The need for a knowledge system in sleep and chronobiology.
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Chronobiology Phenomena↗
Biomedical subjects
P Zee
Publications and source records attributed to P Zee.
Pathophysiology and treatment of enuresis in adults.
Monosymptomatic nocturnal enuresis (MNE) in children is partly the result of inadequate reduction in the rate of urine output at night. This nocturnal polyuria is due to the lack of a rise in the anti-diuretic hormone, arginine vasopressin (AVP), and can be reduced or eliminated by treatment with desmopressin at bedtime. Since there is a 1% incidence of MNE among adults, this study investigated the circadian pattern of solute and water balance in nine young adult enuretics before and during desmopressin therapy and compared the results with nine-age- and sex-matched, healthy controls. Before treatment, enuretics and controls had similar total fluid intake, urine output, urine osmolality, plasma osmolality, plasma total protein, mean arterial pressure and plasma AVP. The circadian pattern of fluid intake was also normal in enuretics. This abnormality could not be attributed to a deficiency of plasma AVP or an increase in solute excretion, since both variables were similar to controls. Rather, their nocturnal polyuria appeared to be due to a marked nocturnal reduction in renal sensitivity to the antidiuretic effect of vasopressin. In seven enuretics, restudied during treatment with desmopressin (10-30 micrograms o.d.), circadian urine output was normal and enuresis was absent. These results indicate that: (i) The circadian pattern of urine output in healthy adults is largely due to a nocturnal decrease in solute excretion rather than a rise in plasma AVP; (ii) The subset of adults with persistent MNE also have nocturnal polyuria as a result of insensitivity to the antidiuretic action of AVP; (iii) These defects can be corrected by treatment with desmopressin.
Adult↗
High prevalence of sleep disturbance in cirrhosis.
Sleep disturbance is a classic sign of hepatic encephalopathy. However, there are limited data regarding its prevalence in cirrhotic patients without overt hepatic encephalopathy. We assessed the characteristics of sleep in cirrhosis using a sleep questionnaire (n = 44) and actigraphy (n = 20). The results were compared with those of subjects with chronic renal failure and those of healthy controls. Presence of subclinical hepatic encephalopathy, chronotypology profile, and individual's affective state were also analyzed. The questionnaire indicated an elevated number of cirrhotic patients (47.7%) and patients with chronic renal failure (38.6%) who complained of unsatisfactory sleep compared with healthy controls (4.5%, P < .01). Actigraphy corroborated the deterioration of sleep parameters in cirrhotic patients with unsatisfactory sleep. The sleep disturbance in cirrhosis was not associated with clinical parameters nor with cognitive impairment. Cirrhotic subjects and patients with chronic renal failure with unsatisfactory sleep showed higher scores for depression and anxiety, raising the possibility that the effects of chronic disease may underlie the pathogenesis of sleep disturbance. However, in contrast to chronic renal failure, unsatisfactory sleep in cirrhosis was associated with delayed bedtime, delayed wake-up time, and evening chronotypology. In conclusion, a sleep disturbance is frequent in cirrhotic patients without hepatic encephalopathy and may be related to abnormalities of the circadian timekeeping system.
Activity Cycles↗
Abnormalities of circadian rhythmicity in liver disease.
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Circadian Rhythm↗
Attention deficit hyperactivity disorder associated with orbitofrontal epilepsy in a father and a son.
The authors report on a father and son with frontal lobe epilepsy and symptoms of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity is a syndrome defined by criteria that include inattention, impulsive behavior, impaired concentration and motor restlessness. It does not require medical or neurobehavioral evaluation to determine an underlying etiology. The father is a 45-year-old man evaluated for possible ADHD. His referral came after the diagnosis of ADHD in his 6-year-old son who responded well to treatment with methylphenidate HCL. Neurobehavioral evaluation of the father suggested frontal lobe dysfunction. Magnetic resonance imaging and electroencephalography (EEG) were normal. Brain 99mTc HMPAO single-photon emission computed tomography (SPECT) revealed left orbitofrontal hypoperfusion. Additional history from his wife revealed episodic symptoms suggestive of nonconvulsive epilepsy that included nonresponsive staring, complex automatic behavior, and amnesic lacunas. Treatment of the father with carbmazepine produced dramatic improvement. Subsequent evaluation of his son, currently on maintenance treatment with methylphenidate HCL for ADHD, elicited a history consistent with atonic and simple motor partial epilepsy. The son's brain SPECT revealed bilateral orbitofrontal hypoperfusion defects. Attention deficit hyperactivity disorder is a syndrome that may be caused by frontal lobe lesions or epilepsy. In the setting of possible ADHD, neurological evaluation is warranted. Although overreliance on structural imaging or EEG in such an evaluation must be discouraged, brain SPECT may be useful to evaluate patients with symptoms of attention disorders for frontal epilepsy.
