Liver dysfunction in alcoholics in Western Nepal.

To estimate liver function tests in patients with alcoholic fatty liver disease, alcoholic hepatitis and alcoholic cirrhosis and to compare the levels of enzymes between the groups. A hospital based case control study was carried out at Nepalgunj Medical College, Nepal from January 2013 to June 2013. A total of 150 alcoholic associated liver disorders patients aged between 20-70 years and 50 sex age matched normal healthy controls were taken to assess liver function tests (LFTs) by measuring Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Gamma glutamyltranspeptidase (GGT) & Albumin. The mean±SD of liver function tests (LFTs) of patients of alcoholic fatty liver disease is highest followed by alcoholic hepatitis patients. All the 3 groups of alcoholic associated liver disorders patients when compared to normal healthy control subjects showed statistically significant increase in the levels of AST (p<0.000), ALT (p<0.000), ALP (p<0.006), GGT (p<0.000), & Albumin (p<0.000). Liver function tests values for alcoholic associated liver disorders patients when compared to the healthy control subjects was significantly altered.

Comparison of lipid profile in type-2 obese diabetics and obese non-diabetic individuals. a hospital based study from Western Nepal.

BACKGROUND: Type-2 diabetes mellitus is an independent risk factor for coronary artery disease and risk of coronary disease is three to four fold increased in patients with diabetes compared with non-diabetic population and 60-80% 0f type-2 diabetics are obese. METHODS: This study was conducted in Nepalgunj Teaching Hospital, Kohalpur, Banke, Nepal, between 1st March, 2011 and 28th February, 2012. A total of 150 samples were taken to assess the lipid profile in type-2 diabetic patients associated with obesity and 25 obese controls for their lipid profile. Venous blood samples were taken from all the subjects in the morning after fasting overnight. Exclusion criteria included pregnancy, chronic infectious disease, heart failure; renal failure and drug allergy were confirmed from the subject's personal physician report and a detailed history. The data was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. RESULTS: The mean ± SD age of diabetic patients with obesity was 53.76± 6.23 while the mean ± SD age of control was 49.61 ± 4.8. Out of 150 patients 105 (70%) were males and 45 (30%) were females. Among control subjects 16 (64%) were males and 9 (36%) were females. Obese type-2 diabetic patients when compared to obese control subjects showed statistically significant increase in the levels of serum total cholesterol (p < 0.001), serum triglycerides (p < 0.001), serum LDL-cholesterol (p < 0.001) while serum HDL-cholesterol levels did not show statistically significant difference in the two group (p > 0.05). CONCLUSION: This study showed obese diabetic individuals have dyslipidemia and more prone to develop cardiovascular diseases.

Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis.

BACKGROUND: Oesophageal motility, as measured by manometry, is normal in the majority of patients with eosinophilic oesophagitis (EO). However, manometry measures only the circular muscle function of the oesophagus. The goal of the present study was to assess circular and longitudinal muscle function during peristalsis in patients with EO. METHODS: Ultrasound imaging and manometry were simultaneously acquired during swallow-induced peristalsis in patients with EO and controls to measure the longitudinal muscle and circular muscle contraction, respectively. A probe with an ultrasound transducer was positioned 2 cm and then 10 cm above the lower oesophageal sphincter and five, 5 ml water swallows were recorded before and after edrophonium. RESULTS: There is no difference in the incidence of swallow-induced peristalsis and manometric pressures (a marker of circular muscle contraction) between controls and patients with EO. However, changes in the muscle thickness (a marker of longitudinal muscle contraction) are markedly diminished in patients with EO, at both 2 and 10 cm above the lower oesophageal sphincter. The longitudinal muscle response to edrophonium is markedly blunted in patients with EO. Normal subjects demonstrate synchrony between the circular and longitudinal muscle contraction during peristalsis that is affected by edrophonium. On the other hand, patients with EO demonstrate mild asynchrony of circular and longitudinal muscle contraction during swallow-induced contractions that is not altered by edrophonium. CONCLUSIONS: In patients with EO, there is selective dysfunction of the longitudinal muscle contraction during peristalsis. It is proposed that the longitudinal muscle dysfunction in EO may contribute to dysphagia.

