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Biomedical subjects

M Konn

Publications and source records attributed to M Konn.

At least 19 recordsLinked to original sources

Postoperative abnormal prothrombinemia in patients with cefoperazone: report of two cases.

Two cases of postoperative abnormal prothrombinemia presumably caused by the administration of cefoperazone are herein described. One patient, who had bile duct cancer with obstructive jaundice, underwent resection of the extrahepatic bile duct with hepaticojejunostomy (Roux-en-Y anastomosis) and partial resection of the liver following percutaneous transhepatic cholangial drainage. He developed abnormal prothrombinemia and bleeding 10 days after surgery. The other patient, who had undergone a total gastrectomy 17 years earlier, suffered from pulmonary tuberculosis. She was initiated anti-tuberculous regimen and simultaneously was worked-up for her severe anemia, and was found to have ascending colon cancer. She underwent a right hemicolectomy, cholecystectomy, and repair of ventral incisional hernia, and subsequently developed abnormal prothrombinemia and bleeding 12 days after surgery. Both patients received a chemical bowel preparation prior to surgery. Prothrombin time was normal preoperatively in both patients. Both patients were treated with fresh frozen plasma and intravenous menatetrenon, which improved the clotting disorder within 24h. Antibiotics containing the N-methyl-thio-tetrazol side chain should thus be used with particular prudence in patients with abnormal prothrombinemia and a tendency to develop bleeding disorders.

Cefoperazone↗

Sinusoidal flow block after warm ischemia in rats with diet-induced fatty liver.

Donor livers with massive fatty infiltration reportedly are susceptible to ischemia/reperfusion injury after transplantation, which contributes to risk of primary nonfunction. We investigated the effect of warm ischemia and reperfusion on sinusoidal microcirculation in rats with fatty livers from a choline-deficient diet. Rats were subjected to partial hepatic warm ischemia for 30, 60, or 90 min. In a second study, an anti-ICAM-1 monoclonal antibody was injected intraportally 2 min after a 60-min ischemic period. In both studies, injury was assessed by liver histology 6 hr after vascular clamp release and by animal survival. After 30 min of hepatic warm ischemia, almost all control and fatty-liver rats survived 7 days. After 60-min ischemia, however, survival was significantly less in rats with fatty livers than in controls with normal livers (10% vs 90%, P < 0.0001). Histologically, rats with fatty livers showed marked sinusoidal congestion, especially in the midzone of the acinus, while control rats showed no disturbance in microcirculation. In rats with fatty livers treated with intraportal injection of an anti-ICAM-1 antibody, sinusoidal microcirculation was well preserved and the 7-day survival rate after warm ischemia was improved (50% vs no antibody 10%; P = 0.0112). In fatty livers, midzonal sinusoidal flow block occurs after hepatic warm ischemia and reperfusion. Although intraportal injection of an anti-ICAM-1 monoclonal antibody corrected this microcirculatory failure, animal survival was not as good as for controls without fatty livers. These results suggest that both sinusoidal microcirculatory failure and ischemic hepatocellular damage contribute to warm ischemia/reperfusion injury in fatty livers.

Animals↗

Late development of bile duct cancer after sphincteroplasty: a ten- to twenty-two-year follow-up study.

BACKGROUND: Transduodenal sphincteroplasty is designed to destroy the sphincteric muscle fibers, producing a terminal choledochoduodenostomy. In the absence of Oddi's sphincter, intestinal contents with both activated pancreatic juice and bacterial flora are refluxed into the bile duct and remain there for a prolonged time. The long-term effect of producing the reflux has not been evaluated to date. METHODS: One hundred nineteen consecutive patients undergoing transduodenal sphincteroplasty between February 1973 and July 1984 were included in this study. Postoperative clinical courses of 108 patients could be evaluated by means of a retrospective review of the hospital records. Median follow-up was 18 years. RESULTS: Eight cases (7.4%) of primary bile duct cancer were found among the 108 cases at intervals of 1 to 20 years after sphincteroplasty. Two patients had concurrent hepatolithiasis. The patency of sphincteroplasty was confirmed in all cases, and the bile was infected in seven cases. Pathologic specimens obtained demonstrated cholangiocarcinomas and various degrees of atypical hyperplastic lesions under the background of chronic cholangitis. CONCLUSIONS: Chronic cholangitis can be an important causative factor in late development of bile duct cancer after sphincteroplasty. Any patients treated with choledochoduodenostomy should be closely monitored for late cholangiocarcinoma.

