Sleep problems in children and adolescents in an attention deficit hyperactivity disorder service.

OBJECTIVES: Sleep problems are common amongst children and adolescents with attention deficit hyperactivity disorder (ADHD). The purpose of this study was to investigate sleep problems in children and adolescents attending a specialist ADHD service. METHODS: This was a cross-sectional online survey combined with a retrospective chart review, conducted in the ADHD Assessment, Diagnosis, Management, initiation, Research and Education (ADMiRE) service, the first public specialist ADHD service for young people in Ireland. Participants were caregivers of children and adolescents with ADHD attending ADMiRE. Sleep was assessed using The Children's Sleep Habits Questionnaire (CSHQ) and ADHD symptoms were assessed using an abbreviated version of the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV). Details regarding patient demographics, co-morbidities and medication were collected from patient records. RESULTS: Eighty-four percent of young people scored above the clinical cut-off for a sleep disorder. The most frequently reported sleep problems were related to sleep onset and sleep duration, and 64% of respondents met the criteria for two or more sleep problems. ADHD severity was associated with greater sleep problems. Co-morbid physical, neurodevelopmental, and mental health disorders as well as stimulant use were not associated with greater sleep problems. CONCLUSION: Sleep problems are very common amongst children and adolescents with ADHD. This study has demonstrated an association between more sleep problems and ADHD severity. These findings highlight the need for both effective ADHD treatment to ensure optional sleep in young people as well as effective interventions for sleep problems to prevent worsening of ADHD symptoms.

The insulin hypoglycemia-induced inhibition of gonadotropin-releasing hormone pulse generator activity in the rhesus monkey: roles of vasopressin and corticotropin-releasing factor.

Insulin-induced hypoglycemia (IIH) profoundly inhibits the activity of the hypothalamic GnRH pulse generator. The aim of this study was to determine the role of vasopressin and CRF in this response. Ovariectomized rhesus monkeys with chronically implanted recording electrodes in the mediobasal hypothalamus and with intracerebroventricular (icv) cannulas in the lateral ventricle were placed in primate chairs, and blood samples were taken every 10 min. Pulse generator activity was monitored electrophysiologically by detecting characteristic increases in hypothalamic multi-unit activity (MUA volleys) and by attendant LH pulses measured in peripheral blood. Arginine vasopressin (AVP) infused via the i.c.v. cannula (50 micrograms/60 microliters.h) in eight monkeys failed to decrease pulse generator activity, as measured by the frequency of MUA volleys, but decreased mean serum LH concentrations (P < 0.001) while increasing serum cortisol levels (P < 0.02). Central administration of an AVP antagonist ([deamino-Pen1, O-Me-Tyr2-Arg8] vasopressin) in four monkeys at a rate (180 micrograms/60 microliters.h) that had previously been found to block the aforementioned effects of coadministered AVP failed to prevent the IIH-induced inhibition of GnRH pulse generator activity and LH secretion in the same animals. On the other hand, a CRF antagonist, [D-Phe12,Nle21,38,C alpha MeLeu37] rat CRF-(12-41), infused i.c.v. at a rate of 500 micrograms/60 microliters.h in four monkeys, delayed the inhibition of pulse generator frequency in response to IIH. These results suggest that AVP does not mediate the hypoglycemia-induced inhibition of GnRH pulse generator frequency in the rhesus monkey, but that CRF may be involved in this response.

On the mechanism of the positive feedback action of estradiol on luteinizing hormone secretion in the rhesus monkey.

In women and rhesus monkeys, both the negative and positive feedback actions of estradiol (E2) on gonadotropin secretion (inhibition followed by a surge) can be exerted directly at the level of the pituitary gland. We have tested the hypothesis that the positive feedback action of E2 represents but an "escape" from its negative feedback inhibition of gonadotropin secretion consequent to a desensitization of the gonadotropes occasioned by sustained exposure to elevated concentrations of the steroid. We have attempted to replicate such a desensitization by blocking the negative feedback action of E2 by the administration of a potent estrogen receptor antagonist devoid of any agonistic properties (ZM 182,780) to rhesus monkeys in the midfollicular phase of the menstrual cycle (n = 14). The estrogen antagonist, administered at a dose that in separate experiments completely blocked both the negative and the positive feedback effect of exogenous E2 on pituitary LH secretion, failed to produce a surge-like increase in serum LH concentrations. The present results do not support the hypothesis that the LH surge is the consequence of the removal of the negative feedback action of E2. Evidence is presented that ZM 182,780, in contrast to its inhibition of E2-induced LH surges, cannot block the inhibition of hypothalamic GnRH pulse generator activity by E2.

