[A case of ALL with Candida liver abscess treated with amphotericin B through portal vein].
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Adolescent↗
Biomedical subjects
S Motomura
Publications and source records attributed to S Motomura.
Low-dose cytosine arabinoside for treating hypocellular acute leukemia in the elderly.
Ten previously untreated elderly patients with hypocellular acute leukemia received a low dose of cytosine arabinoside (Ara-C), 10 mg/m2 injected subcutaneously every 12 hours for 14-28 days. Six patients achieved a complete remission (CR) for periods ranging for 6-23 months (median 8.5 months) and the others had a partial remission (PR). Relapse has occurred in three patients to date. The median survival ranged from 10-24 months (median 14.5 months). Only two of the six patients, in whom bone marrow biopsy was performed at CR, had a normal cellularity. This change, however, did not appear to be a significant prognostic factor in those patients. In seven patients who achieved a CR or PR low-dose Ara-C was administrated as maintenance therapy at the same low dose for 10 days each month. Treatment was well tolerated in all patients despite for myelosuppression. There were no drug-related deaths. These observations suggest that low-dose Ara-C is effective in treating elderly patients with hypocellular acute leukemia.
Acute Disease↗
Case report: fulminant hepatitis C viral infection after allogeneic bone marrow transplantation.
The authors describe two patients with acute leukemia who died of fulminant hepatitis caused by hepatitis C virus (HCV) after an allogeneic bone marrow transplant, the first such cases reported in Japan. Both had developed posttransfusion hepatitis during chemotherapy to induce remission and for consolidation. Six months after blood transfusion, the blood serum of each patient was positive for HCV antibody and HCV RNA. In each case, there was a transient improvement in liver function after the transplant. However, within 5 months of receiving the transplant and coincident with the withdrawal of cyclosporin A, each patient developed an acute exacerbation of hepatitis. The fulminant hepatitis in our patients may, therefore, have been caused by the reactivation of HCV induced by the immunosuppressive therapy followed by a reconstitution of the immune system.
Adult↗
Adult T-cell leukemia/lymphoma (ATL)--clinical, histopathological, immunological and immunohistochemical characteristics.
Twenty-one patients with ATL were assessed. The predominant physical findings were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly and leukemic manifestations. The predominant histopathological findings in both skin and lymph node specimens were the diffuse medium-sized cell type and the diffuse mixed cell type. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA-DR. That is, the predominant neoplastic cell phenotype was the helper T-cell, which was CD3+, CD4+, CD7+, CD25+, CD45RA+ and HLA-DR+, and CD29- and CD45RO- in peripheral blood and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA-DR+, and CD45RA- in the skin. In other words, we have described the phenotypic heterogeneity of ATL cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells in different organs--the skin, peripheral blood and lymph nodes--of the same patient.
Adult↗
[Food poisoning caused by enteroinvasive Escherichia coli (O164:H-)--a case in which the causative agent was identified].
Food poisoning due to "Godofu (Sasayuki tofu)" as a main causative foodstuff which broke out on July 14, 1988. There were 670 out of 918 persons who ingested this food who became ill (incidence 73.0%). The main symptoms were diarrhea (93.4%), fever (77.5%), abdominal pain (64.5%), and vomiting (19.9%). A high degree of fever and watery diarrhea were characteristic of this poisoning. The average latent period was 35 hours with a range of one to 156. The O164:H- strains of enteroinvasive Escherichia coli (EIEC) were detected from 22 of the 32 fecal samples collected from the patients, five of ten samples collected from workers engaged in tofu making, and one sample of left-over Godofu. The virulence of EIEC strains isolated from the patients, workers, and left-over food was confirmed by invasion into HeLa and HEp-2 cells, Sereny test, and ELISA test to detect invasive plasmid-derived protein of the organism (conducted at Tokyo Metropolitan Research Laboratory of Public Health). These EIEC strains were sensitive (less than or equal to 0.19 to 6.25 micrograms/ml) to GM, ABPC, CBPC, CER, CET, NA, PB, MINO, TC and CP as well as KM and OFLX which were used for treatment. However, their susceptibility to FOM varied to some extent (6.25 to 25.0 micrograms/ml) and one strain isolated from a tofu worker was resistant to MINO, TC, FOM and CP (25 to greater than or equal to 100 micrograms/ml). Since investigation revealed that Godofu was left at room temperature about 29 degrees C until ingested, we did a experiment to check the bacterial growth in Godofu under similar conditions at the time of outbreak.(ABSTRACT TRUNCATED AT 250 WORDS)
Escherichia coli↗
Beta 2-adrenoceptor-mediated positive dromotropic effects on atrioventricular node of dogs.
