[Evaluation of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases from gastric cancer--comparative analysis for intra-arterial group and non-intra-arterial group].

We evaluated the effects of intra-arterial infusion chemotherapy for liver metastases and lymph node metastases of gastric cancer. Of 410 patients undergoing gastrectomy in our department from July 1993 to December 2000, 29 (7.1%) had liver metastases. Intra-arterial infusion chemotherapy was carried out for 15 patients with liver metastases and 10 patients with lymph node metastases. There were 11 patients with liver metastases evaluated as follows: PR 5, NC 2, PD 4. Two patients with lymph node metastases were PR. In a comparison between the intra-arterial and non-intra-arterial chemotherapy group, it was observed among the patients with synchronous liver metastases that the survival period of the intra-arterial group was significantly longer than that of the non-intra-arterial group (p = 0.0164 logrank test). On the supposition that the survival period is counted from the day of computed tomography metachronous liver metastases was detected, in all liver metastases patients, the survival period of the intra-arterial group was significantly longer (p = 0.0212 logrank test). These results showed that the intra-arterial infusion chemotherapy is a useful treatment for gastric cancer patients with liver metastases.

Inhibition of factor Xa suppresses the expression of tissue factor in human monocytes and lipopolysaccharide-induced endotoxemia in rats.

BACKGROUND: Activated factor X (FXa) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response. Tissue factor (TF) is an initiator of blood coagulation. We investigated whether FXa induces TF expression in human peripheral monocytes and whether treatment with FXa inhibitor reduces TF expression in an experimental model of rat endotoxemia. METHODS: Human peripheral mononuclear cells were used to determine TF expression induced by FXa. Experimental rat endotoxemia was induced by intravenous bolus injection of lipopolysaccharide (LPS). A specific FXa inhibitor, DX-9065a, was administered subcutaneously immediately after LPS injection. RESULTS: FXa induced TF expression in monocytes without intervention of thrombin and the expression was suppressed by FXa inhibitor. In the experimental model of rat endotoxemia, TF and TF mRNA expression levels in the liver were reduced by DX-9065a. Moreover, administration of DX-9065a suppressed the rise in plasma concentrations of thrombin-antithrombin III complex (TAT) and monocyte chemoattractant protein-1 (MCP-1). CONCLUSIONS: Our results indicated that FXa can induce TF expression in human peripheral monocytes and that inhibition of FXa reduces TF expression in the liver of rat endotoxemia. These results suggest that FXa is an important factor for TF expression in sepsis.

Neutrophils express tissue factor in a monkey model of sepsis.

BACKGROUND: Although tissue factor (TF) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response, its source in sepsis remains controversial. Recently, we found that, in addition to monocytes and endothelial cells, neutrophils may express TF in a rabbit model. The purpose of this study was to determine whether neutrophils could be a source of TF in a monkey model of sepsis. METHODS: TF messenger RNA (mRNA) and protein in neutrophils were assayed by in situ hybridization and immunohistochemistry in tissues obtained from monkeys after injection of lipopolysaccharide (LPS) (n = 3) and after injection of saline as a control (n = 2). Coagulation parameters were measured before and at 1.5 and 3 hours after injections. RESULTS: In LPS-treated monkeys, TF mRNA and protein were induced not only in monocytes and endothelial cells, but also in neutrophils accumulating in the liver 3 hours after LPS injection. Thrombin-antithrombin III complex and fibrin degradation products D-dimer levels were significantly increased at 3 and 1.5 hours after LPS injection compared with controls. CONCLUSIONS: Neutrophils are a source of TF and are implicated in direct activation of the coagulation cascade in the early phases of sepsis in the monkey. These results give important information for the treatment of sepsis.

Separate histogenesis of combined hepatocellular and cholangiocellular carcinoma in two patients.

Double primary liver carcinomas, i.e. hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) are rare. Two patients in whom double primary liver carcinomas were surgically resected are described herein. Case 1: A 51-year-old Japanese man with chronic type B hepatitis underwent hepatectomy for primary HCC with intrahepatic metastasis. Case 2: A 67-year-old Japanese man with a history of rectal cancer and CCC underwent lateral hepatic segmentectomy for a suspected recurrence of intrahepatic CCC. Lack of direct contact between tumors, no evidence of histological transition and clearly different immunohistochemical staining for cytokeratin support a distinct histogenesis of the tumors in these two patients. The findings indicate that combined HCC and CCC can arise synchronously or metachronously as an intrahepatic double cancer.