Ultrastructure and distribution of substance P-immunoreactive sensory collaterals in the guinea pig prevertebral sympathetic ganglia.

A light and electron microscopic study has been made of the substance P-immunoreactive networks formed by sensory nerve fibres in the prevertebral sympathetic ganglia of the guinea pig to seek confirmation that these networks arise from collateral branches of sensory fibres passing through the ganglia and to explore the synaptic and other specialized relationships established by these networks. Slices from coeliac-superior mesenteric and inferior mesenteric ganglia of young adult males, perfusion-fixed by paraformaldehyde, were immunostained with a monoclonal antibody to substance P, and the immunolabelling was visualized by a peroxidase reaction. Immunolabelled fibres passing through the ganglia were seen by light microscopy to give off varicose collaterals that ramified in the ganglionic neuropil. Electron microscopy showed that the parent fibres were almost exclusively unmyelinated. Many collaterals ran directly beneath the basal lamina bordering the intraganglionic tissue spaces, and the varicosities either remained superficially exposed under the basal lamina or sank deeper into the supporting Schwann cells, becoming apposed to dendrites of the ganglionic neurones, upon which they formed synapses, or to other nerve terminals. The incidence of these specific associations was quantified, singly and in combination. Synapses could be situated at the same level as unlabelled synapses on the same dendrite, and exposed varicosities could lie within 0.5 micron of exposed, postsynaptic dendrites. These observations confirm a collateral, synaptic nature for the networks and suggest additional nonsynaptic modes of release and sites of transmitter action. They are consistent with the hypothesis that the system serves a nocifensor function of axon reflex type.

Inputs to motoneurones in the hypoglossal nucleus of the rat: light and electron microscopic immunocytochemistry for choline acetyltransferase, substance P and enkephalins using monoclonal antibodies.

Light and electron microscopic peroxidase-antiperoxidase immunocytochemistry has been used to localize choline acetyltransferase, substance P and enkephalin in the hypoglossal nucleus of the rat. Choline acetyltransferase immunoreactivity was observed in motoneurone cell bodies and proximal dendrites, in large varicosities in the surrounding neuropil and in nerve terminals in synaptic contact with immunostained motoneurones. Most choline acetyltransferase immunostained terminals which made synaptic contact with motoneurone cell bodies and proximal dendrites possessed prominent subsynaptic cisterns and belong to the terminal type referred to in the literature as C or L. Substance P and enkephalin immunoreactivity did not occur in motoneurones but was seen in fibres and synaptic terminals. Substance P immunoreactive fibres made multiple axosomatic contacts while enkephalin immunoreactive terminals made synaptic contact mainly with large and small dendrites. C terminals were not stained for either substance P or enkephalin. This study provides immunocytochemical support for the classic identification of hypoglossal motoneurones as cholinergic and in addition shows that these neurones are innervated by a number of morphologically and chemically distinct terminal types. C terminals have previously been shown to contain cholinesterase and our demonstration that these terminals contain choline acetyltransferase thus provides additional evidence for their cholinergic nature and for a cholinergic innervation of hypoglossal motoneurones. The origin of the immunoreactive terminals was not identified in this study but possible candidates include the raphe nuclei for substance P. and propriobulbar interneurones for choline acetyltransferase.

Rapid serodiagnosis of gram-positive bacterial endocarditis.

OBJECTIVES: To characterize a serological test for diagnosing endocarditis caused by Gram-positive cocci. METHODS: We have developed an indirect enzyme-linked immunosorbent assay (ELISA) for the serological detection of Gram-positive infections. The test measures serum IgG directed towards lipid S, a recently identified exocellular glycolipid antigen which is related to lipoteichoic acid. We have previously shown the test to be of value in serodiagnosis of central venous catheter-associated sepsis and infection of orthopaedic prostheses caused by coagulase-negative staphylococci. We now describe the application of this test in endocarditis. RESULTS: Serum IgG levels to lipid S were significantly elevated in 34 patients with Gram-positive bacterial endocarditis confirmed as 'definite' by the Duke criteria as compared to 50 control patients. The test had a sensitivity of 88% and a specificity of 88%. CONCLUSIONS: The assay is independent of culture results or endocardial imaging, making it complementary to currently used investigations. It may therefore be possible to refine the current Duke criteria for diagnosing endocarditis. We describe an algorithm which incorporates lipid S serology into a positive diagnostic strategy.

