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Biomedical subjects

S F Lowry

Publications and source records attributed to S F Lowry.

At least 163 records · Page 9Linked to original sources

Body protein kinetics during perioperative intravenous nutritional support.

The kinetics of whole body protein metabolism in eight patients with benign disease were evaluated during perioperative isocaloric and isonitrogenous intravenous feedings. A prime infusion of 15N-glycine with determination of urinary end product enrichment and stochastic analysis was used to determine protein kinetics. Surgically induced increases in body protein turnover, synthesis and breakdown were evident on the fifth postoperative day. Abdominal operation was associated with a rise in urinary 3-methylhistidine (3MH) excretion. The postoperative alteration in the relationship between 3MH excretion and body protein breakdown suggests that even mild to moderate surgical injury induces tissue specific changes in protein metabolism. Resting energy expenditure remained unchanged from that of the preoperative levels on the fifth postoperative day. Despite significant changes in body and tissue specific protein kinetics, there is no change in the apparent efficiency of oxygen use for protein homeostasis postoperatively. The failure to observe a relationship between energy expenditure and protein metabolism suggests that only a small proportion of body oxygen uptake is directed toward protein homeostasis after elective surgical procedures. A comparison of perioperative complete intravenous feeding to hypocaloric regimens will be necessary to evaluate more fully the impact of protein and energy balance upon cellular and body protein homeostasis after injury.

Aged↗

One hundred and fourteen fistulas of the gastrointestinal tract treated with total parenteral nutrition.

During a period of five years, all patients with fistulas of the gastrointestinal tract who received total parenteral nutrition as a part of the therapy were evaluated retrospectively. One hundred and eight patients with 114 fistulas of the gastrointestinal tract were studied. There were 58 male and 50 female patients. The mean age of the patients was 58 years old. Fifty-one per cent (58) of all fistulas resulted from surgical complications and 30 per cent from inflammatory disease. The most common origin of the fistula was the small intestine (48 per cent), with the large intestine being the next most common origin (26 per cent). Ninety-eight of the fistulas were treated successfully. The mean time for closure from the time of diagnosis was 30.9 days. Sixty-one per cent (69) of all fistulas closed spontaneously, the use of parenteral nutrition resolved 37 per cent (42) and 24 per cent (27) resolved after surgical control of sepsis. Twenty-five per cent (29) of the fistulas required definitive surgical closure. Sixteen patients died prior to resolution of the fistula, 11 deaths were directly related to septic complications of the fistula and one died as a result of hemorrhage of the fistula tract. The direct fistula-related mortality rate was 10.5 per cent. Whereas the mortality rate for fistulas remained stable, spontaneous closure rates continue to improve. This is attributed to improved "para-surgical" care, appropriate nutritional support and early and aggressive control of sepsis. Ninety to 95 per cent of fistulas that spontaneously resolve will do so within four to five weeks. Inflammatory disease of the intestine and radiation induced fistulas continue to respond poorly to medical management.

Adult↗

Tracer priming in human protein turnover studies with [15N]glycine.

Sixty-three studies in healthy normal volunteers (n = 29), malnourished cancer (n = 8) or non-cancer patients (n = 9), and postoperative radical cystectomy patients (n = 17) were conducted to evaluate the primed constant infusion labeling technique for the estimation of whole-body protein turnover under a variety of dietary conditions. [15N]Glycine was used as the tracer with a prime to infusion ratio of 1300 to 3300 min and a continuous-infusion rate of 0.11 to 0.33 micrograms 15N . kg-1 . min-1 for 24 to 36 hr. The isotopic steady-state enrichment was reached in all subjects both in urinary urea and ammonia between 10 and 26 hr (mean 18 +/- 2). During protein calorie fasting the attainment of isotopic steady state is much quicker (10 to 18 hr) with a primed constant infusion than with a constant infusion alone (approximately 38 hr). A P/I ratio greater or less than 1800 (min) usually resulted in a delay of plateau attainment without affecting the protein turnover values. Reliable estimates of protein kinetics in humans can be made in clinical conditions with a 26-hr infusion of glycine at the rate of 0.28 microgram 15N . kg-1 . min-1 with a P/I ratio of 1800 min, collecting six urine samples every 2 hr from 16 hr and analyzing for both urinary urea and ammonia enrichments.

Ammonia↗

Orotic acid excretion during starvation and refeeding in normal men.

