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Biomedical subjects

M Fukushima

Publications and source records attributed to M Fukushima.

At least 253 records · Page 14Linked to original sources

[Renal metastasis originating from liver cancer].

The patient was a 52-year-old man. He was suspected of having right renal carcinoma with hepatic metastasis and was referred to our hospital. The result of percutaneous needle biopsy on the right renal tumor showed a renal cell carcinoma. For the treatment, he underwent transcatheter arterial embolization (TAE) and intramuscular injection of interferon alpha. However, he was getting weaker and weaker and two months later he died due to hepatic failure. The result of autopsy showed that the renal carcinoma was a metastatic tumor from the primary hepatic cancer. This case was thought to be the second case of metastatic renal tumor from hepatic cancer reported in the Japanese literature.

Carcinoma, Hepatocellular↗

[Quality control in clinical trials].

Quality control (QC) in clinical trials means the procedures which insure protection of human subjects from research risk, reliability of the data, and thereby assures internal consistency. This has been developed since 1970s in the US, by establishing various regulations which are now called GCP. From the viewpoint of total QC, it should be emphasized that rigorous review of protocol by the Institutional Review Board and obtaining Informed Consent are prerequisites for insuring the quality of the given trial at high scientific level. When pursuing a clinical trial, first of all, facilities of the institutions and the ability of investigators must be of high quality. For this reason, at each institution previous data related to trials should be thoroughly reviewed and analyzed prior to developing a protocol. Educational courses in QC in clinical practice are invaluable. QC of diagnosis means, for example, central pathology review and standardization of diagnostic procedures and process. Secondly, at each institution, data managers collect the data and submit them to the central office at the indicated time. In order to evolve clinical trial, continuous education for data managers and expansion of their job are encouraged. Thirdly, at the statistical center independent from the research group office, subject-specific data managers, the biostatistical staff, must check submitted forms for completeness, consistency and accuracy. Finally, at the data analysis, quality evaluation of the research should also be carried out. Throughout the trial, monitoring and audit are particularly important to assure quality. The sponsor has the responsibility of monitoring the trial and make rigorous onsite visits, and the individual study group also have a monitoring program, while the FDA and the NCI audit by themselves. The purpose of audit is not only to assure data reliability but also to check out patient compliance to drug, education as to regulations and rules of clinical trials and the analysis of violations so as to provide suggestions to improve medical care.

Clinical Trials as Topic↗

[Estimation of pathways of 5-fluorouracil anabolism in human cancer cells in vitro and in vivo].

Possible pathways of intracellular phosphorylation of 5-fluorouracil (5-FU) in human cancer cells were investigated in vitro and in vivo. We used two inhibitors which regulate the anabolism of 5-FU for the purpose of elucidation of its pathways; one is oxonic acid (Oxo), an inhibitor of orotate phosphoribosyltransferase (OPRTase), catalizing a formation of FUMP from 5-FU, and another is 2, 6-dihydroxypyridine (DP), an inhibitor of uracil ribosyltransferase which catalizes a conversion of 5-FU to 5-fluorouridine. Although the pathway of 5-FU phosphorylation in murine tumor cells was varied, about 80% of human cancer cells tested were found to utilize the first pathway in which 5-FU was converted to FUMP by OPRTase. Thus, the phosphorylation of 5-FU via the first pathway was markedly inhibited by Oxo in 4 strains of 5 gastric cancer cells, 7 of 8 colorectal cancer cells and 3 of 4 lung cancer cells. In xenografts of human gastric and colorectal adenocarcinoma in which 5-FU phosphorylation is regulated by Oxo in vitro, the production of 5-fluoronucleotides and its incorporation into RNA after iv administration of 5-FU significantly decreased by co-administration of Oxo, suggesting that the nature of an anabolic pathway of 5-FU in the tumor cells in vitro reflects in vivo behavior. We also confirmed that the phosphoribosylpyrophosphate level in tumor cells was importantly related to determination of the metabolic pathway of 5-FU. These results would suggest that possible modulation of 5-FU lies on the augmentation of 5-FU efficacy.

