The role of alanine in the nitrogen conserving quality of the branched-chain amino acids in the postinjury state.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to H Freund.
Explore the source record for details and available documents.
One of the controversies in the nutritional therapy of patients with renal failure is the respective role of either the essential amino acids alone or both essential and nonessential amino acids in the treatment of these patients. During a period when essential amino acids were unavailable, a large number of patients with acute renal failure was treated with a modified solution consisting of both essential and nonessential amino acids. The solution consisted of 3.8 grams of nitrogen in 46 per cent dextrose in units of 750 milliliters. A mean of 2,322 +/- 151 calories was administered to this group of patients. Over-all, the survival rate was 9 per cent as opposed to 75 per cent in the previous group treated with essential amino acids only and hypertonic dextrose, 40 per cent, in the group of historical controls treated with hypertonic dextrose. The groups are not strictly comparable because the group treated with both essential and nonessential amino acids may not have been strictly comparable, particularly with a slightly longer duration of renal failure, higher initial blood urea nitrogen level and lower urine volume than either of the other two groups previously treated. While adequate stabilization, but not a decrease in the blood urea nitrogen level, may be achieved from the use of both essential and nonessential amino acids, the excessive mortality seen may be related to differential effects of essential amino acids in supporting host resistance, while nonessential amino acids do not. The results of this study suggest that, until the safety and efficacy of a mixture of essential and nonessential amino acids in renal failure can be demonstrated, essential amino acids remain the treatment of choice as the nutritional support of patients with acute tubular necrosis.
Explore the source record for details and available documents.
Therapy of chronic hepatic encephalopathy is often frustrating, limited as it is by the ability to adequately nourish such patients. Protein is needed for repair, but such patients are intolerant of protein. Previous work from this and other laboratories has suggested that the distorted plasma amino acid pattern may be causally related to hepatic encephalopathy. A single, well-studied, long-term patient received therapy with a branched-chain amino-acid-enriched elemental diet that not only enabled adequate nutrition with protein but resulted in improvement in hepatic function as well as reversal of some aspects of hepatic encephalopathy that heretofore have been deemed irreversible. The results confirm that branched-chain-enriched amino acid diets previously successful in the intravenous mode may be successfully used in chronic long-term support of patients with protein intolerance, with improvement in hepatic function secondary to improvement in nutrition.
An improved measuring system based on the Coulter principle and developed in our laboratory is used to size human blood platelets. The mean volume of platelets in 24 healthy subjects is found to be 8.45 micron 3 with a standard deviation of 1.07 micron 3; the typical size-distribution curve is unimodal and asymmetrical, with a marked skew to the right. The effects of different reagents on platelet size (shape factor x volume) are evaluated. Platelets increase in size by 23% following suspension in isotonic, phosphate-buffered saline and incubation with 10 microM adenosine diphosphate; no change is observed when the suspending medium is autologous plasma. Cooling the platelets to 0-4 degrees C results in a size increase of 25%; rewarming to 37 degrees C restores them to their initial size within 2 hr. A similar increase occurs when the platelets are incubated with 1-10 mM colchicine. It is proposed that these reagents, which are known to produce changes in the orientation of the marginal bundle of microtubules, cause platelets to undergo disc-sphere transformations. Calculations are made which show that such transformations increase platelet size by 27% as measured electrically, and we conclude that the so-called volume changes reported in the literature reflect shape changes only and that no true volume increase actually takes place.
Chromium is required for maintenance of normal glucose tolerance. After complete bowel resection and five months of total parenteral nutrition, severe glucose intolerance, weight loss, and a metabolic encephalopathy-like confusional state developed in a patient. Serum chromium levels were at the lowest normal level. Supplementation of 150 microgram of chromium per day reversed the glucose intolerance, reduced insulin requirements, and resulted in weight gain and the disappearance of encephalopathy. The low levels of chromium and response to chromium supplementation suggest that chromium deficiency can arise in long-term total parenteral nutrition.
