Paraoxonase (PON1) polymorphism & its relation with lipids in north west Indian Punjabis.

We investigated 190 healthy, unrelated and randomly selected, north-west Indian Punjabis (M:102; F:88) for paraoxonase (PON1) polymorphism by dual substrate method and also determined lipid variables i.e., total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) and triglycerides (TG) in them to determine any relationship between PON1 activity, PON1 phenotypes and lipids. The basal plasma paraoxonase (PON) activity, and PON activity in presence of 1 Mol NaCl (salt activated paraoxonase i.e., SAP) were estimated by using paraoxon as substrate whereas the, phenyl acetate esterase (A) activity was estimated by using phenylacetate as substrate. Based on the ratio of SAP/A activity, three distinct phenotypes of PON1 could be determined with gene frequencies of PON*A (low activity) and PON*B (high activity) allele being 0.847 and 0.153 respectively. In the whole population on partial correlation after normalising the variables and after adjusting the lipids for age and body mass index (BMI), a significant negative correlation was observed between SAP/A ratio and TC (r = -0.290; P < 0.01) and LDL (r = -0.154; P < 0.05). However, on analysis of covariance (ANCOVA) after normalizing the lipid variables and adjusting these for age and body mass index (BMI), no significant difference could be observed in lipid profile of these three phenotypes. The lack of a significant relationship between lipids and PON1 phenotypes, suggests that PON phenotype does not significantly influence the lipid profile in north-west Indian Punjabis. However, a significant negative correlation between the PON activity and TC and LDL suggests that low PON activity could be a risk factor for atherosclerosis in these subjects.

Liver span and weight in health and disease.

BACKGROUND: The liver mass, made up of independent functional units called acini, correlates with liver functions. Hepatic morphological changes causing alteration in its size and volume occur in various hepatic disorders. METHODS: Antemortem clinical liver span and postmortem liver weight was studied in 23 critically ill patients. Out of these, 8 had fulminant hepatic failure, 7 had chronic liver disease with encephalopathy and 8 had other serious illnesses (chronic renal failure 3; ischaemic heart disease 3; cerebrovascular accidents 2). We also studied postmortem liver span and liver weight in 173 healthy individuals dying of accident/terrorist attacks. RESULTS: Antemortem liver span in 23 critically ill patients was 9.9 +/- 4.7 cm (mean +/- S.D.) and postmortem liver weight was 1536.9 +/- 704.7 g (mean +/- S.D.). Antemortem liver span correlated well with the postmortem liver weight (r = 0.9635). Postmortem liver span in 173 healthy individuals was 16.3 +/- 2.7 cm (mean +/- S.D.) and liver weight was 1301.5 +/- 358.8 g (mean +/- S.D.). There was very good correlation between the postmortem liver span and liver weight (r = 0.516), height (r = 0.410) and body weight (r = 0.340) in these individuals. CONCLUSION: Liver span fortells the liver weight, hence, the functional liver mass in diseased and healthy individuals.

Effect of omeprazole on gastric bicarbonate secretion in patients with duodenal ulcer.

BACKGROUND: Omeprazole, a H+/K+ ATPase inhibitor, has been shown to reduce gastric bicarbonate secretion in cats. However, there has been no study on the effect of omeprazole on bicarbonate secretion in patients with duodenal ulcer (DU). METHODS: Fifteen men with duodenal ulcer (mean age 38 years, range 22-57) were included. Baseline gastric acid output, bicarbonate secretion, and parietal and nonparietal secretions were estimated before and after omeprazole therapy (20 mg/day) for four weeks. RESULTS: Omeprazole administration did not significantly alter bicarbonate secretion (3.3 [1.2] vs 2.4 [0.4] mmol/h), though there was significant reduction in gastric acidity (44.2 [6.6] vs 20.7 [4.6] mmol/L, p < 0.01). CONCLUSION: Omeprazole reduces acid secretion but does not affect gastric bicarbonate secretion in patients with DU.

Routes of transmission in the hepatitis E epidemic of Saharanpur.

