RESUMO
PROBLEM: A 58-year-old man presented with transient vertigo and pulsatile tinnitus. METHODS: High-resolution computed tomography, magnetic resonance imaging, excision, and subsequent immunohistochemical assays were performed. RESULTS: Imaging showed a soft tissue mass in the epitympanum and mastoid with bone erosion of the tegmen tympani and a dural tail sign, suggesting meningioma. Subsequently, because of signs of clinical progression, a canal-wall-up attico-antromastoidectomy was performed, with near-complete removal of a granulomatous, ossifying, haemorrhagic mass. CONCLUSIONS: Radiological imaging was critical in determining the extent of the mass and excluding other pathologies. Due to the atypical clinical and radiological signs, the final diagnosis of capillary haemangioma of the middle ear and temporal bone was made only after surgical resection and histopathological examination with immunohistochemistry, which excluded meningioma. The contiguous occurrence of cutaneous capillary haemangioma of the lateral face and neck was an important clue to the diagnosis.
Assuntos
Neoplasias da Orelha/complicações , Hemangioma Capilar/complicações , Zumbido/etiologia , Vertigem/etiologia , Neoplasias da Orelha/diagnóstico , Hemangioma Capilar/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada MultidetectoresRESUMO
Lunge feeding by rorqual whales (Balaenopteridae) is associated with a high energetic cost that decreases diving capacity, thereby limiting access to dense prey patches at depth. Despite this cost, rorquals exhibit high rates of lipid deposition and extremely large maximum body size. To address this paradox, we integrated kinematic data from digital tags with unsteady hydrodynamic models to estimate the energy budget for lunges and foraging dives of blue whales (Balaenoptera musculus), the largest rorqual and living mammal. Our analysis suggests that, despite the large amount of mechanical work required to lunge feed, a large amount of prey and, therefore, energy is obtained during engulfment. Furthermore, we suggest that foraging efficiency for blue whales is significantly higher than for other marine mammals by nearly an order of magnitude, but only if lunges target extremely high densities of krill. The high predicted efficiency is attributed to the enhanced engulfment capacity, rapid filter rate and low mass-specific metabolic rate associated with large body size in blue whales. These results highlight the importance of high prey density, regardless of prey patch depth, for efficient bulk filter feeding in baleen whales and may explain some diel changes in foraging behavior in rorqual whales.
Assuntos
Balaenoptera/fisiologia , Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Modelos Biológicos , Animais , Fenômenos Biomecânicos , Mergulho/fisiologia , Euphausiacea/fisiologia , Hidrodinâmica , Densidade DemográficaRESUMO
OBJECTIVES: This study aimed to validate the Dutch version of the Spatial Hearing Questionnaire (SHQ). The original English SHQ by Tyler et al. is a useful and reliable self-reported assessment of spatial hearing. It has excellent construct validity and significantly correlates with other measures of auditory function. Our goal is to have similarly high internal consistency reliability and construct validity for the Dutch version of the SHQ. METHODS: We obtained the Dutch version of the original American English SHQ by the process of translation and back-translation. The SHQ was assessed in 71 patients at the Ear, Nose and Throat (ENT) department of Antwerp University Hospital. Internal consistency reliability was evaluated using Cronbach's alpha value. Factor analysis was performed and compared to results from previous psychometric analysis of the original SHQ. Construct validity was checked by comparing scores obtained in patients with asymmetric and symmetric hearing loss. RESULTS: The internal consistency of the Dutch version of the SHQ was very high with a Cronbach's alpha value of 0.98. Comparison of a group with asymmetric and symmetric impaired patients revealed significant differences in the SHQ total score and most subscale scores, emphasizing good construct validity. CONCLUSIONS: The SHQ was successfully translated to Dutch. The psychometric characters of the Dutch questionnaire are similar to the original SHQ in English, with high internal consistency reliability. The Dutch version of the SHQ, Vragenlijst voor Ruimtelijk Horen, is a valid and reliable instrument for measuring spatial hearing abilities in both clinic and research settings.
