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Biomedical subjects

J L Mullen

Publications and source records attributed to J L Mullen.

At least 109 records · Page 6Linked to original sources

Reduction of operative morbidity and mortality by combined preoperative and postoperative nutritional support.

A previously developed and validated predictive nutritional assessment model (Prognostic Nutritional Index) was applied to a heterogenous surgical population. Without knowledge of the then undeveloped PNI, adequate preoperative nutritional repletion (TPN) was provided on clinical indications alone to 50 of 145 patients with the remaining 95 patients receiving no preoperative total parenteral nutrition. Analysis of the two groups found no baseline differences in nutritional status, type and severity of disease and/or operative therapy, and other potentially important variables. In the high-risk stratified group as defined by admission nutritional assessment and calculated PNI (greater than or equal to 50%), adequate preoperative TPN reduced postoperative complications 2.5-fold (p < 0.01), postoperative major sepsis six-fold (p < 0.005) and mortality five-fold (p < 0.01). Clinical "eyeball" evaluation of nutritional status cannot identify high-risk individuals. This nutritional assessment predictive model (PNI) identifies the subset of operative candidates in whom adequate preoperative nutritional support significantly reduces operative morbidity and/or mortality.

Bacterial Infections↗

Measurement of protein synthesis rates with [15N]glycine.

[15N]glycine (95+%) was infused into 170- to 220-g rats at a constant rate of 2-8 mg [15N]glycine/h for 2-24 h. Two sets of experiments were done. In one set, the rats were killed at varying time intervals, the liver was removed, and the fractional rate of liver protein synthesis was estimated from the amount of 15N incorporated into liver protein, the enrichment of the liver tissue free amino nitrogen, and the time course. In the second set of experiments, the rats were killed after a [15N]glycine infusion of 18-22 h. The whole-body protein synthesis rate was estimated from the urinary 15N enrichment at plateau by the method of Picou and Taylor-Roberts (Clin. Sci. 36: 288-296, 1967). It was compared against the value found by measuring the 15N enrichment of the whole-rat homogenate and calculating the synthesis rate from the formula of Garlick et al. [Biochem. J. 136: 935-945, 1973). The results are i) The 15N enrichment of glycine in either liver protein or liver tissue free amino acids was proportional to the 15N enrichment of the mixed protein or tissue free amino acids, respectively. ii) Continuous infusion-isotopic plateau methods underestimate the fractional protein synthesis rate of rat liver. iii) The methods of Picou and Taylor-Roberts and of Garlick et al. gave similar values for the whole-body protein synthesis rate.

Amino Acids↗

Effect of parenteral nutrition on protein synthesis and liver fat metabolism in man.

We studied the effect of parenteral nutrition with amino acids and hypertonic glucose on protein synthesis and liver fat metabolism. Patients with operable gastrointestinal tract malignancies were divided into two groups. Group I ate the hospital diet ad libitum for the 7-10 days preceding surgery. Group II were given adjuvant parenteral nutrition (APN) for 7-10 days prior to the surgical removal of the tumor. Daily nutrient intake and nitrogen balance were determined. [15N[glycine (1-2 g) was infused at a constant rate for 12-18 prior to surgery. During surgery, blood, liver, and muscle specimens were taken for 15N analysis. Fractional protein synthesis rates were estimated by the method of Garlick et al. (Biochem. J. 136: 935-945, 1973). The fat content and distribution pattern in the liver was determined by gas chromatography-mass spectrometry. The following results were found. 1) APN increaed the albumin synthesis rate. 2) The fraction of linoleate in the total liver fatty acids were reduced by 75% in the APN patients. 3) Some of the APN patients developed fatty livers during the study. When the APN patients were subdivided on the basis of whether they had fatty livers, it was found that only those patients who did not accumulate fat showed an improvement in their plasma albumin concentration during the period of parenteral nutrition.

Fatty Acids↗

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.

Diet↗

Implications of malnutrition in the surgical patient.