A large waterborne epidemic of hepatitis E occurred in the city of Saharanpur (Uttar Pradesh, India) between December 1992 and April 1993. A random survey was conducted in the affected area of Saharanpur. Source of water supply, number of family members, number and characteristics of affected persons were noted. Blood, stool and water samples were collected. The incidence of hepatitis was 14% in the affected area of the city. A total of 3682 individuals were affected with the disease. Attack rate for adults was significantly higher than the children aged < 15 years (17% vs 7%; p < 0.0001). Among the adults, the attack rate was higher for males than females (23% vs 12%; p < 0.0001). The incidence of hepatitis was greater in persons using the municipal water supply (17%) as compared to hand pump (0.9%) or tubewell water (0%). There was a single peak in the epidemic. Of the 56 fresh cases, 38 (64%) occurred within two weeks, 14 within 2-4 weeks and 4 within 4-6 weeks of index cases. Serologic markers for acute hepatitis A, B and C were absent. IgM anti-HEV was positive in 20 out of 24 sera tested. Immune electron microscopy detected 27-34 nm virus-like particles (VLPs) in 2 of 8 stool specimens and in 1 of 3 water samples. The epidemic occurred due to leakage of municipal water supply pipes passing through the sewerage holes. A large waterborne epidemic of hepatitis E resulted due to contaminated water supply. VLPs were detected in water. Adults and males were commonly affected. There was no person-to-person spread.

Liver span--a comparative appraisal of various methods.

BACKGROUND: Alterations in the size and shape of liver occur in a wide variety of conditions. Liver span can be estimated by using clinical, radiological or radioisotopic methods. Chest dimensions may alter the liver span. METHOD: We evaluated the liver span in 51 healthy individuals by clinical, radiological and radioisotopic methods and its relation with chest dimensions. RESULTS: The liver span by clinical, radiological and radioisotopic methods was 10.8 +/- 1.1 cm, 12.6 +/- 1.5 cm and 13.6 +/- 1.7 cm, respectively. Liver span varied with clinical and radiological or radioisotopic method and it correlated with height of chest cage and subcostal angle in these individuals. CONCLUSION: The liver span varies with the method used and it is correlated with chest dimensions.

Silent gastroesophageal reflux in patients with bronchial asthma.

Gastroesophageal reflux (GER) is a common occurrence in patients with asthma. We performed a prospective study to detect GER in patients with asthma using pH monitoring. Twenty consecutive patients (mean age 48 +/- 14 yr, range 23-70; 13 men) with asthma of unexplained etiology were evaluated. Esophageal and gastric pH were studied both while introducing and pulling out pH probe. Upper GI endoscopy was done in all the patients before doing pH monitoring. Esophageal pH was recorded at 25 cm, 30 cm and 35 cm from the incisors. Mean esophageal pH values while introducing pH probe were 2.9 +/- 1.08 (0-5.1), 2.5 +/- 1.2 (0-5) and 1.6 +/- 1.5 (0-4.6) at 25 cm, 30 cm and 35 cm from incisors respectively. The gastric pH was 0.5 +/- 0.4 (0-2). While pulling out pH probe, pH values were 1.5 +/- 1.4 (0-4.7), 2.4 +/- 1.5 (0-5.1) and 2.9 +/- 1.4 (0-5.4) at 35 cm, 30 cm, and 25 cm from incisors respectively. Of 20 patients, 19 had pH of 4 or lower at 25 cm, 30 cm and 35 cm from incisors. The mean pH value was lower at 35 cm than at 30 cm and 25 cm (1.6 +/- 1.5 vs 2.5 +/- 1.2 and 2.9 +/- 1.08, p < 0.04). In conclusion majority of adults with asthma have silent GER as detected on pH monitoring.

Acetylsalicylic acid-induced biochemical changes in gastric juice: a failure of adaptation?

