Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders.

OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

Detection of molecular hydrogen in the atmosphere of Mars.

Four hydrogen (H2) lines have been detected in a spectrum of Mars observed with the Far Ultraviolet Spectroscopic Explorer. Three of those lines are excited by the solar Lyman beta photons. The line intensities correspond to a column H2 abundance of 1.17 (+/-0.13) x 10(13) per square centimeter above 140 kilometers on Mars. A photochemical model for the upper atmosphere that simulates the observed H2 abundance results in an H2 mixing ratio of 15 +/- 5 parts per million in the lower atmosphere. The H2 and HD mixing ratios agree with photochemical fractionation of D (deuterium) between H2O and H2. Analysis of D fractionation among a few reservoirs of ice, water vapor, and molecular hydrogen on Mars implies that a global ocean more than 30 meters deep was lost since the end of hydrodynamic escape. Only 4% of the initially accreted water remained on the planet at the end of hydrodynamic escape, and initially Mars could have had even more water (as a proportion of mass) than Earth.

Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in nursing home patients with Alzheimer's dementia.

BACKGROUND: Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimer's disease (AD). OBJECTIVES: Elderly nursing home patients (n=105) with possible or probable AD were entered into a multicenter study to determine the long-term efficacy and safety of olanzapine in treatment of psychotic symptoms and behavioral disturbances due to AD. METHODS: Following a double-blind, 6-week exposure to fixed-dose olanzapine (5, 10, or 15 mg/d), patients entered an additional 18-week, open-label, flexible-dose treatment. Baseline was defined from the start of the extension phase. RESULTS: Patients improved significantly on the primary efficacy measure, defined a priori, which consisted of the sum of the Agitation/Aggression, Delusions, and Hallucinations items ('Core':) of the NPI/NH. Olanzapine also significantly improved scores for the NPI/NH total and the Core item-associated Occupational Disruptiveness of the NPI/NH, as well as the BPRS total and CGI Severity-of-Alzheimer's scores. Barnes Akathasia scores improved significantly from baseline, while Simpson-Angus and AIMS scores were not significantly changed. Treatment-emergent symptoms included somnolence, accidental injury, and rash. No significant changes were seen in ECGs, including QT(c) interval, nor in weight or vital signs, including orthostasis. CONCLUSIONS: Low-dose olanzapine appears to be effective and well tolerated for treatment of behavioral disturbances and psychotic symptoms due to AD in elderly patients.

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder.

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Deficiency of molecular hydrogen in the disk of beta Pictoris.

Molecular hydrogen (H2) is by far the most abundant material from which stars, protoplanetary disks and giant planets form, but it is difficult to detect directly. Infrared emission lines from H2 have recently been reported towards beta Pictoris, a star harbouring a young planetary system. This star is surrounded by a dusty 'debris disk' that is continuously replenished either by collisions between asteroidal objects or by evaporation of ices on Chiron-like objects. A gaseous disk has also been inferred from absorption lines in the stellar spectrum. Here we present the far-ultraviolet spectrum of beta Pictoris, in which H2 absorption lines are not seen. This allows us to set a very low upper limit on the column density of H2: N(H2) 6 x 10-4. As CO would be destroyed under ambient conditions in about 200 years (refs 9, 11), our result demonstrates that the CO in the disk arises from evaporation of planetesimals.

HST and VLT investigations of the fragments of comet C/1999 S4 (LINEAR).

At least 16 fragments were detected in images of comet C/1999 S4 (LINEAR) taken on 5 August 2000 with the Hubble Space Telescope (HST) and on 6 August with the Very Large Telescope (VLT). Photometric analysis of the fragments indicates that the largest ones have effective spherical diameters of about 100 meters, which implies that the total mass in the observed fragments was about 2 x 10(9) kilograms. The comet's dust tail, which was the most prominent optical feature in August, was produced during a major fragmentation event, whose activity peaked on UT 22.8 +/- 0.2 July 2000. The mass of small particles (diameters less than about 230 micrometers) in the tail was about 4 x 10(8) kilograms, which is comparable to the mass contained in a large fragment and to the total mass lost from water sublimation after 21 July 2000 (about 3 x 10(8) kilograms). HST spectroscopic observations during 5 and 6 July 2000 demonstrate that the nucleus contained little carbon monoxide ice (ratio of carbon monoxide to water is less than or equal to 0.4%), which suggests that this volatile species did not play a role in the fragmentation of C/1999 S4 (LINEAR).

