J.Duncan Phillips

Effects of chronic corticosteroids and vitamin a on the healing of intestinal anastomoses

The ability of vitamin A to reverse the inhibitory effects of chronic corticosteroids on cutaneous and fascial wound healing is well established. To investigate this in the unique low-collagen environment of the intestinal anastomosis, 35 rabbits received twice-daily injections of either saline (control), dexamethasone (0.1 mg/kg/day), dexamethasone plus low-dose vitamin A (1,000 IU/kg/day), or dexamethasone plus high-dose vitamin A (10,000 IU/kg/day) for a 2-week period. Animals then underwent creation of single-layer, inverting small and large intestine anastomoses. All injections were continued postoperatively. A fifth group received only dexamethasone preoperatively and dexamethasone plus high-dose vitamin A postoperatively. On postoperative day 7, animals underwent in situ assessment of anastomotic bursting pressure and subsequent histologic examination using a modified Ehrlich/Hunt scale. Corticosteroids significantly impaired the healing of small and large intestine anastomoses, with decreased bursting pressures and histologic parameters at 1 week. Only high-dose vitamin A significantly reversed this inhibitory effect, whether given preoperatively or only postoperatively.

Pulmonary edema and fluid mobilization as determinants of the duration of ECMO support

The physiological variables that govern recovery of pulmonary function during neonatal extracorporeal membrane oxygenation (ECMO) remain poorly understood. We hypothesized that pulmonary hypertension (PHN) resolves soon after starting ECMO and that neonatal weight gain, pulmonary edema, and fluid mobilization are major determinants of recovery of pulmonary function and the ability to decrease ECMO support. To evaluate this, 17 consecutive neonates requiring ECMO for severe respiratory failure were reviewed. PHN was studied by daily echocardiography to assess the direction of ductal shunting. To evaluate fluid flux, pulmonary function, and edema during ECMO, we measured body weight, urine output, and ECMO flow every 12 hours. To evaluate pulmonary edema, serial chest radiographs obtained every 12 hours were randomly reviewed and scored by two radiologists with a semiquantitative chest radiograph index score (CRIS). By 25% of bypass time, PHN had resolved in all patients. However, at that time, weight had increased to 9.16% +/- 1.78% above birth weight, and the CRIS was 44% worse than the value just prior to ECMO. From 25% time on bypass, as urine output increased, patient weight and CRIS progressively decreased, allowing ECMO support to be weaned. At the time of discontinuation of ECMO support, weight had decreased to 2.0% +/- 1.3% above birth weight, and urine output remained steady at 3.0 +/- 0.3 mL/kg/h. Within 24 hours of stopping ECMO, the CRIS showed a 58% improvement compared to maximal scores during ECMO. We conclude that PHN decreases early in ECMO and that edema and its mobilization are important determinants of the improvement in pulmonary function and duration of ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Reconstruction of malfunctioning ileoanal pouch procedures as an alternative to permanent ileostomy

During the past 13 years, 261 patients with ulcerative colitis and 29 with colonic polyposis underwent endorectal pullthrough (ERP) at UCLA Medical Center. Of the first 111 consecutive patients to undergo ERP, 5 returned to a permanent ileostomy because of persistent symptoms related to reservoir stasis. Transabdominal shortening of the reservoir was performed in 38 of the 111 patients; 24 experienced marked clinical improvement. Fourteen of the 38 patients had persistent stasis and required shortening of the ileal spout either transanally (5 patients) or via an abdominoperineal approach (9 patients). Eighteen of the initial 111 patients underwent one-stage abdominoperineal reservoir reconstruction. During the past 4 years, 8 of 149 consecutive patients with a primary lateral isoperistaltic reservoir underwent subsequent abdominoperineal reservoir reconstruction. Fourteen of 18 patients with a straight pullthrough with reservoir underwent reconstruction to a lateral isoperistaltic reservoir. An aggressive operative approach to the management of pouchitis and reservoir stasis (diarrhea, frequency, urgency, incomplete emptying) has resulted in only 4 of the last 246 consecutive patients returning to a permanent ileostomy. Several changes in the operative technique have evolved during the 13-year period. Important features for optimal pouch function appear to include: (1) a short rectal muscle cuff, (2) a small ileal reservoir, (3) a short ileal spout, (4) removal of all rectal mucosa, and (5) aggressive correction of rectal strictures.

