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Biomedical subjects

S Handa

Publications and source records attributed to S Handa.

At least 181 records · Page 10Linked to original sources

Serial changes in coagulant activities after thrombolytic therapy for acute myocardial infarction.

Early reocclusion and bleeding complications are still unresolved problems in thrombolytic therapy for acute myocardial infarction (AMI). In the present study, 16 patients treated with either fibrin-specific tissue-type plasminogen activator (t-PA) or nonspecific urokinase (UK) were studied to determine the effects of thrombolytic therapy on serial hemostatic states. Hemostatic states of each patient were estimated by measuring various plasma markers at one- to two-hour intervals during the first six hours of therapy, daily during the next three days, and subsequently on day 7. Two markers of plasma thrombin generation, thrombin antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F 1 + 2), showed an activated coagulant state immediately after thrombolytic therapy. The amount of thrombin generation indicated by these markers showed significant positive correlation with direct markers of fibrinolysis such as fibrin degradation products (FDP), while it did not show any correlation with the markers for plasmin generation. The potential for coagulation as indicated by prothrombin time (%) decreased with thrombolysis using fibrin nonselective agents, owing perhaps to destruction of coagulant factors by free plasmin. Fibrinolytic activity induced by thrombolytic therapy for AMI caused transient activation of the coagulant system, which could contribute to early reocclusion. Fibrin nonselective agents decreased the potential for coagulation by destroying clotting factor through the generation of free plasmin. These data provide theoretical support for simultaneous administration of anticoagulant therapy with fibrin-specific thrombolytic agents.

Aged↗

Short term methotrexate therapy in psoriasis.

Data on 82 psoriatics (62 males and 20 females) with either chronic recalcitrant, erythrodermic, generalized pustular or severe palmoplantar psoriasis treated with methotrexate (MTX) have been reviewed. MTX was given in a single oral weekly dose of 3.75-30 mg based on body weight. Seven patients with a relative contraindication for MTX use were also treated safely with MTX. An attempt was made to withdraw MTX as quickly as possible with the intention of providing drug free period of 4-6 months coinciding this period with the seasonal remissions in disease activity. MTX could be withdrawn in up to 90 per cent patients within an average of 25 wk. The total cumulative dose could also be reduced by this method as also the need to repeat liver biopsies.

Adolescent↗

[Exercise and rest myocardial scintigraphy with 201TlCl/99mTc-MIBI dual energy acquisition using triple-energy window scatter correction].

We carried out dual 201Tl/99mTc-MIBI imaging, to reduce the time required for exercise myocardial scintigraphy. We investigated 4 different protocols. In protocol (A), Tl was injected at rest followed by the injection of MIBI at peak exercise. Dual SPECT images were obtained by 201Tl/99mTc simultaneous acquisition. Protocol (B) means reverse either, in which MIBI was injected at rest followed by the administration of Tl at peak exercise. In protocol (C), exercise was performed first with MIBI-injection, and then Tl was injected at rest after one hour later. Simultaneous acquisition was also performed. In protocol (D), after the rest Tl-imaging, MIBI was injected at peak exercise, and then the MIBI-imaging was done. In protocol (A), (B) and (C), simultaneous acquisition was performed using TEW (Triple-Energy Window) scatter correction. Thanks to using dual isotopes, all procedures could be completed within 1-2 hours, which was much shorter than the conventional myocardial perfusion imaging. Scatter correction was useful for accurate diagnoses, when the simultaneous imaging is performed.

Exercise Test↗

[Pharmacokinetic, bacteriological and clinical studies on cefozopran in the pediatric field].

