Relapsing cervical cord lesions on MRI in patients with HTLV-I-associated myelopathy.
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Biomedical subjects
Publications and source records attributed to N Tokunaga.
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We present a case of high-pressure suction drainage for poststernotomy mediastinitis. A 67-year-old man who underwent coronary artery bypass grafting because of angina pectoris was noted massive dirty exudate fluid (putrid secretions) from median sternal wound on the 6th postoperative day. The sternal wounds were completely reopened and all sternal wires removed. Thorough debridement was performed. The mediastinum was then washed out with warn normal saline. The polyurethane foam was shaped to fit the resulting sternal defect and placed within the cavity just below the skin edge. The suction tube was inserted inside the foam and the area was covered with the adhesive drape. After 45 days suction drainage the sternal wound was closed, after which he was discharged.
BACKGROUND: Gene therapy is an innovative therapeutic approach for cancer. An adenoviral vector expressing the tumour suppressor p53 gene (Ad/p53) is currently under clinical evaluation for various cancers. We recently developed a binary adenoviral vector system that can express the strong proapoptotic gene Bax (Ad/PGK-GV16+Ad/GT-Bax: Ad/Bax). AIMS: To evaluate the potential of Bax gene therapy for gastric cancer, we assessed its antitumour effect in comparison with that of p53. METHODS: The human gastric cancer cell lines MKN-1, MKN-7, MKN-28, and MKN-45 were treated with Ad/Bax or Ad/p53, and cell viability, transgene expression, and caspase activation were assessed in vitro. To compare the antitumour effects of Ad/Bax and Ad/p53 treatment in vivo, subcutaneous tumours and peritoneal dissemination of MKN-45 cells were generated in nude mice. Each mouse underwent intratumoral or intraperitoneal administration of viruses and the growth of implanted tumours was observed after treatment. RESULTS: Treatment with Ad/Bax and Ad/p53 resulted in marked Bax and p53 protein expression and effective apoptosis induction in MKN-1, MKN-7, and MKN-28 cells in vitro. In contrast, MKN-45 cells showed resistance to Ad/p53 and only treatment with Ad/Bax resulted in activation of caspase 3 expression and massive apoptosis. Ad/Bax treatment was more effective in suppressing both subcutaneous and peritoneally disseminated MKN-45 tumours compared with Ad/p53 treatment. CONCLUSION: Ad/Bax treatment significantly inhibited the growth of even p53 resistant gastric cancer in vitro and in vivo. Therefore, adenovirus mediated Bax gene transfer may be useful in gene therapy for gastric cancers.
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BACKGROUND: In spite of many reports, it remains unclear whether the presence of tumor cells in circulating blood flow predicts a poor prognosis. METHODS: Competitive seminested reverse transcriptase-polymerase chain reaction (RT-PCR), a technique for the quantitative detection of tumor cells, was applied to detect the presence of tumor cells in portal and peripheral blood samples from 121 patients with colorectal carcinoma and to clarify their clinical significance. This technique can detect one carcinoembryonic antigen (CEA) mRNA-expressing tumor cell in 1 x 10(5) normal lymphocytes. RESULTS: Six of 33 healthy volunteers (18%) demonstrated a positive reaction to this technique. CEA mRNA expression was detected in the portal blood in 51% of patients and in the peripheral blood in 42% of patients. The results from the two blood samples were consistent in 91% of patients. The positive expression rates for portal blood in patients with T1 tumors and those with TNM Stage I disease were 38% and 45%, respectively. The positive rate was significantly higher in patients with colon carcinoma and those with Stage III or IV disease. CEA mRNA expression, quantitatively measured (x 10(-8)/beta-actin), was 22.9 +/- 35.1 in the portal blood and 19.9 +/- 40.0 in the peripheral blood, with no statistically significant difference. A significant positive correlation was noted between portal and peripheral CEA mRNA expression levels according to Spearman correlation analysis (correlation coefficient = 0.78; P < 0.01). Multivariate analysis revealed that the positive rate and level of CEA mRNA expression in the portal and peripheral blood did not appear to be influenced by the established prognostic factors. CONCLUSIONS: The presence of circulating tumor cells might be of less value as a prognostic factor because they also can be detected in patients with early-stage colorectal carcinoma and appeared to be independent of the conventional prognostic factors.
