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Biomedical subjects

W C Orr

Publications and source records attributed to W C Orr.

At least 19 recordsLinked to original sources
PubMed2005

The effect of acid suppression on sleep patterns and sleep-related gastro-oesophageal reflux.

BACKGROUND: Several studies have demonstrated that night-time gastro-oesophageal reflux affects sleep quality, and thereby impairs daytime functioning. AIM: To determine whether treatment with a proton-pump inhibitor (rabeprazole) would improve both objective and subjective measures of sleep. METHODS: Individuals with complaints of significant gastro-oesophageal reflux disease were studied by polysomnography and 24-h pH monitoring on two separate nights. On one occasion, participants received 20 mg rabeprazole b.d., and on another they received placebo. Both study conditions were preceded by a week of treatment with either rabeprazole or placebo. The order of treatments was randomized. RESULTS: Rabeprazole significantly reduced overall acid reflux, but it did not significantly reduce night-time acid contact. Rabeprazole treatment significantly improved subjective indices of sleep quality. There were no significant differences on objective measures of sleep between placebo and rabeprazole treatment. CONCLUSIONS: Consistent with other studies of pharmacological treatments for gastro-oesophageal reflux, subjective measures of sleep improved with heartburn medication but objective measures were not affected.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Review article: sleep and its relationship to gastro-oesophageal reflux.

Gastro-oesophageal reflux disease (GERD) is among the most common gastrointestinal conditions in the USA. For most symptomatic patients, reflux events occur during both daytime and night-time hours. Whereas daytime reflux events tend to be frequent but brief, reflux events that occur during sleep are comparatively less frequent but significantly longer. Longer oesophageal acid-clearance and acid-mucosal contact times during sleep are at least partly due to several physiological changes associated with sleep, including dramatic declines in saliva production and frequency of swallowing, decreased conscious perception of heartburn and consequent arousal and clearance behaviours, and slower gastric emptying. Obstructive sleep apnea syndrome and obesity seem to predispose some patients to nocturnal GERD, and the presence of either of these conditions may help to identify patients with symptoms consistent with GERD. Recognition and treatment of night-time GERD are important because it can be associated with decreased quality of life (including sleep disruption) and increased risk of serious oesophageal and respiratory complications.

Circadian Rhythm↗
PubMed2003

The efficacy of omeprazole twice daily with supplemental H2 blockade at bedtime in the suppression of nocturnal oesophageal and gastric acidity.

BACKGROUND: It has been presumed that nocturnal acid breakthrough may pose a risk for the development of nocturnal gastro-oesophageal reflux. AIM: To investigate the occurrence of gastro-oesophageal reflux and acid breakthrough during polygraphically monitored sleep under conditions of powerful acid suppression with omeprazole 20 mg b.d. and an additional dose of ranitidine at bedtime. METHODS: Nineteen individuals with symptomatic gastro-oesophageal reflux disease were studied. Each individual was studied on two occasions subsequent to 1 week of 20 mg of omeprazole treatment b.d. Subjects underwent 24-h oesophageal and gastric pH recording, with polysomnographic monitoring. Participants received either 150 mg ranitidine at bedtime or placebo, prior to a provocative meal. RESULTS: Ranitidine administration resulted in a significant (P < 0.01) reduction in the percentage of time the intragastric pH < 4.0. There was no significant difference with regard to measures of gastro-oesophageal reflux, and reflux events were not noted to occur with a significantly greater frequency during periods of nocturnal acid breakthrough compared with control intervals without acid breakthrough. CONCLUSIONS: The administration of 150 mg ranitidine at bedtime did not significantly alter the occurrence of sleep-related gastro-oesophageal reflux.

Adult↗
PubMed2003

Detection of gastric slow wave uncoupling from multi-channel electrogastrogram: validations and applications.

