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Biomedical subjects

W C Orr

Publications and source records attributed to W C Orr.

At least 55 records · Page 3Linked to original sources

Patterns of gastric myoelectrical activity in human subjects of different ages.

The aim of this study was to investigate the developmental change of gastric myoelectrical activity in humans. Five groups of healthy subjects were studied, including 10 preterm newborns, 8 full-term newborns, 8 full-term infants (ages 2-6 mo), 9 children (ages 4-11 yr), and 9 adults. Gastric myoelectrical activity was recorded using surface electrogastrography for 30 min before and 30 min after a test meal in each subject. Spectral analysis methods were applied to compute the parameters of the electrogastrogram (EGG). The results showed that the percentage of 2- to-4-cycles/min (cpm) slow waves was 26.6 +/- 3.9% in the preterm newborns, 30.0 +/- 4.0% in full-term newborns, 70 +/- 6.1% in 2- to 6-mo-old infants (P < 0.001 compared with newborns), 84.6 +/- 3.2% in 4- to 11-yr-old children (P < 0.03 compared with infants), and 88.9 +/- 2.2% in the adults (P > 0.05 compared with children). In conclusion, gastric slow waves are absent at birth, and there is a maturing process after birth. Age-matched controls are necessary for the interpretation of EGG data from neonates and infants, whereas EGG data in children are the same as in adults.

Adult↗

Molecular analysis of the Drosophila catalase gene.

The main objective of this study was to isolate and characterize the catalase gene and accompanying cis-regulatory regions in Drosophila melanogaster. Genomic clones were obtained on the basis of cross-hybridization to catalase cDNA and a 7-kb SalI-KpnI fragment encompassing the catalase gene was introduced into Drosophila by P element-mediated transformation. A single transgene, when placed in a catalase null background, was sufficient to restore resistance to H2O2 as well as reduce susceptibility to early death. DNA sequence of the catalase gene domain was obtained. This included 1365 bp of sequence upstream of the transcription initiation site and 1423 bp downstream of the termination codon. The Drosophila catalase gene is composed of 3 exons, encoding 19, 307, and 180 amino acids, which are separated by 3520- and 96-bp introns. Sequence analysis of the promoter domain is presented, revealing multiple sequence similarities between catalase and Cu,Zn superoxide dismutase promoter domains. Developmental RNA get analysis shows that peaks of catalase mRNA accumulation correspond roughly with major peaks of ecdysone titer during third instar and pupal stages. Candidate ecdysone response element sequences are noted downstream of the catalase polyadenylation site.

Amino Acid Sequence↗

Role of sham feeding in postprandial changes of gastric myoelectrical activity.

The aim of this study was to evaluate the role of sham feeding in postprandial changes of gastric myoelectrical activity. Eighteen asymptomatic healthy volunteers (10 men, 8 women; mean age: 31), with no history of gastrointestinal disease were studied. Gastric myoelectrical activity was recorded for 30 min at baseline, 30 min after sham feeding, and 1 hr after eating, using surface electrogastrography. The electrogastrogram (EGG) was analyzed by spectral analysis. It was found that the changes of postprandial EGG parameters were significantly correlated with those after sham feeding (EGG dominant power: r = 0.6, P < 0.01; dominant frequency: r = 0.8, P < 0.001; percentage of regular slow waves: r = 0.7, P < 0.003). We concluded that intrinsic gastric electrical activity can be altered by sham feeding and the cephalic phase of digestion plays an important role in the postprandial response of gastric myoelectrical activity.

Adult↗

Effect of severe gastroesophageal reflux on sleep stage in patients with aperistaltic esophagus.

Polysomnography and esophageal pH studies were conducted in 13 patients with an aperistaltic esophagus; seven of these had scleroderma and six were patients treated for achalasia. The percentage total time of pH<4.0 when recumbent exceeded 30% for both groups. There was a total of 51 reflux events for both groups. There were 22 reflux events recorded for both groups that were less than 5 min in length and 29 events greater than 5 min. In 26 of 32 (81%) instances, patients either began awake and went to sleep during a reflux event or did not awake during a reflux event. Only six of 32 (19%) reflux events caused sleep disruption. We conclude that even the severe reflux demonstrated in this subset of patients does not always disrupt sleep. Patients may have severe prolonged reflux and not arouse.

