Biomedical subjects

T Shinkai

Publications and source records attributed to T Shinkai.

At least 145 records · Page 8Linked to original sources

PubMed1986

Effects of chronic hyperthyroidism on the lifespan of the rat.

The life durations of hypo- and hyperthyroid Wistar rats were measured under clean conventional conditions. The amount of exogenous T4 (thyroxine), which is sufficient to elevate T4 levels in the blood, decreased with age. The rats which were made hypothyroid by the neonatal T4 treatment had a longer lifespan than control. The lifespans of hyperthyroid rats, to which T4 solutions were given as drinking water during either the first or the second half of the life period, were shorter than control. The life-shortening effect of T4 was not detected when T4 was administered to already aged animals. These results indicate that the effect of T4 administration is not due to the direct promotion of the diseases which cause the death, but to the acceleration of aging during the young or middle-aged period.

Aging↗

PubMed1986

A case of small cell lung cancer successfully treated with VM26.

A 79-year-old man was admitted to our hospital for a close examination of an abnormal shadow on a routine chest roentgenogram. A large tumorous shadow in the right S1 segment, and hilar and mediastinal node swelling were observed. Transbronchial biopsy revealed that the histologic type of the tumor was oat cell carcinoma. The clinical stage was considered to be limited disease. Because of his age, 79 years, he was treated with VM26 as a single agent. VM26 was administered by intravenous drip infusion of 60 mg/m2 daily for five consecutive days every three to four weeks. After the third course of treatment with VM26, he achieved partial response, and then radiation therapy to the primary site and the hilar and mediastinal nodes was given at a total dose of 6,000 rad. There have been few phase II studies of VM26 in patients with small cell lung cancer (SCLC). Further phase II studies should be conducted for confirmation of the reproducibility of the phase II study of VM26 in SCLC, and the efficacy of combination chemotherapy including VM26 against SCLC should also be tested.

Aged↗

PubMed1986

Phase II study of UFT in patients with advanced non-small cell lung cancer.

A phase II study of UFT (a mixture of uracil and tegafur; molar ratio of uracil to tegafur = 4) was undertaken in 21 patients with advanced non-small cell lung cancer (NSCLC). UFT was administered orally at a dose of 400 mg/m2 every day, for more than four weeks. Of 16 adequately treated patients, one (6.3%) showed a partial response. Toxic effects included minimal myelosuppression, anorexia, nausea, vomiting and epigastralgia. Gastrointestinal toxicity was well tolerated. Considering the poor response and mild toxicity, a further phase II study of higher-dose UFT is necessary for patients without prior therapy.

Adult↗

PubMed1986

Phase II study of mitoxantrone in patients with non-small cell lung cancer.

A phase II study of mitoxantrone was performed in 24 patients with non-small cell lung cancer (NSCLC). Mitoxantrone was administered by intravenous drip infusion of 12 mg/m2 every three weeks. There were no responders among the 21 evaluable patients including five patients without prior therapy. The major hematological toxic effect was leukocytopenia. Thrombocytopenia and decrease in hemoglobin were slight. A change in the electrocardiogram was observed in one patient and one patient experienced cardiogenic shock. Mitoxantrone is not acceptable for the treatment of NSCLC because of its low antitumor activity, and careful observation is needed for administration of this agent to patients with pre-existing risk factors, such as prior anthracycline exposure, mediastinal radiation or underlying cardiovascular disease.

Aged↗

PubMed1986

The protective effect of 2-mercapto-ethane sulfonate (MESNA) on hemorrhagic cystitis induced by high-dose ifosfamide treatment tested by a randomized crossover trial.

High-dose ifosfamide (one or two courses of 6 g/m2) with or without mesna was administered to 13 patients with advanced non-small cell lung cancer. The protective effect of 2-mercapto-ethane sulfonate (mesna) against the urotoxic side effects induced by ifosfamide was examined by a randomized crossover trial. A significant reduction in the incidence of hematuria was observed in the patients receiving mesna. Macroscopic hematuria was observed in only one patient who received treatment with mesna versus seven patients treated with ifosfamide alone. Other symptoms, such as frequency and dysuria, tended to be diminished in the patients receiving mesna, although the difference was not statistically significant. Our results suggest that mesna is effective in preventing or diminishing ifosfamide-induced hemorrhagic cystitis. Concomitant use of mesna should allow the administration of a high dose of ifosfamide although more extensive studies are needed to define the optimal dose and schedule of administration of mesna to prevent or attenuate the hemorrhagic cystitis.