Assuntos
Localização de Som , Inquéritos e Questionários/normas , Adulto , Idoso , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Psicometria , Percepção da FalaRESUMO
Humpback and blue whales are large baleen-bearing cetaceans, which use a unique prey-acquisition strategy-lunge feeding-to engulf entire patches of large plankton or schools of forage fish and the water in which they are embedded. Dynamically, and while foraging on krill, lunge-feeding incurs metabolic expenditures estimated at up to 20.0 MJ. Because of prey abundance and its capture in bulk, lunge feeding is carried out at high acquired-to-expended energy ratios of up to 30 at the largest body sizes (â¼27 m). We use bio-logging tag data and the work-energy theorem to show that when krill-feeding at depth while using a wide range of prey approach swimming speeds (2-5 m/s), rorquals generate significant and widely varying metabolic power output during engulfment, typically ranging from 10 to 50 times the basal metabolic rate of land mammals. At equal prey field density, such output variations lower their feeding efficiency two- to three-fold at high foraging speeds, thereby allowing slow and smaller rorquals to feed more efficiently than fast and larger rorquals. The analysis also shows how the slowest speeds of harvest so far measured may be connected to the biomechanics of the buccal cavity and the prey's ability to collectively avoid engulfment. Such minimal speeds are important as they generate the most efficient lunges. Sommaire Les rorquals à bosse et rorquals bleus sont des baleines à fanons qui utilisent une technique d'alimentation unique impliquant une approche avec élan pour engouffrer de larges quantités de plancton et bancs de petits poissons, ainsi que la masse d'eau dans laquelle ces proies sont situés. Du point de vue de la dynamique, et durant l'approche et engouffrement de krill, leurs dépenses énergétiques sont estimées jusqu'à 20.0 MJ. À cause de l'abondance de leurs proies et capture en masse, cette technique d'alimentation est effectuée à des rapports d'efficacité énergétique (acquise -versus- dépensée) estimés aux environs de 30 dans le cas des plus grandes baleines (27 m). Nous utilisons les données recueillies par des capteurs de bio-enregistrement ainsi que le théorème reliant l'énergie à l'effort pour démontrer comment les rorquals s'alimentant sur le krill à grandes profondeurs, et à des vitesses variant entre 2 et 5 m/s, maintiennent des taux de dépenses énergétiques entre 10 et 50 fois le taux métabolique basal des mammifères terrestres. À densités de proies égales, ces variations d'énergie utilisée peuvent réduire le rapport d'efficacité énergétique par des facteurs entre 2x et 3x, donc permettant aux petits et plus lents rorquals de chasser avec une efficacité comparable à celle des rorquals les plus grands et rapides. Notre analyse démontre aussi comment des vitesses d'approche plus lentes peuvent être reliées à la biomécanique de leur poche ventrale extensible, et à l'habilitée des proies à éviter d'être engouffrer. Ces minimums de vitesses sont importants car ils permettent une alimentation plus efficace énergétiquement.
RESUMO
Rorqual whales (Balaenopteridae) obtain their food by lunge feeding, a dynamic process that involves the intermittent engulfment and filtering of large amounts of water and prey. During a lunge, whales accelerate to high speed and open their mouth wide, thereby exposing a highly distensible buccal cavity to the flow and facilitating its inflation. Unsteady hydrodynamic models suggest that the muscles associated with the ventral groove blubber undergo eccentric contraction in order to stiffen and control the inflation of the buccal cavity; in doing so the engulfed water mass is accelerated forward as the whale's body slows down. Although the basic mechanics of lunge feeding are relatively well known, the scaling of this process remains poorly understood, particularly with regards to its duration (from mouth opening to closure). Here we formulate a new theory of engulfment time which integrates prey escape behavior with the mechanics of the whale's body, including lunge speed and acceleration, gape angle dynamics, and the controlled inflation of the buccal cavity. Given that the complex interaction between these factors must be highly coordinated in order to maximize engulfment volume, the proposed formulation rests on the scenario of Synchronized Engulfment, whereby the filling of the cavity (posterior to the temporomandibular joint) coincides with the moment of maximum gape. When formulated specifically for large rorquals feeding on krill, our analysis predicts that engulfment time increases with body size, but in amounts dictated by the specifics of krill escape and avoidance kinematics. The predictions generated by the model are corroborated by limited empirical data on a species-specific basis, particularly for humpback and blue whales chasing krill. A sensitivity analysis applied to all possible sized fin whales also suggests that engulfment duration and lunge speed will increase intra-specifically with body size under a wide range of predator-prey scenarios. This study provides the theoretical framework required to estimate the scaling of the mass-specific drag being generated during engulfment, as well as the energy expenditures incurred.