The effects of acute food deprivation and subsequent refeeding on urinary orotic acid excretion were examined in nine healthy adult male subjects. During inpatient metabolic ward conditions, the volunteers were fed a nutritionally complete, pyrimidine- and purine-free diet for three days and subsequently underwent a ten-day fast followed by a ten-day period of refeeding by total parenteral nutrition. Mean daily excretion of 4.33 +/- 0.23 mg (2.77 +/- 0.12 mg/g creatinine) of orotic acid during the enterally fed state was significantly reduced (mean 46 +/- 5%) in all subjects during starvation. This reduction in the excretion of orotic acid during starvation is more likely related to a lowered rate of production and utilization. The starvation adaptation of orotate excretion occurred more rapidly than did the decrease in urinary nitrogen loss. All subjects showed an increase (mean 48 +/- 14%) in the excretion of orotic acid during the first day of refeeding which continued throughout the refeeding phase. A significant positive correlation was shown between the daily orotic acid excretion and nitrogen intake (r = 0.98) or protein balance (r = 0.83). The response to refeeding of acutely malnourished normal male is an increase in orotic acid excretion with a decrease in whole body protein catabolism.

Adult↗

Whole-body protein breakdown and 3-methylhistidine excretion during brief fasting, starvation, and intravenous repletion in man.

Simultaneous whole-body protein breakdown (using 15N-glycine) and urinary 3-methylhistidine (3MH) excretion rates were determined in six hospitalized normal volunteers after 10 days of starvation and a subsequent 10-day period of total parental nutrition (TPN). These data were contrasted to whole-body protein breakdown and urinary 3MH excretion in ten depleted (14.8% body weight loss) patients with benign intraabdominal disease studied in the basal (48 hours without nutrient intake) and intravenously refed states. The rates of whole-body protein breakdown were significantly reduced from basal (brief fasting or starvation) conditions in both normal volunteers (p less than 0.01) and depleted patients (p less than 0.01) during TPN. The rate of protein catabolism normalized for creatinine excretion in patients was higher than that observed in normal subjects during both basal (p less than 0.05) and intravenous feeding conditions. Daily urinary 3MH excretion was reduced during intravenous feeding in both starved normal volunteer (235 +/- 13 mumol/d to 197 +/- 9 mumol/d p less than 0.05) and in depleted patients (209 +/- 31 mumol/d to 140 +/- 35 mumol/d), and an apparent linear relationship between protein breakdown and urinary 3MH, normalized for creatinine excretion, was obtained in both volunteer and patient (r = 0.85) populations during fasting-refeeding. However, separate regression analysis of the protein breakdown and 3MH responses of both volunteer and patient groups under conditions of fasting, starvation, and refeeding revealed significant differences between volunteer and patient populations during intravenous refeeding (p less than 0.01). Further analysis of 3MH excretion in relationship to nitrogen balance during refeeding suggests a complex relationship between urinary 3MH excretion and whole-body protein metabolism that may be partly related to the degree of antecedent malnutrition.

Adult↗

Vitamin requirements of intravenously fed man.

The continued refinements in the application of intravenous feeding must include the provision of optimal micronutrients if the clinical utility of this technique is to be fully realized. From the above discussion, it is readily apparent that our understanding of vitamin requirements during IVF is fragmentary at best. This limited knowledge has unfortunately been extrapolated to the daily regimen of nearly all parenterally nourished patients. The fact that this is done without apparent ill effect should not deter future investigation, particularly in the critically injured or organ failure patient where subtle vitamin deficiencies may be masked by concurrent illnesses. Research should be directed toward the assessment of tissue vitamin concentration and function, with correlations to the degree of energy expenditure and/or nitrogen turnover exhibited by the patient.

Adult↗

Cancer cachexia and protein metabolism.

Metabolic abnormalities arising from malnutrition and malignancy are seen in patients with cancer cachexia. To discriminate between the effects of pure malnutrition and tumour-specific metabolic alterations, the kinetics of whole-body metabolism were determined in 7 untreated, malnourished cancer patients and in 11 patients with benign disease, also malnourished, by means of primed constant infusion of 15N-glycine. Patients in both groups received 500 kcal/day as 5% glucose solution without any nitrogen. Whole-body protein turnover was 32% and 35% higher in the cancer patients than in the non-cancer patients and starved normal subjects respectively. Similarly, the rate of protein synthesis was 35% and 54% higher in the cancer patients than in the non-cancer patients and starved normal subjects respectively. Our study supports the view that aberrations of host metabolism in patients with cancer cachexia are different from those in non-cancer patients suffering equivalent weight loss.

Aged↗

Influence of nutritional status on exertion-induced forearm amino acid metabolism in normal man.

