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Biomedical subjects

T Okuda

Publications and source records attributed to T Okuda.

At least 361 records · Page 20Linked to original sources

[Clinical evaluation of a combination treatment with cefbuperazone and amikacin in infections complicating with hematological disorders].

The efficacy and the safety of a combination regimen using cefbuperazone (CBPZ) and amikacin (AMK) were evaluated in severe infections in patients with hematological diseases. Twenty two patients were subjected to this combination therapy; among these, 18 patients were evaluable for the effectiveness. They included 9 cases of leukemia, 5 cases of malignant lymphoma, 2 cases of aplastic anemia, and 2 cases of angio-immunoblastic lymphadenopathy with dysproteinemia. Excellent responses were obtained in 5 patients and good responses in 5 patients, with a total effectiveness of 55.6%. Efficacy rates for individual types of infections were; 2/2 in sepsis, 6/14, or 42.9% in suspected sepsis, 1/1 in urinary tract infection, and and 1/1 in upper respiratory infection. The combination treatment was also effective in 4 of 6 cases in which neutrophil counts were less than 500/mm3 prior to therapy. Side effects were observed in only one patient. Mild proteinuria occurred in a 80-year-old male in 6 days after the regimen was started, but was not serious. These results indicate that a combination of CBPZ and AMK is safe and effective for the treatment of infections even in patients with compromised immunodefenses.

Adolescent↗

[The importance of uterine vascular systems in the maintenance of pregnancy].

The mesometrial artery (MA), which is the final part of the uterine artery in guinea pig, supplies nutrients and oxygen to the fetus and placenta during pregnancy. Accompanying fetal growth, MA increases 8-fold in diameter, and 30- to 50-fold in weight, protein content and deoxyribonucleic acid (DNA) content. The importance of MA in the maintenance of pregnancy was examined by comparing the proliferative rate of MA during pregnancy and abortion induced by antiprogesterone RU38486 30 mg/kg. MA was incubated in Medium 199 with 185kBq/ml 3H-thymidine for 4h and the rate of 3H-incorporation into MA was used as the proliferative rate. The proliferative rate of MA during the first trimester (day less than 20) was 2,825 +/- 1,036 Bq/mg.h, which is almost 100 times higher than the rate in diestrus animals. During the later course of pregnancy, the proliferative rate decreased logarithmically, being 352 +/- 58 (40 less than or equal to d less than 50), 158 +/- 23 (50 less than or equal to d less than 60) and 75 +/- 10 (60 less than or equal to d). The proliferative rate of MA was measured also in animals which received RU38486 30 mg/kg at 24-48 h prior to the measurement and whose fetuses were still alive. The proliferative rates of MA in such animals decreased markedly to 141 +/- 21 (40 less than or equal to d less than 50) and 37 +/- 8 (50 less than or equal to d less than 60) (p less than 0.01), which means that the proliferation of MA is reduced even before the death of the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

[Clinical evaluation of cefpiramide for infections in leukemia and related disorders].

Forty one patients with infections associated with leukemia and related disorders were treated with cefpiramide (CPM). In 26 patients among them, we were able to evaluate the effectiveness of CPM against infections. Fifteen patients were not evaluated, because 6 patients were subjected to additional therapy such as gamma-globulin and other antibiotics, 5 were prophylactically treated, 2 had fever episode which were retrospectively reviewed to be originated from tumor mass, 1 received too short a duration of administration of CPM (2 days) to evaluate its effectiveness, and 1 with whom no precise data were recorded. Excellent responses were observed in 10 patients (38.5%) and good responses in 6 (23.1%) among these 26, with a total efficacy rate of 61.5%. Whereas, we found only one patient who showed an unfavorable side effect out of 31 patients including the 26 and 5 other patients who were prophylactically treated. The side effect observed was a mild bleeding tendency occurred in 77 years old female at 11 days after CPM was administrated. The bleeding tendency was easily diminished with the cessation of CPM treatment and a parenteral use of vitamin K. These results suggest that CPM is an effective and safe antibiotic for the treatment of infections in patients with leukemia and related disorders.

