摘要:

Multiple sclerosis is an immune-mediated disease of the CNS, and T cells appear to play a central role in its pathogenesis. In an animal model, T cells specific for myelin basic protein (MBP) induce a syndrome (experimental autoimmune encephalomyelitis) with symptoms similar to multiple sclerosis. This suggests that T cells specific for this protein may be pathogenic in multiple sclerosis.Anti-T cell vaccines that induce regulation of autoreactive T cells are effective treatments for experimental autoimmune encephalomyelitis. These anti-T cell vaccines include whole T cell vaccination, T cell receptor peptide immunisation, oral administration of myelin antigens and major histocompatibility complex (MHC) class II peptide immunisation.Preliminary experience in patients who have multiple sclerosis with the first 3 approaches suggests that anti-T cell vaccines represent feasible treatments for this disorder.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

The treatment of patients with drug-resistant schizophrenia is a major challenge for both the clinician and the patient, and requires systematic and comprehensive management.Patients should initially be assessed to clarify that they are resistant to therapy, as opposed to noncompliant or undertreated. The dosage of existing antipsychotic should be increased. If no response is observed or intolerable adverse effects occur, an alternative typical antipsychotic should be tried. In the event of nonresponse to this alternative agent, a trial with clozapine (an atypical antipsychotic) can be initiated. In patients failing to respond to any single antipsychotic, there are some alternative somatic treatments often used in combination with antipsychotics. These include lithium, carbamazepine, benzodiazepines, &bgr;-adrenergic receptor antagonists, levodopa, reserpine and some antidepressant medications.The reasons for nonresponsiveness are not solely drug related, with psychological and social factors also contributing. Therefore, non-drug strategies, i.e. psychological and social methods, should be used in combination with pharmacological treatments to offer the patient the most consistent benefit.The results of all types of treatment should be evaluated regularly and carefully to allow clear conclusions concerning potential benefits to be made.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Learning disabilities are a group of conditions diagnosed when the individual's achievement in reading, mathematics or written expression is substantially below that expected for his/her age, schooling and level of intelligence. Learning disability does not include learning abnormality resulting primarily from communication disorders, impaired vision or hearing, social or emotional disturbances or cultural differences.A number of classification systems of learning disabilities have been proposed. A clinical-neuropsychological system recognises 5 types of learning disorders based on abnormalities of: (i) phonological processing; (ii) spatial cognition; (iii) executive function; (iv) social recognition; and (v) long term memory.Underlying abnormalities of cognitive processes, mostly auditory and language processing but also visual-perceptual abnormalities, are frequently present in individuals with learning disabilities. Comorbid conditions include attention deficit hyperactivity disorder, conduct disorder and social skills abnormalities.Learning disabilities can be a result of a number of conditions affecting the CNS, but the disorder is predominantly genetically transmitted. Chromosome 6 has recently been implicated in reading difficulties. A number of biological abnormalities have been found in patients with learning disabilities. Anatomical abnormalities include reversal of normally present brain asymmetries and the presence of foci of cerebral microdysgenesis and ectopias. Abnormal regional brain glucose metabolism has been demonstrated in patients with reading difficulties. Neurophysiological abnormalities include abnormal cognitive eventrelated potentials and possible abnormalities of the magnocellular visual pathway.Treatment modalities for learning disabilities include cognitive-educational psychological and pharmacological measures. Although there are no medications directly affecting the learning ability of these patients, central stimulants, clonidine or antidepressants may enhance learning ability through an effect on frequently present comorbid conditions.The prognosis of a patient with learning disabilities depends on the severity of the disability, intelligence level, the presence or absence of comorbid conditions, and environmental support.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

