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Biomedical subjects

K Muro

Publications and source records attributed to K Muro.

At least 55 records · Page 3Linked to original sources

[Self-expanding nitinol stents for treatment of bilateral main bronchial stenosis caused by esophageal cancer].

A 68-year-old man was admitted because of dyspnea. Nine months earlier, he had undergone radiotherapy for esophageal carcinoma. Chest CT scan obtained on admission showed a tumor shadow behind the tracheal carina. Bronchoscopy revealed that the lower trachea and bilateral main bronchi were compressed from the back and narrowed by the esophageal cancer. To maintain the airway, under fluoroscopic and guide-wire control, a self-expanding nitinol stent (SENS, Accuflex, Microvasive) was implanted in the lower trachea and left main bronchus. At the same time, other SENS was similarly implanted in the lower trachea and right main bronchus. During the implantation, the left nitinol stent was connected to the side of the right nitinol stent to form a T-shape. There was little sputum at the joint portion of the stents and the ventilation of both lungs remained adequate. Severe dyspnea markedly improved after placement of two nitinol stents. Knitted SENS is made of a nickel titanium alloy. SENS was formulated for use in the management of biliary obstruction. However, it is highly flexible and easy to implant. So, it is suitable for the treatment of airway obstruction. Although the implantation of SENS in extensive tracheobronchial stenosis has not previously been reported, it should be useful for prevention of airway obstruction.

Aged↗

Diagnostic utility of endoscopic ultrasonography for preoperative rectal cancer staging estimation.

The preoperative staging accuracy of endoscopic ultrasonography (EUS) was assessed in 38 rectal cancer patients who underwent rectal EUS and curative surgery from July 1992 to September 1994. We used a GF-UM20 instrument with both 12- and 7.5-MHz transducers. Compared with the histological findings, the diagnostic accuracy rate for EUS was 76% (29/38) for the invasion depth and 85% (sensitivity) and 72% (specificity) for level one lymph node metastasis, resulting in an overall preoperative staging accuracy of 74% (28/38). The diagnostic accuracy of invasion depth was poor (only 45%: 5/11) in cases shown histologically to be a1 (tumor invasion through muscularis propria into parietal fat), but ranged from 90 to 100% when the a1 cases were excluded. The diagnostic accuracy for level one lymph node metastasis was proportional to the nodal size. The size of lymph nodes that had been diagnosed as metastatic and non-metastatic (P < 0.05) differed significantly. Eighteen (86%) of the 21 metastatic nodes with histologically massive invasion were detected preoperatively by EUS. Eight of the 11 undetected metastatic nodes were either less than 4 mm in diameter or showed only slight invasion. Most (81%) of the level one metastatic nodes larger than 5 mm were found. The worst preoperative staging diagnostic accuracy was for stage II cases (63%: 5/8), and in four of the 10 misdiagnosed cases, the stage was underestimated due to slight nodal invasion or skip metastasis (2 cases each). Although it was difficult to diagnose nodal metastasis correctly in these cases, preoperative staging using EUS was considered useful for diagnosing almost 80% of our rectal cancer cases.

Humans↗

Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy.

Immunohistochemical analysis was performed to determine the clinical role of p53 mutations in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy. The subjects of this study were 20 patients with previously untreated esophageal carcinomas with evidence of T4 disease and/or distant node metastases. Treatment comprised protracted 5-fluorouracil and 2-h cisplatinum infusions along with radiation treatment with a total radiation dose of 60 Gy. Tumor specimens from 18 of the 20 patients were analyzed immunohistochemically. Mutant p53 protein expression in the biopsy materials from the primary tumors was analyzed by immunohistochemical staining using a polyclonal antibody, RSP53. Expression of p53 was detected immunohistochemically in 10 (56%) of the 18 esophageal tumors, the cancer cell nuclei of which were diffusely stained. There were no significant differences between the patient backgrounds of the p53-"positive" and "negative" groups. Four (40%) of the 10 patients with p53 expression achieved overall complete remissions (CRSs) and 7 (70%) of these 10 achieved CRs of their primary tumors. In contrast, none of the 8 p53-negative patients achieved overall CRs and two (25%) achieved CRs of their primary tumors. The CR rates overall and of primary tumors tended to be higher in the p53-positive than negative group, but the differences were not significant. The survival rate for the 10 patients with p53 expression was better than that for the 8 negative ones (P>0.01): their median survival times were 12 and 4.5 months, respectively. Expression of p53 protein may be an indicator of a favorable prognosis in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy.

