Prematurity Reduces Functional Adaptation to Intestinal Resection in Piglets

Background: Necrotizing enterocolitis and congenital gastrointestinal malformations in infants often require intestinal resection, with a subsequent risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal adaptation following resection of the distal intestine with placement of a jejunostomy differs between preterm and term neonates. Methods: Preterm or term piglets were born by cesarean section and fed enterally for 2 days. On day 2, piglets were subjected to 50% distal intestinal resection with placement of a jejunostomy. On the following 4–5 days, piglets received parenteral nutrition with gradually increasing doses of enteral nutrition (bovine colostrum). Intestinal tissue samples were collected at delivery and 2 and 6–7 days after birth for histological examination and assessment of digestive enzyme activities. Results: Preterm and term piglets showed similar increases in intestinal weight and digestive enzyme activities from birth to 2 days. On days 6–7 after birth, the remnant intestine showed a similar density (g/cm) and mucosal mass in term and preterm piglets, but villus height, crypt depth, enzyme activities (sucrase, maltase, dipeptidyl peptidase IV [DPPIV]), and hexose uptake capacity were significantly higher in term piglets (P < .05). Preterm piglets were more prone to develop hypoglycemia, respiratory distress syndrome, dehydration, and circulatory instability after surgery compared with term piglets. Conclusion: Studies on intestinal adaptation after resection are feasible in both preterm and term piglets, but intensive clinical support is required when rearing preterm piglets with SBS. Physiological instability and immaturity of the intestine may explain the fact that immediate adaptation after resection is reduced in preterm vs term neonates.     

Modulation of Intestinal Inflammation by Minimal Enteral Nutrition With Amniotic Fluid in Preterm Pigs

Background: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder, associated with the difficult transition from parenteral to enteral feeding after preterm birth. We hypothesized that minimal enteral nutrition (MEN) with amniotic fluid (AF), prior to enteral formula feeding, would improve resistance to NEC in preterm pigs. Methods: Experiment 1: IEC‐6 cells were incubated with porcine (pAF) and human AF (hAF) to test AF‐stimulated enterocyte proliferation and migration in vitro. Experiment 2: Cesarean‐delivered, preterm pigs were fed parenteral nutrition and MEN with pAF, hAF, or control fluid (MEN‐pAF, MEN‐hAF, or MEN‐CTRL; all n = 9) for 2 days before tissue collection. Experiment 3: Preterm pigs were fed MEN diets as in experiment 2, but followed by 2 days of enteral formula feeding, which predisposes to NEC (NEC‐pAF, NEC‐hAF, or NEC‐CTRL; n = 10–12). Results: Both pAF and hAF stimulated enterocyte proliferation and migration in vitro. In experiment 2, MEN‐pAF and MEN‐hAF pigs showed increased body weight gain and reduced intestinal interleukin (IL)–8 and colonic IL‐6 levels, indicating reduced inflammatory response. In experiment 3, body weight gain was highest in the 2 groups fed AF as MEN, but NEC incidences were similar (NEC‐pAF) or increased (NEC‐hAF) compared with controls. Conclusions: Intake of pAF or hAF improved body growth and modulated intestinal inflammatory cytokines during a period of parenteral nutrition, but did not protect against later formula‐induced NEC in preterm pigs. Further studies are required to show if MEN feeding with species‐specific AF, combined with an optimal enteral diet (eg, human milk), will improve adaptation during the transition from parenteral to enteral feeding in preterm neonates.     

Acute Increases in Murine Tumor Echogenicity After Antivascular Ultrasound Therapy

Objective. This study was designed to determine whether the echogenicity of neoplastic tissues changed as a result of low‐intensity insonation and whether such alterations were related to an anti‐vascular effect. Methods. In 21 mice, implanted melanomas were insonated at either 1, 2, or 3 MHz using low‐intensity ultrasound (spatial‐average temporal‐average intensity, 2.1 W/cm²). B‐mode (mean gray scale) and contrast‐enhanced power Doppler (percentage area of flow) measurements were made on each tumor before and after therapy. Results. There was an increase in the echogenicity of the tumors with the increase in the frequency of the therapy beam and an accompanying decrease in tumor vascularity. Conclusions. Although the mechanisms responsible for the echogenicity change are not fully understood, it appears that an increase in the tumor mean gray scale was, at least in part, related to tissue inhomogeneities formed after disruption of the tumor neovasculature.     