Normal volunteers were evaluated in the postabsorptive state, following 10 days of protein-calorie starvation, and during intravenous feeding ( ivf ) to determine the impact of nutritional status upon exertion-induced muscle amino acid metabolism. An isolated forearm model allowed an evaluation of recovery of metabolism following 1 min of submaximal isotonic exercise. Forearm blood flow returned to near basal levels within 15 min after exertion during postabsorptive and ivf conditions, but remained greater than or equal to 150% of basal at 1 hr after exercise during starvation. At 30 and 60 min after exercise, forearm plasma flux of total and essential amino acids were unchanged from basal in the postabsorptive state. However, the pattern of essential amino acid flux demonstrated a relative reduction in isoleucine and leucine efflux compared with basal, and this pattern persisted throughout 1 hr of recovery. During starvation, a significant (P less than 0.05) increase in total and essential amino acid efflux was observed throughout the recovery period. Starvation was also associated with significant increases in alanine and lysine efflux during recovery. Intravenous feeding was associated with a significant (P less than 0.05) uptake of essential amino acids with respect to basal levels at 30 min after exercise. At 60 min, there was a shift to total amino acid efflux but no change from basal flux for essential amino acids. During ivf , the pattern of essential amino acid uptake returned to basal within 1 hr after exertion.

Adult↗

A prospective, randomized study of adjuvant parenteral nutrition in the treatment of sarcomas: results of metabolic and survival studies.

A prospective, randomized study was performed to evaluate the use of total parenteral nutrition (TPN) in a group of young patients receiving aggressive chemotherapy for metastatic or locally recurrent sarcomas. Fourteen patients were randomly selected to receive TPN and 18 to receive conventional oral nutritional support (CN). During the study period (from first dose of chemotherapy to recovery from myelosuppression), the TPN patients received between 1020 and 2100 calories/m2/day (median 1650) and between 5.3 and 12.4 gmN/m2/day (median 8.9), while the CN patients received between 380 and 880 calories/m2/day (median 685) and between 0.0 and 3.7 gmN/m2/day (median 1.5). The mean daily nitrogen balance during the study period for the TPN group (-3.0 to + 1.3 gmN/m2/day, median -0.7) was significantly higher (p = 0.005) than that of the CN group (-6.2 to -0.7 gmN/m2/day, median -2.6). Serum protein levels (albumin, total protein, and transferrin) did not differ between the two treatment groups. The proportion of patients responding to therapy and the long-term survival rates were similar in the treatment groups. Thus despite established improvement in nitrogen balance, no survival or therapeutic advantage was demonstrated for the adjuvant parenteral nutrition group. Further studies of the role of parenteral nutrition as an adjuvant to cancer chemotherapy are needed to determine which populations of patients will benefit from its use.

Adolescent↗

The effect of total parenteral nutrition on chemotherapy-induced myelosuppression. A randomized study.

We studied the effect of total parenteral nutrition on recovery from myelosuppression in patients receiving intensive chemotherapy. Twenty-seven patients (ages 11 to 33 years) with locally recurrent or metastatic Ewing's sarcoma, rhabdomyosarcoma, or osteosarcoma were randomly selected to receive either conventional oral nutrition or total parenteral nutrition concurrently with intensive chemotherapy. The control group (15 patients) received significantly fewer calories (range 380 to 880/m2 per day, median 685 versus range 1,020 to 2,100 median 1,650) and less nitrogen (0-3.7 g/m2 per day, median 1.5 versus range 5.3 to 12.4, median 8.9) than the group receiving total parenteral nutrition (12 patients). Assessment of recovery from myelosuppression was based on the length of time the absolute granulocyte count was below 500/mm3, the length of time the platelet count was below 40,000/mm3, the number of days the platelet count was below 20,000/mm3, and the number of blood transfusions required. There was no statistical difference in any of the parameters evaluated between the group that received total parenteral nutrition and the control group (p less than 0.05); granulocyte and platelet recovery and the difference in transfusion requirements favored the control group with marginal statistical significance (p = 0.05). The frequency of clinical infections was similar in the patients receiving total parenteral nutrition (five of 12) and in those receiving conventional oral nutrition (five of 15). Thus, although total parenteral nutrition could be safely administered in this severely myelosuppressed population, no benefit could be defined in recovery from bone marrow suppression or frequency of clinical infections.

Adolescent↗

Metabolic alterations in a noncachectic animal tumor system.

