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A dose-response study in situational insomnia with zopiclone, a new tranquilizer.

Patients scheduled for next-day elective surgery were included in a randomized double-blind trial that compared the hypnotic and adverse effects of a placebo and four doses (3,5,6,9,13.5 mg) of a new compound, zopliclone. Sleep patterns were evaluated using a questionnaire; side effects were noted, and tests evaluating coordination and alertness were performed. Except for dreams and morning responses, there were significant differences in sleep indices at all dose levels. The 3.5-mg dose produced some significant differences compared with the placebo. All responses to the higher three doses were statistically significant; however, there was only a slight increase in effectiveness between 6 and 9 mg. Alertness, coordination tests, blood pressure, and adverse effects did not differ significantly among doses, except for the incidence of drowsiness and a bitter after-taste in the mouth.

Adolescent↗

[The human genome--chromosome 7].

The seventh chromosome achieved maximum popularity due to locus CFTR the pathological alleles of which cause one of the frequent metabolic hereditary disorders--cystic fibrosis. It is also the site which causes the development of some types of retinitis pigmentosa (RP9, RP10), osteogenesis imperfecta and dominant forms of myotonia congenita. On the long arms there is a complicated multi-segmental gene system of receptors of T-lymphocytes, TCRB, important in cell immunity and it is assumed that it is also the locus of taste perception of phenylthiocarbamide (PTC) is located there.

Chromosomes, Human, Pair 7↗

Case report: multiple endocrine neoplasia type 2B misdiagnosed as familial dysautonomia.

BACKGROUND: Familial dysautonomia (FD) is a rare autosomal recessive disorder of the peripheral nervous system, affecting exclusively Jewish children of Ashkenazi extraction. The typical clinical features consist of somatic abnormalities: failure to thrive, characteristic facies, excessive sweating, labile blood pressure, recurrent aspiration pneumonias, lack of tears, and diminished and later absent deep tendon reflexes with generalized reduction of pain sensation. Oro-dental features include a lack of tongue fungiform papillae, impairment of taste, oro-dental self-mutilation, dental crowding, excessive plaque and calculus accumulation, salivary over production and low caries experience. CASE REPORT: A child with multiple endocrine neoplasia type 2B (MEN 2B) received, at the age of 11 months, an incorrect diagnosis of familial dysautonomia (FD). At the age of 6 years, a paediatric dentist experienced with FD noticed a normal number and shape of tongue fungiform papillae, while expecting to find a smooth tongue lacking those structures. The presence of numerous submucosal neuromata initiated a meticulous neurological and endocrine work-up, which established the diagnosis of MEN 2B. This led to an early detection and appropriate treatment of asymptomatic medullary thyroid carcinoma (MTC).

Adolescent↗

Weight variations in patients receiving topiramate migraine prophylaxis in a tertiary care setting.

BACKGROUND: Migraine is a highly prevalent chronic neurologic disorder. Frequent headache attacks require prophylactic treatment, and side effects are limiting prescribing factors among traditional agents for migraine prophylaxis. Beta-blockers, antidepressants, calcium channel blockers, and anticonvulsants have been used since the 1960s, and their efficacy has been demonstrated in several controlled studies. However, weight gain commonly occurs with most of these drugs and makes adherence to treatment a troublesome issue for many patients. Topiramate is a new anticonvulsant with proven efficacy in migraine and other conditions, which reportedly confers weight loss in patients receiving doses up to 300 mg/day. OBJECTIVE: The aim of this study was to evaluate adherence, weight loss, tolerability, and response to topiramate in adult migraineurs receiving treatment in a tertiary care center. METHODS: During a 2,5-year period, all patients receiving topiramate for migraine were evaluated after 3 months of treatment. The parameters evaluated were adherence to treatment, frequency in reduction of attacks > 50%, the presence and amount of weight loss, and adverse events. RESULTS: Among 175 patients included, 134 (76.6%) adhered to the regimen, whereas 4% interrupted before the 3-month evaluation and 19.4% did not return for follow-up. Among the 134 patients evaluated, 82 (61.2%) revealed headache-frequency reduction > 50%; 105 (78.4%) patients experienced weight loss (range 1-10 kg; average, 3.4 kg). The most frequent side effects were paresthesia (39.6%); emotional disturbances, including depression, irritability, and anxiety (17.9%); thinking impairment (12.7%); memory disturbances (12.7%); and altered taste (11.9%). CONCLUSION: Despite methodologic limitations, we conclude that good adherence to topiramate in a "real-world" headache clinic occurred in most of the study participants. The majority of patients also experienced weight loss and reductions in headache frequency, with an acceptable side-effect profile.

