[A case of antidiuretic hormone-producing malignant teratoma of the anterior mediastinum].
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Biomedical subjects
Publications and source records attributed to S Matsuda.
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The pharmacokinetics, the safety and the efficacy of purified recombinant human granulocyte colony-stimulating factor (rh G-CSF) expressed in Chinese hamster ovary (CHO) cells were studied in normal healthy adults. Following the single subcutaneous dose, G-CSF levels in sera elevated in a dose-dependent way, with C-max of approximately 140 pg per ml, T-max of 4 hours and T-half of 5 hours at a dose of 10 micrograms per ml. In accord with the elevation, blood neutrophil counts rose promptly and transiently without any changes in the other blood cell counts. Degree and duration of the neutrophilia were apparently proportional to the rh G-CSF dose and, in turn, the G-CSF levels in sera. Single daily injections of rh G-CSF at a dose of 10 micrograms per body per day for 7 consecutive days did not bring on any accumulation of rh G-CSF in sera, and repeatedly induced neutrophilias following every injection. During the course of the injections, the chemiluminescence generating ability of blood neutrophils also rose. Peak value of the transient neutrophilias and level of the abilities tended to go down after 3 or 4 consecutive injections, presumably due to the limited number of mature neutrophils which can be released from the bone marrow in response to rh G-CSF. However, it was found that the M/E ratio becomes higher after the repeated dosing with an increased proportion of myeloid immature cells as well as increase in the levels of both erythroid and myeloid precursor cells in the bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.
A multi-center open study was conducted to investigate cefuzonam (CZON, L-105) regarding to its pharmacokinetic, bacteriological and clinical aspects in the field of obstetrics and gynecology with the participation of 31 medical institutions and the related facilities. The results are summarized as follows. 1. Peak MICs of CZON for Staphylococcus aureus, coagulase (-) staphylococci, Escherichia coli, Klebsiella pneumoniae, Bacteroides fragilis group, Peptostreptococcus spp. isolated from obstetrical and gynecological infections with relatively high frequencies were 0.39, 0.20, 0.024, 0.024-0.05, 12.5, 0.20 microgram/ml, respectively, with an inoculum size of 10(6) CFU/ml. 2. When 1 g of CZON was given through bolus injection, the maximum concentration (Cmax) of CZON in pelvic dead space exudate was 18.7 micrograms/ml at 60.9 minutes (Tmax) after the injection; Cmax's in all female genital tissues were observed at 0.6-27.9 minutes and ranged from 11.9-26.3 micrograms/g. The Cmax 8.3 micrograms/ml, in the pelvic dead space exudate was noted at 97.0 minutes after the end of the intravenous drip infusion of 1 g over 1 hour, and Cmax's in genital tissues were 14.3-30.0 micrograms/g at the end of infusion. With 1 hour drip infusion of 2 g, Cmax's in genital tissues were 35.0-53.9 micrograms/g at the end of infusion. 3. The clinical efficacy of CZON was evaluated in 206 evaluable patients with obstetric and gynecologic infections. Efficacy rates classified by types of infections were 97.1% (67/69) for intrauterine infections, 81.6% (31/38) for intrapelvic infections, 91.8% (45/49) for adnexitis, 95.2% (20/21) for infections of the external genital organs and 86.2% (25/29) for other infections. 4. Side effects were observed in 7 of the 262 patients: eruption in 6 cases, itching in 2, diarrhea in 1. Abnormal laboratory test values were noted in 9 of the 256 patients. Most of them were slight elevation of hepatic function values. CZON showed satisfactory clinical efficacy and potent antibacterial activity, hence it appears that CZON will be a very useful antibiotic for obstetric and gynecologic infections.
For the present, we don't have any reliable definition of the early cancer in hepato-biliary and pancreatic region. In this paper three examples of comparatively early cancer were taken up; (1) among hepatocellular carcinoma, so called, small liver cancer; (2) among gallbladder carcinoma and bile duct carcinoma, those whose extent of infiltration within pm and fm respectively; (3) among pancreatic carcinoma, those whose maximum diameter are 2 cm. And the system of imaging diagnosis was discussed as well as the discussion of their clinical characteristics, imaging diagnosis and the differential diagnosis.
Pharmacokinetic and clinical studies on imipenem/cilastatin sodium (IPM/CS) in the perinatal period were carried out, and the results obtained are summarized below. 1. IPM/CS transfers to umbilical cord plasma and amniotic fluid were effective. Passage of IPM/CS into mother's milk was as little as with other beta-lactam antibiotics. 2. Among 81 patients with perinatal infections, clinical efficacies were excellent in 16 patients, good in 62, poor in 3, with an efficacy rate of 96.3%. In addition, IPM/CS was effective in 6 patients for prophylaxis. 3. Out of 82 isolates examined for bacterial responses, 69 isolates were eradicated and 8 isolates were decreased. Especially, of 13 isolates of Enterococcus faecalis, 12 were eradicated. 4. In 109 patients administered with IPM/CS, vomiting was observed in 1 patient. No abnormal laboratory test values were observed. 5. IPM/CS was an effective and safe new antibiotic in perinatal infections. We recommend a normal dose of IPM/CS of 0.5 g/0.5 g twice a day and a dose for severe infections of 1 g/1 g twice a day in the perinatal period.
