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1.
S. A. Likhachev T. N. Chernukha G. V. Zabrodets O. V. Gleb V. V. Alekseevets V. S. Terekhov 《Human physiology》2017,43(8):870-874
This study was aimed at assessing clinical features of camptocormia as one of the dystonia symptoms and evaluating the efficacy of various treatments for this condition. The study involved 39 patients with dystonia and camptocormia symptoms. We analyzed the clinical features of dystonic camptocormia and evaluated the results of pharmacotherapy and botulinum therapy as well as neuromodulation methods, namely transcranial magnetic stimulation and deep brain stimulation. A phased and integrated approach was shown to be required for managing patients with camptocormia caused by dystonic hyperkinesis. Local botulinum toxin injections and deep brain stimulation are the most effective treatments. More extensive use of low-frequency transcranial magnetic stimulation may be advisable for everyday practical use in patients with dystonic camptocormia. 相似文献
2.
Douglas Waugh 《CMAJ》1988,138(9):837-844
Blepharospasm, the most frequent feature of cranial dystonia, and hemifacial spasm are two involuntary movement disorders that affect facial muscles. The cause of blepharospasm and other forms of cranial dystonia is not known. Hemifacial spasm is usually due to compression of the seventh cranial nerve at its exit from the brain stem. Cranial dystonia may result in severe disability. Hemifacial spasm tends to be much less disabling but may cause considerable distress and embarrassment. Patients affected with these disorders are often mistakenly considered to have psychiatric problems. Although the two disorders are quite distinct pathophysiologically, therapy with botulinum toxin has proven very effective in both. We review the clinical features, proposed pathophysiologic features, differential diagnosis and treatment, including the use of botulinum toxin, of cranial dystonia and hemifacial spasm. 相似文献
3.
Dystonias are a clinically and causally heterogeneous group of movement disorders characterized by involuntary muscle contractions that lead to twisting, turning and repetitive movements that can be very painful. Isolated (primary) dystonia is classified clinically as a disease in which dystonia is the only neurological symptom (with or without tremor). Dystonia accompanied by other clinical symptoms (such as parkinsonism or myoclonus) is classified as combined dystonia (dystonia-plus). However, dystonia can be a symptom of any disease of the central nervous system that affects the motor system (e.g. neurodegenerative, ischemic, traumatic processes). During the last 20 years, the development of new molecular genetic technologies has led to the discovery of new genes underlying many dystonia subtypes and to a deeper understanding of the pathophysiology of dystonia. Furthermore, new classification schemes have emerged. This review provides an overview of the genetically determined dystonias, with emphasis on the so-called isolated and combined forms. The summary of phenotypic characteristics associated with specific genetic mutations should enable the clinician to initiate appropriate molecular genetic diagnostics on the basis of concrete clinical manifestations. 相似文献
4.
深部脑刺激器(deep brain stimulator),也经常被称为脑起搏器,是可植入人体设备,并连续不断地传送刺激脉冲到深部脑组织的特定区域,即所谓的深部脑刺激(deep brain stimulation,DBS).迄今为止,深部脑刺激是治疗严重顽固抗药性运动障碍疾病(如帕金森病,原发性震颤及肌张力异常等)的最有效的外科治疗手段之一.此外,广大的科研工作者也不断地探索应用DBS治疗其他神经及精神异常(如,癫痫和强迫症)的新的临床应用.尽管应用DBS治疗运动障碍非常有效,并也迅速被探索性地应用到其他神经障碍治疗中,但其作用机制仍然不是十分清楚,成为学者们争论的热点.DBS治疗效果的作用机制通常有两种基本的观点:高频刺激抑制学说及高频刺激兴奋学说.基于最近发表的关于中枢神经系统内的高频刺激效应的资料、数据及相关评论,两种机制共存并发挥作用的DBS作用假说被提出,认为DBS通过施加高频刺激干扰并控制了核团病理性紊乱随机活动,同时施加兴奋性刺激到其他基底节的网络,以实现对帕金森病的治疗. 相似文献
5.
