Pentoxifylline in the treatment of experimental peritonitis in rats.

The objective of this study was to determine the effect of pentoxifylline on the clinical and pathologic course of experimentally induced peritonitis in rats. This drug is a methyxanthine derivative that has vasodilating properties and may decrease platelet aggregation. Peritonitis was induced in 40 Wistar rats by creating a closed ileal loop 4 cm long 5 cm from the ileocecal valve. The animals were divided into two groups of 20 animals each. The first group served as controls, while each animal of the second group received 17 mg/kg/day of pentoxifylline intramuscularly from the day of operation until 30 days postoperatively. The survival rate was significantly increased in the group receiving pentoxifylline and adhesion or abscess formation was considerably reduced. We concluded that the administration of pentoxifylline prolongs significantly the survival of animals with experimental peritonitis and reduces the development of adhesions and abscesses in the peritoneal cavity. This beneficial effect may be attributed to decreased fibrinogen deposits and increased fibrinolytic activity within the peritoneal cavity, thus rendering the bacteria more susceptible to cellular and noncellular clearing mechanisms.

Traumatic hemopericardium and chronic constrictive pericarditis.

Chronic constrictive pericarditis following traumatic hemopericardium has been reported in recent years, but it has not been reproduced experimentally in dogs. The present study attempted to produce posttraumatic constrictive pericarditis in 34 experimental animals. Hemopericardium by means of trauma to the epicardium or pericardium was produced by a sharp instrument or by the injection of autologous blood inside the pericardial sac. All animals were killed at intervals between 3 and 31 months. The animals in which hemopericardium was induced by injecting blood into the pericardial cavity showed no changes. The hemopericardium was completely resolved without noticeable residual trace. Animals having hemopericardium as a result of trauma evidenced a well-developed constrictive pericarditis that was documented clinically, hemodynamically, and histologically. These experimental findings indicate that chronic constrictive pericarditis may well be due to traumatic hemopericardium rather than to specific infection.

K-ras oncogene mutations in neoplasias of kidney transplanted patients: preliminary results with a new technique.

K-ras oncogene activations by point mutations are frequent in many forms of human cancers but there is a special category of cancers occurring in immunosuppressed patients after kidney transplantation in which the frequency of K-ras oncogene activation has not been fully studied. We used a new sensitive and easy method for the detection of this mutation, and in 8 DNA samples studied from various neoplasias of 8 patients after kidney transplantation, we found 4 mutations. Our preliminary results indicate that the activation of K-ras oncogene at codon 12, is a common event among the kidney transplanted patients who present a neoplasia, even in the least aggressive forms of the disease, contrary to the sporadic cases.

In vitro effects of heparin on SW480 tumor cell-matrix interaction.

We investigated the in vitro effects of heparin on the growth and interaction of SW480 colon adenocarcinoma cells with the extracellular matrix proteins laminin, fibronectin and collagen IV. Cell adhesion assays were performed in wells precoated with the proteins mentioned. Tumor cell migration and invasiveness were assayed in Transwell cell culture chambers. SW480 cell adhesion to the matrix proteins and migration to laminin/fibronectin precoated filters were inhibited by heparin in a dose- dependent manner, whereas cell growth and invasion through collagen IV gel were not affected. Our results suggest that heparin influences the SW480 cell-matrix interaction in vitro and inhibits crucial steps of the metastatic process in an experimental model.

Chromosomal markers associated with metastasis in two colon cancer cell lines established from the same patient.

The purpose of this study was to identify specific chromosomal abnormalities that might be involved in colon cancer metastasis. For this reason, we performed extensive karyotypic analysis on two colon cancer cell lines (SW480 and SW620) established from two surgical biopsies taken at different intervals and representing different stages of the disease from the same patient. Despite the karyotypic heterogeneity, several marker chromosomes were shared between the two cell lines, indicating their common origin. We hypothesized that these shared chromosomal aberrations might be critical for the continuous growth of the tumor cells and, therefore, were retained through progression of the disease. Duplication of 16q and new or additional structural chromosomal abnormalities involving breakpoints 3p21, 8p11, 10q25, 13q14, 14q11 and 15q15 were observed as the characteristic anomalies only in the SW620 cell line. As SW620 was established from the abdominal metastatic lesion of the patient, we postulated that the acquisition of these new markers in the progression steps of the primary tumor might represent "hot-spots" that possibly contain genes crucial for metastatic potential in colon cancer.

Prediction of malignancy in solitary thyroid nodules in a country with endemic goiter.

From January 1962 through October 1975, 455 patients with single thyroid nodules were operated on at King Paul Hospital. Malignancy was proved in forty-three patients. The overall incidence of carcinoma was 9.5 per cent. A higher incidence of cancer was found in patients less than ten years of age (40 per cent), between eleven and twenty years of age (20 per cent), and more than sixty-one years of age (17.4 per cent). Malignant nodules were more frequent in males (17.5 per cent) than in females (8.3 per cent). Radioactive iodine scanning does not distinguish benign from malignant nodule. Solitary thyroid nodules require operative excision supplemented with replacement therapy.

