Metastasis of a human pancreatic adenocarcinoma (RWP-1) in nude mice.
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Biomedical subjects
Publications and source records attributed to M D Turner.
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Two human pancreatic cancer lines, RWP-1 and RWP-2, have been established from 2 patients with primary pancreatic cancer metastatic to the liver. The patients' tumors, the xenografted tumors, and tumors obtained by inoculation of nude mice with cultured RWP-1 and RWP-2 cells are all moderately-well-differentiated ductal cell adenocarcinomas. Ultrastructural analysis supports the tissue histopathology findings. Xenografts of RWP-1 tumors double every 10 days, whereas the doubling time of RWP-2 xenografts is 22 days. Both tumors contain mucin. RWP-1 and RWP-2 cells have a doubling time in culture of 45 hr and form colonies in soft agar. RWP-1 cultures appear to be morphologically heterogeneous; two distinct epithelial cell types can be identified. RWP-1 and RWP-2 have modal chromosome numbers of 64 and 62, respectively. Appreciable levels of glucose-6-phosphate dehydrogenase and lactic dehydrogenase were found in both cell lines and xenografts. RWP-1 and RWP-2 cells produce appreciable amounts of carcinoembryonic antigen, 1090 and 414 ng/10(6) cells, respectively.
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Blood flow distribution in tissues of mongrel dogs during hypothermia was studied with radionuclide-tagged microspheres. The animals were cooled at 21 degrees C and rewarmed under thiamylal sodiuni anesthesia. During hypothermia, cardiac output fell to 20% of the control; the highest rate of blood flow relative to normothermic values was observed in the subendocardium of the left ventricle, and the lowest in the hypophysis. Each tissue showed specific reactions to hypothermia. During hypothermia the myocardial and brain-stem blood flows were about 40% of the control; almost all of the digestive tract, striated muscle, adrenal gland, and hypophysis blood flows were maintained at 20% or less of the control. After rewarming, cardiac output recovered to values significantly lower than control. The myocardium, brain, renal cortex, and striated and smooth muscle recovered to control levels; however, blood flow to the digestive organs, bronchial artery flow to the lung, and flow to the endocrine organs did not completely recover by 2 after rewarming.
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The purpose of our study of hemorrhagic shock in dogs was to examine the efficacy of adding Ringer's lactate to shed blood replacement in increasing animal rates. The standard Wiggers' hemorrhagic shock technic was used in two groups of ten animals each. Intravascular pressures, cardiac outut, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2 and pH, electrolyte changes, and survival rates were determined. There was a positive correlation between changes in cardiac output, central venous oxygen content, and PO2 and extracellular fluid PO2 as measured using subcutaneously implanted Silastic tubing and perforated plastic balls. Four of the dogs that received shed blood alone survived, whereas five of the dogs that received shed blood plus Ringer's lactate survived. This difference was not statistically significant.
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Ten dogs were used to study antral gastrin secretion in hemorrhagic shock. Dogs that had a vagotomy were compared with normal dogs. Acute hemorrhage, imposed upon operative stress, produced increased gastrin secretion in normal dogs but not in dogs after vagotomy. During the acute hemorrhage, the level of circulating gastrin in normal dogs increased to about 50 to more than 100 per cent of the control values. The concentration of gastrin in the dogs having a vagotomy was essentially unchanged in the face of acute hemorrhage. Results of this study suggest that the increased concentration of circulating gastrin in normal dogs subjected to severe stress may play a role in the development of a stress ulcer.
Four cases of Barrett's esophagus are presented. Three cases presented with significant esophageal bleeding and one case presented with high esophageal stricture. Gastrointestinal panendoscopy was done in each case and multiple biopsies were taken. The biopsies were utilized for histomorphology, pepsinogen agar gel electrophoresis, and tissue gastrin assays. Tissue gastrin levels in esophageal mucosa were elevated in 2 cases when compared to controls with and without hiatus hernia. Pepsin and acid secretory studies were done by isolating the esophagus. Barrett's esophagus was shown to produce pepsin by both chemical studies (2 cases) and agar gel electrophoresis at pH 5.7 (3 cases), and was also shown to produce acid. The mucosa contained either cathepsin or cathepsin and pepsinogens in all cases. Nissen's fundoplication was performed in all of the patients. Of 3 patients who were bleeding, 2 who consented for this operation stopped bleeding after the operation. It is to be noted that the usual clinical treatment of antacids, bedrest, and raising the head end of the bed failed in all of the patients. The follow-up of 9 months to 3 years postoperatively has shown persistence of Barrett's mucosa with no evidence for any reversion to normal esophageal type.
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The objectives of this study were to compare in dogs the effects of massive infusion of Ringer's lactate, 5% dextrose in water, and whole blood. Special interest centered upon lung function, central venous pressure, and dilutional effects upon the blood components. Three groups of 5 healthy dogs each received respectively Ringer's lactate, 5% dextrose, or whole blood over 60 minutes in the amount of 135 ml/kg. Arterial blood gases and pH, right atrial and systemic arterial pressures, hemoglobin and hematocrit values, and plasma sodium, chloride, potassium and protein levels were determined. Coagulograms and serum osmolality were examined in the early experiments. The purpose of the whole blood infusion was primarily to serve for comparison in the study of dilutional effects upon blood components. There was no statistically significant change in the arterial blood gas values or pH following Ringer's lactate infusion. The infusion of 5% dextrose in water produced moderate decline in arterial Pco2 and a temporary, slight fall in blood pH. Ringer's lactate infusion produced a prompt and statistically significant rise in central venous pressure. The infusion of 5% dextrose was followed by a late moderate decline in arterial blood pressure, possibly due to marked dilution of plasma sodium, chloride and potassium. It is concluded that massive Ringer's lactate infusion is capable of increasing right atrial pressure and presumably cardiac output. In healthy dogs, lung function was not impaired sufficiently to alter arterial blood gas values. However, where other previous or concomitant factors have diminished pulmonary reserve, fluid overload may impose a serious additional burden upon cardiopulmonary function.
An instrument for producing closely controlled and repeatable hemorrhagic shock in laboratory animals is described. A Sarns roller pump, controlled by an electronic device, is used to pump blood in and out of the animal at a constant rate. Photoelectric cells are used to sense pressure changes and depending on their configuration, the pump runs forward or backward or stops. Pressures are accurately maintained, bleeding and reinfusion rates are controlled, and a record of bleeding patterns is provided.
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