Humans control their movements using adaptive proprioceptive feedback from muscle afferents. The interaction between proprioceptive reflexes and biomechanical properties of the limb is essential in understanding the etiology of movement disorders. A non-linear neuromuscular model of the wrist incorporating muscle dynamics and neural control was developed to test hypotheses on fixed dystonia. Dystonia entails sustained muscle contractions resulting in abnormal postures. Lack of inhibition is often hypothesized to result in hyperreflexia (exaggerated reflexes), which may cause fixed dystonia. In this study the model-simulated behavior in case of several abnormal reflex settings was compared to the clinical features of dystonia: abnormal posture, sustained muscle contraction, increased stiffness, diminished voluntary control and activity-aggravation. The simulation results were rated to criteria based on characteristic features of dystonia. Three abnormal reflex scenarios were tested: (1) increased reflex sensitivity-increased sensitivity of both the agonistic and antagonistic reflex pathways; (2) imbalanced reflex offset-a static offset to the reflex pathways on the agonistic side only; and (3) imbalanced reflex sensitivity-increased sensitivity of only the agonistic reflex pathways. Increased reflex sensitivity did not fully account for the features of dystonia, despite distinct motor dysfunction, since no abnormal postures occurred. Although imbalanced reflex offset did result in an abnormal posture, it could not satisfy other criteria. Nevertheless, imbalanced reflex sensitivity with unstable force feedback in one of the antagonists closely resembled all features of dystonia. The developed neuromuscular model is an effective tool to test hypotheses on the underlying pathophysiology of movement disorders. 相似文献
6.
M R DeLong 《Federation proceedings》1978,37(8):2171-2175
This review considers the evidence for possible involvement of central nervous system pacemaker neurons in several clinical disorders of movement. Two basic types of tremor are discussed from this point of view, i.e., 4--7/sec parkinsonian tremor, of possible thalamocortical origin, and 7--11/sec essential tremor of possible olivo-cerebellar origin. The importance of motor programs and abnormalities in their utilization are considered with reference to the loss of motor function in parkinsonism (? loss of motor programs), and the inappropriate release of such programs as a possible basis for the involuntary movements seen in other movement disorders, such as chorea, athetosis, dystonia, and hemiballismus. The possible role of pacemaker neurons controlling such programs is considered. Finally, the subject of locomotion and the pacemaker model of the spinal locomotor pattern generator for stepping are considered in relation to clinical disorders of gait. While critical evidence is lacking for pacemaker inovlvement in any of these disorders, their possible role is emphasized. 相似文献
7.
Breakefield XO Blood AJ Li Y Hallett M Hanson PI Standaert DG 《Nature reviews. Neuroscience》2008,9(3):222-234
Dystonias comprise a group of movement disorders that are characterized by involuntary movements and postures. Insight into the nature of neuronal dysfunction has been provided by the identification of genes responsible for primary dystonias, the characterization of animal models and functional evaluations and in vivo brain imaging of patients with dystonia. The data suggest that alterations in neuronal development and communication within the brain create a susceptible substratum for dystonia. Although there is no overt neurodegeneration in most forms of dystonia, there are functional and microstructural brain alterations. Dystonia offers a window into the mechanisms whereby subtle changes in neuronal function, particularly in sensorimotor circuits that are associated with motor learning and memory, can corrupt normal coordination and lead to a disabling motor disorder. 相似文献
8.
Alexander Christoph Rüst Beat Knechtle Patrizia Knechtle Thomas Rosemann 《Journal of brachial plexus and peripheral nerve injury》2011,6(1):1-4
Patients with complex regional pain syndrome (CRPS) often suffer from an array of associated movement disorders, including dystonia of an affected limb. We present a case of a patient with long standing CRPS after a brachial plexus injury, who after displaying several features of the movement disorder previously, developed painful dystonia of chest wall musculature. Detailed neurologic examination found palpable sustained contractions of the pectoral and intercostal muscles in addition to surface allodynia. Needle electromyography of the intercostal and paraspinal muscles supported the diagnosis of dystonia. In addition, pulmonary function testing showed both restrictive and obstructive features in the absence of a clear cardiopulmonary etiology. Treatment was initiated with intrathecal baclofen and the patient had symptomatic relief and improvement of dystonia. This case illustrates a novel form of the movement disorder associated with CRPS with response to intrathecal baclofen treatment. 相似文献
9.
Until now, the equilibrium-point hypothesis (λ model) of motor control has assumed nonintersecting force-length characteristics
of the tonic stretch reflex for individual muscles. Limited data from animal experiments suggest, however, that such intersections
may occur. We have assumed the possibility of intersection of the characteristics of the tonic stretch reflex and performed
a computer simulation of movement trajectories and electromyographic patterns. The simulation has demonstrated, in particular,
that a transient change in the slope of the characteristic of an agonist muscle may lead to temporary movement reversals,
hesitations, oscillations, and multiple electromyographic bursts that are typical of movements of patients with dystonia.
