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Biomedical subjects

R D Beauchamp

Publications and source records attributed to R D Beauchamp.

At least 91 records · Page 5Linked to original sources
PubMed1988

Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by alpha-difluoromethylornithine.

We studied the effect of inhibition of polyamine biosynthesis by alpha-difluoromethylornithine on the growth of a human gastric adenocarcinoma (CLEES) xenotransplanted in nude mice. CLEES is a well-differentiated gastric adenocarcinoma of the intestinal type. The doubling time has ranged from 7 to 10 days through 11 passages. Electron microscopic and immunohistochemical studies comparing the original tumor and xenotransplants showed similar structure and similar amounts of carcinoembryonic antigen. Polyamine biosynthesis is required for cell division. alpha-Difluoromethylornithine inhibits ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. In this study, 48 athymic mice were used in two experiments. In the first experiment, two groups of 12 mice each were inoculated with CLEES tumor cells and received either tap water or a 3% alpha-difluoromethylornithine solution as drinking water. Tumor size was measured twice weekly. Tumor size was significantly decreased from controls by the fourth week of treatment and at all points of analysis thereafter for 7 wk. In the second experiment, alpha-difluoromethylornithine significantly reduced tumor concentrations of the polyamines putrescine and spermidine. In addition, the tumor content of DNA was significantly reduced in treated mice (0.64 +/- 0.16 mg) compared to controls (4.76 +/- 0.92 mg). Our data suggest that inhibition of polyamine biosynthesis may be a useful component of multidrug chemotherapy for human gastric adenocarcinoma. Establishment of tumor lines such as this gastric adenocarcinoma will facilitate further studies on the biological behavior of human gastric cancer and its response to chemotherapeutic manipulation in vivo.

Adenocarcinoma↗
PubMed1988

Growth factors and intestinal neoplasms.

Signals that control normal and neoplastic epithelial proliferation are not completely understood. We have reviewed the importance of the possible roles of the following control mechanisms: polyamine biosynthesis, intraluminal nutrients, gastrointestinal hormones and growth factors, bowel resection, carcinogens, and oncogenes. The mechanisms by which these agents act and the precise roles they play in normal and abnormal proliferation of intestinal mucosa have not yet been clearly defined. Peptide hormones and growth factors exert their mitogenic effects by first interacting with specific receptors in the cell membrane. Oncogenes induce production of growth factors or replace growth factors and, by themselves, stimulate growth. We believe that no single agent is likely to be responsible; rather, multiple agents are involved in stimulation of growth of normal and neoplastic intestinal epithelial cells. A clear understanding of the factors responsible for regulation of normal and abnormal intestinal cell growth will greatly facilitate the development of therapeutic strategies for the prevention and treatment of gastrointestinal cancers.

Animals↗
PubMed1987

Inhibition of pentagastrin-stimulated up-regulation of gastrin receptors and growth of mouse colon tumor in vivo by proglumide, a gastrin receptor antagonist.

We have recently demonstrated that gastrin stimulates growth of mouse colon cancer (MC-26) in vivo by regulation of gastrin receptors (GR). In the present study, we have tested the effect of proglumide (PGL), a GR antagonist, on the trophic and GR-regulatory effects of gastrin on MC-26 tumors. Four groups of 12 mice each were inoculated with 5 X 10(4) MC-26 cells and given injections of either normal saline (control), pentagastrin (PG), PGL, or both PG + PGL for 21 days. At the end of the treatment period, body, tumor, fundic, and colon weights were noted and GR measured. Two types of specific gastrin-binding sites were found on tumor cell membranes of control mice, one with high binding affinity (Kd = less than 1.0 nM) and low capacity (GR), and the other with a very high capacity and a low affinity (Kd = greater than 0.1 microM) (type 2 gastrin-binding sites). Only the type 1 GR were observed on the fundic mucosal and colon membranes. PG treatment resulted in a significant weight increase of the tumors with an up-regulation of only type 1 GR. On the other hand, PG had no significant effect on fundic mucosal and colonic GR levels, but caused a significant increase in fundic mucosal weights. PGL completely inhibited both the trophic and GR up-regulatory effects of PG on tumors, but incompletely reduced the PG-stimulated fundic mucosal weight gain, indicating differential sensitivity of tumor and normal tissues to PGL. PGL, in the absence of PG, was slightly trophic for normal fundic mucosa, but had no effect on MC-26 tumors and normal colon. The one striking effect of PGL, in the presence of PG, was the significant lowering of the binding affinity of type 1 GR for gastrin on both the tumor and normal gastrointestinal tissues. This effect may be another mechanism by which PGL interferes with the actions of PG on MC-26 tumors and fundic mucosa of mice.