Possible role of platelet-activating factor in the in vivo expression of tissue factor in neutrophils.

BACKGROUND: Recently, we demonstrated that neutrophils express tissue factor (TF) in a model of acute obstructive cholangitis (AOC). However, the regulation of TF expression was not clear. In this study, we clarified the role of platelet-activating factor (PAF) in TF expression in neutrophils. MATERIALS AND METHODS: In a model of AOC, intravenous PAF antagonist, (SM-12502, 200 mg/kg) was administered 5 min before sepsis was induced. Normal saline was given as a control. Coagulation parameters and TF activity were monitored for 6 h. Thereafter, the liver was harvested for histological examination. RESULTS: The percentage of neutrophils which stained positive for TF was significantly reduced by SM-12502 (74.9 +/- 19.3% vs 96.3 +/- 2.8%) (P < 0.01). The number of leukocytes infiltrating the liver was also significantly reduced. Coagulation abnormalities, TF activity, and focal necrosis of the hepatocytes were reduced by SM-12502. CONCLUSIONS: SM-12502 inhibits TF expression in neutrophils which have infiltrated the liver sinusoids, reducing the subsequent infiltration of leukocytes. These results suggest that PAF plays an important role in the expression of TF in neutrophils in vivo.

Macrophages and neutrophils infiltrating into the liver are responsible for tissue factor expression in a rabbit model of acute obstructive cholangitis.

Acute obstructive cholangitis (AOC) is one of the most fatal outcomes in sepsis, and frequently complicates disseminated intravascular coagulation (DIC). Recently we found that the plasma tissue factor (TF) level increased and changed in parallel with plasma markers of DIC in patients with AOC. To elucidate the role of TF in the pathogenesis of coagulopathy in AOC, we investigated the plasma levels of TF and its localization by immunohistochemical staining in rabbit models of AOC. Plasma TF activity significantly increased 3 h after the insult (0.63 +/- 0.1¿9 U/ml; p < 0.01) compared with that beforehand (0.05 +/- 0.02 U/ml), then reached a maximum level at 6 h (0.94 +/- 0.16 U/ml). The fluctuations in plasma TF activity correlated with those of the coagulation parameters including platelet count, fibrinogen, prothrombin time, and antithrombin III activity. Immunohistochemically, enhanced expression of TF was mainly detected in macrophages and neutrophils that had infiltrated into the liver sinusoids and around the bile duct, but not in the sinusoidal endothelial cells. A double immunofluorescence study revealed the concomitant presence of TF and fibrin at sites where macrophages and neutrophils had conglomerated. However, we could not detect an apparent change in TF expression in the lung or kidney. These data suggest that macrophages and neutrophils infiltrating into the liver sinusoids and around the bile duct play a pivotal role in TF expression, leading to coagulopathy in the acute phase of obstructive cholangitis in rabbits.

[Surgical treatment of interrupted aortic arch with aorticopulmonary window].

From January, 1988, through September, 1993, 3 neonates underwent one-stage repair for interrupted aortic arch (IAA) with aorticopulmonary window (APW). Their mean weight was 3.0 kg (2.7-3.3 kg). IAA was Celloria-Patton classification type B in two patients and type A in the other. In all cases, APW was Mori's classification type II. Two patients took a sudden turn for worse during the stay of our hospital and underwent emergency operation. Surgical procedures were as follows; In the first patient, aortic arch reconstruction was performed with phi 8 mm Golaski graft, under extracorporeal circulation for only upper body under moderate hypothermia. After distal anastomosis, perfusion for lower body was restarted through the graft branch, then proximal anastomosis was done. In the other two patients, arch reconstruction was performed by end to side direct anastomosis under total circulatory arrest and deep hypothermia, and APW was divided during recirculation, rewarming period. In the first patient, graft was anastomosed to the defect of the ascending aorta. In the other two patients the defect of the aorta was directly closed. The defect of the pulmonary artery was closed directly in two patients and with autopericardium in the other. There was no operative deaths. Two cases who underwent emergency operation due to sudden turn for worse didn't become well soon. Thus, we concluded that surgical intervention should be done as soon as possible before patient became critically ill and one-stage repair should be recommended because of the difficulty of palliation such as PA banding in this disease.