Current methodology of single channel electrogastrography is unable to detect coupling or uncoupling of gastric slow waves, which is crucial for gastric emptying. In this study, a new methodology, called cross-spectral analysis method, was established to compute the coupling percentage of multi-channel gastric slow waves recorded using serosal electrodes and electrogastrogram (EGG). Two experiments were performed to validate the method and demonstrate its applications in clinical research. In experiment 1, simultaneous recordings of gastric slow waves were made in five dogs from serosal electrodes and cutaneous electrodes. In experiment 2, four-channel fasting EGGs were made in 10 volunteers for 30 min during waking and 30 min during non-rapid eye movement (REM) sleep. The validation study (experiment 1) showed that the slow wave coupling calculated from the EGGs was correlated with that computed from the serosal recordings. The gastric slow wave coupling percentages detected from both serosal and cutaneous recordings were significantly impaired during vasopressin infusion (6.3 +/- 2.6 vs 62.4 +/- 6.3, P < 0.001 for serosal recordings; 6.7 +/- 3.0 vs 57.2 +/- 2.7, P < 0.001 for cutaneous recordings), and the coupling percentages respectively calculated from serosal and cutaneous recordings were significantly correlated during the baseline recording period (R = 0.922, P < 0.05) and vasopressin infusion period (R = 0.916, P < 0.05). In experiment 2, the gastric slow wave became less coupled when healthy volunteers fell asleep. The percentage of slow wave coupling calculated from the EGGs was 68.2 +/- 17.9% during waking but 41.9 +/- 20.8 during non-REM sleep (P < 0.05). The method developed in this study is reliable for the detection of slow wave uncoupling from multi-channel EGGs. Gastric slow wave coupling is impaired during vasopressin infusion and sleep. These data suggest that this method has potential applications in physiological and clinical studies.

Adult↗
PubMed2002

Efficacy of a motilin receptor agonist (ABT-229) for the treatment of gastro-oesophageal reflux disease.

BACKGROUND: ABT-229 is a potent motilin agonist without significant antibiotic activity. It has been shown to improve gastric emptying in humans and to increase lower oesophageal sphincter pressure in cats. AIM: To assess the efficacy of four different doses of ABT-229 (1.25 mg, 2.5 mg, 5 mg, 10 mg b.d.) compared to placebo in the treatment of gastro-oesophageal reflux disease, and to determine its safety in patients with gastro-oesophageal reflux disease. METHODS: In a double-blind, multicentre study, 324 patients with heartburn were randomized to receive four different doses of ABT-229 or placebo for 8 weeks. The efficacy was evaluated by Patient Symptom Questionnaire, daily diary, endoscopy and global evaluation of efficacy. RESULTS: There were no statistically significant improvement scores for any of the ABT-229 treatment groups vs. the placebo group in any of the efficacy parameters. Reflux symptom scores were significantly worse after treatment in the dyspeptic group. ABT-229 appeared to be well tolerated and safe in total daily doses up to 20 mg. CONCLUSION: ABT-229 appears to have limited, if any, clinical utility in the treatment of gastro-oesophageal reflux disease.

Dose-Response Relationship, Drug↗
PubMed2001

Selectivity of protein oxidative damage during aging in Drosophila melanogaster.

The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.

Aconitate Hydratase↗
PubMed2001

The peroxiredoxin gene family in Drosophila melanogaster.

Five peroxiredoxin genes have been identified in Drosophila melanogaster on the basis of a genome-wide search. Three of the genes (DPx-4156, DPx-4783, and DPx-5037) fall into the 2-Cys subgroup, while the other two (DPx-2540 and DPx-6005) belong to the 1-Cys subgroup. Using cDNAs, all five were expressed in E. coli and the purified recombinant proteins were shown to reduce H(2)O(2) in the presence of dithiothreitol. The three 2-Cys Prx were also shown to be active in the thioredoxin system and were, consequently, classified as thioredoxin peroxidases. Antisera raised against the DPx-4783 recombinant protein crossreacted with all family members and recognized protein species of the predicted sizes (22-27 kD). All five family members, when individually overexpressed in Drosophila S2 cells, conferred some resistance to H(2)O(2) treatment, as measured by cell viability. Functional diversification of the Drosophila peroxiredoxin family members was suggested by two lines of evidence: (i) the patterns of mRNA accumulation varied for the different genes during development and (ii) recombinant proteins fused to an epitope tag and overexpressed in Drosophila cells, differed in subcellular localizations--three proteins occurred in the cytosol, one was localized to the mitochondria, and one was found to be secreted.

Amino Acid Sequence↗
PubMed2001

Antioxidant status and stress resistance in long- and short-lived lines of Drosophila melanogaster.