Adult↗

Olfactory dysfunction and related nutritional risk in free-living, elderly women.

OBJECTIVE/DESIGN: To determine the nutritional risk associated with measured olfactory dysfunction in free-living, elderly women through analytic observational methods. Olfactory perception was measured orthonasally (odor: butanol threshold and odor identification) and retronasally (flavor: orange flavor threshold in sweetened gelatin). SETTING/SUBJECTS: Elderly women were recruited from New Haven, Conn, through posters and direct contact. Screening of 120 elderly women identified 80 with high personal functioning to participate (mean age = 76 +/- 6 years, range = 65 to 93 years). All data were collected in subjects' homes. MAIN OUTCOME MEASURES: Nutritional risk was assessed in several ways: food behavior questionnaire; food preference questionnaire; interviews based on the National Cancer Institute food frequency questionnaire; five nonconsecutive, 24-hour food records; and weight, height, waist, and hip measurements. STATISTICAL ANALYSES: Correlation and regression analyses determined the separate association between olfactory perception and nutrition variables. RESULTS: Nearly half of the women (37 of 80) had olfactory dysfunction. The following nutritional risk pattern was associated with lower olfactory perception: lower interest in food-related activities (eg, enjoying cooking, eating a wide variety of foods); lower preference for foods with predominant sour/bitter taste (eg, citrus fruits) or pungency (eg, horseradish); higher intake of sweets; less intake of low-fat milk products; and nutrient intake profile indicative of higher risk for cardiac disease. APPLICATIONS: Olfactory dysfunction may make it more difficult for elderly women to maintain a diet to control risk for chronic disease. Practitioners should target nutrition intervention to elderly women with measured or self rated difficulty in preventing odors or olfactory flavor. Capitalizing on primary-taste quality and texture may help to compensate for the loss of olfactory flavor perception.

Aged↗

Sumatriptan in the treatment of acute migraine with aura.

The efficacy of the selective 5HT1-like agonist sumatriptan in acute treatment of classical migraine (i.e. migraine with aura) was assessed in a double-blind, placebo-controlled, parallel group randomized trial. An oral dose of 200 mg was chosen on the basis of the efficacy rates achieved (70-85%) with 70-280 mg in open studies (1, 2). The dose of 200 mg was also chosen for the study because preliminary data from an oral pilot study indicated that efficacy increased with increasing dose up to 200 mg. Each patient was treated for a maximum of three separate attacks of migraine with aura within a three months' period. Three attacks were treated so that we could examine consistency of response across more than one attack. For attack 1, 200 mg sumatriptan was significantly more effective, safe and well tolerated than placebo at relieving headache 2 h after treatment was given (p = 0.023). In subsequent attacks, i.e. in attacks 2 and 3, there was no such significant effect of sumatriptan compared with placebo in relieving headache. This reduced efficacy of sumatriptan in the second and third attacks may be due to a high incidence of vomiting induced by the high dose of dispersible formulation and also by the bitter taste of the tablets. In addition, there was an increase in placebo response in attacks 2 and 3 compared to the first attack.

Acute Disease↗

Clinical experience with an elemental diet.

An elemental diet of defined composition and simple chemical form was nutritionally tested in a variety of surgical patients. Complete absorption in the upper gastrointestinal tract and minimal fecal residue proved especially advantageous in patients undergoing abdomianl surgery, and the diet also showed usefulness in patients with feeding problems. The patients responded well clinically, although some of them showed taste fatigue. Minimal variations in blood coagulation and chemistry indicated that the diet was safe, at least as it was used in the patients studied.

Abdomen↗

Sumatriptan nasal spray for migraine: a review of studies in patients aged 17 years and younger.