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We attempted to prove the occurrence of generalized vasospasms in cases with eclampsia/preeclampsia and HELLP syndrome and to suggest the existence of an angiospastic syndrome of pregnancy. Sixteen cases with severe preeclampsia were evaluated. Among them, three cases were complicated by eclampsia and one case with HELLP syndrome. Cranial magnetic resonance angiography (MRA) was performed in 15 cases, and celiac angiography was performed in one case. Vasospasms were observed in 12 cases (75.0%), including all cases involving eclampsia and HELLP syndrome, and cerebral infarction was observed in one case. Typical vasospasms were found by MRA in the middle and posterior cerebral arteries with peripheral ischemic changes in cases with severe preeclampsia and eclampsia. Vasospasms of the hepatic arteries were observed by celiac angiography in a case with HELLP syndrome. Vasospasms are characteristic for patients with eclampsia/preeclampsia and HELLP syndrome, and the existence of an angiospastic syndrome of pregnancy is proposed.
We investigated coagulation/fibrinolysis parameters for significant differences between patients with early-onset severe preeclampsia (< 32 weeks gestation, wG) and those with late-onset severe preeclampsia (> or = 32 wG). A decrease in antithrombin (AT), protein C (PC), and free protein S (PS) activities and an increase in plasmin-alpha2-plasmin inhibitor complex (PIC), thrombin-antithrombin complex (TAT), and FDP D-dimer (D-dimer) were observed. However, there were no statistical differences between the two groups. Once preeclampsia occurred and it developed severe, the changes in coagulation/fibrinolysis parameters became more severe in spite of early-onset preeclampsia or late-onset preeclampsia. We also investigated coagulation/fibrinolysis abnormalities in 101 patients with severe preeclampsia. A significant increase in WBC, RBC, Hb, Ht, TAT, PIC, and D-dimer and a significant decrease in platelet (Plt) counts and AT activity were observed. deltaPlt (the difference between platelet counts in early gestation and before delivery) was -5.0 x 10(4)/microL in cases with severe preeclampsia. Among patients with severe preeclampsia, coagulation/fibrinolysis changes before delivery were typical for patients with cesarean section compared with those with successful vaginal delivery. These facts suggest that an excessive hypercoagulable state is associated with the termination of pregnancy resulting from the aggravation of preeclampsia. From the viewpoint of coagulation/fibrinolysis changes, the termination of pregnancy could be recommended when the levels of parameters exceed the following values; deltaPlt > -6.0 x 10(4) microL, D-dimer > 4 microg/mL, AT activity < 79%, TAT > 26 ng/mL, and PIC > 1.2 microg/mL. Particularly, deltaPlt and D-dimer are useful bedside predictive markers in order to decide the optimal time for the termination of pregnancy in patients with severe preeclampsia.
We experienced three cases and four successful deliveries with congenital afibrinogenaemia and propose the following guidelines for the prenatal and peripartum management: (i) genital bleeding usually begins at 5 weeks' gestation and spontaneous abortion always occurs at 6-8 weeks' gestation without fibrinogen infusion; (ii) the fibrinogen level must be at least 0.60 g/l and, if possible, higher than 1.0 g/l during the pregnancy; (iii) the necessary amounts of fibrinogen increase as the pregnancy progresses and the preterm labour occurs; (iv) the fibrinogen level under the continuous infusion of fibrinogen during labour must be at least 1.5 g/l and, if possible, higher than 2.0 g/l to prevent placental abruption; (v) the puerperium is usually uneventful with a reduced dose of fibrinogen infusion.
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In a step toward a clinical trial, the tumor response and survival of a weekday-on/weekend-off schedule of UFT was compared with its conventional daily schedule in a cancer-bearing rat model. The dose-intensive schedule--600 mg of UFT for 5 days followed by 2 drug-free days--amounts to a weekly dose similar to the conventional schedule of 400 mg/day. The weekday-on/weekend-off schedule provided increased survival and significantly greater antitumor activity than the conventional daily schedule, with no difference in adverse reactions. A study was also conducted in human subjects to measure fluorouracil (5-FU) concentrations that identified the pharmacokinetic activity during the 2 drug-free days of the weekday-on/weekend-off schedule. The plasma 5-FU concentration declined markedly after 24 hours, but the concentration in the tumor remained at a relatively high level after 2 days off the drug. A one-year clinical study evaluated the compliance and toxicity of the weekday-on/weekend-off UFT schedule as adjuvant chemotherapy for colorectal cancer. Based on the findings of all these studies, the weekday-on/weekend-off schedule for UFT as adjuvant chemotherapy for colorectal cancer can be recommended for a clinical trial.