The purpose of this study was to understand the nature of the biochemical and physiological variations between genetically different lines of Drosophila melanogaster. Selection for early or delayed reproduction has given rise to lines with substantial and heritable differences in longevity. The hypotheses tested were that either: (i) a compensatory slowing of metabolism, (ii) increased antioxidative enzyme activities, or (iii) elevated resistance to stressful conditions underlie these differences in longevity. The metabolic rate, metabolic potential (i.e. total amount of oxygen consumed during average lifespan) and speed of walking were all greater in long-lived than in short-lived flies, but there was no enhancement of antioxidant defenses. In fact, catalase activity was significantly lower in the long-lived flies. Long life was largely maintained under heat stress and starvation conditions, and was maintained to a lesser extent upon exposure to paraquat, a superoxide radical generator. In contrast, the 'short-lived' flies had a longer lifespan under cold stress and hyperoxia, also an inducer of radical generation. These results contradict the first two hypotheses and suggest that alleles underlying either long or short life are linked with enhanced resistance to specific kinds of stress, which may account for the preservation of these alleles in the parental population.

Animals↗
PubMed2001

The role of age and salivation in acid clearance in symptomatic patients with gastro-oesophageal reflux disease.

BACKGROUND: Cisapride has been shown to have not only prokinetic effects, but also salivary stimulating effects. Both of these mechanisms play an important role in the acid clearance of the oesophagus. AIM: To access the efficacy of cisapride in facilitating acid clearance in patients with symptomatic gastro-oesophageal reflux disease. METHODS: Fifteen older adults and 15 younger adults with symptomatic gastro-oesophageal reflux disease completed the study. The acid clearance test was accomplished by infusing 15 mL of 0.1 N HCl into the distal oesophagus, and the number of swallows was determined to achieve an oesophageal pH of 4.0. This was accomplished under baseline conditions and salivary stimulation with a peppermint lozenge. After 1 week of treatment with cisapride (10 mg, q.d.s.), the acid clearance test was repeated. RESULTS: The lozenge produced a significant decrease in the number of swallows compared to baseline in both groups (P < 0.01). There was a significant decrease in the number of swallows after the treatment with cisapride compared to baseline in both groups (P < 0.01). No significant difference was found in the number of swallows when comparing cisapride with lozenge. CONCLUSIONS: Cholinergic stimulation of salivation is an effective means of facilitating oesophageal acid clearance. Drugs, such as 5 hydroxytriptamine (5-HT)4-receptor agonists, should be considered as potentially important compounds in the treatment of gastro-oesophageal reflux disease.

Aged↗
PubMed2001

Diarrhea- and constipation-predominant IBS patients differ in postprandial autonomic and cortisol responses.

OBJECTIVE: As the primary link between brain and gut, autonomic and endocrine dysfunction may play a role in the pathophysiology of the irritable bowel syndrome (IBS). The aim of this study was to assess autonomic, endocrine, and symptomatic responses to food intake in diarrhea-predominant and constipation-predominant IBS patients, compared to normals. METHODS: Twelve women with diarrhea-predominant or alternating IBS (IBS-D), 12 women with constipation predominant IBS (IBS-C), and 20 healthy women participated. GI symptoms, saliva cortisol concentration, heart rate, and heart rate variability were assessed at baseline and after a meal. Spectral analysis of heart rate variability was used as a measure of the sympathovagal regulation of the heart rate. RESULTS: Both groups of IBS patients showed a significant postprandial increase in GI symptoms. IBS-D showed a significant increase in the low frequency/high frequency band ratio and a decrease in the high frequency band power during the first postmeal period, which was significantly different, not only from controls, but also from IBS-C. IBS-D also showed a significant postprandial increase in cortisol, which was not evident in controls or IBS-C. There was a significant correlation between the vagal response and the postprandial increase in GI symptoms in IBS-D (r = 0.6, p < 0.05). CONCLUSIONS: These findings support the notion that the IBS symptom groups are characterized by different physiological responses to visceral stimuli, and point to a role of autonomic pathways in IBS symptomatology.

Adult↗
PubMed2000

Decreased mitochondrial hydrogen peroxide release in transgenic Drosophila melanogaster expressing intramitochondrial catalase.