Attention Deficit Disorder with Hyperactivity↗
Alterations in the circadian system in advanced age.
In addition to light, a variety of non-photic stimuli can induce phase shifts in the circadian clock of rodents. We have examined the effects of advanced age on the response of the circadian clock to both photic and non-photic stimuli in old hamsters (i.e., over 16 months of age). Among the age-related changes in the circadian rhythm of locomotor activity are: (1) alterations in the phase angle of entrainment to the light-dark cycle; (2) an altered response to the phase-shifting effects of light pulses; (3) changes in the time it takes to re-entrain to a new light-dark cycle; and (4) a loss of responsiveness to the phase-shifting or entraining effects of stimuli which induce an acute increase of activity. Many of the effects of ageing on the circadian clock system can be simulated in young animals by depleting brain monoamine levels, suggesting that ageing alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal suprachiasmatic nuclear tissue. Determining the physiological basis of age-related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian functioning can be restored, should lead to new insight into the functioning of the circadian clock and may suggest new approaches to the normalization of disturbed circadian rhythms.
Aging↗
Effects of age on the circadian system.
While aging has been associated with changes in the period and amplitude of circadian rhythms, little is known about how aging influences the response of the circadian clock to environmental stimuli. In this paper, we report on recent studies designed to determine the effects of advanced age on the response of the circadian clock to both photic and nonphotic stimuli in old hamsters (e.g., over 16 mo of age). Among the most pronounced age-related changes in the circadian rhythm of locomotor activity are: (a) alterations in the phase-angle of entrainment to the light-dark cycle; (b) an increase in the magnitude of phase shifts induced by pulses of light presented at specific circadian times; and (c) a loss of responsiveness to the phase shifting or entraining effects of stimuli which induce an acute increase of activity. Depletion of brain monoamine levels in young animals can induce changes in the responsiveness of the circadian clock to environmental stimuli which are similar to those which occur spontaneously in old animals, suggesting that aging alters monoaminergic inputs to the clock. Some of the age-related changes in the response of the clock to an activity-inducing stimulus can be reversed by implanting old animals with fetal SCN tissue. Determining the physiological basis for age related changes in the responsiveness of the clock to both internal and external stimuli, and the mechanisms by which normal circadian function can be restored, should lead to new insight into the functioning of the circadian clock and may lead to new approaches for normalizing disturbed circadian rhythms.
Aging↗
Aging alters the entraining effects of an activity-inducing stimulus on the circadian clock.
In young hamsters, a single injection of the short-acting benzodiazepine, triazolam, can induce permanent phase shifts in the circadian clock, while repeated injections of triazolam entrain the circadian clock to the period of the injections. Triazolam appears to act on the circadian clock by inducing an acute increase in the activity of the animals, which in turn phase-shifts the circadian clock. Surprisingly, single injections of benzodiazepines do not phase-shift the activity rhythm of old hamsters, despite the fact that such treatment induces similar acute changes in the activity state of young and old animals. We compared the entraining effects of repeated injections of triazolam on the circadian clock of young and old hamsters; while six out of seven young hamsters were entrained to the triazolam injections, only one out of seven old animals was entrained by this treatment. Three of the remaining six old hamsters showed a lengthening of the activity rhythm, while no consistent effect on the period of the activity rhythm was observed in the remaining three old animals. These results indicate that the circadian system of old hamsters becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state, and suggest that aging is associated with a weakened coupling between the activity-rest cycle and the circadian clock.
Aging↗
Quantitating hepatic encephalopathy in rats after portacaval anastomosis.
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Animals↗
Portal-systemic shunting and the disruption of circadian locomotor activity in the rat.
