Biomedical subjects

D O Jacobs

Publications and source records attributed to D O Jacobs.

At least 55 records · Page 3Linked to original sources

PubMed1990

Safety of glutamine-enriched parenteral nutrient solutions in humans.

To determine the safety of glutamine-enriched parenteral nutrition, seven normal volunteers were admitted to the Clinical Research Center for three 5-d study periods. The subjects received infusions of parenteral nutrients containing increasing doses of glutamine (0, 0.285, and 0.570 g.kg body wt-1.d-1) substituted for alanine and glycine. Each study period was preceded by greater than or equal to 2 wk of normal food intake. The diets were isocaloric (1.2X estimated basal metabolic rate) and isonitrogenous (1.5 g protein.kg-1.d-1) with nonprotein calories given as dextrose (38%) and fat emulsion (62%). The diets were all well tolerated and there were no untoward effects. Plasma glutamine concentrations increased significantly with glutamine administration but plateaued at concentrations approximately 25% above control values. Ammonia and glutamate, potentially toxic metabolites of glutamine, did not change significantly with glutamine enrichment. Nitrogen balance and hormonal concentrations were unchanged during the three dietary periods. Results of mental-status examinations and continuous performance testing were normal and unchanged throughout the three periods. Glutamine-enriched parenteral nutrient solutions are well tolerated with no associated signs of toxicity in normal humans.

Adult↗

PubMed1989

The effects of tumor necrosis factor and their selective inhibition by ibuprofen.

High doses of tumor necrosis factor (TNF) cause hypotension, metabolic acidosis and, death. At Brigham and Women's Hospital, the effects of a sublethal, 6-hour infusion of TNF (0.57 X 10(5) Units/kg body weight) in twelve anesthetized dogs were studied. The dose caused falls in mean arterial pressure from 153 mmHg to 96 mmHg, pulmonary artery pressure (-4.5 mmHg), central venous pressure (-2.5 mmHg) and pulmonary capillary wedge pressures (-5.25 mmHg). Associated with these responses were a fourfold increase in urine volume (22.4 ml/kg/6 hours as compared to 5.2 ml/kg/6 hours in controls), significant pyrexia (from 38.1 C to 39.5 C, rectal), tachycardia (from 125 to 175 beats/minute), and hypermetabolism. In addition, leukopenia and increased circulating stress hormone concentrations were observed. Blood glucose concentrations fell from 4.68 mM/1 to 3.97 mM/1 (84-71 mg/dl) within 3 hours of TNF infusion, whereas lactate and pyruvate concentrations increased. These alterations occurred in the absence of severe hypotension or acidosis and were similar to changes observed after endotoxin administration or gram-negative septicemia. Pretreatment of the animals with the cyclooxygenase inhibitor ibuprofen abolished most of the hemodynamic changes and attenuated other responses. These findings support the hypothesis that TNF is an important mediator of septic responses and that some of the effects of TNF are mediated via cyclooxygenase pathways.

Adrenocorticotropic Hormone↗

PubMed1989

Tumor necrosis factor enhances glucose uptake by peripheral tissues.

Anesthetized dogs received a constant intravenous infusion of tumor necrosis factor (TNF) or saline over 6 h. Glucose kinetics were studied by determining the rate of glucose turnover and hindlimb substrate flux. Cardiovascular responses were monitored and concentrations of counterregulatory hormones were also measured. TNF infusion caused a fall in blood glucose concentration from 4.6 +/- 0.1 to 3.9 +/- 0.2 mmol/l by 6 h (P less than 0.05). This mild hypoglycemia was associated with increased circulating levels of cortisol, glucagon, and epinephrine. The rate of glucose production increased from 26.5 +/- 2.1 to 32.5 +/- 0.7 mumol.min-1.kg body wt-1 (P less than 0.05) over the 6-h infusion period; this response was associated with increased glucose disappearance (26.4 +/- 2.2 to 32.7 +/- 0.9 mumol.min-1.kg body wt-1, P less than 0.05) and enhanced clearance (5.7 +/- 0.5 to 9.0 +/- 0.6 ml.min-1.kg body wt-1, P less than 0.05). As blood glucose levels fell, hindlimb glucose uptake and glucose clearance increased markedly in TNF-infused animals as compared with controls despite a 50% fall in mean serum insulin concentration. The exchange of lactate, pyruvate, and total amino acid nitrogen across the hindlimbs was similar in both groups of animals. However, arterial concentrations of lactate and pyruvate rose to two to three times their initial values. The hypoglycemia associated with the infusion of TNF results from a disparity between the rate of glucose appearance and disappearance. There is an increased uptake of glucose across the hindlimb; this response appears to be independent of insulin concentrations and may be related to direct effects of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

