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Inhibitory effect of propylthiouracil-induced hypothyroidism in rat on oxidative drug metabolism.

The effect of propylthiouracil (PTU) pretreatment on in vivo and in vitro oxidative drug metabolism was determined in the rat. Whereas pentobarbital sleeping time (PBST) and zoxazolamine paralysis time (ZZPT) were used as indices of in vivo drug metabolizing activity, biotransformation of aminopyrine and aniline by hepatic microsomal preparations were used as indices of in vitro drug metabolizing enzymes activities. PTU pretreatment significantly prolonged both PBST and ZZPT. Whereas PTU did not affect microsomal protein concentration or cytochrome P-450 content, it significantly decreased microsomal cytochrome c reductase and aniline hydroxylase activities. These changes in enzymatic activities were observed in microsomal preparations from either non-fasted or 24-hr fasted rats. Our results suggest that PTU-induced hypothyroidism modifies the metabolism and effectiveness or toxicity of concomitantly administered drugs.

Aminopyrine↗

Subchronic toxicity studies of the antidiabetic herbal preparation ADD-199 in the rat: absence of organ toxicity and modulation of cytochrome P450.

The subchronic toxicity of the aqueous antidiabetic herbal extract ADD-199, prepared from Maytenus senegalensis, Annona senegalensis, Kigelia africana and Lanneawelwitschii, and administered at a daily dose of 100 or 500 mg/kg body weight over 30 days, was investigated in male Wistar albino rats. Certain haematological, urine and plasma biochemical parameters, and modulation of some hepatic cytochrome P450 (CYP) isozymes were measured as indices of organ specific toxicity or potential for drug interactions. ADD-199 did not affect plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and albumin or creatinine kinase (CK) levels. It also did not affect plasma creatinine and urea levels. Furthermore, ADD-199 neither affected PCV nor blood Hb, RBC, reticulocytes, platelets, lymphocytes and granulocyte levels. It, however, caused significant dose-dependent reductions in WBC counts at day 15 with varying degrees of recovery by day 30. It also reduced the rate of body weight increases after week 3. However, no changes were observed in organ weights at termination. ADD-199 did not significantly affect zoxazolamine-induced paralysis and pentobarbital-induced sleeping times as well as certain CYP isozyme activities in rats. These findings suggest that ADD-199 had no overt organ specific toxicity and did not demonstrate a potential for drug interactions via CYP-mediated metabolism in the rat on subchronic administration.

Animals↗

Silicone tracheal cannula.

This presentation is to introduce a silicone tracheal cannula which has been designed for use in selected cases instead of a tracheotomy tube. The design of the cannula was developed in the laboratory and has now been used clinically over a period of four years in 26 cases. Special features of the cannula include a one-size diameter which is suitable for all adults. An inner flange is shaped so as to conform with the inner aspect of the anterior wall of the trachea and to prevent rotation and anterior displacement of the cannula. The inner flange is angulated to allow for proper direction of the long axis of the cannula. An outer flange fits into one of a number of grooves and prevents posterior displacement of the cannula. Thus far the silicone tracheal cannula has been used in cases of sleep apnea, bilateral vocal cord paralysis in the position of adduction, intermittent glottic insufficiency, laryngeal carcinoma, chronic lung disease, and short-term necessity for a tracheotomy. Special equipment has been designed for ease of the surgical procedure required for insertion of the cannula. A one-way valve has been designed which is easily applied to the cannula. A variation of the silicone tracheal cannula has been designed for long-term use.

Catheterization↗

Effect of unisexual Schistosoma mansoni infections on hepatic drug metabolism of mice.

The effect of unisexual schistosome infection on the activities of several hepatic enzymes was studied in mice. The activities of hepatic drug-metabolizing enzymes in mice infected with either female or male schistosomes were not significantly different from those of noninfected control animals. However, the total amount of heme pigment in the liver of infected mice was 2.7 (female infection) and 8.9 (male infection) times greater than that of control animals. The durations of hexobarbital sleeping times and of zoxazolamine paralysis in unisexual schistosome infections did not differ from those of uninfected controls. Therefore, an accumulation of schistosome pigment without egg deposition, as in this unisexual infection study, does not result in a severe reduction of hepatic drug-metabolizing capacity.