The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease.

BACKGROUND: Elderly patients with Alzheimer's disease (AD) commonly exhibit psychotic symptoms, prompting clinicians to administer antipsychotics. This article compares the effects of olanzapine and placebo in the emergence of hallucinations or delusions in AD patients with symptoms of agitation/aggression but little or no psychotic symptomatology at baseline. METHOD: A multicenter, double-blind, placebo-controlled study was conducted in nursing home patients with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or psychosis. Patients (N = 206) were randomly assigned to receive either placebo or fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH). Three subsets of patients were identified on the basis of their symptoms at baseline: those with no clinically significant hallucinations, those with no clinically significant delusions, and those with no clinically significant delusions or hallucinations. RESULTS: Of the patients without hallucinations or delusions at baseline (N = 75), the placebo-treated patients showed significantly greater development of these symptoms compared with olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without baseline hallucinations (N = 153), the placebo-treated patients showed greater hallucinations score increases than did olanzapine-treated patients overall (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87) showed no significant treatment effects. Olanzapine had a favorable safety profile in each patient subset. CONCLUSION: These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.

A novel augmentation strategy for treating resistant major depression.

OBJECTIVE: Treatment-resistant depression is a significant public health concern; drug switching or augmentation often produce limited results. The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression. METHOD: An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent, nonbipolar, treatment-resistant depression without psychotic features. Subjects were randomly assigned to one of three groups: olanzapine plus placebo, fluoxetine plus placebo, or olanzapine plus fluoxetine. RESULTS: Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions. CONCLUSIONS: Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone.

Ultraviolet groove efficiency of a holographic grating: implications for a dual-order spectrograph.

The ultraviolet groove efficiency for a holographically ruled diffraction grating with a trapezoidal profile has been measured. The efficiencies for the +/-1 and the zero orders are in good agreement with those derived from scalar theory. The +/-1 orders have equal efficiency as a function of wavelength. The peak of the sum of fitted groove efficiency functions is 76%, a level that is competitive with the groove efficiency of a mechanically blazed grating. We suggest that a normal-incidence grating mount with detectors at both orders will offer a system with twice the efficiency and provide a built-in redundancy. We discuss design considerations for reducing astigmatism equally in both orders in such dual-order mountings.

Olanzapine versus haloperidol in schizoaffective disorder, bipolar type.

BACKGROUND: The present analysis was performed on data from a subsample of patients with schizoaffective disorder, bipolar type, who participated in a multicenter, double-blind study comparing olanzapine to haloperidol. METHODS: Patients with schizoaffective disorder bipolar type, characterized as currently manic, mixed, depressed, or euthymic, were assessed weekly for 6 weeks during treatment with either olanzapine or haloperidol. Manic symptoms were measured using the sum of six items of the BPRS, and depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. In addition, cognitive functioning was measured using the sum of seven items from the PANSS. Repeated measures analyses were performed using random coefficients regression of the serial measurement of manic, cognitive, and depressive symptoms. RESULTS: A significant treatment difference was detected overall, indicating that olanzapine was significantly more effective than haloperidol in reducing symptoms of depression and improving patients' cognitive symptoms. The superiority of olanzapine over haloperidol in the reduction of manic symptoms did not reach statistical significance (P=.052). The greatest improvement in both manic and cognitive symptoms was seen in the olanzapine-treated 'currently manic' subgroup, and least improvement in the haloperidol-treated 'euthymic' subgroup. Depressive symptoms were most improved in the olanzapine-treated 'depressed' subgroup, and least improved in the corresponding haloperidol subgroup. CONCLUSIONS: Overall, olanzapine was superior to haloperidol with respect to thymoleptic effects in patients with schizoaffective disorder, bipolar type.

Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group.

BACKGROUND: Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD. METHODS: A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory-Nursing Home version. RESULTS: Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo. CONCLUSION: Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.

Onset of action of antipsychotics in the treatment of mania.

