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Michiya Kobayashi

Publications and source records attributed to Michiya Kobayashi.

63 records · Page 4Linked to original sources

In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans.

AIMS: To investigate the correlation between in vitro permeation of 11 beta-lactam antibiotics across rat jejunum and their oral bioavailability in humans. METHODS: The absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P(app)) were determined. RESULTS: A steep, sigmoid-type curve was obtained for the relationship between P(app) in the absorptive permeation and human oral bioavailability. When the ratios of P(app) in the absorptive direction to P(app) in the secretory direction were plotted against human oral bioavailability, a much improved correlation was obtained (r = 0.98, P < 0.001). The addition of glycylglycine to both mucosal and serosal media modified the permeation of ceftibuten and cephalexin from the absorptive to the secretory direction. CONCLUSIONS: For 11 beta-lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.

Administration, Oral↗

[The transport mechanism of polycationic compounds across intestinal and renal cell membrane].

This article reviewed the transport mechanism of polycationic compounds across rat intestinal and renal cell membranes. The inside-negative diffusion potential stimulated the initial uptake of dicationic compounds into intestinal brush-border membrane vesicles, and a good correlation was observed between lipophilicity and the amount of diffusion potential-dependent transport of the dications. On the other hand, tri- and tetracationic compounds were not affected by the diffusion potential because of their much lower lipophilicity. The membrane surface potential affected to the transport of polycationic compounds, similar to monocationic compounds. Therefore it appears that the membrane surface potential plays a common role in the transport of mono- and polycationic compounds across cell membranes. On the intestinal basolateral membrane, it was found that there was a Na+/putrescine symporter. This recognized dicationic compounds and transported them from the blood into intestinal cells. This transporter did not recognize spermine and spermidine. Furthermore, we found a novel transport system, a Na+/spermine antiporter, on the rat renal brush-border membrane. This transporter recognized aliphatic polycation, which has more than four amino groups, and actively secreted spermine and trientine into the renal proximal tubules in vitro and in vivo. However, this transporter did not recognize trientine-copper complex. These results are useful for the prediction of the intestinal absorption and renal excretion of polyamine derivatives.

Animals↗

Three-dimensional demonstration of cystic duct by helical CT scanning.

BACKGROUND/AIMS: We evaluated the usefulness of helical CT scanning with drip-infusion cholangiography for the delineation of choleductal anatomy in preparation for laparoscopic cholecystectomy. METHODOLOGY: One hundred and five cases underwent laparoscopic cholecystectomy for cholecystolithiasis in our department from March 1993 to July 1998. Endoscopic retrograde cholangiography was carried out in 58 cases and helical CT scanning with drip-infusion cholangiography, including, three-dimensional CT in 31 cases. We, retrospectively, investigated three-dimensional helical CT scanning with drip-infusion cholangiography in the point of three-dimensional demonstration of cystic duct anatomy and try to classify the findings. RESULTS: Three-dimensional helical CT scanning with drip-infusion cholangiography visualized three-dimensional anatomy of the cystic duct clearly. For the detection of the biliary disease such as stones and polyps, however, endoscopic retrograde cholangiography is superior (sensitivity; 89.7%) to two-dimensional helical CT scanning with drip-infusion cholangiography (sensitivity; 64.5%) and three-dimensional helical CT scanning with drip-infusion cholangiography (sensitivity; 22.6%) except for large lesions. We have classified the three dimensional helical CT scanning with drip-infusion cholangiography findings in three types. CONCLUSIONS: Three-dimensional helical CT scanning with drip-infusion cholangiography is not only less invasive but also more useful for the delineation of three-dimensional anatomy of the bile duct.

Bile Ducts, Intrahepatic↗

Early gastric cancer giving rise to bone and brain metastases--a review of the Japanese literature.

