Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Evaluation of Efficacy of Microwave Irradiation in Disinfecting Dental Gypsum Casts: An Ex Vivo Study

The aim of this study is to assess the efficacy of microwave irradiation in disinfecting gypsum casts and also to compare its efficacy with validated method of chemical disinfection. The present study is an ex vivo study conducted on a sample of five irreversible hydrocolloid impressions in vitro and on ten patients gypsum casts in vivo following standard impression techniques to check the efficacy of microwave oven irradiation and compare its efficacy with standard chemical method of disinfection. Results were analysed using Mann–Whitney test and Wilcoxon signed rank test. Untreated gypsum casts showed cfu/ml counts with a median log value of 6, while microwave-irradiated ones had median cfu/ml counts of 0. Casts poured from chemically disinfected impressions demonstrated cfu/ml counts with a median log value of 5. Microwave irradiation was found to be effective in disinfecting gypsum casts when compared to chemical disinfectant in disinfecting dental impressions.     

Laparoscopic repair of paraesophageal hernia

Laparoscopic repair of paraesophageal hernias is rapidly replacing the traditional open approach. Regardless of the approach, certain aspects of repairing paraesophageal hernias have proven to be beneficial and others remain controversial. This article addresses the effectiveness of the laparoscopic approach, the accepted and controversial technical aspects of repair, and which patients should undergo surgical correction of the hernia.     

Laparoscopic Heller myotomy and Roux-en-Y gastric bypass: a novel operation for the obese patient with achalasia

Morbid obesity is a disease encompassing multiple, significant comorbidities. The only current, reliable, durable treatment of obesity is surgical intervention, most commonly gastric bypass. Achalasia, a swallowing disorder of esophageal motility and failure of the lower esophageal sphincter (LES) to relax, is rarely seen in the morbidly obese patient. Treatment is directed at disruption of the LES to allow passage of food. As medical management usually fails in both disease processes, surgical treatment is often chosen. The patient with both morbid obesity and achalasia presents an unusual challenge for surgical treatment. The standard surgical approach for each disease does not address the other, and may have deleterious consequences on the other condition if approached unilaterally. We present the first case of a patient treated with a concomitant laparoscopic esophagogastric myotomy (LEM) and laparoscopic Roux-en-Y gastric bypass (LRYGBP).     

Endoscopic therapy for gastroesophageal reflux disease: can it replace antireflux surgery?

This article addresses emergent endoluminal technologies currently available for the treatment of gastroesophageal reflux disease (GERD) and compares it to the laparoscopic Nissen fundoplication. To date the mainstay of GERD therapy has been achieved with either open or laparoscopic fundoplication or life-long medical treatment. Endoluminal treatment modalities attempt to augment the gastroesophageal junction (GEJ) function by various techniques. We searched the Medline database from 1980 to 2004 for studies on endoscopic GERD techniques and laparoscopic fundoplications. Product investigators were contacted for data presented in abstract form only. Endoluminal management of GERD include using radiofrequency energy, injection of biocompatible polymers and endoluminal sutures to alter the GEJ and reduce reflux. Early results while encouraging, should be evaluated thoroughly and with caution before widespread use can be advocated. Endoscopic treatment of GERD has future promise, however, more experience and perhaps further refinement in techniques and technology must occur before widespread clinical application can be encouraged.