The effect of antireflux treatment on patients with gastroesophageal reflux disease undergoing a mental arithmetic stressor.

BACKGROUND: Acute stress exacerbates heartburn in gastroesophageal reflux disease (GERD) patients by enhancing the perceptual responses to intraesophageal acid. The aim of the study was to determine if antireflux treatment can still alter stimulus response functions to acid in patients undergoing acute stress as compared with placebo. METHODS: Symptomatic GERD patients with erosive esophagitis (EE) or an abnormal pH test were included. Patients underwent stimulus response functions to intraesophageal acid perfusion using the mental arithmetic stressor test. Thereafter, patients were randomized (2 : 1 ratio) to either esomeprazole 40 mg once daily or placebo for 8 weeks. On the last day of treatment, subjects underwent stimulus response functions to intraesophageal acid perfusion using a similar stressor as baseline. KEY RESULTS: A total of 31 patients were randomized into the treatment arm (mean age 48.6 ± 2.8, M/F 21/10) and 16 into the placebo arm (mean age 52.3 ± 4.3, M/F 12/4). In the esomeprazole group, there was a significant increase in lag time to symptom perception (P = 0.02) and decreased in intensity rating (P = 0.01) as well as acid perfusion sensitivity score (P = 0.01). There was no significant difference in any of the stimulus response functions to acid in the placebo group between baseline and treatment. Interpersonal sensitivity was the only independent clinical predictor factor for response to antireflux treatment. CONCLUSIONS & INFERENCES: Long-term antireflux treatment with a proton pump inhibitor is effective in reducing esophageal perception responses to acid during acute stress.

Increased oesophageal acid exposure at the beginning of the recumbent period is primarily a recumbent-awake phenomenon.

BACKGROUND: A significant increase in oesophageal acid exposure during early recumbent period has been demonstrated. AIM: To determine if acid reflux during the early recumbent period occurs in the recumbent-asleep or recumbent-awake period using a novel integrative actigraphy and pH programme. METHOD: Thirty-nine subjects with heartburn at least three times a week were included. Subjects underwent pH testing concomitantly with actigraphy. Simultaneously recorded actigraphy and pH data were incorporated using a novel integrative technique to determine sleep and awake periods. Characteristics of acid reflux were compared between the recumbent-awake and recumbent-asleep periods. RESULTS: Seventeen (44.7%) subjects had acid reflux events during recumbent-awake period as compared to seven (18.4%) in the corresponding recumbent-asleep period (P = 0.046). The mean number of acid reflux events in recumbent-awake period was significantly higher than in the corresponding recumbent-asleep period (8.1 +/- 4.4 vs. 3.2 +/- 1.5, P < 0.001). In the recumbent-awake period, 38.4% of acid reflux events were associated with GERD-related symptoms as compared with 3.7% of acid reflux events during the corresponding recumbent-asleep period (P = 0.01). CONCLUSION: Increased acid reflux in the early recumbent period occurs primarily during the recumbent-awake and not during the recumbent-asleep period.

Riser's reflux--an eye-opening experience.

BACKGROUND: Patients with gastro-oesophageal reflux disease (GORD) commonly report waking up in the morning with a sour or bitter taste in their mouth. The aim of the study was to compare the prevalence and frequency of acid reflux events prior to and immediately after awakening from sleep in the morning between GORD patients and normal subjects. METHODS: Thirty-nine patients with heartburn at least three times a week and abnormal pH test and nine healthy controls were included. All subjects were evaluated by demographic and GORD Symptom Checklist questionnaires. Subjects underwent pH testing concomitantly with actigraphy. A novel technology that simultaneously integrates raw actigraphy and pH monitoring data was utilized to determine the presence, frequency, and characteristics of acid reflux events prior to (up to 1 h) and immediately after (10 and 20 min) awakening from sleep in the morning. KEY RESULTS: Nineteen (48.7%) of the GORD patients had an acid reflux event within the first 20 min after awakening from sleep in the morning as compared to only seven (17.9%) during the hour prior to awakening. Within the first 10 and 20 min after awakening, patients had a total of 32 and 60 acid reflux events, respectively, as compared to 14 during the 1 h prior to awakening (P < 0.05). None of the healthy control patients demonstrated any reflux events during these three studied periods (P < 0.001). CONCLUSIONS & INFERENCES: Riser's reflux is very common among GORD patients and possibly may explain reports of early-morning GORD symptoms.