Adolescent↗

[Clinical evaluation of a combination therapy with aztreonam and clindamycin for severe infections in leukemia and related disorders].

A combination of aztreonam (AZT) and clindamycin (CLDM) was evaluated for severe infections associated with leukemia and related disorders. AZT is a monobactam antibiotic which has strong bactericidal effect against Gram-negative bacteria including Pseudomonas aeruginosa. CLDM which has strong antibacterial spectrum against Gram-positive and anaerobic bacteria, was chosen as a partner of AZT in order to complement the weak points of AZT. Fifty six patients were treated with the combination therapy. Among them, 51 patients were evaluable for the effectiveness. Five patients were excluded from the evaluation because 3 patients were subjected to additional therapy with other agents such as amikacin, miconazole and pulse therapy of a large dose of methylprednisolone, one had a fever episode apparently due to primary disease, and the remaining one was discontinued of the combination therapy of administration due to mild nausea after 3 days. Excellent responses were obtained in 17 (33.3%) patients and good responses in 20 (39.2%) patients, with a total rate of effectiveness of 72.5%. One patient with whom the combination therapy was stopped due to nausea, was included in the final evaluation of side effects. Side effects were observed in 2 patients of 50 and 40 years of ages (2/52, 3.8%), both of whom suffered with nausea. In the 50 years patient of acute myeloblastic leukemia, nausea occurred in a slight degree in 3 hours after the combined regimen was started. But, it disappeared during the continuation of the combination therapy. In the 40 years patient of acute myelomonocytic leukemia, mild nausea occurred after 3 day administration of the combined regimen. It disappeared soon after the cessation of the treatment. These results indicated that a combination of AZT and CLDM was an effective and safe regimen for the treatment of severe infections in patients with hematological disorders.

Adult↗

Mutant monoclonal antibodies with select alteration in complement activation ability. Impact on immune complex functions in vivo.

Mutagenesis of mAb is a useful means for studying the biologic and pathologic functions of immune complexes. Treatment of the Hy-1.2 hybridoma-producing IgG2a-anti-TNP antibodies with ethylmethanesulfonate provided us with a mutant clone, producing antibodies with reduced capacity for C activation. The antibodies retained normal Ag-binding capacity, staphylococcal protein A reactivity, and association to FcR for IgG on murine macrophages. No significant polypeptide deletion or class-switch was observed, but a significant change in clonotype was revealed by IEF. Intravenous injection of the mutant antibodies in immune complex form induced different tissue distributions of Ag in mice; i.e., more in kidneys and less in spleen, and developed more mesangial deposits in renal glomeruli compared with those of the wild type. Moreover, the production of granulomatous lesions in vivo caused by immune complexes of TNP-Sepharose was augmented by using mutant antibodies. These lesions demonstrated an enhanced accumulation of macrophages with multinucleated giant cells. Availability of this kind of mutant mAb is thus helpful in the elucidation of the biologic functions and consequences of immune complexes.

Animals↗

Effect of preanesthetic famotidine on gastric volume and pH.

The effect of preanesthetic 20 mg of famotidine on gastric fluid volume and pH were studied in patients scheduled for elective surgery. One hundred and twenty-eight patients were divided into four groups-control, intravenous, intramuscular and oral with 32 patients in each group. Patients in placebo group received no famotidine and served as control. Patients in the intravenous and intramuscular groups were administered famotidine one hour before surgery. Patients in the oral group were administered famotidine the night before and on the morning of surgery. Gastric volume in the control group was 19.1 +/- 10.8 ml; in the intravenous group, 7.4 +/- 6.4 ml; in the intramuscular group, 7.3 +/- 6.9 ml; and in the oral group, 7.1 +/- 6.9 ml. Gastric pH was 3.4 +/- 2.3, 6.8 +/- 1.1, 6.9 +/- 1.6, and 6.7 +/- 1.2 in groups one through four, respectively. When compared to the control group, famotidine significantly decreased gastric volume and increased gastric pH. There were no statistical differences among the different modes of administration. No adverse effects were observed in this study. It is concluded that preanesthetic management of 20 mg of famotidine reduced the risk of acid aspiration pneumonitis.

