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Starting total parenteral nutrition (TPN) the day after acute surgical stress has beneficial effects on body weight, nitrogen balance, and colonic anastomosis bursting pressure in normally nourished rats. In view of the reported favorable utilization of high-concentration branch-chain amino acids (BCAA) following severe stress, we compared enteral (TEN) to parenteral (TPN) nutrient infusions containing increased BCAA starting the day of operation. Twenty-four male Sprague-Dawley rats, in two groups paired by weight under IP pentobarbital anesthesia underwent jugular vein catheter (CVP) insertion, laparotomy, gastrostomy, colon anastomosis, dorsal skin incision and SC polyvinyl alcohol sponge insertion. The rats were maintained for 6 days with continuous IV infusion in the TPN group (gastrostomy plugged) and continuous gastric infusion for the TEN group (CVP plugged). Urine and feces were collected daily. The infusions contained 1000 to 1002 Kcal, 847 to 845 nonprotein Kcal, 38 to 39 g of amino acids, 206 to 209 g of carbohydrates, and 2.8 to 2.9 g of rat per liter in the TEN and TPN, respectively, with identical ratios of dietary essential amino acids to nonessential amino acids (52/48), and 28.34% BCAA in the TPN and 33.10% BCAA in the TEN. There were 491 mg/100 mL of glutamine in the TEN and 170 mg of glutamic acid in the TPN. Amino acids were infused at 8.59 g/kg per day for TEN and 8.34 g/kg per day for TPN. The vitamins, minerals, and trace minerals were essentially the same in the TEN and TPN except for the absence of iron, iodine, selenium, and molybdenum in the TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved healing occurs in nutritionally depleted rats given early postoperative compared with delayed feeding. The present study was designed to test the hypothesis that delay in postoperative feeding of rats normally nourished at the time of operation would also be detrimental to wound healing. Fully nourished rats weighing 288 to 342 g were divided into three groups (10 rats per group). All rats had central vein catheters inserted, celiotomy with division and reanastomsis of the colon and dorsal skin incisions, under ip pentobarbital anesthesia. With no oral intake allowed postoperatively, group 1 rats were maintained in iv 5% Dextrose electrolytes and vitamins (5% DSV); group 2 was given the 5% D/SV until the third postoperative day when they were placed on TPN (4.5% amino acids 15% Dextrose, 10% Intralipids); and group 3 was given TPN from the first postoperative day. Rats were sacrificed 6 days postoperatively and final weight, skin wound breaking strength (WBS) and colon anastomosis bursting pressure (CBP) were measured. Findings were % weight change -27.8 +/- 1.5 for Group 1, -12.6 +/- 1.0 for Group 2, and -6.9 +/- 8 for group 3 (p less than 0.0001). Wound measurements for STS on fresh specimens were 88.6 +/- 10.0 g for group 1, 89.1 +/- 8.4 g for group 2, and 87.1 +/- 11.1 g for group 3. WBS for formalin-fixed specimens were 313.5 +/- 29.7 g for group 1, 323.4 +/- 38.4 g for group 2, and 382 +/- 25.2 g for group 3 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of 6-day dietary arginine supplementation on the weight gain, blood glucose, thymus weight, thymic lymphocyte content, and in vitro thymic lymphocyte immune reactivity was studied in obese (C57BL/6J-OB/)B) and heterozygous lean mice. Control mice were fed a commercial laboratory chow (1.8% arginine content) and drank tap water, while supplemented mice were given 0.5% arginine in the chow and 0.5% arginine solution for drinking. All mice ate and drank ad libitum. Supplemental arginine significantly decreased the weight gain (1.2 g vs. 2.2 g, p less than 0.01) and blood glucose levels (303 mg% vs 236 mg%, p less than 0.02) of the OB/OB mice; no such effects were noted in the lean heterozygotes, all of which had normal blood glucose levels. OB/OB mice had thymus glands which weighed less and contained significantly fewer lymphocytes than their lean littermates. In vitro mitogen-stimulated thymic lymphocyte protein synthetic rates were equal in chow-fed lean and OB/OB mice. In both groups, supplemental arginine significantly increased thymus weight, the number of thymic lymphocytes per gland, and thymic lymphocyte immunoreactivity in vitro. The hormonal secretagogue activity of arginine on the pituitary may explain its beneficial effects on the rate of weight gain, hyperglycemia, and depressed thymic immune function of OB/OB mice.