Electrical and mechanical activity in the human lower esophageal sphincter during diaphragmatic contraction.

To determine the effect of contraction of the diaphragm on the lower esophageal sphincter (LES) pressure, we studied eight healthy volunteers during spontaneous breathing, maximal inspiration, and graded inspiratory efforts against a closed airway (Muller's maneuver). Electrical activity of the crural diaphragm (DEMG) was recorded from bipolar esophageal electrodes, transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures, and LES pressure was recorded using a sleeve device. During spontaneous breathing, phasic inspiratory DEMG was accompanied by phasic increases in Pdi and LES pressure. With maximal inspiration, DEMG increased 15-20-fold compared with spontaneous inspiration, and LES pressure rose from an end-expiratory pressure of 21 to 90 mmHg. Similar values were obtained during maximal Muller's maneuvers. LES pressure fell promptly when the diaphragm relaxed. Graded Muller's maneuver resulted in proportional increases in the Pdi, LES pressure, and DEMG. The LES pressure was always greater than Pdi and correlated with it in a linear fashion (P less than 0.001). We conclude that the contraction of the diaphragm exerts a sphincteric action at the LES, and that this effect is an important component of the antireflux barrier.

Association studies for agro-physiological and quality traits of triticale x bread wheat derivatives in relation to drought and cold stress.

Correlation coefficient analysis conducted on 22 triticale x bread wheat derivatives along with six checks to select true- breeding derivative(s) for future hybridization programme with tolerance to drought and cold stress conditions as well as better quality traits revealed significant correlation of grain yield with spikelets per spike, biological yield, harvest index, leaf area index. Interestingly, the grain yield and drought susceptibility index showed no association. However, with cold tolerance it showed significant positive correlation indicating the desirability of certain plant traits under cold stress. The grain yield exhibited no association with quality traits which might assist in the predictability of high yielding varieties with high protein, total sugars, reducing sugars and non-reducing sugars. Path coefficient analysis revealed that biological yield had the highest positive direct effect on grain yield followed by harvest index, specific leaf weight, stomatal number, 1000 grain weight, stomatal size, spikelets per spike and days to heading. Therefore, indirect selection for these plant traits in order should be exercised in selecting drought tolerant genotypes. Two genotypes (RL-124-2P2 and RL 111P2) were found to be drought and cold tolerant with high grain yield, spikes per plant, spikelets per spike and leaf area index.

Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients.

BACKGROUND: The mechanism of esophageal pain in patients with nutcracker esophagus (NE) and other esophageal motor disorders is not known. Our recent study shows that baseline esophageal mucosal perfusion, measured by laser Doppler perfusion monitoring, is lower in NE patients compared to controls. The goal of our current study was to perform a more detailed analysis of esophageal mucosal blood perfusion (EMBP) waveform of NE patients and controls to determine the optimal EMBP biomarkers that combined with suitable statistical learning models produce robust discrimination between the two groups. METHODS: Laser Doppler recordings of 10 normal subjects (mean age 43 ± 15 years, 8 males) and 10 patients (mean age 47 ± 5.5 years., 8 males) with NE were analyzed. Time and frequency domain features were extracted from the first twenty-minute recordings of the EMBP waveforms, statistically ranked according to four independent evaluation criterions, and analyzed using two statistical learning models, namely, logistic regression (LR) and support vector machines (SVM). KEY RESULTS: The top three ranked predictors between the two groups were the 0.5 and 0.75 perfusion quantile values followed by the surface of the EMBP power spectrum in the frequency domain. ROC curve ranking produced a cross-validated AUC (area under the curve) of 0.93 for SVM and 0.90 for LR. CONCLUSIONS & INFERENCES: We show that as a group NE patients have lower perfusion values compared to controls, however, there is an overlap between the two groups, suggesting that not all NE patients suffer from low mucosal perfusion levels.

Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high-resolution manometry.

BACKGROUND: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. METHODS: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. KEY RESULTS: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. CONCLUSION & INFERENCES: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.

Oesophago-gastric junction opening function: assessment using ultrasound imaging and the effects of atropine.

Relaxation and opening of the oesophago-gastric junction (OGJ) is crucial for oesophageal transport. A novel ultrasound technique was used to determine OGJ opening, before and after atropine, in 12 normals. An ultrasound probe, a solid-state pressure transducer and an infusion tube were placed inside a 20-mm diameter bag, which was placed across the OGJ. At various bag pressures ultrasound transducer was pulled across the bag. Acquired B-mode ultrasound images were converted into M-mode image to display the oesophagus, OGJ and stomach. At low bag-pressure (< 20 mmHg), the OGJ but not oesophagus and stomach, is collapsed around the bag. Increasing bag pressure results in gradual opening of the OGJ from distal end. M-mode image identified the narrowest region of OGJ and corresponding cross-sectional area (CSA) was measured. Mean bag pressure to initial OGJ opening was 18 mmHg. Linear relationship between bag-pressure and OGJ-CSA was observed. Atropine reduced opening bag pressure and shifted the OGJ pressure-CSA curve upward without altering slope, i.e. compliance. Our novel ultrasound technique to study the OGJ opening function shows two distinct components; firstly, related to the tonic OGJ contraction and secondly, to passive or viscoelastic properties of the OGJ.

Flow across the gastro-esophageal junction: lessons from the sleeve sensor on the nature of anti-reflux barrier.

The principles of fluid flow are critical to the understanding of flow across the gastro-esophageal (GE) junction or gastro-esophageal reflux. The mechanism by which sleeve sensor measures lower esophageal sphincter (LES) pressure is also based on the principle of fluid flow across the GE junction and can provide important insights into the nature of anti-reflux barrier. We present arguments regarding the role of the length of LES, intra-abdominal length of the LES, flap valve at the GE junction and the angle of His on the strength of anti-reflux barrier. Our conclusion is that in the presence of normal anatomy of the GE junction (absence of hiatus hernia) the pressure at the GE junction is the most important determinant of the strength of anti-reflux barrier.

Oesophageal wall stress and muscle hypertrophy in high amplitude oesophageal contractions.

Excessive wall stress is a known stimulus for muscle growth. We recently reported a thickened muscularis propria in patients with high amplitude oesophageal contractions (HAEC). The goal of this study was to determine oesophageal wall stress in normal subjects and patients with HAEC. A manometry catheter equipped with a high frequency ultrasound (US) transducer was used to record pressure and US images simultaneously in 10 healthy subjects and 11 patients with HAEC. Recordings were obtained at 2 and 10 cm above the lower oesophageal sphincter during water swallows. The changes in circumferential wall stress during oesophageal contraction in both groups are relatively small because of an increase in the wall thickness-to-radius ratio during contraction. Patients show a greater muscle thickness than normal subjects at rest and at the peak of contraction. The wall stress in patients is elevated at the 2 cm but not at the 10-cm level as compared to normal subjects. Wall strain is not different between the two groups. Increase in wall thickness during oesophageal contraction maintains low wall stress. A greater wall stress in patients with HAEC may be a stimulus for the increased wall thickness.

Esophageal perforation. A reassessment of the criteria for choosing medical or surgical therapy.

