Gastrointestinal tract involvement in patients with potential celiac disease beyond the small intestine: An early proof with IgA anti-tissue transglutaminase-2 antibody deposits

Background: IgA anti-tissue transglutaminase-2 antibody (anti-TG2Ab) deposits in intestinal and extraintestinal organs have been used to link the respective pathological changes in these organs with celiac disease (CeD). Aims: To know if parts of intestine other than the duodenum, such as esophagus, stomach, and colon, have any pathology related to potential CeD or have mucosal IgA anti-TG2 Ab deposits. Settings and Design: A prospective case–control study conducted from April 2018 to December 2019. Materials and Methods: Nine patients with potential CeD and 27 age- and gender-matched patients with irritable bowel syndrome were recruited as cases and controls, respectively. Mucosal biopsies were collected from esophagus, stomach, duodenum, and rectosigmoid regions, histological changes were evaluated, and IgA anti-TG2 Ab deposits were analyzed in these regions by two-color immunohistochemical staining. Statistics: Data were analyzed using statistical software Stata 14.0. Results: No distinct difference in mucosal lymphocytosis were identified between biopsies of patients with potential CeD and controls at the following sites: esophagus (11.1% vs 0%, P = 0.079), stomach (14.3% vs 7.7%, P = 0.590), and rectum (20% vs 0%, P = 0.067). Co-localized IgA anti-TG2Ab deposits were observed more in potential CeD than in controls at esophagus 22.2% (2/9) vs 0%, P = 0.012; stomach 66.7% (6/9) vs 11.5% (3/26), P < 0.001; and duodenum 66.7% (6/9) vs 0%, P < 0.001 but not at rectum 0% (0/4) vs 0% (0/25). Conclusion: Although histological changes are not distinct, a subset of subjects with potential CeD has pan-intestinal involvement other than in the duodenum.

Correlation of Helicobacter pylori virulence genotype & severity of mucosal inflammation in gastric biopsies from two geographically diverse regions in India

Background: H. pylori-associated gastritis in patients from the high-altitude area of Ladakh showed severe gastritis, mucosal nodularity, atrophy, and cancer in comparison to those from North India. This study served to analyze if differences in the H. pylori virulence genotypes decide the extent of gastric mucosal inflammation. Methods: Fifty gastric biopsies each from patients with H. pylori-associated gastritis from Ladakh and a tertiary care center in North India were included. The presence of H. pylori strain was confirmed with Warthin starry stain and polymerase chain amplification of the H. pylori-specific 16S rRNA. The cagA, vacA s1, s2, and m1, m2 alleles, and dupA virulence genotypes were studied in all archival samples, followed by their histological correlations. Results: cagA (P 0.009) and vacAs1 m1 (P 0.009) genes were distinctly more in H. pylori strains colonizing the biopsies of North Indian patients. In contrast, the cagA -ve vacAs2 m2 strains were significantly more in H. pylori strain colonizing the biopsies from Ladakhi patients. dupA genotype was almost similarly present in strains from both regions. Among these, only cagA and dupA virulence genes were associated with severe mucosal neutrophilic activity and deep infiltration of H. pylori strains in North Indian patients. Conclusions: Differences in virulence genotypes of H. pylori in gastric biopsies from North Indian and Ladakhi patients were found not significant in deciding the severity of H. pylori-associated gastritis.