The objective of this study was to develop strategies for manipulating oxidative stress transgenically in a multicellular organism. Ectopic catalase was introduced into the mitochondrial matrix, which is the main intracellular site of H2O2 formation and where catalase is normally absent. Transgenic Drosophila melanogaster were generated by microinjection of a P element construct, containing the genomic catalase sequence of Drosophila, with the mitochondrial leader sequence of ornithine aminotransferase inserted upstream of the coding region. Total catalase activities in whole-body homogenates of 10-day-old flies from four transgenic lines were approximately 30-160% higher than those from the parental and four vector-only control lines. Expression of catalase in the mitochondrial matrix was confirmed by immunoblotting and catalase activity assays. Mitochondrial release of H2O2 was decreased by approximately 90% in the transgenic lines when compared to levels in vector-only controls. This in vivo system provides a novel model for examining the functional significance of decreased mitochondrial H2O2 release.

Animals↗
PubMed2000

Catalase expression in Drosophila melanogaster is responsive to ecdysone and exhibits both transcriptional and post-transcriptional regulation.

In the present study, we have examined catalase protein and mRNA levels and the factors that may regulate catalase expression in Drosophila melanogaster during development. Both mRNA and protein changes are in general accord with variations in ecdysteroid titer during development. Differences in mRNA and protein accumulation profiles, particularly in embryos and young adults, suggest that catalase may be regulated at both transcriptional and post-transcriptional levels. It was possible to induce catalase expression by administering exogenous 20-hydroxyecdysone (Ec) in culture at certain stages of development (usually at time points corresponding to previously observed hormone and catalase peaks). Experiments with exogenous administration of Ec, cycloheximide, and actinomycin D suggest a complex interplay of factors affecting catalase expression. In cultured third instar larvae, superinduction of catalase occurred in the presence of both Ec and cycloheximide. If ecdysteroid production was suppressed prior to antibiotic treatment by temperature upshift of the conditional mutant dre4(e55), superinduction occurred mostly at the protein level. In cultured adult abdomens, we observed induction by Ec and superinduction in the presence of hormone and translation or transcription inhibitors. Unlike what was observed in larvae, superinduction of catalase protein was dramatically more pronounced in control flies.

Animals↗
PubMed2000

Current issues concerning the role of oxidative stress in aging: a perspective.

The main tenet of the oxidative stress hypothesis of aging is that accrual of molecular oxidative damage is the principal causal factor in the senescence-related loss of ability to maintain homeostasis. This hypothesis has garnered a considerable amount of supportive correlational evidence, which is now being extended experimentally in transgenic Drosophila over-expressing antioxidative defense enzymes. Some of these studies have reported extensions of life span, while others have not. Interpretation of life spans in poikilotherms is complicated by a number of factors, including the interrelationship between metabolic rate and longevity. The life spans of poikilotherms can be extended multi-fold by reducing the metabolic rate but without affecting the metabolic potential, i.e., the total amount of energy expended during life. A hypometabolic state in poikilotherms also enhances stress resistance and activities of antioxidative enzymes. It is emphasized that extension of life span without simultaneously increasing metabolic potential is of questionable biological significance.

Aging↗
PubMed2000

Gastric myoelectric activity in older adults treated with cisapride for gastro-oesophageal reflux disease.

BACKGROUND: The incidence of both gastro-oesophageal reflux disease (GERD) and upper gastrointestinal motility disorders appears to increase with age. However, there is a dearth of data concerning the utility of a prokinetic agent such as cisapride in the treatment of older adults with symptomatic GERD. AIM: To investigate the incidence of electrogastrographic abnormalities in older adults with and without GERD symptoms, as well as the effect of cisapride therapy on symptoms of GERD and electrogastrographic responses. METHODS: We report on 18 older adults with symptomatic GERD and 10 older adult controls (mean ages 71 and 75 years, respectively). Subjects underwent electrogastrographic evaluation pre- and postprandially under baseline conditions and after 1 month of treatment with 10 mg q.d.s. of cisapride. RESULTS: Heartburn frequency and postprandial fullness were both significantly (P < 0. 05) reduced after cisapride treatment. Acid contact time was not significantly changed. The percentage of 2-4 cpm activity in the electrogastrographic analysis was significantly (P < 0.05) increased with cisapride treatment, and the instability coefficient was significantly (P < 0.05) diminished with cisapride treatment. CONCLUSIONS: Enhanced gastric functioning and reduction in heartburn suggest that cisapride is efficacious in the treatment of older adults with symptomatic GERD, and that gastric dysrhythmias and postprandial fullness are resolved with cisapride treatment.

Aged↗
PubMed2000

Time-frequency analysis of heart rate variability using short-time fourier analysis.

