Continuous hyperthermic peritoneal perfusion (CHPP) with a solution which contains 30 mg mitomycin C and 300 mg cisplatin has been introduced as a prophylactic treatment for peritoneal recurrence after curative resection of 79 advanced gastric cancers. The control group consisted of 81 patients with advanced gastric cancer who underwent curative surgery during the same period. CHPP was performed for 60 minutes by perfusing MMC- and CDDP-containing saline solutions warmed at 43.5 degrees C by a special CHPP device. In patients with pathologically confirmed serosal invasion-positive tumors, the survival rate of the CHPP group was significantly higher than that of the control group. A survival advantage for stage IV patients was also obtained by CHPP. However, there was no survival advantage between the CHPP group and the control group with serosal invasion-negative tumors. Adverse effects were observed in four patients who underwent CHPP: One developed severe bone marrow suppression, and transient hyperazotemia was observed in the other three. There was no difference in the incidence of mortality and morbidity between the two groups. These results indicate that CHPP is a safe, readily available prophylactic therapy for peritoneal recurrence after gastric cancer surgery.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Role of endogenous platelet-activating factor in caerulein-induced acute pancreatitis in rats: protective effects of a PAF-antagonist.

The role of endogenous platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis was investigated by determining whether CV-6209, a selective PAF antagonist, confers protection against caerulein-induced acute pancreatitis in rats. Continuous intravenous infusion of caerulein (5 micrograms/kg x h) induced time-dependent increase in serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas, and produced histologic evidence of acute pancreatitis. Pretreatment with CV-6209 (1 mg/kg) significantly inhibited the elevation of serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas. Caerulein-induced tissue oedema and recruitment of leucocytic cells were markedly ameliorated with CV-6209. Platelet-activating factor may be released endogenously and may play a role during acute pancreatitis.

Acute Disease↗

PubMedDate not supplied

Role of endogenous platelet-activating factor (PAF) in endotoxin-induced portal hypertension in rats.

To determine the role of platelet-activating factor (PAF) in endotoxin-induced portal hypertension, we performed continuous recording of both blood pressure (BP) and portal venous pressure (PVP) in rats following the administration of intravenous PAF (25 ng/kg), intraportal PAF (25 ng/kg), intraportal endotoxin (2 mg/kg), and intraportal endotoxin (2 mg/kg) for 1 min subsequent to pretreatment with a specific PAF-antagonist (CV-6209, 1 mg/kg, i.v.). Basal resting values of both BP (102.3 +/- 9.3 mmHg) and PVP (7.7 +/- 1.2 mmHg) fell rapidly after intravenous infusion of PAF (BP: 36.7 +/- 5.8 mmHg; PVP: 5.7 +/- 0.8 mmHg) and followed by gradual return. Intraportal PAF infusion elicited a rapid but less severe depression of BP (57.2 +/- 9.4 mmHg) as compared with intravenous PAF infusion, whereas PVP was increased transiently around 4 min after treatment (11.0 +/- 5.3 mmHg). A similar degree of PVP elevation (10.7 +/- 2.0 mmHg) was observed between 8 and 20 min after intraportal administration of endotoxin. Depression of BP was initiated 12 min after endotoxin administration but was not severe (76.6 +/- 12.8 mmHg). CV-6209 significantly alleviated the endotoxin-induced elevation of PVP and completely inhibited the hypotension. These observations suggest that: (i) PAF-induced elevation of PVP is a direct response of the liver to PAF; and (ii) endogenous PAF plays an important role in the endotoxin-induced portal hypertension.

Animals↗

PubMedDate not supplied

Heterogeneous distribution of microcirculatory disturbance in the gastric mucosa during gastric hypercontraction in rats.

Gastric mucosal lesions induced by gastric hypermotility are characteristically observed along the gastric mucosal folds. To determine the role of microcirculatory disturbance in this particular condition, we measured the gastric mucosal haemodynamics after vagal stimulation and also examined histologically the transparent specimens of the transverse section of the contracted stomach in rats. Gastric mucosal haemodynamics measured with a reflectance spectrophotometer showed the repetition of ischaemia-reperfusion during gastric hypermotility. The rapidly frozen and transparent specimen of the corpus showed that gastric mucosa was stretched at the crest and compressed at the base of the mucosal folds. Characteristic distribution of red blood cells was observed; it was dense at the crest of the mucosal folds and sparse at the base. These results suggest that gastric hypermotility may induce the distinctive heterogeneous microcirculatory disturbance in the folds and may contribute to the characteristic localization of mucosal lesions.