To Study 25 (OH) D Levels In Patients With Non Alcoholic Fatty Liver Disease

BACKGROUND: Non–alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and its increasing incidence has been well documented from Asian countries. Diabetes mellitus (DM), obesity, hyperlipidemia are predisposing factors for NAFLD.Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA) flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes.Therefore this study was planned to estimate serum 25 (OH) D levels in patients with NAFLD. Aims and objectives: To estimate the serum vitamin D levels in patients with NAFLD and to find out the association if any between the Vitamin D deficiency and NAFLD. Material and method: This observational and analytical study was conducted in department of General Medicine, Himalayan Institute of Medical Sciences, Dehradun from November 2015 to November 2016. A total of 70 patients of NAFLD diagnosed by ultrasonography and 70 healthy volunteers were included in the study. Data was analyzed using SPSS version 22.0. Chi square and unpaired t test were used. A ‘p’ value of <0.05 was considered significant. Results: NAFLD patients had low serum 25 (OH) levels as compared to healthy volunteers which was statistically significant.Higher BMI (>23 kg/m2) was established as a risk factor for NAFLD.HDL and LDL levels were significantly lower in NAFLD patients. Higher plasma glucose level was risk factor for NAFLD but there was no significant difference in vitamin D levels. Conclusion: The serum vitamin D levels were lower in NAFLD patients as compared to healthy volunteers and obesity was associated as a risk factor for NAFLD and vitamin D deficiency.

Evaluation of small-subunit rRNA touchdown polymerase chain reaction for direct detection of Entamoeba histolytica in human pus samples from patients with amoebic liver abscess.

Purpose: The aim of the present study was to evaluate the use of touchdown polymerase chain reaction (TD-PCR) for the detection of Entamoeba histolytica in liver pus samples obtained from patients with a clinical diagnosis of amoebic liver abscess (ALA) using small-subunit rRNA (SSU rRNA) as the target gene. Materials and Methods: Microscopic examination in vitro culture and serological test for the detection of E. histolytica in 67 pus samples obtained from ALA patients was performed. Molecular studies were carried out by both conventional PCR and TD-PCR targeting the SSU rRNA gene using the same sets of primers and the results were compared. Results: TD-PCR detected the presence of E. histolytica in 86.5% of the liver pus samples within 2.5 h as compared with 82.08% by conventional PCR within 3.5-4 h. Conclusion: TD-PCR assay may serve as a relatively better detection method for E. histolytica over conventional PCR with respect to the turnaround time, increased sensitivity, specificity and yield.

Effects of alpha-1 adrenergic receptor antagonist, terazosin, on cardiovascular functions in anaesthetised dogs.

Initially a dose-response curve of phenylephrine was constructed at dose strengths of 1-16 microg/kg in a cumulative manner. Phenylephrine caused a significant rise in the mean arterial pressure, left ventricular systolic pressure, left ventricular contractility, stroke volume and a significant decline in the heart rate. Terazosin was administered in three selected doses of 10, 100 and 300 microg/kg. Following each dose of terazosin, dose-response curve of phenylephrine was constructed. Terazosin, per se, decreased the basal mean arterial pressure, left ventricular systolic pressure, left ventricular contractility and stroke volume significantly in a dose dependent manner with an increase in the heart rate with no significant change in the cardiac output. The baroreflex sensitivity at all the three doses remained unchanged. In conclusion, the present findings support the view that terazosin reduces the blood pressure in a physiologically more favorable manner by maintaining the neural integrity of the cardiovascular system.

Radiofrequency ablation: a new therapeutic modality for the management of hepatocellular cancer.

We report two patients of hepatocellular cancer who recently underwent radiofrequency ablation at our center. Both underwent successful ablation of the tumour requiring 1-2 sessions of upto 15 minutes. There were no post procedure complications. One of the patients had developed another lesion after 10 months of follow up and underwent another session of RFA, while the second patient is doing well after one year of the procedure.

Symptom score does not correlate with gastritis grade and Helicobacter pylori infection in non ulcer dyspepsia.