Acute Disease↗

Simultaneous overexpression of copper- and zinc-containing superoxide dismutase and catalase retards age-related oxidative damage and increases metabolic potential in Drosophila melanogaster.

The objective of this study was to elucidate the nature of the mechanisms by which overexpression of copper- and zinc-containing superoxide dismutase (Cu,Zn-SOD) and catalase extends life span of Drosophila melanogaster. Experimental flies containing single extra doses of Drosophila Cu,Zn-SOD and catalase genes were compared with appropriate controls at different ages. Overexpression of Cu,Zn-SOD and catalase caused a retardation in the accumulation of 8-hydroxydeoxyguanosine during aging and in response to the exposure of live flies to x-rays. The age-related loss of glucose-6-phosphate dehydrogenase activity (Glu-6-P dehydrogenase) and the increase in the rate of mitochondrial H2O2 generation were less steep in the experimental than control flies. The rate of in vivo oxygen consumption in the latter two-thirds of life span was higher in the experimental than in the control flies. Furthermore, the metabolic potential, or the total amount of oxygen consumed during an average life span, was about 30% greater in the experimental than the control flies. Altogether, results of this study indicate that overexpression of Cu,Zn-SOD and catalase ameliorates the age-related accumulation of molecular oxidative damage and susceptibility to such damage in response to acute oxidative stress while prolonging the metabolic life of flies. The concept that oxidative stress is a causal factor in the aging process is supported.

8-Hydroxy-2'-Deoxyguanosine↗

Heart rate variability during specific sleep stages. A comparison of healthy subjects with patients after myocardial infarction.

BACKGROUND: Heart rate variability (HRV) is typically higher during nighttime. This evidence supports the concept that overall, sleep is a condition during which vagal activity is dominant. Myocardial infarction (MI) results in a loss in the overall nocturnal HRV increase. However, the characteristics of HRV during specific sleep stages in normal subjects and, more importantly, after MI, are unknown. This study describes HRV during sleep stages in normal subjects and in patients with a recent MI. METHODS AND RESULTS: HRV was measured from 5 minutes of continuous ECG recording in 8 subjects with no clinical evidence of coronary artery disease (age, 47 +/- 4 years) and in 8 patients with a recent MI (age, 51 +/- 2 years; NS versus control subjects) in the awake state, non-rapid eye movement (REM), and REM sleep. In normal subjects, the low- to high-frequency ratio (LF/HF) derived from power spectral analysis of HRV decreased significantly from the awake state to non-REM sleep (from 4 +/- 1.4 to 1.22 +/- 0.33, P < .01). During REM sleep, the LF/HF increased to 3 +/- 0.74 (P < .01 versus non-REM, NS versus awake). In post-MI patients, the LF/HF showed an opposite trend toward an increase from 2.4 +/- 0.7 to 5.11 +/- 1.4 (NS, P < .01 versus the control subjects). REM sleep produced a further increase in the LF/HF up to 8.9 +/- 1.6 (P < .01 versus awake and versus REM in control subjects). CONCLUSIONS: Myocardial infarction causes a loss in the capability of the vagus to physiologically activate during sleep. This results in a condition of relative sympathetic dominance even in a situation such as sleep, normally described as a condition of vagal dominance and, consequently, low risk for lethal events. The evidence that the sleep-related vagal activation is lost after MI may provide new insights to understanding the nocturnal occurrence of sudden death.

Electrocardiography↗

Mitochondrial superoxide and hydrogen peroxide generation, protein oxidative damage, and longevity in different species of flies.