Aged↗

A case of advanced gastric cancer complicated by severe toxicity induced by a combination of tegafur, uracil and mitomycin C, and associated with abnormal pharmacokinetics.

A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treated with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C (MMC) (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped immediately. On day 21, the WBC decreased to 900/microl and high fever developed. Despite treatment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400/microl and she recovered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic examination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPC), a large area under the time-versus-concentration curve (AUC) and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear.

Adenocarcinoma↗

[Self-expanding nitinol stents for treatment of tracheobronchial and esophageal stenosis caused by lung cancer].

A 57-year-old man was admitted because of dysphagia. Two year earlier, endoscopic ND-YAG laser treatment had been performed for squamous cell carcinoma of the tracheal carina. The esophagus was compressed and narrowed by invasion of lung cancer. After ballooning, under endoscopic and fluoroscopic control, a self-expanding nitinol stent (SENS, Ultraflex, Microvasive) was implanted in the esophagus. Immediately after esophageal prosthesis implantation, severe dyspnea and stridor developed because of tumor strictures in the left main bronchus. Under fluoroscopic and guide-wire control, SENS (Accuflex, Microvasive) was implanted in the tracheobronchial tree. Dyspnea, dysphagia and stridor were markedly improved after placement of two nitinol stents. Highly flexible, knitted, self-expanding nitinol stent is made of a nickel titanium alloy. Although the implantation of SENS in tracheobronchial stenosis has not previously been reported, it should be useful for prevention of airway obstruction.

Alloys↗

Expression of the adult T-cell leukemia-derived factor, human thioredoxin, in the allotransplanted canine lung.

The relationship between the expression of adult T-cell leukemia-derived factor, human thioredoxin (ADF/TRX), and rejection in transplanted canine lungs was investigated in this study. Of a total 27 adult mongrel dogs, 24 underwent allotransplantation of the left lung with no immunosuppressant and the other three underwent autotransplantation of the left lung. Of the allotransplanted dogs, five were killed on postoperative day (POD) 1, five on POD 2, seven on POD 3, and seven on POD 5, while all three autotransplanted dogs were killed on POD 5. Histological examination was performed on the 24 allotransplanted left lungs (group A), 12 autologous right lungs (group B), and bilateral lungs of the three autotransplanted dogs (group C). The lung tissue was stained with anti-ADF antibody, and the high-ADF-producing cells (ADFh cells) in a randomly chosen field were counted as an index of ADF expression. As the signs of rejection in the group A lungs became more severe with time, the ADFh cells increased in number: 1.68 +/- 1.15, 6.08 +/- 3.44, 14.03 +/- 6.09, and 47.74 +/- 18.89, on PODs 1, 2, 3, and 5, respectively. However, the number of ADFh cells in the group B and group C lungs did not become significantly different from that on POD 1 in group A. These results suggested that ADF/TRX expression may be useful for the early diagnosis of rejection of transplanted lungs.

Animals↗

Expression of adult T-cell leukemia-derived factor in bronchoalveolar lavage cells after canine lung transplantation.

Lung transplantation is now an accepted therapeutic option for patients with end-stage lung disease, and an early diagnosis of rejection is essential in the management of these patients. Adult T-cell leukemia-derived factor (ADF), known as a human homolog of thioredoxin, has been shown to be induced by a variety of stresses. In this study we examined ADF expression in lung tissues and bronchoalveolar lavage cells after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Allotransplantations were performed in adult mongrel dogs, and immunosuppression was performed from the day of operation to the fifth postoperative day. No immunosuppressant was given from the sixth to the tenth postoperative days. Animals were put to death on the tenth postoperative day. Bronchoalveolar lavage was performed on the fifth and tenth postoperative days, and the lavage cells and lung tissues were examined immunohistochemically with anti-ADF antibody. The grades of rejection were as follows: grade 1 in two animals, grade 2 in three animals, and grade 3 in two animals. The percentages of ADF high-producer cells in bronchoalveolar lavage cells on the fifth and tenth postoperative days were 4.29% +/- 2.65% and 26.6% +/- 3.99%, respectively (p < 0.01). The percentages of ADF high-producer cells in normal healthy dogs and in those with grade 1, grade 2, and grade 3 rejection were 3.00% +/- 1.64%, 20.5% +/- 9.00%, 25.5% +/- 6.06%, and 34.5% +/- 6.50%, respectively. The percentage in each rejection group was significantly higher than that in normal healthy dogs (p < 0.05). These results suggest that examination of bronchoalveolar lavage cells with ADF staining may be useful in the early diagnosis of rejection.