BACKGROUND: Non ulcer dyspepsia (NUD) is being postulated as one of the gastroduodenal manifestations of H. pylori infection. H. pylori infection may result in clinical symptoms as well as histological changes in NUD. AIM: To compare clinical symptom score and histological changes in H. pylori (Hp) positive and negative untreated NUD patients. METHODS: Forty six patients with dyspeptic symptoms and normal upper GI endoscopic examinations were included in this study. During endoscopy 2 biopsies each were taken from the antrum and body of the stomach. These biopsies were used for rapid urease test (RUT) and histological examination. Patients were diagnosed to have Hp infection if either of two tests were positive. There were two groups of patients: Hp positive and Hp negative NUD patients. Clinical scoring using Glasgow dyspepsia score (Max. 20) and histological analysis, using Sydney system (Max score 11) was done and compared for both the groups of patients. Clinical scoring, RUT and histological scoring were blinded to each other. RESULTS: H. pylori was present in 29(63%) of the 46 patients. Mean clinical score for H. pylori positive patient was 10.9 while for Hp negative patient was 11.4. Total histological score for Hp positive and Hp negative patients was 3.37 Vs 1.76 (antrum) and 3.68 Vs 1.29(body) (p < .001), respectively. The only histological change found to be statistically significant between Hp positive and Hp negative patients was presence of lymphoid follicles (p < .05). CONCLUSION: Clinical scoring does not correlate with the presence of H pylori or histological severity. In NUD patients positive for H. pylori, there is a significant increase in the severity of gastritis both in the antrum and the body.

Randomized trial of a quadruple-drug regimen and a triple-drug regimen for eradication of Helicobacter pylori: long-term follow-up study.

BACKGROUND: In developing countries, H. pylori eradication rates are suboptimal. A quadruple-drug regimen may improve on the eradication rate achieved with triple-drug regimen. METHODS: 64 consecutive patients with active duodenal ulcer associated with H. pylori infection were randomized to receive either a one-week triple-drug regimen (lansoprazole, clarithromycin, secnidazole) or a one-week quadruple-drug regimen (lansoprazole, amoxycillin, colloidal bismuth subcitrate, secnidazole). H. pylori eradication and ulcer healing were assessed 4 weeks after completion of therapy. Patients were followed up at 24 weeks and 52 weeks for H. pylori recurrence. RESULTS: Both the regimens eradicated H. pylori in 75% (95% CI 0.6-0.9) of patients. The ulcer-healing rate with the triple-drug regimen was 97% (95% CI 0.91-1.0) and 91% (95% CI 0.91-1.0) with the quadruple-drug regimen. No ulcer or H. pylori recurrence occurred in patients eradicated with the triple-drug regimen, whereas 8.3% of patients eradicated with the quadruple-drug regimen had ulcer as well as H. pylori recurrence during the 52-week follow up. CONCLUSION: Triple-drug regimen achieves similar eradication rates as quadruple-drug regimen in H. pylori infection.

14C urea breath test does not predict density of Helicobacter pylori in duodenal ulcer disease.

BACKGROUND & OBJECTIVES: The density of Helicobacter pylori in the gastric mucosa has prognostic significance, higher densities being associated with greater chances of development of duodenal ulcer and chronic atrophic gastritis as well as poor eradication by drug therapy. The aim of this study was to assess if 14C-urea breath test counts reflect bacterial density. METHODS: Sixty patients with endoscopically proven active duodenal ulcer and H. pylori positivity as determined by rapid urease test and gastric histology were studied. Gastric antral and corpus biopsies were graded for chronic gastritis, activity (presence of polymorphonuclear cells) and bacterial density (at surface and in pits) based on the Sydney system on a scale of four grades ranging from 0 to 3 (absent, mild, moderate and severe). 14C urea breath test was performed in all the patients. RESULTS: Chronic gastritis as well as activity was more prevalent as well as severe in the antrum as compared to the corpus. H. pylori density was also significantly more in the antrum as compared to the corpus both at the surface as well as in the pits. H. pylori density correlated with the grade of chronic gastritis and activity both in the antrum and in the corpus. Urea breath test counts ranged from 331.3 cpm (counts per minute) to 8770.5 cpm and these did not correlate with histological H. pylori density at any of the sites. INTERPRETATION & CONCLUSIONS: 14C urea breath test does not reflect H. pylori density on histology in patients of duodenal ulcer disease.

Management of amebic and pyogenic liver abscess.

The management of pyogenic liver abscess differs radically from that of amebic liver abscess. Medical management is the cornerstone of therapy in amebic liver abscess while early intervention in the form of surgical therapy or catheter drainage and parenteral antibiotics is the rule in pyogenic liver abscess. The prognosis of amebic abscess is much better than that of pyogenic abscess and usually a quick response to therapy is seen in amebic abscess.

A peptide inhibitor of HIV-1 protease using alpha, beta- dehydro residues: a structure based computer model.

HIV-1 encodes an aspartic protease, an enzyme crucial to viral maturation and infectivity. It is responsible for the cleavage of various protein precursors into viral proteins. Inhibition of this enzyme prevents the formation of mature, infective viral particles and therefore, it is a potential target for therapeutic intervention following infection. Several drugs that inhibit the action of this enzyme have been discovered. These include peptidomimetic inhibitors such as ABT-538 and saquinavir, and structure based inhibitors such as indinavir and nelfinavir. Several of these have been tested in human clinical trials and have demonstrated significant reduction in viral load. However, most of them have been found to be of limited clinical utility because of their poor pharmacological properties and also because the viral protease becomes rapidly resistant to these drugs on account of mutations in the enzyme. One way to overcome these limitations is to design an inhibitor that interacts mainly with the conserved residues of HIV-1 protease. By a rational drug design approach based on the high resolution X-ray crystal structure of the HIV-1 protease with--MVT 101 (a substrate based inhibitor) and the specific design principles of peptides containing dehydro-Alanine (delta Ala) derived from our earlier studies, we have designed a tetrapeptide with the sequence: NH2-Thr-delta Ala-delta Ala-Gln-COOH. Energy minimization and molecular modelling of the interaction of the designed tetrapeptide with the inhibitor binding site indicate that the inhibitor is in an extended conformation and makes excessive contacts with the viral enzyme at the interface between the protein subunits. The designed inhibitor has 33% of its interaction with the conserved region of HIV-1 protease which is of the same order as that of MVT 101 with the enzyme.

Non-sucrose sweetener for pain relief in sick newborns.

A prospective controlled blind study was carried out in the Special Care Unit for Newborns to assess the effect of commercially available sweetener on pain relief in newborns. Response to intramuscular injection and the pain stimulus was studied in twenty-five sick newborns, 13 preterm and 12 term, in a blinded fashion. Pain score, duration of cry, heart rate and oxygen saturations were studied. Basal response, responses with sterile water or sweetener were recorded in each baby. Responses to sweetener versus no solution and sweetener versus sterile water were compared by applying paired t-test. The reduction in pain score with sweetener was significant when compared with no solution. The difference was not significant when compared with sterile water. Similarly, duration of cry and heart rate with sweetener were significantly less when compared to sterile water or to no solution. However, the difference in oxygen saturation was not significantly different. Sweetener has an analgesic effect in sick babies. This can minimise adverse effects associated with painful procedures.

Evaluation of endoscopy-based diagnostic methods for the detection of Helicobacter pylori.

BACKGROUND: Helicobacter pylori is an etiological factor in duodenal ulcer. Few studies have objectively assessed the accuracy of diagnostic methods for the detection of H. pylori. METHODS: The sensitivity and specificity of histology, touch smear, rapid urease test (RUT) and brush cytology of endoscopic antral biopsy from patients with duodenal ulcer were compared. Forty-nine patients were evaluated before, and 34 after, eradication therapy. Each time, sampling was done for all 4 tests. The infection status for each sample was established by a positive concordance of results of three of four tests. RESULTS: The highest degree of agreement was between RUT and cytology (kappa = 0.69). Brush cytology (100%) followed by RUT (94.5%) were the most sensitive tests. Histology had the highest specificity (89.3%). A combination of RUT or brush cytology with histology had the maximum chance of detecting H. pylori. As single tests, brush cytology and touch smear had high diagnostic accuracies with a Youdin J value of 1.79 and 1.78, respectively. CONCLUSION: The best method for diagnosis of H. pylori is a combination of the rapid urease test or brush cytology with histology. Brush cytology or touch smear are diagnostic tests of choice if a single test is desired.