Ceftriaxone (CTRX), an injectable cephem antibiotic agent, was studied for its pharmacokinetic properties and clinical usefulness in perinatal infections in obstetrics and gynecology on a multicenter basis. The study results are summarized below. 1. Following the one-shot intravenous injection of CTRX 1 g to pregnant women before labor, the maternal serum level of CTRX reached a peak at 131.8 micrograms/ml soon after the injection then it began to decrease gradually. T 1/2 was 6.7 hours. The umbilical serum level reached a peak at 16.0 micrograms/ml at 4.9 hours post-dose and decreased gradually with a half-life of 8.1 hours. The umbilical serum level was higher than the maternal serum level at about 12 hours post-dose. The amniotic fluid level reached a peak of 9.6 micrograms/ml at 12.8 hours post-dose. T 1/2 was 15.2 hours. The amniotic fluid level at about 15 hours post-dose or later exceeded the maternal serum level and was almost equal to the umbilical serum level at 24 hours post-dose. 2. Clinical usefulness was evaluated in 79 evaluable cases out of 89 treated for various infections at puerperium or for prophylaxis of infections at cesarean section or premature rupture of membranes (PROM). The efficacy rate was 100% in 7 cases of prenatal infections such as urinary tract infection and 30 cases of postnatal infections such as puerperal intrauterine infections. In 42 cases treated for prophylaxis in cases of cesarean section or PROM, the efficacy rate was 92.9%. Bacteriologically, 29 strains of pathogens were isolated from 26 cases. The disappearance rate of the pathogens was 96.0% as 23 strains were eradicated, 1 strain was substituted and no change was observed in 1 strain with unknown results in 4 strain. Skin rash and itching appeared in 1 patient as an adverse effect (1.1%). There were 10 cases of abnormal clinical laboratory test results such as elevated transaminase level were observed in 7 patients (7.9%). From the results, CTRX was considered to be a useful drug for the perinatal infection in the obstetrics and gynecology fields.
Flomoxef (FMOX) has a broad antibacterial spectrum against Gram-positive and Gram-negative bacteria; especially its potent antibacterial activity against Staphylococcus aureus is a significant advantage that may not be found with other cephem compounds. In our determination of its antibacterial potency against various clinical isolates obtained from clinical materials (amniotic fluid, intrauterine secretions, exudates of the pelvic dead space) of patients with various infections, we obtained results representing specific features of this drug. From the results, the drug may be expected to produce an excellent effect in the treatment of various infections. Our study on drug concentrations in body fluids and genital tissues demonstrated a good transfer of this drug into various tissues; in every tissue examined, the drug administered by the usual method in the usual dose yielded a concentration exceeding MIC for principal pathogens, thus promising a good clinical response. Indeed a high clinical efficacy rate of 90.1% (good to very good responses) was obtained in a clinical trial involving 222 cases. Administration of the drug in 2 g quantity daily produced a high response rate of 92.8%. It was especially noteworthy that a good response was obtained in 30 of 32 cases (93.8%) in which other cephem compounds had failed. In evaluation of the bacteriological effect, furthermore, the drug showed an excellent rate of bacterial elimination. In conclusion, this drug is expected to be greatly useful in the light of its good transfer into genital tissues and its strong antibacterial activities against Gram-positive cocci, Gram-negative bacteria and anaerobes as well as against multiple bacterial infections predominating among women with genital infections.
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We report a case of pure choriocarcinoma of the left testis with multiple pulmonary and cerebellar metastases. A 25-year-old male was referred to our clinic because of painless swelling of the left scrotal content and multiple nodules shown in the chest X-ray. At hospitalization, the examination also revealed cerebellar metastasis. With left high orchiectomy, the lesion was confirmed to be pure choriocarcinoma. In spite of several treatments including surgical removal of metastatic brain tumor and combination chemotherapy, he died on the 79th hospital day. Pure choriocarcinoma of the testis is an uncommon disease. Only 46 cases have been reported in the literature before 1987.
Clinical studies were carried out on imipenem/cilastatin sodium (IPM/CS) in the perinatal period, and the results are summarized below. 1. IPM/CS was administered to a total of 10 patients including 7 with puerperal intrauterine infections and 3 with pyelonephritis at a dose of 0.5 g/0.5 g twice daily through intravenous drip infusion. IPM/CS showed satisfactory results. Clinical efficacies were excellent in 1 patient, good in 9 with an efficacy rate of 100%. 2. As for bacteriological evaluation, 12 strains out of 14 detected in 8 patients before the treatment were eradicated upon IPM/CS administration, with an eradication rate of 85.7%. The remaining 2 strains persisted. 3. Neither subjective and objective side effects nor abnormal laboratory test values were observed in any of the patients or their babies.