The objective of this study was to further elucidate the role of oxidative stress in the aging process by determining whether or not the rates of mitochondrial superoxide anion radical and hydrogen peroxide (H2O2) production, the activity of cytochrome c oxidase, and the concentration of protein carbonyls are correlated with the life span potential of different species. A comparison was made among five different species of dipteran flies, namely, Drosophila melanogaster (fruit fly), Musca domestica (house fly), Sarcophaga bullata (flesh fly), Calliphora vicina (blow fly) and Phaenecia sericata (a species of blow flies), which range more than 2-fold in their life span potentials. The average life span potential of these species was found to be inversely correlated with the rates of mitochondrial superoxide and H2O2 production and with the level of protein carbonyls, and to be directly related to the activity of cytochrome c oxidase. The significance of these findings in context of the validity of the oxidative stress hypothesis of aging is discussed. It is inferred that longer life span potential in these insect species is associated with relatively low levels of oxidant generation and oxidative molecular damage. These results accord with our previous findings on different mammalian species.

Animals↗

Patterns of 24-hour oesophageal acid exposure after acute withdrawal of acid suppression.

AIM: To measure 24-h ambulatory oesophageal pH data in patients with gastro-oesophageal reflux disease prior to, during and after acute treatment with comparable doses of omeprazole and ranitidine. METHODS: The subjects were 20 adults with at least 8% acid contact time. Ten subjects were treated for 1 week with omeprazole 20 mg q.d.s. and 10 subjects with ranitidine 300 mg t.d.s. All subjects were examined at the end of 1 week of therapy and subsequent to cessation of treatment (1 day for ranitidine and 3 days for omeprazole). RESULTS: Both drugs produced a statistically significant (P < 0.05) decrease in acid contact time with acute treatment. Omeprazole produced a significantly greater decrease in acid contact time when compared to ranitidine. Subsequent to treatment cessation, the total acid contact time for omeprazole remained significantly less than the baseline level, while ranitidine returned to levels which were not significantly different from the baseline. CONCLUSION: These data provide no evidence for a 'reflux rebound' subsequent to the cessation of acute acid secretory suppression.

Adult↗

Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster.

The hypothesis that oxygen free radicals are causally involved in the aging process was tested by a study of the effects of simultaneous overexpression of copper-zinc superoxide dismutase and catalase. As compared to diploid controls, transgenic flies carrying three copies of each of these genes exhibited as much as a one-third extension of life-span, a longer mortality rate doubling time, a lower amount of protein oxidative damage, and a delayed loss in physical performance. Results provide direct support for the free radical hypothesis of aging.

Aging↗

Comparative effects of H2-receptor antagonists on subjective and objective assessments of sleep.

BACKGROUND: Clinically, it is common for patients to experience drowsiness in association with consumption of H1-receptor antagonists. Reported side-effects with H2-receptor antagonists include insomnia and somnolence. The present study was designed to assess and compare the effects of three H2-receptor antagonists (cimetidine, famotidine, and ranitidine) on nocturnal and daytime sleepiness. METHODS: This is a double-blind crossover study on 12 normal volunteers. Subjects were studied under conditions of placebo, cimetidine (400 mg b.d.), famotidine (20 mg b.d.), and ranitidine (150 mg b.d.) for one week. Sleep was assessed at the end of each one-week interval via polysomnographic evaluation conducted on nights 6 and 7 of drug administration. On the day between the two nights in the sleep laboratory, a multiple sleep latency test was conducted. RESULTS: The results revealed a significant reduction in the sleep onset latency with famotidine administration, but since there were no effects of any of the medications in the multiple sleep latency test, this finding is of dubious clinical significance. Cimetidine revealed a small increase in subjective estimates of sleepiness. No effects on sleep-related respiratory parameters were noted. CONCLUSIONS: This study demonstrates the lack of effect of peripheral administration of H2-receptor antagonists on sleep stages, while subjective or objective assessment of daytime alertness revealed small effects of famotidine and cimetidine.

Adult↗

A laboratory validation study of a portable system for remote recording of sleep-related respiratory disorders.