Clinical Trial↗

Detection of karyotypic abnormalities in most patients with acute nonlymphocytic leukemia by adding ethidium bromide to short-term cultures.

A modified short-term culture method, in which cultured bone marrow cells were treated with ethidium bromide to prevent chromosome condensation was used to study the chromosomes of 70 patients with acute nonlymphocytic leukemia. Clonal karyotypic abnormalities were detected in 60 patients. Among these, 35 patients showed one of recurrent type specific alterations. A close relationship between karyotypes and clinical outcome was shown: thus, t(8;21) or a single miscellaneous chromosomal defect associated with a favourable prognosis whereas t(9;11) or a complex karyotype related to a poor prognosis. The ten cytogenetically normal patients did not appear to have a favourable prognosis.

Adult↗

Cytogenetic evidence of clonal proliferation of leukemic progenitor cells from patients with acute promyelocytic leukemia (APL).

We have studied in-vitro growth of leukemic progenitor cells (L-CFU) in ten patients with acute promyelocytic leukemia (APL). All patients showed consistently an extraordinarily high incidence of cluster formation under the stimulation of human placental conditioned medium (HPCM) and/or phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM). Cytogenetic analyses of clusters or colonies disclosed the presence of a 15;17 translocation. These findings may represent the close relationship between specific chromosomal aberration, t(15;17), and the growth pattern of L-CFU of APL in vitro.

Adult↗

Heterogeneous colony forming ability in vitro of the abnormal clone-derived granulocyte-macrophage precursors in myelodysplastic syndromes.

The clonal origin of granulocyte-macrophage colony forming cells (CFU-GM) in the myelodysplastic syndrome (MDS) was cytogenetically studied. Chromosome analysis was carried out on single GM-colonies from six patients with MDS, whose bone marrow cells had chromosome abnormalities. Abnormal clone-derived CFU-GM were grown in four patients under the presence of human placental conditioned medium. In the remaining two, all analysed colonies revealed a normal karyotype, although the majority of metaphase cells showed an abnormal karyotype in bone marrow preparations. These results indicate that the abnormal clone-derived CFU-GM in MDS have a clone-by-clone variation in colony forming ability in vitro.

Adult↗

Monoclonal antibody directed against neuroendocrine properties of both normal and malignant cells.

A monoclonal antibody, 6H7, was produced by the immunization of small cell carcinoma of the lung (SCCL). Immunohistochemical examination indicated that 6H7 reacted not only with SCCL but also various neuronal and/or endocrine tumors such as neuroblastoma, pheochromocytoma, carcinoid and adrenal cortical tumors. 6H7 was also reactive with normal neuroendocrine tissues including brain, spinal cord, thyroid follicular cells, pancreatic islet cells and adrenal cells. 6H7 did not react with squamous cell carcinomas, one large cell carcinoma or most adenocarcinomas of the lung, or carcinomas of the stomach, colon, pancreas, breast and esophagus. The antigen recognized by 6H7 was analyzed on gel filtration after purification of the antigen by liquid chromatography which indicated the molecular weight of the antigen to be 270,000-300,000. From SDS-PAGE analysis the antigen reactive with 6H7 appeared to consist of polypeptide dimers of 128,000.

Animals↗

Responses of sodium balance, blood pressure, and other variables to sodium loading in Papua New Guinea highlanders.