Animals↗

Adjuvant therapy of gastric cancer: the Japanese experience.

The 5-year survival rate of patients with advanced gastric cancer who undergo curative resection is gradually increasing and currently ranges between 67.1% to 76.4% at the five major cancer centers in Japan. A belief that minimal residual disease has a high probability of being cured with adjuvant therapy prompted Japanese investigators to develop the D2 dissection with extended lymphadenectomy, more detailed pathologic staging, perioperative chemotherapy, and chemoimmunotherapy. This review focuses on comparative trials performed in Japan studying the use of adjuvant therapy with either chemotherapy alone or chemotherapy plus immunotherapy in the treatment of patients with curatively resected gastric carcinoma. Preoperative and intraperitoneal therapy also has been evaluated. At present, however, no chemotherapy has been shown to impact favorably on the survival of gastric cancer patients, whereas the biological response modifiers, PSK or OK-432, seem to add some benefit to chemotherapy in the adjuvant setting. Carefully designed randomized controlled trials with sufficient size which include a surgery-alone control arm are the only way to establish the efficacy of adjuvant therapy.

Antibiotics, Antineoplastic↗

[A successful treatment using SMANCS-TAE for hepatocellular carcinoma with tumor thrombus in the portal trunk].

A 62-year-old man was admitted to our hospital for treatment of HCC with a thrombus growing from the right branch to the trunk of the portal vein. His hepatic functional reserve was fairly good. Serum levels of AFP and PIVKA-II were elevated to 1,780 ng/ml and 27 AU-ml, respectively. The hepatic arteriogram showed a hypervascular tumor approximately 4 cm in diameter in the right anterior segment and many ill-defined small tumor stains around the main tumor. Portal phase of superior mesenteric arteriogram revealed filling defect in the portal trunk, and no visualization of the right branch of portal vein. SMANCS-Lipiodol was infused via right hepatic artery, and Spongel was infused via right anterior branch of hepatic artery. Three months after the first therapy, the tumor markers normalized. A computed tomography scan showed that the main tumor and the tumor thrombus were markedly decreased in size, whereas the hepatic angiogram revealed tumor stains around the main tumor. SMANCS-Lipiodol was again infused via proper hepatic artery. He has remained well for 16 months after the first treatment. The combination of the arterial infusion of SMANCS-Lipiodol with the selective TAE was very effective for this case, probably because his hepatic functional reserve was fairly good and the left branch of portal vein was patent. It was suggested that SMANCS-Lipiodol with the selective TAE could be one therapy to be considered for a patient like this case.

Carcinoma, Hepatocellular↗

Sensitivity and applicability of different methods for detection of terminal transferase in leukemia.

The sensitivity of terminal deoxynucleotidyl transferase (TdT) assay methods was examined by using a mixture of the TdT-positive lymphoblastic leukemia cell line NALM-18 and the TdT-negative erythroleukemia cell line K-562. The biochemical assay could detect TdT activity in the mixture containing NALM-18 cells at concentrations of more than 10 percent. The immunofluorescent (IF) method could detect positive cells in the mixture containing NALM-18 cells at concentrations of more than 1 percent. Furthermore, an approximately 10(5)-fold increase in sensitivity was obtained by the combination of RT-PCR and subsequent Southern blotting, as compared to biochemical assay. In many leukemia cases the expression of TdT-mRNA corresponded well to that of TdT protein. However, in some patients with leukemia, only TdT-mRNA was detectable by RT-PCR without any expression of TdT protein. A PCR-based technique enables us to detect TdT transcripts at the highest sensitivity, but does not allow the characterization of each positive cell. IF analysis is simple and sensitive, but may sometimes cause nonspecific reactions. All these techniques have some advantages and some faults, therefore, the results obtained from clinical studies using these techniques should be interpreted with caution.