The functional significance of beta 2-adrenoceptors in atrioventricular (AV) nodal conduction was investigated by using canine isolated blood-perfused AV node preparations. Dose-dependent shortening of the atrio-His bundle (A-H) interval by dl-procaterol hydrochloride hemihydrate (0.03-1 nmol) injected intra-arterially into the AV node artery was affected little by an infusion of dl-atenolol (10 nmol/min) into the same artery, whereas the dose-response curve for the positive dromotropic effect of procaterol was shifted markedly to the right by approximately 1.5 and 2.5 log units with ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylamino-bu tan-2-ol]- hydrochloride (1 and 10 nmol/min). The positive dromotropic effect of dl-T-1583 [alpha-(3,4,5-trimethoxyphenethylaminomethyl)-3,4-dihydroxybenzyl- alcohol] hydrochloride (30-300 pmol), a selective beta 1-adrenoceptor agonist, was shifted to the right by approximately 1.2 log units with dl-atenolol (10 nmol/min) but was affected little by ICI 118551 (10 nmol/min). The dose-response curve for l-isoproterenol hydrochloride (3-100 pmol) was shifted to the right by 0.7 log unit with ICI 118551 (10 nmol/min) and by 1.7 log units with atenolol (10 nmol/min). The dose-response curve for dl-norepinephrine (0.03-1 nmol) was shifted to the right by 1.0 log unit with atenolol only, whereas the curve for l-epinephrine (0.03-1 nmol) was shifted by 0.45 log unit with ICI 118551 (10 nmol/min). These results suggest that both beta 1- and beta 2-adrenoceptors, which coexist on the AV node, play a functional role in AV nodal conduction.
Adrenergic beta-Agonists↗
[Effects of a new antiarrhythmic drug, KW-3407, on canine ventricular arrhythmia models].
The antiarrhythmic and direct cardiovascular effects of the new antiarrhythmic agent KW-3407, 5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11- dihydro[1]benzoxepino[3,4-b]pyridine 1.5 fumarate, were examined. To evaluate antiarrhythmic effects, two-stage coronary ligation-, digitalis- and adrenaline-induced spontaneously occurring arrhythmias were used. KW-3407, 20 mg/kg/10 min, suppressed these three arrhythmia models, similar to flecainide, mexiletine and phenytoin. The antiarrhythmic plasma concentrations, IC50, of KW-3407 for 24-hr and 48-hr coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 18.1, 14.4, 18.3 and 21.4 micrograms/ml, respectively; and these values were similar to one another. In the canine blood perfused atrioventricular (AV) node, sinoatrial node and papillary muscle preparations, KW-3407 decreased the sinoatrial rate and contractile force, and increased the coronary blood flow and AV conduction times, but these effects were weaker than those of disopyramide and flecainide and were short-lived. These results indicate that KW-3407 can be expected to become a clinically useful antiarrhythmic drug.
Animals↗
Characterization of the beta adrenoceptor subtype(s) mediating the positive inotropic effects of epinine, dopamine, dobutamine, denopamine and xamoterol in isolated human right atrium.
