[Clinical evaluation on SM-4300 for severe infections complicated with hematological disorders--a comparative study with cross-over method].
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Biomedical subjects
Publications and source records attributed to T Sugihara.
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Membrane lipid analyses and electron spin resonance (ESR) studies of membrane fluidity were carried out on the red cells of a Japanese patient with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA). Increased amounts of phosphatidylcholine (PC) and cholesterol were found in the membrane lipids of the affected patient, despite normal plasma lipids. The order parameter of cholesterol-free pure phospholipid liposomes prepared from this patient's red cells was decreased, apparently because of the increased PC. In contrast, the order parameter of the total red cell lipid liposomes (containing free cholesterol) was essentially normal. The overall fluidity of the intact red cells was determined by ESR with a spin probe, 5-SAL. Again, the order parameters were normal in the intact red cells of the patient with HPCHA. This suggests that the concomitant increase of membrane cholesterol and phosphatidylcholine serves to maintain normal membrane fluidity in the HPCHA red cells.
Clinical studies on a new cephalosporin antibiotic, cefotaxime (CTX) were carried out in 79 patients with various types of infections in internal medicine. The efficacy rates were 65.8% in 39 cases of respiratory tract infections, 94.1% in 17 cases of biliary tract infections, 75.0% in 12 cases of urinary tract infections, 80.0% in 11 cases of other infections, and 75.3% in all cases. After CTX therapy, body temperature was improved in 76.7% of all 79 patients, particularly being excellent in all cases of biliary tract infections. Furthermore, symptoms such as cough, dyspnea, chest pain, moist rale and anorexia were improved to a great degree after CTX therapy. Adverse reactions and abnormal laboratory findings consisted of mild liver injury in 1 out of 79 cases. CTX was assessed to be an effective antibiotic for various types of infections in internal medicine.
Serum tissue polypeptide antigen (TPA) levels were measured in 33 patients with esophageal cancer, 39 with stomach cancer and 50 with colon cancer. At the same time five glycoproteins, namely immunosuppressive acidic glycoprotein (IAP), alpha 1-antichymotripsin (alpha 1-ACT), acid soluble glycoproteins (ASP), sialic acid and carcinoembryonic antigen (CEA), were measured for comparison. The mean TPA values were 59.0 +/- 15.4 U/l in 61 normal subjects, 103.6 +/- 104.2 U/l (positive rate, 24.2%) in esophageal cancer patients, 111.9 +/- 49.8 U/l (71.8%) in stomach cancer patients and 124.8 +/- 195.5 U/l (40%) in colon cancer patients. The serum TPA levels in patients with stomach cancer rose with an increased number of involved lymph nodes and with a higher degree of infiltrative growth and increased with the advancement of tumor growth postoperatively. Serum TPA levels correlated well with those of alpha 1-ACT, IAP and ASP in stomach cancer patients and with those of CEA, ASP and sialic acid in colon cancer, but not in esophageal cancer patients. It is suggested that the serum TPA might represent one of the reactant proteins and/or tumor-associated antigens that appear to be dependent upon the cancer status.
Prognosis of 43 patients with esophageal squamous cell carcinoma with pre-operative irradiation and that of 50 patients by surgical excision alone were compared by five year survival rate. The pre-operative radiation treatment comprised a daily doses of 2 Gy. given for consecutive days, up to total dosage of 40 Gy. (T.D.F.66). The operative excision was done two weeks after the the completion of the radio-therapy. In early cases (st. I, II), five year survival rate of the pre-operative irradiation group was 59.8% and 74.2% for surgical treatment alone group. In advanced cases (st. III, IV), the radiation group and surgical treatment alone group showed 21.8% and 15.1% respectively. Among advanced cases, the result in relation to the location of tumor in the esophagus was studied. In the cases which the tumor was located at the upper and middle intra-thoracic esophagus, five year survival rate in pre-operative radiation group was 21.4% versus no survivor in surgical excision alone. In contrast, five year survival rate was better by surgical treatment alone among these advanced cases located at the lower esophagus. The pre-operative irradiation treatment is indicated for esophageal cancer which is advanced and located in the upper and middle intra-thoracic esophagus.