This study was done to introduce new parameters derived by time frequency analysis of heart rate variability data. Four simulation experiments were carried out to compare the short-time Fourier transform (STFT) analysis method to the traditional overall spectral analysis method. Sinusoidal signals were generated with identical total power in the high-frequency band, but varying time-frequency and time-amplitude information. The STFT method was also applied to heart rate variability data from the stages of normal human sleep. Data analysis included computation of the power in the high-frequency band by overall spectral analysis. The instability coefficients (ICs) of the frequency and power in the high-frequency band were derived by STFT analysis. The ICs derived by the STFT method were able to describe time-frequency and time-amplitude variations in sinusoidal signals which contained identical total power in a specified frequency range. The ICs of the frequency and power were able to differentiate variations in vagal activity between the stages of human sleep and waking. The ICs represent new parameters derived by the STFT method, and allow the detection and quantification of short-lasting time-frequency and time-amplitude variations that remain obscured by overall spectral analysis.

Adult↗
PubMed2000

Proximal migration of esophageal acid perfusions during waking and sleep.

OBJECTIVE: Proximal acid migration resulting from gastroesophageal reflux has been implicated in aerodigestive complaints and disorders. This study was designed to investigate the effects of acid volume, posture, and sleep on proximal esophageal acid migration (drop in pH to <4.0). METHODS: The study was performed in 15 healthy adults. A distal esophageal acid perfusion technique to simulate gastroesophageal reflux was used. Esophageal acid perfusions of 1 ml and 3 ml were accomplished at a site 5 cm above the proximal border of the lower esophageal sphincter in the upright and supine positions during waking, and during polysomnographically monitored sleep. Esophageal pH was recorded by two sensors located in the mid- and proximal esophagus at 10 and 15 cm above the lower esophageal sphincter. RESULTS: Acid volume clearly increased the incidence of migration to the mid and proximal sensors during both waking and sleep, and also significantly increased acid clearance time. Posture failed to significantly affect the incidence of acid migration and acid clearance. Sleep clearly enhanced migration to the proximal pH sensor of even those perfusions as small as 1 ml. For instance, 40% of 1 ml perfusions during sleep migrated to the proximal sensor compared with <1% during waking. Acid clearance times were significantly longer during sleep as measured by the mid- and proximal esophageal pH sensors. CONCLUSIONS: In healthy individuals, volume enhances the likelihood of migration to both mid- and proximal esophagus, and significantly prolongs clearance time in the waking state. Posture appears to be a less significant parameter with regard to both the incidence of acid migration and acid clearance. Sleep is a significant risk factor for acid migration to the proximal esophagus for even minute volumes, and markedly prolongs acid clearance.

Adult↗
PubMed2000

Autonomic regulation of cardiac function during sleep in patients with irritable bowel syndrome.

OBJECTIVE: Several studies have provided evidence of abnormal autonomic activity in irritable bowel syndrome (IBS), suggesting that abnormal central nervous system-autonomic nervous system arousal mechanisms may be part of its pathophysiology. The goal was to investigate cardiac sympatho-vagal balance during waking and the different stages of sleep using heart rate variability analysis in IBS patients compared to healthy controls. METHODS: A total of 15 IBS patients (13 female, two male, mean age 34.9 +/- 2.1 yr) and 15 controls (13 female, two male, mean age 36.2 +/- 2.3 yr) were studied during 1 h of pre-sleep quiet waking and during seven-hours of sleep. Polysomnography was used for the determination of state of consciousness. Electrocardiography provided the beat-to-beat intervals, which were then subjected to spectral analysis for determination of the percentage of energy in the low and high frequency bands, respectively. The low frequency/high frequency band ratio was also calculated. For each subject, heart rate variability analysis was performed using 15-min segments of waking, non-rapid eye movement sleep, and rapid eye movement sleep. RESULTS: The low frequency band power was significantly greater in IBS patients during waking. No group differences were found in high frequency band power during any state. The low frequency to high frequency band ratio was significantly greater in IBS patients during rapid eye movement sleep. CONCLUSIONS: IBS patients have greater sympathetic activity during waking and greater overall sympathetic dominance during rapid eye movement sleep. These results support the presence of autonomic abnormalities in patients with IBS. The possibility is discussed that sympathetic dominance during rapid eye movement sleep may play a role in sensitizing the gut to waking stimulation.

Adult↗