The movement patterns of three patients with idiopathic dystonia during attempts at fast single-joint movements (in the elbow,
wrist, and ankle) were recorded and compared with the results of the computer simulation. This approach considers that motor
disorders in dystonia result from faulty control patterns that may not correlate with any morphological or neurophysiological
changes. It provides a basis for the high variability of dystonic movements. The uniqueness of abnormal motor patterns in
dystonia, that precludes statistical analysis across patients, may result from subtle differences in the patterns of intersecting
characteristics of the tonic stretch reflex. The applicability of our analysis to disordered multijoint movement patterns
is discussed.
Received: 26 July 1993/Accepted in revised form: 22 December 1993 相似文献
10.
J. -M. Lacrosse 《PSN》2007,5(1):83-89
A sociologist who cares to know how a society’s political organisation influences the anthropogenesis of individuals will find that the evolution of psychopathological individuals provide a prime vantage point. That evolution shows how pervasive and deeply rooted in society is the psychology of the individual: individuals are unable to escape the social history enveloping their external environments. In this paper, the author underlines that becoming a person in post-modern society, in which socialisation works through extreme individualisation, is a problem: individuals are no longer able to look at themselves from the point of view of the political whole in which they could then find a place. The author argues that new disorders (depression-related fatigue, antisocial violence, aggressive fear of abandonment, hyperkinesis, and others) are signs of failure in personal authonomy. In every case, there is a bipolarity of extreme independence and dependent behaviour. Arguably, these as yet ‘unidentified clinical objects’ can be related to borderline personality disorders, although the latter concept must be re-examined. 相似文献
11.
Klein C Friedman J Bressman S Vieregge P Brin MF Pramstaller PP De Leon D Hagenah J Sieberer M Fleet C Kiely R Xin W Breakefield XO Ozelius LJ Sims KB 《Genetic testing》1999,3(4):323-328
Early-onset, generalized primary torsion dystonia (PTD) is an autosomal dominantly inherited disorder, characterized by involuntary movements and abnormal postures. The majority of cases are caused by a 3-bp deletion in the DYT1 gene on chromosome 9q34 that allows for specific genetic testing. We developed a simple, reliable, and cost-effective, PCR-based screening method for this mutation. Testing results from a cohort of 550 cases, including patients with different forms of dystonia and unclassified movement disorders, revealed that 72.2% of the patients with typical early-onset generalized PTD carried the GAG deletion in the DYT1 gene. Among 300 cases with late-onset focal/segmental dystonia, only 3 patients tested positive for the GAG deletion whereas 12.8% of the patients with an unclassified movement disorder were GAG positive. Our results confirm a genotype/phenotype correlation in early-onset PTD and show that application of strict clinical criteria leads to accurate prediction of carrier status in more than two-thirds of patients with this type of dystonia. Currently, we suggest that testing be recommended in individuals with age of onset of dystonia below 30 years and/or a positive family history of early-onset PTD. Testing is not recommended in patients with onset of symptoms after 30 years or in asymptomatic individuals under the age of 18. 相似文献
12.
Objective
The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness.Method
Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia.Results
The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder.Conclusions
Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation. 相似文献13.
脑深部电刺激(deep brain stimulation,DBS)是近20年来神经外科领域发展最迅猛的技术。DBS是通过刺激发生器发出的高频电脉冲信号刺激脑神经核团或神经传导束来调节异常的神经环路。DBS已经成为治疗特发性震颤、帕金森病、肌张力障碍等运动障碍病的常规手术方法。自1997年深部脑刺激通过美国FDA认证用于治疗特发性震颤以来,已有超过数万名运动障碍患者接受该疗法,而国内脑深部电刺激最早在1999年应用于帕金森病临床治疗,迄今也有数千例患者接受了植入手术。近年,脑起搏器的临床适应症不断扩大,从最初的运动障碍病逐渐发展到治疗其他神经和精神疾病,如抽动秽语综合征、强迫症、抑郁症、神经性厌食症、难治性疼痛、癫痫、植物状态和阿尔茨海默病等,虽然DBS的治疗机理还不很清楚,但可以预见未来DBS将成为众多神经和精神疾病的重要治疗方法。 相似文献
14.