Treatment for esophageal perforation has traditionally been surgery, but development of more effective antibiotics and parenteral nutrition has led to a cautious trend toward nonoperative management. The goal of this investigation was to identify relevant presenting features that would guide a physician in making the therapeutic choice between medical and surgical therapy. Twenty-five consecutive patients with esophageal perforation--20 iatrogenic and five spontaneous--were reviewed. Treatment was medical in 12 cases and surgical in 13. The findings indicate that many patients with esophageal perforation can be treated medically. The following guidelines are suggested for selecting nonoperative treatment: (1) clinically stable patients; (2) instrumental perforations detected before major mediastinal contamination has occurred or perforations with such a long delay in diagnosis that the patient has already demonstrated tolerance for the perforation without the need for surgery; and (3) esophageal disruptions well contained within the mediastinum or a pleural loculus.

Genetic variability in triticale x bread wheat derivatives under normal and phosphorus stress regimes.

Twenty six hexaploid triticale (X Triticosecale Wittmack) X bread wheat (Triticum aestivum L. em Thell) derivatives, along with 2 bread wheat and 2 triticale checks, were grown in normal and P-stress environments. Spikes/plant and grain yield/plant, followed by peduncle length, Were the most sensitive to phosphorus deficiency, which also caused a delay in heading and maturity. The heritability and genetic advance for grain yield/plant were high in the stress environment, reflecting the effectiveness of direct selection. The 1000-grain weight, grains/spike and plant height were the important traits for phenotypic selections in both the environments.

Measurement of peak esophageal luminal cross-sectional area utilizing nadir intraluminal impedance.

BACKGROUND: Multichannel intraluminal impedance (MII) is currently used to monitor gastroesophageal reflux and esophageal bolus clearance. We describe a novel methodology to measure maximal luminal cross-sectional area (CSA) during bolus transport from MII measurements. METHODS: Studies were conducted in-vitro (test tubes) and in-vivo (healthy subjects). Concurrent MII, high resolution manometry, and intraluminal ultrasound (US) images were recorded 7-cm above the lower esophageal sphincter. Swallows with two concentrations of saline, 0.1 and 0.5 N, of bolus volumes 5, 10, and 15 cc were performed. The CSA was estimated by solving two algebraic Ohm's law equations, resulting from the two saline solutions. The CSA calculated from impedance method was compared with the CSA measured from the intraluminal US images. KEY RESULTS: The CSA measured in duplicate from B-mode US images showed a mean difference between the two manual delineations to be near zero, and the repeatability coefficient was within 7.7% of the mean of the two CSA measurements. The calculated CSA from the impedance measurements strongly correlated with the US measured CSA (R(2) ≅ 0.98). A detailed statistical analysis of the impedance and US measured CSA data indicated that the 95% limits of agreement between the two methods ranged from -9.1 to 13 mm(2) . The root mean square error of the two measurements was 4.8% of the mean US-measured CSA. CONCLUSIONS & INFERENCES: We describe a novel methodology to measure peak esophageal luminal CSA from the nadir impedance during peristalsis. Further studies are needed to determine if it is possible to measure patterns of luminal distension during peristalsis across the entire length of the esophagus from the MII recordings.

Review article: supra-oesophageal manifestations of gastro-oesophageal reflux disease and the role of night-time gastro-oesophageal reflux.

Gastro-oesophageal reflux disease (GERD) has been associated with a variety of supra-oesophageal symptoms, including asthma, laryngitis, hoarseness, chronic cough, frequent throat clearing and globus pharyngeus. GERD may be overlooked as the underlying mechanism for these symptoms because typical GERD symptoms may be absent, despite abnormal oesophageal acid exposure. Two basic mechanisms linking GERD with laryngeal symptoms have been proposed: direct contact of gastric acid with the upper airway, in some cases due to micro-aspiration, and a vagovagal reflex triggered by acidification of the distal portion of the oesophagus. Gastro-oesophageal reflux (GER) during sleep is believed to be an important mechanism for the development of supra-oesophageal complications of GERD, such as asthma and idiopathic pulmonary fibrosis (IPF). Several physiological changes during sleep, including prolonged oesophageal acid contact time, decreased upper oesophageal sphincter pressure, increased gastric acid secretion, decreased salivation, decreased swallowing and a decrease in conscious perception of acid, render an individual more susceptible to reflux-induced injury. Supra-oesophageal symptoms often improve in response to aggressive acid-suppressive therapy. However, many unanswered questions remain regarding the appropriate approach to diagnosis and treatment of patients with GERD-related supra-oesophageal symptoms. In this article we review the relationship between supra-oesophageal symptoms and GERD and, where possible, highlight the evidence supporting the role of night-time reflux as a contributing factor to these symptoms.