An improved model of experimental gastroschisis in fetal rabbits

Previous animal models of gastroschisis have been associated with high mortality and variable degrees of intestinal evisceration. Using current fetal surgical techniques, an improved model of gastroschisis in fetal rabbits was developed. Twenty-eight time-mated New Zealand white rabbits underwent hysterotomies and fetal exposure on gestational day 25 (33-day gestation). Control fetuses (C) underwent fetal manipulation only. Gastroschisis fetuses (GS) had creation of right midabdominal wall defects. Twenty-five of 28 does (89%), 9 of 13 C fetuses (69%), and 18 of 22 GS fetuses (82%) survived. At the time of cesarean delivery 5 days later, GS fetuses had significantly lower body weights, intestinal lengths, and mucosa/submucosa height ratios (a measure of bowel wall edema), and significantly greater intestinal densities when compared with C fetuses (P less than .05, t test). This study demonstrates that (1) gastroschisis abdominal wall defects can be created in fetal rabbits with high survival rates; (2) experimental gastroschisis is associated with a profound decrease in fetal weight; and (3) eviscerated intestine is heavier, shorter, and thickened compared with normal control intestine, mimicking the clinical situation.

Fetal rabbit intestinal absorption : implications for transamniotic fetal feeding

Delivery of nutrients to the fetus via the developing gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. Previous studies have demonstrated significant increases in fetal length and weight following continuous intraamniotic nutrient infusions in animals. The ideal composition of intraamniotic feedings has yet to be determined. Thirteen time-mated rabbit does underwent ceserean section between gestational days 27 and 33 to deliver 54 fetuses. The everted intestinal sleeve technique was used to measure radiolabeled carbohydrate and amino acid uptake rates from 1-cm segments of midjejunum. Uptake of galactose was more than double that of glucose and fructose. Active uptake of glucose, fructose, and galactose increased by 3.3-fold, 6.2-fold, and 2.1-fold, respectively, during the final 7 days of gestation when expressed as uptake per mg intestine. In contrast, uptake of the amino acids leucine, lysine, and proline decreased by 41%, 34%, and 17%, respectively, during the final 5 days of gestation. The demonstrated changes in intestinal absorption and nutrient delivery in the rabbit model, during the last days of gestation, suggest that certain substrates are absorbed more rapidly than others. Galactose may be the preferred intraamniotic carbohydrate for fetal growth.

Uptake and distribution of continuously infused intraamniotic nutrients in fetal rabbits

Nutrient delivery via the fetal gastrointestinal tract may be a potential prenatal treatment for intrauterine growth retardation. Uptake from continuous intraamniotic infusions with nutrient incorporation into developing fetal tissues has not previously been shown. To study this, ovarian-end fetuses of 18 time-mated rabbit does underwent amniotic cavity catheterization and either esophageal ligation (EL) or sham operation (SH) on gestational day 23 (term, 33 days). Saline plus 14C D-glucose and 3H proline were infused into the amniotic fluid for 4 days. Nutrients absorbed by the EL fetus represent only those taken up into the maternal circulation and subsequently redelivered hematogenously to the fetus. Radioactivity of fetal blood and organs was determined using a liquid scintillation counter. All infused does and 10 of 18 infused fetuses (56%) survived the entire study period. In SH fetuses, uptake of 14C per mg of tissue was highest in the lung and significantly greater in the stomach, jejunum, ileum, and lung than in fetal blood (P less than .05). Uptake of 3H per mg of tissue was also highest in the lung and significantly greater than fetal blood in the stomach, small intestine, lung, and liver (P less than .05). Each organs 14C and 3H uptake was greater in SH than in EL fetuses (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Nephrolithiasis and urine ion changes in ulcerative colitis patients undergoing colectomy and endorectal ileal pullthrough

Nephrolithiasis occurs in 5 to 13% of patients with ulcerative colitis (UC) who undergo colectomy and abdominal ileostomy, presumably from chronic dehydration and urinary concentration. Whether endorectal ileal pullthrough with ileal reservoir (PTR) changes the incidence of stones (primarily calcium oxalate) after colectomy is not known. Urinary excretion of Na2+, K+, Ca2+, Mg2+, phosphate, urate, oxalate, and citrate was measured in a prospective study of 12 UC patients undergoing PTR with temporary end ileostomy. Twenty-four-hour urine samples were obtained before colectomy (t1), after colectomy but before ileostomy closure (t2), and 5 months after ileostomy closure (t3). Urine volumes decreased from 831 +/- 101 cc (mean +/- SE) at t1 to 715 +/- 101 cc at t2 and then increased to 1278 +/- 421 cc at t3 (significant, with P less than 0.01 by t test). Urinary excretions of Mg2+, oxalate, and citrate were low in UC patients compared to those in controls (15 healthy adult volunteers). Excretion of Ca2+ increased significantly following temporary ileostomy while excretion of Mg2+ fell. Excretion of Ca2+ fell and excretion of Mg2+ and citrate increased following PTR. We conclude that PTR patients have increased urine volumes and urinary ion changes known to decrease the risk of developing renal stones.