This review considers the epidemiology, clinical manifestations and functional consequences of migraine in children and adolescents and surveys the studies establishing the efficacy and tolerability of sumatriptan nasal spray in this patient population. Although therapeutic advances in paediatric and adolescent migraine have lagged behind those in adult migraine, the first systematic studies of migraine medications in young patients have brought about progress in the past five years. These studies show that therapeutic approaches suitable for adult patients are not always applicable to paediatric and adolescent patients. Because of the unique characteristics of paediatric and adolescent migraine, it has been difficult to demonstrate in young patients the efficacy of oral sumatriptan and other triptan tablets, which are the medications of choice for adult migraine. With sumatriptan, this finding has proven to be a consequence of the form in which the drug was administered rather than the inherent properties of the drug. The availability of sumatriptan nasal spray allows the benefits of migraine-specific therapy to be extended to children and adolescents. In both well-controlled, single-episode studies and long-term, multiple-episode studies, sumatriptan nasal spray has been effective and well tolerated for the acute treatment of migraine in children and adolescents. Except for unpleasant taste, which is not significantly distressing to patients, sumatriptan nasal spray has a tolerability profile similar to thatof placebo in young patients.

Administration, Intranasal↗

Genetic evidence for noradrenergic control of long-term memory consolidation.

Memory formation involves dynamic interactions among many brain structures and their linking pathways. The noradrenaline (NA) system in the CNS plays an important role in a wide variety of neurological and psychological functions. Alteration in the NA system is implicated in the pathological states of some neuropsychiatric disorders. Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines. The regulatory mechanism of the TH reaction is generally considered to play a key role in controlling the catecholaminergic actions. Mice heterozygous for the mutation of the gene encoding TH exhibit the reduced TH activity in tissues. These mice have a moderate reduction in NA accumulation and release in brain regions. The mutant mice exhibit deficits in the water-finding task associated with latent learning performance, suggesting the impairment in memory formation. Spatial learning performance measured by the water maze task is normal in the mutants. However, they display deficits in long-term memory formation of conditioned learning evaluated with three distinct behavioral paradigms, including active avoidance, cued fear conditioning, and conditioned taste aversion, without affecting short-term memory. These memory deficits are restored by the drug-induced stimulation of NA activity at the postconditioning phase. Analysis of the mutant mice indicates that the central NA system is essential for the consolidation process in long-term memory of conditioned learning. The process appears to be implicated in the NA activity in the cerebral cortex and/or amygdaloid complex.

Amygdala↗

[Chronic and predominantly sensory polyneuropathy in Toroku Valley where a mining company produced arsenic].

We report 9 patients (5 males, 4 females, ages 63-77) with chronic polyneuropathy. They were exposed to arsenic for about 15-40 years in Toroku Valley, Takachiho-Town, Miyazaki Prefecture, Japan, where a mining company produced arsenic from 1920-1962. Predominantly sensory polyneuropathy was the most significant neurological finding. In 5 of them, superficial and deep sensation was equally affected over the entire body, including head, face, and mucous membranes of the mouth. The corneal reflexes were absent or sluggish. Pin-prick and light-touch perception was absent in their hands and legs. Another sensory disorder such as glove and stocking-type was seen in 4 of them. All 9 patients were comfortable with extremely hot water in their beverages, their baths, and their wash basins compared with controls. But these patients felt that their temperature sensation was normal. Motor involvement was minimal. Although motor-nerve conduction velocities were normal or reduced minimally, sensory-nerve conduction velocities were moderately reduced. Sural-nerve biopsy revealed reduction of both small myelinated and unmyelinated fibers, which occurs with axonal degeneration of peripheral nerves. Other main symptoms and signs were tension-type headaches, non-painful tonic spasms of limbs, and losses or significantly decreased sensations of taste and smell. Dantrolene-sodium was effective for the treatment of their non-painful tonic spasms of limbs. As for the general medical condition of these patients, all of them had suffered from chronic bronchitis and skin eruption during childhood or in their early life or in their young adulthood when the mine was producing arsenic. At the time of this study only four of them suffered from chronic bronchitis and none of them had skin eruptions or discoloration of the skin, 37 years after closure of the mine. These 9 patients were diagnosed as having chronic arsenic poisoning and arsenic polyneuropathy. The multiplicity of symptoms found in these patients--anosmia, ageusia, chronic bronchitis, tension-type headaches, and non-painful tonic spasms of limbs--differs from the symptoms previously reported cases with arsenic poisoning. This may be due to combined overexposure to environmentally hazardous arsenic by effluent gas, dust, and drinking water in Toroku Valley. As concerns the sensory disorders described above, it is necessary to investigate sensory conduction pathways, including cerebral sensory cortex, spinal cord, and skin sensory receptors such as Pacini corpuscles, and Meissner corpuscles. Unfortunately, no information has been obtained about this problem because there were no autopsy cases.

