPGT) and aryl esterase, were assayed after single and multiple oral administrations of AM or AM and SP. The enzyme activities were hardly inhibited by the treatment, indicating that the inhibition of CYP and hydrolytic enzymes by SP was approximately denied. These results suggest that SP does not significantly affect the pharmacokinetics of AM and PX in rats. However, the pharmacokinetic drug interaction between both drugs in man may not always be ignored.

Administration, Oral↗
PubMed1999

[Effect of mitomycin C dissolved in a reversible thermosetting gel on outcome of filtering surgery in the rabbit].

PURPOSE: Based on our previous report that showed enhanced transfer of mitomycin C to the sclera and the conjunctiva by dissolving the antiproliferative in a reversible thermo-setting gel, we conducted a study to investigate the efficacy of the mitomycin C-gel in the rabbit. METHODS: We subconjunctivally injected 0.1 ml of the mitomycin C-gel solution containing several amounts of the drug. Trephination was performed in the injected region 24 hours later. Intraocular pressure measurement, and photography and ultrasound biomicroscopic examination of the filtering bleb were done 1, 2, and 4 weeks postoperatively. RESULTS: The gel containing 3.0 micrograms or more mitomycin C significantly enhanced bleb formation in addition to reducing the intraocular pressure. CONCLUSION: The reversible thermo-setting gel seems to facilitate filtration following glaucoma filtering surgery in the rabbit and deserves further investigation as a new method of mitomycin C application.

Animals↗
PubMed1999

[Three cases of carotid cavernous sinus fistulas where the main ocular manifestation was restricted ocular motility].

BACKGROUND: Some cases of carotid cavernous sinus fistulas (CCFs) have few ocular congestive signs and symptoms. These cases need to be accurately diagnosed as having CCFs. CASES: Three patients with CCFs without ocular congestive signs or symptoms developed unilateral abducens restriction and visited our clinic. FINDINGS: Color Doppler imaging revealed retrograde flow of the superior ophthalmic veins bilaterally in the three cases. The diagnose of CCF was confirmed by cerebral angiography. CONCLUSION: It is sometimes difficult to diagnose CCF, when a patient without ocular congestive signs or symptoms shows disturbed ocular motility as the only ocular manifestation. In such cases, color Doppler imaging may show the presence of CCF.

Aged↗
PubMed1999

Isoforms of nitric oxide synthase in the optic nerves of rat eyes with chronic moderately elevated intraocular pressure.

PURPOSE: To investigate the hypothesis that nitric oxide (NO) in the optic nerve heads of rats with chronic moderately elevated intraocular pressure (IOP) contributes to neurotoxicity of the retinal ganglion cells, the presence of the three isoforms of nitric oxide synthase (NOS) was determined in the tissue. METHODS: Unilateral chronic moderately elevated IOP was produced in rats by cautery of three episcleral vessels. Histologic sections of optic nerves from eyes with normal IOP and with chronic moderately elevated IOP were studied by immunohistochemistry and by immunoblot analysis. Polyclonal antibodies to NOS-1, NOS-2, NOS-3, and glial fibrillary acidic protein (GFAP) were localized with immunoperoxidase. RESULTS: In the optic nerve of rat eyes with normal IOP, NOS-1 was constitutively present in astrocytes, pericytes and nerve terminals in the walls of the central artery. NOS-2 was not present in eyes with normal IOP. In these eyes, NOS-3 was constitutively present in the vascular endothelia of large and small vessels. Rat eyes treated with three-vessel cautery had sustained elevated IOP (1.6 fold) for at least 3 months. In these eyes, no obvious changes in NOS-1 or NOS-3 were noted. However, at time points as early as 4 days of chronic moderately elevated IOP, NOS-2 appeared in astrocytes in the optic nerve heads of these eyes and persisted for up to 3 months. Immunoblot analysis did not detect differences in NOS isoforms. CONCLUSION: The cellular distributions of constitutive NOS isoforms in the rat optic nerve suggest physiological roles for NO in this tissue. NOS-1 in astrocytes may produce NO as a mediator between neighboring cells. NO, produced by NOS-1 in pericytes and nitrergic nerve terminals and by NOS-3 in vascular endothelia, is probably a physiological vasodilator in this tissue. In eyes with chronic moderately elevated IOP, NOS-2 is apparently induced in astrocytes. The excessive NO production that is associated with this isoform may contribute to the neurotoxicity of the retinal ganglion cells in eyes with chronic moderately elevated IOP.

Animals↗
PubMed1999

Problems regarding the integration of medical images into the total hospital information system.

Since 1989, the integration of medical images into the total hospital information system (HIS) has been investigated and developed at Kochi Medical School. The basic concept of the integration is that, in the same way they can view text based data, doctors can retrieve and view images using the PC terminals of the total HIS. The possibility of utilizing the PC terminals of the total HIS as image viewing stations was investigated. A test run was performed in the period from October 1995 to July 1997. The test run revealed that fast image access is crucial in order for the system to be useful for doctors. After making various improvements, the final system became well used in the clinical practice. However, in order to progress to the film-less stage, the final system still has three problems that must be solved: quality of the image display, operation of multi-exams, and quality assurance of the digital image.

Computer Systems↗
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

Volumetric object modeling for surgical simulation.

Surgical simulation has many applications in medical education, surgical training, surgical planning and intra-operative assistance. However, extending current surface-based computer graphics methods to model phenomena such as the deformation, cutting, tearing or repairing of soft tissues poses significant challenges for real-time interactions. This paper discusses the use of volumetric methods for modeling complex anatomy and tissue interactions. New techniques are introduced that use volumetric methods for modeling soft-tissue deformation and tissue cutting at interactive rates. An initial prototype for simulating arthroscopic knee surgery is described which uses volumetric models of the knee derived from 3-D magnetic resonance imaging, visual feedback via real-time volume and polygon rendering, and haptic feedback provided by a force-feedback device.

Arthroscopy↗
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↗