Assuntos
Ingestão de Alimentos/fisiologia , Modelos Biológicos , Baleias/fisiologia , Algoritmos , Animais , Fenômenos Biomecânicos/fisiologia , Tamanho Corporal/fisiologia , Metabolismo Energético/fisiologia , Reação de Fuga/fisiologia , Euphausiacea/fisiologia , Comportamento Alimentar/fisiologia , Cadeia Alimentar , Boca/anatomia & histologia , Boca/fisiologia , Baleias/anatomia & histologiaRESUMO
Blue whales are often characterized as highly stable, open-ocean swimmers who sacrifice maneuverability for long-distance cruising performance. However, recent studies have revealed that blue whales actually exhibit surprisingly complex underwater behaviors, yet little is known about the performance and control of these maneuvers. Here, we use multi-sensor biologgers equipped with cameras to quantify the locomotor dynamics and the movement of the control surfaces used by foraging blue whales. Our results revealed that simple maneuvers (rolls, turns, and pitch changes) are performed using distinct combinations of control and power provided by the flippers, the flukes, and bending of the body, while complex trajectories are structured by combining sequences of simple maneuvers. Furthermore, blue whales improve their turning performance by using complex banked turns to take advantage of their substantial dorso-ventral flexibility. These results illustrate the important role body flexibility plays in enhancing control and performance of maneuvers, even in the largest of animals. The use of the body to supplement the performance of the hydrodynamically active surfaces may represent a new mechanism in the control of aquatic locomotion.
Assuntos
Balaenoptera/fisiologia , Comportamento Predatório , Natação , Animais , Fenômenos Biomecânicos , HidrodinâmicaRESUMO
The largest animals are marine filter feeders, but the underlying mechanism of their large size remains unexplained. We measured feeding performance and prey quality to demonstrate how whale gigantism is driven by the interplay of prey abundance and harvesting mechanisms that increase prey capture rates and energy intake. The foraging efficiency of toothed whales that feed on single prey is constrained by the abundance of large prey, whereas filter-feeding baleen whales seasonally exploit vast swarms of small prey at high efficiencies. Given temporally and spatially aggregated prey, filter feeding provides an evolutionary pathway to extremes in body size that are not available to lineages that must feed on one prey at a time. Maximum size in filter feeders is likely constrained by prey availability across space and time.
Assuntos
Tamanho Corporal , Cadeia Alimentar , Baleias/anatomia & histologia , Baleias/fisiologia , Animais , Evolução Biológica , Biomassa , Ingestão de Energia , Euphausiacea , Comportamento Alimentar , Oceanos e MaresRESUMO
Baleen whales are gigantic obligate filter feeders that exploit aggregations of small-bodied prey in littoral, epipelagic, and mesopelagic ecosystems. At the extreme of maximum body size observed among mammals, baleen whales exhibit a unique combination of high overall energetic demands and low mass-specific metabolic rates. As a result, most baleen whale species have evolved filter-feeding mechanisms and foraging strategies that take advantage of seasonally abundant yet patchily and ephemerally distributed prey resources. New methodologies consisting of multi-sensor tags, active acoustic prey mapping, and hydrodynamic modeling have revolutionized our ability to study the physiology and ecology of baleen whale feeding mechanisms. Here, we review the current state of the field by exploring several hypotheses that aim to explain how baleen whales feed. Despite significant advances, major questions remain about the processes that underlie these extreme feeding mechanisms, which enabled the evolution of the largest animals of all time.
Assuntos
Comportamento Alimentar , Baleias , Animais , Tamanho Corporal , HidrodinâmicaRESUMO
The Rapid Office Strain Assessment (ROSA) was developed to assess musculoskeletal disorder (MSD) risk factors for computer workstations. This study examined the validity and reliability of remotely conducted, photo-based assessments using ROSA. Twenty-three office workstations were assessed on-site by an ergonomist, and 5 photos were obtained. Photo-based assessments were conducted by three ergonomists. The sensitivity and specificity of the photo-based assessors' ability to correctly classify workstations was 79% and 55%, respectively. The moderate specificity associated with false positive errors committed by the assessors could lead to unnecessary costs to the employer. Error between on-site and photo-based final scores was a considerable â¼2 points on the 10-point ROSA scale (RMSE = 2.3), with a moderate relationship (ρ = 0.33). Interrater reliability ranged from fairly good to excellent (ICC = 0.667-0.856) and was comparable to previous results. Sources of error include the parallax effect, poor estimations of small joint (e.g. hand/wrist) angles, and boundary errors in postural binning. While this method demonstrated potential validity, further improvements should be made with respect to photo-collection and other protocols for remotely-based ROSA assessments.
