Alterations of enteric nerve plexus in experimental gastroschisis: is there a delay in the maturation?

Background/Purpose

After surgical correction of gastroschisis, intestinal transitory hypoperistalsis usually occurs. Long-term parenteral nutrition often is necessary leading to a higher morbidity associated with this malformation. The etiology of this transitory intestinal hypomotility is unknown. It may be caused by a reversible inflammatory process in the intestinal wall or other causes, including an alteration of the maturation of intestinal neural plexus, because the disturbance disappears spontaneously after a variable period. The aim of this work was to study the neuronal cells of the myenteric plexus of the fetal intestine in experimental gastroschisis. The main hypothesis was that the transitory intestinal dismotility seen in gastroschisis could be secondary to alteration in the maturation of the enteric nervous plexus.

Methods

Twenty-seven time-mated rabbits, on gestational day 25, were submitted to a midline laparotomy; the gravid bicornuate uterus was exposed and opened, and the more distal fetuses relative to the vaginal opening had the abdominal wall opened by a small incision to produce gastroschisis (n = 29). The fetuses not submitted to gastroschisis were used as controls (n = 12). The amniotic fluid was carefully aspirated from the opened uterus and saved for later repositions. On gestational day 30, the does were again submitted to general anesthesia, and the fetuses were delivered by cesarean section. The fetal intestine was removed, the adjacent mesentery excised, and intestinal specimens were harvested for histologic studies. The specimens were stained for acetyl-cholinesterase activity (AChE) to assess the maturity of the nervous enteric cells and for lactate dehydrogenase (LDH) that identify specifically immature nervous cells. The histologic sections stained by LDH were submitted to histomorphometric analysis of the nervous cells through an image system analysis (Kontron 300). The results were submitted to statistical analyses (P < .05).

Results

Macroscopic alterations of the fetal gastroschisis intestine are similar to the human findings: shortening of the intestine, intestinal wall thickening, and a hypertrophied muscular layer. In the gastroschisis group, histologic AChE activity was decreased in comparison with control intestines. The histomorphometric assessment in slices stained with LDH, which identify immature nervous cells, showed that the neuronal intestinal cells of the gastroschisis group were significantly smaller and more numerous relative to the control group.

Conclusions

There were significant differences in the nervous plexus of the intestine of fetuses with gastroschisis relative to the controls. The observed morphologic changes may be caused by alteration in the maturation of the intestinal neuronal in gastroschisis. This alteration may explain the transitory intestinal hypomotility observed in infants after surgical correction of gastroschisis.     

In utero repair of gastroschisis in the sheep (Ovis aries) model

Objective

Gastroschisis is associated with inflammatory changes in the exposed bowel which leads to intestinal dysmotility after postnatal repair. The insult is a combined effect of amniotic fluid exposure and mechanical constriction. We hypothesized that in utero anatomic repair is possible in a sheep model, and that it may halt the inflammatory damage caused by both mechanisms.

Methods

Gastroschisis was surgically created in mid-gestation (day 75) in 8 sheep fetuses. On gestational day 100, 2 fetuses underwent open fetal gastroschisis repair, where the eviscerated bowel was returned to the peritoneal cavity, and the abdominal wall was primarily closed. All fetuses were harvested at 135 days of gestation.

Results

Six fetuses survived the initial operation, and both fetuses that underwent gastroschisis repair survived to term. At 100 and 135 days of gestation, the eviscerated bowel showed progressive signs of inflammation and peel development. The gross and microscopic inflammatory changes in the gastroschisis bowel at 100 days of gestation were completely resolved at term following in utero repair.

Conclusion

In utero anatomic repair of gastroschisis is possible in mid-gestation in the fetal lamb model, and it appears to ameliorate the inflammatory process.     

Effects of intrauterine treatment on interstitial cells of Cajal in gastroschisis

Aim

An experimental study was performed to investigate the effects of amnio-allantoic fluid exchange and intrauterine bicarbonate treatment on intestinal damage and interstitial cells of Cajal (ICC) in gastroschisis.