A rare congenital heart disease in an elderly long-distance runner: a case report.

Introduction. Cor triatriatum is a rare congenital heart disease found incidentally in children. Although cor triatriatum can be an incidental finding in asymptomatic adults; it is extremely rare to find elderly patients without symptoms and is unique in a long distance runner. Case Presentation. We present the case of an 83-year-old long-distance runner with cor triatriatum sinistrum and atrial fibrillation who continues to be asymptomatic and has continued to run long distances, retaining his excellent functional capacity. Conclusion. Cor triatriatum sinistrum is a rare congenital disease, which is often found incidentally in children. Although it is also seen in adults without symptoms at normal exertion, it is rare to have this condition in long-distance runners especially in elderly people with other structural heart disease, that is, atrial fibrillation and mitral regurgitation.

Effects of exogenous testosterone on sonic muscle mass in the weakfish, Cynoscion regalis.

Three testosterone (T) implant experiments were carried out to investigate the hormonal control of seasonal hypertrophy in the sound producing, or sonic, muscles of the weakfish Cynoscion regalis. The first experiment examined the role of T in the seasonal increase in sonic muscle mass noted in adult male weakfish during the spring and summer spawning period. Specimens held over-winter were implanted with T or vehicle prior to the natural spawning season. The sonic muscle mass of the T-implanted group increased two and a half-fold over a period of 3 weeks, while that of the sham-implanted group did not change. At the end of the experiment, the cross-sectional area of the sonic muscle fibers in the T-implanted group averaged 500 microns 2, while that of the sham-implanted group averaged 300 microns 2. In a second experiment, the elevated sonic muscle mass of spawning male weakfish was sustained with pharmacological levels of plasma T for a period of 4 months following the spawning season. The sonic muscle mass of the sham-implanted group decreased to typical postseason values. In a third experiment, male and female age-0 weakfish were held over-winter and then implanted with T in advance of their first natural spawning season. The sonic muscles of the T-treated male specimens attained twice the mass of those of the sham-implanted male specimens in 3 weeks time. No sonic muscle development was noted in any of the female specimens.

Effects of fish size and temperature on weakfish disturbance calls: implications for the mechanism of sound generation.

To categorize variation in disturbance calls of the weakfish Cynoscion regalis and to understand their generation, we recorded sounds produced by different-sized fish, and by similar-sized fish at different temperatures, as well as muscle electromyograms. Single, simultaneous twitches of the bilateral sonic muscles produce a single sound pulse consisting of a two- to three-cycle acoustic waveform. Typical disturbance calls at 18 degrees C consist of trains of 2-15 pulses with a sound pressure level (SPL) of 74 dB re 20 microPa at 10 cm, a peak frequency of 540 Hz, a repetition rate of 20 Hz and a pulse duration of 3.5 ms. The pulse duration suggests an incredibly short twitch time. Sound pressure level (SPL) and pulse duration increase and dominant frequency decreases in larger fish, whereas SPL, repetition rate and dominant frequency increase and pulse duration decreases with increasing temperature. The dominant frequency is inversely related to pulse duration and appears to be determined by the duration of muscle contraction. We suggest that the lower dominant frequency of larger fish is caused by a longer pulse (=longer muscle twitch) and not by the lower resonant frequency of a larger swimbladder.

Weakfish sonic muscle: influence of size, temperature and season.