Assuntos
Ergonomia/métodos , Doenças Musculoesqueléticas/etiologia , Doenças Profissionais/etiologia , Fotografação , Local de Trabalho , Periféricos de Computador/normas , Computadores/normas , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Fotografação/métodos , Reprodutibilidade dos Testes , Local de Trabalho/normasRESUMO
OBJECTIVES: To determine the effectiveness of fluoxetine hydrochloride at fixed doses of 20 mg/d, 40 mg/d, and 60 mg/d in patients with obsessive-compulsive disorder (OCD) and to evaluate its safety. METHODS: Fixed-dose fluoxetine hydrochloride (20 mg/d, 40 mg/d, 60 mg/d) was compared with placebo in two randomized, double-blind, parallel, 13-week trials of identical design in 355 outpatients with OCD aged 15 to 70 years (DSM-III-R criteria; 1 year's duration or longer; depression secondary if present). RESULTS: Fluoxetine (all doses) was significantly (P < or = .001) superior to placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (mean baseline-to-end-point decrease, 4.6, 5.5, and 6.5 vs 0.9, respectively, studies pooled) and other efficacy measures (P < or = .01). A trend suggesting greater efficacy at 60 mg/d was observed. Most patients (79.2%) completed the study. Eight adverse events were statistically significantly more frequent with fluoxetine and one, with placebo. For some events, incidence tended to increase with increasing dosage; however, few patients discontinued treatment for any single event. CONCLUSION: Fluoxetine was associated with a statistically significant reduction in OCD severity, including time engaged in obsessional and/or compulsive behaviors. Adverse events infrequently led to study discontinuation.
Assuntos
Fluoxetina/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Placebos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Tardive dyskinesia is a serious and common complication of neuroleptic treatment. Olanzapine is a novel antipsychotic agent exhibiting regional mesolimbic dopaminergic selectivity and a broad-based pharmacology encompassing serotonin, dopamine, muscarinic, and adrenergic receptor binding affinities. The authors' goal was to compare the incidence of tardive dyskinesia among patients receiving olanzapine and those receiving the conventional dopamine 2 antagonist haloperidol. METHOD: Data were analyzed from three actively controlled and blind long-term responder studies of subjects meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine (N = 707, up to 20 mg/day, 237 median days of exposure) or haloperidol (N = 197, up to 20 mg/day, 203 median days of exposure) who did not have evidence of tardive dyskinesia at baseline. All of the subjects had a chronic disease course (mean greater than 10 years), and there were no significant between-treatment group differences in demographic or disease characteristics. The Abnormal Involuntary Movement Scale and research diagnostic criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia. RESULTS: The incidence of newly emergent tardive dyskinesia at any visit after baseline, at the final visit, and at the final two clinical assessments was statistically significantly lower among olanzapine-treated patients than among haloperidol-treated patients. CONCLUSIONS: These findings support an atypical extrapyramidal symptom profile and the potential of a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol among patients requiring maintenance antipsychotic treatment.
Assuntos
Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/epidemiologia , Haloperidol/efeitos adversos , Pirenzepina/análogos & derivados , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas , Relação Dose-Resposta a Droga , Esquema de Medicação , Discinesia Induzida por Medicamentos/etiologia , Feminino , Haloperidol/uso terapêutico , Humanos , Incidência , Masculino , Olanzapina , Pirenzepina/efeitos adversos , Pirenzepina/uso terapêutico , Placebos , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
We reviewed 20 English-language weight-reduction studies, reported between 1967 and March 1993, of the effect of > or = 6 mo of pharmacologic therapy on weight loss and its maintenance to determine the clinical benefits of extended treatment, propose treatment guidelines, and identify future research needs. Pharmacologic agents included phentermine, mazindol, fenfluramine, dexfenfluramine, and fluoxetine. Study designs varied with respect to blinding, use of a single agent vs a combination, dosing, length of therapy, patient selection, adjunctive therapy, and visit frequency. At endpoint, weight loss varied from study to study but a plateauing of weight loss or weight regain was observed after approximately 6 mo. The benefits of extended treatment appear to outweigh the risks for those patients who are unable to lose sufficient weight without pharmacologic therapy but who maintain adequate weight loss with long-term pharmacologic therapy. Future studies should define and evaluate pharmacologically responsive and unresponsive subgroups.