BACKGROUND: Acetylsalicyclic acid (ASA) causes gastric mucosal damage which diminishes with continued use due to adaptation. METHODS: To determine the net effect of these processes on the gastric juice, we estimated acid, osmolality, bicarbonate concentration in nonparietal gastric juice, calcium, potassium and sodium in 18 patients (9 men; mean age 32 years, range 20-46) with irritable bowel syndrome, before and after 600 mg of ASA taken post-cibum thrice daily for 4 weeks. Osmolality was determined by an osmometer, acidity by titration, and Na+, K+ and Ca++ using a sodium-potassium-calcium analyzer; bicarbonate was derived from the two-component model of Feldman. RESULTS: Gastric juice K+ and Na+ increased significantly from mean (SE) 14.6 (0.5) and 197.5 (16.3) to 16.7 (0.4) and 256.8 (18.1) mEq/L, respectively. The other parameters remained unchanged. CONCLUSION: After four weeks of ASA ingestion there is a dichotomy of gastric mucosal injury and adaptation, with preservation of acid secretion but continued loss of Na+ and K+.

Comparison of two substrates in determination of plasma cholinesterase activity & genetic variability.

Two substrates, acetyl thiocholine iodide ATCI and benzoylcholine chloride BCC were compared for the determination of plasma cholinesterase ChE levels and after incorporation of dibucaine and sodium fluoride in the assay, their usefulness in determining plasma ChE genetic variability was assessed in 64 healthy subjects. With both substrates, plasma ChE levels were found to be in the reference range. However, ATCI could detect only two variants with the usual phenotype UU in 60 of 64 [93.75%] subjects whereas with BCC 6 different groups could be determined. Though both substrates are of equal value in estimation of plasma ChE levels, BCC is definitely superior in determining its genetic variants.

Effect of sucralfate on gastric bicarbonate secretion in patients with duodenal ulcer.

BACKGROUND: Sucralfate is known to protect gastroduodenal mucosa and thereby facilitate healing of peptic ulcer. The mechanism of action of this drug is still not fully known. METHODS: We studied the effect of sucralfate treatment on gastric bicarbonate secretion in 16 patients with duodenal ulcer. RESULTS: Sucralfate administration (3 g daily for 4 weeks) stimulated bicarbonate secretion from 3.1 +/- 1.2 mmol/h to 4.6 +/- 2.0 mmol/h (p < 0.05). Gastric juice volume as well as non-parietal volume secretion also increased significantly after sucralfate therapy (p < 0.05). CONCLUSION: Sucralfate causes stimulation of non-parietal volume-dependent gastric bicarbonate secretion.

Airway response to acid instillation in esophagus in bronchial asthma.

OBJECTIVE: An increased incidence of gastroesophageal reflux has been reported in patients with bronchial asthma. We studied the pulmonary effects of acid instillation in the esophagus. METHODS: Fifteen patients with bronchial asthma and 15 healthy adults in the age group 15-50 years were studied. The control subjects were first screened for bronchial hyperreactivity by a methacholine challenge test. Patients and controls were both subjected to modified Bernstein test. Spirometry was done at baseline and after each instillation of either acid or saline. Respiratory and reflux symptoms were noted after each infusion and antacid administration. RESULTS: Five patients and one control subject had history of reflux symptoms (p < 0.05) and six patients had nocturnal asthma. There was a significant fall in FEV1/FVC after acid infusion patients; this improved significantly after antacid administration. All six patients with nocturnal asthma had respiratory signs or symptoms and had more than 20% fall in FEV1 on acid instillation in the esophagus, while none in the control group developed the same. CONCLUSIONS: Gastroesophageal reflux occurs more frequently in patients with bronchial asthma and acid instillation in the esophagus triggers bronchoconstriction.

Increased glutathione cycling and vitamin E of P. falciparum infected erythrocytes fail to prevent spontaneous haemolysis.

In an attempt to understand the pathogenesis of anaemia in Plasmodium falciparum infection, the status of erythrocyte glutathione and vitamin E content in relation to the susceptibility of infected red cells to peroxide haemolysis was examined. Synchronized cultures of the parasite with either ring-, trophozoite or schizont-infected red cells showed a gradual increase in the reduced glutathione content which was significantly higher (p < 0.05) in schizont-infected cells. Trophozoite-infected cells revealed significant increase in oxidized glutathione (p < 0.01) suggesting an increase in glutathione utilization during active erythrocytic schizogony of the parasites. The membrane antioxidant vitamin E also showed an increased accumulation in trophozoite- and schizont-infected red cells (p < 0.05) but not in the uninfected or ring-infected erythrocytes. Despite a favourable change in these antioxidants, the infected as well as uninfected red cells from parasite cultures showed enhanced peroxide haemolysis (uninfected, p < 0.05; ring-rich, p < 0.05, trophozoite- and schizont-rich, p < 0.001). The study provided direct evidence for enhanced susceptibility of red cells to lysis, including those of uninfected cells exposed to parasite products. This might explain the cause for much higher red cell loss and anaemia during P. falciparum infection than all the infected cells put together.