Adult↗

Characterization of glycosaminoglycans in regenerating canine liver.

BACKGROUND/AIMS: Liver regeneration after partial hepatectomy is accompanied by hepatocyte proliferation and alteration of the extracellular matrix. Glycosaminoglycans, which are components of the extracellular matrix, interact with other matrix components, and are related to hepatocyte growth. The aim of this study was to investigate the relationship between hepatocyte proliferation and changes in glycosaminoglycan. METHODS: Hepatocyte proliferation and changes in glycosaminoglycan were investigated in dogs after 55% partial hepatectomy. Hepatocyte mitosis was investigated by immunohistochemistry using anti-proliferating cell nuclear antigen antibody. The amount of glycosaminoglycan was determined by the carbazole-sulfuric acid method. We used a new method for analysis of glycosaminoglycan chains, involving endo-beta-xylosidase digestion and fluorescence labelling, to investigate the components of glycosaminoglycan. RESULTS: Hepatocyte mitosis was increased after hepatectomy, reaching a peak at postoperative day 7. The total amount of hepatic glycosaminoglycan reached a maximum at 1 to 2 weeks afer hepatectomy, and the ratio of the components showed a concomitant change, the amount of heparan sulfate increasing, and that of chondroitin sulfate/dermatan sulfate decreasing. Increased heparan sulfate has shorter chains at 1 to 2 weeks after hepatectomy. CONCLUSIONS: These results suggest that the transient changes in heparan sulfate with a decreased chain length and chondroitin sulfate/dermatan sulfate and observed during liver regeneration are associated with hepatocyte proliferation.

Animals↗

[A case of unresectable pancreatic cancer successfully treated with continuous venous daily infusion of 5-FU and low-dose CDDP].

This case was a 61-year-old male diagnosed with pancreatic cancer who had a celiotomy. The tumor invasion involved the pancreas body and head. Ultrasonograph examination revealed that all the celiac artery, supramesenteric artery, and portal vein were occluded in the tumor. Because of the unresectability of the tumor, a palliative operation was carried out, and during the following 9 months he was given UFT 300 mg daily. Because abdominal ascites accompanied the tumor growth, the patient underwent combination chemotherapy of cisplatin 5 mg/day x 5/week and continuous infusion of 5-fluorouracil 250 mg/day for 4 weeks. Remarkable reduction of the abdominal ascites and decline of the tumor markers (CEA, CA19-9) was observed in the course of the chemotherapy. Bone marrow function was suppressed by the agents, but granulocyte colony stimulating factor (G-CSF) was very effective for recovery from the damage. Two months after discharge, abdominal ascites recurred. The patient received the same serial chemotherapy for 6 weeks, and now is followed as an outpatient.

Antineoplastic Combined Chemotherapy Protocols↗

The effects of intraportal prostaglandin E1 administration on hepatic warm ischemia and reperfusion injury in dogs.

To determine the route of prostaglandin E1 (PGE1) administration which would have the greatest protective effect against hepatic warm ischemia, two experiments were performed using dogs. The pharmacokinetics of PGE1 were investigated in a preliminary study, after which, the effects of PGE1 in a 90-min warm ischemic liver model were examined. The dogs were divided into three groups of ten, according to the treatment given: group A was an untreated control group, group B received PGE1 intravenously, and group C received PGE1 intraportally. The PGE1 was infused continuously at a rate of 0.02 microliters/kg/min before and after ischemia. All the dogs in groups A and B died within 24 h of induced ischemia. Whereas, six of the ten dogs in group C survived for over 3 days. The arterial ketone body ratio was not maintained in groups A and B, but it was in group C. Furthermore, in group C the serum lipid peroxide level, which reflects hepatocellular membrane damage, was maintained at a lower level than that in the other groups after ischemia. Electron microscopy revealed sinusoid destruction and changes in both the plasma membrane and parenchymal cell mitochondria in groups A and B, while in group C these structures were well preserved. These findings confirmed that intraportally administered PGE1 improved the hepatic microcirculation and stabilized the hepatocellular membranes. Our results indicate that intraportal administration of PGE1 has a greater protective effect than intravenous administration against warm ischemic liver injury.

