Efficacy of a reduced triazolam dose in elderly insomniacs

Elderly persons with insomnia are unique because the cause of their insomnia differs from that of younger people and their metabolism of benzodiazepine hypnotics differs as well. This study used nocturnal polysomnography and daytime sleep/wake tendency measures (Multiple Sleep Latency Test, MSLT) to assess the efficacy and safety of a reduced triazolam dosage (0.125 mg) in elderly subjects with insomnia. After 2 nights and an intervening day of screening each subject received triazolam and placebo for 2 consecutive nights presented in a counterbalanced design. Compared to placebo the reduced triazolam dose induced and maintained sleep thereby increasing total sleep time. Sleep stage distribution and the frequency of apneas and periodic leg movements was not altered. The improved sleep was associated with a restoration of the normal pattern of daytime alertness. The correspondance of this clinical data to known pharmacokinetic data is discussed.     

Daytime carryover of triazolam and flurazepam in elderly insomniacs

The effects of triazolam (0.25 mg) or flurazepam (15 mg) were evaluated in 13 elderly (ages 64-79) insomniacs. Subjects were reasonably healthy, ambulatory, and complained of disturbed sleep. Sleep apnea syndromes were ruled out by nocturnal polysomnogram. Sleep, daytime sleepiness [Multiple Sleep Latency Test (MSLT) and Stanford sleepiness scale (SSS)], performance, and mood [Profile of Mood States (POMS)] were assessed on five consecutive days. Placebo was given on nights 1 and 2; active medications were given on nights 3-5. Sleep time was increased by approximately 1 h in both groups. MSLT showed increased sleepiness with flurazepam and decreased sleepiness with triazolam. MSLT scores were unrelated to nocturnal sleep parameters in the flurazepam group and showed a pattern of correlation, though nonsignificant, in the triazolam group. Vigilance was impaired with flurazepam and unchanged with triazolam. Other performance tests showed slight improvement or no change with drugs. Mood tended to be improved after flurazepam ingestion and unchanged after triazolam. These findings suggest that, although both compounds improve nocturnal sleep in elderly insomniacs, there is significant residual sedation with flurazepam and improved daytime alertness with triazolam. Neither compound had a significant effect on nocturnal respiration in these non-sleep-apneic elderly subjects.     

Efficacy of a reduced triazolam dose in elderly insomniacs

Elderly persons with insomnia are unique because the cause of their insomnia differs from that of younger people and their metabolism of benzodiazepine hypnotics differs as well. This study used nocturnal polysomnography and daytime sleep/wake tendency measures (Multiple Sleep Latency Test, MSLT) to assess the efficacy and safety of a reduced triazolam dosage (0.125 mg) in elderly subjects with insomnia. After 2 nights and an intervening day of screening each subject received triazolam and placebo for 2 consecutive nights presented in a counterbalanced design. Compared to placebo the reduced triazolam dose induced and maintained sleep thereby increasing total sleep time. Sleep stage distribution and the frequency of apneas and periodic leg movements was not altered. The improved sleep was associated with a restoration of the normal pattern of daytime alertness. The correspondance of this clinical data to known pharmacokinetic data is discussed.     

Sensitivity to hymenoptera in adult males

The authors studied the sera of 86 selected adult male office workers for IgE antibodies to yellow jacket and honey bee venoms and to environmental inhalants and foods. Structured histories provide information about the experiences of these men with the Hymenoptera and other immunological information. Three men (3%) gave a history of a local or general reaction to the Hymenoptera but no antibodies were detected. Ten men (12%) had IgE antibodies to yellow jacket or honey bee venoms but none gave a history of a reaction. Nine of these men were atopic. The authors speculate that IgE antibodies to the Hymenoptera in atopic adult males may be more common than is currently recognized.     

Sensitivity to cholecystokinin-tetrapeptide in major depression

Background: Sensitivity to the panicogenic effects of cholecystokinin-tetrapeptide (CCK-4) is enhanced in panic disorder patients relative to normal controls (NC). In the present study, we determined whether sensitivity to CCK-4 is enhanced in patients with major depressive disorder (MDD) with no history of panic attacks. We also determined whether CCK-4 would exacerbate depressive symptoms. Methods: The study used a double-blind, randomized, placebo-controlled design. Behavioral and cardiovascular response to a submaximal dose (20 μg) of CCK-4 was studied in seven patients with MDD and 12 NC subjects. Results: None of the subjects panicked with placebo, whereas 29% of MDD and 17% of NC subjects panicked with CCK-4. There was no significant difference between groups on the frequency of CCK-4-induced panic or the number and intensity of panic symptoms. No significant difference was detected for cardiovascular response to the CCK-4 challenge. CCK-4 did not worsen depressive symptoms in MDD patients. Limitations: Small number of study subjects. Conclusions: These data indicate that MDD patients show a response to CCK-4 that is comparable to NC. The lack of effect of CCK-4 on depressive symptoms suggest that central CCK receptors may not play an important role in the pathophysiology of MDD.     

