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H C Sax

Publications and source records attributed to H C Sax.

At least 37 records · Page 2Linked to original sources
PubMed1994

The role of the gut in critical illness.

The gastrointestinal tract is a major immunologic organ that must be maximally supported during critical illness. Gastrointestinal tissues require direct contact with nutrients to support their own rapid cellular turnover rate and carry out the multitude of metabolic and immunologic functions needed for successful adaptation to stress. Disruption in the ecologic equilibrium of the gastrointestinal tract often occurs during critical illness and the therapies provided. Problems encountered include stress ulcers, intestinal ischemia, bacterial overgrowth, aspiration pneumonia, bacterial translocation, sepsis, and the systemic inflammatory response syndrome. Early enteral nutrition has been shown to be a viable, economic, and physiologically beneficial way to support the gastrointestinal tract during critical illness. The fortification of enteral formulas with glutamine, arginine, or fiber is being studied to determine each one's unique role in the gut and immunologic changes that occur with severe stress.

Critical Illness↗
PubMed1994

Starvation induces differential small bowel luminal amino acid transport.

BACKGROUND: The importance of small intestinal mucosa functions has been emphasized in recent years because gut metabolism becomes better defined. One of the major activities of the enterocyte is amino acid transport, which is important not only for the organism but also for the integrity of the mucosa. Bowel rest during the postoperative period is marked by decreased calorie and protein intake with atrophy of the brush border mucosa. We sought to determine whether active amino acid transport is altered during 72 hours of fasting. METHODS: New Zealand white rabbits were fed (control) or fasted for 72 hours. Brush border membrane vesicles were prepared from scraped jejunal mucosa, and their purity was assessed by marker enzyme enrichment (17- to 25-fold). Transport of tritiated glutamine, arginine, alanine, methylamino-isobutyric acid (MeAIB), and leucine into brush border membrane vesicles was measured by rapid mixing filtration. RESULTS: Fasted animals lost on average 138 +/- 51 gm of body weight. Glutamine and arginine transport were decreased in rabbits fasted for 72 hours compared with controls; alanine, MeAIB, and leucine transport were maintained. The decrease in Glutamine transport was due to a decrease in Vmax (545 +/- 22 versus 836 +/- 93 pmol/mg protein/10 sec; p < 0.05), consistent with a decrease in the number of functional transporter proteins. Km values were similar in both groups (644 +/- 25 versus 624 +/- 18 mumol/L), indicating no change in carrier affinity. CONCLUSION: Differential changes occur in brush border amino acid transport during a 3-day period of bowel rest. The apparent gut nutritive transporters for Glutamine and arginine are decreased, although the gluconeogenic transporters for alanine, MeAIB, and leucine are maintained. These adaptive changes may help explain the difficulties seen in postoperative and critically ill patients on prolonged bowel rest.

Amino Acids↗
PubMed1993

Enteral and parenteral feedings. Guidelines and recommendations.

The clinician is confronted with many options in choosing appropriate nutritional support for a patient. Several major issues emerge. 1. Supplemental nutritional support is appropriate in patients who will not be able to take oral calories for more than 7 days. Individuals with preexisting deficits due to lifestyle or disease should have support started more promptly. 2. The use of TPN as a preoperative adjunct in surgical patients appears to be beneficial only to those with severe malnutrition. 3. In the vast majority of patients, the enteral route is preferred. Total parenteral nutrition appears to be beneficial in those with inadequate absorptive capacity, fistula, acute hepatic/renal failure, inflammatory bowel disease, and as an adjunct to cancer therapy. 4. Complications associated with enteral and parenteral nutrition delivery can be minimized by careful attention to detail and adequate monitoring of responses. 5. An exciting area beyond the scope of this monograph is the emergence of the field of "Nutritional Pharmacology" where one manipulates the patient's diet to achieve a desired physiologic result, just as one will change antibiotics or pressors. This will provide an additional tool to the clinician in the treatment of critically ill patients.

