A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss.

BACKGROUND: Previous studies have documented a high incidence of gallstone formation following gastric-bypass (GBP)-induced rapid weight loss in morbidly obese patients. This study was designed to determine if a 6-month regimen of prophylactic ursodiol might prevent the development of gallstones. METHODS: A multicenter, randomized, double-blind, prospective trial evaluated 3 oral doses of ursodiol: 300, 600, and 1,200 mg versus placebo beginning within 10 days after surgery and continuing for 6 months or until gallstone development, for patients with a body mass index (BMI) > or = 40 kg/m2. All patients had normal intraoperative gallbladder sonography. Transabdominal sonography was obtained at 2, 4, and 6 months following surgery, or until gallstone formation. RESULTS: Of 233 patients with at least one postoperative sonogram, 56 were randomized to placebo, 53 to 300 mg ursodiol, 61 to 600 mg ursodiol, and 63 to 1,200 mg ursodiol. Preoperative age, sex, race, weight, BMI, and postoperative weight loss were not significantly different between groups. Gallstone formation occurred at 6 months in 32%, 13%, 2%, and 6% of the patients on the respective doses. Gallstones were significantly (P < 0.001) less frequent with ursodiol 600 and 1,200 mg than with placebo. CONCLUSION: A daily dose of 600 mg ursodiol is effective prophylaxis for gallstone formation following GBP-induced rapid weight loss.

Leiomyosarcoma of the rectum: the military experience.

Leiomyosarcoma of the rectum is a rare neoplasm and may behave in a highly malignant manner. Our experience with a single case prompted a review of the Armed Forces Central Medical Registry (AFCMR), where six other cases were found from the total AFCMR population. Four patients were treated with abdominoperineal (AP) resection; three had local excision only. Three patients developed metastatic disease and two of those died. The authors recommend prompt wide excision (AP resection) for any case of leiomyosarcoma of the rectum.

Spontaneous mediastinal emphysema.

Several cases of spontaneous mediastinal emphysema have been seen and treated at two Air Force Hospitals. All have responded to nonsurgical treatment, and have been returned to normal duty or school.

Protein synthesis dynamics in human gastrointestinal malignancies.

The malnourishing effects of cancer and its treatments haveprovided a strong clinical incentive for the nutritional support of cancer patients with intravenous hyperalimentation (IVH), but potential enhancement of tumor growth by additional substrate provision has generated concern. Twenty-five patients undergoing surgical treatment for gastrointestinal cancer were studied on one of two preoperative dietary regimens: ad libitum oral diet or intravenous hyperalimentation. Using a stable isotope tracer, N-glycine, in vivo tissue fractional protein synthesis rates were determined from operative specimens of tumor and normal gastrointestinal tissue. Despite substantial advantage in caloric and protein intake, and nitrogen retention, tumors in IVH-fed patients were synthesizing protein no faster (14.2%/day) than those in orally fed patients (15.1/day). Tumor fractional protein synthesis rates (PSRs) correlated (r = + 0.708, P less than 0.005) with the PSR of the tissues from which they arose. IVH maintained gut PSR at the level occurring in the orally fed patients. Parenteral nutritional support in cancer patients does not maintain protein synthesis rates at levels greater than those present with regular oral diets. Although not a direct measure of tumor growth, these data provide preliminary evidence that optimal nutritional support of the cancer patient may be possible without undesirable stimulation of tumor growth.

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.

Direct right atrial catheterization for total parenteral nutrition.

A case report of a patient with severe nutritional deficiency and no adequate access to the central venous system for total parenteral nutrition is presented. Operative placement of a catheter directly into the right atrium allowed adequate nutritional support and led to a marked improvement in the clinical status of the patient and a gain of weight from 67 to 98 pounds. The technique of the procedure and its limited indications are discussed.

Changes in protein synthesis after trauma: importance of nutrition.

The effect of trauma (femur fracture) on protein synthesis in rats given four different parenterally administered nutrient formulations ("diets") was investigated. Diet I was a maintenance formulation. It contained sufficient amino acids and glucose to keep the rats in nitrogen balance but was inadequate to support growth. Diet II was amino acids only, diet III was severely hypocaloric glucose, and diet IV was diet I minus the amino acids. The rats received parenterally all nutrients for the duration of the 4-5 day study. Twenty-four hours posttrauma, the fractional synthesis rates of liver, lung, heart, kidney, and muscle were estimated by infusing [15N]glycine for 17.5-19 h. (T.P. Stein, J.C. Oram-Smith, M.J. Leskiw, H.W. Wallace, L.C. Long, and J.M. Leonard. The effects of protein and calorie restriction on protein synthesis in the rat. Am. J. Physiol. 230: 1321-1326, 1976.) Two trends were found: i) on the amino acid-containing diets (I and II), most protein synthesis rates were increased posttrauma. Lung was the exception: no change was found; ii) rats on the amino acid deficient diets (III and IV) showed a decrease in the fractional muscle and lung synthesis rates posttrauma. We concluded that in this rat trauma model the requirement is mostly for amino acid nitrogen posttrauma.

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.

Effect of nitrogen and calorie restriction on protein synthesis in the rat.

The effect of a deficiency of calories and/or nitrogen on protein metabolism in the rat was investigated. During the 5 days of the study, the rats received all nutrients except water via intravenous hyperalimentation. Four diets were used: I) 1.25 g amino acids, 12.5 g glucose/day; II) 1.25 g amino acids/day; III) 1.25 g glucose/day; and IV) 12.5 glucose/day. The rate of protein synthesis in heart, lung, muscle, kidney, and liver was estimated by a modification of the technique of Garlick et al. (The diurnal response of muscles and liver protein synthesis in vivo in meal-fed rats. Biochem. J. 136: 935-945, 1973) except that [15N]glycine was used as the tracer. Heart and lung protein synthesis was depressed by both caloric and nitrogen restriction. Muscle protein synthesis was only significantly affected by omission of calories from the diet. Kidney nitrogen content increased with the amino acid diets and decreased with the nitrogen-deficient diets. The major response of the liver to a dietary deficiency was to lose nitrogen via an increase in the rate of liver protein catabolism.

The effects of semistarvation and parenteral nutrition on the gastric mucosa of rats.

The effects of semistarvation and parenteral nutrition on the gastric mucosa were studied in 24 Wistar rats (250 to 350 grams). The animals were divided into three dietary regimens: Group I-standard rat chow ad libitum; Group II-50 cc. per day of a hyperalimentation solution containing 30% glucose + 5% amino acids; Group III-50 cc. per day of 5% glucose. The animals were fed for a period of 7 days. Gastric mucosal fluxes of Na+, Li+, and H+ then were measured after the gastric instillation of two gastric wash solutions, one primarily an HC1 solution, the other a solution of HC1 plus sodium taurocholate. Gross examination of the gastric mucosal surfaces were recorded. Compared to Group I (oral diet), Groups II and III demonstrated a decrease in volume in gastric secretion during the test period (p less than 0.005); and an increase in net negative hydrogen flux (p less than 0.005). Compared to Group II (hyperalimented), Group III (semistarved) demonstrated an increased net negative H+ flux (p less than 0.01), but no difference in volume of secretion. Only Group III demonstrated a difference in H+ flux after the addition of sodium taurocholate (p less than 0.05). Gastric lesions were significantly increased in Group III, as compared to Groups I and II. Semistarvation renders the gastric mucosa of the rat more susceptible to injury. Adequate intravenous nutrition alone protected against these effects.