Animals↗

Rejection and expression of thioredoxin in transplanted canine lung.

Thioredoxin (TRX) production has been shown to be induced by a variety of stresses. In this study, we examined TRX expression in lung tissues after canine lung transplantation to determine whether it could be induced by allogenic stimulations and could be used to diagnose early rejection. Thirty-five adult mongrel dogs were used in all. In group A, 24 dogs underwent allotransplantation of the left lung with no immunosuppressant and were sacrificed at various times; 5 were sacrificed on postoperative day (POD) 1; 5 on POD 2; 7 on POD 3; and 7 on POD 5. In group B, 5 donor right lungs were used for negative control. In group C, 3 dogs underwent autotransplantation. In group D, 8 dogs underwent allotransplantation of the left lung with optimal immunosuppression and were sacrificed at POD 28. Lung tissues were stained with anti-TRX antibody, and the TRX high-producer (TRXh) cells in a randomly chosen field were counted as the index of TRX expression. In group A, the number of TRXh cells were as follows: 1.68 +/- 1.14 in grade 0; 4.87 +/- 1.07 in grade 1; 10.42 +/- 4.24 in grade 2; 27.34 +/- 17.96 in grade 3; and 50.90 +/- 17.36 in grade 4. In group B, the number of TRXh cells was 1.82 +/- 1.01. There was a significant difference between each rejection grade in group A and group B (p < 0.01), and we could observe TRXh cells in the early stage of rejection. These results suggest that analysis of TRXh cells in lung tissues may be useful in the early diagnosis of rejection.

Animals↗

Effect of recombinant human adult T cell leukemia-derived factor on rat lung reperfusion injury.

The formation of reactive oxygen species (ROS) is a major factor responsible for reperfusion injury in lungs. Adult T cell leukemia derived factor (ADF), a polypeptide made of 104 amino acids, is induced by a variety of stresses including X-ray, ultraviolet, H2O2, and mitogen. ADF has a reducing activity, which catalyzes the proton transfer between thiol-radical of cystein-containing proteins. Furthermore, ADF has a protective activity of ROS which are formed by xanthine oxidase and other alternative pathways in vitro. Using a rat in vivo model of lung ischemia, we examined the protective effect of recombinant human ADF (rhADF) against ischemia reperfusion injury of the lung. Ischemia, lasting for 75 min, was induced in the left lung of rats at 23 degrees C. The lung was then reperfused. These animals were divided into two groups: group 1 (n = 6, treatment with normal saline) and group 2 (n = 6, treatment with 28 micrograms/g of rhADF). One minute after the beginning of reperfusion, arterial oxygen tension (PaO2) decreased significantly in both groups (p < 0.01), without any significant intergroup difference (55.5 +/- 9.8, 49.8 +/- 8.6 mm Hg, respectively). Twenty minutes after reperfusion, PaO2 was significantly higher (p < 0.05) in group 2 (113.0 +/- 8.1 mm Hg) than in group 1 (72.3 +/- 13.6 mm Hg). The wet/dry weight ratio was significantly higher in group 1 (7.31 +/- 0.54) than in group 2 (5.82 +/- 0.36). Histologically, lung injury tended to be milder in group 2 than in group 1. These results suggest that rhADF has a protective effect against ischemia reperfusion injury of the rat lung.

Animals↗

Effects of trehalose in canine lung preservation.

BACKGROUND: The effect of trehalose on the preservation of canine lungs was studied with the use of Euro-Collins solution (ECS). METHODS: In group 1, five lungs were perfused and preserved with a modified ECS in which trehalose (35.0 gm/L) was used instead of glucose. In group 2, six lungs were perfused and preserved with a modified ECS in which glucose was replaced by 70.0 gm/L trehalose. In group 3, six lungs were perfused and preserved with ECS. After preservation for 12 hours, left lung transplantation was performed. RESULTS: The PaO2 values in groups 1 and 2 at 130 minutes after reperfusion were 264.9 and 257.5 mm Hg, respectively. These PaO2 values were significantly higher than the corresponding PaO2 value in group 3 (114.8 mm Hg). All the transplanted lungs in groups 1 and 2 had normal structures on histologic examination, whereas five of the group 3 lungs showed severe pulmonary edema. CONCLUSIONS: These findings show that trehalose is effective in the preservation of lungs for 12 hours.