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For the purpose of examining the mechanisms for the overproduction of megakaryocytes and platelets in essential thrombocythemia (ET), marrow megakaryocytic colony-forming units (CFU-Meg) were characterized using a methylcellulose culture system in nine patients with ET, and they were compared with those of 16 control subjects and four patients with secondary thrombocytosis (ST). The number of CFU-Meg per 10(5) cells in ET was significantly higher (p less than .001) than that in the controls (5.8 times of the controls) or that in ST. ET showed endogenous CFU-Meg (58 +/- 16% of the total CFU-Meg) that could form megakaryocytic colonies without phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM) as a source of Meg-CSA. The controls and the patients with St revealed no endogenous CFU-Meg. The dose-response studies with PHA-LCM revealed that CFU-Meg from ET are highly sensitive to low concentrations of PHA-LCM compared to CFU-Meg from the control and ST. Erythropoietic burst-forming units (BFU-E) were monitored as a control progenitor, because the patients with ET studied did not have erythrocytosis. Although five out of nine patients with ET had endogenous BFU-E, the percentages of endogenous BFU-E were small (4-10%). The number of BFU-E in ET was not different from the control value. Thus, ET is associated with an enlarged CFU-Meg compartment that shows abnormal growth patterns when cultured in vitro, while the growth abnormality of BFU-E is small, which may underlie the hematological features of ET. The culture of CFU-Meg should be clinically useful for differentiating ET from ST.
The early formation of neuronal connections in the cervical cord of chick embryos at stages 17 to 31 was studied by observing axonal courses with Golgi preparations and the distribution of synapses with electron microscopy. The results are summarized as follow: 1. Synaptic contacts between spinal interneurons and ipsilateral as well as contralateral motor neurons first develop at stage 22. The early central pathways from the dorsal root to the ventral root may be formed at stage 25 with intervention of interneurons of the primordial dorsal horn, which is composed of neurons of the zona spongiosa and the nucleus proprius of the dorsal horn, and at stage 27 with the intervention of interneurons of the zona intermedia, the nucleus proprius of the ventral horn and the primordial dorsal horn as well. 2. These polysynaptic, bilateral central pathways appear to be established just before the arrival of supraspinal descending fibres at the cervical cord, and one or two days before the formation of ipsilateral monosynaptic spinal reflex arch. 3. These early spinal central pathways are connected by synapses with spherical synaptic vesicles, and almost all of these synapses are of the axo-dendritic type and located in the spinal white matter.
Forty five patients were examined in order to evaluate the usefulness of glucagon and insulin as a therapy of fulminant hepatitis. Thirty patients were treated with simultaneous infusion of glucagon and insulin, whereas prednisolone was given at a daily dose of 60 to 90 mg in 15 cases. In the former group, 1 mg of glucagon and 10 units of regular insulin were infused over a period of 2 to 6 hours. Two such treatments were given per day in the early critical period of fulminant hepatitis. The therapeutic effect of glucagon and insulin was evaluated in comparison with that of prednisolone, and additionally, with a combination therapy of either blood exchange or plasmapheresis in both groups. The survival rate was superior in the group treated with glucagon and insulin (46%) and in the one with combined infusion of these hormones plus plasmapheresis (33%).
A method for labeling leukemic cells in vitro with 111In-oxine is described. Intravascular survival data and organ distribution of 111In-oxine-labeled leukemic cells in patients with acute leukemia are presented. No evidence of diminished cell viability or significant elution of the label could be found by the in vitro studies. Disappearance curves of 111In-labeled leukemic cell radioactivity in the circulation were a single exponential with average T1/2 value of 15.3 +/- 2.5 hr (mean +/- SEM), which was found to be prolonged when compared with the results of 4 hematologically normal subjects (7.0 +/- 0.8) and those of previously reported DF32P studies. Migratory patterns of the labeled leukemic cells, obtained by a scintillation camera, demonstrated sequestration in the lungs 5 min after the infusion, and thereafter, the uptake into the spleen and liver gradually increased. We believe that the properties of 111In-oxine might overcome many of the difficulties of studying leukemic cell kinetics with cells labeled with tritiated thymidine.
Chromosome studies of cells from megakaryocytic colonies (CFU-Meg) as evidenced by a megakaryocyte-specific monoclonal antibody, TP80, from a patient with chronic myelogenous leukemia (CML) in the blast crisis (BC) revealed the same aberrant karyotype, 52,XY,+9,+9,+18,+19,+21,+22,t(9;22)(q34;q11),t(9;22), as that having newly appeared in the peripheral blood. Cells from erythroid bursts (BFU-E) showed only the standard 46,XY,t(9;22) karyotype, and cells from granulocyte/macrophage colonies (CFU-GM) had either of these karyotypes. These results demonstrated that the whole megakaryocytic line and part of the granulocyte/macrophage line had been involved in the BC while the erythroid line totally belonged to the original clone. Chromosome analysis coupled with immunophenotyping of hemopoietic colonies was useful for a definite diagnosis of megakaryoblastic crisis of CML in this patient.