The relationship between complaints of night-time heartburn and sleep-related gastroesophageal reflux.

This study investigated whether the complaint of night-time heartburn (NHB) as opposed to daytime heartburn (DHB) is a reliable reflection of actual sleep-related reflux events. Three groups of individuals were studied: individuals with complaints of NHB at least twice per week (n = 24), individuals with complaints of DHB (n = 23), and normal participants without any complaints of regular heartburn during the day or night (n = 25). All three groups were studied on one occasion with combined pH monitoring and polysomnography, and subjective questionnaires about sleep disturbance and sleep quality were given to all participants. The NHB group had significantly more sleep-related reflux events compared with both DHB and control groups (P < 0.01). DHB subjects had significantly (P < 0.05) more sleep-related reflux events than normal controls. Total acid contact time (ACT) was significantly (P < 0.05) elevated in the NHB group compared with both the DHB and control group. Sleep-related ACT was also significantly (P < 0.05) elevated in the NHB group compared with the other two groups, while upright (daytime) ACT was not significantly different. The NHB group was significantly (P < 0.05) worse regarding measures of both objective and subjective sleep quality. Subjects with exclusively DHB do have sleep-related reflux that is greater than normal controls. Subjects with NHB have significantly more sleep-related reflux, and both objective and subjective sleep abnormalities compared with normal controls. Complaints of NHB reflect sleep-related reflux events and may be indicative of a more clinically significant condition.

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.

Consequences of frequent nocturnal gastro-oesophageal reflux disease among employed adults: symptom severity, quality of life and work productivity.

BACKGROUND: Effects of frequent nocturnal symptoms of gastro-oesophageal reflux disease (GERD-FNS) on health-related quality of life (HRQOL) and work productivity are not well documented. AIM: To assess symptom severity, production loss, and HRQOL among employed adults with and without GERD-FNS. METHODS: Using several validated outcome measures in a web survey design, GERD was pre-specified as GERD Symptom and Medication Questionnaire score >9, and > or =1 episode of heartburn or acid regurgitation during the preceding week. GERD-FNS patients were those reporting > or =2 symptom-nights during the previous week; their outcomes were compared with those of patients having minimal or no nocturnal symptoms (GERD-NNS) and vs. non-GERD controls. RESULTS: Data were collected from 1002 GERD patients (476 GERD-FNS, 526 GERD-NNS) and 513 controls. Severe symptoms were more common, sleep abnormalities were more frequent (P < 0.0001) and SF-36 scores lower (P < 0.05, all scores) among GERD-FNS patients vs. GERD-NNS patients. GERD-related work loss was greater among those with GERD-FNS vs. GERD-NNS (P < 0.0001). Work loss and functional limitations were more pronounced when comparing GERD-FNS cases vs. non-GERD controls. CONCLUSION: Employed adults with frequent nocturnal GERD report more severe symptoms, and are associated with impaired sleep, HRQOL and work productivity compared with controls and patients with minimal or no nocturnal symptoms.

A female sterile screen of the Drosophila melanogaster X chromosome using hybrid dysgenesis: identification and characterization of egg morphology mutants.

We have conducted a hybrid dysgenic screen of the X chromosome for mutations affecting female fertility, with particular attention to those causing abnormal egg and eggshell morphology. In a screen of 4017 dysgenic strains, 398 mutants derived from 168 different germ lines were isolated and assigned to eight classes according to their diverse phenotypes. One interesting class consists of mutants that block oogenesis at specific stages. Our analysis has focused on mutations affecting eggshell formation, including mutants that lay morphologically abnormal sterile eggs as well as those that lay no eggs but exhibit blocks in the late stages of oogenesis. A subset of 48 mutants was assorted into 30 allelic groups by inter se complementation and genetically localized by interval mapping. Two multiallele complementation groups, de1 (7 alleles) and ne1 (8 alleles), were identified as well as five two-allele complementation groups. A search for alleles among mutants generated in other female sterile screens was unsuccessful, pointing to the distinctive nature of the dysgenic mutant collection. The single case of allelism determined in this study was one with a lethal allele of the Broad-Complex, l(1)npr, suggesting a possible involvement of ecdysone in choriogenesis. A subset of 18 dysgenic strains was analyzed for P element hybridization and 16 of these were found to have hybridization signals in the appropriate cytogenetic interval. By examining these signals in two or more alleles of the same complementation group, we have been able to tentatively localize two mutations. Light and electron microscopy of the eggshell in 43 different strains has revealed a variety of effects. The respiratory appendages were defective in 27 of these mutants. Effects on the ultrastructure of the main body of the endochorion were not strongly correlated with the appendage defects, and could be classified as minor (14 mutants) or major (16 mutants). Although 13 mutants showed no ultrastructural chorion defects, six of these had defective respiratory appendages.