Epidemiology and clinical outcome of enterococcal bacteraemia in an acute care hospital.

OBJECTIVE: To determine the epidemiology and clinical outcome of enterococcal bacteraemia in an acute care hospital. MATERIALS AND METHODS: This is a retrospective study on enterococcal bacteraemia in an acute hospital from January 1999 to June 2001. Patients' clinical case notes were reviewed and their demographic, clinical and microbiological data were recorded. RESULTS: A total of 42 patients (25 males and 17 females) were included in the study, their mean age was 74.8+/-10.9 years. The majority of them had underlying diabetes mellitus and neurological disease. Seventeen patients required intensive care. Sources of enterococcal bacteraemia were identified in 21 cases (urinary tract, 13 patients; hepatobiliary, five; cardiovascular, two and soft tissues, one patient). Eighteen patients had prior invasive procedures. All the Enterococcus species isolated were vancomycin-susceptible; however, eight were ampicillin-resistant and 13 had high-level gentamicin resistance. Shock, disseminated intravascular coagulopathy, acute renal failure and cardiorespiratory arrest occurred in 42% of the cases. Antibiotics were prescribed appropriately in 31 patients and seven deaths were recorded. Of the 11 patients who received inappropriate therapy, six deaths were recorded. Inappropriate antibiotic therapy was associated with mortality. The mortality rate was 31%. Only one patient had a relapse of enterococcal bacteraemia from urinary tract infection secondary to underlying ureteric stricture. There were no vancomycin resistant cases. CONCLUSION: Urinary tract infection was the most common source of enterococcal bacteraemia. Appropriate antibiotics were essential in treating bacteraemia to reduce mortality. Vancomycin-resistant Enterococcus was not detected. The presence of comorbid conditions and invasive procedures in patients with enterococcal bacteraemia were found in 86 and 71% of patients, respectively.

Pregnenolone metabolism in testicular homogenates of macaques (Macaca fascicularis): some effects of relaxin and freezing.

The metabolism of varying quantities of pregnenolone has been studied in nuclei-free homogenates from Macaca fascicularis testes by using capillary gas chromatography, after derivatization of metabolites as O-methyl oximes/trimethylsilyl ethers. Evidence was obtained indicating that both pathways for testosterone biosynthesis were operating. 5-Androstene-3 beta, 17 beta-diol was formed in especially high quantities. Two 16-androstenes, namely 5,16-androstadien-3 beta-ol and 5 alpha-androst-16-en-3 beta-ol, were also quantitatively important as metabolites. Co-incubation of stored homogenates with relaxin resulted in 80-100% reduction of the formation of all metabolites quantified except for 5 alpha-androst-16-en-3-one, which was stimulated. Freezing the homogenates at -10 degrees C for 3 weeks resulted in marked 4- to 6-fold reduction in the yields of testosterone and of the 5-ene and 4-ene metabolites from pregnenolone.

Identification of the reaction products of the purified hyaluronidase from stonefish (Synanceja horrida) venom.

Recently we purified to homogeneity hyaluronidase from stonefish (Synanceja horrida) venom, for the first time from a marine source [Poh, Yuen, Chung & Khoo (1992) Comp. Biochem. Physiol., in the press]. In the present study the reaction products of the hyaluronidase purified from stonefish venom were analysed. It produced tetra-, hexa-, octa- and deca-saccharides as major end products, but not disaccharides. The structure of the tetrasaccharide product was determined by enzymic analysis, in conjunction with h.p.l.c. and by 1H n.m.r., as GlcA beta 1-3GlcNAc beta 1-4GlcA beta 1-3GlcNAc. Chemical shifts of the structural-reporter-group protons of the constituent monosaccharides for the tetrasaccharide have been assigned. The enzyme did not act on chondroitin sulphate or dermatan sulphate. The results indicate that the stonefish hyaluronidase is an endo-beta-N-acetylglucosaminidase specific for hyaluronate.

Purification and partial characterization of hyaluronidase from stonefish (Synanceja horrida) venom.