To determine if the extent of portal-systemic shunting (PSS) influences the disruption of circadian function in chronic liver disease, locomotor activity was examined in two rat models with varying degrees of PSS, i.e., portal vein ligation (PVL) and end-to-side portacaval anastomosis (PCA). Animals were housed in individual activity cages under conditions of 12 hour light/12 hour darkness (weeks 0-3), then under conditions of constant dim light (weeks 4-7). Cages were equipped with running wheels connected to a continuous recorder, and daily tracings of running activity were recorded for 7 weeks. Computer analysis of wheel revolutions per hour with a chi 2 periodogram was used to calculate Qp, a measure of the amplitude of a circadian rhythm. The degree of PSS was measured by means of radioactive microspheres injected into the ileocolic vein and spleen. PVL rats were found to have PSS from the splenic and mesenteric territories of 88% and 27%, respectively; circadian periodicity was maintained in all PVL rats. PCA rats had complete shunting (greater than 99%) and showed a range of disrupted circadian rhythms from blunting of the amplitude to complete absence of the locomotor activity rhythm. This spectrum of disorganization occurred in spite of similar degrees of liver atrophy and weight gain. Whereas PCA in rats markedly disturbs the circadian rhythm of locomotor activity, animals with considerably less PSS from PVL exhibit normal behavior. The extent of PSS could be a variable affecting the expression of circadian rhythms in liver disease.
Animals↗
Prevalence of obesity in children after therapy for acute lymphoblastic leukemia.
To confirm an impression that many survivors of acute lymphoblastic leukemia (ALL) are overweight or obese, we retrospectively examined the medical records of 414 patients for height and weight at diagnosis, at completion of treatment, and at annual intervals thereafter. The body mass index, weight/height2, was used as a measure of fatness; population norms for the index were established from 9,003 people between the ages of 1 and 30 years who were examined in a national health survey. The percentile of each patient's index was determined at each observation date. At diagnosis, the study sample was skewed toward leanness; however, at cessation of therapy, the fatness distribution resembled population norms. Statistically significant increases in fatness occurred during the first year off therapy, at the end of which 35% of the children were above the 80th percentile (i.e., overweight) and 12% were above the 95th percentile (i.e., obese). Only 12% were below the 20th percentile. This skewed distribution persisted during the subsequent 4-year follow-up period. Cranial irradiation was associated with a large increase of fatness in one group available for comparisons. Our findings indicate that the first year following cessation of therapy is a time of excessive weight gain among pediatric ALL patients.
Humans↗
Nutritional improvement of poor urban preschool children. A 1983-1977 comparison.
The nutritional status of preschool children from 1,219 families living in an urban poverty area was surveyed in 1983 and these results were compared with findings from a similar survey of the same community done in 1977. A second comparison was made of children whose families participated in a commodity supplementary food program and those whose families did not participate. Results of the 1983 survey indicated improvements in median serum levels of vitamins A and C, hemoglobin, and red blood cell volume. Nevertheless, 9% to 18% of the children had low or deficient levels of vitamins A, C, B1, and B2, hemoglobin, serum iron, and transferrin saturation. Also a greater number of the preschoolers were categorized as thin. Annual incomes for families had significantly decreased from 1977 when the median value for food recipients was +3,078 to a median of +1,848 in 1983. Considering the decrease in other resources, federal food assistance programs seem to be the only identifiable factor contributing to the improvement in nutritional status over 1977.
Avitaminosis↗
Impairment of lipid emulsion metabolism associated with carnitine insufficiency in premature infants.
Carnitine status and its relation to lipid metabolism were determined in 11 premature infants (less than 34 weeks of gestation) receiving parenteral nutrition. Intravenous administration of lipid emulsion increased serum concentrations of free fatty acids at 2, 4, and 8 h after infusion. Despite this increase, serum levels of ketone bodies remained low, reaching only 40 to 45% of levels in full-term infants receiving enteral feeds. In premature infants, levels of plasma total and free carnitine were about half those in full-term infants and were not altered by lipid infusion. The results indicate limited potential for lipid emulsion as a source of energy in premature infants, possibly because carnitine insufficiency restricts fatty acid oxidation.
Carnitine↗
Safflower oil emulsion administration during parenteral nutrition in the preterm infant. 1. Effect on essential fatty acid status.