Enteral Nutrition↗
PubMed1992

Total parenteral nutrition-induced changes in gut mucosal function: atrophy alone is not the issue.

BACKGROUND: Total parenteral nutrition (TPN) has been implicated in gut atrophy and breakdown of barrier function leading to bacterial translocation (BT) in animals. BT during TPN, however, is not found consistently, and it has therefore been suggested that macromolecular permeability may occur independently of BT during TPN. METHODS: Male Sprague-Dawley rats were administered isocaloric standard TPN enterally, parenterally, or split equally between the two routes or allowed food ad lib. A second group of rats was administered isocaloric TPN with and without 4% lipids, and changes in gut barrier function were assessed by measuring lactulose permeability. RESULTS: Rats receiving TPN both enterally and parenterally maintained histologic intestinal structure to the same degree as rats fed enterally and those allowed food. Although parenteral feeding led to significant gut atrophy and cecal bacterial overgrowth, BT was not increased. Gut permeability to lactulose, however, was increased significantly in the TPN groups. Lipid content did not affect outcome. CONCLUSIONS: These results suggest that gut atrophy, BT, and permeability to macromolecules are not necessarily related. Gut-origin septic states during TPN or trauma may be caused by an increased escape of macromolecules from the gut, and BT may be an end result rather than a primary cause of such septic episodes.

Animals↗
PubMed1989

Transduodenal sphincteroplasty and transampullary septotomy for primary sphincter of Oddi dysfunction.

We examined 29 patients without stone disease or pancreatic ductal ectasia who underwent transduodenal sphincteroplasty and transampullary septotomy for symptoms of biliary colic or pancreatitis. The combination of biliary symptoms and a fibrotic ampulla of Vater portends a favorable surgical outcome in virtually all such patients. Patients with pancreatitis did worse overall, perhaps due to the existence of unappreciated subclinical parenchymal disease not related to sphincter dysfunction. Although endoscopic retrograde cholangiography was sensitive in demonstrating abnormalities of the pancreaticobiliary system, its specificity as a predictor of good results was poor. It seems prudent to temper one's enthusiasm for sphincteroplasty in the patient with pancreatitis, whereas patients with biliary symptoms, the postcholecystectomy syndrome, or both will usually benefit significantly from this procedure.

Adult↗
PubMed1988

Current concepts of protein turnover and amino acid transport in liver and skeletal muscle during sepsis.

The metabolic response to trauma and sepsis is characterized by a negative nitrogen balance, accelerated muscle proteolysis, increased ureagenesis, and stimulated acute-phase protein synthesis in liver. Inhibited uptake of amino acids and accelerated protein breakdown in muscle increase the flux of amino acids from the periphery to the liver. Concomitantly, hepatic uptake of amino acids is stimulated and protein synthesis and gluconeogenesis in the liver are enhanced. These events are important to the survival of patients with sepsis. Stimulated ureagenesis resulting in nitrogen loss from the body is another important aspect of hepatic nitrogen metabolism following trauma and sepsis. The mediator(s) initiating metabolic changes is not yet exactly defined, although regulatory protein(s) released from stimulated macrophages (particularly interleukin 1 and tumor necrosis factor) may play a major role in altered amino acid and protein metabolism in muscle and liver during sepsis. However, these factors alone are probably not responsible for the metabolic disturbances, since the catabolic hormones cortisol, glucagon, and the catecholamines can simulate the metabolic pattern observed in sepsis. Other possible mediators include prostaglandins and thyroid hormones. It is possible that the interaction between different types of mediators is necessary for the full manifestation of host responses to severe injury and sepsis.

Amino Acids↗
PubMed1988

Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis.