The influence of temperature, size and season on the sounds produced by the sonic muscles of the weakfish Cynoscion regalis are categorized and used to formulate a hypothesis about the mechanism of sound generation by the sonic muscle and swimbladder. Sounds produced by male weakfish occur at the time and location of spawning and have been observed in courtship in captivity. Each call includes a series of 6-10 sound pulses, and each pulse expresses a damped, 2-3 cycle acoustic waveform generated by single simultaneous twitches of the bilateral sonic muscles. The sonic muscles triple in mass during the spawning season, and this hypertrophy is initiated by rising testosterone levels that trigger increases in myofibrillar and sarcoplasmic cross-sectional area of sonic muscle fibers. In response to increasing temperature, sound pressure level (SPL), dominant frequency and repetition rate increase, and pulse duration decreases. Likewise, SPL and pulse duration increase and dominant frequency decreases with fish size. Changes in acoustic parameters with fish size suggest the possibility that drumming sounds act as an 'honest' signal of male fitness during courtship. These parameters also correlate with seasonally increasing sonic muscle mass. We hypothesize that sonic muscle twitch duration rather than the resonant frequency of the swimbladder determines dominant frequency. The brief (3.5 ms), rapidly decaying acoustic pulses reflect a low-Q, broadly tuned resonator, suggesting that dominant frequency is determined by the forced response of the swimbladder to sonic muscle contractions. The changing dominant frequency with temperature in fish of the same size further suggests that frequency is not determined by the natural frequency of the bladder because temperature is unlikely to affect resonance. Finally, dominant frequency correlates with pulse duration (reflecting muscle twitch duration), and the inverse of the period of the second cycle of acoustic energy approximates the recorded frequency. This paper demonstrates for the first time that the dominant frequency of a fish sound produced by a single muscle twitch is apparently determined by the velocity of the muscle twitch rather than the natural frequency of the swimbladder.

Induction of UV-resistant DNA replication in Escherichia coli: induced stable DNA replication as an SOS function.

The striking similarity between the treatments that induce SOS functions and those that result in stable DNA replication (continuous DNA replication in the absence of protein synthesis) prompted us to examine the possibility of stable DNA replication being a recA+ lexA+-dependent SOS function. In addition to the treatments previously reported, ultraviolet (UV) irradiation or treatment with mitomycin C was also found to induce stable DNA replication. The thermal treatment of tif-1 strains did not result in detectable levels of stable DNA replication, but nalidixic acid readily induced the activity in these strains. The induction of stable DNA replication with malidixic acid was severely suppressed in tif-1 lexA mutant strains. The inhibitory activity of lexA3 was negated by the presence of the spr-51 mutation, an intragenic suppressor of lexA3. Induced stable DNA replication was found to be considerably more resistant to UV irradiation than normal replication both in a uvrA6 strain and a uvr+ strain. The UV-resistant replication occurred mostly in the semiconservative manner. The possible roles of stable DNA replication in repair of damaged DNA are discussed.

The effects of seasonal hypertrophy and atrophy on fiber morphology, metabolic substrate concentration and sound characteristics of the weakfish sonic muscle.

Male weakfish Cynoscion regalis possess highly specialized, bilateral, striated sonic muscles used in sound production associated with courtship. Androgen-driven hypertrophy of the muscles during the late spring spawning period results in a tripling of sonic muscle mass followed by post-spawning atrophy. This study examined the morphological and biochemical changes underlying seasonal changes in sonic muscle mass and the functional effects of these on contraction as measured by sound production. Sonic muscle fiber cross-sectional area (CSA) increased significantly during the period of hypertrophy and then decreased by nearly 60%. Both the CSA of the contractile cylinder and that of the peripheral sarcoplasm decreased significantly by late summer, with the peripheral ring of sarcoplasm virtually disappearing. Muscle protein content followed a similar trend, suggesting a major loss of structural elements during atrophy. Muscle glycogen and lipid content decreased precipitously in early June during the period of maximal sound production. Sound pressure level increased and sound pulse duration decreased with increasing sonic muscle mass, indicating that sonic muscle fibers contract with greater force and shorter duration during the spawning season. Neither the pulse repetition rate nor the number of pulses varied seasonally or with muscle mass, suggesting that the effects of steroids on the acoustic variables are more pronounced peripherally than in the central nervous system. Seasonal sonic muscle hypertrophy, therefore, functions as a secondary sexual characteristic that maximizes vocalization amplitude during the spawning period.

Ventricular arrhythmias induced by ischaemia-reperfusion are unaffected by myocardial glutathione depletion.