Adult↗

PubMed1986

A case report of a three-year survivor with advanced non-small cell lung cancer producing alpha-fetoprotein.

An 80-year-old patient with poorly differentiated adenocarcinoma of the left lung with metastasis to both lungs and supraclavicular lymph nodes, stage III M1 (T2N2M1), was treated with cisplatin (cis-diamminedichloroplatinum, CDDP) at a dose of 80 mg/m2 intravenously. He achieved a partial response, however, he could not continue therapy with CDDP because of its renal toxicity. He was then given etoposide and vindesine as a single chemotherapeutic agent, but no response was observed. Therefore, CDDP was administered again in a fractionated regimen, the first course of treatment achieved a minor response, but the second course resulted in stable disease. He therefore received combination chemotherapy consisting of mitomycin, vindesine and CDDP, and tumor regression of more than 30% was observed after one course of this combination chemotherapy. After three years from the initiation of chemotherapy, he had no symptoms except for hoarseness, and has been followed up on an ambulatory basis. In addition, the tumor was producing alpha-fetoprotein (AFP), which was shown by immunohistochemical staining with polyclonal antibody against AFP. The changes in serum AFP level correlated well with the disease status.

Adenocarcinoma↗

PubMed1986

In vitro chemosensitivity patterns of carcinoma of the lung in human tumor clonogenic assay.

One hundred and sixty-eight different specimens of human carcinoma of the lung were tested for in vitro drug sensitivity using the human tumor clonogenic assay (HTCA) originally described by Hamburger and Salmon. One hundred and twenty-two (73%) specimens grew adequately for chemosensitivity testing. Most tumors were resistant to chemotherapeutic drugs, but in vitro sensitivity, regardless of the type of drugs, varied markedly from specimen to specimen. Although response rates to individual drugs ranged between 9% and 23%, half the specimens tested were sensitive in vitro to at least one drug. A higher in vitro sensitivity rate was observed in small cell lung carcinoma (31%) than in non-small cell lung carcinoma (17%). The frequency of in vitro sensitivity was greater for patients who had received no prior chemotherapy than those who were in relapse. These in vitro results are similar to current clinical experience. There was a significant association between in vitro sensitivity of cells from a primary tumor as compared to its metastases. Overall HTCA appears to be useful in selecting appropriate chemotherapy for individual patients with carcinoma of the lung.

Antineoplastic Agents↗

PubMed1986

Cisplatin and vindesine combination chemotherapy for non-small cell lung cancer: a randomized trial comparing two dosages of cisplatin.

Forty-five patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2 every week) plus either high-dose cisplatin (120 mg/m2 every 4 weeks) or low-dose cisplatin (80 mg/m2 every 3 weeks). All patients were previously untreated. The response rate for the high-dose regimen of cisplatin was 39% (9/23) and that for the low-dose regimen of cisplatin was 33% (7/21); the difference was not statistically significant. Only one patient treated with high-dose cisplatin achieved complete response, lasting 6.5 months. The median duration of response was 5.6 months (range, 2.7-7.7) in the high-dose cisplatin group and 6.8 months (range, 1.9-8.9) in the low-dose cisplatin group. The median survival times for the 23 patients treated with the high-dose regimen of cisplatin and for the 21 patients treated with the low-dose regimen of cisplatin were 9.0 and 10.8 months, respectively. Significantly more azotemia occurred in the high-dose cisplatin group than in the low-dose cisplatin group (P less than 0.05). Combination chemotherapy with cisplatin and vindesine showed significant antitumor activity in patients with non-small cell lung cancer. However, the high-dose regimen of cisplatin did not result in a significantly better response rate or survival advantage, and was associated with greater toxicity.

Adult↗

PubMed1986

A case report of synchronous small cell lung cancer and gastric cancer successfully treated with carboplatin.