Animals↗
PubMed1987

Role of cholecystokinin in canine pancreatic exocrine response to bombesin stimulation.

The role of cholecystokinin in bombesin-stimulated pancreatic secretion in dogs was examined by the use of a specific cholecystokinin antagonist, proglumide. The primary component of bombesin-stimulated pancreatic secretion at the lowest tested dose was due to cholecystokinin, with only 25 percent of bombesin-stimulated protein output preserved during proglumide infusion. Maximal stimulation of cholecystokinin release was achieved by even the lowest dose of bombesin, whereas dose-related increases in bombesin-stimulated protein secretion were observed. This increase in exocrine secretion is probably explained by increased direct bombesin stimulation. Our findings suggest that the maximal dose of bombesin is lower for cholecystokinin release than its effective dose for enzyme secretion. We conclude that, in all probability, postprandial release of bombesin (or its analogue, gastrin-releasing peptide) affects pancreatic function primarily through release of cholecystokinin.

Animals↗
PubMed1986

Intraarticular triamcinolone hexacetonide in the management of chronic arthritis in children.

The use of intraarticular triamcinolone hexacetonide in the management of persistent arthritis of the knee joint that is unresponsive to nonsteroidal anti-inflammatory drugs was prospectively evaluated in 40 children with chronic arthritis. Of 49 knees that were injected, 63.3% maintained complete resolution of effusion and other signs of inflammation at the 6-month followup. This favorable outcome correlated with a young age, a short disease duration, and a higher dose of triamcinolone hexacetonide. At the 12-month followup, 45% of the injected knees remained in remission.

Arthritis, Juvenile↗
PubMed1986

Diagnostic role of gastrointestinal hormones in patients with chronic pancreatitis.

Thirty-three patients with chronic pancreatitis were studied in an effort to correlate release of gastrointestinal hormones (GIH) with the degree of pancreatic insufficiency. A prospective examination was conducted of fat-stimulated release of pancreatic polypeptide (PP), cholecystokinin (CCK), and neurotensin. Seventy-two-hour fecal fat determination, endoscopic retrograde pancreatography (ERP), and the bentiromide-PABA test were used to correlate the clinical stage of disease. The ERP was classified as positive only if the changes were advanced (or "marked") according to the Cambridge Classification. Five patients were defined to have mild disease, 13 moderate, and 15 severe. Any patient with clinical evidence of chronic pancreatitis and ERP changes that were less than advanced and had normal fecal fat and bentiromide tests received a grade of mild. Patients with one abnormal test were graded moderate, and those with two or three abnormal results were graded severe. In the 33 patients, the integrated 60-minute release of pancreatic polypeptide (PP) was 37.4 +/- 6.1 ng-60 min/ml in those five patients with mild disease, 102.3 +/- 10.3 ng-60 min/ml in the 13 patients with moderate disease, and 7.6 +/- 2.2 ng-60 min/ml in the 15 patients with severe disease. The integrated 60-minute release of neurotensin was 3.8 +/- 0.4 ng-60 min/ml in mild disease, 2.0 +/- 0.3 ng-60 min/ml in moderate disease, and 0.2 +/- 0.1 ng-60 min/ml in severe disease. CCK release did not correlate with the severity of disease. Enhanced release of PP appeared to correlate well with moderate stage of chronic pancreatitis, and depressed PP release with severe disease. Stimulated levels of PP and neurotensin appear to be useful in the diagnosis and staging of chronic pancreatitis. It is concluded that measurement of fat-stimulated release of PP and neurotensin may be useful to assess severity of disease in patients with chronic pancreatitis.

