Atrial natriuretic peptide levels during and after acute cardiac tamponade in dogs.

The ability of the atrial wall to secrete atrial natriuretic peptide was studied in eight dogs during 2 h of cardiac tamponade and for 2 h after decompression of the pericardium. Cardiac tamponade was induced by instillation of 5% dextrose in water into the pericardial cavity until aortic systolic pressure was reduced by 30% to 35%. Heart rate, cardiac output and atrial, pericardial and aortic pressures were measured at 60 and 120 min of tamponade and at 5, 30, 60, 90 and 120 min after decompression. Blood samples were withdrawn at the same time for the determination of atrial natriuretic peptide and aldosterone levels. Aortic pressure decreased significantly during tamponade and increased after decompression to near control levels. Right and left atrial pressures as well as intrapericardial pressure increased significantly during tamponade and returned to control levels after decompression. The effective transmural pressure, which was reduced during tamponade, was increased significantly at 5 min after decompression. Cardiac output was significantly reduced during tamponade and returned to pretamponade levels after decompression. Over the total experimental period, no significant changes in the levels of atrial natriuretic peptide were observed, whereas aldosterone increased significantly. It is concluded that the increased atrial pressure observed during cardiac tamponade did not stimulate the secretion of atrial natriuretic peptide. Furthermore, atrial distension observed immediately after decompression was not sufficient or of long enough duration to induce measurable increases in atrial natriuretic peptide levels. Finally, the secondary hyperaldosteronism did not activate atrial natriuretic peptide secretion either during cardiac tamponade or after decompression.

The use of isobutylcyanoacrylate as a tissue adhesive in abdominal surgery.

BACKGROUND: The use of cyanoacrylate substances as tissue adhesives is of valuable aid in surgery, especially in cases of injuries of the intraabdominal organs, where the haemorrhage is very difficult to control. MATERIALS AND METHODS: We investigated the efficiency of isobutyl-2-cyanoacrylate as a tissue adhesive in the haemostasis and adhesion of different types of wounds in solid and hollow organs. Forty-six dogs underwent single-organ (26 dogs) and combined-organ (20 dogs) procedures; cuneiform excisions of the liver and the spleen, as well as incisions of the small intestine were carried out. The wound surfaces were coated with isobutyl-2-cyanoacrylate and approximated. RESULTS: The majority (91.3%) of the surgical operations were uncomplicated, in which a very good macroscopical and histological result was achieved. Histological examination of the surgical injuries, performed 4 months later, confirmed complete wound healing. CONCLUSION: Isobutyl-2-cyanoacrylate proved to be a very effective tissue adhesive for both solid and hollow organs, even for high risk surgical operations.

Evidence for the existence of non-esterified cholesterol carried by albumin in rat serum.

Isolation of non-esterified [14C]cholesterol bound to albumin from rat serum, 8 days after i.p. injection of [14C]cholesterol, was achieved by affinity chromatography, using Cibacron blue F3GA bound to Sepharose 4B and by Sephadex G-150 column chromatography. Both methods permit isolation of large quantities of cholesterol-loaded albumin, free of globulins and lipoproteins. The isolated albumin-cholesterol fraction was estimated to be 4.6 mg/100 ml serum, which represents approx. the 24% of the non-esterified cholesterol present in the rat serum. Albumin-cholesterol, cholesterol glucoside, cholesterol hemisuccinate and hydroxylated derivatives of cholesterol produced a biphasic curve of changes in synaptosomal plasma membranes (SPM)-bound (Na+ + K+)-stimulated ATPase activity. Low concentrations of the ligand progressively increased the enzyme activity, while increasing the ligand concentration above that which maximally stimulated the enzyme activity, produced a progressive inhibition. Lipoproteins did not have any effect on the enzyme activity. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene-labeled SPM, increased in albumin-cholesterol derivatives-treated SPM, which is consistent with a general decrease in membrane bilayer fluidity. The results provide evidence that the 'albumin-cholesterol' fraction of the serum may directly affect the cell membrane-bound enzyme activity.

Prognosis of mammary carcinoma in young women.