A forty-year-old female consulted a hospital complaining of epigastralgia. She underwent endoscopy, which showed irregular shaped ulceration with fold convergence; the biopsy specimen revealed poorly differentiated adenocarcinoma. She underwent subtotal gastrectomy and lymph node dissection. Histological findings revealed the signet-ring-cell cancer confined to the mucosa and no lymph node metastasis. The serum carcinoembryonic antigen was elevated 2 years and 11 months after operation. Bone scintigraphy demonstrated multiple accumulation and bone biopsy of the sacrum revealed the metastatic gastric cancer. She underwent chemotherapy and radiation, however, later complained of nausea, vomiting, and diminished visual acuity. Brain computed tomography revealed multiple brain metastasis. She died 3 years and 6 months after her operation. We reviewed the 39 reported cases of early gastric cancer with bone metastasis in Japan, which suggests that signet-ring-cell carcinoma and poorly differentiated carcinoma have a possibility of bone metastasis even though the early gastric cancer is confined to the mucosa.

Adult↗

Postoperative pancreatic fistula following distal pancreatectomy for pancreatic neoplasm; can pancreatic fistula be prevented?

BACKGROUND/AIMS: Pancreatic fistula is a potentially fatal complication in pancreatic surgery. The objective of this study was to analyze the incidence of pancreatic fistula in patients who underwent distal pancreatectomy for pancreatic neoplasm. METHODOLOGY: Forty-seven patients who underwent distal pancreatectomy for neoplasm of the pancreas at Kochi Medical School between October 1981 and December 2002 were studied. Comparative analysis was carried out to identify the correlations between the incidence of pancreatic fistula and parameters of preoperative evaluation, intraoperative procedure, and postoperative laboratory investigation. RESULTS: The incidence of pancreatic fistula in patients who underwent distal pancreatectomy for pancreatic neoplasm was 27.7%. Intraoperatively, the frequency of pancreatic fistula was significantly high in patients who underwent distal pancreatectomy without lymph node dissection and ligation of the splenic artery. No significant difference was recognized between the conventional surgical division and auto suture staple groups, however, in the ultrasonically activated scalpel (USAS) group, no pancreatic fistula was observed. A multivariate analysis revealed that independent high incidence of pancreatic fistula were 1) the situation of the tumor at pancreatic body, 2) the procedure of D2 lymph node dissection, and 3) the ligation of the root of splenic artery. In the group with the presence of pancreatic fistula, the serum amylase level on the first postoperative day was significantly higher than that in the group without fistula. CONCLUSIONS: Our findings supported that pancreatic fistula may be preventable by use of the USAS and treatment of acute pancreatitis in the early postoperative stage.

Adult↗

Postoperative pancreatic fistula following surgery for gastric and pancreatic neoplasm; is distal pancreaticosplenectomy truly safe?

BACKGROUND/AIMS: A pancreatic fistula is a potentially fatal complication in digestive tract surgery. The aim of this study was to review the prevention and treatment of pancreatic fistula as performed by our department. METHODOLOGY: Three hundred and seventeen patients with gastric neoplasm and 34 patients with pancreatic neoplasm who underwent surgical resection between 1981 and 2001 at Kochi Medical School were studied. Comparative analysis of the incidence of pancreatic fistulae and the mortality rate was carried out according to an operation type and time. RESULTS: Among the 317 patients who underwent total gastrectomy due to gastric neoplasm, 30 (9.5%) showed pancreatic fistulae. The incidence of pancreatic fistulae in patients who underwent distal pancreatectomy for pancreatic neoplasm was 29.4%. The mortality rate of patients who underwent total gastrectomy was 4.4% and there was a tendency for mortality rate to decrease in the second decade compared to the first. The mortality rate of patients who underwent distal pancreatectomy was 5.9%. CONCLUSIONS: Mortality rate tended to decrease with advanced operative procedures, however, the incidence of pancreatic fistulae did not decrease. In pancreatic fistulae, it was found that the type of treatment was important. Intraoperative and postoperative drainage management for pancreaticosplenectomy will likely become much more important.

Adolescent↗

Posterior gastric artery in angiograms and its surgical importance.