Oesophageal wall stretch: the stimulus for distension induced oesophageal sensation.

Recently, we reported a novel ultrasound technique to assess the biomechanical properties of the oesophagus in humans. To investigate whether the oesophageal sensation induced by oesophageal distension correlates with wall tension, wall stress or wall strain, we studied 20 healthy subjects using a manometry catheter equipped with a high-compliance bag and a high-frequency intraluminal ultrasound probe. Oesophageal distensions were performed by injecting 1-20 mL water into the bag for 20-30 s. Subjects scored the nature (heartburn or chest pain) and severity of sensation in response to distension, before and after atropine (15 microg kg(-1), i.v.). Ultrasound images of oesophagus were digitized and measurements were made to calculate oesophageal wall tension, stress and strain during distensions. Subjects experienced mostly heartburn, not chest pain, in response to oesophageal distension. Oesophageal wall strain and bag pressures correlated best with the oesophageal sensation. Atropine reduced bag pressure but did not affect the distension induced heartburn and chest pain. We conclude that heartburn is a common sensation in response to oesophageal distension in normal subjects. A strong correlation between wall strain and oesophageal sensation suggests that the wall stretch is the stimulus for nociceptive mechanoreceptors of the oesophagus.

The effect of mechanoreceptor stimulation of the laryngopharynx on the oesophago-gastric junction.

Stimulation of the pharynx by injection of minute amounts of water induces prolonged period of lower oesophageal sphincter (LOS) relaxation and augmentation of the crural diaphragm (CD) contraction. The purpose of this study was to determine the effects of stimulating mechano-receptors at the laryngopharynx on the LOS and CD by using an air pulse stimulation device. Air pulses were delivered via the internal channel of a flexible endoscope. Oesophageal, LOS, and CD pressures; CD electromyogram; and oesophageal pH 5 cm above the LOS were recorded in nine healthy subjects. Stimulation of the laryngopharynx induced LOS relaxation in the absence of swallow and oesophageal peristalsis. The stimulation of epiglottis and arytenoid produced higher incidence of LOS relaxation compared to the base of tongue. The magnitude of LOS relaxation differed significantly between the three anatomical sites, with greater relaxation occurring at the epiglottis and arytenoid compared with the base of the tongue. None of the LOS relaxations induced by laryngeal stimulation resulted in inhibition of the CD or gastroesophageal reflux. We conclude that stimulation of the laryngopharyngeal mechanoreceptors induces LOS but not CD relaxation. The LOS relaxation induced by laryngopharyngeal stimulation is not accompanied by acid reflux in fasting state.

Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study.

