Heterotopic gastric mucosa in the cystic duct.

Heterotopic gastric mucosa in the gallbladder is rare (with about 100 reported cases), and its occurrence is even rarer in the biliary ductal system.The authors report a pediatric case of heterotopic gastric mucosa in the cystic duct associated with cholelitiasis.

3-Indolyl sultams as selective CRTh2 antagonists.

CRTh2 (DP(2)) is a prostaglandin D(2) receptor implicated in the recruitment of eosinophils and basophils within the asthmatic lung. Here we report the discovery of a novel series of 3-indolyl sultam antagonists with low nM affinity for CRTh2. These compounds proved to be selective over the other primary prostaglandin D(2) receptor (DP1) as well as the thromboxane A(2) receptor (TP).

Reversal of severe parenteral nutrition-associated liver disease in an infant with short bowel syndrome using parenteral fish oil (Omega-3 fatty acids).

Total parenteral nutrition is an important adjunct in the care of neonates with surgical disorders. Cholestasis is at present the most worrisome complication of this technique; it is difficult to treat and may progress to eventual cirrhosis and liver failure. This article reviews the pertinent clinical and nutritional data in a surgical patient with short bowel syndrome who developed parenteral nutrition-associated liver disease successfully treated with fish-oil based lipids.

Splenic cyst in a wandering spleen: laparoscopic treatment with preservation of splenic function.

BACKGROUND: Wandering spleen and splenic cyst are rare benign congenital conditions that can both cause severe complications related to torsion or trauma. CASE REPORT: A 14-year-old girl presented a mobile 10-cm-long abdominal mass in the left lower quadrant associated with mild abdominal pain. The diagnosis of an 8-cm-long nonparasitic cyst in a wandering spleen was confirmed by computerized tomography and negative serum indirect hemagglutination titer for hydatid disease. Laparoscopic unroofing of the cyst and splenopexy in a vycril mesh was performed. RESULTS: No problems were encountered during laparoscopic surgery. Postoperative course was uneventful, and at a 1-year follow-up, the spleen is viable and maintains a normal position in the phrenorenal angle. CONCLUSIONS: In the child, treatment of wandering spleen associated with a cyst should aim at the prevention of vascular accidents and at conservation of the spleen. We achieved these goals with unroofing and splenopexy through laparoscopic surgery.

Diversion of the fecal stream resolves ulcerative colitis complicating chronic granulomatous disease in an adult patient.

Chronic granulomatous disease (CGD) is a primary phagocytic disorder characterized by greatly increased susceptibility to severe bacterial and fungal infections. Patients with CGD may have gastrointestinal manifestations, commonly colitis, usually mimicking Crohn disease. We report an adult case, the second in literature, of CGD with severe colitis displaying histologic features of ulcerative colitis. The patient had a prompt improvement (continuing up to more than 5 y of follow-up) of the clinical picture after ileostomy and fecal diversion.

Colonic stricture mimicking Hirschsprung's disease: a localized cytomegalovirus infection.

The diagnosis of congenital cytomegalovirus (CMV) infection is best established by isolating the virus from urine or saliva within the first 2 weeks of life. Detection beyond this point may reflect perinatal acquisition of CMV. Cytomegalovirus is usually transmitted by direct human-to-human contact through vertical or horizontal routes. Infected persons can excrete CMV in urine, saliva, semen, cervical secretions, or breast milk. Because the virus establishes latent infections, blood products and solid organs can also transmit CMV. In the surgical literature, intestinal CMV-infected cells in infants have prevalently been associated with neonatal necrotizing enterocolitis, and only very few cases of primary CMV infection of the gastrointestinal tract of surgical interest in immunocompetent neonates have been reported. We describe a neonate with congenital or perinatal CMV infection with gastrointestinal involvement who developed a colonic stricture and manifested a clinical picture simulating Hirschsprung's disease. The intestinal lesion was a localized segmental CMV infection of the colon in which inflammation dominated the histopathologic finding. Chorioretinitis was also present.

Identification of a novel extracellular cation-sensing G-protein-coupled receptor.

The C family G-protein-coupled receptors contain members that sense amino acid and extracellular cations, of which calcium-sensing receptor (CASR) is the prototypic extracellular calcium-sensing receptor. Some cells, such as osteoblasts in bone, retain responsiveness to extracellular calcium in CASR-deficient mice, consistent with the existence of another calcium-sensing receptor. We examined the calcium-sensing properties of GPRC6A, a newly identified member of this family. Alignment of GPRC6A with CASR revealed conservation of both calcium and calcimimetic binding sites. In addition, calcium, magnesium, strontium, aluminum, gadolinium, and the calcimimetic NPS 568 resulted in a dose-dependent stimulation of GPRC6A overexpressed in human embryonic kidney cells 293 cells. Also, osteocalcin, a calcium-binding protein highly expressed in bone, dose-dependently stimulated GPRC6A activity in the presence of calcium but inhibited the calcium-dependent activation of CASR. Coexpression of beta-arrestins 1 and 2, regulators of G-protein signaling RGS2 or RGS4, the RhoA inhibitor C3 toxin, the dominant negative Galpha(q)-(305-359) minigene, and pretreatment with pertussis toxin inhibited activation of GPRC6A by extracellular cations. Reverse transcription-PCR analyses showed that mouse GPRC6A is widely expressed in mouse tissues, including bone, calvaria, and the osteoblastic cell line MC3T3-E1. These data suggest that in addition to sensing amino acids, GPRC6A is a cation-, calcimimetic-, and osteocalcin-sensing receptor and a candidate for mediating extracellular calcium-sensing responses in osteoblasts and possibly other tissues.

Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists.

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.

Further evidence on totally transanal one-stage pull-through procedure for Hirschsprung's disease.

BACKGROUND/PURPOSE: Fifteen consecutive children aged 20 days to 12 years with biopsy-proven Hirschsprung's Disease (HD) underwent a transanal pull-through procedure over a 17-month period. These patients have been divided into 2 groups. The first was a series of 9 patients, which helped us gain familiarity and confidence with technical and postoperative gestational problems, and the second series was of 6 patients, which fully corroborates and adds further evidence on the minimally invasive nature of the technique. Mucosectomy of aganglionic bowel, access to the peritoneal cavity, division of rectosigmoid mesenteric vessels, pull-through of normoganglionic colon, colectomy, and coloanal anastomosis all were performed transanally. Patients underwent a program of progressive anal dilatations and were assessed for postoperative clinical course, continence, constipation, diarrhea, postoperative enterocolitis, perianal excoriations, and anal stricture. RESULTS: Mucosectomy was done under direct vision. Operating time ranged from 150 to 350 minutes. The average length of bowel resected was 13.5 cm with a range of 8 cm to 25 cm. There were neither intraoperative nor significant postoperative complications. All but 2 patients accepted full oral feedings on postoperative day 2. Mean hospital stay in the first series of 9 patients was 7 days, range, 5 to 12 days; that of the second series of 6 patients was 5 days, range, 4 to 8 days. All children currently experience 1 to 6 bowel movements per day at a follow-up period of 1 to 17 months. CONCLUSIONS: A one-stage pull-through procedure for HD can be performed successfully with a completely transanal approach. This technique is associated with excellent early clinical results. Many more cases and a longer follow-up period will be required to compare long-term results with other one-stage procedures for definitive treatment of HD.

Interaction of GABA receptor/channel rho(1) and gamma(2) subunit.

PURPOSE: To determine whether protein-protein and functional interactions can occur between gamma-aminobutyric acid (GABA)(A) receptor/channels gamma(2) subunit and the retina-specific GABA(C) rho(1) subunit. METHODS: Protein-protein interaction was characterized by immunocoprecipitation of these subunits in brain and spinal cord with anti-gamma(2) subunit antibody and by Western blot analysis with anti-rho(1) subunit antibody. The rho(1) and gamma(2) subunits were detected in the adult rat brain and spinal cord lysates that had been previously precipitated with the specific antibodies against the rho(1) and gamma(2) subunits, respectively. A two-microelectrode voltage clamp was used to measure GABA-induced currents in oocytes. In addition, a yeast two-hybrid system was used to detect the interactions of these subunits in vivo. RESULTS: Based on yeast transformed with the N-terminal fragment of the gamma(2) subunit (gamma(2)-N'), the N-terminal fragment of the rho(1) subunit (rho(1)-N'), and the full-length rho(1) subunit, the protein-protein interaction of the GABA(A) gamma(2) subunit and the GABA(C) rho(1) subunit was found in yeast grown in triple-dropout medium (deficient in Leu, Trp, and His) and expressing the LacZ reporter gene. Interaction of the rho(1) and gamma(2) subunits was investigated by functional studies in which gamma(2) (gamma(2)-N' with 837 bp) and rho(1) cRNAs were coinjected in Xenopus oocytes. In studies of the functional interaction, after injection of the gamma(2) subunit mutant cRNA containing a N-terminal fragment, GABA-induced rho(1) originated currents declined to 16% of the control level of homooligomeric rho(1) current. This inhibitory effect of coexpressing gamma(2) subunit mutants with rho(1) subunit on the rho(1)-originated current in oocytes was dose dependent. In addition, coexpression of the GABA rho(1) and gamma(2) subunits in oocytes altered pharmacologic properties of the homooligomeric receptor/channel formed by rho(1) or gamma(2) subunits. Further evidence was provided by results obtained with specific antibodies showing that the rho(1) subunit was coimmunoprecipitated with the gamma(2) subunit from the retina, brain, and spinal cord. CONCLUSIONS: The results indicate that protein-protein and functional interactions can occur between the GABA(A) gamma(2) subunit and the GABA(C) rho(1) subunit. Therefore, the functional role of GABA receptor/channels in the brain, retina, and spinal cord is more diversified because of the possible assembly between the GABA(A) gamma(2) subunit and GABA(C) rho(1) subunit.