Animals↗

Effects of three recombinant human leukocyte interferons on drug metabolism in mice.

Three recombinant human leukocyte interferons (IFLrA, IFLrD, and a hybrid IFLrA/D) that differ markedly in their antiviral activity in murine L cells were examined for their effects on hepatic microsomal drug metabolism in adult female CD-1 mice. When administered for 1 or 3 consecutive days, IFLrA/D, which exhibited the highest antiviral activity in murine L cells, caused a dose-dependent decrease in cytochrome P-450 content and in the rate of metabolism in vitro of benzo[a]pyrene, hexobarbital, 7-ethoxycoumarin, benzphetamine, and zoxazolamine. The concentration of cytochrome b and the activity of NADPH-cytochrome c reductase were also depressed when IFLrA/D was administered for 3 days. Similar but somewhat smaller changes were observed following treatment of mice with IFLrD, which possessed approximately 1% of the antiviral activity of IFLrA/D in murine L cells. In contrast, IFLrA, which was essentially devoid of antiviral activity in the mouse cell line, failed to depress cytochrome P-450 levels and in vitro drug metabolism activity in a consistent or dose-dependent manner. Cytochrome P-450 content and the in vitro rate of metabolism of benzphetamine and zoxazolamine were maximally depressed 8-24 hr after a single intraperitoneal injection of 1.5 micrograms of interferon per mouse; at this time the interferons were no longer detectable in serum. Near-normal levels of cytochrome P-450 and in vitro drug metabolism activity were restored by 48 hr after a single injection of interferon. Treatment of mice with 1.5 micrograms of IFLrA/D once daily for 3 days prolonged hexobarbital sleeping time but not zoxazolamine paralysis time, whereas neither of these was influenced by treatment with IFLrA or D. The results indicate that an interferon-dependent process reduces the level of microsomal cytochrome P-450 in liver and potentiates the pharmacological actions of certain drugs in mice.

Animals↗

The structure of night sleep and cardiac rhythm in patients suffering for many years from hypo- and akinesia.

The polygram of night sleep was studied in 3 patients, who due to a lesion to the CNS and peripheral nervous system were in a state of long-term akinesia and artificial lung ventilation. The cyclic organization of sleep and its transition from stage to stage, as a whole corresponded with those in healthy subjects. However, there was a general tendency in all patients to a reduction of sleep spindles. There was also a tendency to the stability of heart rate during night sleep. The relationship between delta-sleep and sleep spindles and motor activity is discussed.

Adult↗

Eating seizures and emotional facial paresis: evidence suggesting the amygdala is a common anatomophysiological substratum.

The medial basotemporal lobes (hippocampus, amygdala, parahippocampal gyrus) are considered to be parts of the system responsible for nonvolitional facial movements. In patients with temporal lobe epilepsy, lower facial weakness during emotional expression has been found to occur almost exclusively contralateral to the temporal lobe with the epileptogenic focus. Repetitive and chronic stimulation of the amygdala during eating has also been postulated as a probable mechanism for eating seizures. The authors present the illustrative aspects of both facial asymmetry and eating seizures in a case of mesial temporal lobe epilepsy (MTLE). This report provides evidence that the amygdala may be the common anatomical basis for three different aspects of this patient: emotional facial paresis, eating seizures, and sleep paroxysmal microarousals.

Adult↗

Early diagnosis and stage classification of vocal cord abductor paralysis in patients with multiple system atrophy.