A 53-year-old man complained of anorexia and abdominal distention of one month's duration. The chest X-ray demonstrated a mass in the left lung with hilar and mediastinal adenopathy and a lytic lesion in the right fourth rib. A transbronchoscopic biopsy of the mass revealed oat cell carcinoma (WHO classification). The endoscopic evaluation also revealed a gastric lesion (IIc type). Biopsy of this lesion indicated signet ring cell gastric cancer. An abdominal CT scan demonstrated multiple liver metastases. Based on these findings, the patient was diagnosed as having synchronous lung and gastric primaries, with liver and bone metastasis from lung cancer. Carboplatin (CBDCA) was administered by intravenous drip infusion of 450 mg/m2. After a second treatment with CBDCA about 3 weeks later, the patient achieved a partial response at the primary site of lung cancer as well as at the liver and bone metastases. In addition, repeat endoscopy of the stomach demonstrated a complete regression. A biopsy specimen taken by gastroscopy was negative for cancer cells. Subsequent chemotherapy for small cell lung cancer was administered with cyclophosphamide, adriamycin, and vincristine, and to date there is no evidence of recurrence. Further studies on CBDCA treatment of small cell lung cancer and gastric cancer are needed to establish the efficacy of this drug against these two histologically different cancers.

Adenocarcinoma, Mucinous↗

PubMed1986

Chemosensitivity test for human small cell lung cancer cell lines in vitro.

The in vitro response to seven chemotherapeutic drugs of three established human small cell lung cancer (SCLC) cell lines (NCI H69, H128, N231) was tested by a double soft agar clonogenic assay. Colony formation by the three cell lines was universally reduced more than 50% by continuous exposure to peak plasma concentrations of all the drugs. However by exposure to one-tenth of the peak plasma concentrations, the colony growth of H69 was reduced to 25.6% and 37.7% by etoposide and teniposide, respectively, and that of N231 was reduced to 46.7%, 39.0%, 27.5% by carboplatin, etoposide and teniposide, respectively. On the other hand colony formation by the three cell lines was not suppressed more than 50% by one-hour exposure to any of the drugs tested at one-tenth of the peak plasma concentrations. By one-hour exposure to drugs at the peak plasma concentrations, colony formation by H69, H128 and N231 was reduced more than 50% by cisplatin, etoposide, teniposide and nimustin, by adriamycin, teniposide and ACNU, and by adriamycin, etoposide, teniposide and nimustin, respectively. It was concluded that these three cell lines have similar sensitivity to seven drugs commonly used against small cell lung cancer.

Antineoplastic Agents↗

PubMed1986

Long-term survival in patients with small cell lung cancer.

Of the 66 patients with small cell lung cancer (SCLC) who were treated by combination chemotherapy with or without radiation therapy from July 1978 to December 1983 at the National Cancer Center Hospital, Tokyo, 12 (18%) survived over two years and nine (14%) have remained disease-free over three years. The two-year survival rates were compared according to the patient characteristics of sex, performance status (PS), extent of disease, histologic subtype, regimen of the initial chemotherapy and response to treatment. Sex, extent of disease and response to the initial chemotherapy were the most important prognostic factors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patients who were treated by surgical resection after chemotherapy, achieved complete response (CR) with chemotherapy with or without radiation therapy. Eleven of the 12 two-year survivors achieved CR. Because of the small number of patients in our study, it will be necessary to evaluate further the influence of prognostic factors in patients with SCLC in future studies.

Adult↗

PubMed1986

Cytogenetic effects of multiagent chemotherapy on the peripheral lymphocytes of patients with small cell lung cancer.

Peripheral lymphocytes of 8 patients with small cell lung cancer (SCLC), who received combination chemotherapy consisting of cisplatin and VP-16 (PVP), were examined for frequency of sister chromatid exchange (SCE) and chromosomal aberrations. Three of the 8 patients were treated with the PVP regimen only; however, the others had previously been treated with multiagent chemotherapy consisting of a cyclophosphamide, adriamycin, and vincristine (CAV) regimen or a cyclophosphamide, ACNU and vincristine (CAV') regimen with or without radiotherapy. Significantly increased SCE frequency was observed in previously untreated patients 3 or 4 days after PVP treatment, compared with the pretreatment values. The earlier analysis in the previously treated patients also showed increased SCE frequency, which seemed to return to the normal value as time elapsed after PVP. In addition, abnormal chromosome count distribution and/or increased incidence of structural changes were observed in cultures from all the patients. In general, striking changes in chromosomes were observed in previously treated patients. The aberrations observed in pretreated patients consisted of chromatid gaps and breaks, exchanges, fragments and dicentric chromosomes. In addition to these abnormalities, double minutes like microchromosomes were seen irrespective of radiotherapy. Further studies are needed to elucidate whether any of the chromosomal aberrations observed in this study could participate in the induction of secondary neoplasms.