The substantial prevalence of malnutrition in the hospitalized patient population has only been recently recognized. Preoperative nutritional and immunological assessment was performed prospectively on admission in 64 consecutive surgical patients. Factors measured included weight loss, triceps skinfold, midarm muscle circumference, creatinine-height index, serum albumin level, serum transferrin level, total lymphocyte count, serum complement level, serum immunoelectrophoresis, lymphocyte T rosettes formation, neutrophil migration, and delayed hypersensitivity. Using these criteria for malnutrition, 97% of the patients had at least one abnormal measurement and 35% had at least three abnormal measurements. Patients were monitored for complications during their hospital course. Serum albumin level, serum transferrin level, and delayed hypersensitivity reactions were the only accurate prognostic indicators of postoperative morbidity and mortality. Substantial unrecognized malnutrition exists in the surgical patient population. An isolated indicator of malnutrition should be interpreted with caution. The visceral protein compartment (serum albumin and serum transferrin levels and delayed hypersensitivity) is the most accurate prognostic indicator of postoperative morbidity and mortality. Perioperative nutritional support may reduce operative morbidity and mortality in the malnourished operative candidate.

Adult↗

Percutaneous decompression of benign and malignant biliary obstruction.

Percutaneous transhepatic catheterization of the biliary tree was performed in 41 patients with obstructive jaundice. In 39 patients, the catheter was successfully advanced past the obstructing lesion into the distal common duct and duodenum to establish internal biliary drainage. The remaining two patients had the obstructed biliary tract drained externally. Chronic internal catheter drainage was instituted in five patients with stricture and ten with malignant obstruction as a means of palliating symptomatic jaundice. Twenty-two patients had marked reduction in serum bilirubin levels and pruritus, eight patients had moderate decreases in serum bilirubin levels, and six patients did not improve despite adequate catheterization due to hepatic parenchymal disease. This procedure effectively decompresses the severely obstructed biliary tree prior to surgery and can also palliate patients with unresectable malignant biliary obstruction and stent high-risk, benign strictures.

Adenoma, Bile Duct↗

Multiple carcinomas following therapy for Hodgkin disease.

A 52-year-old man developed synchronous squamous-cell carcinoma of the larynx and middle one-third of the esophagus following treatment of Hodgkin disease. This patient fell into the subgroup of patients treated by intensive radiation therapy followed by intensive chemotherapy. The link between the therapy and subsequent carcinoma is suggestive. Long-term follow-up care of patients with Hodgkin disease demands continuing evaluation of this possible complication.

Antineoplastic Agents↗

Serum 5'-nucleotide phosphodiesterase as a predictor of hepatic metastases in gastrointestinal cancer.

Isoenzyme V of 5'-nucleotide phosphodiesterase (5'-NPD-V) is present in the peripheral sera of patients with hepatic metastases. A total of 122 patients underwent prospective serologic analysis followed by operation for primary tumors of the gastrointestinal tract and careful evaluation of the liver. A positive 5'-NPD-V assay was found in fifty-nine of sixty patients with liver metastases. A negative 5'-NPD-V assay was found in forty-three of sixty-two patients with no evidence of hepatic metastases. The accuracy of the test was 84 per cent, and the predictive value was 75 per cent. Serum 5'-NPD-V was abnormal significantly more frequently in patients with metastatic liver disease than were liver scans or carcinoembryonic antigen (CEA), alpha fetoprotein, serum glutamic oxalacetic transaminase (SGOT), and total serum bilirubin or serum alkaline phosphatase levels.

Evaluation Studies as Topic↗

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.

Adenocarcinoma↗

Cecal necrosis after open-heart operation.

Two patients with isolated transmural ischemic necrosis of the cecum after cardiopulmonary bypass are discussed. Superimposed upon the multiple cardiovascular abnormalities in these patients, cardiopulmonary bypass adds another risk factor for nonocclusive intestinal infarction. In patients undergoing open-heart procedures, postoperative nonspecific abdominal complaints should be evaluated with a high degree of suspicion for this lethal complication. An intensive diagnostic effort is indicated, including contrast and angiographic radiological studies. Consideration of early abdominal exploration is indicated.

Aged↗

Ten years experience with intravenous hyperalimentation and inflammatory bowel disease.

A retrospective analysis was conducted on 74 patients with inflammatory bowel disease who were treated with intravenous hyperalimentation at the Hospital of the University of Pennsylvania between the years 1967-1976. Intravenous hyperalimentation can ameliorate the inevitable protein-calorie malnutrition present in patients with inflammatory bowel disease. Combined with complete bowel rest, intravenous hyperalimentation can effectively function as the primary treatment or as an adjunct to the surgical management of the complications of inflammatory bowel disease. Intravenous hyperalimentation can be safely administered to these severely ill patients, almost certainly improving survival rates in the patients treated.

Adult↗

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.

Adult↗