To examine alterations in amino acid metabolism after trauma and sepsis, male Sprague-Dawley rats underwent no operation (control, CON), celiotomy (trauma, TRA), or cecal ligation and puncture (sepsis, CLP). After 16 hr, plasma amino acid concentrations were determined. A second group of similarly prepared animals underwent isolated liver perfusion, and net amino acid uptake or release was determined over 30 min. Sepsis significantly decreased total amino acid concentration in portal plasma (CON, 3486 +/- 156 nmole/ml; TRA, 3407 +/- 150 nmole/ml; CLP, 2738 +/- 148 nmole/ml). Glutamine concentrations were uniformly lower in portal plasma than in arterial plasma in all states. There were depressed concentrations of the branched chain amino acids (BCAA) in portal plasma after trauma but not sepsis. In the isolated liver perfusion model, a marked increase in amino acid uptake was induced by sepsis (CON, 39.9 +/- 7.9 mumol/g liver protein; TRA, 49.5 +/- 17.3 mumol/g liver protein; CLP, 124 +/- 11 mumol/g liver protein). In addition, there was significantly greater uptake of threonine, asparagine, proline, methionine, tyrosine, and arginine. Although the BCAA isoleucine and valine were taken up to a greater extent in sepsis, the overall BCAA uptake was not significantly greater in sepsis than in control (CON 6.92 +/- 2.15 mumol/g liver protein vs CLP 15.8 +/- 1.9 mumol/g liver protein). The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Increased synthesis of secreted hepatic proteins during abdominal sepsis.

To study the effect of intraabdominal sepsis on hepatic protein synthesis, male Sprague-Dawley rats underwent celiotomy with either cecal ligation and puncture (CLP) or sham operation. Eight and sixteen hours later total hepatic protein synthesis was measured by flooding dose technique. Specific synthetic rates of structural or secreted hepatic proteins were further studied 16 hr after CLP in an isolated perfused liver model. Total hepatic protein synthesis was significantly elevated at 16 hr (59 +/- 6%/day vs 37 +/- 6%/day, P less than 0.05), but not 8 hr post-CLP. Structural hepatic protein synthesis was unchanged after CLP; however, the synthetic rates of the acute-phase secretory proteins alpha 1-acid glycoprotein, transferrin and complement component C3 were significantly increased 16 hr after CLP. However, the albumin synthetic rate was not increased during sepsis. We conclude that sepsis causes augmentation of hepatic protein synthesis primarily to increase acute-phase proteins for host defense.

Abdomen↗
PubMed1988

Methods for studying protein synthesis and degradation in liver and skeletal muscle.

Different methods used for measuring protein turnover in liver and skeletal muscle are described, with special emphasis on technical and practical aspects and the advantages and limitations of different techniques. In the first part of the review, the concept of precursor specific radioactivity and its importance for accurate determination of protein synthesis rate is discussed. In the second part, different in vivo techniques for protein turnover measurements are reviewed, including continuous administration of tracer amino acid, flooding dose technique, indirect measurement of protein synthesis, and estimation of protein degradation in vivo. In the third part of the report, in vitro techniques are described, including measurement of protein turnover in incubated liver slices, perfused liver, isolated hepatocytes, incubated isolated muscles or muscle biopsies, and perfused rat hemicorpus. In vivo techniques are preferred when accurate absolute values of protein turnover rates are desired. In vitro techniques offer the advantage of standardized conditions, maintaining strict control of substrate and hormone concentrations, and eliminating complicating interactions with other tissues. For several in vitro techniques, a good correlation has been demonstrated between relative changes in protein turnover in vitro and in vivo in different conditions.

Animals↗
PubMed1988

Use of autologous spiral vein grafts for vascular reconstructions in contaminated fields.

Vascular reconstructions in heavily contaminated fields can be particularly challenging. Prosthetic grafts are rarely suitable because of the risk of infection, but the saphenous vein is usually too small for isodiametric replacement of large arteries and veins. Although surgeons rarely consider the use of spiral vein grafts, they may occasionally be the ideal autogenous vascular replacement because they can be tailored to fit a vessel of any size. We report the use of spiral vein grafts in three patients requiring vascular reconstructions in the presence of heavy bacterial contamination.

