摘要:

Thyrotropin-releasing hormone (TRH; protirelin) is the smallest known peptide hormone. It has central effects, unrelated to its endocrine effects, via an action at the pituitary-thyroid axis.TRH has been used successfully to treat children with neurological disorders including intractable epilepsy. The effectiveness of TRH, and an analogue of the peptide (DN-1417), has been reported as both add-on and monotherapy in the treatment of progressive myoclonic epilepsy. West syndrome, Lennox-Gastaut syndrome, complex partial seizures, severe myoclonic epilepsy in infancy, and early infantile epileptic encephalopathy. No serious adverse effects have been reported. TRH may, thus, be considered to be a possible treatment for intractable epilepsy, especially for children with West syndrome and Lennox-Gastaut syndrome. However, it should be noted that the studies were not placebo-controlled or double-blind in design, and most were performed in Japan (the peptide has not been widely studied as a treatment for epilepsy in other countries).The relatively prolonged duration of action of TRH may indicate that the mechanism of its anticonvulsant action differs from that of other anticonvulsant drugs. It is likely that TRH contributes to the plasticity of the seizure network, in analogy to its known trophic effect on spinal motoneurons. Additional research is required to further elucidate the mechanism of action of TRH in children who have epilepsy that is refractory to conventional treatment, and further efforts should be made to develop more potent and selective TRH analogues for neurological disorders.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Nitric oxide (NO) is a messenger that is involved in many physiological events including host defence, vascular tone and neurotransmission. It plays a role in many nervous system functions including synaptogenesis during brain development, synaptic plasticity associated with learning and memory, and regulation of cerebral blood flow. NO is produced from at least 3 different NO synthase (NOS) isoforms: neuronal NOS (type-1; nNOS), immunological NOS (type-2; iNOS) and endothelial NOS (type-3; eNOS).Under conditions of excessive formation. NO may elicit neuropathological changes. For example, excess NO from nNOS has been implicated in neuronal damage associated with stroke, excitotoxins, mitochondrial toxins and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Activation of iNOS may play a role in the pathogenesis of multiple sclerosis and severe AIDS dementia, while derangements in NO formation from eNOS may play a role in the pathogenesis of migraine headaches. Thus, the development of specific NO inhibitors has become a major challenge. Selective inhibitors are beginning to be developed for the various isoforms of NOS, which raises the possibility that medicinal chemists will be able to develop well tolerated and selective NOS inhibitors that may be used for the treatment of CNS disorders that are due to derangements of NO.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Brain abscesses are relatively infrequent encounters during daily practice. However, clinicians are urged to diagnose the disease early and treat patients promptly because of the high risk of mortality and morbidity associated with any delay.Since the availability of computed tomography (CT), the diagnosis and treatment of patients with brain abscesses has improved dramatically. The combination of surgical and medical management has reduced the mortality rate for this disease from 40 to 60% in the pre-CT era to the current rate of 0 to 6%. While stereotaxic aspiration and drainage of the abscesses have revolutionised surgical treatment, new broad-spectrum antibacterials with good penetration into the brain abscess cavity have further improved the outcome of treatment. In selected cases, nonsurgical management alone can be completed successfully with various third generation cephalosporins, metronidazole, or &bgr;-lactam/&bgr;-lactamase inhibitor combinations. By these means, effective treatment has become a reality in multiple cerebral abscesses that have a deep-seated location, a condition that once carried a very high mortality.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Depot administration of antipsychotics has several advantages over oral administration for the treatment of chronic schizophrenia. First, when given by a healthcare professional who has adequate knowledge of the concept, depot administration facilitates the use of a lowest effective dosage strategy. Secondly, the depot form has the obvious benefits of relapse prevention, allowing patients to cope with life in society (rather than in institutions) and providing them with a more stable social situation. This permits the addition of various nonpharmacological therapy elements, which, in turn, will increase the patient's compliance and, eventually, his/her quality of life.Nevertheless, it is apparent that depot antipsychotics are underutilised in some areas because of the belief by some that they represent ‘forced treatment’. However, if schizophrenic patients are properly informed about the advantages of depot antipsychotic administration, they will usually cooperate satisfactorily with the treatment. This increased compliance is a positive therapeutic element, especially since depot antipsychotics are likely to be lifelong treatments.Further research into the use of depot administration of antipsychotics is necessary to optimise treatment by increasing efficacy and reducing adverse effects. If this can be achieved, this type of treatment will further increase relapse prevention and lead to the successful addition of nonpharmacological therapy strategies.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

The presence of a cognitive deficit in patients with schizophrenia has been postulated for over a century, but has only relatively recently become generally accepted. Knowledge of the nature of the deficit may well lead to insights into the pathology of schizophrenia. However, the investigation of cognitive deficits is complicated by the presence of confounding factors, the most important of which is the antipsychotic medication taken by patients with schizophrenia. On a more positive note, if antipsychotic drugs have an effect on the cognitive processes of schizophrenic patients, this in turn may allow a better understanding of the mechanism of action of these drugs.In this article, we review 30 patient studies that investigated the effect of antipsychotic drugs on tests of cognitive function, including a series focusing on clozapine. The practical difficulties in designing patient studies of this type are profound. In particular, the differences between studies in terms of sample size, time of testing and type of statistical analysis are marked. The presence of important confounding variables is unavoidable; the studies reviewed varied greatly in the type and extent of the efforts taken to control for these variables. Although there is poor consistency between the results of these studies, a trend suggesting that antipsychotics improve cognitive function in patients with schizophrenia is discernable.The relationship between antipsychotics and laterality is also reviewed. Consistency between results is again poor, and no conclusions can be drawn at this juncture, although the possibility of progress using neuroimaging techniques appears to be promising.The anticholinergic effects of antipsychotics and other medications are also important, since it is likely that anticholinergic compounds have a detrimental effect on cognition. This can only complicate the investigation of the effect of antipsychotics on cognition, which may be mediated by action at several neuroreceptors. The damaging effect of anticholinergic compounds on cognitive function may have direct clinical implications.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Recent intervention studies have shown that periconceptional supplementation with folic acid-containing multivitamins or pharmacological doses of folic acid alone can reduce the occurrence and recurrence of neural tube defects. This primary preventive method may also reduce the occurrence of other major congenital abnormalities, mainly cardiovascular and urinary tract defects. The underlying biological mechanisms of this protective effect are still not understood, but naturally occurring folates (polyglutamates) or synthetic folic acid (monoglutamate) have a key role.At present, 3 approaches to supplementation with folic acid exist: (i) consumption of a diet that is rich in folate and other vitamins: (ii) periconceptional supplementation: and (iii) fortification of food to ensure appropriate folic acid consumption for all women of childbearing age who are capable of becoming pregnant.The debate over supplementation concerns which vitamins (folic acid-containing multivitamins or folic acid alone?) and what dosages (0.4, 0.8 or 4 to 5 mg/day of folic acid?) are to be given to whom (is it worthwhile differentiating between women at high and low risk?).

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS