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Biomedical subjects

J L Rombeau

Publications and source records attributed to J L Rombeau.

At least 19 recordsLinked to original sources

Increased in vitro release of soluble interleukin 2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease.

Increased concentrations of the soluble form of the interleukin 2 receptor have been observed in the sera of Crohn's disease and ulcerative colitis patients. In this study we have observed the spontaneous release of soluble interleukin 2 receptor by unstimulated, isolated normal and inflammatory bowel disease colonic lamina propria mononuclear cells. Lamina propria mononuclear cells from Crohn's disease patients (median = 204 U/ml (interquartile range 126-396, n 17) secreted significantly (p less than 0.01) more soluble interleukin 2 receptor than normal controls (median = 124.5 U/ml (108-131), n 12). No statistically significant differences were seen between ulcerative colitis (median = 135 U/ml (92-196), n 20) and normal controls. Moreover, significantly (p less than 0.01) increased amounts of soluble interleukin 2 receptor were secreted by colonic diverticulitis lamina propria mononuclear cells (median = 259 U/ml (149-282), n 15) which were used as disease specificity controls. Time course experiments showed that the majority of soluble interleukin 2 receptor was released by isolated lamina propria mononuclear cells in the first six days of culture. Upon stimulation with pokeweed mitogen, Crohn's disease (median = 2258 U/ml (1435-3584), n 14), normal control (median = 2622 U/ml (2030-3180), n 14) and diverticulitis lamina propria mononuclear cells (median = 2745 U/ml (1733-3192), n 10) reached similar maximal soluble interleukin 2 receptor secretion levels, while ulcerative colitis lamina propria mononuclear cells secreted significantly (p less than 0.005) less soluble interleukin 2 receptor (median = 912 U/ml (494-1259), n 17). These results suggest that enhanced shedding/secretion of soluble interleukin 2 receptor by intestinal lymphocytes may account in part for increased serum soluble interleukin 2 receptor concentrations during chronic intestinal inflammatory reactions.

Cells, Cultured

Recombinant human growth hormone enhances the metabolic efficacy of parenteral nutrition: a double-blind, randomized controlled study.

This multicenter, randomized, double-blind study was performed to investigate whether recombinant GH improves the efficacy of total parenteral nutrition (TPN). Fifteen stable patients requiring parenteral feeding due to gastrointestinal/pancreatic disease were studied. Constant maintenance TPN providing approximately 30 kcal/kg day and approximately 1.6 g protein/kg.day was administered during an initial 7-day baseline period. After randomization, daily sc injections of saline (control, n = 9) or GH (10 mg/day, n = 6) were administered a 14-day treatment period as nutrient intake remained constant. Elemental balances for nitrogen (N), potassium (K), phosphorus (P), and sodium (Na) were determined daily and serial blood indices, vital signs, and other clinical parameters were monitored. Nutrient balances approached equilibrium during the baseline week in both groups. With GH administration, a significant increase in N, K, and P balance occurred; in contrast, nutrient balances did not change significantly from baseline values in control patients. The cumulative change (delta) in nutrient balances from the baseline week was also significantly greater in the GH-treated patients (delta N: control+2 +/- 7 g vs. GH+36 +/- 6. g, P less than 0.005; delta K:+57 +/- 45 mmol vs.+199 +/- 19 mmol, P less than 0.03; delta P: -27 +/- 30 mmol vs. +91 +/- 69 mmol, P less than 0.02). Plasma insulin-like growth factor-I concentrations rose 5-fold and serum cholesterol rose slightly with GH; no other significant change in group mean blood values occurred. One patient receiving GH and chronic prednisone therapy developed moderate hyperglycemia and mild peripheral edema; no other deleterious effects attributable to GH were observed. GH was well tolerated and significantly enhanced nutrient retention compared to standard parenteral feeding alone. GH improves the efficacy of parenteral nutrient utilization in patients requiring TPN.

Adolescent

Experimental short-bowel syndrome: effect of an elemental diet supplemented with short-chain triglycerides.

To determine whether short-chain triglycerides (SCTs, 1:1 triacetin:tributyrin, wt:wt) enhance intestinal adaptation in short-bowel syndrome (SBS), male Sprague-Dawley rats underwent 60% distal small-bowel resection with cecectomy and received either a chemically defined diet (CD) or a CD containing 40% of nonprotein energy as either medium-chain triglycerides (MCTs) or SCTs. After 12 d the SCT group had significantly increased jejunal mucosal weight compared with the MCT and CD groups and had significantly increased segment weight and mucosal protein compared with the CD group. In the colon the SCT group had significantly increased segment and mucosal weights and mucosal protein and DNA compared with both the MCT and CD groups. Body-weight change and measurements of serum ketones, albumin, glucose, and triglycerides revealed no significant differences among groups. SCTs improved jejunal and colonic adaptive growth and maintained comparable nutritional status in SBS when compared with CD alone or CD with MCTs.

3-Hydroxybutyric Acid

Identification of human appendicitis by in vitro nuclear magnetic resonance.

The spin-lattice relaxation time, T1 as determined by nuclear magnetic resonance techniques, correlates positively with tissue water content. The latter relationship has been observed in rabbits with experimentally induced appendicitis whose inflamed appendiceal tissues had significantly higher T1's and water contents than tissue from normal controls. The present experiment studied these relationships in humans. Tissue water content and T1 were measured on appendiceal tissue from 10 patients with documented appendicitis and from 6 controls without the disease. All T1's were determined within 30-60 min of removal of the appendix at operation. The mean in vitro T1 of appendiceal tissue from patients with appendicitis was significantly higher than that of controls (527 +/- 15 msec versus 430 +/- 17 msec, mean +/- SEM, P less than 0.002). In addition, a strong positive correlation was noted between T1 and tissue water content (r = 0.70, P less than 0.01). Based on these findings, the use of in vivo magnetic resonance imaging techniques to detect human appendicitis noninvasively warrants investigation.

Adolescent

Parenteral nutrition supplemented with short-chain fatty acids: effect on the small-bowel mucosa in normal rats.

When enteral nutrition is excluded from animals maintained solely with total parenteral nutrition (TPN), atrophy of the intestinal mucosa is observed. Short-chain fatty acids (SCFAs) are produced in the colon by the fermentation of dietary carbohydrates and fiber polysaccharides and have been shown to stimulate mucosal-cell mitotic activity in the intestine. This study compared the effects of an intravenous and an intracecal infusion of SCFAs on the small-bowel mucosa. Rats received standard TPN, TPN with SCFAs (sodium acetate, propionate, and butyrate), TPN with an intracecal infusion of SCFAs, or rat food. After 7 d jejunal and ileal mucosal weights, DNA, RNA, and protein were determined. Standard TPN produced significant atrophy of the jejunal and ileal mucosa. Both the intracecal and intravenous infusion of SCFAs significantly reduced the mucosal atrophy associated with TPN. The intravenous and intracolonic infusion of SCFAs were equally effective in inhibiting small-bowel mucosal atrophy.

Animals

Dietary fiber: a brief review and potential application to enteral nutrition.

Advances in enteral nutrition include the provision of organ-specific fuels to improve gut structure and function. Examples of these fuels include soluble fiber as a fuel precursor, and the SCFAs acetate, propionate, and butyrate. Butyrate appears to exert its trophic effect primarily in the colon, whereas the combined SCFAs affect the whole gastrointestinal tract. The provision of these fuels may be indicated for selected patients with intestinal dysfunction.

Dietary Fiber

Nutritional care for patients with Crohn's disease.

Protein calorie malnutrition, in addition to deficits of other nutrients, occurs frequently among patients with Crohn's disease. In most instances the mechanisms by which these deficits occur are multifactorial. The most appropriate method to assess nutritional status includes a nutritionally oriented medical history and physical examination combined with a measurement of serum albumin. If the gut can be used safely, enteral nutrition is the preferred feeding method for Crohn's disease patients needing nutritional support. The advantages of enteral nutrition are stimulatory effects on gastrointestinal structure and function and reduced cost when compared to parenteral feeding. If the gastrointestinal tract cannot be used safely, parenteral nutrition is recommended. The presence of Crohn's disease among prepubertal children produces serious growth failure which can be reduced or arrested by appropriate nutritional interventions. Significant numbers of Crohn's disease patients ar now receiving both enteral and parenteral nutrition in the home setting.

Adult

The effect of pectin on hepatic lipogenesis in the enterally-fed rat.

The fermentation of pectin by colonic bacteria produces short-chain fatty acids (SCFA) which are then absorbed by the host. The purpose of this study was to determine whether pectin, added to a chemically defined diet, would increase hepatic lipogenesis and whether this effect is mediated by intestinal bacteria. Eighteen Sprague-Dawley rats underwent placement of a feeding gastrostomy and a swivel apparatus. Postoperatively, rats were randomly assigned to one of three groups: 1) No Pectin received a fat-free chemically defined diet, 2) Pectin received the same diet with the addition of 1% (w/v) pectin, and 3) Neomycin received the same diet with 1% w/v pectin and neomycin (80 mg/kg of body weight daily). On the 5th postoperative d, all diets included 12.5% (v/v) deuterium as D2O. After the infusion of the labeled diets for 24 hr, the content and deuterium enrichment of liver palmitate, stearate and oleate were measured and the production rates calculated. The liver content and production rates of these fatty acids were higher in Pectin animals than in either the No Pectin or Neomycin animals. Since the effect of pectin on hepatic lipogenesis was reduced by the concomitant administration of the intestinal antibiotic neomycin, it appears that this effect depends on the bacterial fermentation of pectin. It is postulated that the SCFA produced during pectin fermentation promote lipogenesis via a direct stimulatory effect, in addition to being carbon donors.

Animals

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

Dexamethasone administration induces increased glutaminase specific activity in the jejunum and colon.

Exogenous glucocorticoids markedly increase the in vivo uptake and utilization of glutamine by the intestine. Since glutamine is the major oxidative fuel for the small intestine, we investigated whether glucocorticoids induce changes in the specific activity of the enzymes that mediate glutamine degradation (glutaminase) and synthesis (glutamine synthetase). Male Sprague-Dawley rats received a 7-day elemental diet. On Day 5, animals were randomized to one of four groups and received either saline (Control) or one of three doses of dexamethasone im: 0.1 mg/kg (Lodex); 0.3 mg/kg (Middex); or 0.6 mg/kg (Hidex). Forty-eight hours later jejunal and colonic segments were assayed for protein, glutaminase, and glutamine synthetase activity. A stress dose of dexamethasone (Hidex) produced a significant increase in both jejunal and colonic glutaminase specific activity (P less than 0.02 vs Control and P less than 0.05 vs Control, respectively). These data suggest a mechanism whereby glucocorticoids increase the intestinal utilization of glutamine by increasing the specific activity of intestinal glutaminase.

Animals

Inhibition of TPN-associated intestinal mucosal atrophy with monoacetoacetin.

Total parenteral nutrition (TPN) is associated with intestinal mucosal atrophy. Acetoacetate is oxidized in preference to glucose by both enterocytes and colonocytes and is not present in TPN. The purpose of this study was to determine whether replacement of a portion of glucose calories with monoacetoacetin, the glycerol ester of acetoacetate, could inhibit TPN-associated intestinal atrophy. Male Sprague-Dawley rats (200-250 g) underwent superior vena caval cannulation and were assigned to receive chow ad libitium (CHOW), TPN with 0.86 M monoacetoacetin (ACAC), or TPN with 0.86 M glycerol to control for the glycerol component of monoacetoacetin (GLYC). Nitrogen balance was measured over 7 days after which time the animals were weighed and sacrificed. Jejunal and colonic segments were harvested and the mucosal weight, protein, RNA, and DNA contents measured. All groups showed comparable weight gain. Cumulative nitrogen balance was positive for both TPN groups. Significant decreases in mucosal parameters occurred in both TPN groups compared to the CHOW group, but atrophy was significantly inhibited in both jejunum and colon of the ACAC group compared to the GLYC group. Thus, the substitution of monoacetoacetin for glucose calories in parenteral nutrition solutions inhibited TPN-related atrophy of intestinal mucosa while maintaining normal growth.

Acetoacetates

Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection.

After massive small bowel resection, total parenteral nutrition (TPN) is prescribed to maintain nutritional status. However, TPN reduces the mass of the remaining intestinal mucosa, whereas adaptation to small bowel resection is associated with increased mucosal mass. Short-chain fatty acids (SCFAs) have been shown to stimulate mucosal cell mitotic activity. This study determined whether the addition of SCFAs to TPN following small bowel resection would prevent intestinal mucosal atrophy produced by TPN. Adult rats underwent an 80% small bowel resection and then received either standard TPN or TPN supplemented with SCFAs (sodium acetate, propionate, and butyrate). After 1 wk, jejunal and ileal mucosal weights, deoxyribonucleic acid, ribonucleic acid, and protein contents were measured and compared with the parameters obtained at the time of resection. Animals receiving TPN showed significant loss of jejunal mucosal weight, deoxyribonucleic acid, ribonucleic acid, and protein and ileal mucosal weight and deoxyribonucleic acid after small bowel resection, whereas animals receiving SCFA-supplemented TPN showed no significant change in the jejunal mucosal parameters and a significant increase in ileal mucosal protein. These data demonstrate that SCFA-supplemented TPN reduces the mucosal atrophy associated with TPN after massive bowel resection and thys may facilitate adaptation to small bowel resection.

Adaptation, Physiological

Small bowel disaccharidase activity in the rat as affected by intestinal resection and pectin feeding.

This study investigated the effects of small bowel resection (SBR) and a pectin-supplemented elemental diet (ED) on intestinal disaccharidase activity. Rats underwent placement of feeding gastrostomy and swivel apparatus. Control animals were returned to their cages while resected animals underwent an 80% SBR. Postoperatively, animals received either a pectin-free ED or the ED supplemented with 2% pectin. After 2 wk jejunal and ileal mucosal sucrase, maltase, and lactase activities and protein content were determined. Feeding the ED after SBR resulted in significant increases in all three ileal segmental disaccharidase activities but only maltase activity was significantly increased in the jejunum. The pectin-supplemented ED, however, significantly enhanced the adaptation of jejunal and ileal segmental sucrase, maltase, and lactase activity to SBR with the increase in all three jejunal disaccharidase activities being significantly greater than that of the resected animals fed the ED alone.

Adaptation, Physiological

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

Enteral and parenteral nutrition in patients with enteric fistulas and short bowel syndrome.

Significant advances in the use of enteral and parenteral nutrition in patients with either enteric fistulas or short bowel syndrome include increased usage of enteral nutrition because of its trophic effects on the gut and increased usage of both enteral and parenteral nutrition in the home setting. Current investigations are directed toward identifying gut-specific fuels and dietary and pharmacologic enhancement of nutrient utilization.

Adaptation, Physiological

Enteral nutrition in the critically ill.

Although total parenteral nutrition has greatly influenced the clinical management of the critically ill, enteral nutrition can provide much needed support in the intensive care unit. In order to employ the best enteral nutrition, one must understand its rationale, delivery principles, equipment, feeding techniques, and diets, as well as patient selection and monitoring.

Critical Care

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