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The skin extensibility was measured at 12 anatomical sites of the living body using the BIO-SKIN TENSION METER equipped with a strain-gauge. The subjects were 82 healthy males whose ages ranged from four months to 73 years. The differences in degree of extensibility according to age are summerized as follows. Two age groups, the below one year old and the one-to-two year-old group, showed significant extensibility in most, but not all of the measured sites. The 50-year-and-older group did not show any significant differences in the degree of extensibility as compared to the 20-29 year-old group. Degree of wound retraction, would closing tension and skin extensibility were measured after the first and second operations of serial excision. Results of measurements are summerized below. The highest degree of decreased extensibility was observed at 3 months after surgery, and the recovery of skin extensibility was observed at 6 to 9 months postoperatively depending on the measuring sites and excised widths. Serial excision yielded more satisfactory results than one stage excision with regard to suture of the wound due to the reduced degree of wound retraction and closing tension. An interval of 6 months between operations was recommended for serial excision on face of less than 20 mm, on arm of less than 30 mm and excision of less than 35 mm on the trunk, and an interval of 9 months was judged to be appropriate for serial excision exceeding 50 mm on trunk. Recommended excision widths in serial excision for children are as follows; less than 30 mm on the face, less than 45 to 50 mm on the arm, less than 85 to 100 mm on the trunk.
A sensitive solid phase enzyme immunoassay (EIA) was developed for the measurement of factor IX antigen (IX:AG), using rabbit antihuman factor IX antiserum and beta-D-galactosidase, which enabled us to detect IX:AG as low as 10(-4)U/ml. 37 patients with severe hemophilia B have been investigated by EIA, inhibitor neutralization assay and bovine brain prothrombin time. They could be divided into four genetic variants. 25% had normal levels of IX:AG but decreased levels of factor IX clotting activity. On crossed immunoelectrophoresis of the hemophilia B+ and hemophilia BM, we could not find abnormalities in electrophoretic mobilities compared to normal subjects in the presence of 1 mM Ca++ lactate.
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A combination chemotherapy "VEMA" consisting of vincristine (VCR), cyclophosphamide (Endoxan, EX), methotrexate (MTX) and nimustine (ACNU) has been carried out for the treatment of small cell bronchogenic carcinoma since September, 1978. "VEMA" regimen consists of VCR 1.3 mg/m2 iv push on day 1, EX 500 mg/m2 iv infusion on day 1 and 2, MTX 28 mg/m2 iv push on day 1, 2 and 3, and ACNU 67 mg/m2 iv push on day 3. This dose schedule was repeated every 3 to 4 weeks. The regimen was given to 14 patients and 12 patients were evaluable. In the 12 evaluable cases, 2 case of complete response (CR), 7 cases of partial response (PR) and 2 cases of effusion effective were obtained. Response rate of CR + PR was 90%. Response rate including CR, PR and effusion effective was 91.7%. The major clinical toxicity of "VEMA" therapy was bone marrow suppression. Other side effects were anorexia, nausea, vomiting, alopecia and stomatitis: etc; however, these side effects were not life threatening to terminate "VEMA" therapy. In conclusion, "VEMA" regimen is a new potent combination chemotherapy in the treatment of small cell bronchogenic carcinoma.
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UFT-E, enterogranules of tegafur-uracil (at molar ratio of 1: 4) was developed in order to minimize GI toxicity of UFT. Pharmacokinetic study after single oral administration of 300 to 1200 mg of UFT-E was carried out in cancer patients measuring tagafur, uracil and 5-FU levels in serum, normal tissue and tumor tissue using HPLC and GC-mass. In the all doses studied, curves of serum tegafur after administration of UFT-E were consistently higher than those of uracil and 5-FU. Peak 5-FU levels were observed at 2-4 hours after administration of UFT-E. Maximum 5-FU levels ranged 0.1-3.0 mcg/ml and were variable in each patient even at the same doses. The serum 5-FU level was correlated with tegafur and uracil levels, especially with the latter. The curves of serum 5-FU of UFT-E were different from those of UFT, and the peak time of UFT-E occurred 2 or 3 hours later than that of UFT and the decrease of 5-FU level was slower. The concentrations of 5-FU in tumor tissue (T) were observed in most of the cases compared with those in normal tissue (N) (T/N ratio of more than 2.0 was observed in 16/23 patients), especially in the patients received higher doses of UFT-E and in the patients with GI cancers. In the phase I study of oral daily consecutive administration of UFT-E in 23 cancer patients, the GI side effects such as anorexia, nausea, vomiting and diarrhea, were observed in 5 out of 23 patientsr.(ABSTRACT TRUNCATED AT 250 WORDS)
A 79 year old man with a history of myocardial infarction and cerebral infarction was admitted to our hospital in August, 1982. The hematological examination showed anemia and leukopenia (myeloblast 12%), and bone marrow aspiration confirmed the diagnosis of acute myeloblastic leukemia (FAB, M2). Because his general condition was poor, he was treated with small dose of Ara-C (10 mg/m2/12 hr, subcutaneous injections), obtaining complete remission. In cases of acute myeloblastic leukemia in elderly patients where other intensive treatments are contraindicated, it appears to be useful to employ a method of small dose of Ara-C therapy.
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