Cefozopran (CZOP, SCE-2787), a newly developed parenteral cephem antibiotic, was administered to children with bacterial infections. We determined its antibacterial activity, pharmacokinetics, efficacy and safety in these patients. 1. Antibacterial activity MICs of cefmetazole, ceftazidime, cefuzonam, flomoxef and CZOP were determined against a total of 19 strains. For Gram-positive cocci, MICs of CZOP ranged from 0.39 to 0.78 microgram/ml against Staphylococcus aureus (3 strains), from 0.05 to 6.25 micrograms/ml against Streptococcus pneumoniae (5 strains), and 12.5 micrograms/ml against Enterococcus faecalis (1 strain). These MICs were generally similar to those of other cephems, but the MIC of CZOP against E. faecalis was lower than those of the other cephems examined. For Gram-negative bacilli, MICs of CZOP were 25 micrograms/ml against Citrobacter freundii (1 strain), and 6.25 micrograms/ml against Pseudomonas aeruginosa (1 strain). These values were similar to or lower than those of other cephems, MICs of CZOP against Haemophilus influenzae (7 strains) ranged from 0.1 to 0.39 microgram/ml. However, the MIC of CZOP against Serratia marcescens (1 strain) was higher than 100 micrograms/ml, and CZOP was as ineffective as the other cephems against this organism. 2. Pharmacokinetics CZOP was administered to children at 20 or 40 mg/kg via intravenous injection, and determinations were made for its serum concentrations, urinary concentrations and concentrations in cerebrospinal fluid (CSF) using the bioassay. Serum concentrations at 30 minutes after administration were 60.4 micrograms/ml with a dose of 20 mg/kg to one patient and 93.9 and 99.0 micrograms/ml with 40 mg/kg to two patients. The corresponding half-lives were 1.55 hours for 20 mg/kg administration, and 1.10 and 3.41 hours for 40 mg/kg, while the AUCs were 136.5 micrograms.hr/ml for 20 mg/kg, and 194.4 and 264.5 micrograms.hr/ml for 40 mg/kg. The rates of urinary recovery in the first 8 hours after administration were 45.0% in the patient receiving 20 mg/kg, and 84.6 and 97.6% in the two patients receiving 40 mg/kg. The concentrations in the CSF determined in 3 patients with purulent meningitis ranged from 2.6 to 16.0 micrograms/ml 1 hour after administration, and the CSF/serum concentration ratio ranged from 6.5 to 39.0%. These values for pharmacokinetic parameters obtained in the bioassay were similar to those obtained using HPLC. 3. Clinical evaluation Forty-eight patients were clinically evaluated. Of these patients, 75% were less than 3 years of age and there were slightly more male children than female children.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

[Bacteriological, pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field].

Antibacterial activities were determined and pharmacokinetics and a clinical studies were performed on biapenem (L-627), a novel parenteral carbapenem antibiotic, in infections in children. The following results were obtained: 1. MICs of L-627 against clinical isolates were as follows: Among Gram-positive bacteria, MICs were 0.78 microgram/ml to > 100 micrograms/ml against 3 strains of methicillin-resistant Staphylococcus aureus (MRSA), and 0.10 microgram/ml to 0.39 microgram/ml against 8 strains of methicillin-sensitive S. aureus (MSSA), MICs against 5 of them were similar to those of imipenem (IPM), and MICs against 3 of them were slightly higher than those of IPM. MICs were < or = 0.025 microgram/ml to 0.39 microgram/ml against 7 strains of Streptococcus pneumoniae, and were similar to those of IPM, and lower than those of ceftazidime (CAZ) and piperacillin (PIPC). Among Gram-negative bacteria, MICs were 0.78 microgram/ml and 3.13 micrograms/ml against 2 strains of Haemophilus influenzae, and were similar to those of IPM. 2. Maximum plasma concentrations determined by the bioassay method after intravenous infusion of L-627 over 30 minutes at doses of 6.0 and 12.0 mg/kg, respectively, in 2 different pairs of 2 children each (total 4 cases) were observed upon completion of the treatment. Maximum concentrations at a dose of 6.0 mg/kg were 28.8 micrograms/ml and 24.6 micrograms/ml, and at a dose of 12.0 mg/kg were 65.4 micrograms/ml and 39.6 micrograms/ml, exhibiting a dose response. Plasma half lives in the beta phase were 0.97 and 1.20 hours at 6.0 mg/kg, and 0.72 and 0.94 hour at 12.0 mg/kg. Plasma concentrations determined by the HPLC method were lower than those determined by the bioassay. 3. Urinary excretion rates in the first 5.5 hours after the 6.0 mg/kg dose were 81.4 and 75.3%, and after the 12.0 mg/kg dose were 91.0 and 73.8%, and these values were higher than those obtained using HPLC. 4. Concentrations of L-627 in cerebrospinal fluid were determined in 2 cases of purulent meningitis. In one case, 30.3 mg/kg of L-627 was infused intravenously over 30 minutes and concentrations on days 1, 3, 7 and 14 observed at 60, 60, 45 and 45 minutes after respective dosages were 7.60, 1.30, 1.42 and 0.38 microgram/ml. Cerebrospinal fluid-plasma concentration ratio was determined on days 7 and 14 to be 5.5 and 1.2% respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗

[Basic and clinical studies on cefditoren pivoxil in pediatric field].

Cefditoren pivoxil (CDTR-PI, ME1207) granules, a new oral cephem, was given to pediatric patients with infectious diseases to evaluate antibacterial activities against clinical isolates, pharmacokinetics, clinical efficacy and safety, and the following results were obtained. 1. In sensitivity test, 30 strains were used comprised of 5 species, isolated from the patients before administered with CDTR-PI. Against Staphylococcus aureus, MICs of 7 agents, cefditoren (CDTR), cefaclor, cefixime, cefteram, cefotiam, cefpodoxime and methicillin, were determined. Against other 4 species, MICs of the above 6 agents excluding methicillin were determined. Among Gram-positive cocci tested, the MICs of CDTR were 0.78 to 100 micrograms/ml or higher against S. aureus (16 strains), < or = 0.025 microgram/ml against Streptococcus pyogenes (5 strains), and 0.10 or 0.39 microgram/ml against Streptococcus pneumoniae (2 strains). These values were equal to or lower than those of conventional cephems and of methicillin. Among Gram-negative rods tested, the MICs of CDTR were < or = 0.025 microgram/ml against Haemophilus influenzae (3 strains), and 0.10 or 0.20 microgram/ml against Escherichia coli (4 strains). Also, these values were equal to or lower than those of conventional cephems. 2. When CDTR-PI granules was orally administered in a single dose of 3.0 mg/kg to 1 patient and that of 6.0 mg/kg to 2 patients 30 minutes after meal, plasma CDTR concentrations reached their maxima 4 hours after administration in the former patient and 1 or 2 hours after administration in the latter 2 patients, and the peak plasma concentrations were 1.91, 3.46 and 4.82 micrograms/ml with half-lives of 1.01, 0.81 and 0.88 hours and AUCs of 8.62, 9.89 and 13.52 micrograms.hr/ml, respectively. Dose-dependency was observed for the peak plasma concentrations and AUCs also tended to depend on dose excepting for the AUC in one 6.0 mg/kg patient. 3. The urinary concentrations in the above patients reached their peaks at 4 to 6 hours after administration in one 3.0 mg/kg patient and at 4 to 6 hours and 2 to 4 hours after administration in two 6.0 mg/kg patients, and the corresponding values were 126.0, 195.0 and 234.0 micrograms/ml, respectively. Recovery rates in the first 8 hours after administration were 18.2, 24.6 and 21.3%, respectively. 4. Of 53 patients with 13 diseases, CDTR-PI was clinically judged "excellent" in 32 (60.4%) and "good" in 21 (39.6%), showing excellent efficacy. 5. Bacteriologically, excellent results were obtained, i.e., 29 (96.7%) of 30 strains from 5 species were eradicated. 6. Side effects were observed in none of the 54 patients treated.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

[Percutaneous transluminal coronary angioplasty and directional coronary atherectomy: a short review of recent progress].

Since the invention of Gruentzig AR in 1977, percutaneous transluminal coronary angioplasty (PTCA) has become a widely accepted therapeutic measure for the treatment of patients with ischemic heart disease (IHD), as well as coronary artery bypass grafting (CABG). The rate of initial success in PTCA elevated up to more than 90% recently, in accordance with the progress in technology and the operator's skill. The limitations of PTCA are acute coronary occlusion which occurs in a few percent during or just after the procedure, and restenosis which occurs in thirty to fourty percent within six months. Some new devices have been invented to add better results for the patients. Directional coronary atherectomy (DCA) is one of the devices to remove atheroma in narrow segment, instead of splitting it. DCA can create a larger and smoother lumen than that created with PTCA, and it may be expected to reduce the restenosis rate. The therapeutic choice in IHD is still controversial. At present, several clinical trials are being conducted in order to evaluate and compare medical therapy, CABG, and PTCA. These results will provide informations to help the decision making in the management of the patients with IHD.

Angioplasty, Balloon, Coronary↗

A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure.

There is a strong association between Guillain-Barré syndrome (GBS) and Penner's serotype 19 (PEN 19) of Campylobacter jejuni. Sera from patients with GBS after C. jejuni infection have autoantibodies to GM1 ganglioside in the acute phase of the illness. Our previous work has suggested that GBS results from an immune response to cross-reactive antigen between lipopolysaccharide (LPS) of the Gram-negative bacterium and membrane components of peripheral nerves. To clarify the pathogenesis of GBS, we have investigated whether GM1-oligosaccharide structure is present in the LPS of C. jejuni (PEN 19) that was isolated from a GBS patient. After extraction of the LPS, the LPS showing the binding activity of cholera toxin, that specifically recognizes the GM1-oligosaccharide was purified by a silica bead column chromatography. Gas-liquid chromatography-mass spectrometric analysis has shown that the purified LPS contained Gal, GalNAc, and NeuAc, which are sugar components of GM1 ganglioside. 1H NMR methods [Carr-Purcell-Meiboom-Gill (CPMG), total correlation spectroscopy (TOCSY), and nuclear Overhauser effect spectroscopy (NOESY)] have revealed that the oligosaccharide structure [Gal beta 1-3 GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] protrude from the LPS core. This terminal structure [Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] is identical to the terminal tetrasaccharide of the GM1 ganglioside. This is the first study to demonstrate the existence of molecular mimicry between nerve tissue and the infectious agent that elicits GBS.

Adult↗

[Clinical evaluation of myocardial perfusion imaging with 99mTc-tetrofosmin].

Myocardial perfusion imaging with Tc-99 m-1,2-bis (bis (2-ethoxyethyl) phosphino) ethane (Tc-99 m-tetrofosmin) was performed in 26 patients with ischemic heart disease (IHD) or suspected to have IHD. The agent was administered both at rest and at peak exercise. Exercise and rest studies were performed on the same day or on different days. The injected dose ranged from 296 MBq-740 MBq. Image quality was adequate for diagnosis, and was superior to that of T1-201 scintigraphy. Results from the tetrofosmin imaging corresponded well with findings of T1 scintigraphy, with a segmental concordance of 87%. Sensitivity and specificity were 70% and 93%, respectively. Our results suggested that tetrofosmin could be a promising Tc-99m labeling agent for the evaluation of myocardial perfusion.

Evaluation Studies as Topic↗

Structure of novel gangliosides, deaminated neuraminic acid (KDN)-containing glycosphingolipids, isolated from rainbow trout ovarian fluid.

Two acidic glycosphingolipids were isolated and purified from rainbow trout ovarian fluid. They were designated as ovarian fluid gangliosides ofg-2a and ofg-2b. Both of these glycolipids were found to contain glucose, galactose, and N-acetylgalactosamine in a molar ratio of 1:2:1, but they differ by the presence of 2 mol of deaminated neuraminic acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in ofg-2a and 1 mol each of KDN and 9-O-acetyl-KDN in ofg-2b. On the basis of composition analysis, methylation analysis, mild acid hydrolysis, fast atom bombardment mass spectrometry (FABMS), 400-MHz 1H nuclear magnetic resonance spectroscopy, and immunochemical analysis using a monoclonal antibody (mAb.kdn3G), the complete structures of these gangliosides were determined to be KDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2a [(KDN)GD1a] and 9-O-AcKDN alpha 2-->3Gal beta 1-->3GalNAc beta 1-->4(KDN alpha 2-->3)Gal beta 1-->4Glc beta 1-->Cer for ofg-2b [(KDN)GD1a(OAc+)]. The ceramide moieties (Cer) in both ofg-2a [(KDN)GD1a] and ofg-2b [(KDN)GD1a(OAc+)] were found by combining of the results from fatty acid analysis and FABMS measurements to be made up of 4-sphingenine and mainly a C24:1 fatty acyl chain (nervonate). The structures of ofg-2a and ofg-2b are novel, and they represent the second example of naturally occurring KDN-gangliosides. Mild acid hydrolysis of both ofg-2a and ofg-2b resulted in formation of (KDN)GM1a.

Animals↗

Glycosphingolipid compositions of human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV)-infected cell lines.

Glycolipid compositions of cells infected by human retroviruses (human immunodeficiency virus, HIV and/or human T-cell lymphotropic virus type I, HTLV-I) have been studied. Eight cell lines, comprising two HTLV-I-infected T-cell lines (MT-2 and MT-4), two HTLV-I-negative T-cell lines (Jurkat and MF), a macrophage cell line (U937), and three HIV-infected counterpart cell lines (MT-4/HIV, Jurkat/HIV and U937/HIV) were used. The neutral glycolipids and gangliosides isolated from these cell lines were compared. Among them, the HTLV-I-infected T-cell lines, MT-2 and MT-4, showed similar patterns for both neutral glycolipids and gangliosides. Neutral glycolipids (GlcCer and LacCer) of MT-2 and MT-4 cells were markedly decreased, and a ganglioside, GM3, of theirs was decreased to only a trace amount compared to that in other cell lines. Gangliosides of MT-4 and MT-4/HIV were further separated on an Iatrobeads column, and were identified as GM2, GM1a and GD1a by methylation and liquid secondary ion mass spectrometric analyses. Since the patterns of neutral glycolipids and gangliosides of MT-2 and MT-4 are unique, as compared to those of HTLV-I-negative cells, it is suggested that these changes are related to HTLV-1 infection. No prominent differences in the ganglioside compositions between HIV-infected and non-infected cell lines could be observed. But it is noteworthy that the contents of asialo-GM2 in Jurkat/HIV and MT-4/HIV cells were increased as compared to those in the parental cell lines.

Carbohydrate Sequence↗

Assessment of the distribution of nerve conduction velocities in alcoholics.

To assess the effects of chronic alcohol ingestion on the faster and slower nerve fibers (alpha fiber group) in the peripheral nervous system, the distribution of nerve conduction velocities (DCV) and conventional maximal motor and sensory nerve conduction velocities (MCV and SCV) in the median nerve were measured in 23 male patients with severe alcoholic dependency (DSM-III-R), aged 30-64 (mean, 50) years, and in 23 age-matched healthy men. The DCV was expressed by the conduction velocities below which 10, 20,..., 80, and 90% of active fibers lie (V10, V20,..., V80, and V90 velocities). The V40 to V90 velocities of the DCV were significantly slower in the alcoholics than in the control subjects; the SCV and MCV in the alcoholics were also significantly slowed. These findings suggest that the faster large myelinated nerve fibers are more sensitive to chronic alcohol ingestion than the slower large myelinated nerve fibers.

Adult↗

Measurements and analyses of electrophoretic mobilities of RAW117 lymphosarcoma cells and their variant cells.

The electrophoretic mobilities of the cells of malignant lymphosarcoma cell line RAW117-P and its variant H10 with a highly metastatic property to the liver have been measured at various ionic strengths. The cells of parental cell line (RAW117-P) show higher mobility values in magnitude than those of its variant line (RAW117-H10) in the whole range of electrolyte concentration measured. We have also measured the sialic acid amount carried by cells of both lines. The content of sialic acids in RAW117-H10 cells is observed to be about 27% less than that in RAW117-P cells. The mobility data obtained have been analyzed by a novel mobility formula for colloidal particles with ion-penetrable surface charge layers. The observed mobility difference between RAW117-P cells and RAW117-H10 cells is found to be due to the difference in friction exerted by the cell surface layers on the liquid flow around the cells between these two types of cells and to the difference in fixed-charge density in their surface layers, which is caused by the 27% decrease in sialic acid content. A possible explanation for this mobility difference between these two types of cells is given.