One hundred and sixty-two women with carcinoma of the breast, age 40 years or younger, were treated from 1950 to 1969. Mammary cancer is not uncommon in this age group. The 5 year survival rate among our operable patients was about 50 percent. The 5 year survival rate among patients 20 to 35 years of age was slightly higher than that in patients 36 to 40 years old. In stage B and more advanced breast cancer in young women, the outlook was poorer than in women 41 years and older. When axillary involvement is present during gestation or in the immediate postpartum period, the prognosis is especially poor. Young women have an unusually high proportion (35 percent) of low-grade, infrequently metastasizing tumors, such as medullary, intraductal, papillary, and lobular carcinomas. The presence of cancer in the axillary nodes at operation is the most important factor affecting prognosis in mammary cancer. From this study we can see no reason to consider carcinoma of the breast in young women a more lethal disease than that seen in their older counterparts.

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.

Cell senescence and a mechanism of clonal evolution leading to continuous cell proliferation, loss of heterozygosity, and tumor heterogeneity: studies on two immortal colon cancer cell lines.

Extensive karyotypic analysis was performed on early and late passages of two continuous human cell lines, SW480 and SW620, that were derived from the same colon cancer patient. We cultivated these two cell lines in vitro for a period of 24 months and periodically examined their chromosome constitution. SW480 cells, from passage 138, were injected subcutaneously into 20 nude mice. The tumors that grew in nude mice were then cultivated in vitro for several passages to compare histopathologic findings and tumor growth patterns with clonal chromosomal profiles. Despite some karyotypic diversity, the two cell lines exhibited common marker chromosomes and followed similar patterns of evolution. During subsequent passages, acquisition of new chromosomal abnormalities gave rise to sidelines with a near-diploid genome that frequently underwent endoreduplication. Genomic instability seemed to play an important role in the emergence, growth, and subsequent elimination of the heterogenous sidelines by selection, clonal expansion, and cell death by senescence. Despite continuous growth, both the cell lines occasionally showed telomeric associations and random dicentric and multicentric formations. These lesions were considered evidence of cell senescence and were related to the disappearance of particular sidelines through evolution. Successful evolutionary steps were characterized by elimination of pre-existing marker chromosomes that were subsequently replaced in the karyotype by their cytologically intact homologous chromosomes possibly after selective endoreduplication. Frequent loss of heterozygosity for the chromosomes taking part in this process is postulated. We suggest that one of the mechanisms by which cancer cells bypass senescence may be related to their potential for continuous clonal diversification.

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.

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.

The effect of various types of splenectomy on the development of B-16 melanoma in mice.

260 CB57BL/J6 mice were used in an experimental protocol designed to investigate the effects of 4 different varieties of splenectomy on the growth rate of subcutaneously implanted GB-16 melanoma. In addition, the mean and absolute survival of the mice, the histopathology of the tumour and the effects of the same procedures on the immunological status of the tumour-bearing animals as assessed by serum IgG levels and immunoelectrophoresis were determined. The effects of the timing of the splenectomy and the removal of the primary tumour after splenectomy on the above parameters were also annotated. The following were found: First, splenectomy performed 1 week after B-16 melanoma tumour implantation in mice i.e. in the early period of oncogenesis, lengthened the survival of the grafted experiments, delayed tumour growth, reduced the "activity" of the tumour and caused pseudoencapsulation of the tumour by fibrous tissue. It increased, but not by a statistically significant degree (p > 0.05), the circulating levels of the IgG immunoglobulin. Second, splenectomy performed 4 weeks prior to grafting of the same tumour did not affect the circulating IgG levels, nor did it prolong survival; however, it reduced the rate of tumour growth and pseudoencapsulation of the tumour was observed. Third, splenectomy at the early stages of oncogenesis in combination with surgical removal of the primary tumour increased absolute and mean survival, delayed the tumour growth rate, increased the time to relapse and reduced the "activity" of the pseudocapsulated tumour.

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.

Surgical management of diseases of the adolescent female breast: a clinicopathologic study.

Sixty-three patients, ages 10 to 20 years with diseases of the breast were operated on during a 10 year period. A variety of pathologic entities were found. The most common were diagnoses fibroadenoma, cystic disease, and cellulitis with abscess formation. Malignancy was found in three patients: lobular carcinoma in situ in one, angiosarcoma in the second, and lymphosarcoma in the third.

Serum zinc levels and urinary zinc excretion in patients with bronchogenic carcinoma. Effects of tumor resection.