Explore the source record for details and available documents.
Five more cases are added to the 88 reported cases of successfully treated newborns with congenital colonic atresia and stenosis. Because colonic atresia and stenosis are lethal conditions when untreated, early diagnosis and operative treatment are major requisites for survival. A two-stage procedure consisting of an emergency colostomy for decompression as the first stage and an elective resection with anastomosis a few months later is recommended. The need for thorough exploration of the abdomen is emphasized because atresias may be multiple or may be associated with additional gastrointestinal anomalies.
This paper describes an approach to prevent reflux and ascending cholangitis after hepatic portoenterostomy for biliary atresia. The method utilizes the terminal ileum and right colon as the conduit and a Nisson-type plication to the area of the ileocecal valve. It was used in one patient.
Explore the source record for details and available documents.
Postinjury metabolism is characterized by breakdown of muscle protein as substrate for energy production and gluconeogenesis and by the resultant loss of lean body mass and weight loss. The branched chain amino acids (BCAAs) which are principally oxidized by the skeletal muscle have been implicated in recent in vitro and in vivo studies as having special anticatabolic and regulating effects in skeletal muscle. We studied the anticatabolic effects of the BCAAs in 35 patients undergoing operative injury of moderate severity. In a prospective randomized and blinded manner patients were infused for five days starting immediately after surgery with either 5% dextrose or 5% dextrose with an amino acid solution containing 22, 35 or 100% BCAAs. All patients survived and there were no major postoperative complications. Mean hospital stay was 17 days for patients receiving amino acids and 19 days for patients receiving 5% dextrose only (p = ns). All three groups receiving amino acid solutions were in nitrogen equilibrium or in a slight positive nitrogen balance, while the group receiving 5% dextrose only was in a mean negative nitrogen balance of 6.6 +/- 0.6 gN/day. The differences between the three groups receiving amino acids were slight and not significant. Weight loss was 2 +/- 0.7 kg in the 5% dextrose group, 1 +/- 0.7 kg in the 22% BCAAs group, 0.5 +/- 0.5 kg in the 35% BCAAs group and the 100% BCAAs group gained 0.4 +/- 1.8 kg. Blood chemistries in the different groups and during the study period remained within normal limits except for ammonia levels rising significantly in the 5% dextrose group and SGOT levels rising in the 22% and 35% BCAA groups. With mild variations the plasma amino acid patterns in all groups were similar to the normal pattern, even in the 100% BCAAs group receiving an unbalanced amino acid solution, suggesting the complete cessation of amino acid efflux from muscle, the muscle depending solely on the exogenous supply of BCAAs to satisfy its metabolic requirements. The results suggest that early nutritional suppport in the postoperative period will result in nitrogen equilibrium and that the infusion of the three BCAAs only in the postoperative state is as effective in preventing muscle catabolism as other more balanced amino acid solutions. In the postinjury state balanced amino acid solutions rich in BCAA may prove beneficial.
