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To study interaction of specific antibodies with the GABA receptor/channel, antisera were raised against the extracellular domains of the GABAA receptor/channel beta2 subunit, gamma2 subunit and the GABAC receptor/channel rho1 subunit. The specificity of the antibodies was characterized by immunocytochemistry and by Western blotting of transfected FDC-P1 cells expressing recombinant GABA receptor/channel subunits. The effects of the antibodies on whole-cell currents in Xenopus laevis oocytes expressing homomeric recombinant GABA receptor/channel beta2, gamma2, and rho1 were studied using two-microelectrode voltage clamp. In the absence of GABA, anti-alpha2, anti-gamma2, and anti-rho1 antisera elicited whole-cell currents in oocytes expressing beta2, gamma2, and rho1 subunits, respectively. The effect of antibody on channel activation was concentration-dependent. The whole-cell currents induced by anti-beta2 and anti-gamma2 were several-fold greater than those induced by application of 100 microm GABA. In Xenopus oocytes expressing recombinant rho1 subunits, GABA-induced whole-cell currents were inhibited by the anti-rho1 antibody. In contrast, the GABA-induced whole-cell currents were potentiated several-fold by anti-beta2 and anti-gamma2 antibodies in Xenopus oocytes expressing homomeric beta2 and gamma2 subunits. Our studies indicate that antibodies specific to the N-terminal domain of GABA receptor/channel subunits can modulate the neurotransmitter receptor function. [ABSTRACT FROM AUTHOR]

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.

Background and Aims: The differential diagnosis between tuberculosis (TB) and lymphadenitis caused by nontuberculous mycobacteria (NTM) in children is often based on epidemiologic and clinical data. The aim of this study was to identify epidemiologic and clinical variables associated with TB lymphadenitis in children attending 2 TB out-patient clinics in northern Italy during a 10-year period., Patients and Methods: All children less than 16 years of age attending the study sites suspected of mycobacterial disease from 1999 through 2008 were included in the analysis. Logistic regression was used to evaluate the variables independently associated with TB lymphadenitis., Results: From 299 children diagnosed with mycobacterial disease 121 children (40%) had a clinical diagnosis of cervical mycobacterial lymphadenitis: 38 TB (31%) and 83 NTM lymphadenitis (69%) cases. Increasing age (OR, 1.29; 95% CI, 1.02-1.69; P = 0.04), being foreign born (OR, 11.60; 95% CI, 1.37-114.20; P = 0.02), and having an abnormal chest radiograph (OR, 18.32; 95% CI, 2.37-201.68; P = 0.008) were independently associated with TB lymphadenitis. In the selected model, a 5-year-old foreign born child with cervical lymphadenitis and abnormal findings on chest radiograph has an estimated 0.90 probability of having TB disease. On the other hand, an Italy born child of the same age with cervical lymphadenitis and normal chest radiograph has a 0.04 probability of having TB., Conclusion: Epidemiologic and clinical data are useful tools in the differential diagnosis between TB and NTM lymphadenitis when etiologic diagnosis is not available.

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)., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Chylothorax is the accumulation of chyle in the pleural space. In newborns the congenital form is often prenatal diagnosed, while the late variety originates to damage to the thoracic duct by cardiac surgery, diaphragmatic hernia, etc. Clinical presentation results from the accumulation of pleural fluid and the symptoms depends on the size of the effusion. The treatment needs both medical and surgical care. The pleural cavity should be drained via thoracocentesis, and total parenteral nutrition should be started. Afterward fat-free diet with the addition of medium-chain triglycerides could be initiate. Somatostatin and octreotide have been successfully employed, mainly in post-surgery chylothorax. Surgery should be considered when medical management fails. Some approaches are reported, and thoracic duct ligation, pleurodesis and pleuroperitoneal shunts are the most utilized. The prognosis of chylothorax depends on the etiology, and it is consequence of a variety of treatments that may influence the outcome.

Nowadays short bowel syndrome (SBS) is quite frequent, because of more aggressive surgical and medical approaches to the management of neonatal intra-addominal catastrophes. Intestinal rehabilitation can be reached in case of SBS with a strategy that merges nutritional, pharmacologic and surgical approaches to achieve the ultimate goal of enteral nutrition. Long-term clinical nutrition which combines total parenteral nutrition (TPN) and enteral nutrition is required for the adaptation process. Long-term TPN can, however, be associated with mechanical, septic and metabolic complications, most of which have been consistently reduced by a better understanding of the prerequisites for its application and by improvements in parenteral solutions. Parenteral nutrition associated cholestasis (PNAC) and liver disease (PNALD) remain indeed the most worrisome complications and bear with them a high mortality rate. Their prevention will further improve the role of TPN in patients with SBS. The etiology of PNAC and PNALD, although elusive, is thought to be multifactorial and proposed theories also include problems arising from lipid emulsions. Parenteral nutrition, that includes n-3 fatty acids, appear to diminish the extent of the inflammatory response thought to be responsible for PNAC and PNALD. This article will attempt to review the role of TPN in the rehabilitation process and discuss energy and macronutrients requirements.

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.

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.

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.

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.

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.

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.

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.