[Methicillin-resistant Staphylococcus aureus endocarditis following patch closure of ventricular septal defect].

Mediastinitis due to methicillin-resistant Staphylococcus aureus was found on the ninth postoperative day after patch closure of ventricular septal defect (VSD) in a six-month-old girl. Intravenous administration of vancomycin and debridement of the wound followed by irrigation with povidone iodine and vancomycin led to wound disinfection, but blood cultures continued positive. On the 22nd postoperative day, an echocardiographic examination revealed vegetations in the right ventricle. An emergency open heart operation was undergone. The largest vegetation was 1 x 2 cm in size, originating from the intracardiac patch used for closure of the VSD. The pulmonary and tricuspid valves were also involved. After removal of the infected tissues, including the two cusps of the pulmonary valve and a part of the tricuspid valve, the ventricular septal defect was closed again with a woven Dacron patch. The defect in the tricuspid valve was repaired. Postoperative examinations revealed severe pulmonary regurgitation and mild tricuspid regurgitation, but the cardiac function was good and neither vegetation nor leakage around the patch was recognized.

Molecular cloning and sequencing of a cDNA clone encoding a new calcium binding protein, named calgizzarin, from rabbit lung.

We purified a new EF-hand type calcium binding protein from chicken gizzard smooth muscle, tentatively named calgizzarin (Todoroki, H., et al. J. Biol. Chem. (1991) in press. Based on the internal peptide sequence of calgizzarin, we isolated and sequenced a cDNA clone coding for calgizzarin from a rabbit lung cDNA library. This clone (pCALG) has 309 nucleotides of open reading frame including termination codon TGA, 621 nucleotides of the 5' leader and 186 nucleotides of the 3' noncoding region. The polypeptides deduced from the open reading frame were consisted of 102 amino acid residues with a molecular weight of 11,429. Computer aided homology analysis revealed that calgizzarin exhibits a 43.2% homology to S-100 alpha, 38.6% to S-100 beta and 40.0% to annexin II light chain, p10. By Northern blot analysis, with pCALG, a band of 1.1 kbp was detected in rabbit lung, suggesting pCALG contains nearly full length of mRNA.

Purification, characterization, and partial sequence analysis of a newly identified EF-hand type 13-kDa Ca(2+)-binding protein from smooth muscle and non-muscle tissues.

A novel Ca(2+)-binding protein, tentatively designated calgizzarin, has been purified to apparent homogeneity from chicken gizzard smooth muscle by W-7 (N-(6-aminohexyl-5-chloro-1-naphthalenesulfonamide))-Sepharose affinity chromatography and ion-exchange chromatography. Application of W-7-Sepharose affinity chromatography to various tissues revealed that calgizzarin-like proteins were abundant in bovine aorta and rabbit lung. Using the same procedure, we could purify a calgizzarin-like protein from rabbit lung. Calgizzarin has a Mr of 13,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and approximately 30,000 as determined by gel filtration on a TSK G 3000SW high performance liquid chromatography column, suggesting that calgizzarin seems to be a rodlike protein. The isoelectric point of calgizzarin was found to be pH 5.8. Calgizzarin can exist as a dimer by forming a disulfide bridge. The 45Ca autoradiographic technique showed that the protein binds to Ca2+. On an alkaline/urea gel, calgizzarin migrated faster in the presence of EGTA than in the presence of CaCl2, thereby indicating a Ca(2+)-dependent conformational change in this protein. The partial amino acid sequence (65 amino acid residues) of calgizzarin was seen to be SLLAVFQRYAGREGDNLKLSKKEFRTFMNTELASFTKNQKDPAVVDRMMKRLDINSDGQLDFQEF, and two putative Ca(2+)-binding sites (GREGDNLKLSKKE and D INSDGQLDFQE) were detected. So far as the obtained 65-amino acid sequence is concerned, calgizzarin has approximately a 50% sequence homology with S-100 alpha, 47% with S-100 beta, and 39% with pEL-98 protein.