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.

Obstructive sleep apnea associated with tonsillar hypertrophy in adults.

Six adults with tonsillar enlargement were shown via all-night polygraphic recordings to have varying degrees of upper airway obstruction during sleep. All but one of these patients were noted to have profound and debilitating daytime sleepiness. All patients had extremely loud snoring with anecdotal reports of apnea. Postoperatively all patients reported a marked reduction in snoring and substantial improvement in their daytime sleepiness. Postoperative sleep laboratory evaluation in four cases revealed nearly complete obliteration of upper airway obstruction and improvement in several objective sleep measurements, such as sleep-onset latency. We conclude that even relatively mild tonsillar enlargement can play an important role in the pathogenesis of obstructive sleep apnea.

Progesterone therapy in obese patients with sleep apnea.

Seven morbidly obese patients with sleep-related upper airway obstruction (UAO) were studied before and during progesterone treatment. All subjects had severe daytime somnolence, and five of the seven had congestive heart failure. All subjects were studied for one or two consecutive baseline nights in the sleep laboratory. Six of the seven subjects showed a mean of greater than 100 UAOs. Patients were treated for two to four weeks with medroxyprogesterone acetate, 20 mg three times daily. At the end of the treatment period, the sleep studies were repeated. There was no significant difference in the incidence, mean duration, or rate per minute of apneic episodes occurring before and with progesterone treatment. Severe hypoxemia during sleep persisted with treatment, as did the occurrence of cardiac arrhythmias. There was a significant improvement in the waking Pao2 with progesterone treatment.

Sleep patterns and gastric acid secretion in duodenal ucler disease.

Five normal volunteers and five patients with duodenal ulcer (DU) disease were studied for five consecutive nights. All subjects underwent placement of a nasogastric tube, continuous collection of gastric juice, and continuous electroencephalographic monitoring of sleep. Gastric juice was collected in 20-minute samples by remote suction (Gomco). Blood samples were drawn every 20 minutes on the third night via an indwelling venous needle. Results showed no significant correlations between the sleep variables and the gastric acid secretion measures or between the sleep variables and serum gastrin levels. Acid secretion decreased from hour 1 to hour 2 in controls and in patients with inactive DU disease, while it increased in patients with active DU disease. Each subject had at least one night of recording in which continuous gastric secretion was less than 0.1 mEq per 20-minute sample. It appears unlikely that the gastric discomfort of DU patients can be attributed to acid hypersecretion triggered by rapid eye movement sleep.

CuZn-SOD promoter-driven expression in the Drosophila central nervous system.

The aim of this study was to ascertain the status of CuZn superoxide dismutase (CuZn-SOD) expression in the central nervous system of Drosophila melanogaster. Immunoblot analysis of dissected tissue extracts revealed low levels of the CuZn-SOD protein in adult brains relative to other adult and larval tissues. To explore further this observation, three different reporter constructs containing different elements of the CuZn-SOD promoter domain were used for the generation of transgenic flies. A high level of reporter gene expression occurred during the second wave of neurogenesis (third instar and early pupal stages) in scattered, proliferating neuroblasts (NBs) and in proliferation centers of the optic lobe. In mature, postmitotic neurons, this expression was lower relative to other tissues. In adult flies, at all ages examined, there was little if any detectable reporter gene expression in cells of the central nervous system. These results suggest that one of the key components of the antioxidant defenses, CuZn-SOD, is quite low in postmitotic neural tissue, rendering it particularly susceptible to oxidative damage during aging.

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.

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.

Effect of age on superoxide dismutase, catalase, glutathione reductase, inorganic peroxides, TBA-reactive material, GSH/GSSG, NADPH/NADP+ and NADH/NAD+ in Drosophila melanogaster.