Low serum zinc levels and high urinary zinc excretion were found in 25 patients with bronchogenic carcinoma. Twenty of them underwent successful removal of the tumor by lobectomy or pneumonectomy; in the other 5 patients surgical exploration revealed unresectable pulmonary lesions. The latter had significantly lower serum zinc and higher urinary zinc levels than the patients in whom surgical removal of the tumor could be performed. Tumor resection was followed by restoration of serum and urinary zinc to normal. In contrast, in the inoperable patients a further decrease in serum zinc and no significant change in urinary zinc excretion were noted 15 days after thoracic exploration. In both patient groups a significant negative correlation existed between preoperatively obtained values of serum and urinary zinc. Hypozincemia in patients with bronchogenic carcinoma may result from an increase in urinary zinc losses, probably related to a decrease in zinc binding to plasma proteins. Determination of serum and urinary zinc may be useful in evaluating the prognosis of primary lung 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.

Cushing's syndrome. Analysis of 18 cases.

Eighteen patients with Cushing's syndrome were analyzed retrospectively. Eleven patients had diffuse or adenomatous hyperplasia, 5 an adenoma and 3 a carcinoma. Iodocholesterol scanning provides considerable help in localization of the disease. Surgical treatment, while curative for benign cases, affects only slightly the course of malignant disease.

Hepatography.

A method of hepatography in dogs is described in which contrast medium is infused via the external jugular and superior and inferior venae cavae and hepatic veins. Hepatograms taken by infusing different contrast media in the normal liver and in the liver subjected to parenchymatous damage are also analyzed in detail.

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.

Effect of impaired vasa vasorum flow on the structure and mechanics of the thoracic aorta: implications for the pathogenesis of aortic dissection.

OBJECTIVE: To investigate the alterations of structure and mechanical properties of the aortic wall, resulting from impairment of vasa vasorum flow. METHODS: Eight healthy Landrace pigs were subjected to interruption of vasa vasorum flow to the upper segment of their descending thoracic aorta. Under sterile conditions, the periaortic tissue was excised and the contiguous intercostal arteries were ligated. Ten sham-operated pigs were used as controls. Fifteen days postoperatively, the animals were sacrificed and their upper descending thoracic aortas were removed. Histology, and collagen and elastin content determination by image analysis technique were performed. Mechanical analysis of aortic strips was carried out with a uniaxial tension device and stress-strain curves were obtained. RESULTS: In contrast to normal aortic walls of the control group, histology of the avascular aortas revealed severe ischemic necrosis of the outer media along with abnormal straightening of the elastin and collagen fibers, without significant collagen and elastin content changes. The borderline between the outer ischemic and inner non-ischemic media was sharp, and an outset of dissection was observed at this point. Mechanical analysis showed that at the same level of strain, the ischemic aorta was significantly stiffer at both low (P=0.03) and high strains (P=0. 003). CONCLUSIONS: Impairment of blood supply to the thoracic aorta leads to abnormal morphology of elastin and collagen fibers of the outer media, resulting in increased aortic stiffness under a wide range of stresses. In the clinical setting, decreased vasa vasorum flow, reportedly occurring in arterial hypertension, may increase the stiffness of the outer media of the thoracic aorta and produce interlaminar shear stresses, contributing to the development of aortic dissection.

Functioning metastatic parathyroid carcinoma.

A case of 53-year-old woman with a parathyroid adenoma and a parathyroid carcinoma with functioning metastases to the lungs, mediastinum and pleura is reported. The administration of inorganic phosphate solution failed to control hypercalcemia. The therapeutic methods available to deal with metastases are discussed.

Total esophagectomy without thoracotomy for cancer.

Total extrathoracic esophagectomy was performed in 16 patients with neoplasms arising in the thoracic and cervical esophagus and the hypopharynx. The procedure was combined with posterior mediastinal gastric pull up in all but two patients who had previous gastrectomy and were managed with colon interposition. Splenectomy was avoided in all patients. Although, in the presence of TNM stage III and IV disease, the procedure was performed mostly for palliation, it resulted in only two deaths and it led to rapid initiation of oral alimentation. Extrathoracic esophagectomy constitutes a safe and simple alternative to other ablative or palliative procedures in the treatment of hypopharyngeal and esophageal malignancies.