We have previously shown that supplemental vitamin E has a cytoprotective effect in the liver of rats with chronic CCL4-induced liver cirrhosis. In this study, we hypothesized that vitamin E would have a protective effect in acute liver injury induced by D-galactosamine. D-Galactosamine-induced injury has been thought to be due to a synergistic direct toxic effect and presence of intestinal bacteria and/or endotoxins. D-Galactosamine was used to induce acute "hepatitis" (1.5-2.0 g/Kg body weight, ip). Rats were placed on either standard chow or the same chow supplemented with vitamin E (300 mg DL-alpha-tocopherol/Kg diet) and 6 days later were given D-galactosamine. There was significantly improved early (5-day) survival and late (14-day) survival in the vitamin E-supplemented group. The vitamin E beneficial effect was manifested also by decreased liver fat and collagen content and decreased SGPT level. Because bacterial endotoxins have been implicated as playing a role in the pathogenesis of D-galactosamine hepatitis, the same experiment was carried out using germ-free and conventional rats. There was significantly improved survival in both the germ-free and conventional vitamin E-supplemented groups both at 5 and 14 days. There was no significant difference between conventional and germ-free rats with or without vitamin E supplementation. In summary (a) vitamin E improves the early fat and collagen accumulation in the liver, decreases SGPT level, and improves survival in the D-galactosamine experimental model of acute liver injury in both conventional and germ-free rats; and (b) D-galactosamine toxicity is probably not mediated through intestinal bacteria and/or endotoxins.

In the Phase I study, the new anthracycline aclacinomycin A was given to 22 advanced cancer patients on a schedule of daily intravenous administration for five days repeated every four weeks. The limiting toxicity was myelosuppression, which was severe at a dose of 30 mg/m2 per day for five days. Platelet nadirs were more marked than those of white cells and occurred at day 21. Some patients had moderate nausea and vomiting. No hepatic or renal toxicity was observed, and alopecia was minimal. Cardiac function was monitored prospectively, using radionuclide left ventricular ejection fractions and serial ECGs. One patient developed transient atrial fibrillation; and one other, who had previously received 380 mg/m2 doxorubicin, developed congestive heart failure. Otherwise there was no evidence of cardiac toxicity. No tumor regressions were seen. We conclude that 1509 mg/m2 given in five daily 30 mg/m2 fractions is a maximum tolerated dose of aclacinomycin A. This is higher than the reported MTD of 120 mg/m2 for single bolus injection. We recommend a Phase II starting dose of 25 mg/m2 per day for good-risk patients and 20 mg/m2 per day for poor-risk patients when the drug is given on this schedule.

The radionuclide, gallium-67, accumulates in a wide variety of neoplastic and inflammatory lesions. Diffuse bilateral lung localization of 67Ga occurred in two cases of interstitial pneumonitis associated with bleomycin therapy. Clinical symptoms and laboratory evaluation of pulmonary status correlated with scintigraphic studies in these two patients, while discrepancies between scintigraphic and roentgenographic findings were observed.

Stress or injury-induced phenomena, such as impaired wound healing and immune depression, may be related to impaired function of certain leukocyte populations. Since vitamin A prevents some aspects of stress, we studied its effect on various white cell populations in normal and injured rats. Supplemental vitamin A (150,000 IU/kg chow) to normal rats resulted in marked increases in thymic weight and lymphocytes without any effct on adrenal weight. The basal chow contains 13,700 IU vitamin A per kg. In rats subjected to moderately severe injury (dorsal wounding or unilateral femoral fracture), supplemental vitamin A greatly diminished the thymic involution observed in chow-fed controls and delayed or minimized the accompanying adrenal hypertrophy. In uninjured rats, supplemental vitamin A induced in three to four days a temporary circulatory leukocytosis characterized by lymhocytosis, monocytosis, and a relative neutropenia. These changes in the blood picture persisted one day after femoral fracture. On the second and third day postfracture the lymphocyte and neutrophil values returned to normal while the monocytosis persisted. Polyvinyl alcohol sponges implanted next to the fracture site demonstrated that supplemental vitamin A consistently increased the number of white blood cells migrating into the wound area and showed significantly larger numbers of monocytes/macrophages. These data suggest that vitamin A influences the numbers and nature of white cells involved in immune, inflammatory, and wound healing processes. In addition to the known antiglucocorticoid activity of vitamin A, these effects may represent a direct beneficial action of dietary vitamin A supplements for stressed and injured animals.