Aged↗

PubMed1986

Cytogenetic effects of etoposide (VP-16) on human lymphocytes; with special reference to the relation between sister chromatid exchange and chromatid breakage.

The effects of etoposide (VP-16) on sister chromatid exchange (SCE) and chromosome abnormalities were studied by using human peripheral lymphocytes. This drug produced a significant increase in the SCE frequency and chromosomal aberrations such as breaks, exchanges, and tetraploidy with or without endoreduplication. Analysis of the breakpoints of chromatid deletion with respect to their association with SCE in the metaphases from the second division demonstrated that VP-16-induced deletions arose with little dependence on the site of SCE. It is suggested that chromatid deletions induced by this drug derive from unrepaired chromatid breaks rather than from incomplete exchanges.

Cells, Cultured↗

PubMed1986

[Intervillous blood-gas status, especially oxygenation during cesarean section].

Intervillous (IV), arterial (MA), and umbilical venous (UV) and arterial (UA) blood-gas values were measured in 36 healthy pregnant women. The patients were divided into three equal groups and underwent elective cesarean sections under spinal block. Oxygen was administered through a nasal cannula (group OL) or a mask (group OH), through group RA received no oxygen inhalation. Mean MAPO2 in each group was 102.0, 213.9 and 482.4 mmHg, respectively. Intervillous PO2 (Mean +/- SD mmHg) was 49.0 +/- 7.1 in group RA, 63.1 +/- 14.5 in group OL, 84.6 +/- 25.2 in group OH, oxygen saturation (%) was 83.2 +/- 6.0, 89.6 +/- 5.5 and 94.3 +/- 2.6, respectively, and oxygen content (CO2: ml/dl) was 12.7 +/- 0.9, 13.7 +/- 1.0 and 14.4 +/- 0.5, severely. There were significant differences in the intervillous oxygen values among the three groups. The intervillous acid-base value in group RA (pH: 7.389 +/- 0.013, PCO2: 33.9 +/- 2.3 mmHg and BD: 4.4 +/- 0.9 m mol/l) showed no significant differences from those of the other groups. Mean UVCO2 was somewhat greater than mean IVCO2 in any group due to the relatively higher oxygen affinity of fetal blood. Both IV and UVPO2 were not so elevated with oxygen inhalation and this was assumed to be due to characteristics of the oxyhemoglobin dissociation curve. The other results produce reliable evidence that placental circulation is not affected by maternal hyperoxia and that an increase in (IV-UA)PO2 facilitates oxygen transfer to the fetus.

Carbon Dioxide↗

PubMed1986

Antiemetic efficacy of high-dose intravenous metoclopramide and dexamethasone in patients receiving cisplatin-based chemotherapy: a randomized controlled trial.

High-dose intravenous (IV) metoclopramide has shown efficacy with few side effects for the treatment of nausea and vomiting on the day of cisplatin administration. From November 1984 to January 1986, two randomized trials in an antiemetic study were conducted. In trial I, the antiemetic effect of a short course of high-dose dexamethasone was compared with that of high-dose metoclopramide in 29 patients with lung cancer receiving chemotherapy containing cisplatin (80 mg/m2 IV) in a randomized controlled trial. Dexamethasone was given IV at a dose of 16 mg 1/2 hr before and 8 mg, 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Metoclopramide was given IV at a dose of 2 mg/kg, 1/2 hr before and 1 1/2, 3 1/2 and 5 1/2 hr after cisplatin. Major emetic control (0-2 episodes of vomiting) during the 24 hr after cisplatin administration was achieved in 55% (6/11) and 67% (12/18) of the patients receiving dexamethasone and metoclopramide, respectively, without serious toxicity. The duration of nausea or anorexia was similar for the two treatment groups. In trial II, the combination of metoclopramide and dexamethasone was compared with metoclopramide alone to assess the additive antiemetic effect of the two drugs in 23 patients with lung cancer receiving cisplatin at a dose of 120 mg/m2 IV in a randomized cross-over study. A major antiemetic response was observed in 27% (3/11) and 92% (11/12) of the patients receiving metoclopramide alone and metoclopramide plus dexamethasone, respectively (p less than 0.005). The duration of nausea and anorexia was similar for the two treatment groups. Patients tended to prefer the combination of metoclopramide and dexamethasone; however, the difference was not statistically significant (p = 0.14) in the small number of patients entered in this study. Despite excellent control of acute chemotherapy-induced emesis, 45% of 52 patients experienced delayed nausea and vomiting more than 24 hr after cisplatin administration even among those who had had an excellent short-term response to the antiemetic agents.

