Matthew S. Clifton

Urocortin 2 Expression in the Rat Gastrointestinal Tract Under Basal Conditions and in Chemical Colitis

It is becoming increasingly evident that the urocortins (Ucns) and their receptors are involved in the initiation and development of inflammation in the gastrointestinal (GI) tract. There has not been a systematic study of the basal expression of Ucns or their receptors in the GI tract. Here, we examined basal expression of Ucn 2 and its high-affinity receptor, CRF-R2 in the rat GI tract. Ucn 2 mRNA was expressed throughout the small and large intestine. Surprisingly, CRF-R2 mRNA expression was detected in only a subset of GI regions that expressed Ucn 2. Immunohistochemical study showed that both Ucn 2 immuno-reactivity (Ucn 2-IR) and CRF-R2-IR were consistently seen in the neurons of the myenteric plexus and the nerve fibers innervating the circular muscle. By and large, Ucn 2-IR was detected in all layers, including the mucosal and the submucosal layers throughout the GI regions. In contrast, CRF-R2-IR was very low or undetectable in the mucosal layers of all regions examined. The role of Ucn 2 and CRF-R2 was then examined in a rat model of chemically-induced colitis. In the early phase of colitis, Ucn 2 mRNA levels peaked, whereas, in striking contrast, CRF-R2 mRNA expression decreased approximately 2.5-fold below control levels. At the peptide level, Ucn 2-IR was specifically induced in a large population of immune cells that infiltrated the lamina propria and submucosa of the distal colon, whereas CRFR2-IR was detected in only a small fraction of infiltrated immune cells. CRF-R2-IR was dramatically reduced in the neurons of the myenteric plexus. Thus, we show, for the first time, that in the acute phase of inflammation, Ucn 2 levels are increased whereas expression levels of its only identified receptor, CRF-R2, are decreased. This suggests that Ucn 2 exerts its effects only in part via CRF-R2.

Fetoscopic Transuterine Release of Posterior Urethral Valves: A New Technique

Fetal urinary tract obstruction with oligohydramnios produces pulmonary hypoplasia and renal dysplasia. Decompression of the obstructed urinary tract may restore amniotic fluid and allow lung growth, but transabdominal catheter shunt decompression is often inadequate and does not allow for cycling of the bladder, while open procedures cause significant maternal morbidity. Disruption of the anatomic obstruction, usually posterior urethral valves in a male fetus, would be ideal but has proven technically difficult. Here we describe a new technique of percutaneous fetal cystoscopy and disruption of posterior urethral valves, and the case report of our first application of this technique. We pre-sent a case of a 17-week male fetus with posterior urethral valves which underwent fetal cystoscopy for mechanical disruption of posterior urethral valves. This minimally invasive approach to disruption of posterior urethral valves in a fetus is a novel method for decompressing the urinary tract. The technique offers a minimal degree of maternal morbidity and, if instituted early enough, can restore amniotic fluid volume, avert fatal pulmonary hypoplasia and may preserve renal function.

Use of tissue expanders in the repair of complex abdominal wall defects

BACKGROUND/PURPOSE Closure of abdominal wall defects in children poses a challenge for pediatric surgeons. We describe a technique using tissue expanders placed either intraperitoneally or in the abdominal wall to aid in the reconstruction of a variety of complex abdominal wall defects. METHODS The tissue expanders are inserted under general anesthesia. Initial expansion is done in the operating room with attention to peak airway pressure, urine output, and end-tidal carbon dioxide. The expanders are inflated in the outpatient setting via percutaneous access until the calculated inflation volume is achieved. They are then removed; and definitive closure is accomplished using a combination of native tissue flaps, abdominal component separation techniques, biomaterials, and synthetic material. RESULTS Six children underwent tissue expansion for treatment of abdominal wall defects (omphalocele, n = 3), trauma (n = 1), and thoracopagus twins (n = 1 pair). One to 4 expanders were used per patient, with all having a successful reconstruction of their abdominal walls. Two to 3 operations were required to restore abdominal domain and consisted of expander insertion, removal with reconstruction, and possible revision of the reconstruction. CONCLUSIONS Tissue expanders possess a broad range of applications for abdominal wall reconstruction and can be used in patients of all ages.