Base Sequence↗

[A randomized controlled study of post-operative adjuvant therapy in non-small cell lung cancer].

The efficacy of postoperative adjuvant chemo- and chemoimmunotherapy in non-small cell lung cancer was evaluated in a multicentric prospective randomized study. From September 1987 to June 1990, resected lung cancer patients were randomly stratified into three groups. Group A received 2 courses of chemotherapy with CDDP and VDS following operation. Group B was administered UFT daily for 1 year after 2 courses of CDDP. Group C received intrapleural administration of OK-432 after lung resection, then UFT and OK-432 once every 2 weeks for 1 year. Out of 94 cases, analyses were carried out on 87 of eligible cases. The five-year survival rate was 56.8% in stage I (43 cases), 73.3% in stage II (12 cases), 18.8% in stage IIIA (24 cases), 50% in stage IIIB (2 cases) and 33.3% in stage IV (6 cases). The five-year survival rate in group A was 32.2%, 55.2% in group B and 53.9% in group C, and no statistical difference was recognized between 3 groups. But in the cases of noncurative resection, the 5-year survival rate was significantly low in group A compared with Group B or C. Similarly, the cases with low-grade TP (<6.0 g/dl) or low response of PPD skin reaction (< 12mm) showed a significantly low 5-year survival rate only in group A. From these results, it was suspected that aggressive chemotherapy provides no benefit for postoperative lung cancer patients with advanced disease.

Adult↗

[A case of inflammatory pseudotumor of the lung with suppressed immune response in the patient with renal cell carcinoma after nephrectomy and administration of interferon].

A 60-year-old man with renal cell carcinoma was treated of right nephrectomy and high dose administration of Interferon-alpha (IFN) in 1990. Three and half years after operation, he complained of cough and hemoptysis. Chest X-ray showed a abnormal shadow (5.5 x 3.5 cm) in the upper lung field. On chest CT, a tumor mass with small cavity was located at S2, attended with the speculation and pleural indentation. A rough nodule suspected daughter tumor was pointed out near the tumor mass. Laboratory investigation revealed mild leucocytosis, an elevated ESR and C reactive protein. On lymphocyte subset, CD 4/8 ratio was 0.8 and NK cell activity was 11%. Immunosuppressive acid protein (IAP) in serum was 1,137 ng/ml. No organisms or malignant cells could be demonstrated in the biopsy materials or sputum. Right thoracotomy and upper lobectomy was carried out. Postoperative pathological diagnosis was inflammatory pseudotumor. Namely, the lesion was occupied with variable admixture of lymphocytes, plasma cells, histiocytes, phagocytes included hemosiderin, foam cells and whorled fibrosis. Daughter tumor was scar tissue. Now, he is well without recurrence and his immune response is within normal level. Some discussion of the literature was mentioned.

Autoimmune Diseases↗

[Prognosis of hepatic metastasis from colorectal cancer following arterial infusion chemotherapy--assessment from the percentage of tumor involved area and tumor markers].

Prognosis of hepatic metastasis from colorectal cancer following arterial infusion chemotherapy was studied from the percentage of tumor involved area (PTIA) and tumor markers. The PTIA was calculated by the following formula: sigma S'/ sigma S, with S' as the tumor area and S as the liver area on each CT slice. The PTIA was 0.76 to 31.1%, and the average was 6.84%. As for the correlation between the PTIA and the prognosis, a statistically significant reverse correlation was found in the cases of death (r = -0.455, p < 0.05, n = 22). In the tumor regression effect of NC cases, the 50% survival time was 24.4 months in cases showing a decrease in CEA or CA19-9 and 18.7 months in the cases showing an increase. Prognosis of the former cases was significantly better than that of the latter cases (p < 0.05). Therefore, PTIA and the decrease in CEA or CA19-9 in the cases of hepatic arterial infusion chemotherapy for metastasis from colorectal cancer seemed important factors reflecting prognosis.

Antineoplastic Agents↗

[Analysis of processes of elevating calcaneum bone stiffness in young women--from the view point of their life-style].