In patients with chronic heart failure cardiac beta-1 adrenoceptors are reduced, whereas beta-2 adrenoceptor changes vary depending on the etiology of the disease. Beta Adrenoceptor agonists can be used for short-term inotropic support in chronic heart failure; their clinical efficacy might depend on which beta adrenoceptor subtype(s) mediates their positive inotropic effect. Thus, the beta adrenoceptor subtype(s) involved in the positive inotropic effects of clinically used beta adrenoceptor agonists was characterized on isolated electrically driven human right atria by the use of the selective beta-1 adrenoceptor antagonist CGP 20712 A (300 nmol/l) and/or the selective beta-2 adrenoceptor antagonist ICI 118,551 (30 nmol/l). Epinine evoked positive inotropic effects through stimulation of beta-1 and beta-2 adrenoceptors to about the same degree, whereas dobutamine acted mainly at beta-1 adrenoceptors but had a significant beta-2 adrenoceptor component. Both agonists were full agonists causing the same maximum increase in contractile force (Emax) as did isoprenaline or Ca++ (Emax = 1.0). In contrast, denopamine was a partial selective beta-1 adrenoceptor agonist (Emax = 0.75-0.85). Dopamine was in the presence of uptake1-blockade (by 5 mumol/l phenoxybenzamine) a partial agonist (Emax = 0.60-0.70) acting selectively at beta-1 adrenoceptors; in the absence of uptake1-blockade, however, dopamine was a full agonist, indicating that part of its positive inotropic effect is indirect via the release of endogenous noradrenaline. Xamoterol did not exert positive inotropic effects, but concentration-dependently slightly decreased basal force of contraction.
Adrenergic beta-Agonists↗
[Malignant histiocytosis associated with central neurological symptoms and cerebrospinal fluid involvement].
A 53-year-old woman was admitted with fever and general fatigue in December, 1988. A diagnosis of malignant histiocytosis (MH) was made based on her high level of LDH, thrombocytopenia, mild splenomegaly without systemic lymphadenopathy. There was also bone marrow infiltration large atypical cells and erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual disturbance and left lagophthalmos were recognized in March 1990. These signs indicated central nervous system (CNS) relapse which disappeared after intrathecal methotrexate injection. The same symptoms and signs appeared after another, 5 months. Tumor cells were found not only in the central spinal fluid but also in bone marrow. CNS and bone marrow recurrence were treated with intrathecal methotrexate injection VEPA therapy and cranial irradiation. We diagnosed this case as MH, based on the clinical features which did not include systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement was observed in bone marrow cells. Only one case of CNS infiltration diagnosed when alive has previously been reported in Japan. We report here a very rare case in which by medical treatment CNS infiltrations was improved twice.
Facial Nerve Diseases↗
The effect of 1-hydroxyvitamin D3 for prolongation of leukemic transformation-free survival in myelodysplastic syndromes.
Leukemic transformation (LT) free survival was studied in 30 patients with myelodysplastic syndromes (MDS). In 15 cases, 4-6 micrograms/day of 1-hydroxyvitamin D3 was administered, for a median duration of 17 months (D-group), other subjects had no therapy (N group). LT free survival of the D group had significant advantage over that of the N group according to the Kaplan-Meier method (P less than 0.001). In addition, 7 cases in the N group developed acute leukemia, in contrast to only one in the D group (P less than 0.05). These results suggest that oral administration of 1-hydroxyvitamin D3 prevents the progression of MDS to overt leukemia under the effect of differentiation capacity from blasts to monocytes.
Acute Disease↗
Comparison of cardiovascular effects of a novel class Ic antiarrhythmic agent, NIK-244, with those of flecainide in isolated canine heart preparations cross-circulated with a donor dog.
To assess the cardiovascular effects of a new class I antiarrhythmic agent, NIK-244, and to compare them with those of flecainide, canine isolated, sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. NIK-244 injected intraarterially into the isolated preparations showed dose-related negative chronotropic, negative inotropic, and coronary vasodilator effects, which are comparable to those of flecainide, and it also showed a dose-related negative dromotropic effect on both atrio-His (AH) and His-ventricular (HV) conduction. The prolongation of AH interval by NIK-244 was significantly more potent than that by flecainide, while that of the HV interval by NIK-244 was slightly more potent, but not significantly, compared with that by flecainide. NIK-244 administered intravenously into the donor dog showed bradycardic and depressor effects in both the donor dog and the cross-circulated sinus node and papillary muscle preparations, which are comparable to the effects of flecainide. Although the negative dromotropic effects of NIK-244 on both the donor dog heart and the cross-circulated atrioventricular node preparation started more slowly, they were more potent and longer-lasting than those of flecainide. Our results suggest that NIK-244 may be a more powerful and longer-lasting antiarrhythmic agent than flecainide, since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which is the most important depolarizing current responsible for the intraatrial and His-Purkinje-ventricular conduction.
Animals↗
Donor-HLA-incompatible marrow transplantation with an anti-donor cytotoxic antibody in the serum of the patient.