INTRODUCTION: An important consideration in treating acute mania is the promptness with which a chosen therapy can bring symptom amelioration. This article reviews the available published data from controlled, blinded studies regarding the latency of responses to antipsychotics in patients with acute mania. METHODS: Articles for this review were obtained from a search of the Medline database (1966- 1999), using the following keywords and phrases: antipsychotic, atypical, bipolar disorder, mania, neuroleptic, typical. The bibliographic sections of articles gleaned from this search were used to direct further inquiries. RESULTS: Although information regarding the onset of action of antipsychotics is limited, we discovered data for four typical and three atypical antipsychotics. Drugs with the fastest onsets include haloperidol, risperidone, and olanzapine, with onsets appearing in 2 6 days. Chlorpromazine and thiothixene were at the slowest end of the continuum, with onsets of 2 weeks or longer. Data regarding pimozide are mixed, with some studies showing an onset equivalent to that of the 'fast' compounds and others showing one similar to that of the 'slow' compounds. CONCLUSIONS: Choice of therapy should consider not only efficacy and safety, but also onset speed. Atypical antipsychotics appear to offer safer, faster, and more effective therapies.

Far-ultraviolet imaging spectroscopy of Io's atmosphere with HST/STIS.

Well-resolved far-ultraviolet spectroscopic images of O I, S I, and previously undetected H ILyman-alpha emission from Io were obtained with the Hubble space telescope imaging spectrograph (STIS). Detected O I and S I lines (1250 to 1500 angstroms) have bright equatorial spots (up to 2.5 kilorayleighs) that shift position with jovian magnetic field orientation; limb glow that is brighter on the hemisphere facing the jovian magnetic equator; and faint diffuse emission extending to approximately 20 Io radii. All O I and S I features brightened by approximately 50 percent in the last two images, concurrently with a ground-based observation of increased iogenic [O I] 6300-angstrom emission. The H ILyman-alpha emission, consisting of a small, approximately 2-kilorayleigh patch near each pole, has a different morphology and time variation.

Narcissistic Ghosts in Rowland-Mounted, Concave Gratings with nu = 0 degrees : a Cautionary Note.

Narcissistic ghost lines in a Rowland-grating spectrograph have been identified as arising from the reimaging of bright spectral features, which are incident on the face of a detector photocathode [Cesium iodide (CsI) on a microchannel plate], back onto the detector by the grating in zero order. The mean of the wavelength of the diffracted light and the apparent wavelength of the ghost allows the angle of the grating normal with respect to the input beam (alpha) to be determined. Measurements of ghost intensity as a function of wavelength are presented and are found to range between 7 x 10(-4) and 7 x 10(-3) of the parent line. We find that the sum of the CsI photocathode reflectivity and quantum efficiency <1/2, showing the bulk of the light incident upon the detector, is neither reflected nor detected. We caution that any Rowland circle spectrograph with a detector normal nearly aligned with the grating normal and with a sufficiently reflective detector face (or surrounding mounting structure) will suffer from these narcissistic ghosts.

Detection of soft X-rays and a sensitive search for noble gases in comet Hale-Bopp.

An image of comet Hale-Bopp (C/1995 O1) in soft x-rays reveals a central emission offset from the nucleus, as well as an extended emission feature that does not correlate with the dust jets seen at optical wavelengths. Neon was found to be depleted in the cometary ice by more than a factor of 25 relative to solar abundance, which suggests that ices in Hale-Bopp formed at (or later experienced) temperatures higher than 25 kelvin. A helium line emission at a wavelength of 584 angstroms was detected and may be attributable to charge transfer of solar wind alpha particles in the cometary coma. Ionized oxygen and another helium line contribute to an emission observed at 538 angstroms.

The activity and size of the nucleus of comet Hale-Bopp (C/1995 O1) [see comment].

Analysis of Hubble Space Telescope (HST) images of comet Hale-Bopp (C/1995 O1) suggests that the effective diameter of the nucleus is between 27 to 42 kilometers, which is at least three times larger than that of comet P/Halley. The International Ultraviolet Explorer and HST spectra showed emissions from OH (a tracer of H2O) and CS (a tracer of CS2) starting in April 1996, and from the CO Cameron system (which primarily traces CO2) starting in June 1996. The variation of the H2O production rate with heliocentric distance was consistent with sublimation of an icy body near its subsolar point. The heliocentric variation in the production rates of CS2 and dust was different from that of H2O, which implies that H2O sublimation did not control the CS2 or dust production during these observations.