The increased energy expended by the host to synthesize substrate, which is utilized by the tumor, is a potential cause of cancer cachexia. In vivo glucose and alanine kinetics were examined by tracer methodology in a sarcoma-bearing rat model. The effects of 3-mercaptopicolinic acid, a potent inhibitor of gluconeogenesis, was also examined on this model. Both tumor-bearing (TB) and nontumor bearing (NTB) animals were gaining weight prior to study and the tumors were relatively small. The TB animals had significantly lower plasma glucose and higher blood lactic acid levels compared with NTB animals. After inhibition of gluconeogenesis, the plasma glucose decreased and the blood lactate increased significantly more in TB than NTB animals. The glucose turnover rate was significantly greater in TB compared with NTB animals, as was the rate of glucose recycling and the rate of gluconeogenesis (alanine leads to glucose), both energy demanding processes. These results suggest that the tumor-bearing animal, even prior to significant cachexia, has an excess demand for energy, the provision of which may be a significant factor in malignant cachexia.

Alanine↗

Zinc and copper replacement during total parenteral nutrition.

A prospective study of zinc and copper replacement concurrently with total parenteral nutrition was undertaken during 29 courses of total parenteral nutrition in 20 tumor-bearing patients. Urinary excretion of zinc and copper was prospectively studied in eight of these subjects. While progressive declines in zinc and copper blood levels occurred in four unsupplemented control patients, maintenance of plasma trace metal concentrations within normal limits was accomplished by daily intravenous zinc and copper. A daily intravenous intake of 70 to 80 micrograms/kg of zinc and 60 to 65 micrograms/kg of copper were generally associated with normal blood levels and positive urinary balance of these trace elements. This study outlines a safe and effective zinc and copper replacement regimen in patients undergoing total parenteral nutrition.

Adolescent↗

Protean manifestations of neonatal hyperinsulinism.

Endogenous hyperinsulinism is the leading cause of persistent hypoglycemia in children under one year of age. Classically, the symptoms of neonatal hypoglycemia have been referable to central nervous system dysfunction, with seizures described in nearly all patients. Our experience with eight neonates emphasizes the protean manifestations of this disease. One patient presented with a maternal history of diuretic use, and developed asymptomatic hyperinsulinism documented by provocative testing. The hyperinsulinism cleared after two weeks of medical therapy. This transient hyperinsulinism may have been secondary to use of a thiazide-type diuretic. A second patient presented, as a neonate, with a large abdominal mass but no seizure activity. Exploratory laparotomy revealed an 11 x 5 x 3 cm pancreatic tumor, which required splenectomy, 60% gastrectomy and duodenectomy for removal. Histologic examination demonstrated an insulin-secreting hamartoma. A third patient died suddenly without prior symptoms, and was found to have striking nesidioblastosis on pathologic examination. One infant presented with absence of the abdominal musculature (prune belly syndrome) and features of the Beck-with-Wiedeman syndrome, as well as profound hypoglycemia. Only three patients had seizures, and an additional patient had jitteriness. Pathologic diagnoses were: nesidioblastosis (n = 2); islet cell hyperplasia (n = 1); adenoma (n = 1); hamartoma (n = 1); transient hyperinsulinism (n = 1). One patient's pancreas showed areas of nesidioblastosis, islet cell hyperplasia, and a discrete adenoma in the region of the common bile duct. Careful diagnostic testing is essential in these patients, inasmuch as hypoglycemia is poorly tolerated by neonates and infants. Using the diagnostic algorithm presented here, all patients' endogenous hyperinsulinism was documented quickly and efficiently. Recognition of the broad spectrum of symptoms with which these patients may present is essential if serious neurologic sequelae are to be avoided.

Chlorthalidone↗

Deep venous thromboembolism in patients undergoing inguinal lymph node dissection for melanoma.

Deep venous thromboembolism (DVT) was studied in 44 patients with clinical Stage I, II, and III melanoma undergoing staging and therapeutic inguinal lymph node dissection. The ability of two noninvasive methods of surveillance, the phleborheograph (PRG) and the 125I fibrinogen scan to detect deep venous thrombosis was determined by comparison with prospective bilateral lower extremity venograms. In addition, the therapeutic impact, both beneficial and detrimental, of low dose heparin, 5000 units administered subcutaneously two hours prior to and every eight hours after operation was determined in a double blind study. The sensitivity of the PRG and 125I fibrinogen scan were both 20%. There were five deep venous thrombi, and two pulmonary emboli for a combined incidence of DVT of 13.6% for the entire patient population. However, there was no significant difference in the incidence of DVT between the two groups. The heparin-treated patients had an increased total volume (796 +/- 516 versus 388 +/- 208 ml; p less than 0.05), and duration of wound drainage (9 +/- 4 versus 13 +/- 6 days; p less than 0.05).

Bed Rest↗

Glucose turnover and gluconeogenesis in a patient with somatostatinoma.