Effect of pentagastrin on gastric bicarbonate secretion in patients with duodenal ulcer & healthy controls.

We studied the gastric acid and bicarbonate secretion rates in 12 patients with duodenal ulcer and 6 age matched healthy controls. Measurements of gastric juice volume (nonparietal and parietal), acidity and osmolality were done. The ulcer patients secreted more acid, parietal and nonparietal fluid than controls under basal conditions and after subcutaneous pentagastrin injection (6 micrograms/kg body weight). However, the gastric bicarbonate secretion was similar in the duodenal ulcer patients and controls, both under basal state as well as after pentagastrin stimulation. The gastric acidity was similar in ulcer patients and control subjects under both the states (49.3 +2- 4.5 vs 50.0 +/- 6.0 mmol/l basally, 85.2 +/- 8.9 vs 63.4 +/- 6.6 mmol/l after pentagastrin injection respectively). Thus, gastric bicarbonate secretion was similar, whereas parietal and nonparietal volume secretions were increased in patients with duodenal ulcer as compared to controls.

Evaluation of commercially available antacid tablets.

Antacids are commonly used for the treatment of acid peptic disease. There is a need to study the relative merits of various brands of antacids available commercially. Twenty three brands of antacid tablet preparations were evaluated with regard to their composition, cost, dispersion time, pH, neutralising capacity and time taken for neutralisation. The cost of various tablets ranged from Rs 0.13 to Rs. 1.48 per tablet and the dispersion time from 20 to 90 minutes. The pH of the dispersed tablet solution ranged from 5.7 to 9.5. The neutralising capacity varied between 8 to 169 meq/tablet and the neutralizing time between 20 and 45 minutes. The cost: neutralizing ratio was calculated and ranged from 102 to 9867 x 10(-3) Rs/meq. A scoring system with a maximum score of 12 has been devised. The study provides a guide for choosing a more potent, quick neutralising and low cost antacid preparation.

Sodium and potassium content of liquid antacids.

Sodium and potassium contents of 37 commercially available liquid antacid preparations were estimated. Only nine preparations had sodium content below 60 mmol/L. The potassium content was below 1 mmol/L in 26 preparations. We conclude that caution should be exercised in selecting liquid antacid preparations in whom critically ill patients for electrolyte overload could prove harmful.

Evaluation of antacid gel preparations available commercially in the Indian market.

A scoring system based on the neutralising capacity, cost efficiency and time of buffering of twenty four commercially available antacid gels was analysed. A gel scoring eight out of the ten points was considered as the best antacid. The study provides a practical guide in choosing a quick neutralizing and low cost antacid gel.

Functional characterization of intestinal intraepithelium & lamina propria lymphocytes from Giardia lamblia infected mice.

Quantitation of T cell subsets in intraepithelium and lamina propria during the course of experimental G. lamblia infection in the inbred mice revealed increased influx of Thy 1.2+ (T cells) and Lyt 2.2+ (suppressor/cytotoxic T cells) during the establishment (3-5 day post-inoculation) and acute (9-11 day post-inoculation) phases of infection. The influx of these cells reduced as the parasite load declined. In contrast, no significant changes were noticed in lamina propria and intraepithelium Lyt 1.1+ (helper T cell) cells during the establishment or acute phase but such cells increased significantly in the decline (17-21 day post-inoculation) phase of infection. Further, both intraepithelium and lamina propria lymphocytes isolated from uninfected or infected animals failed to kill G. lamblia trophozoites in vitro in the absence or presence of antigiardial antibodies. Our data suggest that the clearance of G. lamblia trophozoites was not mediated by cytotoxic T cells. However, the induction of helper T cells during the declining phase of infection might be an important mechanism for the induction of parasite specific antibody response leading to the immune elimination of G. lamblia trophozoites from the gut.