Assuntos
Depressores do Apetite/uso terapêutico , Obesidade/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Depressores do Apetite/farmacologia , Ensaios Clínicos como Assunto , Humanos , Fatores de Tempo , Resultado do TratamentoRESUMO
A randomized, double-blind clinical trial was designed to compare two ratios of carbidopa to levodopa (10 mg of carbidopa to 100 mg of levodopa [Sinemet 10/100] and 20 mg of carbidopa to 100 mg of levodopa [Sinemet 20/100]) with levodopa (100 mg) alone. Twenty-nine male patients (46 to 78 years of age) with clinically definite idiopathic Parkinson's disease of mild to moderate severity were selected and hospitalized for the three-week period of the study. Medications being taken at time of entry were phased out during week 1. Fixed daily increments of medications were given during week 2, and adjusted during week 3 to achieve best clinical response with fewest side effects. Qualitative and quantitative examinations of neurologic function showed that upper extremity measurements of resting tremor, rigidity, and finger-tapping speed, and lower extremity measurements of foot coordination and tandem gait (both types of speed tests) showed significantly more improvement in patients receiving the 20:100 combination than in those receiving the 10:100 combination or levodopa alone. Adverse effects were similar and minimal in each of the three groups. Results indicate that increasing the amount of carbidopa from 10 to 20 mg per 100-mg dose of levodopa gives a greater therapeutic response in Parkinson's disease than does a 10:100 carbidopa-levodopa ratio or levodopa alone.
Assuntos
Carbidopa/administração & dosagem , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Idoso , Carbidopa/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologiaRESUMO
Megavoltage CNS irradiation was given to 20 patients with clinically definite multiple sclerosis (MS) to determine if de novo CNS IgG synthesis could be eradicated. In all five patients given 1,200 rads, a transient reduction in the de novo CNS IgG synthesis rate was noted. In ten patients given 1,800 rads, the following occurred: a reduction in synthesis rate in three patients, a reduction followed by enhancement in two, only enhancement in four, and no change in one. In all five additional patients, a therapy of adrenocorticotropic hormone (ACTH) followed by prednisone in combination with 1,800 rads produced greater and more persistent decreases in CNS IgG synthesis, but did not block the enhancement effect. Only two of 19 patients who had abnormal CNS IgG synthesis rates had reductions to normal; no patients showed changes in the number or pattern CSF IgG oligoclones. Hence, no treatment eradicated de novo CNS IgG synthesis. A persistent decrease in CSF leukocytes occurred in all 20 patients due to the reduction of small lymphocytes (not dose related). The blood-brain-barrier to albumin concentration was transiently damaged in 11 of 15 patients given irradiation, but when patients were premedicated with ACTH/prednisone therapy, no damage was found. None of the patients demonstrated neurological improvement, change in the activity of their disease, or persistent adverse effects.
Assuntos
Sistema Nervoso Central/efeitos da radiação , Imunoglobulina G/biossíntese , Esclerose Múltipla/imunologia , Hormônio Adrenocorticotrópico/uso terapêutico , Adulto , Albuminas/líquido cefalorraquidiano , Sistema Nervoso Central/imunologia , Líquido Cefalorraquidiano/citologia , Quimioterapia Combinada , Feminino , Humanos , Imunoglobulina G/antagonistas & inibidores , Leucócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/radioterapia , Prednisona/uso terapêutico , Dosagem RadioterapêuticaRESUMO
Data on critical frequency of photic driving (CFPD), frequency following response (FFR), and visual, somatosensory (peroneal nerve), and brain-stem auditory evoked potentials (EPs) were obtained from 20 patients who had clinically definite multiple sclerosis and ten healthy normal subjects in a controlled, balanced study under normothermic and hyperthermic (+1 degrees C) conditions with a test-retest interval of one week. Normal subjects' test results showed no changes during hyperthermia. Patients' EP and CFPD data correlated well with history, clinical signs, and symptoms during both normothermia and hyperthermia. The FFR test data were equivocal and not fully analyzed. Data from the four other tests showed additional patient abnormalities during hyperthermia. Multimodality testing increased the number of patient abnormalities compared with single tests, and the number increased further during hyperthermia. Test-retest reproducibility was higher during hyperthermia.