Materials and Methods

Thirteen-day-old fertilized chick eggs were randomly allocated into 4 groups as control, gastroschisis, gastroschisis + amnio-allantoic fluid exchange, and gastroschisis + bicarbonate treatment groups. In the treatment groups, amnio-allantoic exchange and bicarbonate treatments were performed for 3 days, after creating gastroschisis. Specimens were processed for hematoxylin-eosin and c-kit immunohistochemistry on the 18th day of incubation, after macroscopic examination. The intestines were evaluated with light microscopy for the presence of mucosal congestion and muscular and serosal edema. Mean muscular thickness and density of ICC were measured.

Results

Mean muscular thickness significantly increased in the gastroschisis group when compared with control and treatment groups. Labeling intensity, morphology, and localization of the ICC were similar in all groups. Mean ICC density significantly decreased in the gastroschisis group when compared with the control group (P < .01), and it significantly increased after amnio-allantoic fluid exchange treatment (P < .01).

Conclusions

The decrease in ICC density encountered in damaged intestinal loops in gastroschisis was prevented with intrauterine treatment. The beneficial effects of amniotic exchange on intestinal motility may depend on both prevention of intestinal damage and preservation of ICC density and function. The density of ICC might be a reliable numeric parameter both to predict intestinal motility disorders in gastroschisis and to compare the effectiveness of intrauterine treatment methods.     

Antenatal diagnosis of bowel dilatation in gastroschisis is predictive of poor postnatal outcome

Purpose

Although gastroschisis infants usually have a good outcome, there remains a cohort of babies who fare poorly. We inquired whether the presence of bowel dilatation in utero is predictive of postnatal course in infants with gastroschisis.

Methods

We compared the clinical course of infants who had bowel dilatation with those who did not. Bowel dilatation was defined as more than 20 mm in cross-sectional diameter on ultrasound at any gestational age. Outcome measures used were length of time of parenteral nutrition, death, and surgery for intestinal failure.

Results

A review of 170 infants with gastroschisis identified 74 who had dilatation of more than 20 mm (43.5%). There was no significant difference in the incidence of intestinal atresia in those with bowel dilatation and those without (P = .07). Those with bowel dilatation spent a longer period on parenteral nutrition. There were significantly more deaths in the group with bowel dilatation (P = .01). There was no significant difference in the number of infants requiring surgery for intestinal failure between the 2 groups (P = .47).

Conclusions

We found that sonographically detected bowel dilatation more than 20 mm in utero in fetuses with gastroschisis may have value in predicting clinically significant adverse postnatal outcomes.     

The effect analysis and comparison between gastroschisis and tracheal ligation on experimental diaphragmatic hernia in fetal rabbits

Purpose

The authors analyzed and compared the effects of experimentally induced gastroschisis and tracheal ligation on pulmonary hypoplasia in fetal rabbits with congenital diaphragmatic hernia.

Methods

Twenty-three pregnant rabbits underwent fetal surgery on gestational day 24 through 27. Left diaphragmatic hernia was created in 1 fetus (DH group) from each rabbit, and a left diaphragmatic hernia with gastroschisis (GS group) or tracheal ligation (TL group) was created in another fetuses. The fetuses were delivered on gestational day 27 through 33. Histologic and morphometric examination of the lungs were performed in each group.

Results

In the DH group, the lungs were hypoplastic with a decrease in lung weight to body weight ratio and an increase in pulmonary arterial wall thickness. The alveolar septae were markedly thickened and diminished alveolar air spaces. In GS and TL groups, the alveolar septae were thickened but narrower than those of the DH group, air spaces were increased, and the pulmonary arterial wall was only slightly thickened.

Conclusions

Pulmonary hypoplasia seen in newborn rabbits after experimentally induced diaphragmatic hernia is less severe in those rabbits with concurrently made gastroschisis or tracheal ligation. From the histologic viewpoint, the effects of gastroschisis and tracheal ligation on pulmonary hypoplasia in diaphragmatic hernia have no differences.     

Intestinal transplantation for short bowel syndrome secondary to gastroschisis

Background/Purpose

Gastroschisis is the most frequent cause of pediatric intestinal transplantation. This study reviews our experience of intestinal transplantation secondary to gastroschisis to elucidate those factors affecting the outcome of children with short bowel syndrome.

Methods

A retrospective review was performed for children who underwent intestinal transplantation for gastroschisis at the University of Miami between June 2003 and August 1994.

Results

Thirty-two transplants were performed in 28 children with gastroschisis during the study period. Associated intestinal anomalies were present in 22 infants (atresia [n = 14], volvulus [n = 3], and/or ischemia [n = 16]). Spontaneous prenatal closure of gastroschisis, a rare anomaly associated with bowel atresia and ischemia because of a very small abdominal defect, was seen in 9 patients. Most of the patients had a complicated course and required multiple abdominal surgeries before transplant. Fifteen (53.6%) patients are currently alive at a median follow-up of 23.5 months. Short-term survival rate has significantly improved in recent years.

Conclusions

Patients with complex gastroschisis and intestinal anomalies have a significant risk for progression to short bowel syndrome. Intestinal transplantation can be a lifesaving option and provides a satisfactory outcome for children with short bowel syndrome secondary to gastroschisis.     

Delivery of gastroschisis patients before 37 weeks of gestation is associated with increased morbidities

Background

Despite advances in the care of neonates with gastroschisis, patients present with significant morbidities. Preterm delivery of neonates with gastroschisis is often advocated to avoid the intestinal damage that may be sustained with prolonged exposure to amniotic fluid. However, preterm delivery may impose additional morbidities to this disease process.

Methods

We conducted a retrospective review of patients with gastroschisis born from 1989 to 2007. Demographic and clinical data were collected. Preterm healthy neonates, with gestational age from 26 to 36 weeks, were used as controls.

Results

Preterm infants with gastroschisis had a 14 times higher risk for any of the recorded morbidities. As compared to term neonates with gastroschisis, preterm neonates with gastroschisis had a higher rate of sepsis, longer duration to reach full enteral feedings, and longer length of stay. Although the preterm infants with gastroschisis were less likely to be small for gestational age at birth, they were as likely as the term infants with gastroschisis to have failure to thrive at discharge and had a greater drop in weight percentile during hospitalization.

Conclusions

Preterm delivery should be avoided because there is no clear benefit to the gut in avoiding derivative injuries. Meticulous attention should be given to the nutritional needs of patients with gastroschisis.     

Increasing prevalence of gastroschisis repairs in the United States: 1996-2003

Purpose

Local and state registries have shown recent increases in the prevalence of gastroschisis in the United States and abroad. The purpose of this study was to use a nationally representative database to identify national trends in the prevalence of gastroschisis repairs.

Methods

Records of infants undergoing gastroschisis repair were identified in the Nationwide Inpatient Sample from 1996 to 2003. Birth data were obtained from the National Center for Health Statistics and used to calculate the rate of procedures/live births stratified by US census region. Survey statistics were used to account for the sampling design of the Nationwide Inpatient Sample database.

Results

Between 1996 and 2003, a total of 9459 gastroschisis repairs were performed in the United States (3 procedures for every 10,000 births). A significant increase in the population-based rate of these procedures was observed in each census regions and nationwide. A twofold higher procedure rate was observed in 2003 than in 1996 (rate ratio, 2.0; 95% confidence interval, 1.1-2.9; P < .001). No significant change in unadjusted hospital mortality was observed regionally or nationally.

Conclusions

The population-based rate of gastroschisis repairs significantly increased regionally and nationwide between 1996 and 2003, paralleling recent trends described at the local and state level.     

Peroperative Gastrograffin bowel lavage in gastroschisis

Aims

The aim of the study was to evaluate potential benefits in the use of peroperative bowel lavage with Gastrograffin in neonates with gastroschisis.

Methods

A retrospective analysis of newborns with gastroschisis was performed over a 10-year period in 2 centers in the United Kingdom. Two groups were studied wherein one had peroperative bowel lavage with Gastrograffin and the other did not.

Results

Data were collected on 116 patients of whom 93 were suitable for analysis. There were no statistically significant differences in primary closure rate, duration of ventilation, parenteral nutrition, or hospital stay. Intestinal obstruction occurred more frequently in the nonlavage group.

Conclusion

Gastrograffin lavage peroperatively in gastroschisis offers no potential advantage in reducing ventilatory requirements, parenteral nutrition, and hospital stay. It also does not achieve greater primary closure rates, but may reduce the incidence of intestinal obstruction.     

Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells

Background

A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene—encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis.

Methods

At 18.5 day’s gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [α-SMA]) immunohistochemistry, and trasmission electron microscopy (TEM).

Results

In the controls, SMC were c-kit+ and α-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach’s plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and α-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and α-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature.

Conclusions

ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.     

Amniotic fluid ferritin as a marker of intestinal damage in gastroschisis: a time course experimental study

Background/Purpose

Intestinal damage (ID) is closely related to morbidity and mortality in gastroschisis. This study was performed to determine the intraamniotic substances that may correlate ID and also to verify their time course levels that would be useful for determining when ID starts in gastroschisis.

Methods

In this study, 13-day-old fertilized chick eggs were used. The amnioallantoic membrane was perforated to create amnioallantoic cavity in all embryos. Gastroschisis was created in gastroschisis group to simulate human gastroschisis. Amnioallantoic fluid samples were collected from the embryos on the 13th to 19th gestational days, and the intestines of each group were harvested for evaluation. Amnioallantoic levels of interleukin-8, ferritin, alkaline phosphatase, and amylase were measured. Serosal thickness of the intestines in each group was evaluated.

Results

Increasing amnioallantoic fluid levels of interleukin-8, alkaline phosphatase, and amylase were found in both groups. In contrast to control group, ferritin levels, as a sign of inflammation, were found increased only in gastroschisis group. Histopathologic examination of intestines in the gastroschisis group showed a significant increase in the serosal thickness especially after the 16th day.

Conclusion

Increases in amnioallantoic fluid levels of ferritin show promise as a marker for determining ID encountered in gastroschisis but warrant further investigation.     

Fibrobronchoscopic treatment of foreign body aspiration in children: an experience of 5 years in Hangzhou City, China

Objective

The aims of the study were to evaluate duration of symptoms, clinical manifestation, radiological findings, fibrobronchoscopic findings, and the complications of airway foreign body (FB).

Methods

A retrospective review of 304 children who had airway FB removed via fibrobronchoscopy from January 1997 to June 2003 was conducted in the Children's Hospital of Zhejiang University School of Medicine, China. Two hundred eight boys and 96 girls were included. Their ages ranged from 2 months to 11 years, and the median was 18 months.

Results

Three patients died; 81.24% of the patients had a history of FB aspiration, and the most frequent clinical manifestation was paroxysmal coughing (89.25%). Positive radiological findings were found in 90.13% of patients, and the most common type of FB was peanut (35.53%). Serious complication of lung was found in 65 patients, and the associated factors were age, sex, and times of fibrobronchoscopy and location of FB in the right or left lung.

Conclusions

FB aspiration remains a major cause of morbidity and mortality in childhood. Education aimed at increasing diagnostic acumen of the physicians and heightening of public awareness are the most important steps needed to reduce the morbidity and mortality.     

A multicenter, randomized, double-blind, placebo-controlled trial of the prokinetic agent erythromycin in the postoperative recovery of infants with gastroschisis

Background/purpose

The recovery of gut function after repair of gastroschisis is frequently prolonged, and these infants are prone to complications associated with parenteral nutrition. This trial was designed to investigate the effect of the prokinetic agent, erythromycin, on the attainment of full enteral feeding in infants after primary repair of uncomplicated gastroschisis.

Methods

A multicenter, randomized, double-blind, placebo-controlled trial was used to investigate the effect of enteral erythromycin (3 mg/kg/dose 4 times daily) compared with placebo on the attainment of full enteral feeding tolerance after primary repair of uncomplicated gastroschisis. Eleven neonatal surgical units in the United Kingdom participated in the study. The primary end-point was the time taken to achieve continuous enteral feeding at 150 mL/kg/24 hours sustained for 48 hours.

Results

Of 70 eligible infants, 62 were recruited and randomly divided. There were 30 patients in group I (placebo) and 32 in group II (erythromycin). The groups were comparable in terms of mean gestational age, mean birth weight, extent of evisceration, and degree of intestinal peel. There was no statistically significant difference between the 2 groups in the time taken to achieve full enteral feeding (27.2 v 28.7 days; P = .75). Similarly, no significant differences were found in the incidence of catheter-related sepsis, duration of parenteral nutrition, or time to discharge between the 2 groups.

Conclusions

Enterally administered erythromycin at a dose of 3 mg/kg 4 times daily conferred no advantage in the time taken to achieve full enteral feeding after primary repair of uncomplicated gastroschisis.     

A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis

Background

Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial.

Methods

Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay.

Results

Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation.

Conclusions

Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis.     

The effect of gastroschisis on experimental diaphragmatic hernia in fetal rabbits

Purpose

In this study, the authors analyzed the effect of experimentally induced gastroschisis on pulmonary hypoplasia in fetal rabbits with congenital diaphragmatic hernia (CDH).

Methods

Twenty-three pregnant rabbits underwent fetal surgery on gestational day 24 through 27. A left diaphragmatic hernia was created in 1 fetus (DH group) from each rabbit, and a left diaphragmatic hernia with gastroschisis was created in another fetus (GS group). The fetuses were delivered on gestational day 27 through 33. Histologic and morphometric examination of the lungs in each group was done.

Results

In the DH group, the lungs were hypoplastic with a decrease in lung weight to body weight ratio and an increase pulmonary arterial medial wall thickness. The alveolar septae were markedly thickened with increased interstitial tissue and diminished alveolar air spaces. In the GS group, the alveolar septae were thickened but narrower than those of DH group, and air spaces were increased. The pulmonary arterial wall was markedly thickened in the DH group but only slightly thickened in the GS group.

Conclusions

Pulmonary hypoplasia seen in newborn rabbits after experimentally induced diaphragmatic hernia is less severe in those rabbits with both gastroschisis and DH.     

Method to our madness: an 18-year retrospective analysis on gastroschisis closure

Background

The advent of preformed silos has facilitated routine bedside placement often without any attempt of intestinal reduction. It is unclear whether a strategy of routine silo (RS) placement with delayed fascial repair is beneficial over attempted primary repair (aPR) and silo placement only for those patients who cannot be reduced. We retrospectively compared clinical outcomes of neonates having aPR to those having RS placement to determine the impact of routine silo use and silo duration on gastroschisis care.

Methods

Neonatal records from patients with gastroschisis at a single children's hospital between 1990 and 2008 were reviewed. Demographic and outcome data were recorded and subjected to statistical analyses. Documentation of attempted intestinal reduction was used as a surrogate marker for aPR. The remaining patients were placed in the RS group.

Results

Two hundred forty-eight neonates with gastroschisis were identified. Thirteen were excluded for congenital or clinical issues which precluded aPR. Of the remaining 235 patients, neonates with RS had significantly more ventilator days (6.2 vs 4.4; P = .0011), more time of total parenteral nutrition (36.5 vs. 28.5; P = .0018), longer length of stay (LOS, 46.5 vs. 40.5; P = .0011), and greater hospital charges ($216,000 vs $172,000; P < .0001) than patients who had aPR. There was no significant difference observed in complications or survival. Linear regression modeling demonstrated that time to closure was significantly related to LOS as an independent variable. Each day to closure was associated with 2.2 extra days of hospitalization and approximately $9557 in hospital charges.

Conclusion

Although limited by retrospective biases, this study demonstrates that time to closure is the most significant variable related to LOS in gastroschisis. This relationship is intuitive since longer time to closure is probably determined by the severity of gastroschisis. The method of closure, by primary repair or silo, is of secondary importance. Conversely, unnecessarily increasing the time to closure may increase the LOS. The speed of reduction, whether through primary repair or by silo, should be guided by physiologic principles.     

Intravenous landiolol, a novel β(1)-adrenergic blocker, reduces the minimum alveolar concentration of sevoflurane in women

Study Objective

To investigate the effect of intravenous (IV) landiolol, a novel β₁-adrenergic blocker, on the minimum alveolar concentration (MAC) of sevoflurane in adult women.

Design

Prospective, randomized study.

Setting

University hospital.

Patients

42 ASA physical status 1 and 2 women, aged 24-57 years, who were scheduled to undergo elective abdominal surgery.

Interventions

Anesthesia was induced in all patients by vital capacity rapid inhalation induction of sevoflurane. In the landiolol group, administration of landiolol began when patients took a vital-capacity breath: 0.125 mg/kg/min for one minute and then 0.04 mg/kg/min. Normal saline was administered in the control group.

Measurements

MAC was determined by a technique adapted from the conventional up-down method.

Main Results

The MAC of sevoflurane was 2.2% ± 0.2% in the control group and 1.7% ± 0.2% in the landiolol group, a statistically significant difference (P = 0.0005).

Conclusions

IV landiolol reduces the MAC of sevoflurane in women by approximately 20%.     

Effects of prenatal dexamethasone on the intestine of rats with gastroschisis

Background/purpose

Intestinal lesions observed in gastroschisis (Gx) are accompanied by neonatal gastrointestinal dysfunction. This study examines the effects of transplacental dexamethasone on the eviscerated intestine of fetal rats with Gx.

Methods

Gx was created surgically in rat fetuses on gestational day 18, and the dams were treated either with 0.4 mg/kg intraperitoneal dexamethasone or with vehicle only on days 19 and 20. The intestine recovered on day 21 were processed for total DNA and protein. Immuno-histochemical staining for ki-67, TUNEL, and synaptophysin were used for assessing the proportions of proliferating and apoptotic cells and the density of intramural ganglia. Analysis of variance (ANOVA) was used for comparison among groups. Significance level was set at P less than .05.

Results

Body weight was reduced in Gx fetuses in comparison with controls. Intestinal weight per centimeter and mucosal and seromuscular layer thicknesses were increased in Gx and Gx + dexa groups. Total intestinal DNA was diminished in Gx animals but it was near normal in Gx + dexa ones. Total intestinal protein was similar in all groups. DNA and protein per centimeter of bowel were very increased in Gx animals but only slightly in Gx + dexa ones. Proliferating cells were decreased in Gx animals and increased in Gx+dexa ones, whereas the opposite was observed for apoptosis. Density of intramural ganglia was decreased significantly in both Gx groups.

Conclusions

Late intrauterine exposure to dexamethasone of rat fetuses with Gx decreased wall thickening, normalized total DNA, and induced proliferation in the exposed bowel while limiting apoptosis. This medication could have some yet incompletely defined beneficial effects on the wall of the eviscerated bowel in Gx.     

Outcomes in children with intestinal failure following listing for intestinal transplant

Purpose

The purpose of this study was to describe the population of pediatric patients waiting for intestinal transplant and to evaluate the risk of death or transplant by specific disease states.

Methods

We studied the United Network for Organ Sharing (UNOS) database (Jan 1,1991 to 5/16/08) for patients 21 years old or younger at first listing for intestinal transplant and examined their age, sex, weight, and diagnoses. Time to list removal was summarized with cumulative incidence curves. Multinomial logistic regression was used to compare relative risk ratios for removal from the list for transplant, death, or other reasons.

Results

We identified 1712 children listed for intestinal transplant (57% male, 51% <1 year, weight 8.1 kg [IQR, 6.1-14.1] at listing). Median age and weight at transplant (n = 852) were 1 year (IQR, 1-5) and 10 kg (IQR, 6.5-16.3). Regression analysis demonstrated significant differences in outcomes among disease conditions (P < .001). Compared to the gastroschisis group, the relative risk ratio for death versus transplant was higher in the necrotizing enterocolitis group (P = .015), lower in the short gut syndrome group (P = .001), and not different in the volvulus group (P = .94) after adjustment for weight and sex.

Conclusions

We conclude that the relative risk of transplant vs death varies significantly by the disease condition of the patient.     

In situ inhibition of uterine activity by indomethacin: possible relevance to preterm labor prevention after fetal surgery

Purpose

This report is an analysis of the effects of local indomethacin delivery on uterine activity in vitro.

Methods

Isolated strips of time-dated pregnant rats’ myometrium were placed within controlled tissue baths. Spontaneous muscular activity was recorded by a force transducer connected to a polygraph at cumulative concentrations of indomethacin. Statistical analysis was by single-factor analysis of variance (ANOVA), with P values of less than .05 considered significant.

Results

Within a narrow concentration range, the effects of indomethacin on frequency and amplitude of myometrial contractions were nonmonotonic, with an increase in frequency at levels that began to depress amplitude. However, both amplitude and frequency were significantly depressed and eventually totally abolished at most concentrations studied (P < .05).

Conclusions

Indomethacin administered in situ consistently inhibits or completely arrests overall myometrial activity. The concept of local myometrial delivery of indomethacin, possibly via slow release systems, may prove clinically useful as an adjuvant to its systemic administration in preterm labor prevention after fetal surgery, warranting further trials in vivo.