Jung Hwan Shin Hyeyoung Park Gwan Hee Ehm Woong Woo Lee Ji Young Yun Young Eun Kim Jee-Young Lee Han-Joon Kim Jong-Min Kim Beom Seok Jeon Sung-Sup Park 《PloS one》2015,10(8)
Introduction
SCA17 is an autosomal dominant cerebellar ataxia with expansion of the CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. SCA17 can have various clinical presentations including parkinsonism, ataxia, chorea and dystonia. SCA17 is diagnosed by detecting the expanded CAG repeats in the TBP gene; however, in the literature, pathologic repeat numbers as low as 41 overlap with normal repeat numbers.Methods
The subjects in this study included patients with involuntary movement disorders such as cerebellar ataxia, parkinsonism, chorea and dystonia who visited Seoul National University Hospital between Jan. 2006 and Apr. 2014 and were screened for SCA17. Those who were diagnosed with other genetic diseases or nondegenerative diseases were excluded. DNA from healthy subjects who did not have a family history of parkinsonism, ataxia, psychiatric symptoms, chorea or dystonia served as the control. In total, 5242 chromosomes from 2099 patients and 522 normal controls were analyzed.Results
The total number of patients included in the analysis was 2099 (parkinsonism, 1706; ataxia, 345; chorea, 37; and dystonia, 11). In the normal control, up to 44 repeats were found. In the 44 repeat group, there were 7 (0.3%) patients and 1 (0.2%) normal control. In 43 repeat group, there were 8 (0.4%) patients and 2 (0.4%) normal controls. In the 42 repeat group, there were 16 (0.8%) patients and 3 (0.6%) normal controls. In 41 repeat group, there were 48 (2.3%) patients and 8 (1.5%) normal controls. Considering the overlaps and non-significant differences in allelic frequencies between the patients and the normal controls with low-expansions, we could not determine a definitive cutoff value for the pathologic CAG repeat number of SCA17.Conclusion
Because the statistical analysis between the normal controls and patients with low range expansions failed to show any differences so far, we must consider that clinical cases with low range expansions could be idiopathic movement disorders showing coincidental CAG/CAA expansions. Thus, we need to reconsider the pathologic role of low range expansions (41–42). Long term follow up and comprehensive investigations using autopsy and imaging studies in patients and controls with low range expansions are necessary to determine the cutoff value for the pathologic CAG repeat number of SCA17. 相似文献15.
《Critical reviews in biochemistry and molecular biology》2013,48(6):532-549
AbstractTorsin ATPases (Torsins) belong to the widespread AAA+ (ATPases associated with a variety of cellular activities) family of ATPases, which share structural similarity but have diverse cellular functions. Torsins are outliers in this family because they lack many characteristics of typical AAA+ proteins, and they are the only members of the AAA+ family located in the endoplasmic reticulum and contiguous perinuclear space. While it is clear that Torsins have essential roles in many, if not all metazoans, their precise cellular functions remain elusive. Studying Torsins has significant medical relevance since mutations in Torsins or Torsin-associated proteins result in a variety of congenital human disorders, the most frequent of which is early-onset torsion (DYT1) dystonia, a severe movement disorder. A better understanding of the Torsin system is needed to define the molecular etiology of these diseases, potentially enabling corrective therapy. Here, we provide a comprehensive overview of the Torsin system in metazoans, discuss functional clues obtained from various model systems and organisms and provide a phylogenetic and structural analysis of Torsins and their regulatory cofactors in relation to disease-causative mutations. Moreover, we review recent data that have led to a dramatically improved understanding of these machines at a molecular level, providing a foundation for investigating the molecular defects underlying the associated movement disorders. Lastly, we discuss our ideas on how recent progress may be utilized to inform future studies aimed at determining the cellular role(s) of these atypical molecular machines and their implications for dystonia treatment options. 相似文献
16.
P. Roberto Bakker Asmar F. Y. Al Hadithy Najaf Amin Cornelia M. van Duijn Jim van Os Peter N. van Harten 《PloS one》2012,7(12)
Objective
Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 7 candidate genes (GRIN2B, GRIN2A, HSPG2, DRD3, DRD4, HTR2C, and NQO1).Methods
Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 45 tag SNPs in 7 candidate genes, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders.Results
Various tag SNPs reached nominal significance; TD with rs1345423, rs7192557, rs1650420, as well as rs11644461; orofacial dyskinesia with rs7192557, rs1650420, as well as rs4911871; limb truncal dyskinesia with rs1345423, rs7192557, rs1650420, as well as rs11866328; bradykinesia with rs2192970; akathisia with rs324035; and the principal-factor with rs10772715. After controlling for multiple testing, no significant results remained.Conclusions
The findings suggest that selected tag SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account. 相似文献17.