Alprostadil↗

Possible role of hepatic bile mucus glycoprotein in development of intrahepatic gallstones.

To study the role played by hepatic bile mucus glycoprotein in the development of hepatolithiasis, mucus glycoprotein, isolated from the bile of patients with intrahepatic gallstones by gel filtration and ultracentrifugation, was examined for precipitability in control hepatic bile obtained postoperatively from patients successfully treated for cholecysto- and/or choledocho-lithiasis. When the mucus glycoprotein was incubated at 38 degrees C for 48 h in the control hepatic bile in the presence of calcium ions, massive precipitation was produced. The precipitation was inhibited by treating the mucus glycoprotein with acid, alkali, a reducing reagent, or protease, the inhibition being most effective with acid, which splits up carbohydrate chains. This suggests that the precipitability of the mucus glycoprotein resides mainly in its carbohydrate chains. These observations imply that the development of intrahepatic gallstones, calcium bilirubinate stones in particular, could be prevented by degrading mucus glycoprotein in hepatic bile.

Bile↗

Chemical structure of the carbohydrate moiety of fucose-rich glycopeptides from human pancreatic juice.

Human pancreatic juice, obtained from nine patients after partial excision of the pancreas for bile duct cancer, was fractionated in order to isolate its glycopeptides. Three glycopeptides were purified employing ion-exchange chromatography and gel filtration. All the glycopeptides were found to be free of sialic acid and galactosamine but to have an unusually high content of L-fucose. The chemical structures of the three glycopeptides were determined using 500-MHz [1H]-NMR spectroscopy. One of them, glycopeptide, GP-4, possessed a biantennary structure with three L-fucose residues. The second glycopeptide, GP-3, had a triantennary structure with four L-fucose residues, and the third one, G-2, had a tetra-antennary structure with five L-fucose residues. The chemical compositions of these glycopeptides, including the absence of sialic acid and the high L-fucose content, indicate that they represent a new class of glycopeptide present in the normal human pancreas.

Carbohydrate Sequence↗

[Facilitation of hepatic metastasis by surgical stress in mice].

An experimental model for hepatic metastasis with a transplantation route of free-pedicled subcutaneous-embedded spleen was established in BALB/c mice. Colon-26 tumor cells to produce hepatic metastasis were inoculated into the spleen and the influence of surgical stress by means of a 20-min exposure of the abdominal cavity on the incidence of hepatic metastasis was examined. Hepatic metastasis was more promoted by the surgical stress in order when it was given on the same day, the 7th day and the 3rd day of the inoculation. Administration, without surgical stress, of ASGM 1, a specific inhibitor of the natural killer activity, also facilitated the hepatic disease. Administration of OK-432 prior to the surgical stress or ASGM 1 was at least partly effective for prevention of the hepatic metastasis and prolonged the survival of the inoculated mice. Preoperative immunotherapy utilizing OK-432 might be a possible means to prevent hepatic metastasis triggered in colorectal surgery for cancer.

Animals↗

The effect of intraportal PGE1 on warm ischemic liver damage.

To determine the most effective route of administering prostaglandin E1 (PGE1) to inhibit warm ischemic liver damage, 90-min warm ischemia was established in a canine model. The dogs were divided into three groups according to the treatment given. Thus, group A (n = 10) was the control group which received no treatment, group B (n = 7) was administered PGE1 intravenously, and group C (n = 7) was administered PGE1 intraportally. PGE1 was continuously administered before and after the ischemia at a rate of 0.02 microgram/kg/min. The branched-chain amino acid to aromatic amino acid ratio in the hepatic vein, and the arterial ketone body ratio of acetoacetic acid to beta-hydroxybutyric acid, were examined to observe the metabolism of each amino acid and the oxidation-reduction ability of hepatocytes. Both ratios were maintained only in the group C dogs, three of which survived for over 3 days, whereas in groups A and B, all the dogs died within 24 h. The results of this study imply that the intraportal administration of PGE1 was more effective against warm ischemic liver damage than the intravenous administration of PGE1.