BACKGROUND/AIMS: The incidence and the clinical importance of the posterior gastric artery (PGA) have not been clarified. In Japan, as in the West, the incidence of adenocarcinoma of the upper stomach has increased recently. The purpose of this study was to clarify the features of the posterior gastric artery by analyzing a large series of digital subtraction angiography, and to determine its clinical significance. METHODOLOGY: Three hundred and fourteen patients who underwent angiography between 1991 and 2001 at the Kochi Medical School were studied. The length from the root of the splenic artery and the internal diameter of PGA were investigated celiacographically. The correlation of the body mass index (BMI) and the features of PGA were evaluated. RESULTS: PGA was visualized in 175 patients (55.7%) celiacographically. PGA averaged 3.2-7.4cm (mean 5.4) in length from the root of the splenic artery and the size was 0.7-2.1mm (mean 1.4). The rate of depiction in patients with liver cirrhosis (73.2%) was significantly higher than that in those without (30.5%). No significant difference in length or size of PGA was seen by gender, age, or hepatitis viral infection. No correlation was found between the length or size of PGA and BMI. CONCLUSIONS: Our findings show that the anatomical features of PGA can be visualized by clinical methods useful in planning surgical treatment.

Adult↗

Phase I study of paclitaxel and cisplatin for patients with advanced or recurrent gastric cancer.

BACKGROUND/AIMS: The present phase I study was planned to define the toxicities, maximum tolerated dose (MTD), and pharmacokinetics of the combination of paclitaxel and cisplatin in patients with advanced or recurrent gastric cancer, and to recommend a dose for the phase II study. METHODOLOGY: Patients were required to have performance status of 0 to 1, to be between 15 and 74 years of age, and to have adequate organ function. The cisplatin was administered at a fixed dose of 25mg/m2 and paclitaxel was administered at four dose levels (60, 70, 80, and 90mg/m2). Plasma sampling was performed to characterize the pharmacokinetics and pharacodynamics of paclitaxel. RESULTS: All of the 15 patients entered were assessable for toxicity and response and were subject to analysis of dose-limiting toxicity (DLT) and MTD. Neutropenia (grade 4, for 3 days or more; n=2) indicated DLT at dose level 4 (90mg/m2). The MTD for this regimen was 90mg/m2/week of paclitaxel for 3 weeks. Tumor response occurred in 7 of the 15 patients and the overall response rate was 57.1%. The pharmacokinetic profiles of paclitaxel were similar to those observed after the administration of each dose as a single agent. CONCLUSIONS: Our study demonstrated that the level 3 dosage (80mg/m2 of paclitaxel and 25mg/m2 of cisplatin) is recommended for this combination chemotherapy. This phase I study showed favorable antitumor activity and fewer adverse reactions relative to other types of chemotherapy.

Adult↗

Clinicopathological features of type 1 gastric carcinoma: the need to be cautious of superficial lesion surrounding type 1 gastric carcinoma.

BACKGROUND/AIMS: Gastric carcinoma (GC) is one of the most common malignant tumors of the digestive tract and the incidence of adenocarcinoma of the upper one-third of the stomach has increased recently worldwide. The objective of this study was to analyze the clinicopathological variables in patients with GC and examine preoperative diagnosis and the medical treatment strategy of Type 1 GC. METHODOLOGY: Nine hundred and eighty-one patients with GC who underwent surgical resection between 1981 and 2002 at Kochi Medical School were studied. Thirty-five patients with Type 1 GC were compared with non-Type 1 GC patients on postoperative surgicopathological parameters, and changing trends were evaluated. RESULTS: The characteristics of patients with Type 1 GC were different from those of patients with non-Type 1 GC: Their tumors were more often in the upper one-third of the stomach (37% vs. 15%), lesions were histologically differentiated in 80% (vs. 56%), and there were more superficial lesions surrounding Type 1 GC (80% vs. 8%). The absolute value and the rate of Type 1 GC increased significantly from the first half to the second half of the study. CONCLUSIONS: Our findings showed that when Type 1 GC is discovered, physicians should investigate the mucosa around the main neoplasm carefully. The current series suggested that Type 1 GC are associated frequently with superficial lesions, making local resections more difficult, and that Type 1 GC was similar clinicopathologically to carcinoma of the gastric cardia and had different etiologies contributed to its tumorgenesis, compared with non-Type 1 GC, and Type 1 GC may become the key which solves the problem of carcinoma at the gastric cardia.

Adult↗