Adolescent↗
PubMed1987

Early total parenteral nutrition in acute pancreatitis: lack of beneficial effects.

To determine the effect of early aggressive parenteral support in pancreatitis, 54 patients with acute pancreatitis were randomized to receive either conventional therapy (control group) or conventional therapy plus the institution of total parenteral nutrition within 24 hours. The two groups were similar demographically. The total parenteral nutrition group had a significantly higher rate of catheter-related sepsis than did an additional group of contemporaneous patients without pancreatitis who received total parental nutrition (10.5 percent and 1.47 percent, respectively; p less than 0.01). There was no advantage to the use of early total parenteral nutrition; that is, there was no difference in the number of days to oral intake, total hospital stay, or number of complications of pancreatitis. Patients with zero or one Ranson's criterion on admission were more likely to be eating by the seventh hospital day than were those with two or more Ranson's criteria (80 percent and 54 percent, respectively; p less than 0.05). The early institution of total parenteral nutrition in patients with acute pancreatitis did not appear to improve the outcome. Its use should be limited to prolonged periods of no oral intake or treatment of a specific complication, such as a pseudocyst.

Acute Disease↗
PubMed1986

Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns.

The branched-chain amino acids (BCAAs)--leucine, isoleucine, and valine--share unique biochemical properties that may make them useful in altered physiologic states. They can be metabolized independently of liver function to provide energy, other amino acids, or small nitrogenous compounds. This unique ability makes the BCAAs a desirable supplement in liver disease with encephalopathy and, to a lesser extent, in sepsis with hepatic dysfunction. Furthermore, the BCAAs play a role in the regulation of protein synthesis, suggesting beneficial effects in catabolic states such as postoperative stress, trauma, renal failure, and burns. However, initial studies in these areas have presented equivocal results.

Amino Acids, Branched-Chain↗
PubMed1986

Postoperative enteral vs parenteral nutrition. A randomized controlled trial.

Twenty patients undergoing major upper-gastrointestinal-tract or pancreaticobiliary surgery were randomized to receive postoperative nutritional support by total parenteral nutrition (TPN) or elemental diet administered by needle-catheter jejunostomy (NCJ). Both routes of administration provided adequate nutritional support. No unexpected complications were encountered. The NCJ group compared favorably with the TPN group at the end of the seven-day trial. The NCJ group provided significant cost efficiency while maintaining adequate nutritional support.

Adult↗
PubMed1986

Hepatic steatosis in total parenteral nutrition: failure of fatty infiltration to correlate with abnormal serum hepatic enzyme levels.

Total parenteral nutrition (TPN) is associated with hepatic biochemical and morphologic changes. Suggested causes include excessive glucose calories, fatty acid deficiency, and enterically derived hepatotoxins escaping atrophied bowel. Male Sprague-Dawley rats were cannulated or sham operated with internal jugular ligation. The cannulated groups received TPN with a 25% dextrose base, or TPN 12.5% dextrose and given nothing by mouth, or saline solution and allowed to eat ad lib. Sham animals ate ad lib. After 6 days the animals were killed and portal blood was assayed for endotoxin and cultured. Cultures were also taken of the liver. Serum hepatic enzyme concentration and hepatic fat were determined. All cultures and endotoxin assays were negative. Microscopy revealed nonlipid vacuolization in both TPN groups, a finding reproduced by direct portal infusion of endotoxin. There was significant hepatic steatosis in the 25% dextrose base TPN versus all other groups (28.6% liver weight versus 6.3% liver weight; p less than 0.05). This was correlated with caloric intake (28.7 calories/100 gm/day versus 21.2 calories/100 gm/day; p less than 0.05). Liver enzymes were not significantly different among groups. We conclude that hepatic steatosis in TPN is a result of overfeeding a glucose only substrate and that fatty infiltration is independent of changes in blood hepatic enzyme concentrations. Although other morphologic changes of hepatotoxin-induced injury were seen in the TPN group, portal endotoxemia to the level of 1 ng/ml could not be documented.

Animals↗