Aged↗

Annualized incidence and spectrum of illness from an outbreak investigation of Bell's palsy.

BACKGROUND: There are limited clinical and epidemiological data on patients diagnosed with Bell's palsy. While investigating an apparent clustering of Bell's palsy, we sought to characterize the spectrum of illness in patients with this diagnosis. METHODS: A telephone survey of persons with idiopathic facial (Bell's) palsy in the Greater Toronto Area (GTA, population = 4.99 million) and Nova Scotia (population = 0.93 million) from August 1 to November 15, 1997 collected information on subject demographics, neurological symptoms, constitutional symptoms, medical investigation and management. Information regarding potential risks for exposure to infectious agents, past medical history, and family history of Bell's palsy was also collected. Subjects with other secondary causes of facial palsy were excluded. RESULTS: In the GTA and Nova Scotia, 222 and 36 patients were diagnosed with idiopathic facial (Bell's) palsy, respectively. The crude annualized incidence of Bell's palsy was 15.2 and 13.1 per 100,000 population in the GTA and Nova Scotia, respectively. There was no temporal or geographical clustering, and symptomatology did not differ significantly between the two samples. The mean age was 45 years, with 55% of subjects being female. The most common symptoms accompanying Bell's palsy were increased tearing (63%), pain in or around the ear (63%), and taste abnormalities (52%). A significant number of patients reported neurological symptoms not attributable to the facial nerve. CONCLUSION: No clustering of cases of Bell's palsy was observed to support an infectious etiology for the condition. Misdiagnosis of the etiology of facial weakness is common. Patients diagnosed with Bell's palsy have a variety of neurological symptoms, many of which cannot be attributed to a facial nerve disorder.

Bell Palsy↗

Sativex for the management of multiple sclerosis symptoms.

Sativex (R) is a cannabis-based pharmaceutical product containing delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio, delivered in an oromucosal (mouth) spray. It has been approved as adjunctive treatment for neuropathic pain in patients with multiple sclerosis (MS). It is being investigated for the management of other MS symptoms, such as spasticity. THC:CBD spray is regulated as a narcotic. Five randomized controlled trials (RCTs) compared the benefits and harms of THC:CBD spray with placebo. A total of 368 patients with various neurological conditions (including MS) were recruited. In some trials, THC:CBD spray significantly reduced neuropathic pain, spasticity, muscle spasms and sleep disturbances. The most common adverse events (AEs) reported in trials were dizziness, sleepiness, fatigue, feeling of intoxication and a bad taste. Long-term safety and the potential for dependence, abuse, misuse and diversion are unknown.

Administration, Oral↗

Reward and anxiety in genetic animal models of childhood depression.

One of the most important criteria for major depressive disorder in adults and in children and adolescents as well, is the loss of interest in or pleasure from typically enjoyable experiences or activities: anhedonia. Anxiety is frequently co-morbid with depression. We examined reward and anxiety in genetic animal models of childhood depression. Two different "depressed" lines were studied: the Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD) rats and the Wistar Kyoto (WKY) line and their controls, Wistar rats. Recently, we found that prepubertal rats (about 35 days old) from these lines exhibited increased immobility in the swim test, and abnormal social play observed after 24-h isolation. We hypothesized that FSL and WKY prepubertal rats will further show anhedonia in two different behavioral assays: the conditioned place preference test (CPP), examining the rewarding aspect of social interaction and the saccharin preference test. Behavior in the open field paradigm and freezing behavior in the CPP apparatus were also used as measures of anxiety. WKY, but not FSL prepubertal rats, consumed less of the saccharin solution compared to their control line. FSL, and WKY prepubertal rats found social interaction to be rewarding to a similar extent as their control lines, in the CPP test. Only the WKY rats showed anxiety in behavior in the open field and freezing behavior in the CPP paradigm. The results suggest that WKY prepubertal rats are anxious and sensitive to stress-induced anhedonia, while FSL prepubertal rats exhibit none of these symptoms.

Age Factors↗

Could valerian have been the first anticonvulsant?