Urocortin 1 modulates immunosignaling in a rat model of colitis via corticotropin-releasing factor receptor 2.

Urocortins (UCNs) and their receptors are potent immunoregulators in the gastrointestinal (GI) tract, where they can exert both pro- and anti-inflammatory effects. We examined the contribution of Ucn1 and its receptors to the pathogenesis, progression, and resolution of colitis. Trinitrobenzene sulfonic acid was used to induce colitis in rats. Ucn1 mRNA and immunoreactivity (IR) were ubiquitously expressed throughout the GI tract under basal conditions. During colitis, Ucn1 mRNA levels fell below basal levels on day 1 then increased again by day 6, in association with an increase in the number of Ucn1-IR inflammatory cells. Ucn1-IR cells were also numerous in proliferating granulation tissue. In contrast to Ucn1 expression, average phosphorylated ERK1/2 (pERK1/2) expression rose above controls levels on day 1 and was very low on day 6 of colitis. Knockdown of corticotropin-releasing factor 2 (CRF(2)) but not CRF(1) by RNA interference during colitis significantly decreased the macroscopic lateral spread of ulceration compared with uninjected controls or animals with CRF(1) knockdown. After knockdown of CRF(2), but not of CRF(1) during colitis, edema resolution assessed microscopically was slowed, and myeloperoxidase activity remained elevated even at day 6. Ucn1 and TNF-α mRNA peaked earlier, whereas pERK1/2 activation was attenuated after CRF(2) knockdown. Thus we conclude that local CRF(2) and pERK1/2 activation is pivotal for macroscopic spread of colitis and resolution of edema. Elimination of CRF(2), but not CRF(1), results in uncoordinated immune and pERK1/2 signaling responses.

Hereditary multiple intestinal atresias: 2 new cases and review of the literature

Intestinal atresias are a common cause of newborn bowel obstruction (Dalla Vecchia LK, Grosfeld JL, West KW, et al, Intestinal atresia and stenosis: a 25-year experience with 277 cases. Arch Surg 1998; 133[5]:490-496). Hereditary multiple intestinal atresias, first reported by Guttman et al in 1973, is the rarest form of multiple atresias (Guttman FM, Braun P, Garance PH, et al, Multiple atresias and a new syndrome of hereditary multiple atresias involving the gastrointestinal tract from stomach to rectum. J Pediatr Surg 1973;8:633-640; Bass J, Pyloric atresia associated with multiple intestinal atresias and immune deficiency. J Pediatr Surg 2002;37:941-942.). It has been proposed to be autosomal recessive, to involve atresias in a variable combination of sites from stomach to rectum, and to be universally fatal (Bilodeau A, Prasil P, Cloutier R, et al, Hereditary multiple intestinal atresia: thirty years later. J Pediatr Surg 2004;39:726-730; Moreno LA, Gottrand F, Turck D, et al, Severe combined immunodeficiency syndrome associated with autosomal recessive familial multiple gastrointestinal atresias: study of a family. Am J Med Genet 1990;37:143-146). Patients have significant intestinal dysfunction and unrelenting sepsis stemming from a poorly defined, severe immunologic defect. Our case report presents 2 full siblings to nonconsanguineous parents with pyloric atresia, multiple small bowel and colonic atresias, and severe immune dysfunction. Care was withdrawn within 3 months of life on both siblings after multiple bouts of sepsis. Data suggest that the immune defect may not be primary, but in fact be secondary to intestinal dysfunction. Although the subjects in this article ultimately had fatal outcomes, a comprehensive immunologic/physiologic picture is presented in hopes of furthering the understanding of this grave disease.