Bovine Colostrum to Children With Short Bowel Syndrome

Background: Management of short bowel syndrome (SBS) aims to achieve intestinal autonomy to prevent fluid, electrolyte, and nutrient deficiencies and maintain adequate development. Remnant intestinal adaptation is required to obtain autonomy. In the newborn pig, colostrum has been shown to support intestinal development and hence adaptive processes. Aim: The efficacy of bovine colostrum to improve intestinal function in children with SBS was evaluated by metabolic balance studies. Materials and Methods: Nine children with SBS were included in a randomized, double‐blind, crossover study. Twenty percent of enteral fluid intake was replaced with bovine colostrum or a mixed milk diet for 4 weeks, separated by a 4‐week washout period. Intestinal absorption of energy and wet weight was used to assess intestinal function and the efficacy of colostrum. Results: Colostrum did not improve energy or wet weight absorption compared with the mixed milk diet (P = 1.00 and P = .93, respectively). Growth as measured by weight and knemometry did not differ between diets (P = .93 and P = .28). In these patients, <150% enteral energy absorption of basal metabolic rate and 50% enteral fluid absorption of basal fluid requirement suggested intestinal failure and a need for parenteral nutrition (PN). Conclusion: Inclusion of bovine colostrum to the diet did not improve intestinal function. Metabolic nutrient and wet weight balance studies successfully assessed intestinal function, and this method may distinguish between intestinal insufficiency (non–PN‐dependent) and intestinal failure (PN‐dependent) patients.     

Glucagon‐Like Peptide 2 Stimulates Postresection Intestinal Adaptation in Preterm Pigs by Affecting Proteins Related to Protein,Carbohydrate, and Sulphur Metabolism

Background: Exogenous glucagon‐like peptide 2 (GLP‐2) stimulates intestinal adaptation after resection in animal models of pediatric short bowel syndrome (SBS). It is unknown whether the molecular mechanisms of such GLP‐2 effects are similar to those of postresection spontaneous adaptation. Using preterm pigs as a model, we hypothesized that GLP‐2 treatment would change the intestinal proteome within the first week after resection, relative to individuals not resected or resected without GLP‐2 treatment. Materials and Methods: Two‐day‐old preterm pigs were subjected to resection of 50% distal small intestine and fed total parenteral nutrition without (SBS) or with GLP‐2 infusion (3.5 µg/kg/h, SBS+GLP‐2) for 5 days. The proteome of the remnant proximal intestine was compared among the SBS, SBS+GLP‐2, and unresected pigs, through gel‐based proteomics. Results: Thirty‐two proteins with differential expression were identified. Ten of these proteins were affected by the resection alone (ie, SBS vs unresected pigs). Five of these resection‐responsive proteins and another 22 proteins were affected by GLP‐2 infusion (ie, SBS+GLP‐2 vs SBS or unresected pigs). Resection alone mainly affected cellular structural proteins, while the added GLP‐2 treatment affected proteins involved in protein processing and the metabolism of protein, carbohydrate, and sulphur. Conclusion: In the first days following resection, proteins affected by resection plus GLP‐2 treatment differed markedly from those affected by the spontaneous intestinal adaptation following resection alone. Whether more long‐term GLP‐2 treatment may affect the intestinal proteome following intestinal resection remains unknown.     

Minimal Enteral Nutrition to Improve Adaptation After Intestinal Resection in Piglets and Infants

Background: Minimal enteral nutrition (MEN) may induce a diet‐dependent stimulation of gut adaptation following intestinal resection. Bovine colostrum is rich in growth factors, and we hypothesized that MEN with colostrum would stimulate intestinal adaptation, compared with formula, and would be well tolerated in patients with short bowel syndrome. Methods: In experiment 1, 3‐day‐old piglets with 50% distal small intestinal resection were fed parenteral nutrition (PN, n = 10) or PN plus MEN given as either colostrum (PN‐COL, n = 5) or formula (PN‐FORM, n = 9) for 7 days. Intestinal nutrient absorption and histomorphometry were performed. In experiment 2, tolerance and feasibility of colostrum supplementation were tested in a pilot study on 5 infants who had undergone intestinal resection, and they were compared with 5 resected infants who served as controls. Results: In experiment 1, relative wet‐weight absorption and intestinal villus height were higher in PN‐COL vs PN (53% vs 23% and 362 ± 13 vs 329 ± 7 µm, P < .05). Crypt depth and tissue protein synthesis were higher in PN‐COL (233 ± 7 µm, 22%/d) and PN‐FORM (262 ± 13 µm, 22%/d) vs PN (190 ± 4 µm, 9%/d, both P < .05). In experiment 2, enteral colostrum supplementation was well tolerated, and no infants developed clinical signs of cow’s milk allergy. Conclusion: Minimal enteral nutrition feeding with bovine colostrum and formula induced similar intestinal adaptation after resection in piglets. Colostrum was well tolerated by newly resected infants, but the clinical indication for colostrum supplementation to infants subjected to intestinal resection remains to be determined.     