Calcaneum bone stiffness in 222 young women was investigated by using an ultra-sound bone densitometer (Achilles). Their exercise experiences, amounts of dairy products (including foods which contain a lot of calcium) consumed and 24 questions on their eating attitudes were also analysed. Stiffness showed a significant (p < 0.05) positive correlation with age, BMI and the onset of menarche by polynomial (2) regressions. Using these three variables, expected stiffness was calculated by multiple regression, and according to the differences between the real and expected stiffness, the subjects were divided into three subgroups. Group H which showed higher stiffness, showed significantly (p < 0.05) higher exercise experiences and had the habit of consuming more dairy products and small fish than the other two groups. In all of the subjects, the most important variable which increased the stiffness was the exercise experience at junior high school and the next was the habit of eating small fish. The subjects who customarily ate their meals with their families were more likely to eat small fish. These findings suggest that family eating habits should be noticed not only in post-menopausal women, but also in young girls.

Adolescent↗

[Pathogenesis and treatments of glucose intolerance with liver cirrhosis in men--lessons from the clinical cases of Fukuoka City Hospital, Department of Internal Medicine, Fukuoka, Japan].

More than 30% of the end stage liver cirrhosis was complicated by the impared glucose tolerance, in some of which insulin supplements may be required to control the blood glucose level. However, there are many unsolved issues on the cause and cares of hyperglycemia in cirrhotic men. Here, we presented a case of liver cirrhosis and hepatocellular caricnoma complicated by the severe glucose intolerance, and summarized our recent insulin therapy on the glucose intolerance of the decompensated liver cirrhosis in Fukuoka City Hospital, Department of Internal Medicine.

Carcinoma, Hepatocellular↗

[Analysis of risk factors for development of bronchopleural fistula after pneumonectomy for lung cancer].

Bronchopleural fistulas (BPF) developed in six (7.9%) of 76 patients who underwent a pneumonectomy for treatment of lung cancer. Five patients (18.2%) underwent a right pneumonectomy and one (3.7%) a left pneumonectomy. All patients were male, had squamous cell carcinoma, and were diagnosed as having BPF within one month after pneumonectomy. Their average age was 60.2 years. Univariate analyses related to development of BPF showed that significant risk factors were preoperative infection (Chi-square test; p < 0.001), right pneumonectomy (Chi-square test; p < 0.05), and metastasis to a subcarinal lymph node (Chi-square test; p < 0.05). However, sex, age, operating time, amount of blood loss during surgery, amount of blood transfused during surgery, history of smoking, degree of lymph node dissection, degree of curability, performance of combined resection, histologic type of tumor, tumor size, presence of residual tumor at the bronchial stump, and suturing method were not significant risk factors for development of BPF. Our stepwise regression analysis related to development of BPF showed that preoperative infection, metastasis to a subcarinal lymph node, right pneumonectomy, and combined resection were significant risk factors. Sometimes it is difficult to preserve the bronchial arteries upon the dissection of metastatic subcarinal lymph nodes which tightly adhere to the bronchial sheath. Moreover, after a conventional right pneumonectomy, the bronchial stump protrudes into the pleural cavity and is not covered by any tissue. Ligation of the bronchial arteries or protrusion of the bronchial stump into the right pleural cavity reduces the blood supply to the bronchial stump to a very low level and causes development of BPF. Therefore, we suggest that control of preoperative infection, wrapping of the bronchial stump, and preservation of the bronchial arteries during mediastinal lymph node dissection are important to prevent development of BPF.

Bronchial Fistula↗

The effect of thymectomy on myasthenia gravis, thrombocytopenia, and granulocytopenia associated with thymoma: report of a case.

We report the case of a 47-year-old woman with thymoma who developed myasthenia gravis, thrombocytopenia, and granulocytopenia, simultaneously, the concurrent association of these four disorders being extremely rare. Thymectomy was performed, and, during the post-thymectomy course, there were surprising findings concerning the recovery of not only the myasthenia gravis but also of the hematologic disorders. Immediately after thymectomy, the myasthenic symptoms completely disappeared, and the granulocyte and platelet counts recovered to within the normal range within a few days. The laboratory data revealed no difference between pre- and post-thymectomy in the release of cytokines (tumor necrosis factor; TNF, interleukin; IL-2, and IL-6), anti-acetylcholine receptor antibody, or platelet-associated IgG. On the other hand, the serum level of anti-neutrophil cytoplasmic antibody (p-ANCA), against the myeloperoxidase of the granulocytes was dramatically decreased, after thymectomy, showing a significant correlation with the granulocyte count. According to our survey of the literature, this is the first report to show that the removal of a thymoma led to the dramatic resolution not only of myasthenia gravis but also of other associated diseases. It is possible that p-ANCA may be regulated by thymoma, thus causing severe granulocytopenia.

Agranulocytosis↗

Changes in bone mineral content following hormone treatment for endometriosis.

The effects of danazol and buserelin on the bone mineral content (BMC) of 19 Japanese women with endometriosis were studied. Subjects received 24-week courses of oral danazol (400 mg/day) or intranasal buserelin (900 micrograms/day). Trabecular BMC of the 3rd lumbar vertebra (L3) was monitored by computerized tomography scans pretreatment, at the end of treatment and 6 months post-treatment. In the buserelin group there was a significant decrease in BMC (10-25.4%, P < 0.01) which was not fully reversed 6 months after therapy, and increased parameters of bone resorption. In the danazol group, there was a slight gain in BMC despite a decrease in serum estrogen. Danazol and buserelin have similar success in the treatment of endometriosis, but the decrease in BMC at L3 suggests that cumulative bone loss may follow repeated buserelin therapy.

Adult↗

Insulin sensitivity, insulin secretion, and glucose effectiveness in obese subjects: a minimal model analysis.

The aim of the present study was to estimate insulin sensitivity (SI), insulin secretion, and glucose effectiveness in 14 obese subjects who were further divided into two groups: one with normal glucose tolerance and the other with impaired glucose tolerance (IGT). Glucose tolerance was determined by criteria of the World Health Organization. All subjects were Japanese. They underwent a modified frequently sampled intravenous glucose tolerance test: glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg body weight given over 5 minutes) was infused from 20 to 25 minutes after administration of glucose. SI and glucose effectiveness at basal insulin (SG) were estimated by Bergman's minimal model method. Body mass index (33.0 +/- 1.8 v 30.9 +/- 1.5 kg/m2, P > .05) and fasting insulin level (127.9 +/- 30.0 v 107.4 +/- 14.4 pmol/L, P > .05) were higher in obese IGT subjects than in normal obese subjects, but were not statistically significant. With regard to fasting glucose level, obese subjects with IGT (5.9 +/- 0.3 mmol/L) had significantly higher levels than those with normal glucose tolerance (5.1 +/- 0.2 mmol/L, P < .01). There was no significant difference in SI between the two groups (0.53 +/- 0.10 v 0.56 +/- 0.13 x 10(-4).min-1.pmol/L-1, P > .05). Pancreatic insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 19 minutes was significantly lower in obese subjects with IGT (3,366 +/- 1,495 pmol/L.min) than in those with normal glucose tolerance (16,400 +/- 4,509 pmol/L.min, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterization of measles viruses isolated after measles vaccination.

Seven measles virus (MV) strains were isolated from children who developed clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide sequence of the H gene, the molecular size of the H protein, the haemadsorption activity on African green monkey red blood cells, and antigenicity as determined by virus neutralization revealed that one strain was of the vaccine type and the remaining six were the wild virus type. Isolation of the virus directly from patients suspected of a vaccine-induced side-reaction and subsequent characterization of such isolated virus may be useful in differentiation between vaccine-induced side-reactions and natural measles.

Antibodies, Monoclonal↗