Assuntos
Potenciais Evocados , Esclerose Múltipla/fisiopatologia , Exame Neurológico , Adulto , Temperatura Corporal , Tronco Encefálico/fisiopatologia , Potenciais Evocados Auditivos , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Temperatura Alta , Humanos , Masculino , Reconhecimento Visual de Modelos , Nervo Fibular/fisiopatologiaRESUMO
ACTH gel and corticosteroids were given to 28 clinically definite multiple sclerosis (MS) patients to determine whether de novo central nervous system (CNS) IgG synthesis (rate and cerebrospinal fluid [CSF] IgG oligoclonal bands) could be eradicated. The most effective treatments were ACTH gel and ACTH gel followed by prednisone, all 11 patients had a significant reduction in rate (p < 0.05), which became normal in eight patients (< 3.3 mg per day). In order of effectiveness, the other drugs used were: dexamethasone or prednisone given orally, and hydrocortisone administered intrathecally. For most treatments, reduction of the rate of CNS IgG synthesis occurred within days and persisted for months after cessation of treatment. The MS CNS immune reaction was not eradicated when IgG synthesis rate became normal, because CSF IgG oligoclonal bands persisted. None of the chronic progressive, severely disabled patients demonstrated significant change in neurologic function or persistent adverse effects.
Assuntos
Corticosteroides/farmacologia , Hormônio Adrenocorticotrópico/farmacologia , Sistema Nervoso Central/metabolismo , Imunoglobulina G/biossíntese , Esclerose Múltipla/metabolismo , Adulto , Idoso , Dexametasona/farmacologia , Humanos , Hidrocortisona/farmacologia , Imunoglobulina G/líquido cefalorraquidiano , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Prednisona/farmacologiaRESUMO
An empirical formula has been developed to calculate the de novo rate of synthesis of IgG in the central nervous system (CNS), based on physiologic principles that govern the passage of albumin and IgG across the blood-brain barrier (BBB). To validate the formula, radiolabeled IgG and albumin from pooled normal sera were followed from the blood to the cerebrospinal fluid (CSF) over 21 days in nine patients with definite multiple sclerosis (MS). IgG synthesis rates were calculated by the isotope exchange method and compared to values obtained with the empirical formula. There was excellent concordance, from a low rate of synthesis of 5 mg per day to a high rate of 120 mg per day. A double radiolabeled IgG experiment in two patients showed that the MS BBB processed normal serum IgG in the same way as IgG derived from autologous MS serum. Accordingly, the empirical formula, which requires only one sample of CSF and matched serum, can reliably and validly estimate the de novo rate of IgG synthesis in CNS of patients with MS.
Assuntos
Sistema Nervoso Central/metabolismo , Imunoglobulina G/biossíntese , Esclerose Múltipla/imunologia , Barreira Hematoencefálica , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Albumina Sérica/análiseRESUMO
BACKGROUND: The obese who seek therapy may also have depression and thus a risk for suicidality (suicidal acts and ideation). For this reason and because of interest in the potential impact of a medication with antidepressant properties on suicidality in a population without a primary diagnosis of depression, we performed a comprehensive analysis of suicidality data from clinical trials in patients seeking weight-reduction therapy. METHOD: Suicidality data from 11 double-blind controlled trials in the United States Investigational New Drug fluoxetine obesity clinical trial data base (3819 randomized outpatients) were reviewed. Trials lasted 6 to 60 weeks (continuous and intermittent therapy designs). They included obese men and women (median body mass index, 35.0 kg/m2). Trials excluded patients treated with antidepressants. Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred. One suicide attempt was reported in a patient receiving placebo after prior fluoxetine therapy (intermittent therapy trial). The overall incidence of suicidal ideation among fluoxetine-treated and placebo-treated patients in the obesity clinical trials was 0.24%. The difference in incidence of emergent suicidal ideation in fluoxetine-treated (0.23%) and placebo-treated patients (0.27%) was not statistically significant. CONCLUSION: Based on these analyses of controlled clinical trials, suicidality occurs but has a low incidence rate in the obese who seek pharmacologic weight-reduction therapy. Fluoxetine-treated and placebo-treated patients did not differ statistically significantly in the incidence of suicidality either during or after discontinuation of therapy.
