Effect of Proton Pump Inhibitor Therapy on Inflammatory Changes in the Gastric Cardia (Carditis)

The etiology of inflammation of the gastric cardia (carditis) is controversial, and gastroesophageal reflux disease (GERD) and H. pylori infection have been proposed as etiological factors. This study aimed to investigate the effect of acid suppression on histological changes in the gastric cardia. Gastric cardia biopsies of reflux patients were evaluated at baseline and after proton pump inhibitor (PPI) therapy. The updated Sydney classification was used to score the biopsies, and carditis scores (pre- and post-PPI therapy) were compared. A total of 31 patients were included, of which 5 patients were excluded, as cardiac mucosa was not documented in either pre- or post-PPI biopsies. The mean duration of PPI therapy was 30 months (SE, 3.04 months). There was no significant change in carditis scores post-PPI therapy. The mean mononuclear and neutrophil scores were 1.23 and 0.35 pre-PPI therapy and 1.73 and 0.62 post-PPI therapy, respectively. No change in mean intestinal metaplasia and atrophy scores was identified. In conclusion, acid suppressive therapy with PPI did not lead to a significant reduction in carditis scores. These results suggest that GERD probably does not play a major role in the pathogenesis of inflammation in the gastric cardia.     

Glutathione-conjugate transport by RLIP76 is required for clathrin-dependent endocytosis and chemical carcinogenesis

Targeted depletion of the RALBP1-encoded 76-kDa splice variant, RLIP76, causes marked and sustained regression of human xenografts of lung, colon, prostate, and kidney cancers without toxicity in nude mouse models. We proposed that the remarkable efficacy and broad spectrum of RLIP76-targeted therapy is because its glutathione-conjugate (GS-E) transport activity is required for clathrin-dependent endocytosis (CDE), which regulates all ligand-receptor signaling, and that RLIP76 is required not only for survival of cancer cells but also for their very existence. We studied RLIP76 mutant proteins and the functional consequences of their expression into RLIP76(-/-) MEFs, identified key residues for GS-E binding in RLIP76, established the requirement of RLIP76-mediated GS-E transport for CDE, and showed a direct correlation between GS-E transport activities with CDE. Depletion of RLIP76 nearly completely blocked signaling downstream of EGF in a CDE-dependent manner and Wnt5a signaling in a CDE-independent manner. The seminal prediction of this hypothesis-RLIP76(-/-) mice will be deficient in chemical neoplasia-was confirmed. Benzo[a]pyrene, dimethylbenzanthracene, and phorbol esters are ineffective in causing neoplasia in RLIP76(-/-). PMA-induced skin carcinogenesis in RLIP76(+/+) mouse was suppressed completely by depletion of either PKCα or RLIP76 by siRNA or antisense and could be restored by topical application of RLIP76 protein in RLIP76(-/-) mouse skin. Likewise, chemical pulmonary carcinogenesis was absent in female and nearly absent in male RLIP76(-/-) mice. In RLIP76(-/-) mice, p53, p38, and JNK activation did not occur in response to either carcinogen. Our findings show a fundamental role of RLIP76 in chemical carcinogenesis.     

Trigeminal Neuralgia in Pregnancy: A Management Challenge

Pregnancy is known to aggravate pre‐existing chronic painful conditions. Trigeminal neuralgia (TN), albeit a disease of the elderly, may afflict pregnant females, which can further complicate its management. Teratogenic effects of the commonly used drugs on the developing fetus limit pharmacological treatment. Moreover, safety of commonly performed interventional therapies is marred by their inherent fetomaternal effects and more importantly the risk for radiation effects on the fetus due to the use of fluoroscopy. This rare coexistence of TN in pregnancy has not been reported before. Here we present a case of TN in a young woman, whose pain was aggravated when she became pregnant, and she was treated successfully by conventional radiofrequency ablation of the Gasserian ganglion.     

Comparison of nebulised magnesium sulphate and salbutamol combined with salbutamol alone in the treatment of acute bronchial asthma: a randomised study

Objective

To test the hypothesis that combined administration of multiple doses of nebulised salbutamol and magnesium sulphate provides additional benefit compared with salbutamol alone in adult patients with acute asthma.

Design

Randomised, double blind, prospective study.

Methods

A total of 100 patients presenting to an emergency department with an acute attack of bronchial asthma were randomised to two groups: nebulisation with a combination of salbutamol and magnesium sulphate (group A) and nebulisation with salbutamol only (group B). Both groups received nebulisation thrice at intervals of 20 minutes. Salbutamol and magnesium sulphate were administered in doses of 0.5 mg and 500 mg, respectively, and the solutions were made isotonic to plasma osmolality. Pulse rate, blood pressure, and peak expiratory flow rate (PEFR) were measured at baseline and at 15, 60, 75, and 120 minutes. Serum magnesium levels and blood gases were measured at 0 and 120 minutes in both groups.

Results

All patients had either acute severe or life threatening asthma. The baseline characteristics were comparable in the two groups. Both groups showed significant rise in PEFR at all time intervals, however, there was no significant difference between the groups in rise in PEFR at any time point. Serum magnesium levels remained within normal limits, and there was no difference in requirement of additional medication during the study or hospital admission rates in both groups. No significant side effects were noted.

Conclusion

This study suggests that there is no therapeutic benefit of adding magnesium sulphate to salbutamol nebulisation in the treatment of patients with acute severe or life threatening asthma.     

Correlation between narrow band imaging and nonneoplastic gastric pathology: a pilot feasibility trial

BACKGROUND: A novel narrow band imaging (NBI) system is able to visualize the mucosal and vascular network in the GI tract. OBJECTIVE: The aim of the current study was to test the feasibility of NBI to predict gastric histologic diagnosis. DESIGN: A pilot feasibility study. SETTING: Veterans Affairs Medical Center. PATIENTS: Forty-seven patients undergoing upper endoscopy for various indications were prospectively enrolled. METHODS: The gastric body and antrum were systematically examined by NBI before targeted biopsies. Images were graded according to the mucosal (ridge/villous and circular) and vascular patterns and correlated with histologic findings in a blinded manner. MAIN OUTCOME MEASUREMENTS: Final histologic diagnosis based on updated Sydney classification system. RESULTS: Overall, 25 patients (53.1%) had a normal biopsy specimen, 13 (27.6%) had non-Helicobacter pylori gastritis, 4 (8.5%) had H pylori gastritis, and 5 (10.6%) had intestinal metaplasia. The sensitivity, specificity, and positive predictive value of a regular mucosal and vascular pattern for the diagnosis of normal mucosa/mild gastritis were 89%, 78%, and 94%, respectively. The sensitivity and specificity of an irregular pattern with decreased density of vessels for the diagnosis of H pylori were 75% and 88%, and that of the ridge/villous pattern for the diagnosis of intestinal metaplasia were 80% and 100%, respectively. LIMITATION: The small number of patients with H pylori and intestinal metaplasia was the main limitation. CONCLUSIONS: This is the first U.S. study of NBI for gastric lesions. NBI may help predict in vivo histologic diagnosis of gastric pathologic conditions with a good degree of accuracy. Future larger studies are needed.     

Ciliated Hepatic Foregut Cyst: An Increasingly Diagnosed Condition

Ciliated hepatic foregut cyst is a rare foregut cystic developmental malformation. It presents as a solitary cystic lesion in segment four of the liver. Histologically, it consists of four distinct layers; namely, the inner ciliate columnar epithelium, subepithelial connective tissue, smooth muscle layer, and an outer fibrous layer. Usually asymptomatic and detected incidentally, other modes of presentation can include portal hypertension, obstructive jaundice, and development of malignancy. We present a case of a young asymptomatic woman with a complex cyst in segment four of the liver, who underwent a laparoscopic resection, focusing our discussion on the review of the literature and the diagnostic dilemma encountered in these rare cases.     

The diagnostic accuracy of esophageal capsule endoscopy in patients with gastroesophageal reflux disease and Barrett's esophagus: a blinded, prospective study

BACKGROUND: Esophageal capsule endoscopy (ECE) is a novel technique that offers noninvasive evaluation of esophageal pathology in gastroesophageal reflux disease (GERD) patients. OBJECTIVE: To assess the diagnostic accuracy of ECE for Barrett's esophagus (BE), erosive esophagitis, and hiatal hernia and to assess the safety profile of ECE. METHODS: Patients with GERD symptoms and those undergoing BE surveillance were prospectively enrolled. All patients underwent ECE followed by standard upper endoscopy. ECE findings were interpreted by examiners blinded to endoscopy results. The gold standard was the findings at endoscopy and ECE results were compared with those at endoscopy. RESULTS: One hundred patients were enrolled of which 94 completed the study. At upper endoscopy, BE was suspected in 53 (mean length 3.1 cm) and confirmed in 45 patients. Erosive esophagitis and hiatal hernia were identified in 18 and 70 patients, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ECE for BE in GERD patients were 67%, 87%, 60%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV of ECE for BE patients undergoing surveillance were 79%, 78%, 94%, and 44%, respectively. The sensitivity, specificity, PPV, and NPV for erosive esophagitis were 50%, 90%, 56%, and 88% and for hiatal hernia were 54%, 67%, 83%, and 33%, respectively. CONCLUSIONS: Current diagnostic rates of ECE for BE are not yet accurate enough for application in clinical practice. An improvement in technology and learning curve assessments are required, until then standard upper endoscopy remains the gold standard.     

Carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with and without coronary artery disease

BACKGROUND: Carotid intima-media thickness and pulse wave velocity are non-invasive markers of atherosclerosis and have been shown to reliably predict presence and extent of atherosclerotic vascular disease. However, studies examining their association with each other have shown inconsistent results. Hence it was sought to assess correlation between carotid intima-media thickness and pulse wave velocity in patients with and without coronary artery disease. METHODS AND RESULTS: Sixty-four patients with angiographically proven coronary artery disease and 84 age-matched individuals without coronary artery disease but having one or more conventional cardiovascular risk factors were included in the study. Individuals with established cerebrovascular disease and peripheral vascular disease were excluded from the study. Carotid intima-media thickness of far wall was measured at three predefined sites (distal common carotid, carotid bifurcation and proximal internal carotid artery) on each side. Brachial-ankle pulse wave velocity was measured non-invasively using VP 1000 (Colin Corporation) automated ABI/ PWV analyzer. There was no significant difference in gender and presence of cardiovascular risk factors in the two groups. Mean and maximum carotid intima-media thickness and brachial-ankle pulse wave velocity were all significantly higher in coronary artery disease patients as compared to patients without coronary artery disease (0.842 v. ( 0.657 mm, p <0.0001; 1.076 v. 0.795 mm, p <0.0001; 1708.63 v. 1547.26 cm/s, p <0.0004 respectively). There was a significant correlation between brachial-ankle pulse wave velocity and both mean and maximum carotid intima-media thickness in patients with coronary artery disease (r = 0.47, p <0.0001 and r=0.41, p < 0.0008 respectively) but not in individuals without coronary artery disease (r=0.01 and -0.1 respectively). CONCLUSIONS: Presence of significant correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with coronary artery disease but absence of the same in individuals without major atherosclerotic vascular disease suggests that the correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity becomes stronger with increasing extent of atherosclerosis.     

Evaluation of Docosahexaenoic Acid in a Dog Model of Hypertension Induced Left Ventricular Hypertrophy

Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.