Prognostic role of tumor-head volume ratio in fetal sacrococcygeal teratoma

Objective: To evaluate the ability of a tumor-head volume ratio to predict outcome and incidence of hydrops in fetuses with sacrococcygeal teratoma. Methods: Seventy-one sonograms were reviewed retrospectively from 28 fetuses with sacrococcygeal teratoma managed in our institution. Head volume (HV) and total tumor volume were calculated from sonograms. Amount of cystic tumor was estimated to determine solid tumor volume (STV) for the STV/HV ratio. Results: Twenty percent of sonograms with STV/HV <1 and 97.3% with STV/HV >1 were associated with 1 or more abnormal sonographic signs (p = 0.000). Overall mortality was 11/27 (41%). There was no mortality in fetuses with a ratio of <1, while 11/18 (61%) of fetuses with ratio >1 died (p = 0.003). Conclusion: The STV/HV ratio may be used to identify fetuses with a high risk of a poor outcome due to high-output cardiac failure and hydrops, and may help guide management.

Prenatal Tracheal Obstruction Due to Double Aortic Arch: A Potential Mimic of Congenital High Airway Obstruction Syndrome

WEB This is a Web exclusive article. ouble aortic arch is a relatively common congenital anomaly of the aortic arch system resulting from failed regression of the fourth pharyngeal arch arteries. Symptoms develop postnatally due to compression of the trachea and esophagus, which are encircled by the left and right aortic arches. The classic history is noisy breathing during the first few weeks of life, and the diagnosis is usually confirmed by postnatal echocardiography or MRI. Prenatal diagnosis is rare [1, 2], and double aortic arch has not been previously described as a cause of prenatal tracheal obstruction, to our knowledge. Congenital high airway obstruction syndrome (CHAOS) is a recognized cause of prenatal central airway obstruction due to intrinsic atresia or stenosis of the larynx or upper trachea. CHAOS causes pulmonary overdistention due to retained bronchial secretions. Increased intrathoracic pressure with impaired venous return is believed to account for the associated development of fetal hydrops. The resulting constellation of large echogenic lungs with flattening or inversion of the diaphragm, dilated fluid-filled airways below the level of obstruction, and fetal hydrops or ascites is considered characteristic of CHAOS on prenatal sonography. Untreated CHAOS inevitably leads to fetal demise or stillbirth [3–5]. We present a case of double aortic arch that caused prenatal central airway obstruction and that mimicked CHAOS on fetal echocardiography and MRI.

Prenatal Diagnosis of Familial Type I Choledochal Cyst

Familial choledochal cysts are extremely rare. High-resolution ultrasound now allows for the antenatal diagnosis of these anomalies. After delivery, elective surgical resection should be planned; however, increases in size, deterioration of liver function, and ascending cholangitis frequently force early intervention. We report an unusual occurrence of siblings with type I choledochal cysts and review the existing literature on cause, genetics, classification, diagnosis, and management of this disease.

1H HR‐MAS spectroscopy for quantitative measurement of choline concentration in amniotic fluid as a marker of fetal lung maturity: Inter‐ and intraobserver reproducibility study

To determine the intra‐ and interobserver reproducibility of human amniotic fluid metabolite concentration measurements (including potential markers of fetal lung maturity) detectable by MR spectroscopy.

Proteus Syndrome: Three Case Reports with a Review of the Literature

Proteus syndrome (PS) is a rare, progressive disorder that manifests as asymmetric, disproportionate overgrowth affecting tissues derived from any germline layer. Cases of PS from 2005–2010 were retrieved from the pathology files at our institution. Two confirmed cases and one possible case of PS were identified. All patients came from different ethnic backgrounds. Patient 1 displayed classic skin and overgrowth lesions. Patient 2 displayed various features, particularly vascular malformations. Patient 3 demonstrated a cerebriform connective tissue nevus alone. These patients demonstrate the spectrum of presentations of PS. Much is left to learn about this disfiguring disease.