In vivo phosphorus 31 magnetic resonance spectroscopy of rat hind limb skeletal muscle during sepsis.

High-energy phosphate metabolism in skeletal muscle is altered during sepsis, although the chronology of events is uncertain. Phosphorus 31 magnetic resonance spectroscopy was used to measure changes in muscle energy stores of the left hind limb musculature of adult male rats during sepsis. Following control scans, cecal ligation and puncture were performed and scanning was repeated 6, 24, and 48 hours after surgery. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), a measure of energy stores, and adenosine triphosphate (ATP) to Pi ratio, a measure of the energy available for immediate use, were determined from peak heights. Intracellular pH was calculated using the distance between Pi and PCr peaks. In surviving animals, a 40% decrease in PCr/Pi ratio (+/- SEM) was observed by 24 hours (22.3 +/- 3.0 at time 0 vs 13.3 +/- 2.8 at 24 hours), whereas energy availability (beta-ATP/Pi) was statistically unchanged (18.2 +/- 2.2 at time 0 vs 15.2 +/- 1.2 at 48 hours). Intracellular pH did not change. Both PCr/Pi and ATP/Pi ratios were inversely correlated with time. In this model of documented peritonitis, skeletal muscle energy metabolism is rapidly altered following severe infection, and these changes can be detected using 31P magnetic resonance spectroscopy.

Adenosine Triphosphate↗

PubMed1988

Comparison of parenteral nutrition and enteral feeding with pectin in experimental colitis in the rat.

The effect of a pectin-supplemented enteral diet on experimental colitis was compared with parenteral nutrition and with a pectin-free enteral diet. Forty-five rats had feeding catheters placed into either the stomach (IG, n = 31) or the superior vena cava (IV, n = 14) and then received acetic acid (colitis) or saline (control) enemas. After the enema, all rats received the same diet, either IG or IV, for 6 d except for 15 rats (IGP, 9 colitis and 6 controls), which had 1% pectin added to the diet. At the end of the feeding period the IGP group had significantly less colonic inflammation and/or necrosis than either IV (p less than 0.03) or IG (p less than 0.04) groups. Nitrogen balance, serum albumin, total iron-binding capacity and body weight did not differ significantly among dietary regimens. Thus, the degree of bowel injury in experimental colitis was decreased when animals were fed a pectin-supplemented enteral diet and this effect was independent of nutritional status.

Animals↗

PubMed1988

The gut: a central organ after surgical stress.

The intestinal tract plays a central role in the protein catabolic response after injury and infection. The mucosa utilizes glutamine and thus spares glucose--presumably sparing this essential fuel source for tissues with an obligate glucose requirement. With inadequate nutritional support or prolonged stress, glutamine levels decrease in both the plasma and the tissue pools, which suggests that glutamine deficiency occurs. This is associated in time with atrophy of the gastrointestinal mucosa. This provision of dietary glutamine results in correction of the abnormally low glutamine concentrations and increased cellularity of the gut mucosa. The derangements in the intestinal mucosa associated with starvation, injury, infection, immunosuppression, chemotherapy, lack of enteral feedings, and other stresses are associated with a breakdown in the barrier function of the gut. Both bacteria and their toxins may enter the host from the intestinal lumen. Through interaction with the reticuloendothelial system, cytokines are produced, which stimulate the pituitary-adrenal axis and thus contribute to the stress response. The elaboration of glucocorticoids facilitates proteolysis, thus increasing glutamine release from skeletal muscle for gut repair. Although this homeostatic mechanism appears to aid mucosal repair and support immunologic responses, severe injury or prolonged glutamine deficits do not adequately support intestinal recovery and allow this cycle to become self-perpetuating (Fig 3). Adequate enteral feedings initiated early in the course of a disease appear to maintain adequate gut barrier function. In the frequent circumstance when feeding by this route is inadequate or impossible, glutamine-containing parenteral feedings offer an appropriate alternative therapy for bowel and immunologic support. Glutamine-containing parenteral feedings are associated with increased mucosal cellularity and improved survival after gut injury. Specific hormones also stimulate mucosal growth, and it is anticipated that a combination of hormones and specific nutrients will provide optimal support of the gut mucosa in the severely ill patient.

Animals↗

PubMed1988

Combined effects of glutamine and epidermal growth factor on the rat intestine.

Glutamine (GLN) is an important fuel and epidermal growth factor (EGF) is a potent mitogen for intestinal mucosa cells. GLN-enriched parenteral nutrition was administered to male Wistar rats, and subcutaneous injections of EGF were given for 3, 6, and 7 days. Control animals were fed a non-GLN-containing solution. Other groups of animals received GLN or EGF alone. Mucosal samples were obtained from the jejunum, ileum, and colon for measurement of weight, DNA, protein, and mucosal thickness. Disaccharidase activity was measured in the jejunum. After 3 days, only animals that received both GLN and EGF had a significant increase in small-bowel mucosal protein and thickness relative to controls. A similar pattern was observed in the colon, where animals that received both agents had a greater mucosal thickness, DNA, and protein content than controls. At 7 days, animals that received EGF or GLN had greater nitrogen retention. In addition, animals that were treated with EGF had elevated sucrase and maltase activity compared with GLN-fed animals at this time. Animals treated with GLN and EGF tended to have increased sucrase activity relative to controls. GLN feeding was associated with increased mucosal DNA and protein contents throughout the intestine for the combined series. EGF increased mucosal DNA and protein in the small intestine but not in the colon. The effect of EGF on the protein content of the small-bowel mucosa was dose dependent. The effects of GLN and EGF on the small bowel and colonic mucosa were additive. These studies suggest that specific nutrients and hormones may be used in combination to decrease the mucosal atrophy that commonly occurs after gut disuse or disease.

Animals↗

PubMed1986

Assessing burn wound depth using in vitro nuclear magnetic resonance (NMR).

There is no accurate noninvasive method for differentiating between partial-thickness and full-thickness cutaneous burn wounds. Full-thickness burns (FTB) result in slower resorption of wound edema than partial thickness burns (PTB). Since proton NMR parameters, particularly the T1 relaxation time, correlate with tissue water content (TWC), the present study determined whether proton NMR could distinguish PTB from FTB. An area of upper dorsum (approximately 15% BSA) of 35 adult rats was immersed in boiling water for either 3 sec (PTB) or 10 sec (FTB). In 10 control rats, the same area was immersed in room temperature water. Rats were sacrificed at either 3 or 48 hr after burn, and skin samples were analyzed to determine spin-lattice (T1) and spin-spin (T2) relaxation times. TWC was then measured gravimetrically by desiccation. Both T1 and T2 times significantly correlated with TWC (T1: r = 0.74, P less than 0.0001; T2: r = 0.75; P less than 0.0001). Both PTB and FTB resulted in significant elevations of T1, T2, and TWC 3 hr after injury (P less than 0.001). At 48 hr postburn the T1, T2, and TWC of the PTB group had decreased to control values (P less than 0.05), while all FTB parameters remained significantly elevated as compared to both the control and the 48-hr PTB parameters (P less than 0.001). In vitro NMR measurements distinguish PTB from FTB in this rat model within 48 hr. These data provide a basis for investigating in vitro NMR techniques for the noninvasive assessment of burn wound depth.

Animals↗

PubMed1985

Early diagnosis of experimental necrotizing enterocolitis using proton nuclear magnetic resonance.

The purpose of this study was (1) to confirm an experimental model of aminophylline-induced necrotizing enterocolitis (NEC); and (2) to determine whether nuclear magnetic resonance (NMR) imaging, based upon proton relaxation values (T1, T2), could detect NEC during its early pathogenesis. Sixty male weanling Lewis rats (avg wt = 75 g) were randomly assigned to one of three experimental groups: (A) superior mesenteric artery (SMA) occlusion (1 min) + aminophylline treatment (40 mg/kg); (B) SMA occlusion; and (C) sham midline laparotomy (control). All surviving animals were sacrificed at 48 hr postoperation and a specimen of ileum was removed for light microscopy (LM), electron microscopy (EM), and NMR analysis. Percentage water content was determined for representative specimens. Mortality occurred only in experimental group A animals (18.2%; P less than 0.05), who had received aminophylline. Microscopy of ileum from sacrificed animals of this group showed changes ranging from mild cellular disruption to severe hemorrhagic necrosis. Early ultrastructural changes consistent with NEC were detectable with EM before LM. Proton relaxation results obtained with NMR showed significant prolongation of T1 (252.5 +/- 4.4 msecs; P less than 0.001) and T2 (69.3 +/- 1.4 msecs; P less than 0.025) during the first stages of NEC. NMR may indeed enable early, safe diagnostic imaging of NEC in infants receiving aminophylline, or those who are otherwise at increased risk for development of this disease.

Aminophylline↗

PubMed1985

The identification of experimentally induced appendicitis using in vitro nuclear magnetic resonance.

Appendicitis was induced in six New Zealand white rabbits. The appendices from these animals had significantly higher spin-lattice relaxation times, T1, as determined in vitro by nuclear magnetic resonance (NMR) (10 controls vs 6 experimentals, 413 +/- 23 vs 455 +/- 41, X +/- SD, P less than (0.02). T1 correlated significantly with the water content of the appendiceal tissue (P less than 0.001). These findings suggest that in vivo NMR imaging techniques weighted on T1 might be able to identify human appendicitis noninvasively by detecting localized edema.

Animals↗

PubMed1985

In vitro detection of fatty liver infiltration in protein-depleted rats using proton nuclear magnetic resonance.

To determine if NMR techniques might be used to detect hepatic steatosis secondary to protein malnutrition, the T1 and T2 relaxation times of liver tissue from rats subjected to long-term protein malnutrition were measured in vitro. The liver tissue from rats fed a protein-deficient rat chow (PD) for 37 days (N = 9) was characterized by increased proportion of fat (P less than 0.001) but decreased water and nitrogen contents (P less than 0.001) relative to controls (N = 9). Mean T1 times were significantly shorter and T2 times significantly longer in liver tissue from protein-depleted animals (P less than 0.001). There was no overlap of T2 times between the protein-depleted and control animals. The consistent changes in T2 that occur with fatty infiltration of the liver should be detectable by current NMR imagers.

Animals↗

PubMed1985

The comparative influence of anesthetics on the in vitro proton NMR relaxation times in rat liver.

To determine the effect of anesthetics on liver relaxation times in rat, two experiments were performed. In the first experiment, normal and protein-depleted rats underwent total hepatectomy under ether anesthesia or following decapitation. In the second experiment, livers were excised from normal rats under ketamine or pentobarbital anesthesia, or following decapitation. Hepatic T1 and T2 were measured for all animals using a RADX 10 MHz spin analyzer. Ketamine produced T1 values significantly different from decapitation. Ketamine, pentobarbital, and ether in normal animals all produced T2 values significantly different from decapitation. It is apparent that anesthetization of rats prior to in vitro measurement of hepatic relaxation times is not equivalent to decapitation; nor are the anesthetics examined equivalent to one another.

Anesthetics↗

PubMed1985

Identification of experimentally induced colitis by in vitro nuclear magnetic resonance.

The present study determined whether in vitro nuclear magnetic resonance could be used to assess experimentally induced colitis in rats. Acute colitis was induced in 6 Sprague-Dawley rats by acetic acid enema, while 6 control animals received saline enemas. All animals were sacrificed 24 hours post-enema, and NMR relaxation times, T1 and T2, of colonic samples were determined on a 10 MHz spin analyzer (RADX, Houston, TX). Colonic water content was determined on the same samples by desiccation. Colitis animals showed significantly higher T1 and T2 relaxation times and tissue water content than controls. T1 and T2 times correlated significantly with tissue water content. Twelve additional animals were studied histologically, six of which received acetic acid enemas and showed extensive transmural colitis. Our results suggest that in vivo proton NMR might be a useful means of non-invasively assessing the degree of colonic inflammation.

Acetates↗

PubMed1984

Impact of a nutritional support service on VA surgical patients.

The impact of a multidisciplinary Nutritional Support Service (NSS) on the reduction of complication was evaluated in 78 consecutive patients who received total parenteral nutrition (TPN) on the same VA surgical service. Patients were placed into one of three groups (pre-NSS, transition-NSS, post-NSS) based on the evolution of the NSS. A significant reduction in catheter sepsis was observed and was attributable to the establishment of an NSS, specifically, a nurse specialist and protocols for catheter insertion and care.

Humans↗

PubMedDate not supplied

Effect of growth hormone on intestinal Na+/glucose cotransporter activity.

BACKGROUND: Growth hormone (GH) has been used alone or as part of a defined regimen in the treatment of patients with short bowel syndrome; however its mode of action remains unclear. Growth hormone has been shown to increase amino acid, water, and electrolyte absorption from the small intestine. The acute effect of growth hormone on intestinal sugar transport has not been described previously. METHODS: Mucosal preparations of rat jejunum were mounted in the Ussing chamber. Growth hormone (2 x 10(-6) M or 8 x 10(-6) M) or vehicle was added to the serosal chamber 1, 3, or 5 hours later. Twenty or 40 minutes after growth hormone addition, 30 mmol/L 3-O-methylglucose was added to both chambers, and the change in short-circuit current (deltaIsc) was recorded. In separate experiments, tissues were pretreated with phloridzin, an inhibitor of Na+/glucose cotransport, before the addition of 3-O-methylglucose. In the final set of experiments, kinetic studies were performed. RESULTS: GH did not induce any alterations in baseline electrical parameters. Only tissues left in the chambers for 5 hours, but not 1 or 3 hours, before GH treatment displayed a greater 3-O-methylglucose-induced deltaIsc than controls (p < .05). The increase in Isc induced by 3-O-methylglucose was 100% phloridzin-inhibitable. Kinetic analysis showed that growth hormone administration is associated with an increase in Na+/glucose cotransporter maximal velocity (Vmax) but no significant change in carrier affinity for substrate (Km). CONCLUSIONS: Growth hormone increases intestinal sugar transport, but only in tissue that has not been exposed to endogenous GH for over 3 hours.

3-O-Methylglucose↗

PubMedDate not supplied

Nitrogen utilization from elemental diets.

Repletion experiments were performed in malnourished, chair-adapted primates to explore recently reported differences in nitrogen utilization from elemental diets. Two elemental diets were fed consecutively for 8 days through a gastrostomy. Diet C (maltodextrins, peptides, crystalline amino acids) resulted in: larger weight gain (F1,6 = 17.93, p less than 0.01); smaller decrease of serum albumin (F1,5 = 11.2, p less than 0.015), larger increase in total iron binding capacity (F1,6 = 30.6, p less than 0.002), and a more positive nitrogen balance (F1,6 = 30.4, p less than 0.002) than diet V (glucose oligosaccharides, crystalline amino acids). Diet C was considered to be more effective in the nutritional repletion of the study animals. Additional experiments were performed in normal human volunteers to investigate the metabolic fate of ingested glutamine and whether the rapid catabolism and excretion of the amido nitrogen of this amino acid, which constitutes 11.56% of total nitrogen in diet V, could explain the differences observed in primates in our study and in human subjects by other authors. Six normal volunteers were fed 15N amino glutamine, 15N alanine, or 15N H4Cl. Similar amounts of 15N from Gln and Ala were excreted in 10 hr. The amido group of glutamine does not seem to be metabolized differently from the alpha-amino group of alanine under the conditions of the study. The marked differences in nitrogen utilization from the study diets could not be explained by the presence of relatively large amounts of glutamine in one of them.

Adult↗

PubMedDate not supplied

Detection of total parenteral nutrition-induced fatty liver infiltration in the rat by in vitro proton nuclear magnetic resonance.

In an effort to determine if NMR techniques might be used to detect TPN-induced hepatic steatosis, the NMR spin-lattice (T1) and spin-spin (T2) relaxation times were measured on liver tissue from rats who received one of five dietary regimens: (1) 100% of nonprotein calories as lipid (Fat); (2) a mixture of 50% lipid and 50% glucose nonprotein calories (50/50); (3) 100% of nonprotein calories as glucose (CHO); (4) intravenous saline and standard laboratory rat chow (Saline); and (5) rat chow alone (Oral). The parenteral diets were isonitrogenous and isocaloric. Serum liver function tests were also measured. Animals in the Fat and 50/50 groups had the greatest amounts of liver fat and significantly longer T1 and T2 times (p less than 0.01) than any other group. Furthermore, the correlation of T2 time with liver fat content (r = 0.82) was far superior (p less than 0.001) to that of serum SGPT (r = 0.48) which was the only liver function test which correlated significantly with liver fat content. In a multiple linear regression analysis, T1 and T2 predicted liver fat content with an r value of 0.84 (p less than 0.001). These data suggest that in vivo NMR imaging techniques might be used to detect TPN-induced fatty infiltration of the liver noninvasively.

Animals↗

PubMedDate not supplied

Effects of glutamine-enriched parenteral nutrition on the exocrine pancreas.

Total parenteral nutrition (TPN) is associated with intestinal and pancreatic atrophy and pancreatic exocrine insufficiency. Recent investigations have demonstrated that the addition of glutamine to intravenous feedings attenuates TPN-associated intestinal atrophy. However, the effect of glutamine-supplemented intravenous feedings on the pancreas of intact animals is unknown. This study compared the effects of an intravenous infusion of a 2% glutamine-enriched diet (GLN) with an isonitrogenous, isocaloric diet without glutamine (CONT) on the composition and structure of the exocrine pancreas in laboratory rats with and without a 60% small bowel resection. In nonresected, TPN-fed animals, pancreatic weight was significantly increased in the GLN group when compared to CONT (645 +/- 33 g vs 554 +/- 20 g, p less than 0.05). Nonresected GLN animals also had increased pancreatic DNA (3.82 +/- 0.19 mg vs 2.91 +/- 0.49 mg, p less than 0.005) and protein contents (93.0 +/- 5.9 mg vs 76.6 +/- 7.0 mg, p = 0.08) compared to control. Similar significant increases in pancreatic weight, DNA, and protein were observed in intestinally resected animals fed the glutamine diet. When data from CONT and GLN animals were pooled and analyzed together, glutamine significantly increased total pancreatic trypsinogen and lipase contents (p less than 0.05). The increase in trypsinogen in resected GLN animals was significantly greater than in CONT animals (283 +/- 22 vs 139 +/- 23, p less than 0.005). Biochemical and morphometric observations demonstrated that the trophic effects of glutamine on the exocrine pancreas were manifest by acinar hyperplasia and not hypertrophy. Glutamine appears to be an important nutrient for pancreatic exocrine tissue during TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