Late administration of antenatal vitamin A promotes pulmonary structural maturation and improves ventilation in the lamb model of congenital diaphragmatic hernia.

PURPOSE: The lungs in congenital diaphragmatic hernia (CDH) are hypoplastic and immature making respiratory support one of the most challenging aspects of caring for these neonates. Vitamin A is essential for normal lung growth and development. It also promotes alveolarization. The aim of this study is to investigate the effects of antenatal vitamin A on lung growth and alveolarization and ventilation in the lamb model of CDH. METHODS: This study was approved by the Animal Care Committee of the State University of New York at Buffalo, and conforms to the National Institute of Health guidelines. Diaphragmatic defects were created at 79-81 days gestation. Group 1 lambs (CDH, n = 5) were untreated. In group 2 (CDH + vitamin A, n = 6) and group 3 lambs (control + vitamin A, n = 3) right jugular venous catheters were inserted at 118-120 days and retinyl palmitate (vitamin A) was administered until 135 days. The control group (n = 5) consisted of twin littermates. Lambs were delivered at 136-139 days and ventilated for 2 h according to a set protocol. The left lungs were harvested and fixed for histology. RESULTS: Lung compliance was significantly higher in CDH + vitamin A (median 0.27, range 0.1-0.48 ml/cmH(2)O/kg) versus CDH lambs (median 0.07, range 0.07-0.18 ml/cmH(2)O/kg), P < 0.05. At 1 h CDH + vitamin A lambs experienced significantly lower PaCO(2) (median 115, range 35-194 mmHg vs. median 192, range 168-234 mmHg) and higher arterial pH (median 7.0, range 6.74-7.35 vs. median 6.73, range 6.5-6.81) than CDH lambs, P < 0.05. The lung weight to body weight ratio of CDH + vitamin A lambs was significantly less than that of CDH lambs (P < 0.05). Histology showed small thick walled air-spaces and no true alveoli in CDH lambs. In contrast, true alveoli and thinning of the inter-alveolar septums were seen in CDH + vitamin A lambs. CONCLUSION: This is the first study to demonstrate an improvement in lung function and structural maturation when antenatal vitamin A is given in a surgical model of CDH.

Antenatal vitamin A decreases ventilation-induced lung injury in the lamb model of congenital diaphragmatic hernia.

OBJECTIVE: Infants with congenital diaphragmatic hernia (CDH) are susceptible to ventilation-induced lung injury. Vitamin A may protect the lung from injury during ventilation. The authors investigated the effects of antenatal vitamin A on ventilation-induced lung injury in CDH lambs using lung myeloperoxidase (MPO) activity as an indicator of lung injury. METHODS: Left-sided diaphragmatic defects were created in 10 lambs at 79-81 days' gestation. Six CDH lambs had right jugular venous catheters inserted at 120 days' gestation and were given vitamin A until 135 days' gestation. Four CDH lambs were not treated. Twin littermates (n = 3) served as controls. All lambs were delivered at 136-139 days of gestation and ventilated for 2 hours. Lambs were sacrificed following ventilation and samples of left lung were snap frozen. MPO was extracted from lung tissue and MPO activity was assayed. RESULTS: CDH lambs treated with antenatal vitamin A demonstrated significantly lower MPO activity than untreated CDH lambs (0.0477 +/- 0.0150 vs. 0.1106 +/- 0.0230 units/mg protein, p < 0.05). CONCLUSION: This is the first study to look at the effect of vitamin A on lung injury in CDH. In the lamb model of CDH, antenatal vitamin A decreases ventilation-induced lung injury.

Fetus-in-fetu: report of a case and a review of the literature.

A 2-week-old girl was found to have an asymptomatic abdominal mass on routine examination. Surgical removal revealed the mass to have 4 limb buds situated relative to a palpable vertebral column. Karyotyping revealed the mass to be 46 XX. The mass was therefore diagnosed as a case of fetus-in-fetu. The literature on this rare entity is reviewed, and the diagnosis and pathogenesis of the disease are discussed.

Minimal access extrapleural esophagoesophagostomy.

BACKGROUND/PURPOSE: Minimal access repair of esophageal atresia is gaining acceptance but usually requires a transpleural approach. An extrapleural approach using a 2-cm incision has been described. The purpose of this study was to develop a less-invasive approach to extrapleural esophagoesophagostomy. METHODS: A 5-8 kg nonsurvivor piglet model was used to develop this technique. The extrapleural dissection was performed under direct vision utilizing transpleural thoracoscopy. A 16-gauge needle and a spatula were used to create an extrapleural space that allowed insertion of a 3-mm trocar. An 8F catheter with a 3-mL balloon was inserted through the trocar and inflated to create enough space to exchange it for a 5-mm trocar. A 12F catheter with a 5-mL balloon was inserted through the 5-mm trocar and inflated to enlarge the space. These steps were repeated at each of the 3 extrapleural port sites until one confluent extrapleural space was created that did not communicate with the transpleural port site. Esophagoesophagostomy was then completed within the extrapleural space. RESULTS: Thoracoscopic guidance and balloon dissection facilitated creation of an adequate extrapleural working space. CONCLUSIONS: This new minimal access extrapleural approach offers an attractive alternative to the currently described minimal access approaches to esophagoesophagostomy.

Beneficial effects of intraluminal nitroglycerin in intestinal ischemia-reperfusion injury in rats.

BACKGROUND: We examined the effects of intraluminal nitroglycerin (NTG) on various physiologic functions and intestinal pathology in intestinal ischemia-reperfusion (IR) injury in rats. MATERIAL AND METHODS: Intraluminal NTG (0.15-3.75 mg/kg) was administered at different doses and stages during the experimental disease, and intestinal permeability and histology, bile flow, and systemic hemodynamics were measured. RESULTS: Prophylactic intraluminal NTG treatment at 0.75 mg/kg, but not at 0.15 mg/kg, significantly attenuated the deleterious changes in intestinal barrier function and mucosal injury caused by IR. However, administration of NTG after ischemia was not effective, even up to 3.75 mg/kg. In vitro intestinal NTG metabolism was significantly decreased following intestinal ischemia. Intraluminal NTG at 0.75 mg/kg significantly attenuated the reduction in bile flow that accompanied IR. Reperfusion induced a precipitous and sustained decrease in mean arterial pressure, which was blunted by intraluminal NTG. CONCLUSIONS: Intraluminal NTG produced several beneficial local and systemic effects in a rat model of intestinal IR. In this disease model, 0.75 mg/kg intraluminal NTG did not exacerbate, but rather reduced, the hypotensive effects induced by IR.

Diagnosing Hirschsprung's disease: increasing the odds of a positive rectal biopsy result.

BACKGROUND/PURPOSE: Rectal biopsies are performed as a definitive means of diagnosing Hirschsprung's Disease (HD) in children presenting with constipation. The authors hypothesized that key features in the history, physical examination, and radiographic evaluation would allow us to avoid unnecessary rectal biopsies. METHODS: A retrospective analysis was conducted on patients undergoing rectal biopsy between 1995 and 2001. Patients with HD were identified (n = 50), and a concurrent cohort of patients with idiopathic constipation (IC; n = 50) was selected. Pertinent features in patients with HD versus those with IC were cross tabulated using Pearson Chi2 testing (significance was P <.05). RESULTS: Sixty percent of patients with HD and 15% of patients with IC experienced onset of symptoms in the first week of life. HD patients more frequently experienced delayed passage of meconium (P <.05), abdominal distension (P <.05), vomiting (P <.05), and transition zone on contrast enema (P <.05). All patients with HD had one or more of these significant features. In contrast, only 64% of patients with IC had one or more of these features. The classic triad of symptoms (ie, delayed passage of meconium, vomiting, and abdominal distension) was present in 18%, and one or more of these symptoms was present in 98% of HD patients. In contrast, only 60% of patients with IC had a history of delayed passage of meconium, vomiting, or abdominal distension. CONCLUSIONS: A history of delayed passage of meconium, abdominal distension, vomiting or the results of a contrast enema identified all patients with HD and excluded HD in approximately 36% of patients with idiopathic constipation. The authors have shown that key features in a patient's history, physical examination, and radiologic evaluation can differentiate between HD and IC. In a child presenting with constipation and none of the above features, it is not necessary to perform a rectal biopsy to exclude HD.

The respiratory advantage of laparoscopic Nissen fundoplication.

BACKGROUND/PURPOSE: Laparoscopic Nissen fundoplication is replacing the open approach in the treatment of children with gastroesophageal reflux. The postoperative respiratory advantages seem obvious but remain unproven. The authors hypothesized that laparoscopic Nissen fundoplication provides postoperative respiratory advantages in neurologically normal children as well as those with mental retardation or profound neurologic impairment. METHODS: The charts of all laparoscopic Nissen fundoplications over a 4-year period were reviewed. Sixty-one laparoscopic procedures were compared with the most recent 61 consecutive open Nissen fundoplications. The following variables were reviewed: age, weight, gender, preexisting comorbidities, operating time, postoperative pulmonary complications, and length of stay. Categorical data were compared for significance utilizing chi2 cross tabulation. Variables representing numerical data were compared by t test. RESULTS: Although there appeared to be a trend toward sicker patients in the open group, the laparoscopic group showed significantly improved rates of extubation, shorter recovery room stays, shorter durations of chest physiotherapy, fewer intensive care unit admissions, more rapid resumption of baseline feedings, and overall decreased length of stay (P < 0.05). Pulmonary benefits also were noted in the neurologically impaired population when analyzed separately. CONCLUSIONS: Laparoscopic Nissen fundoplication confers a definable benefit with a significant pulmonary advantage in both neurologically normal children and those with neurologic impairment.

In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice.

The aim of the present study was to examine the effects of oral supplementation of newborn Balb/c mice with bifidobacteria (B. infantis, B. bifidum) and iron-free apo-lactoferrin (bovine, human) on gut endotoxin concentration and mucosal immunity. Endotoxin concentration was measured in ileocecal filtrates at 7, 14, 21, and 28 days postdelivery by a quantitative limulus amebocyte lysate test. While endotoxin levels in bifidobacteria-fed mice showed a steady rise over time, they were consistently lower than that observed in control animals. Results of lactoferrin supplementation varied depending on the specific time point, but overall by day 28, all treatment groups showed lower intestinal endotoxin concentrations compared to saline fed animals. Neither bifidobacteria nor lactoferrin stimulated an increase in B or T cells, or in cytokine production (IL-6, TNF-alpha, INF-gamma), in Peyer's patches as measured by flow cytometry. Bifidobacteria and lactoferrin were well tolerated as dietary supplements and showed promising potential to reduce gut endotoxin levels.

Immune responses in rhesus rotavirus-challenged BALB/c mice treated with bifidobacteria and prebiotic supplements.

Bifidobacterium species (B. bifidum and B. infantis), with or without prebiotic compounds (arabino-galactan, short-chain fructo-oligosaccharide, iso-malto-dextrins), were orally fed to Balb/c pups (n = 192) to evaluate their potential synergistic effects on modulating the course of rhesus rotavirus (RRV) infection, as well as their ability to mediate the associated mucosal and humoral immune responses. Rotavirus-specific IgA and IgG in serum, rotavirus antigen, and specific IgA in feces were measured by ELISA. Mucosal total IgA and IgG levels were determined in Peyer's patches by flow cytometry. Significantly delayed onset (p = 0.001) and early resolution (p < 0.001) of diarrhea were observed in bifidobacteria-treated, RRV-infected mice compared with RRV-infected control mice. Supplementation with prebiotic compounds did not shorten the clinical diarrhea course more than that observed with bifidobacteria treatment alone. Rotavirus-specific IgA in feces was 16-fold elevated on d 5 postinfection in bifidobacteria-treated, RRV-infected mice compared with the RRV-infected alone group. In addition, the level of rotavirus-specific IgA in serum was four-fold higher in bifidobacteria-treated, RRV-infected litters versus mice challenged with RRV alone on 28 and 42 d postinfection. No enhancement of the immune response was found in RRV-infected mice that were treated with both bifidobacteria and prebiotic compounds over those treated with bifidobacteria only. The findings suggest that bifidobacteria may act as an adjuvant by modulating early mucosal and strong humoral rotavirus-specific immune responses, and mitigate severity of rotavirus-induced diarrhea.