We have previously reported that supplemental vitamin A ameliorates the stress response to a wide variety of noxious agents. The present study was carried out to determine how supplemental vitamin A influences the course of radiation sickness in C3H female mice subjected to 3000 R irradiation of one lower hind limb. All mice ingested a chow diet containing about 13,000 units of vitamin A/kg diet (about half as preformed vitamin A and half as beta-carotene) which supports normal growth, development, and reproduction of normal mice. One hundred fifty thousand units of vitamin A/kg chow was added for the vitamin A supplemented mice. All mice ate and drank ad libitum. The supplemental vitamin A feeding was begun either 3 days before radiation or immediately after radiation. There were no significant differences in the effects of these two regimens. The supplemental vitamin A prevented the weight loss, moderated the adrenal hypertrophy, prevented the thymic involution, and lessened the lymphopenia due to radiation. We conclude that supplemental vitamin A has both prophylactic and therapeutic benefits in radiation-induced disease.

Various arginine HCl supplements (0.5-3%), half added to a basal commercial rodent chow (1.8% arginine) and half to the drinking water, were given to 8- to 9-week-old male CBA/J mice for 6 days. Control animals were fed the basal chow and drank tap water. All mice ate and drank ad libitum. Weight gain and food intake were similar in all groups. All arginine supplements increased significantly: thymic weight (average 22%), thymic lymphocyte content (average 45%), and the in vitro reactivity of thymic lymphocytes judged by the incorporation of 3H-leucine into the TCA-precipitable protein fraction in response to stimulation by phytohemagglutinin and concanavalin A. All these thymic effects resulted from the 0.5% arginine hydrochloride supplement; further increases in arginine supplementation did not increase these effects. These data suggest that supplemental arginine may improve host defence mechanisms and thereby may play an important role in the care of severely injured or ill patients, since it is well established that their defense mechanisms are reduced.

We have shown previously that supplemental vitamin A (Vit. A) increases the early inflammatory response to wounding and enhances the collagen content of the intestine of normal and injured rats. We now report the effect of dietary supplementation with Vit. A on the prevention of duodenal ulcer (DU) in rats caused by intragastric administration of cysteamine-HCl. A major way cysteamine-HCl induces DU formation is by enhancing gastric acid secretion. Adult male rats were divided into two groups: (1) rats fed a standard rat Chow (Purina) (15 IU Vit. A/g diet) containing two to three times the National Research Council recommended daily allowance for Vit. A for normal rats; (2) rats fed the same supplemented with 150 IU of Vit. A palmitate per/g Chow. One week later, all rats were given 1 ml of cysteamine-HCl (135 mg) intragastrically. The rats were maintained on their respective diets. Two days later, all rats were killed with ether, the stomach and duodenum excised, and examined for the presence of ulcers. No gastric ulcers were found in either group. There was a statistically significant decrease in the incidence of DUs in the Vit. A-supplemented group when compared to the control group (p less than 0.01) 48 hr following cysteamine-HCl administration; 32% of the Vit. A-supplemented rats developed a DU whereas 74% of rats fed standard Chow had DUs. Most rats had a single DU in the first part of the duodenum, occasionally a second ulcer was noted in the same area. Dietary supplementation with Vit. A had no effect on gastric acid production. In conclusion, our data show that Vit. A dietary supplementation is effective in preventing formation of DUs caused by cysteamine-HCl administration to rats. This effect does not appear to be due to reduction of gastric acid output.

Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus.