Damage In Gastroschisis Research Articles

The intestinal fatty acid-binding protein as a marker for intestinal damage in gastroschisis.

Background/PurposeWe analyzed the capacity of urinary Intestinal fatty acid-binding protein (I-FABP) to quantify the degree of mucosal injury in neonates with gastroschisis (GS) and to predict the speed of their clinical recovery after surgery.MethodsIn this prospective study, we collected urine during the first 48h after surgery from neonates operated between 2012 and 2015 for GS. Neonates with surgery that did not include gut mucosa served as controls for simple GS and neonates with surgery for intestinal atresia served as control for complex GS patients. The I-FABP levels were analyzed by ELISA.ResultsUrinary I-FABP after the surgery is significantly higher in GS newborns than in control group; I-FABP in complex GS is higher than in simple GS. I-FABP can predict subsequent operation for ileus in patients with complex GS. Both ways of abdominal wall closure (i.e. primary closure and stepwise reconstruction) led to similar levels of I-FABP. None of the static I-FABP values was useful for the outcome prediction. The steep decrease in I-FABP after the surgery is associated with faster recovery, but it cannot predict early start of minimal enteral feeding, full enteral feeding or length of hospitalization.ConclusionUrinary I-FABP reflects the mucosal damage in gastroschisis but it has only a limited predictive value for patients’ outcome.

The role of water-soluble meconium subfraction and lipid-soluble meconium subfraction on the superior mesenteric artery vasoconstriction in chick embryos

ObjectiveIntraamniotic meconium has been responsible for intestinal damage in gastroschisis and meconium-dependent intestinal ischemia has been proposed to induce additional intestinal damage in gastroschisis. This study is aimed to determine the effects of lipid and water-soluble meconium subfractions on the contractility of the superior mesenteric artery (SMA). Materials and methodsThe study was conducted on 18-day fertilized chick embryos (Gallus Domesticus). Meconium is fractioned into water and lipid-soluble components. Only one SMA tissue was prepared from each embryo and suspended in the organ bath. Isometric contraction responses (ICR) were created in SMA tissues by one hour of incubation in Krebs–Henseleit solution for each group. Groups consisted of control, meconium, water-soluble meconium subfraction and lipid-soluble meconium subfraction. ICR of the SMA specimens were evaluated with a transducer-amplifier system on a computer. The data were expressed (mean±1SD) as milliNewton (mN). ResultsThe ICR of the meconium, water-soluble meconium subfraction and lipid-soluble meconium subfraction groups were significantly high when compared to the control group (p<0.01). The meconium and water-soluble meconium subfraction created more contraction response than the lipid-soluble meconium subfraction (p<0.01). The ICR of the meconium group was not different from the ICR of the water-soluble meconium subfraction group (p>0.05). ConclusionWater-soluble meconium subfraction has a profound vasoconstrictor effect on the SMA compared to the lipid-soluble meconium subfraction.

The intestinal damage induced by lipid soluble meconium subfraction is profound compared to the intestinal damage induced by water soluble meconium subfraction

BackgroundIt is unclear which substances in meconium are responsible for intestinal damage in gastroschisis. An experimental study was designed to investigate the effects of the lipid or water soluble subfractions of meconium on the intestines of gastroschisis in a chick model. MethodsMeconium was pooled, homogenated, rota-evaporated dry and diluted. Meconium subfractions were obtained from water soluble and lipid soluble extracts of the meconium. Five days old fertilized chick embryos were used and divided into 5 groups: control, sham, water soluble meconium subfraction, lipid soluble meconium subfraction and whole meconium. All embryos were extirpated on the 18days and the intestines were harvested for histopathological examination. Serosal thickness was measured under light microscopy. ResultsSerosal thickness of the meconium (36.36±2.8μm), the water soluble meconium (14.15±0.93μm) and the lipid soluble meconium (23.88±1.69μm) subfractions groups were significantly increased compared with the control (7.47±0.68μm) and the sham (7.48±0.71μm) groups (p<0.001). Serosal thickness of the lipid soluble meconium subfraction group was significantly increased compared with the water soluble meconium subfraction group (p<0.001). Serosal thickness of the meconium group was significantly increased compared to both the water and the lipid soluble meconium subfraction groups (p<0.001). ConclusionLipid soluble meconium subfraction induces more intestinal damage compared to water soluble meconium subfraction.

Effect of Meconium on the Contractility of the Superior Mesenteric Artery: A Clue to Intestinal Damage in Gastroschisis.

Intestinal damage has been shown to occur when intra-amniotic meconium concentration exceeds threshold level. However, the mechanism of the meconium-induced intestinal damage is still unclear. Intestinal ischemia can cause intestinal damage in gastroschisis. This study was aimed to determine the effects of intra-amniotic meconium on the contractility of superior mesenteric artery (SMA). Eighteen-day-old fertilized chick embryos (Gallus Domesticus) were extirpated and intestines were harvested. The SMA specimens were prepared as 4 mm segments in the organ bath with Krebs-Henseleit buffer. The isometric contraction responses of the SMA specimens were evaluated with norepinephrine, different meconium concentrations, and clear amniotic fluid. Maximum isometric contractions responses (MICR) of the SMA specimens were recorded with an amplifier system on a computer. In the norepinephrine group, MICR was found as 2.92 ± 0.57 mN. While MICR of the 1/100 meconium group (highest meconium concentration) was found as 1.56 ± 0.40 mN, MICR of the clear amniotic fluid group was 0.41 ± 0.07 mN. The MICR of the norepinephrine group was significantly increased compared with the 1/100 meconium and clear amniotic fluid groups. MICR of the 1/100 meconium group was also found to be significantly increased compared with clear amniotic fluid group. No statistically significant difference was found among the meconium subgroups. Intra-amniotic meconium in fetuses with gastroschisis might cause ischemic intestinal damage by reducing the intestinal blood flow. Further studies are needed to show the outcomes of the vasoactive effect of meconium on the SMA blood flow.

To observe the intensity of the inflammatory reaction caused by neonatal urine and meconium on the intestinal wall of rats in order to understand etiology of intestinal damage in gastroschisis

Objectives:The aim of this experimental study was to observe the intensity of the inflammatory reaction caused by neonatal urine and meconium on the intestinal wall of rats to better understand etiology of intestinal damage in gastroschisis.Materials and Methods:A total of 24 adult Wistar rats were used as experimental models to simulate the effect of exposed bowel in cases of gastroschisis. The peritoneal cavity of the rats was injected with substances which constitute human amniotic fluid to study the effect on the bowel. Sterile urine and meconium were obtained from newborn humans. The rats were divided into four groups according to the material to be injected. In Group I (Control group) 3 mL of distilled water was injected, in Group II (Urine group) 3 mL of neonatal urine was injected, in Group III (Meconium group) 5% meconium suspension was injected, while in Group IV, a combination of 5% meconium suspension and urine was injected. A total of 3mL solution was injected into the right inferior quadrant twice a day for 5 days. The animals were sacrificed on the 6th day by a high dose of thiopentone sodium. A segment of small bowel specimen was excised, fixed in paraffin, and stained with hematoxylin-eosin for microscopic analysis for determination of the degree of inflammatory reaction in the intestinal wall. All pathology specimens were studied by the same pathologist.Results:The maximum bowel damage was seen in Group II (Urine group) in the form of serositis, severe enteritis, parietal necrosis, and peeling. A lesser degree of damage was observed in Group III (Meconium group) as mild enteritis (mild lymphoid hyperplasia). The least damage was seen in Group IV (Combination of meconium and urine) and Group I (Control group).Conclusion:The intraabdominal injection of neonatal human urine produces significant inflammatory reactions in the intestinal wall of rats.

Closing Gastroschisis: eine Sonderform der Gastroschisis mit hoher Morbidität und Mortalität

We correlate severe bowel damage in gastroschisis to the rare intrauterine event of narrowing of the abdominal wall around the protruding intestines. We describe this "closing gastroschisis" as a distinct entity. Prenatal ultrasound findings as gastric or bowel dilation were compared to the postnatal findings in order to find markers for an early in utero diagnosis of closing gastroschisis. Early diagnosis could prompt timely delivery to save the compromised bowel and avoid short gut syndrome. We documented the pre- and postnatal course of our patients with gastroschisis from 2007 to 2009. Closing gastroschisis was suspected antenatally and confirmed postnatally. We identified 5 out of 18 patients showing closure of the abdominal wall with varying degrees of bowel damage. Prenatal ultrasound findings were correlated to the postnatally confirmed extent of intestinal damage. We could not find consistent ultrasound markers for prenatal diagnosis of closing gastroschisis. In prenatal ultrasound three patients presented significant gastric dilation and then experienced severe courses postnatally due to segmental gut necrosis. One of these three died and the other two developed short gut syndrome. In one case progressive intraabdominal loop dilation with simultaneous shrinking of the extraabdominal loops occurred corresponding to closing gastroschisis with segmental midgut necrosis. Closing gastroschisis must be seen as a special form of gastroschisis. Extended intestinal damage is often life-threatening. In longitudinal observation dynamics of fetal ultrasound findings can lead to the diagnosis of closing gastroschisis. Progressive intraabdominal loop dilation is always highly suspicious and must lead to close follow-up and timely delivery.

Hydrogel protection: a novel approach to reduce bowel inflammation in experimental gastroschisis

Objective In gastroschisis there is herniation of the fetal bowel into the amniotic cavity that results in severe intestinal dysfunction. In order to reduce bowel exposure to amniotic fluid we used a hydrogel of N-isopropylacrylamide copolymerized with acrylic acid (P(NIPAAm-co-AAc)) to coat the herniated bowel through the use of a fibrin adhesive (Beriplast ®). Study design Gastroschisis was created in fetuses of 31 pregnant Sprague–Dawley rats by evisceration of the bowel through a right paramedian incision in the abdominal wall on day 18.5 of pregnancy. The fetuses were separated in four groups of 12 fetuses: control (C), gastroschisis (G), gastroschisis + fibrin adhesive (GA) and gastroschisis + fibrin adhesive + dry hydrogel (GAH). Animals were harvested at day 21.5 of pregnancy and the hydrogel was removed. Fetuses and bowels were weighed and morphometric analysis was performed. Isoelectric focusing of the amniotic fluid determined its electrical charge. We evaluated the hydrogel swelling ratio ( Q) in the amniotic fluid. Histological analysis and scanning electronic microscopy (SEM) of the bowel and hydrogel were performed. Our primary outcome was bowel intactness after hydrogel removal and our secondary outcome was the effectiveness of the hydrogel in protecting the bowel against amniotic fluid and its components. Differences among the groups were tested by the ANOVA and Tukey–Kramer post-test method and the statistical significance accepted was for p values <0.05. Results The mass of swollen hydrogel was 34 times the mass of dry hydrogel. Isoelectric focusing of the amniotic fluid showed that most of its proteins are negatively charged as the hydrogel. SEM showed that removal of the hydrogel did not damage bowel serosa. Bowel weight, diameter and wall thickness were similar between groups C and GAH but bowel diameter and wall thickness was significantly reduced in C and GAH compared to G and GA ( p < 0.001). Conclusion The P(NIPAAm-co-AAc) hydrogel does not harm the bowel and provides a safe effective protection with reduction of bowel damage in gastroschisis.

Evaluation of diluted amniotic fluid effects on histological changes of intestine of rabbit fetus with gastroschisis

Amniotic fluid exchange is a method for prevention of intestinal damage in gastroschisis, but its techniques are different in studies. We investigated the effects of amnioinfusion exchange on histological changes of intestine and feasibility and safety of amniotic fluid exchange through central vein catheter (CVC) placed in pregnant rabbit uterus. A total of 15 pregnant New Zealand white rabbits were selected. Fetuses were randomly divided into three groups (case, control, sham). On gestational day 25, under general anesthesia with midline laparotomy, the graved bicornuate uterus was exposed. In controls, fetus abdomen was opened by a transverse incision in right lower quadrant region and intestines were eviscerated. In cases, after intestine evisceration, a central venous catheter was passed from mother skin and uterus and fixed to uterus wall. In shams, fetus was delivered on gestational day 32 and its abdomen was opened. In case group, after operation, 1-2 cc of warm saline solution was replaced through catheter every 6 h. On gestational day 32, fetuses of case and control groups were delivered. Mucosal and serosal thickness, muscle thickness, fibrin deposition, serosal collagen and ganglia were compared. Ten fetuses as shams, 7 fetuses as controls and 7 fetuses as case group were studied. Serosal thickness was 4.5 +/- 3.6 microm in shams, 64.2 +/- 28.7 microm in controls and 6 +/- 4.1 microm in cases. Serosal thickness in control group was higher than sham (P < 0.001) and case (P < 0.002) groups. In case group, infiltration of inflammatory cells with mild edema without fibroblast infiltration was seen. Application of the CVC technique was found to be a simple procedure that effectively decreased serosal inflammatory response of intestine in 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.

Urinary trypsin inhibitor present in fetal urine prevents intraamniotic meconium–induced intestinal damage in gastroschisis

Background/Purpose Contact with amniotic fluid causes intestinal damage in gastroschisis, and intraamniotic meconium has been shown to be responsible. Meconium has been shown to contain a significant amount of IL-8, which may be the responsible cytokine for harmful effects of meconium. Neonatal urine contains high amount of urinary trypsin inhibitor (UTI) compared with adult human urine. Urinary trypsin inhibitor has been shown to exert inhibitory effects on IL-8. Therefore, far from being destructive, presence of fetal urine in the amniotic fluid might be beneficial because human urine contains UTI. An experimental study has been performed to investigate whether presence of intraamniotic human urine (consequently UTI) besides meconium is beneficial on intestines of chick embryo with gastroschisis. Methods Five-day-old fertilized chick eggs were used. Gastroschisis was created through amniotic cavity without opening the allantoic cavity. Sterile urine and meconium were obtained from newborn humans. Study was conducted in 2 stages. In the first stage, gastroschisis was created, and meconium suspensions at minimal harmful meconium concentration were prepared using natural and denatured human neonatal urine and instilled into the amniotic cavity. In the second stage of study, various concentrations of UTI plus meconium suspension at minimal harmful meconium concentration was instilled into the amniotic cavity. Results Serosal thickening, inflammation, and focal fibrin deposits were observed in intestines of the groups with meconium and meconium in denatured urine. Histopathologic features of intestines of the group with meconium in natural urine did not differ from the intestines of the control group. Histopathologic examination of intestines of groups with meconium and meconium plus 50 U/mL UTI showed serosal thickening, inflammation, focal fibrin, and collagen deposits. Histopathologic features of intestines of the groups with 1:400 intraamniotic meconium plus 100 and 200 U/mL UTI did not differ from the intestines of control group. Conclusion Urinary trypsin inhibitor 100 U/mL prevented the intestinal damage via inhibiting IL-8, which is contained by 1:400 concentration of meconium. Therefore, besides the existence of threshold level of meconium, the existence of UTI, which is capable of inhibiting IL-8 contained by threshold level of meconium, may be a factor in the occurrence of intestinal damage in gastroschisis.

Effects of amnio-allantoic fluid exchange on bowel contractility in chick embryos with gastroschisis

Background/Purpose: Intestinal damage in patients with gastroschisis is characterized by bowel wall thickening, intestinal dilatation, mesenteric shortening, and a fibrous peel. The prevention of intestinal damage in gastroschisis by amnio-allantoic fluid (AAF) exchange has been reported using histologic and macroscopic evaluation of intestines, but the effects of this treatment on bowel contractility have not been investigated. The current study was performed to determine the effect of AAF exchange on the intestinal contractility in chick embryos with gastroschisis. Methods: Thirteen-day-old fertilized chick eggs were used. Gastroschisis was created through amnio-allantoic cavity. There were 3 study groups: control group, gastroschisis-only group, and gastroschisis-plus-exchange group. The bowels were evaluated by an in vitro muscle strip technique, and the response was expressed as a percentage of the maximum acetylcholine evoked contraction (Emax) in each tissue obtained. Additionally, parasympathetic ganglion cells per 10 plexus at the intestinal wall were counted. Differences between groups were analyzed by analysis of variance (ANOVA) followed by Tukey-Kramer. Probabilities of less than 5% were considered significant. Results: The intestines were thickened and covered by fibrous peel in the gastroschisis-only group when compared with the control group and the gastroschisis exchange group morphologically. There was a statistically significant decrease in contractility in the gastroschisis-only group compared with the control group (P <.05). It exerted 42.03 ± 46.73% contraction of control group's Emax. This decrease in contractility was significantly reversed in the exchange group (P <.05; Emax value of gastroschisis plus exchange group was 71.45 ± 23.54% of control group's Emax). Although the number of ganglia per 10 plexus was 76.7 ± 4.3 in the control group, it was measured 28% less in the gastroschisis-only group (P <.05). There was no significant difference between the ganglion numbers of control and exchange groups. Conclusions: Prenatal AAF exchange treatment prevents decreased bowel contractility in gastroschisis. Gastroschisis does not affect intestinal ganglia morphology, but the number of ganglion cells decreases. AAF exchange prevents these functional and morphologic adverse effects of disease. By these findings the expectancy of a better clinical result in gastroschisis with intrauterine pretreatment by amniotic fluid exchange increases. J Pediatr Surg 37:1589-1593. Copyright 2002, Elsevier Science (USA). All rights reserved.

Induction of fetal diuresis with intraamniotic furosemide increases the clearance of intraamniotic substances: An alternative therapy aimed at reducing intraamniotic meconium concentration

Background/Purpose: Contact with amniotic fluid (AF) causes intestinal damage in gastroschisis. Intraamniotic meconium has been shown to be responsible for intestinal damage, and occurrence of this damage has been shown to depend on the concentration of intraamniotic meconium. When intraamniotic meconium concentration is lowered below threshold level by exchanging AF with saline in gastroschisis, intestinal damage can be prevented. Theoretically, induction of fetal diuresis with intraamniotic furosemide may increase AF volume and fetal swallowing rate, thus, increase absorption of AF by intestines; therefore, the clearance of meconium from the AF may increase. An experimental study was planned to investigate the effects of intraamniotic diuretic injection on the clearance of intraamniotic substances. Methods: Pregnant rabbits on the 23rd to 25th gestational day were divided into 2 groups as furosemide and control. Technetium tc99m labeled “tin colloid” was injected into the amniotic cavity, and AF sample was taken 10 minutes later. Furosemide was injected into the amniotic cavity afterwards. Two and 6 hours later, AF samples were obtained. Intestines were harvested at the end of the study. Control group received intraamniotic saline instead of furosemide. Radioactivities of the AF samples and intestines were determined by gamma counter. Clearance of the radioisotope from AF and intestinal accumulation were calculated. Results: The clearance of the radioisotope from AF was increased significantly in the furosemide group (n = 10) compared with the control group (n = 8; P <.01). Gastrointestinal accumulation of the radioisotope in the furosemide group was 4-fold higher than that the control group (P <.01). Conclusions: Induction of fetal diuresis with intraamniotic furosemide accelerates the clearance of intraamniotic substances. This is probably caused by increased urinary output rate, which increases AF volume and consequently results in increased fetal swallowing of AF. In the diseases like gastroschisis and myelomeningocele, in which the contact with AF causes tissue damage, the elimination of meconium from AF in a somewhat natural manner like this method, should be studied further because it may be an alternative minimal invasive in utero treatment modality. J Pediatr Surg 37:1337-1342. Copyright 2002, Elsevier Science (USA). All rights reserved.

Meconium dependence of bowel damage in gastroschisis

Background/Purpose: Increasing evidence of physiologic in utero defecation supports the hypothesis that bowel damage in gastroschisis may be meconium dependent. In this study, the author investigated the role of meconium on parameters of bowel damage in a fetal rat model of gastroschisis. Methods: Pregnant rats underwent laparotomy at 18 1/2 days gestational age (GA). There were 4 experimental groups of 11 fetuses each; the GM group consisted of fetuses with isolated gastroschisis and was considered to have moderate meconium contamination of the amniotic fluid (MCAF); the GL group consisted of fetuses with gastroschisis and anal ligation, performed to prevent MCAF; the GH group consisted of fetuses with gastroschisis and colon perforation, performed to increase MCAF; and the Sham group consisted of sham operated controls. All fetuses were harvested by cesarean section at 21 1/2 days GA, and the fetal intestine was assessed for peel, intestinal length, intestinal weight per unit length, and histologic appearance. Results: The authors achieved the following fetal survival rates: GM group, 91% (10 of 11); GL group, 78% (7 of 9, the ligation was not successful in 2 fetuses); GH group, 82% (9 of 11). Sham group, 100% (11 of 11). Intestinal length was decreased in fetuses with gastroschisis, and this reduction was related directly to the grade of MCAF (Sham, 18.4 ± 0.6; GL, 11.5 ± 0.5; GM, 10.2 ± 0.6; GH, 9.1 ± 0.6 cm; P <.01). In contrast, intestinal weight per unit length increased in fetuses with gastroschisis, and this increase was related directly to the grade of MCAF (Sham, 7.8 ± 0.5; GL, 9.4 ± 0.5; GM, 11.3 ± 0.5; GH, 16.9 ± 0.7 mg/cm; P <.01). In comparison with the GM group, the degree of peel coverage and bowel adherence were increased markedly in the GH group, whereas the fetuses of the GL group had neither peel nor bowel adherence. Conclusions: All bowel damage parameters were affected by MCAF supporting the hypothesis that bowel damage in gastroschisis is at least partially dependent on meconium exposure. Further research is required to clarify other factors that contribute to bowel damage and to identify risk factors that may allow prenatal identification of severely affected fetuses. J Pediatr Surg 37:31-35. Copyright © 2002 by W.B. Saunders Company.

Intestinal damage in gastroschisis correlates with the concentration of intraamniotic meconium

Background/Purpose: Contact with amniotic fluid (AF) causes intestinal damage in gastroschisis, which has been shown to be caused by intraamniotic meconium. However, whether this intraamniotic meconium–induced intestinal damage is concentration dependent has not been investigated previously. The purpose of this study is to investigate the effects of intraamniotic human meconium at various concentrations on the intestines of chick embryo with gastroschisis. Methods: Five-day-old fertilized chick eggs were used. Gastroschisis was created through the amniotic cavity without opening the allantoic cavity. Sterile meconium was obtained from newborn humans. Meconium suspensions at various concentrations were prepared using saline and instilled into the amniotic cavity. Results: Intraamniotic 1:200 and 1:400 meconium was found to cause intestinal damage. Meconium concentrations lower than 1:400 did not cause intestinal damage. Histopathologic examination of the intestines of the 1:200 and 1:400 meconium groups showed serosal thickening, inflammation, focal fibrin, and collagen deposits. Histopathologic features of the intestines of the 1:600 and 1:800 meconium groups did not differ from the intestines of the control group. Conclusion: Intraamniotic meconium, which is responsible for intestinal damage in gastroschisis, must reach a threshold level to induce intestinal damage. J Pediatr Surg 36:1811-1815. Copyright © 2001 by W.B. Saunders Company.

Intestinal damage in gastroschisis is independent of the size of the abdominal defect

The intestinal damage in gastroschisis (GS) has been attributed to a narrow abdominal wall defect (AWD), among other causes, but this causal effect is difficult to prove in humans. The present experimental study was done to ascertain the damaging effect of clinically extrapolable mild and moderate constriction at the AWD on the intestine of fetuses with GS. AWDs of two different sizes were carried out in the fetal rabbit model: small-ring GS (1.5x bowel diameter, SRG) and large-ring GS (3x bowel diameter, LRG); a group of unoperated littermates served as controls. Fetal body weight, intestinal length and weight, bowel diameter and wall thickness, and histology were checked 7 days later. No statistical difference was found in body weight and bowel diameter among the groups. Intestinal length, weight, and wall thickness were significantly different in the GS groups compared to the controls, but no difference was found between the GS groups. Histology did not show venous stasis, ischemic lesions, or differences in the degree of edema between groups SRG and LRG. Mesothelial hyperplasia was seen in both GS groups. The intestinal changes in length, weight, diameter, wall thickness, and histology in GS should thus not be attributed to the diameter of the AWD.

Nitric oxide synthase inhibition prevents intestinal damage in gastroschisis: A morphological evaluation in chick embryos

Purpose : Increased small bowel nitric oxide (NO) synthase activity accused for postnatal intestinal dysmotility in gastroschisis. The purpose of this study is to evaluate the effect of prenatal NO synthase inhibition on intestinal damage in gastroschisis. Methods : Sixteen-day-old fertilized chick eggs were divided into 4 groups. In the control group, the allantoic and amniotic membranes were opened to create a common cavity. In the gastroschisis group, a defect in the abdominal wall was made, and intestinal loops were exteriorized. In the gastroschisis pretreated with l-NAME group, gastroschisis was created, and l-NAME was administered into the amnioallantoic cavity for 4 days. In the gastroschisis sham pretreated group, after the same surgical procedure as the previous group, same amount of saline was given beside l-NAME. At the end of 20th day of incubation, intestinal morphological changes were investigated macroscopically and microscopically. Results : Macroscopic changes such as shortening, thickening, and fibrous adhesions were found in the exteriorized bowels of the just gastroschisis group and the gastroschisis pretreated saline group. However, there was only mild thickening in the gastroschisis pretreated with l-NAME group. Microscopically, compared with the gastroschisis group, serosal thickness, muscular thickness, and bowel wall thickness were found to be significantly lower in the gastroschisis pretreated with l-NAME group (128.0 ± 19.3 μm and 239.5 ± 3.0 μm v 57.0 ± 8.2 μm and 145.0 ± 9.7 μm). Conclusion : It is possible to decrease intrauterine intestinal morphological changes in gastroschisis by inhibiting NO synthase.

Amnio-allantoic fluid exchange for the prevention of intestinal damage in gastroschisis. III: Determination of the waste products removed by exchange.

Experimental amnio-allantoic fluid (AAF) exchange has been shown to prevent intestinal damage in the chicken embryo gastroschisis model. AAF contains both urinary and gastrointestinal waste products (UWP and GIWP). An experimental study was performed to find the waste products responsible for this intestinal damage. Gastroschisis was created in 20 chick embryos. Half were treated with AAF exchange, the other half were not treated. AAF samples were obtained for biochemical determination of urea nitrogen and creatinine as UWP, bile acids and bilirubin as GIWP at the end of the incubation. Intestines were evaluated by light microscopy. While GIWP (Bile salts and bilirubin) were significantly removed from AAF by exchange, the levels of UWP (urea nitrogen and creatinine) were unaffected. Intestinal wall thickness was less in the exchange group compared to the untreated group. The unchanged levels of UWP after AAF exchange may be attributed to their relatively rapid production compared to GIWP. Dilution of GIWPs by AAF exchange results in prevention of the intestinal damage in gastroschisis.

Amnio-allantoic fluid exchange for prevention of intestinal damage in gastroschisis II: Effects of exchange performed by using two different solutions.

The prevention of intestinal damage in gastroschisis was reported after amnio-allantoic fluid (AAF) exchange using serum saline. However it is not clear why AAF exchange prevents intestinal damage. Are some harmful chemicals withdrawn from AAF by exchange or sodium content of AAF is merely increased? A study was planned to find the end results of AAF exchange performed by using two different solutions in the chicken embryo gastroschisis model. After creation of gastroschisis, three groups were studied. In the first group AAF exchange was not performed. In the second group AAF exchange was performed using 0.075% NaCl solution (physiologic saline for chicken). In the third group AAF exchange was performed using 0.054% NaCl plus 1% dextrose solution. Exchange with two different solutions prevented cellular infiltration and fibrous peel formation in intestines which are observed in the non-treatment group. In the third group, intestinal edema was an additional pathologic finding. This study shows that in gastroschisis, the intestines outside the abdominal cavity are very sensitive to the quality of the fluid in which they are bathed. The intestinal damage resembling that encountered in human gastroschisis can be prevented by removing the harmful chemicals from AAF by exchange.

Amnio-Allantoic fluid exchange for the prevention of intestinal damage in gastroschisis: An experimental study on chick embryos

In gastroschisis, the protruding intestine is usually shortened, thickened, and covered with a fibrous peel. Urine components, which are increased in the amniotic fluid with the onset of renal function, are responsible for these changes. In the chick embryo model of gastroschisis, the authors performed amnio-allantoic fluid exchange to reduce the effect of urinary products. There were three study groups: control, gastroschisis only, and gastroschisis plus exchange. There was a significant decrease in creatinine ( P < .05) and a slight decrease in urea concentrations in the gastroschisisplus-exchange group compared with the gastroschisis-only group. Whereas macroscopic and microscopic studies showed severe fibrosis and bowel-wall thickening in the latter group, the bowel was normal or slightly oedematous in the former. On the basis of this study, the authors suggest that antenatal amniotic fluid exchange might reduce the bowel damage in human foetuses.

Etiology of intestinal damage in gastroschisis III: Morphometric analysis of the smooth muscle and submucosa

The response of intestinal smooth muscle to injury may explain some of the motility derangement observed in infants with gastroschisis. An experimental model of gastroschisis was created and a detailed analysis of the intestinal muscle layer was undertaken to study this response. An abdominal wall defect and evisceration of the bowel were carried out in fetal lambs at 80 days' gestation (full term, 145 days), with delivery at 100 days or 135 days. Smooth muscle cell size and number were determined by detailed morphometric analysis, proliferative rate was determined using proliferating cell nuclear antigen staining, and collagen content was determined by morphometry after verhoeff van Gieson staining. Compared with controls, there was a significant increase in cell number (hyperplasia) in the gastroschisis animals at 100 days and an increase in size (hypertrophy) at 135 days. The proliferation rate of smooth muscle was significantly lower and the submucosal collagen thickness was significantly greater in the gastroschisis animals during both periods. These data suggest that gastroschisis is characterised by initial hyperplasia, with subsequent diminution in smooth muscle proliferation. The hypertrophy may reflect a response to injury in which cell growth instead of proliferation occurs. The persistent elevation in collagen throughout gestation in animals with gastroschisis may be a reflection of this hyperplastic response in the smooth muscle cells and an important factor in the bowel-wall thickening. This deranged pattern of growth may lead to the clinical problems observed in human infants with this disease.