For determination of the responses of sodium balance, blood pressure, and other relevant variables to Na loading in people with a low intake of Na, 10 male Papua New Guinea highland subjects were given additional Na at two levels (128 and 256 mmol/d) for 10 d after a 3-d control period of low-Na diet. Na loading caused a marked positive balance of Na, decreases of aldosterone concentration and renin activity in the plasma, and a decrease of urinary aldosterone excretion. The blood pressure, particularly that measured at noon, increased in the latter half of the Na-loading period, the increase being significant in the group given 256 mmol of sodium daily: the systolic and diastolic blood pressure increased from 92 +/- 8 over 56 +/- 7 mm Hg in the control period to 102 +/- 7 over 60 +/- 4 mm Hg in the latter half of the test period (p less than 0.05).

Adult↗

Penetration of cefpiramide and cefazolin into peritoneal capsular fluid in rabbits.

Penetration of cefpiramide and cefazolin into a specific extravascular fluid was measured with rabbits bearing capsules in the peritoneal cavity. A general feature of slow accumulation and elimination of drugs from extravascular sites having low surface area/volume ratios has also been observed in this study. The capsular concentration-time profiles were well expressed by the following equation: C(CF) = A(CF)[e-kel(CF)(t-to)-e-kp(CF)(t-to)], where C(CF), A(CF), kp(CF), kel(CF), and to indicate capsular concentration at time t, constant for the dimension of concentration, capsule penetration rate constant, capsule elimination rate constant, and lag time before penetration occurs, respectively. The kp(CF), kel(CF), and to were 0.139 h-1, 0.059 h-1, and 0.45 h, respectively, for cefpiramide, and 0.448 h-1, 0.0145 h-1, and 0.14 h, respectively, for cefazolin. A(CF) was 22.7 micrograms/ml for cefpiramide and 4.53 micrograms/ml for cefazolin, being parallel to the area under the plasma concentration-time curve for free drug from to to infinity (20.1 micrograms.h/ml for cefpiramide and 3.43 micrograms.h/ml for cefazolin). In conclusion, it is suggested that as well as kp(CF) and kel(CF), the area under the plasma concentration-time curve for free drug from to to infinity may play an important role regarding the circulating reservoir of drugs in determining capsular concentration-time profiles in experimental models for particular extravascular sites of infection, like abscesses into which drugs cannot easily penetrate.

Animals↗

Pharmacokinetic and pharmacodynamic interactions between furosemide and hydrochlorothiazide in nephrotic patients.

We examined the response of 8 patients with nephrotic syndrome (creatinine clearance 70.4 +/- 16.0 ml/min) to oral furosemide (F; 40 mg) in the absence (control) and in the presence of oral hydrochlorothiazide (HCT; 100 mg). In the 24-hour period after oral F, HCT was shown to increase urine volume and urinary sodium and chloride excretion. Increment was most significant during the 12- to 24-hour period. Enhancement of the diuresis with HCT was associated neither with a significant increase in the area under the curve of plasma F concentration nor an increase in urinary F excretion. Urinary excretion of glucuronidated F, one of the main metabolites of F, however, was decreased with HCT. In summary, HCT significantly enhanced the response to F in nephrotic patients.

Drug Interactions↗

Cytogenetic evidence for a clonal involvement of granulocyte-macrophage and erythroid lineages in a patient with refractory anaemia.

To investigate the clonal origin of refractory anaemia, we carried out cytogenetic studies on single haematopoietic colonies derived from granulocyte-macrophage precursors (CFU-GM) and erythroid precursors (BFU-E). Marrow cells from a patient with refractory anaemia revealed the coexistence of a normal and an abnormal karyotype; 46,XY/45,XY,-15,-18,+der(15q18q). Cytogenetic studies on CFU-GM- and BFU-E-derived colonies obtained from the bone marrow showed the presence of the same karyotypic abnormality carrying the der(15q18q). Colonies carrying a normal diploid karyotype were also detected in the same culture dish. These results indicate that the clone with the der(15q18q) chromosome abnormality arises in a stem cell which can differentiate to at least both granulocyte-macrophage and erythroid lineages.

Adult↗