Animals↗

Clinical evaluation of the use-dependent QRS prolongation and the reverse use-dependent QT prolongation of class I and class III antiarrhythmic agents and their value in predicting efficacy.

We measured the QRS duration during a treadmill exercise test and the QT interval using a 24-hour Holter electrocardiogram at various heart rates to identify use-dependent QRS prolongation and reverse use-dependent QT prolongation of class I and III antiarrhythmic drugs. Use-dependent QRS prolongation was detected in 61%, 53%, and 64% of patients receiving disopyramide, mexiletine, and pilsicainide, respectively. Reverse use-dependent QT prolongation was found in 40% and 70% of patients receiving disopyramide and E4031. Drugs suppressed > or = 75% of the total premature ventricular contractions in all patients who had both use-dependent QRS prolongation and reverse use-dependent QT prolongation, in 79% of patients with use-dependent QRS prolongation alone, in 70% with reverse use-dependent QT prolongation alone, and in 11% with neither use-dependent QRS prolongation nor reverse use-dependent QT prolongation. Use-dependent QRS prolongation and reverse use-dependent QT prolongation were identified noninvasively and were useful in evaluating antiarrhythmic efficacy.

Adult↗

Sequential changes in sympatho-neuronal regulation and contractile function following aortic regurgitation in rabbit heart.

This study was designed to determine the sequential changes in sympatho-neuronal regulation and contractile function of hearts exposed to volume overloading. Aortic regurgitation was produced by perforation of the aortic valve in 20 rabbits. Another 20 rabbits underwent sham operation. They were randomly assigned to a 1-day group, a 1-week group, and a 4-week group. Haemodynamics, myocardial beta-adrenoceptor binding number and catecholamines were measured in each period after production of aortic regurgitation. Left ventricular end-diastolic pressure increased and cardiac output decreased progressively over the week following production of aortic regurgitation, but they returned towards normal during the subsequent 3 weeks. Left ventricular free wall thickness increased 4 weeks after production of aortic regurgitation, and plasma norepinephrine increased 1 day after the procedure. Maximal binding sites of myocardial beta-adrenoceptors (125I-iodocyanopindolol) were decreased 1 day and 1 week after production of aortic regurgitation. Myocardial norepinephrine was also reduced. After 4 weeks, both beta-adrenoceptor binding sites and myocardial norepinephrine content were restored. Alterations in sympatho-neuronal regulation are related to the compensatory processes in volume overloaded hearts.

Animals↗

Keratitis, ichthyosis, deafness (KID) syndrome--the first report from India.

A patient with the keratitis, ichthyosis and deafness (KID) syndrome is described. The patient had recurrent skin infections which led to complete scalp hair loss. The nails were dystrophic. Physical development was normal; however, his intelligence was subnormal. The erythrokeratodermatous plaques over the face, trunk and extremities were characteristic and the skin in general was dry and hyperkeratotic. Palms and soles showed marked thickening with a stippled appearance.

Adolescent↗

Fucosyl-GM1 in human sensory nervous tissue is a target antigen in patients with autoimmune neuropathies.

Several gangliosides of human nervous tissues have been reported to be potential target antigens in autoimmune neuropathies. To explain the diversity of clinical symptoms in patients with antiganglioside antibodies, we have searched for ganglioside antigens that are specific to individual nervous tissues such as motoneurons, peripheral motor nerves, and sensory nerves. Although the major ganglioside compositions were not different among human peripheral motor and sensory nerves, fucosyl-GM1 was found to be expressed in sensory nervous tissue but not in spinal cord, motor nerve, and sympathetic ganglia. Sera from several patients with sensory nerve involvement also reacted with fucosyl-GM1 as well as GM1. Thus, fucosyl-GM1 may be a responsible target antigen for developing sensory symptoms in some patients with autoimmune neuropathies.

Animals↗