Provision of Amniotic Fluid During Parenteral Nutrition Increases Weight Gain With Limited Effects on Gut Structure,Function, Immunity,and Microbiology in Newborn Preterm Pigs

Background: Small enteral boluses with human milk may reduce the risk of subsequent feeding intolerance and necrotizing enterocolitis in preterm infants receiving parenteral nutrition (PN). We hypothesized that feeding amniotic fluid, the natural enteral diet of the mammalian fetus, will have similar effects and improve growth and gastrointestinal (GI) maturation in preterm neonates receiving PN, prior to the transition to milk feeding. Materials and Methods: Twenty‐seven pigs, delivered by cesarean section at ~90% of gestation, were provided with PN and also fed boluses with amniotic fluid (AF; n = 13, 24–72 mL/kg/d) or no oral supplements (nil per os [NPO]; n = 14) until day 5 when blood, tissue, and fecal samples were collected for analyses. Results: Body weight gain was 2.7‐fold higher in AF vs NPO pigs. AF pigs showed slower gastric emptying, reduced meal‐induced release of gastric inhibitory peptide and glucagon‐like peptide 2, changed gut microbiota, and reduced intestinal permeability. There were no effects on GI weight, percentage mucosa, villus height, plasma citrulline, hexose absorptive capacity, and digestive enzymes. Intestinal interleukin (IL)–1β levels and expression of IL1B and IL8 were increased in AF pigs, while blood biochemistry and amino acid levels were minimally affected. Conclusion: Enteral boluses of AF were well tolerated in the first 5 days of life in preterm pigs receiving PN. Enteral provision of AF before the initiation of milk feeding may stimulate body growth and improve hydration in preterm infants receiving PN. Furthermore, it may improve GI motility and integrity, although most markers of GI maturation remain unchanged.     

Wear of a 5 Megarad Cross-linked Polyethylene Liner: A 6-year RSA Study

Background

One cross-linked polyethylene (XLPE) liner is manufactured using a lower dose of radiation, 5 Mrad, which may result in less cross-linking. The reported in vivo wear rate of this XLPE liner in patients undergoing THA has varied, and has included some patients in each reported cohort who had greater than 0.1 mm/year of wear, which is an historical threshold for osteolysis. Previous studies have measured wear on plain radiographs, an approach that has limited sensitivity.

Questions/purposes

We therefore measured the amount and direction of wear at 6 years using Radiostereometric analysis (RSA) in patients who had THAs that included a cross-linked polyethylene liner manufactured using 5 Mrad radiation.

Methods

We prospectively reviewed wear in 30 patients who underwent primary THAs with the same design of cross-linked acetabular liner and a 28-mm articulation. Tantalum markers were inserted during surgery and all patients had RSA radiographic examinations at 1 week, 6 months, 1, 2, and 6 years postoperatively.

Results

The mean proximal, two-dimensional (2-D) and three-dimensional (3-D) wear rates calculated between 1 year and 6 years were 0.014, 0.014, and 0.018 mm/per year, respectively. The direction of the head penetration recorded between 1 week and 6 years was in a proximal direction for all patients, proximolateral for 16 of 24 patients, and proximomedial for eight of 24 patients.

Conclusions

The proximal, 2-D and 3-D wear of a XLPE liner produced using 5 Mrad of radiation was low but measurable by RSA after 6 years. No patients had proximal 2-D or 3-D wear rates exceeding 0.1 mm/year. Further followup is needed to evaluate the effect of XLPE wear particles on the development of long-term osteolysis.