A 42-year-old female with acute mixed lineage leukemia received a marrow transplantation from an HLA non-identical sibling. The serum of the patient showed a positive crossmatch for anti-donor lymphocytotoxic antibody and exhibited a complement-mediated cytotoxicity to donor hematopoietic progenitor cells. In an attempt to reduce the risk of graft rejection, a large volume plasma exchange was performed, which was followed by an infusion of irradiated donor lymphocytes to eliminate remaining antibodies from her serum. The level of anti-donor antibody fell below the sensitivity of the anti-human immunoglobulin lymphocytotoxicity test after the infusion of donor lymphocytes. The cytotoxic activity against donor progenitor cells also disappeared from the serum. Cyclosporin had been administered for 2 weeks before marrow infusion, and methylprednisolone and prednisolone for 1 week before the initiation of conditioning chemoradiotherapy. Conditioning comprised cytosine arabinoside 5.6 g/m2, cyclophosphamide 4500 mg/m2 and fractionated total body irradiation with 15 Gy followed by an infusion of 4.0 x 10(8) cells/kg of unmodified marrow cells. Engraftment of donor cells was documented by HLA typing of peripheral lymphocytes. A sustained engraftment may be obtained in a donor-incompatible HLA non-identical marrow transplantation with anti-donor antibody by elimination of the antibody and achieving an intensive immunosuppression in the recipient before marrow infusion.
Adult↗
[Interaction between diltiazem and sevoflurane in the canine blood-perfused papillary muscle and sinoatrial node preparations].
Experiments were carried out on 17 canine isolated cardiac tissue preparations perfused by arterial blood from donor dogs. Diltiazem was continuously infused i.v. into the conscious (10 dogs) and the sevoflurane anesthetized (2.36%, 7 dogs) donor dogs at a rate of 20 micrograms.kg-1.min-1 for 60 minutes. The changes induced by diltiazem were normalized by the values at the start of diltiazem infusion, and the comparison was made between the two groups. 1) The decrease in heart rate and increase in PQ interval were smaller in conscious dogs than in the anesthetized dogs. 2) Decrease in developed tension in conscious state was smaller than that during sevoflurane anesthesia. 3) There was no significant difference in the decrease in blood pressure or sinoatrial rate between the conscious group and the anesthetized group. These results indicate that sevoflurane anesthesia removes the compensatory reflex which is present in the conscious state and also increases cardiovascular depressant effects of diltiazem.
Anesthetics↗
On the physiologic role of beta-2 adrenoceptors in the human heart: in vitro and in vivo studies.
To study the physiologic role of human myocardial beta-2 adrenoceptors, the beta adrenoceptor subtype(s) involved in the effects of catecholamines in vitro on the force of contraction and in vivo on heart rate were characterized. In vitro on both isolated electrically driven right and left atrial and left papillary muscle preparations, isoprenaline and adrenaline caused positive inotropic effects via beta-1 and beta-2 adrenoceptor stimulation. In the atria both beta-1 and beta-2 adrenoceptor stimulation increased contractile force to a maximum; in left papillary muscle, however, only beta-1 adrenoceptor stimulation maximally increased contractile force, whereas beta-2 adrenoceptor stimulation caused only submaximal increases. Noradrenaline, on the other hand, caused a positive inotropic effect nearly exclusively via atrial and ventricular beta-1 adrenoceptor stimulation. In vivo in 10 healthy volunteers isoprenaline-induced tachycardia was antagonized with equal potency by the beta-2 adrenoceptor-selective antagonist ICI 118,551 and the beta-1 adrenoceptor-selective antagonist bisoprolol indicating that it is mediated by cardiac beta-1 and beta-2 adrenoceptor stimulation to about the same degree. In contrast, exercise-induced tachycardia (that is mediated mainly by noradrenaline released from the neurons) was antagonized only by bisoprolol but not by ICI 118,551. It is concluded that in humans under normal physiologic conditions contractility and/or heart rate is regulated only by cardiac beta-1 adrenoceptors. In situations of stress, however, when large amounts of adrenaline are released from the adrenal medulla, stimulation of cardiac beta-2 adrenoceptors could contribute to additional increases in contractility, heart rate, or both.
Adrenergic beta-Agonists↗
Differential regulation of human cardiac beta-adrenergic and muscarinic receptors by chronic beta-adrenoceptor antagonist treatment.