OBJECTIVES: Proton-pump inhibitors are often recommended in the treatment of laryngitis secondary to gastric reflux. Despite prospective treatment studies reporting high efficacy, only one previous report has been placebo-controlled and blinded. The objective of this study was to determine the efficacy of omeprazole in treating proven reflux laryngitis. STUDY DESIGN: Prospective, placebo-controlled, randomized, double-blind clinical trial. METHODS: Fifty-three patients with one or more reflux laryngitis symptoms were recruited to undergo 24-hour dual-channel pH probe testing. Thirty patients with more than four episodes of laryngopharyngeal reflux were enrolled. By random assignment, 15 patients received 40 mg omeprazole twice a day and the other 15 received placebo for a period of 2 months. Symptoms (hoarseness, throat pain, lump in throat sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn) and endoscopic laryngeal signs (erythema, edema, and mucus accumulation) were recorded initially, at 1 month, and 2 months. RESULTS: In general, most symptom scores improved over time for both the omeprazole and placebo groups. Hoarseness, when patients begin with low hoarseness symptom scores, and throat clearing improved significantly more in patients on omeprazole than in those on placebo during the 2-month study. Throat pain, lump in throat sensation, excessive phlegm, difficulty swallowing, pain with swallowing, and heartburn showed improvement in both treatment arms, signifying the possibility of a placebo effect. Endoscopic laryngeal signs did not change significantly over the course of the study for either treatment group. CONCLUSIONS: A placebo effect appears to exist in the treatment of reflux laryngitis. However, hoarseness, when initially scored low, and throat clearing resulting from reflux laryngitis are effectively treated by omeprazole.

An alternative biofeedback-based behavior modification treatment for a case of chronic constipation.

A 31-year old female with chronic constipation was referred for treatment of a paradoxical contraction of the external anal sphincter (EAS) muscle during straining to defecate. The patient was dependent on laxative use and the digital removal of feces. The present program emphasized biofeedback training of the EAS utilizing the inexpensive, noninvasive procedure of disposable surface electrodes placed on the anal verge. Outcome of treatment resulted in an 89% decrease in laxatives used, complete termination of the digital removal of feces, and a notable decrease in EAS tension. The patient was able to maintain these gains at an 8 month follow-up.

Acinetobacter sepsis in newborns.

OBJECTIVE: To evaluate the clinico-epidemiological profile of Acinetobacter sepsis in neonates. DESIGN: Retrospective study. SETTING: Level II Neonatal Care Unit. SUBJECTS: 79 neonates with blood culture positive for Acinetobacter. METHODS: Relevant information was collected on a predesigned proforma from the case records and analyzed for clinical and epidemiological characteristics. RESULTS: The incidence of Acinetobacter septicemia was 11.1/1000 live births. Fifty-five babies were hospital born, 24 were outborn. Out of these, 64.6% babies were born at term and 40.5% had a birth weight of 2500 g or more. A cluster of 53 cases was seen between May and September 1995. In cases with early onset sepsis (onset < 7 days of postnatal age), difficulty in breathing (n = 54), chest retraction (n = 35) and refusal to feed (n = 46) were seen more commonly as compared to late onset sepsis (p < 0.05). Complications observed included meningitis, bleeding manifestations and necrotising enterocolitis in three, six and five babies, respectively. The organism was sensitive to ciprofloxacin (96.2%), amikacin (92.4%) and gentamicin (87.3%). A response rate of 52.4% was observed with Ciprofloxacin in babies not responding to cefotaxime and amikacin combination. The overall mortality was 13.9%. CONCLUSION: Nosocomial Acinetobacter sepsis may affect fullterm, appropriate for gestational age babies. Clinical presentation is indistinguishable from Gram negative septicemia. Life threatening complications can also occur. Ciprofloxacin may prove to be useful drug in resistant cases.

Role of catecholamines in angiotensin induced hyperglycaemia.

The effects of angiotensin II were studied on blood sugar level in dogs. Intracerebroventricular administration of pressor dose of angiotensin caused a rise in blood sugar level. The hyperglycaemia and pressor response was not affected by bilateral vagotomy and was less marked in adrenalectomized dogs. The hyperglycaemic effect and pressor response was not observed in reserpinized and spinal vagotomized dogs. It is suggested that centrally administered angiotensin stimulates the hypothalamic or medullary accelerator neurons (central sympathetic structures) to cause a marked release of catecholamines from peripheral stores specially adrenal medulla. This excessive release of catecholamines is responsible for hyperglycaemia and pressor response of angiotensin II in dogs.