OBJECTIVES: Vocal cord abductor paralysis (VCAP) is a life threatening complication which may cause nocturnal sudden death in patients with multiple system atrophy. However, the early diagnosis of VCAP is often difficult to make on routine laryngoscopy performed during wakefulness, as stridor, which is the sole symptom of VCAP in the early stage, develops only during sleep. The aim was to investigate laryngeal dysfunction in patients with multiple system atrophy while awake and asleep. METHODS: Seven patients with multiple system atrophy with nocturnal stridor and five control patients were studied. Vocal cord movement was analysed by laryngoscopy while the patients were awake and also during sleep induced by intravenous diazepam. RESULTS: When awake, for the seven patients with multiple system atrophy normal movement of the vocal cords occurred in three, mild abduction restriction in three, and paradoxical movement in one. When asleep, however, all showed obvious paradoxical movement with high pitched inspiratory stridor. In controls, there were no differences in the vocal cord movement between wakefulness and sleep. From these findings, VCAP could be divided into four stages: stage 0 (normal) with normal vocal cord movement during both wakefulness and sleep, stage 1 (mild VCAP) with normal movement during wakefulness and paradoxical movement during sleep, stage 2 (moderately severe VCAP) with abduction restriction during wakefulness and paradoxical movement during sleep, and stage 3 (severe VCAP) with an almost midline position for the vocal cords during both wakefulness and sleep. CONCLUSIONS: Laryngoscopy during sleep can disclose subclinical VCAP, making an early diagnosis of VCAP in patients with multiple system atrophy. Stage 2 of VCAP seems to be a suitable stage for tracheostomy in patients with multiple system atrophy.

Aged↗

Arnold-Chiari malformation and paralysis of the diaphragm.

A woman aged 17 years presented with symptoms of somnolence. A bilateral diaphragmatic paralysis and an Arnold-Chiari malformation were diagnosed. Lung function tests revealed a marked restrictive defect and a blunted ventilatory response to hypercapnia and hypoxia. A sleep study also showed central apneas, an irregular pattern of breathing and marked hypoventilation.

Adolescent↗

[Sleep disorders in Steele-Richardson disease. Polygraphic study of 3 cases].

24 recordings of night-time sleep in three patients suffering from progressive supranuclear paralysis were carried out. There was observed: a tendency to insomnia, disappearance of spindles, an invasion of slow sleep immediately it appeared by the muscular and ocular criteria of paradoxical sleep, a considerable reduction in paradoxical sleep in the strict sense of the term, the latency of which in making its appearance was, however, maintained; progressive invasion of the paradoxical phases by slow waves. These abnormalities differ from those found in Parkinson's disease.

Adult↗

Therapeutic effects of tracheostomy in two cases of hypersomnia with respiratory disturbance during sleep.

Recently the association of hypersomnia and respiratory insufficiency without lesion in the respiratory organ has attracted attention of many investigators. Obese patients with such a condition have been called the Pickwickian syndrome. In this report, two non-obese patients with a similar condition were presented, one with micrognathia and frequent apneic episodes during sleep, and the other with laryngeal stenosis due to paralysis of the bilateral laryngeal nerves and chronic laryngitis. Tracheostomy had a prompt and long-lasting therapeutic effect to make their sleep stable and also to relieve their excessive daytime sleepiness. These findings suggest that the obstruction or stenosis of the upper airway during sleep disturbed their nocturnal sleep, and that their excessive daytime sleepiness was a phenomenon compensating for their disturbed nocturnal sleep.

Adult↗

Differences in neuropsychological correlates between normals and those experiencing "Old Hag Attacks".

240 university students were given The Cognitive Laterality Battery as well as a questionnaire, the answers to which were used to identify those who had experienced an "Old Hag Attack." This refers to a hypnagogic sleep disorder in which there is paralysis and, quite often, terrifying hallucinations. Those suffering from this disorder showed a statistically significantly different profile of scores from normal subjects on The Cognitive Laterality Battery. The implications of this finding for existing theories concerning "Old Hag Attacks" are discussed.

Auditory Perception↗

The pathophysiology of sleep disorders in pediatrics. Part II. Sleep disorders in children.