This study represents the validation of an out-of-laboratory recording system for screening sleep disorders by comparing it to an in-laboratory system which accomplishes complete polysomnography. Forty patient cases were collected. Each patient slept in the sleep laboratory with the simultaneous monitoring of eight channels from the Sleep I/T (CNS, Inc), as well as complete polysomnographic monitoring comparable to that which accomplishes routine patient evaluations utilizing the Sleeplab (CNS, Inc) system. The data collected on the Sleeplab system were analyzed in a computer-assisted manner followed by manual overreading of the raw data. The Sleep I/T data analysis was performed automatically using default parameters. The results revealed no significant differences in the determination of sleep efficiency, respiratory disturbance index (RDI), periodic leg movement (PLM) index, or the desaturation index. For the RDI, the sensitivity was 100 percent and the specificity was 93 percent for correctly detecting an RDI of 15 per hour, and the PLM index had a sensitivity of 89 percent and specificity of 97 percent in detecting episodes greater than 20 per hour. These data demonstrate excellent agreement between this out-of-laboratory system and polysomnography in its ability to detect accurately RDI, PLM index, and saturation levels.

Humans↗

The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage.

OBJECTIVES: The primary objective of the present investigation was to determine from variables obtained from 24-h esophageal pH monitoring significant discriminators between patients with and without erosive esophageal mucosal damage. METHODS: Data obtained from this study were from 24-h esophageal pH monitoring and the results of upper gastrointestinal endoscopy. Statistical methods included the use of multivariate discriminant analysis. RESULTS: The results revealed that the single best measure which discriminated patients with erosive and nonerosive esophagitis was the number of recumbent reflux episodes lasting greater than 5 min. CONCLUSIONS: We conclude from these data that 1) specific evaluation of recumbent reflux and acid exposure can add substantially to the interpretation of 24-h esophageal pH studies, particularly with regard to identifying patients at risk for the development of erosive esophagitis or other potential complications; 2) esophageal mucosal erosions are associated with an increase in percent acid contact time in both the upright and supine positions, but the pattern of reflux, particularly during the nocturnal interval in terms of the number of episodes greater than 5 min, adds significant predictive value in discriminating patients with erosive mucosal damage.

Adult↗

Protein oxidative damage is associated with life expectancy of houseflies.

The objective of this study was to test some of the predictions of the oxidative-stress hypothesis of aging, which postulates that aging is causally associated with the molecular damage inflicted by reactive oxygen species. Protein carbonyl content was used as an index of molecular oxidative modifications. The carbonyl content was found to be associated with the physiological age or life expectancy of flies rather than with their chronological age. Exposure of flies to sublethal hyperoxia (100% oxygen) irreversibly enhanced the carbonyl content of the flies and decreased their rate of oxygen consumption. Results of this study indicate that protein carbonyl content may be a biomarker of aging and support the general concept that oxidative stress may be a causal factor in the aging process.

Animals↗

Effects of Cu-Zn superoxide dismutase overexpression of life span and resistance to oxidative stress in transgenic Drosophila melanogaster.

Reactive oxygen species have been postulated to be a causal factor in the aging process due to their ability to inflict molecular damage. The role of the enzyme copper-zinc superoxide dismutase (Cu-Zn SOD; superoxide:superoxide oxidoreductase; EC 1.15.1.1), which scavenges superoxide anion radicals, as a longevity determinant was examined in transgenic Drosophila melanogaster. A genomic fragment containing the Drosophila Cu-Zn SOD gene was introduced into the germ cells via a P element containing Casper vector. In different transgenic lines, overexpression of SOD by 32-42% above normal had either a minor and/or an insignificant effect on life span of the flies and their ability to withstand experimental oxidative stress, induced by paraquat intake and exposure to hyperoxia (100% oxygen). Transgenics showing a small increase in mean life span also exhibited a corresponding improvement in their resistance to hyperoxia but not paraquat. The maximum life span of populations was not affected.

Animals↗