Fertility after simulated Fowler-Stephens orchiopexy in rats

In order to determine the effects of the Fowler-Stephens orchiopexy (FSO) on fertility, young rats underwent simulated FSO, FSO and concurrent contralateral orchiectomy (FSO/OR), unilateral orchiectomy (OR), or sham operation (controls). Twelve weeks after the operation, each male rat was mated to two proven-fertile female rats for 17 days (three ovulatory cycles). Two weeks later, both male and female rats were killed. No pregnancy resulted from the matings of the FSO/OR males. In contrast, pregnancy ensued in 13 of 16 (81%) females in the FSO group, 9 of 14 (64%) in the OR group, and 11 of 12 (92%) in the control group. There were no fertile males in the FSO/OR group. In the FSO group, eight of eight males induced pregnancy in at least one female; in the OR group, six of seven (86%) males were fertile as were all six males in the control group. No differences in litter size or fetal weight were observed between fertile females in various groups.

Changes in mucosal nutrient transport in small and large ileal reservoirs after endorectal ileal pullthrough.

It has been hypothesized that, following colectomy and endorectal ileal pullthrough with ileal reservoir (PTR), reservoir tissue might lose some of its normal nutrient transport capacity and assume properties of the colon. Whether reservoir size influences the expected alterations in normal mucosal absorption and thus contributes to changes in intraluminal ecology has not previously been investigated. To study this, the everted intestinal sleeve technique was used to measure uptake of four nutrients in two groups of dogs who underwent PTR: five with a small (5 cm) lateral reservoir and five with a large (18 cm) reservoir. Mucosal samples were taken from normal ileum and colon and from reservoirs 3 months postoperation. Active uptake of carbohydrates (glucose), amino acids (proline), and bile acids (taurocholate) and passive uptake of short chain fatty acids (propionate) were markedly decreased in mucosa of both reservoir sizes compared to normal ileum (P less than 0.05, t test) and more closely approximated that of normal colon. Uptake of glucose, proline, and taurocholate in large reservoirs was significantly less than that in small reservoirs (P less than 0.05). We conclude that (1) ileal reservoir mucosa has a significantly reduced capacity for nutrient uptake, (2) ileal mucosa in small reservoirs shows higher nutrient uptake rates than mucosa in large reservoirs, and (3) short, well-emptying reservoirs appear best suited to optimizing the intraluminal environment and thus enhance reservoir function when performing PTR.

Pectus excavatum repair after sternotomy: the Chest Wall International Group experience with substernal Nuss bars

OBJECTIVES Patients with pectus excavatum (PE) after prior sternotomy for cardiac surgery present unique challenges for repair of PE. Open repairs have been recommended because of concerns about sternal adhesions and cardiac injury. We report a multi‐institutional experience with repair utilizing substernal Nuss bars in this patient population. METHODS Surgeons from the Chest Wall International Group were queried for experience and retrospective data on PE repair using sub‐sternal Nuss bars in patients with a history of median sternotomy for cardiac surgery (November 2000 to August 2015). A descriptive analysis was performed. RESULTS Data for 75 patients were available from 14 centres. The median age at PE repair was 9.5 years (interquartile range 10.9), and the median Haller index was 3.9 (interquartile range 1.43); 56% of the patients were men. The median time to PE repair was 6.4 years (interquartile range 7.886) after prior cardiac surgery. Twelve patients (16%) required resternotomy before support bar placement: 7 pre‐emptively and 5 emergently. Sternal elevation before bar placement was used in 34 patients (45%) and thoracoscopy in 67 patients (89%). Standby with cardiopulmonary bypass was available at 9 centres (64%). Inadvertent cardiac injury occurred in 5 cases (7%) without mortality. CONCLUSIONS Over a broad range of institutions, substernal Nuss bars were used in PE repair for patients with a history of sternotomy for cardiac surgery. Several technique modifications were reported and may have facilitated repair. Cardiac injury occurred in 7% of cases, and appropriate resources should be available in the event of complications. Prophylactic resternotomy was reported at a minority of centres.