Adult↗

PubMed1986

A trial of chemotherapy for lung cancer in short-term hospitalization.

Recently the number of patients with lung cancer who receive chemotherapy has been increasing rapidly. Therefore it has become difficult to treat all patients with advanced lung cancer on the basis of accurate protocol in long-term hospitalization. Accordingly we tried to treat patients within one week in each of a number of chemotherapy protocols (short-term hospitalization) and to follow them in the outpatient department. We were able to accept 61 admissions of 38 patients for chemotherapy from June to December 1985. Thus it was possible to take care of more than three times as many patients as could be cared for by long-term hospitalization for chemotherapy. Three patients could not be discharged within one week and eight had to be readmitted because of leucopenia, thrombocytopenia, or dehydration. It was considered to be possible to decrease the number of such patients by more careful and appropriate hydration and to detect them by appropriate intervals of examination in the outpatient department. We concluded that short-term hospitalization is one of the methods which can make chemotherapy of lung cancer more effective.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

[Fundamental study and clinical testing of human tumor clonogenic assay (HTCA)].

Through our retrospective analysis of HTCA and clinical effects as well as fundamental studies, the following results were obtained: In this retrospective study, HTCA for lung cancer showed a predictive accuracy of 71%, a true positive rate of 50% and a true negative rate of 77%. To obtain good predictive accuracy, HTCA should be modified to provide conditions comparable to those in vivo with regard to drug concentration and drug exposure time. More precise analysis of the pharmacokinetics of anticancer agents might yield methodological improvement. A decrease in the chemosensitivity spectrum in vitro was observed after chemotherapy. This might be related to evidence that patients with prior chemotherapy exhibited a poor response rate to chemotherapy. There were no active anticancer agents against specimens with aplating efficiency of more than 0.04%. More extensive prospective trials will be necessary to determine the clinical value of HTCA. HTCA could be a superior assay for detecting the anti-tumor activity of new agents and a useful method for in vitro phase II study.

Antineoplastic Agents↗

PubMed1986

[Neonatal effects of the delivery interval during cesarean section under spinal anesthesia].

The relationships between I-DI (induction to delivery interval) or U-DI (uterine incision to delivery interval) and fetal acid-base status or neonatal clinical condition were studied in 60 healthy parturients undergoing elective cesarean section under spinal anesthesia. The patients were divided into groups, i.e. group A (U-DI less than 90 sec, I-DI greater than 14 min, 18 cases), group B (U-DI less than 90 sec, I-DI greater than 14 min, 12 cases), group C (U-DI greater than 90 sec, I-DI less than 14 min, 15 cases) and group D (U-DI greater than 90 sec, I-DI greater than 14 min, 15 cases). Acid-base values for maternal arterial (MA), umbilical venous (UV) and umbilical arterial blood (UA), and acid-base gradients for (MA-UV) and (UV-UA) in each group were all in the normal range and revealed no significant differences among 4 groups, though U-DI was correlated with UVPCO2, UAPCO2, and (UV-UA) base deficit (r = 0.322, 0.266, -0.256: p less than 0.05). Acid-base states in cases of long and excessively long U-DI (greater than 90 sec and greater than 150 sec, respectively) were more acidotic than those of short U-DI groups (less than 90 sec). Both 1 and 5 minute Apgar scores were 8 or more in all neonates. There was no correlation between I-DI and fetal acid-base values or neonatal clinical conditions. It is conceivable that gentle and careful manipulations of the uterus and fetus rather than shortening of U-DI might be important in preventing against fetal or neonatal depression during cesarean section under spinal block.

Acid-Base Equilibrium↗