To determine the effect of a safflower oil emulsion on the essential fatty acid (EFA) status of preterm infants during parenteral nutrition, subjects were randomized to receive Liposyn at 0.34 g (group 1), 0.68 g (less than 0.5% of lipid from linolenic acid, group 2), or Modified Liposyn at 0.68 g/kg/day (5.0% of lipid from linolenic acid, group 3). Doses of 0.34 and 0.68 g of Liposyn provided linoleic acid in amounts equivalent to 2 and 4% of the estimated caloric requirement (120 cal/kg/day) and 5 and 10% of the actual caloric intake. No significant differences were detected in plasma phospholipid triene/tetraene ratios and arachidonic acid levels between groups 1 and 2 or between groups 2 and 3, respectively. Plasma phospholipid triene/tetraene ratio and arachidonic acid did not change in the lipid-supplemented group throughout the study period, but the former remained significantly lower (p less than 0.001) and the latter significantly greater (p less than 0.001) than in a reference group of infants who received fat-free parenteral nutrition. We conclude that Liposyn administration providing linoleic acid at 2 or 4% of the estimated caloric requirement or 5 or 10% of the actual caloric intake prevented any significant changes in essential fatty acid status from occurring. Moreover, linolenic acid supplementation at 5% of the total lipid intake did not appear to affect arachidonic acid synthesis in the preterm infant.
Arachidonic Acid↗
Safflower oil emulsion administration during parenteral nutrition in the preterm infant. 2. Effect on triglyceride and free fatty acid levels.
During a study to evaluate the effect of a safflower oil emulsion on essential fatty acid status during parenteral nutrition, we also measured plasma triglycerides and plasma free fatty acids (FFA) in a group of preterm infants. Subjects received 0.34 g/kg (group 1) or 0.68 g/kg (group 2) of lipid daily for 5 days. Essential fatty acid status remained normal in both groups, but the changes in plasma triglycerides were greater (p less than 0.025), and hypertriglyceridemia was somewhat more common (p = 0.06) in group 2 than in group 1. Plasma FFA did not differ in either treatment group. However, postinfusion FFA were greater (p less than 0.05) and FFA uptake was less (p less than 0.05) in infants at less than 32 than at 32-34 weeks gestation, but in no instance did postinfusion FFA exceed an FFA/albumin ratio of 6:1. In addition, triglyceride and FFA uptake did not improve during the study, but the changes in plasma triglycerides and FFA were greater (p less than 0.05) at the end than at the beginning of the study.
Emulsions↗
Essential fatty acid status of the premature infant during short-term fat-free parenteral nutrition.
This study was designed to evaluate the effect of fat-free parenteral nutrition on the essential fatty acid status of a group of stable premature infants during the first 10 days of life. Nine infants had a gestational age of less than 32 weeks (Group 1), and 10 infants, 32-34 weeks (Group 2). Five of nine infants in Group 1 and two of 10 infants in Group 2 developed essential fatty acid deficiency (EFAD) (triene/tetraene ratio greater than 0.4). In three infants, EFAD was present by 5 days of age; and in four, between 5 and 10 days of age. The difference in frequency of EFAD between Groups 1 and 2 is statistically significant (p less than 0.05). The development of EFAD as a function of postnatal age could be predicted using a simple regression, y = -0.14 + 0.07x (r = 0.64, p less than 0.0001), where y represents the triene/tetraene ratio and x the postnatal age in days. We conclude that (a) EFAD may develop rapidly in the premature infant; (b) the more immature the infant, the greater the risk of EFAD; (c) the degree of EFAD increases with the duration of fat-free parenteral nutrition.
Chromatography, Thin Layer↗
Effect of postnatal undernutrition on ketone metabolism and its relation to metabolic changes in brain and liver of rats.
The effects of undernutrition on ketone metabolism and its relation to brain growth in developing rats were studied. In the first series of experiments, undernutrition was induced by increasing the litterr size from 4 to 16 pups. Body weight of pups was inversely related to litter size. Increasing the litter size lowered brain weight by 6-16% and liver weight by 20-46%. The ratio of brain weight:body weight was greater by 16 to 39% in the larger litters. Increasing the litter size did not alter concentration of brain lipid. liver glycogen or plasma ketone bodies. In the second series of experiments, undernutrition was induced by restricting maternal dietary intake to 40% of that of the control dam. This undernutrition caused a more pronounced growth retardation than that resulting from increasing litte size. At 14 days of age, the mean body weight of the undernourished group was 44% lower than the control value. The dietary restriction lowered brain weight by 19%, liver weight by 38%, liver glycogen by 47%, brain lipid by 11%, plasma ketone bodies by 30%, glucose by 37% and the rate of hepatic ketogenesis by 28%. The results suggest that brain-growth retardation is related to low brain lipids and impaired ketone metabolism.
Animal Population Groups↗