Seasonal Variation in Skin Sensitivity to Aeroallergens

Purpose

We previously demonstrated seasonal variation in sensitization to aeroallergens in a small group of patients with exercise-induced asthma. This study was performed to confirm the relationship in a much larger population.

Methods

The charts of 1,891 patients who received allergy skin prick tests were reviewed retrospectively. The test results from subjects aged ≤60 years were compared between the groups classified according to the season when the patients received the tests (spring: March-May, summer: June-August, fall: September-November, winter: December-February). The data from 25 respiratory allergy patients who received the tests two or more times and showed a positive response at least once were analyzed longitudinally.

Results

The most prevalent among 29 tested aeroallergens were house dust mites (HDMs) Dermatophagoides pteronyssinus and D. farinae. The skin sensitization rates to D. pteronyssinus (23.2% vs. 32.1%, P=0.004) and D. farinae (22.2% vs. 30.2%, P=0.009) were significantly lower in the summer and higher in the fall (38.3% vs. 26.6% and 35.6% vs. 25.3%; P=0.001 respectively) than those in other seasons in patients with a respiratory allergy (n=1,102). The sensitization rates to weed pollens in the fall (13.9% vs. 8.3%, P=0.006) and to Aspergillus fumigatus in the winter (2.9% vs. 0.7%, P=0.005) were significantly higher. In patients with non-respiratory allergy such as urticaria/anaphylaxis (n=340), the D. farinae sensitization rate was significantly lower in the summer also but higher in the spring. The trend of the HDM sensitization rate being lower in the summer and higher in the fall was observed in the longitudinal study.

Conclusions

Skin sensitivity to aeroallergens such as HDMs, pollens, and molds demonstrates seasonal variation in respiratory allergy patients. Non-respiratory allergy patients also showed seasonal variation in sensitivity to aeroallergens, which might be related to the "priming" effect of allergens.     

Sensitivity to prediction error in reach adaptation

It has been proposed that the brain predicts the sensory consequences of a movement and compares it to the actual sensory feedback. When the two differ, an error signal is formed, driving adaptation. How does an error in one trial alter performance in the subsequent trial? Here we show that the sensitivity to error is not constant but declines as a function of error magnitude. That is, one learns relatively less from large errors compared with small errors. We performed an experiment in which humans made reaching movements and randomly experienced an error in both their visual and proprioceptive feedback. Proprioceptive errors were created with force fields, and visual errors were formed by perturbing the cursor trajectory to create a visual error that was smaller, the same size, or larger than the proprioceptive error. We measured single-trial adaptation and calculated sensitivity to error, i.e., the ratio of the trial-to-trial change in motor commands to error size. We found that for both sensory modalities sensitivity decreased with increasing error size. A reanalysis of a number of previously published psychophysical results also exhibited this feature. Finally, we asked how the brain might encode sensitivity to error. We reanalyzed previously published probabilities of cerebellar complex spikes (CSs) and found that this probability declined with increasing error size. From this we posit that a CS may be representative of the sensitivity to error, and not error itself, a hypothesis that may explain conflicting reports about CSs and their relationship to error.     

Sensitivity to rotational motion in early infancy

Sensitivity to rotational motion, one of the fundamental components of optic flow, was tested in infants aged 2 and 3 months. The infants in both groups showed significant sensitivity to rotational motion only in the high-speed condition (10.62°/s). There was no significant increase in motion sensitivity between 2 and 3 months of age, indicating that there is not a significant developmental change during this period. A comparison of our results with previous findings that showed a significant increase in radial motion sensitivity between 2 and 3 months suggests that different motion sensitivities have different developmental time courses.     

Sensitivity to ingested metabisulfites in asthmatic subjects

While ingesting selected foods and drinks in restaurants, four asthmatic patients reported the sudden onset of severe wheezing and associated anaphylactoid symptoms and signs. Single-blind placebo and potassium metabisulfite (K₂S₂O₅) oral challenges documented asthmatic responses 15 to 30 min after ingestion of K₂S₂O₅. Laboratory investigations failed to demonstrate specific reaginic antibody recognition of K₂S₂O₅ in these patients. Furthermore, their peripheral basophils did not release histamine during in vitro challenges with K₂S₂O₅. It seems likely that additional asthmatic subjects have such sensitivities but are currently assumed to have “food allergies.” Such individuals can be suspected of having this sensitivity by history, and oral K₂S₂O₅ challenges can identify asthmatics who are sensitive.     