Adult↗
PubMed1985

Proglumide, a gastrin receptor antagonist, inhibits growth of colon cancer and enhances survival in mice.

Some tumors are responsive to hormone manipulation. Some gastric and colonic adenocarcinomas from both humans and animals have specific gastrin receptors. A transplantable mouse colon adenocarcinoma cell line (MC-26) contains gastrin receptors; growth of MC-26 colon cancer in vivo is stimulated by pentagastrin (PG). The purpose of this study was to determine whether a gastrin-receptor antagonist, proglumide (PGL), would inhibit growth of MC-26 colon cancer and prolong survival in tumor-bearing mice. Subcutaneous tumors were induced by injecting single-cell suspensions of MC-26 cells into 50 mice divided into 10/group. In Experiment 1, all mice received 1 X 10(5) tumor cells and treatment groups were divided as follows: Group A received intraperitoneal (IP) saline (0.2 ml tid beginning on day 1); B, IP, PGL (250 mg/kg tid) from day of tumor cell inoculation; and C, IP PGL (250 mg/kg tid) from day 7 after tumor implantation. In Experiment 2, mice were inoculated with half the number of tumor cells. Group I mice received saline and Group II received PGL in the same manner starting on day 1. Tumors were measured and all mice were sacrificed on day 23. In Experiment 1, mean tumor area in Group B (PGL-treated) was significantly smaller than Group A on days 11, 14, 17, and 21. Tumors of Group C were significantly smaller than controls on day 21. Survival of PGL-treated mice was significantly prolonged. In Experiment 2, mean tumor area, mean tumor weight, and tumor DNA and RNA content were significantly less in the PGL-treated group than control. It was concluded that growth of a gastrin-responsive colon cancer was inhibited and host survival was enhanced by treatment with a gastrin-receptor antagonist. Hormone manipulation may be a useful treatment for gastrointestinal cancers.

Adenocarcinoma↗
PubMed1981

Primary subacute epiphyseal osteomyelitis.

In eight children with primary subacute osteomyelitis of a femoral or tibial epiphysis, the only complaints were pain and limp. Plain roentgenograms and tomograms showed a well defined lytic lesion in the epiphysis and no evidence of any connection to the metaphysis. Although the bone of the epiphysis was involved in every instance, and the lesion extended to the articular cartilage in most patients, the cartilage itself was not damaged. When the lesions were curetted, six were sterile on routine and anaerobic cultures and on culture for tuberculous and fungal organisms, and Staphylococcus was grown from the other two. In every case the curetted tissue had the characteristic histological appearence of osteomyelitis. All patients were treated with oxacillin and recovered completely. Postoperative roentgenograms showed complete healing with no evidence of damage to the physis or the joint after follow-up of two to eight years.

Acute Disease↗
PubMed1980

Legg-Calvé-Perthes disease: treatment and prognosis.

Our experience in the treatment of Legg-Perthes disease using non-containment, containment, and surgical treatment supports the concept that containment is a key factor in the treatment of Legg-Perthes disease. Patients without excessive lateral extrusion or other signs of "head at risk" and half or more of the femoral head involved probably can be treated for short periods of time in an abduction orthosis. If less than half the femoral head is involved but lateral extrusion is minimal, a period of traction to obtain range of motion and decrease the synovitis may be sufficient treatment. In the more severely involved heads that show the poor prognostic signs of excessive lateral extrusion, bed rest in addition to abduction may statistically offer the best chances for a good result. For patients with severe involvement and excessive lateral extrusion of the femoral head, intertrochanteric osteotomy gave us a better percentage of good results than treatment with abduction and weight bearing. Our intertrochanteric osteotomy series results were comparable to those in the Katz and Brotherton and McKibbin patients treated by abduction and nonweight bearing. Regardless of the method of treatment chosen for a specific patient, it is essential that a good range of motion be obtained and maintained throughout the course of treatment. If this is successfully done, regardless of other factors, the outcome should be satisfactory.

Age Factors↗