Effect of retained components of excised tumor upon coexisting tumor.

Effects of locally treated and retained tumor tissue on the growth of a tumor at another site were investigated using Lewis rats bearing syngeneic fibrosarcoma. When an established tumor had completely regressed upon repeated intratumoral injections of L-phenylalanine mustard (PhM), the growth of secondarily transplanted tumor cells was inhibited. However, early excision of the PhM-injected tumor prevented the development of this effect. To study this effect directly, we excised one of the two established tumors in each thigh, and reinoculated into the excision wound either freeze-lysed 1 X 10(8) tumor cells (TC) or lysate chemically modified with PhM (PTC). We found that TC inoculation into the excision wound in 7 rats inhibited the growth of the remaining tumor and extended survival time (mean +/- SE, 27 +/- 1 days). With inoculation of PTC into the excision wound, the remaining tumor regressed and survival was significantly prolonged (32 +/- 2 days). In contrast, 7 untreated rats, each bearing two tumors, had a mean survival time of 22 +/- 0.1 days. Excision of one tumor (6 rats) did not affect the growth of the remaining tumor or survival time (23 +/- 1 days). We employed PhM to modify the immunogenicity of TC. However, if PhM dissociates from PTC, its cytotoxic effect may directly inhibit growth of the distant tumor. To examine this possibility, we divided 30 rats who had excision of one tumor, into three groups of 10 10.(ABSTRACT TRUNCATED AT 250 WORDS)

Secondary lesions of penetrating cardiac injuries: a frequent complication.

Between July 1962 and July 1978, 29 patients )23 male and 6 female) from 17 to 48 years of age were followed from two weeks to 15 years after penetrating cardiac injuries involving right ventricle (12), right atrium (6), left ventricle (8), left atrium (2), and pulmonary conus (1). Thoracotomies were performed on all patients either in the emergency room during resuscitation or in the operating room. Repair of the injuries were carried out. All patients were followed for presence of residual cardiac damage. To our surprise, secondary complications were noted in 15 of the 29 patients as follows: Coronary damage (3), pseudoanuerysm (2), bullet embolus (1), VSD (4), recurrent pericarditis (1), mitral valve injury (2), aorta caval (1), and aorto pulmonary fistula (1). Between July 1962 and July 1974, only symptomatic patients with subjective and objective findings had detailed cardiac evaluations. Eight of 20 patients were found to have secondary cardiac complications. Since July 1974, seven of nine patients underwent a posttraumatic cardiac evaluation. Six of the seven patients were found to have significant cardiac lesions which were unrecognized at the time of initial operation. The incidence of posttraumatic remediable cardiac lesions is probably higher than previously suspected. An aggressive, detailed postoperative evaluation is recommended for all patients with penetrating cardiac injuries.

Effect of nutritional status and 5-fluorouracil on protein synthesis in parenterally alimented LEW/Mai rats.

LEW/Mal rats bearing transplantable adenocarcinomas were maintained parenterally for 4 days on 1) a regimen adequate in amino acids and glucose and 2) severely hypocaloric glucose. Rats from both groups were given 17.5 mg 5-fluorouracil (FUra)/kg/day as a continuous infusion for 3 days. Cumulative nitrogen balance, fractional tissue protein synthesis rates, and liver and muscle distribution of FUra and its metabolites were determined. Results were compared to those found with a series of control rats that were not treated with FUra. No changes attributable to FUra were found in the starved rats (1.25 g glucose/day). In the fed rats (15 g glucose plus 2.5 g amino acids/day), FUra decreased the liver and diaphragm fractional protein synthesis rates and the nitrogen retention.

Relative rates of tumor, normal gut, liver, and fibrinogen protein synthesis in man.

Fractional protein synthesis rates of tumor, normal intestinal tissue, liver, and fibrinogen were measured in a series of patients with gastrointestinal malignancies. Protein synthesis rates were measured by the continuous infusion of 95+% [15N]glycine. Twelve to eighteen hours prior to the clinically indicated surgical excision of the tumor, 1-2 g of 95+% [15N]glycine was infused at a constant rate into each subject. During the surgical procedure, 0.05-2 g of tumor, normal intestinal tissue, liver, and 30 ml of venous blood were obtained. Protein synthesis rates were estimated from the ratio of 15N incorporated into tissue protein to the 15N enrichment of the tissue-free amino acid pool. The major findings were: i) the 15N enrichment of the tissue-free amino acids in malignant tissue was greater than and proportional to that in the corresponding normal tissue (P less than 0.02); ii) tumor protein synthesis rates were greater and proportional to the corresponding intestinal tissue rates (P less than 0.05); iii) the fibrinogen synthesis rate was greater than the liver protein synthesis rate (P less than 0.01), but there was no correlation between them.

Tumor-caused changes in host protein synthesis under different dietary situations.

The effect of the AC33 tumor on protein synthesis in Lewis-Wistar rats was investigated under four different dietary regimens. The four diets used were: (a) 1.25 g amino acids plus 12.5 g glucose per day, (b) 1.25 g amino acids, (c) 1.25 g glucose per day, and (d) 12.5 g glucose per day. The rats were maintained on these four diets for 4 days. On the 5th day, 65 to 75 mg 99.2% [15N] glycine were added to the infusate and infused at a constant rate for the next 18 hr. The rats were then sacrificed and the liver, lung, heart, kidney, anterior tibialis muscle, and tumor were rapidly removed and frozen in liquid nitrogen. The rate of protein synthesis for these tissues was calculated from the ratio of 15N in the tissue protein to that in the tissue intracellular fluid. The protein synthesis rates were compared with the values found for a series of nontumor control rats fed the same diets. Relative to the control rats, muscle protein synthesis decreased on Diet 1, and liver protein synthesis increased with the three deficient diets.

The contribution of anticoagulants to platelet dysfunction with extracorporeal circulation.

This investigations evaluates the effects of anticoagulants on platelet function. Fresh human blood from 40 nonmedicated volunteers was anticoagulated with 4.3 units per milliliter heparin and/or acid-citrate-dextrose (ACD) solution 1:9. Retention of platelets from whole blood on glass beads was performed by the method of Bowie. Platelet retention of heparinized blood averaged 88.1 +/- S.E. 1.5 per cent; ACD platelets averaged 24.6 +/- S.E. 2.8 per cent. Platelet retention with citrate-phosphate-dextrose (CPD) and ethylenediaminetetraacetic acid (EDTA) yielded 26.0 +/- S.E. 3.9 per cent and 19.1 +/- S.E. 7.5 respectively. The addition of ACD to heparinized blood decreased platelet retention (19.7 +/- S.E. 3.1 per cent). The addition of heparin to ACD or CPD blood did not alter the original decreased retention. Calcium added, even in excess, to blood containing heparin and ACD did not reverse the depressed retention (29.3 +/- S.E. 4.6 per cent). The substitution of CPD gave similar results. With mixtures of separately collected ACD and heparininzed blood, depression of platelet retention was directly proportional to the amount of ACD blood present. Altering the pH of the ACD blood did not affect its depressed retention of platelets. Neutralizing heparinized blood 50 per cent with protamine or Polybrene also significantly depressed platelet retention 34.6 +/- S.E. 5.8 per cent and 35.5 +/- S.E. 4.0 per cent, respectively. Neither protamine nor Polybrene had any effect upon ACD blood. These data indicate that anticoagulants may play a significant role in the depressed platelt function observed during and following extracorporeal circulation.

Unusual manifestations of penetrating cardiac injuries.

Penetrating cardiac injuries frequently first appear in an unusual and insidious manner, and their diagnosis may not be immediately obvious. In a series of 20 cases of cardiac injury, ten cases were indicative of such subtle symptoms, several of which were life-threatening. These unusual manifestations can be categorized as early, intermediate, or late. Early problems of four patients included the following: (1) sudden onset of shock during laparotomy, performed due to apparent abdominal trauma; (2) cardiac arrest on arrival in the emergency room; and (3) cerebral air embolus and mimicked symptoms of possible irreversible anoxic brain damage. The intermediate manifestations of cardiac injury are usually discovered in the early recovery period, and include myocardial infarction with cardiogenic shock and bullet embolus to a peripheral artery. Intermediate manifestations were observed in two patients. Four patients had late complications that included pseudoaneurysm, ventricular septal defect, valvular damage, and recurrent pericarditis. These late complications were observed between one month and 21 years after cardiac injury. This indicates the necessity of long-term follow-up of these patients.

Denatured plasma and platelet function.

Thrombocytopenia and platelet dysfunction are well known complications of extracorporeal circulation. The production of ""denatured'' protein is a common occurrence with extracorporeal circulation even in the absence of a blood-gas interface. We subjected platelet-poor plasma to vigorous bubbling with air and studied the effect of this ""denatured'' plasma on platelets from the same donor. Aggregation induced by ADP, epinephrine or collagen was measured. The bubbled plasma decreased the delay in the onset of aggregation observed with collagen and eliminated the biphasic aggregation response induced by epinephrine. These data indicate that ""denatured'' protein may affect platelet function and may play a role in the thrombocytopenia and altered platelet function associated with extracorporeal circulation.

Nonocclusive mesenteric vascular insufficiency.

A case of nonocclusive mesenteric vascular insufficiency in a patient with congestive heart failure on digitalis and with arrhythmia is presented. The preoperative diagnosis was made through mesenteric arteriography. A course of treatment was followed which we believe prevented intestinal gangrene. This regimen includes measures to increase cardiac output, local pharmacologic agents to induce mesenteric vasodilatation, antibiotics, and oxygen. The viability of the intra-abdominal organs was demonstrated by laparotomy.