Alprostadil↗

[A case of gastric cancer with Borrmann type 4 responding to 5-FU-MMC combined chemotherapy].

A 70-year-old man with advanced Borrmann type 4 was preoperatively treated with 5-FU-MMC combined chemotherapy. The primary tumor including a palpable mass in the abdomen was diminished, and eventually the patient underwent curative resection. This preoperative regimen for advanced Borrmann type 4 gastric cancer might be recommended from the standpoint of less adverse effects of chemotherapy. The patient died suddenly of cardiac infarction in 9 months without recurrent signs.

Adenocarcinoma↗

Survival and recurrence after low anterior resection and abdominoperineal resection for rectal cancer: the results of a long-term study with a review of the literature.

Morbidity, survival, and recurrence in 203 patients treated with curative low anterior resection (LAR) were compared with those in 100 patients treated with curative abdominoperineal resection (APR). The overall 5-year survival figures for the total number of, LAR and APR patients were 75.6 +/- 5.7%, 79.8 +/- 6.4% and 67.7 +/- 9.6%, respectively. The prognosis for cancers situated low enough in the rectum to involve the anal canal was poor even when managed by APR, as evidenced by a low survival at 5 years of 59.0 +/- 9.6% and a high pelvic recurrence rate of 34%. For all except these tumors, LAR proved at least equal to, or better than APR as a curative surgical method for middle and low rectal cancers, on the basis of 5-year survival being 79.8 +/- 6.4% vs 78.7 +/- 5.2%, operative mortality being 1.5% vs 1.0%, morbidity being 39.4% vs 59.0%, and the incidence of pelvic recurrence being 8.9% vs 13.5%. When deciding upon the most appropriate surgical procedure for rectal cancer, especially for middle or low rectal lesions, the patient should not simply be condemned to a permanent colostomy. Thus, we first attempt LAR for every lesion except those which are very advanced or those with anal canal involvement, if technically feasible and suitable for the individual patient.

Adult↗

Enzymic determination of acidic glycoconjugates in human pancreatic juice.

Acidic glycoconjugates (glycosaminoglycans, sulfated glycopeptide, and sialoglycopeptide) were isolated by precipitation with cetylpyridinium chloride from human pancreatic juice after digestion with pronase. The acidic glycoconjugates were found exclusively in the proteinaceous precipitate that occurred during dialysis against a buffer of low ionic strength. The concentration of the acidic glycoconjugates in normal pancreatic juice was about 2.4 mg/L. The acidic glycoconjugates were characterized by electrophoresis on cellulose acetate membrane and chemical analysis before and after digestion with Streptomyces hyaluronidase, chondroitinase AC, chondroitinase ABC, and heparitinase. It was found that the major acidic glycoconjugates were heparan sulfate (39.3%), sulfated glycopeptide (34.4%), chondroitin sulfate (14.2%), and the minor ones hyaluronic acid (6.4%) and sialoglycopeptide (5.7%).

Chondroitinases and Chondroitin Lyases↗

[Treatment of intrahepatic gallstone].

The postoperative outcomes in patients with hepatolithiasis are greatly affected by the presence of residual stones. One hundred and seventeen patients with hepatolithiasis treated in our clinic were analysed. The indication of hepatectomy for hepatolithiasis was determined by the degree of stricture of intrahepatic bile duct. The rate of residual stones was reduced from 54.5% to 14.5% by the introduction of choledochoscopical lithotomy. Thus, pre- and postoperative choledochoscopical examination and lithotomy are shown to play an important role in treatment of the patients with hepatolithiasis.

Adult↗

[An experimental study on development of gallstone disease after curative gastrectomy for cancer--postoperative alteration of the composition of canine gallbladder bile after subtotal gastrectomy with truncal vagotomy].