A study of changes in the status of autonomic nervous system in primary open angle glaucoma cases.

Control of Intra Ocular Pressure (IOP) is influenced by both divisions (sympathetic and para-sympathetic) of Autonomic Nervous System (ANS). The present study was conducted to confirm existence of any association of ANS with primary open angle glaucoma (POAG), if present. Systemic autonomic function tests were assessed in fifty patients of POAG with fifty normal subjects matched for sex and age as control using several well established tests based on cardiovascular reflex responses to standardised stimuli viz. Resting heart rate (RHR), Corrected QT Interval (QTc), T-wave amplitude, Standing to Lying Ratio (SLR); Valsalva Ratio; Galvanic Skin Resistance (GSR) and Cold Pressor Test (CPR). Tests were conducted in the Department of Physiology, Maulana Azad Medical College and associated Glaucoma Clinic of Guru Nanak Eye Centre from june '94-May '95. Subjects were randomly chosen from known POAG cases with IOP--25 +/- 5.08 mm Hg. The results showed decrease in both sympathetic and para-sympathetic activity of autonomic function tests in POAG suggesting associated autonomic dysfunction. Sympathetic under-activity is seen in 36 patients out of 50 (73%), POAG subjects while para-sympathetic activity is decreased in 43 of 50 (86%) of the POAG subjects when compared with normal control group. The results help concluding that POAG is associated with autonomic dysfunction with decreased activity of both sympathetic and para-sympathetic divisions of ANS.

Aetiological spectrum of obstructive jaundice and diagnostic ability of ultrasonography: a clinician's perspective.

BACKGROUND: A vast array of invasive and non invasive diagnostic tests are available to diagnose and establish the etiology of surgical obstructive jaundice (SOJ). Invasive tests may cause cholangitis and imaging techniques like computed tomography(CT) scan and MRI are expensive. The aim of the present study was to test ultrasonography as the primary investigation in patients with SOJ and to elucidate the aetiological spectrum of obstructive jaundice as seen at a tertiary referral center. METHODS: 429 patients diagnosed as having obstructive jaundice on the basis of either CT, endoscopic retrograde cholangiopancreatography(ERCP), fine needle aspiration cytology(FNAC) or surgery underwent real time sonography over a 10 year period from May 1988 to Dec 1997. The diagnostic accuracy of ultrasonography for SOJ was established. RESULTS: Sonography correctly established the presence of obstructive jaundice in 380 of 429 patients. Of 429 patients (mean age 62.5 +/- 34.2 yrs, 229 males and 194 females) the sensitivity of ultrasound to correctly diagnose and establish the site of etiology of obstruction was 94% with a specificity of 96%. Malignant SOJ was much more common than benign causes (75.3% Vs. 24.7%). Carcinoma (Ca) of the gallbladder (28.7%) was the commonest aetiology followed by Ca pancreas (26.5%), choledocholithiasis (12.4%), cholangio Ca (10.8%) benign stricture (10.8%) and ampullary Ca (9.8%). A total of 167 subjects (44%) had high block while 213 (56%) had low block. Block at the porta hepatis was due to gallbladder Ca in 91% of patients. Ca pancreas was the cause of lower end block in 76% of patients. CONCLUSION: SOJ, as seen in this large series of patients was most often due to malignant cause and gallbladder Ca was the commonest cause in North Indian patients. The clinician should utilize the ability of the ultrasound to diagnose the presence of obstructive jaundice and its location.