Effect of aprotinin on fibrinopurulent peritonitis in rats.

The effect of aprotinin on the clinical and pathologic course of experimentally induced peritonitis in the rat was studied. Peritonitis was induced in 40 rats by creating a closed ileal loop 4 cm long 5 cm from the ileocecal valve. The rats were divided into two groups of 20 rats each. Group 1 served as a control group, whereas each animal in Group 2 received a bolus dose of aprotinin (10 ml) intraperitoneally immediately after closing the laparotomy. In the aprotinin-treated group, survival was drastically increased (p less than 0.01) and formation of adhesions and abscesses was considerably reduced. The results of peritoneal cultures showed a decreased incidence of Escherichia coli and Clostridia in the aprotinin-treated group. We conclude that the administration of aprotinin significantly prolongs the survival time of animals with peritonitis and reduces the development of adhesions and abscesses in the peritoneal cavity. This beneficial effect can be attributed to decreased fibrinogen deposits within the peritoneal cavity and the stabilization of the organism after bacterial shock. Thus, bacteria were more susceptible to cellular and noncellular clearing mechanisms.

Scanning of the adrenals in Cushing's syndrome.

131I-19-iodocholesterol adrenal scans were obtained in seven patients with Cushing's syndrome. Characteristic imaging patterns were seen in three patients with bilateral adrenal hyperplasia with symmetrical uptake of the isotope. Two patients with adrenocortical adenoma and one patient with a well-differentiated adrenocortical carcinoma showed intense activity in one adrenal gland and absent activity in the contralateral gland. In one patient with adrenal nodular hyperplasia asymmetrical uptake was found with increased activity in the right adrenal gland where a larger adenomatous nodule was found at histologic examination. Adrenal imaging with radioactive cholesterol is a useful noninvasive technique for the diagnosis and treatment of Cushing's syndrome.

Low-dose heparin treatment does not inhibit SW480 human colon cancer growth and metastasis in vivo.

We investigated heparin effects on the biological behavior of SW480 human colon adenocarcinoma cells in vivo. Tumor growth, pathological features, metastatic potential and karyotype, were studied after the twelve week low-dose heparin treatment of nude mice subcutaneously injected with SW480 cells. A non statistically significant increase in tumor growth was observed (0.05 < p < 0.1, compared to the control group). No differences in tumor histology and karyotype were detected. Two of the six heparin-treated animals exhibited an increase in tumor vascularization. Metastasis to the lungs and liver was not inhibited. These results do not support the role of heparin in the prevention of the in vivo growth and metastasis of SW 480 colon cancer cells.

Thyroid nodules and thyroid carcinoma.

Seventy carcinomas of the thyroid gland were found in 1300 thyroidectomies for an incidence of 5.4%. The incidence of malignancy in single nodules was 9.7% and in multinodular nontoxic goiter 4.3%. The risk of cancer was higher (14.2%) in males than in females (4.3%). The highest incidence of cancer was found in children under the age of 10 (40%). Radioactive iodine scintiscanning was of limited help in differentiating benign from malignant nodules. Early surgery is advised for all patients with single thyroid nodules and all thyroid nodules in children should be excised.

The effect of heparin upon fibrinopurulent peritonitis in rats.

The effect of heparin upon the clinical and pathologic course of experimentally induced peritonitis in the rat was studied. Peritonitis was induced in 40 rats by creating a closed ileal loop 4 centimeters long at a distance of 5 centimeters from the ileocecal valve. The rats were divided into two groups of 20 each. The first group served as the control group while each rat of the second group received 30 units of heparin subcutaneously per day postoperatively. Survival was drastically increased in the group receiving heparin (p = 0.001). Adhesion or abscess formation was considerably reduced in this group. The results of peritoneal cultures showed decreased incidence of Escherichia coli and clostridia in the heparin-treated group. Blood cultures also showed decreased incidence of both aerobes and anaerobes in the treated group. It is concluded from this that the administration of heparin significantly prolongs survival time of animals with peritonitis and reduces the development of adhesions and abscesses in the peritoneal cavity. This beneficial effect could be attributed to decreased fibrinogen deposits within the peritoneal cavity, thus rendering the bacteria more susceptible to cellular and noncellular clearing mechanisms.

Creatine kinase (CK-BB) determination in cerebrospinal fluid after acute experimental head injury.

Early changes of the activity of enzymes such as creatine kinase in the cerebrospinal fluid (CSF) or serum are often investigated after head injuries to assess the extent of brain damage and establish a reliable prognosis. The purpose of the present study was to determine levels of creatine kinase isoenzyme CK-BB in the CSF of rats after experimental head injuries. External head injuries of different severity were inflicted on rats, immediately after which CSF was collected for isoenzyme activity determination. It was found that the levels of CK-BB were significantly elevated immediately after the head injury and that the greater the degree of external cranial injury inflicted, the higher the isoenzyme activity was. The results seem to provide evidence that CK-BB activity is an early indicator of brain damage and that its level may reflect the extent of cerebral damage involved.