Fluorescent hydroxyl emissions from Saturn's ring atmosphere.

Just before earth passed through Saturn's ring plane on 10 August 1995, the Hubble Space Telescope Faint Object Spectrograph detected ultraviolet fluorescent emissions from a tenuous atmosphere of OH molecules enveloping the rings. Brightnesses decrease with increasing distance above the rings, implying a scale height of about 0.45 Saturn radii (Rs). A spatial scan 0.28Rs above the A and B rings indicates OH column densities of about 10(13) cm(-2) and number densities of up to 700 cm(-3). Saturn's rings must produce roughly 10(25) to 10(29) OH molecules per second to maintain the observed OH distribution.

Cardiovascular effects of Leu-enkephalin in the nucleus tractus solitarius of the rat.

Microinjections of Leu-enkephalin into the dorsal vagal complex induced hypotension and bradycardia. Both naloxone, given at a dose conferring selectivity for mu receptors, and the delta antagonist ICI 154,129 prevented the cardiovascular effects of Leu-enkephalin. Naloxone was also found to decrease the gain of the baroreflex. These results suggest that Leu-enkephalin is involved in cardiovascular regulation through activation of delta-, and possibly mu-, opioid receptors in the dorsal vagal complex.

Effects of serotonin-1 and serotonin-2 receptor agonists on neuronal activity in the nucleus tractus solitarius.

Spontaneous neuronal activity in the solitary tract nucleus was recorded extracellularly in a brain slice preparation during bath-application of 5-HT1 and 5-HT2 receptor-selective agonists and antagonists. The 5-HT1A/5-HT1B agonist 5-carboxamidotryptamine depressed activity in 20 of 25 neurons studied. The remaining five neurons were unaffected. The 5-HT1A/5-HT1B antagonist pindolol prevented the 5-carboxamidotryptamine-induced changes, whereas the 5-HT1A antagonist spiroxatrine and the 5-HT2 antagonists ketanserin and mianserin were ineffective. Application of the 5-HT1/5-HT2 agonist alpha-methylserotonin depressed activity in 16 of 19 neurons, whereas the remaining three neurons were unresponsive. Pindolol blocked alpha-methylserotonin-induced changes of activity, but spiroxatrine, ketanserin and mianserin were ineffective. Finally, the 5-HT2 agonist DOI was applied to seven neurons. Six were unresponsive to DOI, and one responded with a depression of activity. These data provide electrophysiological evidence for the presence of 5-HT1 receptors in the nTS, presumably of the 5-HT1B subclass, but cast further doubt on the contribution of 5-HT2 and 5-HT1A receptors to the actions of serotonin in the nucleus.

Cardiovascular effects of serotonin in the nucleus of the solitary tract.

The cardiovascular regulatory role of serotonin [5-hydroxytryptamine (5-HT)] in the solitary tract nucleus (NTS) was investigated in urethan-anesthetized Wistar rats. Unilateral microinjection of 5-HT (5 nmol in 50 nl) into the NTS evoked depressions of both arterial pressure (-20 +/- 1 mmHg) and heart rate (-43 +/- 6 beats/min). Induction of bradycardia and hypotension was repeatable and consistently obtained with injections into the NTS but not into neighboring structures. Microinjection of the nonselective 5-HT receptor antagonist methiothepin or the 5-HT1A/5-HT1B antagonist pindolol prevented any cardiovascular change by subsequent microinjection of 5-HT into the NTS. In contrast, microinjection of the 5-HT2-selective antagonist ketanserin or the 5-HT1A antagonist spiroxatrine had no effect on the subsequent effects of 5-HT. Bilateral vagal denervation prevented the bradycardia induced by 5-HT, whereas the vasodepression remained intact. These data provide evidence that 5-HT in the NTS evokes vagal chronotropic cardioinhibition and sympathetic withdrawal and suggest that this action is mediated by 5-HT1 serotonergic receptors, possibly of the 5-HT1B subtype.