The objective of this study was to investigate the possible role of oxygen free radicals in the aging process by studying the pattern of age-related changes in a broad spectrum of antioxidant defenses and indicators of oxidative stress in adult male Drosophila melanogaster. There were selective, but not universal, changes in the antioxidant defenses and indicators of oxidative stress. Activities of catalase and glutathione reductase and concentration of reduced glutathione decreased during the latter part of life. Superoxide dismutase activity tended to increase with age whereas glutathione peroxidase activity was undetectable. The ratios of reduced/oxidized glutathione and NADPH/NADP+, which are widely regarded as indicators of oxidative stress, decreased in the terminal phase of life. NADH/NAD+ ratio increased in the latter part of life. Concentration of inorganic peroxides increased during the first trimester of life and remained unchanged thereafter while that of thiobarbituric acid-reactants tended to decrease during aging. The main conclusion of this study is that age-related changes in antioxidant defenses and in levels of oxygen free radical reaction products are selective in nature and are quite variable in different species and tissues; however, the level of oxidative stress tends to increase during aging.

Relationship between catalase activity, life span and some parameters associated with antioxidant defenses in Drosophila melanogaster.

This study was conducted on Drosophila melanogaster mutants with different levels of catalase activity in order to assess the role of antioxidant defenses in the aging process. We present here the analysis of two mutant strains: the catn1/catn4 heterozygote which exhibits no detectable catalase activity and the catn2 homozygote which exhibits approximately 14% that of the parent reference strain. Since insects lack glutathione peroxidase activity, catalase activity provides the sole enzymatic mechanism for the removal of H2O2. Average and maximum life spans of flies were unaffected by the absence or low levels of catalase activity. The mutants however exhibited adaptive responses in their metabolic rate or glutathione content. The metabolic rate of flies was significantly lowered in the null mutants. Glutathione concentration tended to increase in flies with the hypomorphic catalase allele (exhibiting 14% of the normal catalase activity). Gamma-glutamylcysteine synthetase activity was significantly higher in the null flies. Activities of superoxide dismutase and glutathione reductase were unaffected. Results of this study indicate that 14% of the normal level of catalase activity allows flies to achieve both a normal life span and a normal metabolic potential. Small decreases in certain antioxidant defenses, frequently observed during aging, may be functionally not very consequential.

Myxedema and obstructive sleep apnea.

Three cases of hypersomnolence, snoring and documented sleep apnea are reported. All three patients were profoundly myxedematous, both clinically and biochemically. Polygraphic studies during sleep documented the presence of repetitive episodes of obstructive sleep apnea in all three patients. These were accompanied by arterial oxygen desaturation. After becoming euthyroid following the administration of the l-thyroxine all patients underwent a repeat evaluation in the sleep laboratory. These studies revealed nearly complete resolution of obstructive sleep apnea in all patients. In addition, several sleep parameters showed marked improvement. These data strongly suggest that the presence of profound daytime sleepiness in hypothyroid patients could be indicative of a potentially lethal complication of myxedema, obstructive sleep apnea.

Effects of maternal smoking and caffeine habits on infantile apnea: a retrospective study.

To evaluate the relationship of antecedent maternal smoking and caffeine consumption habits on the occurrence of apnea in their offspring, rates for central and obstructive apnea were analyzed in a cohort of mother-infant pairs. The mothers of 298 infants with apnea responded to a questionnaire completed prior to a nine-hour polysomnogram performed as part of the patients' evaluations. Cigarette consumption estimates were computed on a 20-cigarette per pack basis, and caffeine intake, based on dietary sources (coffee, tea, chocolate, and colas), was summarized as milligrams of caffeine consumed per day. Rates of central and obstructive apnea of 6 to 10 seconds in duration were calculated. Multiple linear regression analysis determined that smokers tended to be younger and have lower birth weight infants who presented earlier with apnea than infants of nonsmokers. Increased rates of central apnea occurred in infants of smokers as compared with infants of nonsmokers. During pregnancy, a pack per day increase in maternal smoking habit was associated with a 1.88/h increase in central apneas in their offspring (P less than .01). Maternal smoking after delivery had a similar relationship. Obstructive apnea rates were similar in both groups. Both central and obstructive apnea rates associated positively with increasing maternal caffeine consumption. Smoking habits and caffeine ingestion were correlated (P less than .01). Infants with apnea have greater rates of central apnea when their mothers smoke during pregnancy. Therefore, a history of nicotine consumption should be included in the medical history of infants presenting with apnea.

Effect of sleep state and position on the incidence of obstructive and central apnea in infants.

Sixty-four infants with a history of apnea were studied to determine the effects of sleeping position and sleep state (rapid eye movement [REM]) v (non-rapid eye movement [NREM]) on the occurrence of central and obstructive apneas. All-night polysomnographic studies were conducted on each infant, and the spontaneous occurrence of central and obstructive apneic events was determined in the prone, supine, and side positions. Sleeping position did not significantly affect the rate or duration of central or obstructive apneas. Furthermore, neither central nor obstructive apneic episodes were significantly altered by sleep state. These data suggest that, in spite of an ostensible predisposition to upper airway obstruction in the supine position and during rapid eye movement sleep, neither sleeping position nor sleep state appears to affect the rate of duration of apneic events.