Human gene for torsion dystonia located on chromosome 9q32-q34 总被引:13,自引:0,他引:13
L Ozelius P L Kramer C B Moskowitz D J Kwiatkowski M F Brin S B Bressman D E Schuback C T Falk N Risch D de Leon 《Neuron》1989,2(5):1427-1434
Torsion dystonia is a movement disorder of unknown etiology characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Dystonic movements can be caused by lesions in the basal ganglia, drugs, or gene defects. Several hereditary forms have been described, most of which have autosomal dominant transmission with variable expressivity. In the Ashkenazi Jewish population the defective gene frequency is about 1/10,000. Here, linkage analysis using polymorphic DNA and protein markers has been used to locate a gene responsible for susceptibility to dystonia in a large, non-Jewish kinship. Affected members of this family have a clinical syndrome similar to that found in the Jewish population. This dystonia gene (ITD1) shows tight linkage with the gene encoding gelsolin, an actin binding protein, and appears by multipoint linkage analysis to lie in the q32-q34 region of chromosome 9 between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase. 相似文献
18.
Hye Ran Park Jae Meen Lee Gwanhee Ehm Hui-Jun Yang In Ho Song Yong Hoon Lim Mi-Ryoung Kim Keyoung Ran Kim Woong-Woo Lee Young Eun Kim Jae Ha Hwang Chae Won Shin Hyeyoung Park Jin Wook Kim Han-Joon Kim Cheolyoung Kim Dong Gyu Kim Beom Seok Jeon Sun Ha Paek 《PloS one》2016,11(1)
Background
GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.Objectives
This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.Methods
Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84)Results
The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.Conclusions
GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center. 相似文献19.
Within the recent development of brain-machine-interfaces deep brain stimulation (DBS) has become one of the most promising approaches for neuromodulation. After its introduction more than 20 years ago, it has in clinical routine become a successful tool for treating neurological disorders like Parkinson's disease, essential tremor and dystonia. Recent evidence also demonstrates efficacy in improving emotional and cognitive processing in obsessive-compulsive disorder and major depression, thus allowing new treatment options for treatment refractory psychiatric diseases, and even indicating future potential to enhance functioning in healthy subjects. We demonstrate here that DBS is neither intrinsically unethical for psychiatric indications nor for enhancement purposes. To gain normative orientation, the concept of “personality” is not useful – even if a naturalistic notion is employed. As an alternative, the common and widely accepted bioethical criteria of beneficence, non-maleficence, and autonomy allow a clinically applicable, highly differentiated context- and case-sensitive approach. Based on these criteria, an ethical analysis of empirical evidence from both DBS in movement disorders and DBS in psychiatric disease reveals that wide-spread use of DBS for psychiatric indications is currently not legitimated and that the basis for enhancement purposes is even more questionable. Nevertheless, both applications might serve as ethically legitimate, promising purposes in the future. 相似文献
20.
BRILL NQ 《California medicine》1957,86(3):147-152
The independent diagnosis and treatment of mental and nervous disorders according to California law constitutes practicing medicine. By this yardstick, an increasing number of clinical psychologists are entering the private practice of medicine. The medical profession has not provided through its leadership the opportunity for clinical psychologists to utilize their skills in a legitimate and supervised way in the treatment of private patients, nor has the medical profession taken sufficient interest in modern methods of treating patients with psychogenic disorders. If the psychiatric team is a feasible and practical approach to spreading the base of psychiatric treatment in hospitals and clinics, it should be applicable to private practice settings too. In the team setting, the psychologist can render great assistance to the physician in the diagnosis and treatment of patients with psychogenic disorders without compromising the principle that the primary responsibility for the patient is the physician's. By virtue of his training and experience, it is the psychiatrist who is best qualified to supervise the work of the psychologist; and until such time as the medical profession is better acquainted with psychotherapeutic techniques, the employment of psychologist assistants should be (according to good medical practice) left to the psychiatrist. The need for some regulation of the use of the title "psychologist" is increasing in order to protect the public from quacks who pose as psychologists. However, any law which is directed toward elimination of the quack should specifically define psychotherapy and contain provisions for its use under adequate medical supervision. The medical profession is obligated to take its traditional role in providing the best possible treatment for patients who are in need of it, and psychotherapy is an inherent part of treatment. 相似文献