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Biomedical subjects

F Savage

Publications and source records attributed to F Savage.

17 recordsLinked to original sources
PubMed2000

Endothelin receptor expression in colorectal cancer.

The distribution of endothelin-A- and B- (ET(A), ET(B)) receptor subtypes was compared in colorectal cancer to that in normal colon and their expression in the colorectal cancer cell lines LIM1215. HT29, SKCO1, SKCO17 and LoVo was determined, using gross and high resolution autoradiography and quantified by densitometry. ET(A) and ET(B) binding sites were expressed by all the cell lines. There was significantly (p = 0.008) higher expression of ET(A)-receptors by cancers (205.95 dpm x 1000/mm2) compared normal colon (129.19 dpm x 1000/mm2). However, for ET(B)-receptors, this was reversed, with significantly (p = 0.008) higher expression of ET(B) binding in normal colon (207.00 dpm x 1000/mm2) than in tumours (122.35 dpm x 1000/mm2).

Autoradiography↗
PubMed2000

Stimulation of colorectal cancer cell line growth by ET-1 and its inhibition by ET(A) antagonists.

BACKGROUND: The vasoactive peptide endothelin 1 (ET-1) acts via two receptors, endothelin receptors A (ET(A)) and B (ET(B)). ET-1 is overexpressed by human cancers in vivo and in vitro and may be mitogenic for cancer cells. METHOD: To elucidate if ET-1 is a growth regulator the following were investigated in human colorectal cancer cell lines (LIM1215 and HT29): ET-1 production by ELISA; ET receptor expression using radioligand autoradiographic techniques; and responsiveness to ET-1, and to ET(A) and ET(B) antagonism by growth measurements. RESULTS: ET-1 was produced by LIM1215 and HT29 cells (21.3 and 41.7 fmol/ml/10(6) cells (24 hours); 22.6 and 71.7 fmol/ml/10(6) cells (48 hours), respectively). ET(A) and ET(B) receptors were expressed by both cell lines. Addition of ET-1 resulted in a dose dependent increase in cell numbers which was significant at 10(-8)-10(-9) M for LIM1215, with the greatest increase at 10(-8) M (32.7% and 28.4% increase above controls at 48 hours and 72 hours; p<0.05) and at 10(-8)-10(-9) M for HT29, with the greatest increase at 10(-9) M (13.4% and 15.7% increase above controls at 48 hours and 72 hours; p<0.05). ET(A) antagonists BQ123 and BQ610, but not the ET(B) antagonist BQ788, inhibited ET-1 induced proliferation of both LIM1215 and HT29 (p<0.05). CONCLUSION: ET-1 can stimulate the proliferation of colorectal cancer cell lines via the ET(A), but not the ET(B), receptor.

Cell Division↗
PubMed1999

Counselling on breastfeeding: assessing knowledge and skills.

Reported are the results of a randomized controlled trial to assess the effectiveness of the WHO/UNICEF 40-hour course "Breastfeeding counselling: a training course". The course was conducted in a maternity hospital which provides care to a low-income population in a metropolitan area in São Paulo, Brazil. Health workers from 60 health units were randomly assigned to be either participants (20) or controls (40), and their breastfeeding knowledge and skills were assessed before and immediately after the course, as well as 3 months later. Immediately after the course the participants' knowledge of breastfeeding had increased significantly compared to controls. Both their clinical and counselling skills also improved significantly. When assessed 3 months later, the scores remained high with only a small decrease. The implementation of the course was also evaluated. The methods used were participatory observation, key interviews and focus group discussion. In the 33 sessions of the course, the average score was 8.43 out of 10. Scores were highest for content and methodology of the theory sessions, and lowest for "use of time", "clinical management of lactation", and "discussion of clinical practice". "Breastfeeding counselling: a training course" therefore effectively increases health workers' knowledge and their clinical and counselling skills for the support of breastfeeding. The course can be conducted adequately using the material and methodology proposed, but could be more satisfactory if the time allocated to exercises and clinical practice sessions were increased.

Brazil↗
PubMed1997

Effect of methylprednisolone on the ulceration, matrix metalloproteinase distribution and eicosanoid production in a model of colitis in the rabbit.

This study has examined the response of a rabbit model of inflammatory bowel disease to methylprednisolone. Colitis was induced in the colon of rabbits with 40 mg trinitrobenzenesulphonic acid in 25% ethanol (TNBS). The effect of methylprednisolone (0.5 mg/kg/day) on the development of colitis was determined at one week, by examining the colon's macroscopic and microscopic appearance, the distribution of matrix metalloproteinases (MMPs) and by measuring eicosanoid production. Although there was no difference in the area of ulcerated colonic tissue in the treated and untreated TNBS animals, the increase in polymorphonuclear leucocytes was significantly reduced in TNBS rabbits given methylprednisolone. The only difference in the distribution of MMPs was a reduction in the number of polymorphonuclear leucocytes containing gelatinase B. The release of immunoreactive PGE2 and LTB4, but not 6-keto PGF1 alpha, was increased in the TNBS animals and was unchanged by methylprednisolone. These results show that methylprednisolone does not modify the injury produced by TNBS in this model despite reducing the infiltration of polymorphonuclear leucocytes. Hence it suggests that these cells do not contribute to the injury observed, are not the source of the eicosanoids and that gelatinase B is not required in the healing process in this model.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

The characterization of a rabbit model of inflammatory bowel disease.