Sleep disturbances after open heart surgery.

This study was designed to document quantitatively the sleep disturbances that occur after open heart surgery and to investigate a group of patients who underwent a thoracic surgical procedure not involving cardiopulmonary bypass. Nine patients were studied, six after open heart surgery and three after partial or complete pneumonectomy. In each patient, sleep patterns were recorded with use of all night polygraphy before and after operation and for up to 5 weeks on follow-up studies. After open heart surgery, patients manifested considerable suppression of both rapid eye movement and slow wave sleep patterns. In the three patients subjected to thoracotomy these sleep indexes returned to preoperative levels much earlier. Evidence of stage 2 sleep was present in one of the three patients with thoracotomy on the first postoperative night, and in two of the three both rapid eye movement and slow wave sleep returned to preoperative levels by the time of hospital discharge. It is concluded that patients undergoining open heart surgery experience both acute and chronic disruptions of sleep that last well beyond the hospital period of convalescence. These sleep disturbances have considerable relevance for postoperative management.

Postprandial sleepiness: objective documentation via polysomnography.

Fifteen normal volunteers were evaluated to assess the effect of a meal on sleep onset latency. The meal was administered in a counterbalanced design on 1 of 2 successive days. Subjects napped 20 min subsequent to the meal (or at the corresponding time on the no-meal day) and 1 h after the initiation of the first nap. Ten subjects completed the Stanford Sleepiness Scale (SSS) on arriving at the laboratory, and just prior to nap 1 and nap 2. Sleep onset latency after the meal was not significantly different from that obtained under the no-meal condition, but was significantly less on nap 1 as compared with nap 2 irrespective of day or meal. SSS did not reveal subjective differences in sleepiness between the initial estimate and the postmeal estimate. Only five subjects showed a decrease in sleep onset latency postprandially (1-11 min). Although group differences in postprandial sleepiness were not documented, the phenomenon was clearly exhibited by certain individuals. Thus, postprandial sleepiness is not an invariable consequence of meal ingestion; rather, it appears to be affected by numerous variables such as hunger, volume of the meal, and meal constituents.

Heart rate variability during waking and sleep in healthy males and females.

STUDY OBJECTIVES: The study goal was to investigate autonomic activity with heart rate variability analysis during different sleep stages in males and females. DESIGN: The study utilized a 2 Groups (males, females) x 4 States (waking, stage 2 sleep, stage 4 sleep, rapid-eye movement sleep) mixed design with one repeated, within-subjects factor (i.e., state). SETTING: The study was carried out in the sleep laboratory of the Thomas N. Lynn Institute for Healthcare Research. PARTICIPANTS: Twenty-four healthy adults (fourteen females and ten males). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: All participants underwent polysomnographic monitoring and electrocardiogram recordings during pre-sleep waking and one night of sleep. Fifteen-minute segments of beat-to-beat heart rate intervals during waking, stage 2 sleep, stage 4 sleep, and REM sleep were subjected to spectral analysis. Compared to NREM sleep, REM sleep was associated with decreased high frequency (HF) band power, and significantly increased low frequency (LF) to (HF) ratio. Compared to females, males showed significantly elevated LF/HF ratio during REM sleep. Males also demonstrated significantly decreased HF band power during waking when compared to females. No significant sleep- or gender-related changes in LF band power were found. CONCLUSIONS: The results confirmed changes in autonomic activity from waking to sleep, with marked differences between NREM and REM sleep. These changes were primarily due to stage-related alterations in vagal tone. REM sleep was characterized by increased sympathetic dominance, secondary to vagal withdrawal. The data also suggested gender differences in autonomic functioning during waking and sleep, with decreased vagal tone during waking and increased sympathetic dominance during REM sleep in the males.

Genetic markers in familial narcolepsy.

We studied three patients in a single family (father and two sons), all with long histories of overwhelming daytime sleepiness, hypnagogic hallucinations and sleep paralysis. Two of the three had a clear history of cataplexy. Multiple sleep latency tests revealed extremely short sleep onset latencies and at least two sleep onset rapid eye movement periods in each patient. Histocompatibility studies were remarkable for negative HLA-DR2 antigens in all three.