In patients undergoing coronary artery bypass grafting chronic beta 1-adrenoceptor antagonist treatment increased right atrial beta 1-adrenoceptor number, did not affect beta 2-adrenoceptor number and decreased muscarinic M2-receptor number. Concomitantly, the M2-receptor-mediated negative inotropic effect of carbachol was reduced, while the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was not altered. The beta 2- adrenoceptor mediated positive inotropic effect of procaterol, however, was markedly enhanced. We conclude that chronic beta 1-adrenoceptor antagonist treatment increases beta 1-adrenoceptor number, sensitizes beta 2-adrenoceptor function and desensitizes M2-receptor function in the human heart.
Adrenergic beta-Antagonists↗
Molecular heterogeneity of beta-thalassaemia in the Japanese: identification of two novel mutations.
Five unrelated Japanese beta-thalassaemia genes, from one homozygote and four heterozygotes, have been systematically characterized using DNA polymorphism analysis, polymerase chain reaction, dot-blot hybridization and direct sequencing of amplified genomic DNA. Four different molecular defects were observed on three different beta-globin gene frameworks. One of these, the A----G mutation in the TATA box, a previously described mutation, was detected by dot-blot hybridization in one homozygote and one heterozygote with the beta-globin gene of framework 2. The second mutation is a C----T substitution at position 654 of IVS-2, the mutation commonly found in Chinese, which was associated with the framework 1 gene. Another two mutations, both associated with framework 3 genes, are novel ones; an amber mutation in codon 90 (GAG to TAG) and a frameshift (+G) insertion in codon 54, both of which cause a beta 0-thalassaemia phenotype by premature termination of the beta-globin chain synthesis.
Adult↗
Chronic beta 1-adrenoceptor antagonist treatment sensitizes beta 2-adrenoceptors, but desensitizes M2-muscarinic receptors in the human right atrium.
1. In 64 patients undergoing coronary artery bypass grafting the effects of chronic beta 1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial beta-adrenoceptor and muscarinic M2-receptor number and functional responsiveness were investigated. 2. The beta 1-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor number, did not affect beta 2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3. Concomitantly, activation of right atrial adenylate cyclase by 10 microM GTP, 10 microM isoprenaline and 1 microM forskolin was enhanced and inhibition by 100 microM carbachol was diminished. 4. On isolated, electrically driven right atria the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was - even with beta 1-adrenoceptor number increased - not altered, while the beta 2-adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the carbachol-induced negative inotropic effect was decreased. 5. It is concluded that chronic beta 1-adrenoceptor antagonist treatment increases beta 1-adrenoceptor number and concomitantly sensitizes beta 2-adrenoceptor function, but desensitizes muscarinic M2-receptor function in the human heart.
Adenylyl Cyclase Inhibitors↗
Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36).
We have studied the hemodynamic effects of neuropeptide Y (NPY) and its COOH-terminal fragment NPY-(18-36) in conscious rats. Intra-arterial injection of NPY rapidly elevated systemic vascular resistance (SVR), which remained high for greater than 30 min. Cardiac output (CO) decreased, and it remained low for greater than 30 min. Accordingly, blood pressure rose only transiently and returned to base-line values within 5 min. The reduction of CO could be attributed to a decreased stroke volume with an only marginal reduction of heart rate. Thus a direct cardiodepressive effect of NPY rather than baroreflex activation appears to be the major cause of the reduced CO. In vitro experiments excluded the possibility that NPY has direct negative inotropic effects and suggest that its cardiodepressive action is caused by coronary vasoconstriction or by presynaptic inhibition of norepinephrine release. Intra-arterial injections of NPY-(18-36) caused different hemodynamic effects. NPY-(18-36) decreased CO in a manner similar to that seen with NPY but initially did not elevate SVR, resulting overall in a reduced blood pressure. Only later, when blood pressure was reduced, was an elevation of SVR observed, which could be associated with increased plasma levels of catecholamines, angiotensin II, vasopressin, and NPY. Thus NPY-(18-36) mimics the cardiac effects of NPY but does not elicit its vascular effects. As NPY-(18-36) discriminates between NPY receptor subtypes in vitro, we conclude that the cardiac and vascular effects of NPY are mediated by distinct receptor subtypes.
Animals↗