Reduced glutathione (GSH) is a major myocardial antioxidant. Since reperfusion phenomena such as ventricular fibrillation (VF) are associated with oxygen free radical production during ischaemia, myocardial GSH depletion might be expected to increase susceptibility to such phenomena. This possibility was tested in isolated rat hearts using diethylmaleate (DEM) or L-buthionine-SR-sulfoximine (BSO) to deplete myocardial GSH. High dose DEM (860 mg/kg) depleted myocardial GSH from a control mean of 7.64 +/- 0.73 to 3.18 +/- 0.56, low dose DEM (215 mg/kg) to 4.29 +/- 0.53 nmol/mg protein and BSO (4 mmol/kg) from a control mean of 6.94 +/- 0.54 to 2.18 +/- 0.14 nmol/mg protein. Hearts were perfused in the Langendorff mode at 37 degrees C with bicarbonate buffer (K+ = 4.3 mM). Regional ischaemia was induced for 5, 8.5, 10, 20 or 40 min (DEM groups: n = 10/treatment/time point) or 8.5 min only (BSO groups: n = 10/treatment) then hearts were reperfused for 5 min. Reperfusion VF incidence showed a classical "bell-shaped" curve, but there was no difference in VF incidence, VF time-to-onset, arrhythmia duration and "arrhythmia scores" between GSH-depleted and control hearts. Depleting myocardial GSH is not proarrhythmic for reperfusion-induced arrhythmias. It would appear GSH is not significantly involved in protecting against the oxidant stress of reperfusion, or conversely that the reserve of this redox system is so high only severe depletion might show an effect.

On the role of gonadotropin-releasing hormone (GnRH) in the operation of the GnRH pulse generator in the rhesus monkey.

The pulsatile secretion of luteinizing hormone (LH), occasioned by the pulsatile release of gonadotropin-releasing hormone (GnRH), is closely associated with concurrent increases in multiunit electrical activity in the mediobasal hypothalamus (MUA volleys), the electrophysiological correlates of GnRH pulse generator activity. These volleys represent a highly synchronized increase in firing frequency of individual neurons. The origin of these rhythmic oscillations in unit activity and the mechanisms responsible for their synchronization are unknown. The purpose of the present study was to examine the role, if any, of GnRH in the functioning of the GnRH pulse generator in rhesus monkeys. Ovariectomized animals bearing recording electrodes chronically implanted in the mediobasal hypothalamus and fitted with intracerebroventricular (ICV) cannulae in the lateral ventricle and with indwelling cardiac catheters were studied. LH was measured in venous blood withdrawn from the cardiac catheters every 10 min while hypothalamic electrical activity was monitored continuously. In Experiment 1, following a 3- to 4-hour control period, GnRH was infused ICV at a rate of 300 ng/kg body weight (BW)/h over 4-5 h. In Experiment 2, antide, a long-acting GnRH antagonist, was injected ICV in a dose of 105 microg/kg BW after a control period of 3-4 h. Additional control experiments were performed in each animal using vehicle alone. Neither GnRH nor antide affected the frequency of MUA volleys and attendant LH pulses despite significant alterations in LH secretion. These results suggest that, in the rhesus monkey, GnRH may not be involved in the operation of the GnRH pulse generator.

On the mechanism of lactational anovulation in the rhesus monkey.

The relative roles of infant suckling and of maternal prolactin (PRL) secretion in lactational anovulation were studied in ovary-intact and ovariectomized rhesus monkeys nursing young that had been removed from their natural mothers. Hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator activity was monitored electrophysiologically in freely behaving animals by radiotelemetry. Serum luteinizing hormone, PRL, estradiol, and progesterone were also measured. Suckling inhibited GnRH pulse generator activity and ovarian cyclicity in all ovary-intact females but had no such effect on the pulse generator in long-term ovariectomized animals. When PRL secretion was suppressed by daily bromocriptine administration, GnRH pulse generator activity remained significantly inhibited and ovulation was prevented in four monkeys (6 trials), whereas in two females (6 trials) a rapid increase in pulse generator frequency and the resumption of ovarian cyclicity were observed although suckling activity was maintained. One monkey displayed both response types. Although these results indicate that suckling per se is able to restrain GnRH pulse generator activity in the absence of PRL, they also suggest that the relative importance of these determinants is variable depending on factors that remain to be determined. The present study also confirms the permissive role of the ovary in the lactational suppression of GnRH pulse generator activity.

Trading force for speed: why superfast crossbridge kinetics leads to superlow forces.

Superfast muscles power high-frequency motions such as sound production and visual tracking. As a class, these muscles also generate low forces. Using the toadfish swimbladder muscle, the fastest known vertebrate muscle, we examined the crossbridge kinetic rates responsible for high contraction rates and how these might affect force generation. Swimbladder fibers have evolved a 10-fold faster crossbridge detachment rate than fast-twitch locomotory fibers, but surprisingly the crossbridge attachment rate has remained unchanged. These kinetics result in very few crossbridges being attached during contraction of superfast fibers (only approximately 1/6 of that in locomotory fibers) and thus low force. This imbalance between attachment and detachment rates is likely to be a general mechanism that imposes a tradeoff of force for speed in all superfast fibers.