Assuntos
Fluoxetina/uso terapêutico , Obesidade/tratamento farmacológico , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Benzfetamina/uso terapêutico , Índice de Massa Corporal , Comorbidade , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Método Duplo-Cego , Drogas em Investigação/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/psicologia , Placebos , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/epidemiologiaRESUMO
BACKGROUND: The presence or absence of anxiety has traditionally determined choice of an antidepressant ("activating" or "sedating"); however, there is little scientific support for the construct. We conducted a meta-analysis to determine whether comorbid anxiety affected efficacy or predisposed patients to specific adverse events. METHOD: Data were evaluated from 19 randomized, double-blind clinical trials comparing fluoxetine with placebo or a tricyclic antidepressant (TCA) or both in 3,183 patients with major depression (Cochran-Mantel-Haenszel, Mantel-Haenszel incidence difference, analysis of variance, and Pearson's chi-square methods). On the basis of the anxiety/somatization factor within the 21-item Hamilton Rating Scale for Depression (HAM-D21), patients were characterized as anxious (score > or = 7) or nonanxious (score < 7). RESULTS: Fluoxetine was significantly (p < or = .05) more effective than placebo in treating both anxious and nonanxious major depression (mean improvement in HAM-D21 total score, 11.0 versus 8.1 and 8.1 versus 5.5, respectively). Fluoxetine was also statistically significantly more effective than placebo in reducing the HAM-D21 anxiety/somatization factor score (anxious, all patients). The efficacy of fluoxetine and TCAs was comparable (all measures, all groups). Discontinuations for adverse events were statistically significantly higher with fluoxetine than placebo (anxious, 15.2% versus 3.8%; nonanxious, 13.2% versus 6.7%) and with TCAs than fluoxetine (anxious, 28.9% versus 15.5%; nonanxious, 34.1% versus 19.0%). Among events suggestive of "activation" or "sedation," incidence rates ranged from 0.0% to 32.9%; discontinuation rates were low (0.0% to 4.1%), except for somnolence with TCAs (9.4% to 13.2%). CONCLUSION: Anxiety in major depression does not appear to affect response to an antidepressant. Therefore, antidepressant selection should be determined by an agent's overall risk:benefit ratio, not the presence or absence of anxiety.
Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo/tratamento farmacológico , Fluoxetina/uso terapêutico , Adulto , Comorbidade , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/psicologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Cooperação do Paciente , Pacientes Desistentes do Tratamento , Placebos , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: The coincidence of major depressive disorder in bulimia nervosa ranges from 35% to 80%. Because of this comorbidity and because suicidality (suicidal acts and ideation) is an inherent part of depression, assessment of the risk of suicide in patients with bulimia nervosa is of considerable interest. METHOD: Data from United States Investigational New Drug double-blind, placebo-controlled fluoxetine clinical trials in bulimia nervosa were analyzed comprehensively to assess the potential association between fluoxetine treatment and suicidality in 785 patients with DSM-III-R bulimia nervosa. Patients were predominantly women (98%), aged 17 to 63 years; of the randomly assigned patients, 16.9% exhibited 17-item Hamilton Rating Scale for Depression (HAM-D) total scores of 17 or greater at baseline (range, 0-31). Incidence of suicidality was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts occurred; 9 (1.15%) of 785 patients made nonfatal attempts; 24 (3.06%) experienced emergent (text-defined) suicidal ideation. No statistically significant increases in the incidence of suicidal acts or suicidal ideation were observed among fluoxetine-treated compared with placebo-treated patients. A smaller percentage of fluoxetine-treated (2.0%) than placebo-treated (3.8%) patients experienced emergence of substantial suicidal ideation (change in baseline HAM-D Item 3 [suicide item] score of 0 or 1 to 3 or 4 during therapy). A statistically significantly greater proportion of fluoxetine-treated than placebo-treated patients experienced improvement in suicidal ideation (decrease in HAM-D Item 3 score) from baseline to endpoint (p = .026). CONCLUSION: Analyses of the incidence of suicidal acts and suicidal ideation did not indicate an increased risk of suicidality in patients with bulimia nervosa treated with fluoxetine compared with those treated with placebo.