Animals↗

PubMedDate not supplied

Osteoinduction by recombinant human bone morphogenetic protein-2 in muscles of non-human primates.

Heterotopic osteoinduction in a muscle of a medium-sized, non-human primate (Japanese macaque monkey; Macaca fuscata) was investigated with recombinant human bone morphogenetic protein-2 (rhBMP-2) mixed with atelopeptide type I collagen as the carrier. Nine monkeys were divided into three groups of three: groups I (1.25 mg rhBMP-2), II (250 micrograms rhBMP-2) and III (50 micrograms rhBMP-2). Four weeks after implanting into the calf muscle pouch, the implant was examined radiographically and histologically. In one specimen of three in group I, marked radio-opaque shadow, massive chondrogenesis and partial osteogenesis were observed. In the other two specimens, only microscopic calcification signs were recognized. In groups II and III, no findings of heterotopic osteoinduction were radiographically observed; however, nuclei from muscle bundles reacted to rhBMP-2 and were large and round, as in muscle bundles near the site of osteogenesis in group I. A positive control study using rats was carried out in parallel. This was a dose-finding study, with the monkeys in group III acting as a sub-effective dose (placebo) control, and rats acting as an active control, or verum, to show that the techniques are sufficiently sensitive. Bone morphogenetic protein appears to osteoinduce less bony material in soft tissue in primates than in rats.

Animals↗

PubMedDate not supplied

Pachydermoperiostosis with myelofibrosis and anemia: report of a case of anemia of multifactorial causes and its improvement with steroid pulse and iron therapy.

A 26-year-old male patient with pachydermoperiostosis is reported. He had severe anemia with myelofibrosis. Treatment with iron, prednisolone, oxymethorone and 1 alpha (OH)D3 were not satisfactory. But steroid pulse therapy with parenteral iron improved his anemia and pancytopenia, but was not sufficient to relieve the bone marrow fibrosis or splenomegaly. The mechanism of anemia which was considered to be multifactorial including gastro-intestinal bleeding associated with peptic ulcer or erosion and bone marrow failure due to myelofibrosis, is discussed.

Adult↗

PubMedDate not supplied

T-cell receptor V beta gene usage of human cytotoxic T-cell clones obtained from gastric cancer patients.

Nine T-cell clones have been established from tumor-infiltrating lymphocytes (TIL) isolated from ascitic fluid of a gastric cancer patient. Five of them retained cytotoxicity against autologous tumor cells (AuTu), and were all CD4+. Each clone had different usage of T-cell receptor (TCR) V beta gene as assessed by Southern blot analysis. Using AuTu and two allogeneic gastric cancer cell lines as targets, we selected three clones with unique cytotoxic properties. Two of these clones (Clone 1 and 2) preferentially lysed AuTu, but showed no or marginal cytotoxicity against allogeneic gastric cancer cells, and one clone (Clone 7) showed appreciable cytotoxicity against AuTu and allogeneic gastric cancer cells. In the detailed analysis of TCRV beta gene usage, Clone 1, 2, and 7 expressed V beta 13.1/D beta 1/J beta 1.5/C beta 1, V beta 3/D beta 2/J beta 2.4/C beta 2, and V beta 9/D beta 1/J beta 1.4/C beta 1, respectively, and the primary structures of the three TCRVb genes did not share any common features, neither in the sizes of their complementarity determining region 3 (CDR3) nor in their amino acid compositions. Interestingly, PBL of the same patient expressed CDR3 identical to that of Clone 2 and 7, but not that of Clone 1. CDR3 identical to that of Clone 2 and 7 were also detected in TIL of other gastric cancer patients. These results show that some AuTu-specific CTL included in TIL are circulating in peripheral blood, and that the CDR3 identical to that of the CTL is expressed extensively in TIL among different gastric cancer patients. Screening of the expression of the CDR3 in other gastric cancer patients is recommended to develop an immuno-therapy of gastric cancer based on antigenic peptide.

Adenocarcinoma↗