PURPOSE: To assess the available evidence for the belief that valerian, highly recommended in the past for treating epilepsy, possessed real anticonvulsant effectiveness. METHODS: Review of available literature. RESULTS: In 1592, Fabio Colonna, in his botanical classic Phytobasanos, reported that taking powdered valerian root cured his own epilepsy. Subsequent reports of valerian's anticonvulsant effectiveness appeared. By the late 18th and early 19th centuries, it was often regarded as the best available treatment for the disorder. Valerian preparations yield isovaleric acid, a substance analogous to valproic acid and likely to possess anticonvulsant properties, as isovaleramide does. In favorable circumstances, high valerian doses can be calculated to have sometimes provided potentially effective amounts of anticonvulsant substance for epilepsy patients. CONCLUSIONS: Valerian probably did possess the potential for an anticonvulsant effect, but the uncertain chemical composition and content of valerian preparations, and their odor and taste, made it unlikely that they could ever prove satisfactory in widespread use.

Anticonvulsants↗

Oral complications of cancer radiotherapy.

Injury to surrounding tissues during radiotherapy for oral cancer can have devastating physical and psychologic consequences for the patient. Oral complications include xerostomia, dental decay, mucositis, taste loss, osteoradionecrosis, infection, and trismus. In many instances, these problems can be eradicated or controlled with appropriate treatment.

Adult↗

When is facial paralysis Bell palsy? Current diagnosis and treatment.

Bell palsy is largely a diagnosis of exclusion, but certain features in the history and physical examination help distinguish it from facial paralysis due to other conditions: eg, abrupt onset with complete, unilateral facial weakness at 24 to 72 hours, and, on the affected side, numbness or pain around the ear, a reduction in taste, and hypersensitivity to sounds. Corticosteroids and antivirals given within 10 days of onset have been shown to help. But Bell palsy resolves spontaneously without treatment in most patients within 6 months.

Acyclovir↗

The association of xerostomia and inadequate intake in older adults.

Recent studies indicate that nearly one in five older adults has xerostomia (dry mouth). Salivary gland dysfunction and/or inadequate saliva increases the difficulty of these older adults in obtaining proper nutrition. Problems in lubricating, masticating, tolerating, tasting, and swallowing food contribute notably to the complex physiological and psychological manifestations of aging. To our knowledge, the literature has not demonstrated an association between xerostomia and malnutrition in the elderly. We randomly selected 67 older adults from institutionalized and free-living geriatric populations. Nutritional intake analysis was performed on both groups of study subjects, who were found to have xerostomia by use of sialometry, and on control subjects matched for age, sex, and physical status. Intake of total energy, protein, dietary fiber, total fat, saturated fat, cholesterol, sodium, potassium, vitamin A, vitamin C, thiamin, riboflavin, vitamin B-6, calcium, iron, and zinc was compared with the 1989 Recommended Dietary Allowances. Subjects' intakes were also compared with that of a control group. Medical systemic information and number and types of medications were compared among the groups. Statistical analysis of the data indicated significant (p less than .001) inadequacies in the nutritional intake patterns of institutionalized and free-living older adults with xerostomia. Subjects with xerostomia (more than 75% of the free-living and institutionalized seniors) had significant deficiencies of fiber, potassium, vitamin B-6, iron, calcium, and zinc. Taste and food perception were significantly reduced in the elders with xerostomia. Our study indicates the potential contribution of xerostomia to the high prevalence of geriatric malnutrition in the United States.

Aged↗

[Migraine: dihydroergotamine nasal spray--an alternative].

Dihydroergotamine (DHE) formerly had to be administered intramuscularly or intravenously to cope with the migraine attack. The introduction of a new regimen, the DHE nasal spray, a new era in the treatment of the migraine attack has started. The patient is independent of his physician and may avoid the painful attack by taking the treatment already during the aura. The speed and thoroughness of the relief from pain are directly proportional to the promptness with which medication is started after the onset of an attack. The recommended dose of intranasally administered DHE is 2 mg, which means two times 0.5 mg into each nostril. The effect of DHE is mediated by its affinity to the 5-HT1D-receptor. DHE furthermore reacts with other 5-HT receptors and with alpha adrenergic receptors. The side effects of DHE given by nasal route are generally mild to moderate and are primarily local ones like nose or throat problems and a bitter or abnormal taste. Nausea and vomiting rarely occur. Side effect of nasal administered DHE may not be mixed up with side effects caused by ergotamine, another ergotalkaloide with a distinct profile of effects.

Administration, Intranasal↗