Previous evidence has documented the hyperglycemia and glucose intolerance that occur during prolonged infusions of somatostatin and in patients with somatostatinoma. We studied glucose utilization and production and gluconeogenesis (from alanine) in a patient with the somatostatinoma syndrome (peripheral somatostatin levels 20,000 pg/ml) during saline (basal state) and glucose infusion (1.78 mg/kg . min). Plasma glucose levels increased from 163 to 229 mg/100 ml during glucose infusion, whereas lactate, free fatty acid, and glucagon levels did not change. Endogenous glucose production decreased from 7.34 to 0.0 mumol/kg . min, and the percentage of glucose derived from alanine also decreased from 10.5 to 7.4. Glucose clearance decreased from 0.81 to 0.74 cc/kg . min and suggests that the hyperglycemia of the somatostatinoma syndrome is secondary to reduced peripheral glucose utilization secondary to relative insulin deficiency.

Adenoma, Islet Cell↗

Glucose disposal and gluconeogenesis from alanine in tumor-bearing Fischer 344 rats.

For the study of glucose carbon recycling and incorporation of carbon atoms from plasma glucose, [3-3H]glucose and [U-14C]alanine were injected into inbred non-tumor-bearing (NTB) and tumor-bearing (TB) male F344 rats. The glucose and alanine kinetics were determined in relation to antecedent food intake and carcass weight loss. Whereas fed NTB and TB rats appropriately experienced reduced glucose disposal with decreased food intake (0.99 vs. 0.29 mg/min -100 g(-1) compared wtih observations in starved NTB rats), starved TB rats exhibited increased glucose utilization. Both fully fed and cachectic TB groups exhibited increased isotopic carbon recycling compared to the carbon recycling of NTB control groups, whereas starved TB rats did not demonstrate increased recycling compared to the carbon recycling (27% of C-atoms recycled). These findings suggest that alterations of glucose turnover, carbon recycling, and gluconeogenesis in the fed host parallel hypophagia and weight loss, regardless of TB status.

Alanine↗

Local effects of 16, 16-dimethyl prostaglandin E2 on gastric blood flow and acid secretion.

The effects of luminal administration of 16, 16-dimethyl PGE2 on gastric blood flow and histamine-stimulated acid secretion were determined in a double-chambered preparation of canine fundic stomach. This model permitted simultaneous assessment of two segments of mucosa (17 cm2 each), one control and the other test, supplied by the same vascular pedicle. Topical application of 25 microgram 16, 16-dimethyl PGE2 in 15 ml HCl to the test chamber significantly increased mucosal blood flow of the test chamber from 1.2 +/- 0.1 to 2.5 +/- 0.5 ml/min (P less than 0.05) whereas no significant change in mucosal blood flow was noted in the control mucosa. Intravenous infusion of histamine at 1.0 microgram/kg/min stimulated comparable amounts of acid secretion in both segments of mucosa. The addition of 16, 16-dimethyl PGE2 (25 microgram in 15 ml of HCl) in the bathing solution of the test chamber significantly reduced histamine-stimulated acid secretion from 22.5 +/- 3.1 to 8.4 +/- 1.2 microEq/min (P less than 0.01) in the test mucosa whereas the control mucosa showed no evidence of secretory inhibition throughout the experiment. Since the control mucosa was supplied by the same vascular pedicle as the test mucosa, we concluded that the observed vasodilating and antisecretory effects of luminal administration of 16, 16-dimethyl PGE2 were local rather than systemic effects following its absorption from the stomach.

16,16-Dimethylprostaglandin E2↗

Glucose turnover and gluconeogenesis during hypocaloric glucose infusion in tumor-bearing F344 male rats.

Glucose turnover ([3(3)H]glucose) and gluconeogenesis from alanine ([U-14C]alanine) were measured in non-tumor bearing (NTB) and tumor-bearing (TB) inbred F344 male rats during starvation and in response to graded levels of glucose infusion. All groups demonstrated a glucose turnover appropriate to the prevailing steady-state plasma glucose level. Whereas NTB animals exhibited maximal suppression of gluconeogenesis from alanine at infusion rates of 0.39 mg/100 g total body weight/minute, TB animals suppressed alanine-to-glucose conversion only at a glucose infusion rate of 0.71 mg/100 g total body weight/minute. Glucose clearance was consistently higher in TB groups but did not change in either NTB or TB groups during infusion. Blood lactate levels increased in response to glucose infusion only in TB animals. These results suggested that starved TB animals obligately utilized more glucose than did NTB controls but were able to adjust turnover appropriately to plasma glucose levels. However, gluconeogenesis was suppressed only at higher glucose infusion rates in TB rats compared to NTB animals.

Animals↗