Rare Case of Pseudohypoparathyroidism With Normocalcemia Because of a Novel GNAS Mutation.

PTH resistance is characterized by hypocalcemia and hyperphosphatemia in the presence of elevated PTH concentrations, resulting in pseudohypoparathyroidism, which is subdivided into different types according to its different pathogenesis and phenotype. PTH receptor is the alpha subunit of stimulatory G protein (Gsα)-coupled receptor. Pathogenic variants of GNAS gene, encoding for Gsα, lead to reduced Gsα function and PTH resistance. We report a patient with PHP type 1a, with no documented evidence of hypocalcemia, presenting with AHO phenotype and multihormone resistance to PTH, TSH, and GnRH. Her genetic testing showed a novel heterozygous pathogenic variants, a c.934T > G change in exon 11 in adenylate cyclase stimulatory G protein that has not been reported in the literature so far.

Changes in esophageal physiology after paraesophageal hernia repair and Collis gastroplasty.

BACKGROUND: The surgical approach and technique for paraesophageal hernia (PEH) repair is much debated. The changes in the esophageal physiology after PEH repair with a concomitant Collis gastroplasty (PEH-CG) are not clearly known. The aim of this study was to determine the changes in high resolution esophageal manometry (HREM) and esophageal pH testing after PEH-CG. METHODS: Retrospective analysis of all patients who underwent PEH-CG at our institution between 2006 and 2013 was performed. Patients had esophageal pH testing, HREM, barium swallow and an upper endoscopy before and after PEH-CG. RESULTS: A total of 182 patients underwent PEH-CG during the study period. Majority of patients had Nissen fundoplication (176, 96.7%) with Toupet in 6 (3.3%). Basal lower esophageal sphincter pressure (LESP) was lower after fundoplication (20.3 mmHg ± 11.3 vs. 25.8 mmHg ± 15.6, p < 0.001), whereas residual LESP was noted to be higher after fundoplication (7.7 mmHg ± 4.9 vs. 6.1 mmHg ± 6.7, p < 0.009). There were no significant changes in the esophageal motility patterns. There was an improvement in total pH and upright pH but not supine pH post PEH-CG. Normalization of total acid exposure after fundoplication was noted in 31 (59.6%) of the 52 patients who had abnormal total acid exposure prior to fundoplication. CONCLUSIONS: Objective clinical assessment in patients undergoing PEH-CG demonstrates an effective operation for this complex problem. There was an increase in residual LESP but interestingly, decrease in basal LESP. Additionally, there was an improvement in esophageal acid exposure afterwards. These findings will facilitate future management of PEH.

Role of endoscopic therapy in early esophageal cancer.

Esophageal carcinoma is a highly lethal cancer associated with high morbidity and mortality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two distinct histological types. There has been significant progress in endoscopic diagnosis and treatment of early stages of cancer using resection and ablation techniques, as shown in several trials in the recent past. Earlier detection of esophageal cancer and advances in treatment modalities have lead to improvement in the 5-year survival from 5% to about 20% in the past decade. Endoscopic eradication therapy is the preferred modality of treatment in cancer limited to mucosal layer of the esophagus as there is very low risk of lymph node metastasis, leading to high cure rates, low risk of recurrence and with few adverse effects. The most common adverse events seen are strictures, bleeding and rarely perforation which can be endoscopically managed. In patients with recurrent advanced disease or invasive tumor, esophagectomy with lymph node dissection remains the mainstay of treatment. There is debate on post-endoscopic surveillance with some studies suggesting closer follow up with upper endoscopy every 6 mo for the first 1-2 years and then annually for the 3 years while others recommending the appropriate action only if symptoms or other abnormalities develop. Overall, the field of endoscopic therapy is still evolving and focus should be placed on careful patient selection using a multidisciplinary approach.

Bronchial venous plexus in left ventricular dysfunction.

Chronic pulmonary venous hypertension causes dilatation and engorgement of bronchial veins because of a close communication between bronchial and pulmonary veins. We report a case of severe left ventricular systolic dysfunction with chronically elevated pulmonary venous pressure leading to characteristic bronchoscopic findings of engorgement of bronchial veins.

Inhibitors of catechol-O-methyltransferase in the treatment of neurological disorders.

Catechol-O-methyltransferase (COMT) is the enzyme which catalyzes the transfer of a methyl group from S-adenosylmethionine to catechols and catecholamines, like the neurotransmitters dopamine, epinephrine and norepinephrine. COMT has implications in many neurological and psychiatric disorders like schizophrenia, Parkinson's disease (PD), bipolar disorders, etc. and therefore, it serves as an important drug target. Since its characterization in 1957, many inhibitors were designed where the first generation inhibitors were found to be highly toxic, short acting and had poor bioavailability. Currently, two of the second generation inhibitors, tolcapone and entacapone have been used for treatment of PD but are associated with various dopaminergic and gastro-intestinal side-effects. There have been several approaches for the design of novel COMT inhibitors with a good and safe therapeutic profile. The focus of this article is to review the current knowledge on COMT and the role of COMT inhibitors in the treatment of neurological disorders. The inhibitors have been classified into six different classes based on the structural framework. A historical overview of the discovery and development of COMT inhibitors is presented with a special emphasis on new generation of inhibitors till date.