Sensitivity to voice in human prefrontal cortex

We report two functional MRI (fMRI) experiments showing sensitivity to human voice in a region of human left inferior prefrontal cortex, pars orbitalis. The voice-enhanced response was observed for speech as well as non-linguistic vocalizations and was stronger for emotional than neutral vocalizations. This region could constitute a human prefrontal auditory domain similar to the one recently identified in the macaque brain.     

Sensitivity of the reproductive organs to hormones in hypobaric hypoxia

Antihypoxic activity of oxytocin and feasibility of its use as an antihypoxic agent are shown. ACTH and vasopressin have an opposite action. Female rat castration leads to enhancement of FSH and LH activity of the hypophysis. Hypoxia does not influence gonadotrophic activity of castrate and cycling animals. Chronic hypobaric hypoxia depresses myometrial contractility in intact sensitivity to oxytocin. Sensitivity of the ovaries to exogenic FSH and ovarian secretory function decline. Hypoxia has no effect on sensitivity of vaginal epithelium to folliculin, but raises uterine sensitivity to adrenaline.     

Acute administration of triazolam for the daytime sleep of rotating shift workers

Ten rotating shift workers, who changed shifts every 1 to 4 weeks, slept in the laboratory during the first four daytime sleep periods of two consecutive tours of night shift. Prior to the first two sleep periods of one tour, the subjects were given 0.5 mg triazolam. Placebo was administered prior to sleep periods one and two of the other night shift tour. Neither drug nor placebo was given before the third and fourth sleep period of either tour of night shift. Conditions were counterbalanced among subjects. Polysomnography demonstrated that triazolam significantly increased total sleep time and sleep efficiency relative to placebo, primarily by promoting sleep maintenance. No adaptation to daytime sleep was seen during the four consecutive sleep periods without triazolam (placebo, then no drug). Triazolam did not appear to promote adaptation to daytime sleep on the 2 days following triazolam administration.     

Sensitivity to change of the Obsessive Beliefs Questionnaire

The Obsessive–Compulsive Beliefs Questionnaire‐87 (OBQ‐87) has been constructed by leading obsessive–compulsive disorder (OCD) experts to assess dysfunctional beliefs typical for OCD patients. The OBQ‐87 has recently been revised (Obsessive–Compulsive Beliefs Questionnaire‐44 [OBQ‐44]) to improve its psychometric properties. The current investigation entailed two goals: (1) to assess the sensitivity of both Obsessive Beliefs Questionnaire (OBQ) versions to treatment change and other OCD measures; and (2) to assess relations between symptom subtypes, OBQ beliefs and changes in beliefs as a consequence of treatment. One hundred and four patients have completed the OBQ before and after 12 sessions of behaviour therapy. Results suggest that (1) both OBQ versions exhibit an identical medium effect size; (2) overlap between clinical and non‐clinical populations limit the use of the OBQ as a primary measure of treatment change; and (3) the symptom dimension obsessions + checking was related to initial OBQ scores, but no symptom dimensions were related to OBQ pre‐treatment to post‐treatment changes. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message:

• Both versions of the OBQ demonstrate similar sensitivity to treatment change; however the clinical utility of this measure is doubtful.

     

Short-term triazolam use improves nocturnal sleep of narcoleptics.

This study was undertaken to determine whether the use of triazolam by narcoleptic patients leads to improvement of nighttime sleep or excessive sleepiness. Ten narcoleptic patients, 5 males and 5 females, with complaints of sleep disturbance and aged between 18 and 60 years, were assigned to a single-blind within-subject crossover-designed study comparing placebo with 0.25 mg triazolam. All subjects completed sleep questionnaires and underwent 6 nights of polysomnographic testing. Following an adaptation night, subjects received either triazolam or placebo for 2 nights. Objective tests of sleepiness (multiple sleep latency testing/maintenance of wakefulness test) were performed. Sleep efficiency and overall sleep quality were improved on all triazolam nights. Daytime excessive sleepiness was not reduced objectively after triazolam. This study demonstrates that the short-term use of triazolam improves nocturnal sleep quality in narcoleptics. Studies of long-term administration of triazolam are required to determine if the improvement of nocturnal sleep is maintained.