In this part of the chapter we have used new terminology and developed a new system for classification of sleep disorders in children. We suggest that excessive daytime sleepiness should be investigated by clinicians before troubles at school necessitate referral. The narcolepsy-hypersomnia syndrome generally has not been recognized in the pediatric age group. Symptoms of excessive fear of falling asleep need to be viewed in this context. Sleep apnea-hypersomnia has received insufficient attention in the American literature. It is a syndrome that affects both adults and children with potentially disastrous cardiovascular and pulmonary complications. The relationship of the sleep apnea-hypersomnia syndrome to the sudded infant death syndrome remains speculative, although preliminary results from our longitudinal study have indicated a possible link. Both the narcolepsy-hypersomnia and the sleep apnea-hypersomnia syndromes are reviewed in detail. In contrast, we review briefly the NREM dyssomnias, including night terrors, sleepwalking, sleep talking and enuresis. All are well known to clinicians dealing with children, and we have related them to findings emanating from the sleep laboratory. We suggest that they are physiologically rather than psychogenically based and frequently represent immaturities of the central nervous system. Finally, the insomnias of childhood are presented. We emphasize that they are rare, and after ruling out organic conditions and drug-dependency syndromes, cultural styles or family stresses generally account for the majority of complaints.

Apnea↗

Influences of head positions and bite opening on collapsibility of the passive pharynx.

A collapsible tube surrounded by soft material within a rigid box was proposed as a two-dimensional mechanical model for the pharyngeal airway. This model predicts that changes in the box size (pharyngeal bony enclosure size anatomically defined as cross-sectional area bounded by the inside edge of bony structures such as the mandible, maxilla, and spine, and being perpendicular to the airway) influence patency of the tube. We examined whether changes in the bony enclosure size either with head positioning or bite opening influence collapsibility of the pharyngeal airway. Static mechanical properties of the passive pharynx were evaluated in anesthetized, paralyzed patients with sleep-disordered breathing before and during neck extension with bite closure (n = 11), neck flexion with bite closure (n = 9), and neutral neck position with bite opening (n = 11). Neck extension significantly increased maximum oropharyngeal airway size and decreased closing pressures of the velopharynx and oropharynx. Notably, neck extension significantly decreased compliance of the oropharyngeal airway wall. Neck flexion and bite opening decreased maximum oropharyngeal airway size and increased closing pressure of the velopharynx and oropharynx. Our results indicate the importance of neck and mandibular position for determining patency and collapsibility of the passive pharynx.

Adult↗

Respiratory complications and their management in motor neuron disease.

Although respiratory insufficiency is common in the advanced stages of motor neuron disease, some patients may develop distressing respiratory symptoms early in the course of the disease or even present with respiratory failure or arrest. We describe 14 patients with motor neuron disease who were considered for respiratory support; 11 received such support and all derived significant symptomatic improvement without distressing prolongation of life. Of the 8 patients with typical features of amyotrophic lateral sclerosis, 7 had predominant diaphragm weakness and 1 generalized respiratory muscle weakness; 7 received negative pressure ventilation by cuirass which improved both the quality of sleep and exercise tolerance. Three patients with predominantly bulbar disease had nocturnal apnoea or hypoventilation. Two received no support. One, who also developed diaphragm weakness, was treated by a cuirass, continuous positive airway pressure (CPAP), and later nocturnal intermittent positive pressure ventilation (IPPV). Three patients with progressive muscular atrophy had predominant diaphragm weakness or nocturnal apnoea. These patients received nocturnal CPAP, cuirass or IPPV with symptomatic benefit. This series shows that some patients with motor neuron disease, mainly those with symptoms due to respiratory muscle weakness in the absence of severe bulbar impairment, derive symptomatic benefit from supported ventilation.

Adult↗

[Sleep apnea in multiple system atrophy].

Multiple system atrophy(MSA) characterized clinically by any combination of autonomic, extrapyramidal or cerebellar symptoms and signs. MSA patients frequently manifest a variety of sleep-related respiratory disturbances, which are life threatening problems. Above all, a common and serious complication is upper-airway obstructive sleep apnea associated with stridor, which is caused by vocal cord abductor paralysis(VCAP). For the early diagnosis of VCAP, it is important to perform laryngoscopy during sleep, because VCAP does not appear during awakefulness in the early stage of MSA. Polysomnographic study should be obtain to assess the severity of respiratory disturbances. Tracheostomy is reliable treatment for respiratory disturbances due to VCAP, while nasal continuous positive pressure may be a useful treatment for some patients.

Humans↗