1. A marine hyaluronidase was purified 261-fold from the stonefish (Synanceja horrida) crude venom using Sephacryl S-200 HR and heparin affinity-gel chromatography. 2. Stonefish hyaluronidase has a pI of 9.2, a mol. wt of 62,000 and it was purified to a very high spec. act. of 1.6 x 10(6) NFU/mg protein. 3. It was heat sensitive and was inhibited by Cu2+, Hg2+ and heparin. 4. Stonefish hyaluronidase did not contain any haemorrhagic or lethal activity. 5. The N-terminal sequence of stonefish hyaluronidase has been determined to be A-P-S-X-D-E-G-N-K-K-A-D-N-L-L-V-K-K-I-N.

Biological activities of Synanceja horrida (stonefish) venom.

Some biological and neurochemical properties of the venom of stonefish (Syanceja horrida) were investigated. The venom exhibited oedema-inducing, haemolytic, hyaluronidase, thrombin-like, alkaline phosphomonoesterase, 5' nucleotidase, acetylcholinesterase, phosphodiesterase, arginine esterase, and arginine amidase activities. Recalcification clotting time, prothrombin, and kaolin-cephalin clotting times were increased 1.7-2.3- and 2.4-fold respectively. The LD50 (i.v. mouse) was 300 micrograms/Kg. Its effects on uptake and stimulation of neurotransmitter synthesis and release were observed in rat brain synaptosomes. In the presence of 100 micrograms venom, uptake of [methyl-3H] choline in rat brain synaptosomes was inhibited 70%, while that of 4-amino-n-[U-14C] butyric acid was inhibited 20%. The toxin also stimulated the release of [3H]-acetylcholine from the synaptosomes.

Purification and partial characterization of stonustoxin (lethal factor) from Synanceja horrida venom.

1. The lethal factor of the stonefish (Synanceja horrida) venom, designated as the stonustoxin, was purified to homogeneity by a two-step procedure on Sephacryl S-200 High Resolution (HR) gel permeation and DEAE Bio-Gel A anion exchange chromatography. 2. Stonustoxin has a native mol. wt of 148,000 and an isoelectric point of 6.9. 3. SDS-polyacrylamide gel electrophoresis revealed two subunits (designated alpha and beta) with mol. wts of 71,000 and 79,000, respectively. 4. The amino acid composition of both subunits and the N-terminal amino acid sequence of the beta subunit were also determined. 5. Purified stonustoxin had an LD50 of 0.017 microgram/g which is 22-fold more potent than that of the crude venom. 6. The toxin exhibited potent haemolytic activity in vitro and edema-inducing activity with a minimum edema dose (MED) of 0.15 micrograms in mouse paw. The edema effect was not antagonized by diphenhydramine.

The lethal and biochemical properties of Bungarus candidus (Malayan krait) venom and venom fractions.

Bungarus candidus venom exhibited high hyaluronidase, acetylcholinesterase and phospholipase A activities; low proteinase, 5'-nucleotidase, alkaline phosphomonoesterase and phosphodiesterase activities and moderately high L-amino acid oxidase activity. SP-Sephadex C-50 ion exchange chromatographic fractionation of the venom and Sephadex G-50 chromatography of the major lethal venom fractions indicate that the venom contains at least two highly lethal, basic phospholipases A with LD50 (i.v.) values of 0.02 micrograms/g (F6A) and 0.18 micrograms/g (F4A), respectively; as well as two polypeptide toxins with LD50 (i.v.) values of 0.17 micrograms/g and 0.83 micrograms/g, respectively. The major lethal toxin is the basic lethal phospholipase A, F6A, which accounts for approximately 13% of the venom protein and has a mol. wt of 21,000.

Intracellular distribution of pregnenolone metabolites in testis of macaque (Macaca fascicularis).

The metabolism of pregnenolone in subcellular fractions of the testes of the macaque (Macaca fascicularis) has been studied using capillary gas chromatography to characterize and quantify the metabolites, after their conversion into the O-methyloxime and/or trimethylsilyl ether derivatives. The microsomal incubations yielded the greatest quantities of metabolites, with lesser amounts in the mitochondrial fraction. The cytosolic fraction contained no significant quantity of metabolites after incubation, except for 5alpha-androst-16-en-3 beta-ol. This, and other odorous androst-16-enes, found in the microsomal fraction, are of particular interest in the context of animal communication because of their possible pheromonal role. Pregnenolone was converted into androst-5-ene-3 beta,17 beta-diol, androst-4-ene-3,17-dione and testosterone, suggesting that both classical pathways for testosterone synthesis were operating. Testosterone was further converted into 5 alpha-reduced androstanediols, especially in the microsomal fraction.