There are no simple answers to questions such as ‘Which antidepressant is most likely to cause seizures?’ or ‘Which antipsychotic drug is the safest to use in a patient with a seizure disorder?’The risk of psychotropic drug-induced seizures is dependent on many factors beyond inherent differences in the propensity of individual drugs to lower seizure threshold. Individual patient variables that affect the likelihood of drug-induced seizures occurring include a history of epilepsy or seizures, a family history of epilepsy, and postnatal brain damage, head trauma and dementia. Once a drug is selected, seizure risk is directly dependent on dosage, rate and amount of dose titration, and concurrent use of other drugs.Setting aside these other risk factors, the likelihood of drug-induced seizures occurring does differ among psychotropic drugs. Among antipsychotic drugs, clozapine is associated with the highest risk of seizures, followed by chlorpromazine, with other phenothiazines and risperidone having a lower risk and haloperidol the least risk.Among antidepressants, maprotiline, amoxapine, amfebutamone (bupropion) and clomipramine pose the greatest risk along with other tricyclic antidepressants in high doses. Monoamine oxidase inhibitors (MAOIs), trazodone, nefazodone and the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) are associated with a lower risk of seizures.Benzodiazepines with long elimination half-lives are less likely to cause seizures during withdrawal than those agents with short to intermediate half-lives, although the rate and amount of dosage reduction are more important variables.Finally, most psychotropic drugs are metabolised by cytochrome P450 isoenzymes. Concurrent use of enzyme inhibitors or discontinuation of enzyme inducers may cause a significant increase in plasma concentrations of the psychotropic drug, increasing the likelihood of adverse effects and the potential for seizures.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Neurodegeneration produced by toxic levels of glutamate is now suggested to be a causative factor in the pathologies found in a number of neurological diseases. This glutamate-induced toxicity is mainly due to activation of both theN-methyl-D-aspartate (NMDA) and non-NMDA classes of glutamate receptors. Hence, drugs that act as antagonists at these receptors are potentially neuroprotective in many diseases. Noncompetitive antagonists appear to be the preferred type of ligand because their action is not diminished by the levels of glutamate reached during a trauma. In addition, they may have reduced adverse effects compared with competitive antagonists.The group of non-NMDA receptors consists of the &agr;-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors, which can be defined on the basis of their pharmacology or by recombinant gene techniques. The latter methods demonstrate a far more complex picture for the receptors. Studies show the presence of at least 9 different protein subunits, which, when linked in groups of 5, comprise the AMPA and kainate subclasses of glutamate receptors.The native non-NMDA receptor has at least 3 separate binding sites at which non-NMDA receptor antagonists can act: glutamate, desensitisation and intra-ion channel binding sites. The glutamate binding site is the site for competitive antagonists such as 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX). Non-NMDA receptors show rapid desensitisation, which limits the duration of activation of the receptor. One group of noncompetitive antagonists (e.g. GYKI 52466) binds at this desensitisation site. Another group of noncompetitive antagonists, the spider and wasp toxins, bind at the third site within the ion channel.Protection against ischaemic damage is the most well researched indication for the application of non-NMDA receptor antagonists and the one that shows the most promise. However, almost all studies in any indication so far have only been carried out in rodents. Recent evidence suggests that antagonists at non-NMDA receptors are more effective neuroprotective agents than NMDA receptor antagonists after ischaemic attacks, and that their administration can be delayed for up to 12 hours without seriously compromising the extent of neuroprotection.Protection against neuronal loss caused by physical injury to the brain or motor neuron disease are other potential uses for non-NMDA receptor antagonists. The antagonists are less effective than the NMDA receptor antagonists against neuronal loss caused by hypoglycaemia or status epilepticus. Non-NMDA receptor antagonists are also effective as anticonvulsants and as antiemetics during cancer chemotherapy. As antiparkinsonian drugs, they show marked synergistic effects when given in combination with levodopa, but are unlikely to be useful as a monotherapy for this disorder.Despite evidence for potential in a number of disorders, prolonged use of non-NMDA receptor antagonists may be contraindicated due to their adverse effects on memory, cognition, motor activity and autonomic functions. Nephrotoxicity due to poor solubility and a short duration of action are also limitations of at least some of the current generation of non-NMDA receptor antagonists. Minimising these adverse effects, particularly with drugs that are selective for the receptor subunits, and translating the results of animal studies to human conditions will be awaited with interest.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Schizophrenia is a poorly understood syndrome characterised by positive symptoms (hallucinations and delusions), negative symptoms (inability to become involved in and enjoy activities and relationships) and cognitive disorganisation.Largely because of the difficulty the schizophrenic patient has in gaining and maintaining employment, this syndrome is very costly for society. New antipsychotic agents, which are more effective and better tolerated than older drugs, and programmes designed to treat schizophrenic patients in the community rather than in the hospital both offer a great deal of promise. Lengthy, expensive hospitalisations are now quite rare. In that respect, the direct costs of schizophrenia may have lessened somewhat. However, none of the various pharmacological and nonpharmacological treatments available have yet convincingly increased the ability of the schizophrenic patient to work.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS