Herbert W. Wallace

Intravenous nutrition and tumor host protein metabolism.

The difficulty of maintaining adequate nutritional status in cancer patients is well recognized [I, 181. Recently there has been considerable interest in the clinical use of intravenous diets to support these patients [2, 51. Although present evidence strongly suggests that the cancer patient receiving chemoor radiotherapy is significantly benefited by parenteral nutrition, there exists little information on the metabolic changes induced in tumor and host tissue by parenteral nutrition. Unfortunately, nitrogen balance studies are of little value in the cancer patient for they cannot distinguish between host and tumor utilization of nitrogen intake. The use of labeled amino acids has facilitated the measurement of protein synthesis in viva [3, 9, 151. This study involves the use of [15N]glycine as a nitrogen tracer to examine selective utilization of nutrients by host and tumor tissue. The effects of the presence of a tumor and an acute change in nutrient intake are investigated. We have previously reported preliminary data on protein synthetic rates of tumor host tissues [16]. The present study updates our findings on tissue protein synthesis rates and pursues the intracellular localization of the observed tissue changes.

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), pseudoaneurysm (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.

The use of optical emission spectroscopy for human 15N tracer studies

Abstract Optical emission spectroscopy is a convenient method for determing 15N specific activity in a variety of metabolites following the administration of an 15N-labeled amino acid to humans. The only disadvantage, compared to the more conventional isotope ratio mass spectrometer analytical system is that more tracer is needed to give accurate results. When an 15N-labeled amino acid is used as the 15N carrier, the amount of 15N is not above a tracer dose. A suitable procedure is described for performing such studies using [15N]glycine as a tracer. As an experimental example, [15N]glycine was infused into a subject at a rate of 35 mg of N/hr for 8 hr. After 3 hr a meal was consumed by the subject. The urinary urea-15N, ammonia-15N and amino acid-15N profiles were determined.

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.

Artificial Red Cells with Crosslinked Hemoglobin Membranes

Artificial cells containing concentrated hemoglobin (Hb) solution were prepared by interfacial polymerization of Hb with glutaraldehyde (GA) in liquid membrane capsules (LMC). A solution containing 30% of Hb was emulsified in mineral oil as red cell-size microdroplets, and this emulsion was dispersed in an aqueous phase containing glutaraldehyde to form LMC. The LMC were semipermeable templates that held the microdroplets of Hb in suspension while GA diffused through the oil to the microdroplet surfaces. The GA crosslinked Hb at the surface of each microdroplet to form an artificial red-cell membrane encapsulating Hb solution. A water-soluble surfactant was used to eject the cells from the LMC and suspend them in saline. Several surfactants were evaluated. Cell size was controlled by agitation speed during preparation of the original emulsion. Cells of 2.52 = +/- 1.69 micron were prepared. The encapsulated Hb retained capacity to bind and release O2. The cells had a P50 of 8.9 torr (1200 Pa) and a capacity of 0.55 cc O2/g of total Hb, indicating that the crosslinked portion of the Hb did not contribute to O2 transport.

Electrophoretic determination of glycoprotein: An improved method with cleared cellulose acetate membrane

Abstract A staining method for the determination of serum glycoproteins on a cleared cellulose acetate membrane following electrophoresis is described. The resolution, stability, and reproducibility of this technique are evaluated. The entire procedure is relatively rapid and easily applicable to cellulose acetate electrophoresis regardless of the size and shape of the membrane. The glycoprotein values of normal human sera obtained by this method are reported.

Mechanically Induced Intravascular and Extravascular Hemolysis in Dogs

The endogenous production of carbon monoxide and the flow of hemoglobin to and from plasma were measured in 11 anesthetized dogs after pumping blood through an extracorporeal circuit for short periods. Two different pumps were used. In all animals the increase in CO production was greater than could be explained by catabolism of hemoglobin lost from plasma, an average of 11.4 times greater with one pump and 2.49 times greater with the other pump. Evidence is presented that this discrepancy could not be explained by catabolism of heme other than that of hemoglobin, and we therefore concluded that rates of hemoglobin catabolism were much greater than indicated by plasma hemoglobin kinetics and that extravascular hemolysis is a major cause of erythrocyte destruction during mechanically induced hemolysis. Extravascular hemolysis apparently caused an average of 72.9% and 37.2% (with the two pumps) of the total quantity of erythrocytes destroyed during pumping and for 3 hours after pumping.

Intravascular and Extravascular Hemolysis Accompanying Extracorporeal Circulation: A Clinical Study

Eleven patients undergoing open heart surgery were studied by means of a technic previously developed by us to quantitate intravascular and extravascular hemolysis. Endogenous production of carbon monoxide, which correlates quantitatively with red blood cell and hemoglobin catabolism, was measured preoperatively, 5 hr postoperatively, and 24 hr postoperatively. Rates of plasma hemoglobin catabolism and intravascular hemolysis were calculated from serial plasma hemoglobin determinations. Extravascular hemolysis results from catabolism of erythrocytes damaged during perfusion and subsequently sequestered in the reticuloendothelial system. Intravascular hemolysis occurred only during perfusion and averaged 252.22 ± SE 49.64 &mgr;moles heme. Extravascular hemolysis measured for the first 5 hr after perfusion averaged 462.48 ± SE 68.70 &mgr;moles heme, or 64% of the total calculated red blood cell destruction. In all but one of the eight patients studied 24 hr after perfusion, heme catabolism remained elevated (mean, 46.76 ± SE 13.05 &mgr;moles heme/hr compared to a normal value of ≦22 &mgr;moles heme/hr), indicating that extravascular hemolysis was still occurring. This extravascular destruction probably resulted from alterations in the cell membrane induced during the pumping procedure.

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)

Comparison of methods for the measurement of human protein synthesis

Abstract The rate of protein synthesis in one subject was measured four times with [ 15 N]glycine as the tracer. Two pulse-label and two continuous-infusion experiments were done. The two pulse-label experiments gave significantly higher protein synthesis rates (49.7 and 39.8 mg of N/kg body wt/hr) than the continuous-infusion determinations (26.2 and 22.4 mg of N/kg body wt/hr). As an independent test of the validity of the continuous-infusion approach, the rate of protein synthesis in the rat was measured by the continuous-infusion method. The value of 74 mg of N/kg body wt-hr agrees well with literature estimates of rat protein synthesis.