Oral relaxin maintains intestinal blood flow in a rat model of NEC.

PURPOSE: Intestinal vasoconstriction is a critical step in development of necrotizing enterocolitis (NEC). Relaxin (RLXN), a hormone found in breast milk but absent from formula, is a potent vasodilator. We hypothesized that relaxin-supplemented feeds with an NEC protocol would decrease NEC severity and increase intestinal blood flow. METHODS: Timed-pregnant Sprague-Dawley rats were randomly assigned to CONTROL, NEC, NEC+1xRLXN, or NEC+All Feeds RLXN, and all but CONTROL underwent NEC protocol. NEC+1xRLXN and NEC+All Feeds RLXN groups were fed relaxin-supplemented formula with the last feed or every feed. At 48h of life, intestinal blood flow was measured at baseline and after application of 2.5% Delflex® solution. RESULTS: The addition of relaxin to NEC group feeds (1x or All Feeds) improved the degree of ileal injury. Ileal blood flow was decreased in the NEC pups compared to the CONTROLS, but the addition of relaxin to one feed increased baseline ileal blood flow in the NEC group compared to NEC alone. Furthermore, the addition of relaxin to ALL feeds significantly increased baseline ileal blood flow. CONCLUSION: Pups who received relaxin with all feeds had substantially increased ileal perfusion compared to control pups. Our data suggest that relaxin supplementation maintains intestinal blood flow and results in less histologic NEC.

Etiology and incidence of pediatric gallbladder disease.

PURPOSE: The spectrum of pediatric biliary tract disease is changing. The goal of this study was to examine the causes and comorbidities of pediatric gallbladder disease at our institution. METHODS: We performed a retrospective chart review on consecutive patient at Kosair Children's Hospital who underwent cholecystectomy over a 9-year time period ending in 2012. RESULTS: Among the 453 patients in the study group, the average age was 13.3 years and 67.2% were female. Indications for cholecystectomy were gallstones in 285 (63%) and biliary dyskinesia in 140 (33%). Of the patients with gallstones, 68 children (15%) had hemolytic disease. Although the number of cholecystectomies for hemolytic disease was relatively stable throughout our study, the number for biliary dyskinesia and non-hemolytic (cholesterol) cholelithiasis rose by 63% and 216%, respectively. Average body mass index (BMI) for patients with non-hemolytic (cholesterol) stones and biliary dyskinesia were significantly greater than the average BMI for patients with hemolytic stones (P < .0001). In addition, the average BMI for children with non-hemolytic (cholesterol) stones was greater than the average BMI with biliary dyskinesia (P < .0001). CONCLUSION: Symptomatic gallbladder disease increased over the study period. Biliary dyskinesia and children with non-hemolytic disease are responsible for this increase.

Lateral pediatric ectopic thyroid.

We present a case of a left-sided neck mass in an 8-year-old female that proved to be ectopic thyroid tissue. After excision, this patient continues to do well and is euthyroid without recurrence after 8-year follow-up. This is a very rare anomaly in a child, especially in conjunction with a normally located thyroid that is functional. We reviewed the literature of displaced ectopic thyroid tissue.

Recurrent neutropenic enterocolitis in a pediatric patient.

Management of an 8-year-old boy with Hodgkin lymphoma is presented. The patient had several recurrences of neutropenic enterocolitis and eventually required ileocecectomy. A review of the literature on this difficult problem affecting pediatric oncology patients is presented.

Intestinal microcirculatory flow alterations in necrotizing enterocolitis are improved by direct peritoneal resuscitation.

Vasoconstriction of the neonatal intestinal microvasculature is a central mechanistic event in development of necrotizing enterocolitis. We hypothesized that topical treatment of the intestine with dialysate fluid would ameliorate the vasoconstriction in necrotizing enterocolitis (NEC). NEC was induced in experimental groups. Control animals were delivered vaginally and dam-fed (control group). Neonatal pups underwent laser Doppler flow study of the terminal ileum to determine real-time blood flow in the intestinal microvasculature. After baseline flow was determined, dialysis solution was added to the peritoneal cavity and alterations in microcirculation were recorded. Baseline ileal blood flow in the control group was significantly higher than in NEC rat pups at 48 hours post delivery (P < 0.05), but not at 24 hours (P = NS). Ileal blood flow increased in all groups after adding dialysate (P < 0.05), improving ileal blood flow in the 48-hour NEC group and reaching the baseline level of the 48-hour control group (P < 0.05). Our data shows blood flow to be higher in 48-hour controls as compared with 24-hour controls suggesting a time-dependency in the development of intestinal vasoregulatory processes. All groups had an increase in blood flow with dialysate treatment. This may represent a novel initial therapy to improve intestinal ischemia in human necrotizing enterocolitis.

Maternal cigarette smoking and the development of necrotizing enterocolitis.

BACKGROUND: The maternal variables that affect fetal development and correlate with necrotizing enterocolitis (NEC), the most common gastrointestinal emergency in premature infants, are not well defined. We hypothesized that maternal risk factors were the primary determinant of future development of NEC. METHODS: Patients with NEC were identified from an established NICU database and were control-matched with 2 neonates treated at the same institution. The medical records of each patient during the NICU admission as well as the prenatal and delivery record of the patient's mother were reviewed. Perinatal data, including maternal smoking, maternal hypertension, maternal BMI, maternal gestational diabetes, conduct of labor and type of delivery, Apgar scores, types of feedings, and placental pathology, were examined, with P < .05 deemed significant. RESULTS: A total of 73 neonates diagnosed with NEC and 146 matched controls were identified. Medical records for each subject and their mothers were reviewed (438 records total). Maternal cigarette smoking was significantly associated with the future development of NEC (P = .02). Maternal gestational diabetes, maternal hypertension, formula feeding, and pathologic chorioamnionitis or uteroplacental insufficiency did not correlate with NEC. CONCLUSIONS: These data identified maternal cigarette smoking as the only risk factor that is associated with the development of NEC in premature infants. Our data imply that smoking delivers toxins and nicotine to the uterine microenvironment that can affect microvascular development and may predispose the fetus to future NEC.

Direct peritoneal resuscitation augments ileal blood flow in necrotizing enterocolitis via a novel mechanism.

PURPOSE: Endothelin-1, prostaglandins (PGs), and nitric oxide (NO) have been implicated in the intestinal microvascular dysfunction of necrotizing enterocolitis (NEC). We hypothesized that direct peritoneal resuscitation (DPR) dilates the intestinal microvasculature and improves blood flow independent of these mechanisms. METHODS: Rat pups were assigned by litter to experimental NEC or CONTROL groups. Laser Doppler flowmetry evaluation of intestinal microvascular blood flow was studied at baseline, with mediator blockade (endothelin-A receptor, endothelin-B receptor, PG synthesis, or NO synthase) and with DPR. Repeated-measures analysis of variance test was applied with Tukey-Kramer honestly significant difference test (P < .05). RESULTS: At baseline, NEC animals demonstrated significantly decreased ileal blood flow as compared with CONTROLs (P < .05). Endothelin-A receptor and PG inhibition increased flow in the intestinal microvasculature, but this was significantly augmented by the addition of DPR (P < .05). Blockade of NO synthase decreased intestinal blood flow, which was overcome with addition of DPR (P < .05). CONCLUSION: Ileal blood flow was significantly reduced in NEC animals as compared with CONTROLs. The addition of DPR to the peritoneum increased ileal blood flow significantly in all groups in spite of blockade of these known vasoactive mechanisms. Direct peritoneal resuscitation may be a novel strategy to improve intestinal blood flow in NEC.

Ascending aortopulmonary fistula 40 years after previous cardiac surgery.

We present a case of a 64-year-old female presenting with hemoptysis and an ultimate diagnosis of ascending aortopulmonary fistula 40 years after an atrial septal defect repair. A literature review of this rare complication of ascending aortic cannulation includes the pathogenesis and etiology of this rare diagnosis. Aortobronchopulmonary fistula is a rare diagnosis with grave consequences if not treated urgently. We present a case of such diagnosis that was treated with a good outcome.

Dopamine overflow is increased in olfactory bulbectomized rats: an in vivo microdialysis study.

Olfactory bulbectomy (OBX) in rats produces behavioral, physiological, and neurochemical changes that resemble symptoms of depression in humans. The procedure thus serves as a rodent model of affective disorder. Many of the behavioral effects of OBX resemble psychomotor agitation. The possible role of dysregulation of ventral striatal dopamine (DA) systems in this phenomenon was investigated. Basal levels of DA, norepinephrine (NE), homovanillic acid, dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid were examined in the striatum of OBX and sham-operated controls using in vivo microdialysis. OBX rats exhibited significantly higher basal DA levels (192%) and lower NE levels (12%) than sham-operated controls. Locomotor activity in response to novelty and footshock stress was elevated in OBX rats. The finding of higher DA levels in striatum may explain this "agitation-like" behavior, a commonly observed phenomenon in the OBX model.