The absence of a simple, clinically relevant, animal model of inflammatory bowel disease (IBD) hampers research into this disease. In this study, colitis was induced in rabbits by intracolonic installation of 2,4,6-trinitrobenzene sulphonic acid (TNB) in 25% ethanol. Rabbits were killed from zero hours to 6 weeks and their colons examined. Rabbits were examined by endoscopy at weekly intervals. A single dose of TNB in ethanol produced dose dependent inflammation and ulceration, which at its optimum (40 mg) resulted in cobblestoning, strictures, and bowel wall thickening. The damage score at endoscopy was consistent with the score on macroscopic examination of the colon. Histopathological features of inflammation and ulceration observed in all animals that received 40 mg TNB included crypt abscesses, ulceration, crypt architectural distortion and, occasionally, granulomas and pseudopolyps. These changes, which are similar to those observed in IBD, persisted for 6 weeks. No lasting abnormalities were observed in control animals treated with TNB in saline, with ethanol alone, or with saline only. Histopathological similarity and the prolonged duration of inflammation, compared to other models, make this a suitable model for investigating inflammation in the colon. Furthermore, the model is accessible to endoscopy which adds to its value in experimental studies.

Animals↗
PubMed1994

Detection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer.

PURPOSE: This study was designed to select the best monoclonal antibody to stain malignant cells in peritoneal wash fluid, and to investigate the incidence of free malignant cells in preresection and postresection colorectal cancer peritoneal washings using a combination of conventional cytology and immunocytochemistry. METHODS: Peritoneal washings were taken from 35 consecutive patients undergoing colorectal cancer resection. RESULTS: Malignant cells were isolated on a density gradient and identified by conventional cytology and an indirect immunoperoxidase stain. Malignant cells were identified in peritoneal washings from 15 patients (preresection only n = 3, postresection only n = 4, both n = 8). The origin of free malignant peritoneal cells in 11 preresection-positive washings must be the serosa. The origin of these cells in the four postresection-positive patients is uncertain: serosal and luminal spillage were considered unlikely and no circulating cells were found in the mesenteric vessels near the tumor. CONCLUSION: Tumor cells may have leaked out from lymphatics cut during the dissection.

Aged↗
PubMed1993

Detection and enumeration of circulating tumour cells in colorectal cancer.

Immunocytochemistry was used in parallel with conventional cytology to detect circulating malignant epithelial cells in 42 patients undergoing resection for colorectal cancer. Preoperative peripheral and peroperative mesenteric venous blood samples were taken. Tumour cells were isolated on a density gradient and cytospins prepared. Slides were stained by conventional cytology (May-Grünwald-Giemsa) and by an indirect immunoperoxidase technique with the anticytokeratin antibody KG8.13. Using conventional cytology, definite morphological evidence of malignancy was observed in three patients and suspicious features in a further seven. Immunocytochemistry confirmed these findings in all three of the malignant but in only one of the suspicious cases. Counts of immunostained cytospins showed the concentration of tumour cells in blood samples from these four patients to be in the range 0-954 cells/ml. This study supports the use of immunological markers to detect and enumerate malignant cells. This method provides a powerful tool to investigate one aspect of the metastatic process.

Adult↗
PubMed1992

The chemoattractant activity of the vitreous to human scleral fibroblasts following retinal detachment and proliferative vitreoretinopathy.

The results are presented of a migration assay of scleral fibroblasts to 25% diluted vitreous samples from 27 patients with complex retinal detachments divided into three groups: group 1, no proliferative vitreoretinopathy (PVR); group 2, early PVR; and group 3, advanced PVR. There was a statistically significantly greater migration with vitreous samples from group 3 than with group 1 (p less than 0.0001) but no significant correlation for migration with the age of patients, duration of retinal detachment, or number of retinal procedures undertaken. Analysis of vitreous by gel electrophoresis showed that cellular migration was proportional to the number of peptide bands. Vitreous fibronectin levels were measured and there was a positive correlation between fibronectin in the vitreous samples and the migration of fibroblasts to the vitreous (r = 0.68, p less than 0.004).

Adult↗
PubMed1990

The need for action.

Nutrition workers speculated about why poor mothers should decide to bottle feed, when their community in the past had apparently always breastfed effortlessly and successfully. Surveys cross-tabulated feeding methods against socioeconomic variables, but it was difficult to make use of the results. Few thought that there was anything we needed to learn about HOW to make breastfeeding succeed. There was also a tacit assumption that if you had the resources--for example if you were yourself an employed health worker--you could bottle feed safely, so there was no need to worry.

Bottle Feeding↗
PubMed1987

Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence?

An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas.

Animals↗