Animals↗

Effects of trehalose in preservation of canine lung for transplants.

The effect of trehalose, a non-reducing disaccharide which stabilizes and protects membranes, in the preservation of canine lungs was examined when Euro-Collins solution was basically used as a preservant. In group I, five lungs were perfused and preserved in an Euro-Collins solution modified by replacing the glucose with 35.0 g/L of trehalose. Five control lungs (group II) were perfused and preserved with Euro-Collins solution containing 35.0 g/L glucose. In both groups, no vasodilators were used. After preservation for 12 hours, left lung allotransplantation was performed. At 10, 40, 70, and 130 minutes after reperfusion, the right pulmonary artery was clamped for 10 minutes and four parameters were measured: arterial oxygen tension, mean pulmonary arterial pressure, peak inspiratory pressure, and wet/dry weight ratios. The transplanted lung was also examined histologically. At 10, 40, 70, and 130 minutes after reperfusion, oxygen-tension levels from group I were 263.2 +/- 19.2, 283.4 +/- 14.0, 277.5 +/- 19.9 and 264.9 +/- 26.2 mmHg, respectively. In group II, the corresponding values were 191.2 +/- 33.9, 188.0 +/- 40.3, 153.4 +/- 40.0 and 134.7 +/- 49.4 mmHg, respectively. At 70 and 130 minutes the difference were significant (p < 0.05). All transplanted lungs from group I showed normal histology, whereas four dogs in group II developed severe pulmonary edema and one had a partially edematous lung. These findings suggest that simple substitution of trehalose for glucose has a beneficial effect on preservation of canine lung for 12 hours.

Anesthesia↗

Small cell carcinoma of the esophagus with an esophago-mediastinal fistula successfully treated by chemoradiation therapy and intubation: a case report.

A case of esophageal small cell carcinoma with cervical node metastases and an esophago-mediastinal fistula was treated successfully by chemoradiotherapy. The fistula, after irradiation, was handled successfully by esophageal intubation, followed by infusional 5-fluorouracil and cisplatinum chemotherapy, resulting in the closure of the fistula. Two courses of concurrent chemoradiotherapy, followed by additional cisplatinum and etoposide chemotherapy, were administered. The tumor, including the cervical lymph node metastases, disappeared completely after the treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Omentopexy for revascularization of free tracheal grafts in rats.

In rats, we examined the effect of an omentum wrapping on the vascularization of the trachea and on regeneration of the mucosal epithelium in the very early stage after free tracheal grafting. Two pieces of trachea were obtained from each donor rat. One piece was transplanted into the peritoneal cavity of the recipient rat and wrapped with omentum. The other piece was transplanted subcutaneously into the abdominal wall, without omentopexy. Recipients were sacrificed at random on days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels rose significantly earlier in the omentopexy tracheas than in those without omentopexy (p less than 0.01), with all the former showing a normal ciliated, columnar epithelium in the membranous region of the trachea on day 4, accompanied by excellent epithelial regeneration in the cartilaginous region. These results suggest that omentopexy causes revascularization to occur earlier and to be completed in a shorter time, and that it also promotes epithelial regeneration following free tracheal grafting.

Animals↗

Laser Doppler velocimetry measurement of canine mucosal circulation response to bronchial artery reperfusion after lung transplantation.

Left lung transplantation accompanied by reestablishment of the circulation of the bronchial arteries by simultaneous transplantation of part of the aorta was performed on seven dogs. Mucosal circulation of the bronchi at the anastomosis was evaluated using laser Doppler velocimetry (LDV). Since the donor lung must maintain blood supply through the bronchial arteries, the donor aorta from its ascending portion to the descending portion below the outlet for the last bronchial artery was retained with the lung graft. The distal end of the left brachiocephalic artery was sutured to the side of the recipient aorta when the blood supply to the bronchial arteries was to be restored. The LDV values before reperfusion of the bronchial arteries were 20 to 65% (mean: 42.8%) of the preoperative value. Since the LDV values increased to 36 to 125% (mean: 79.9%) of the control, blood flow to the bronchial mucosa increased evidently. Four out of seven dogs died one to two days after the operation due to bleeding and operative stress. One dog was sacrificed on the 4th postoperative day and another on the 16th. The last dog died 40 days after surgery. The unfavorable course of the LDV values in these three dogs suggest that the method used does not ensure an adequate blood supply to the bronchial arteries in the long term.

Animals↗

Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation.

The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly.

Animals↗