Essential fatty acid deficiency (EFAD) has been commonly and readily diagnosed during fat-free total parenteral nutrition (TPN), with only vague awareness of possible functional and clinical derangements secondary to essential fatty acid deficiency. Arachidonic acid is known to be a precursor for prostaglandin (PG) synthesis. Prostaglandins are known to be intermediaries between stimulus and cellular response in a variety of physiologic and pathologic processes; one would suspect therefore that EFAD would result in PG deficiency with resultant multiple derangements in functions regulated by PG. We tested this hypothesis by serially measuring intraocular pressure (IOP) in patients before and during fat-free TPN and after supplementing these patients with fat. In the eye as well as in various other organs PG are believed to act as mediators of adrenergic neurotransmission by a negative feedback mechanism. As catecholamines are potent ocular hypotensive agents, decreased levels of PG due to EFAD will cause increase in catecholamine turnover with a reduction in IOP. Two groups of patients matched as to their age, sex, nutritional status and diseases were studied. One group (control) was receiving a normal diet or fat-containing TPN while the other group was receiving fat-free TPN. IOP in the fat-free TPN group dropped from 13.7 +/- 0.4 mmHg pre-TPN to 9.3 +/- 0.5 mmHg during the first week of fat-free TPN. Within two weeks after supplementation of fat or return to normal oral diet IOP returned to 13.9 +/- 0.3 mmHg. Prostaglandin levels, which were 0.025 +/- 0.004 ng/ml pre-TPN or in control patients decreased to 0.012 +/- 0.002 ng/ml (p < 0.001) during fat-free TPN, to return to normal after fat was added to TPN regime or patients returned to normal oral diet. During fat-free TPN linoleic acid levels decreased to 40% of its initial value with a mild increase upon the addition of fat, while eicosatrienoic acid and the triene:tetraene ratio increased to 6.5 times their initial values. Arachidonic acid levels did not change during fat-free TPN or after repletion with fat. Intraocular pressure determination seem to be a simple, harmless, inexpensive, reliable and sensitive indicator of EFAD. Moreover, IOP determination represent a functional derangement which in a clinical setting lends functional credence to the biochemical changes of EFAD whose entire significance has not yet been determined. Similarly, serial IOP determinations are sensitive in detecting adequate functional repletion of EFAD. As PG are known to act as intermediaries in a variety of physiological processes it seems reasonable to assume that the change in IOP is only one of many different changes and derangements to occur as a result of PG and EFA deficiency.
Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.
This study was designed to investigate whether exercise, when used as an adjunct to parenteral nutrition, has any influence on postoperative muscle catabolism, amino acid metabolism, and nitrogen balance. Twenty male Sprague-Dawley rats were divided into two groups of exercised and nonexercised animals. All animals underwent laparotomy and jugular vein cannulation, were placed in metabolic cages, and were infused with a dextrose-protein solution at 15 kcal and 0.56 g amino acids/100 g body wt per 24 h for a total of 96 h. The exercised animals were run on a treadmill for 15 min/day for a total of 3 days. There was no difference in nitrogen balance and body weight change between exercised and nonexercised animals, as well as no difference between animals who experienced different degrees of exercise. Total and individual plasma amino acids in the exercised group were 15% lower than in the nonexercised group; the total and individual free amino acids in muscle of the exercised group were 66% higher than in the nonexercised group. This pattern of high levels of amino acids in the muscle, coupled with decreased plasma concentrations, is suggestive of increased amino acid turnover in the muscle of the exercised animals. We suggest that, in the postoperative or postinjury period, exercise has a stimulating effect on amino acid turnover in the skeletal muscle resulting from 1) amino acid (mainly the branched-chain amino acids) consumption for energg metabolism and gluconeogenesis, and 2) protein synthesis. The net balance of both results in nitrogen equilibrium similar to that of a nonexercised control group.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A technique for percutaneous catheterization of the internal jugular vein in infants and children was used since January 1975 in 206 patients ranging in age from a few hours to 12 years old. The series included 31 premature infants weighing less than 2,500 grams and 107 babies weighing less than 4,000 grams. Five attempts at cannulation failed. Each catheterization procedure required an average of 1.8 needle insertions before the vein was entered. In 129 patients, the first attempt was successful. Sixteen complications related to the procedure occurred early in our experience, seven of which were life threatening. One death was directly ascribed to the actual insertion of the catheter and mediastinal extravasation of infusion material. Most of the early complications probably could have been injected through the catheter immediately after cannulation, in addition to aspirating the blood and lowering the infusion bottle. The 22 late complications were related to infection; one infant died because of catheter sepsis. To minimize septic complications, an arbitrary limit of seven days was set, after which the catheter was replaced. Cannulation of the internal jugular vein in infants and children should be regarded as a serious surgical procedure to be performed by a trained team and only when properly indicated.