[Surgical treatment of total anomalous pulmonary venous connection under three months of age].

Nine infants under 3 months of age with total anomalous pulmonary venous connection underwent total correction between June, 1986 and September, 1988. The age at operation ranged from 4 days to 59 days, averaging 19 days, and the body weight ranged from 1,814 g to 4,105 g, with a mean of 3,050 g. The types of TAPVC were Darling Ia in 4, Ib in 1 and III in 4. All the patients were operated by the posterior approach under cardiopulmonary bypass with high flow (130-200 ml/kg/min) and mild hypothermia using modified GIK-cardioplegia, topical cooling and aortic cross clamping. Although the incision in the common pulmonary vein trunk was never extended into the pulmonary veins or vertical vein, the length of the mouth was at least 10 mm. In the postoperative management, care was taken to avoid overhydration and rapid volume infusion. Blood pressure was kept just enough to maintain urine output. Heart rate was kept over 170/min for early postoperative days with the use of isoproterenol or atrial pacing. There was no operative or late death. Postoperative course was uneventful in all cases except one with low output syndrome in which mechanical ventilation for 8 days was required. Postoperative catheterization and angiography revealed normal intracardiac pressure values and no pulmonary venous obstruction in all cases. Follow-up period ranged from 10 to 37 months, and there has been no patient with the signs of PVO.

New two-dimensional, echocardiographically directed pericardiocentesis in cardiac tamponade.

Seventeen patients with cardiac tamponade were treated by pericardiocentesis guided by two-dimensional (2-D) echocardiography and a needle guide. The needle guide used in the present study was designed so that the needle path lies within the center of the scan thickness. Before actual puncture, the mask method was performed in a water bath so that the needle progress avoided injury. The needle progress was monitored continuously in real time on the display throughout the procedure. Immediate relief from acute cardiac tamponade was obtained in all except one patient, who was treated by pericardiotomy because of insufficient drainage. In two patients, second drainage was performed because of reaccumulation of the pericardial effusion. There were no major complications. Nine patients recovered and the other patients died of underlying disease. Accurate and efficient visualization of the needle might allow a safer procedure. We conclude that pericardiocentesis guided by 2-D echocardiography using a needle guide may be a safe and easily applied technique for the management of pericardial effusion.

Changes in adenosine triphosphate, 2,3 diphosphoglycerate, and P50 of dog blood following transfusion of autologous red cells pretreated with phosphoenolpyruvate in vitro.

Red cells treated with phosphoenolpyruvate (PEP) in vitro were reinfused into the donor dogs and were monitored for changes in adenosine triphosphate (ATP), 2, 3 diphosphoglycerate (2,3 DPG), and P50. ATP and 2,3 DPG concentrations increased to 116 and 143 percent of control, respectively, when these cells were incubated with 60 mM PEP for 90 minutes at 37 degrees C. The oxygen dissociation curve shifted to the right, and P50 increased from 24.5 to 30.6 torr as a result of the PEP treatment. When one-half of the circulating red cell volume was treated with PEP and reinfused into the animal, the red cell 2,3 DPG increased to 120 percent of pretransfusion values. The 2,3 DPG level remained elevated during the following day and returned to near pretransfusion levels on the third day. The P50 of the circulating blood paralleled the variations in the red cell 2,3 DPG level, and the capacity for oxygen delivery was calculated to be raised by 13 to 38 percent for a period of 24 hours. In contrast, elevated red cell ATP returned to control values immediately after transfusion. In vivo viability, i.e., 24-hour survival and one-half disappearance time, of the cells pretreated with PEP were determined by a single-isotope technique using 51Cr. The results showed that PEP treatment did not injure the red cells. In addition, there was neither acute toxicity nor a deleterious hemodynamic effect when large amounts of PEP were administered intravenously. These results suggest that PEP could be used clinically to improve the capacity of the circulating red cells to deliver oxygen to the tissues.