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BACKGROUND: Two types of end-to-end colorectal anastomosis using a circular stapler, circular stapled anastomosis(CSA) and double stapling anastomosis(DSA), have become the standard technique. The possibility of anastomotic openings of the DSA being smaller and somewhat distorted, because of some portion of the stapled rectal stump not being included in the anastomotic opening, was examined. METHODS: Anastomotic openings created by CSA and DSA were photographed through a sigmoidoscope, and the maximal and minimal diameters and the areas of the anastomotic openings were measured and calculated with an image analyzer. They were examined in the swine rectum immediately after surgery and were also examined in the randomized clinical cases 3 or more months after surgery. RESULTS: It was found that larger anastomotic openings could be created as the diameter of the anastomosed intestine and the cartridge size became wider in both methods immediately after surgery. The shape of anastomotic opening created by DSA was observed to be more oval than round immediately after surgery. The anastomotic stenosis occurred in a small number of patients in both methods within 3 months after surgery. The area of the anastomotic opening created by CSA was about 25% larger than that by DSA immediately after surgery and about 30% larger 3 or more months after surgery. CONCLUSION: CSA provides a larger anastomotic opening than DSA. Anastomotic stenosis occurred in a small number of patients in both methods.
Increased glucose metabolism has been reported to occur in association with colorectal cancer. As positron emission tomography (PET) using [18F]fluorodeoxyglucose is able to depict hypermetabolic sites, it can therefore be used to detect colorectal cancer. A 69-year-old male patient with a recurrent solitary liver metastasis from colon cancer underwent whole-body PET which revealed high [18F]fluorodeoxyglucose uptake in the lesion. Furthermore, PET revealed peritoneal metastases that had not been detected by conventional imaging methods. Consequently, PET proved useful in helping us to avoid performing unnecessary treatment for the liver metastasis. Although it is uncertain whether early identification of recurrence can prolong survival, it may help to prevent unnecessary treatments being carried out. Thus, the application of PET in carefully selected patients could be beneficial to the management of recurrent colorectal cancer.
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Life span is the most interesting and also the most important biologically relevant time to be investigated on the space station. As a model experiment, we proposed an investigation to assess the life span of clone generation of the ciliate Paramecium. In space, clone generation will be artificially started by conjugation or autogamy, and the life span of the cell populations in different gravitational fields (microgravity and onboard 1 x g control) will be precisely assessed in terms of fission age as compared with the clock time. In order to perform the space experiment including long-lasting culture and continuous measurement of cell division, we tested the methods of cell culture and of cell-density measurement, which will be available in closed environments under microgravity. The basic design of experimental hardware and a preliminary result of the cultivation procedure are described.
The concentration of nitric oxide was found to be decreased in a hypersympathetic condition. We carried out experiments on cultured sympathetic neurons from 12-14-days-old chick embryos to investigate the role of vasoactive peptides and amine on nitric oxide production. Stimulation of cultured neurons with endothelin-1, norepinephrine and angiotensin-II initially increases nitric oxide production and subsequently decreases it in a dose-dependent manner (P<0.05, n = 7). Stimulation of Fura-2 acetoxymethyl ester-loaded neurons with endothelin-1, norepinephrine and angiotensin-II increases the calcium influx (within 30-90 s) and it is then restored to the initial level (P<0.05, n = 7). An additional observation was that specific stimulator L-arginine significantly increases the nitric oxide release and calcium influx into the cells, whereas N(W)-nitro-L-arginine methyl ester blunts nitric oxide release dose dependently (P<0.05, n = 7) and does not change the calcium concentration in the cells. We propose that vasoactive peptides and amines inhibit nitric oxide production in the cultured sympathetic neuron by regulation of intracellular calcium concentration.
We hypothesised that long term epidural anaesthesia suppresses sympathetic overactivity in pre-eclampsia. Two equal groups of severe pre-eclamptic patients were treated either with long-term epidural anaesthesia (epidural group) or bed rest, diet control, and an antihypertensive drug (control group). After 7 days of epidural block, mean arterial blood pressures decreased, platelet count and serum total protein increased in all cases while proteinuria decreased in four cases. All patients treated with a long-term epidural therapy continued their pregnancies for more than 3 weeks after admission. The infants in the epidural group had 1-min Apgar scores above 8, a body weight of 2240+/-310 g (mean +/- s.d.) and normal neonatal progress. In contrast, the pregnancies of eight patients in the control group were terminated within 2 weeks of admission due to severe pre-eclampsia or foetal distress, the birth weight of the infants was 1590+/-380 g (mean +/- s.d.) and four had neonatal distress. Progressive worsening in the mean arterial pressure, proteinuria, platelet count and serum total protein was found in these patients. Long-term epidural anaesthesia suppresses the sympathetic hyperactivity and thus improves pre-eclamptic condition which may open a new treatment in case of progressive severe pre-eclampsia.