In connection with gallstone (GS) formation after gastrectomy for cancer, we examined alteration of the composition of gallbladder bile after subtotal gastrectomy with truncal vagotomy. Of 11 mongrel dogs with cholecystostomy, 3 underwent B-I and 4 B-II gastrectomy. Four dogs without gastrectomy were served as controls. Bile was collected for 12 months. Bile acids were quantified by GLC. The bile was cultured for bacteriology. TBA did not significantly differ among the three groups of the dogs. In the two gastrectomized groups, CDA (a secondary bile acid) kept a higher level and CA (a primary bile acid) maintained a lower concentration compared with those in the controls. A remarkable increase of non-conjugated bile acids was recognized in both gastrectomized groups. Lithogenicity was low for all of the 3 groups. All but 1 control dog incurred bile infection that persisted long. Black pigment stones containing calcium bilirubinate developed in 1 of the 3 B-I and 2 of the 4 B-II dogs but none in the controls. The bile infection seemed to be involved in the development of GS. As the alteration of bile composition and GS occurred solely in the gastrectomized dogs, subtotal gastrectomy with truncal vagotomy might precipitate the GS formation.

Animals↗

[Continuous hyperthermic peritoneal perfusion (CHPP) therapy in advanced gastric cancer].

In CHPP therapy for advanced gastric cancer, a perfusate containing 20 mg CDDP and 8 mg MMC in 1,000 ml physiologic saline warmed at 47 degrees C was infused at a constant rate of 200 ml/min into the pouch of Douglas. The intraperitoneal temperature at the supra-pancreatic region was around 39.0 degrees C. To obtain a more stable and higher intraperitoneal temperature, the infusing rate was increased to 400 ml/min. This yielded a 3 degrees C higher temperature (42 degrees C) at the same measuring site. However, the temperature recorded at various intraperitoneal sites did not always reach such an effective range. The maximal plasma concentrations of MMC determined during CHPP at the 200 and 400 ml/min infusion were 0.09 +/- 0.03 and 0.11 +/- 0.03 microgram/ml, and those of CDDP 1.6 +/- 0.4 and 1.7 +/- 0.3 microgram/ml, respectively, all of which were not significantly different. When an intraperitoneal dosage of 20 mg MMC was given to 3 patients, the portal venous blood, at 10 min after the administration, produced a 1.7 times higher concentration of the agent than did the peripheral venous blood. This discrepancy between the two concentrations was much smaller than found by other investigators in animal experiments.

Adult↗

[Five cases of rectal cancer showing remarkable response to suppository administration of tegafur].

Five cases of rectal cancer, one male and 4 females, were preoperatively treated with Tegafur suppositories at 1,500 mg per day, for 8 to 21 days (mean, 14 days). These tumors were 2 early cancers and 3 advanced cancers, the configuration of which were one IIa type, one IIa + IIc type and 3 Borrmann 2 types. Their size ranged from 1.3 to 4.2 cm in diameter. Curative resections were performed in all cases, and the examination of the resected specimen revealed marked effects of Tegafur as follows: 1) Reduction of tumor size, 2) disappearance of cancer wall, 3) degeneration of cancer cells and destruction of cancer glands accompanied by fibrous stroma with infiltration of lymphocytes and plasma cells, 4) formation of xanthogranulomatous tissue with foamy histiocytes, which were characteristic findings showing that cancer tissue had been present there. As a result, rectal cancer clearly showed remarkable response to suppository administration of Tegafur for only about two weeks, if the tumor cells were sensitive to the drug.

Adult↗

[Continuous arterial infusion therapy of recombinant interleukin-2 and cyclophosphamide in hepatoma and liver metastasis].

The continuous arterial infusion of only recombinant interleukin-2 (rIL-2) was used in 9 patients with unresectable liver metastasis of colorectal or biliary cancer. This therapy was undertaken for the activation of tumor infiltrating lymphocytes (TIL), but was not effective. Then we tried continuous arterial infusion of rIL-2 and low-dose cyclophosphamide (CY) for liver metastasis. 3 of the patients who received rIL-2 and CY showed partial remission of disease. This therapy was possibly effective because of the activation of TIL and the suppression of tumor infiltrating suppressor lymphocytes.

Adult↗