摘要:

Wilson’s disease is a rare autosomal recessive disease of copper accumulation and copper toxicity, due to mutations in theATP7Bgene, which leads to a failure of copper excretion in the bile. It presents clinically primarily as liver disease, psychiatric disease, neurological disease, or a combination of these. The neurological disease is a movement disorder, with abnormalities of speech, tremor, incoordination and dystonia being common features. Diagnosis of neurologically presenting patients is usually straightforward, with Kayser-Fleischer rings and a urine copper over 100 μg/day almost invariably present. In the treatment of neurologically presenting patients, penicillamine should always be avoided, because of the high risk of permanent, drug-induced, additional neurological deterioration. A new drug we have developed, tetrathiomolybdate, given for 8–16 weeks, in combination with zinc, is our first choice for treating these patients. In the absence of availability of tetrathiomolybdate, zinc or trientine are the next best choices.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Schizophrenia is a serious mental disorder with a profound impact on patients, their caregivers and society. It is also an expensive disorder to treat, despite being relatively rare. In this paper, prevention of schizophrenia is described in terms of primary, secondary and tertiary prevention. Schizophrenia is regarded as a neurodevelopmental disorder with different phases. Primary prevention essentially involves education programmes about the association of obstetric complications and the increased risk of schizophrenia. Secondary prevention involves intervention at the prodromal phase. We review the literature and discuss the evidence relating to intervention in this phase of the illness. Early intervention could result in reduction in morbidity and better quality of life for the patients and their families. The prodromal phase can now be identified, based on current symptoms, with reliability and predictive validity for the risk of development of schizophrenia in the following year. We also discuss possible risks faced by prodromal patients, such as unnecessary stigmatisation, and the role of drug treatment during intervention at this stage. Any recommendation that anti-psychotic medications be routinely prescribed in this phase should be supported by more research work. Drug and psychosocial intervention is indicated as part of tertiary prevention to prevent further disability in the illness.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

It is well known that epilepsy, antiepileptic drugs (AEDs), and the reproductive system have complex interactions. Fertility is lower in both men and women with epilepsy than in the general population. Moreover, reproductive endocrine disorders are more common among patients with epilepsy than among the population in general. These disorders have been attributed both to epilepsy itself and to use of AEDs.The use of the liver enzyme-inducing AEDs phenobarbital, phenytoin and carbamazepine increases serum sex hormone-binding globulin (SHBG) concentrations in both men and women with epilepsy. Over time, the increase in serum SHBG levels leads to diminished bioactivity of testosterone and estradiol, which may result in diminished potency in men and menstrual disorders in some women, and thus to reduced fertility. Liver enzyme-inducing AEDs also reduce the efficacy of oral contraceptives.Valproic acid medication may have effects on serum androgen concentrations and it reduces serum follicle stimulating hormone levels in men with epilepsy. However, the clinical significance of valproic acid-related reproductive endocrine changes in men is unknown. On the other hand, in women, use of valproic acid appears to be associated with a frequent occurrence of reproductive endocrine disorders characterised by polycystic changes in the ovaries, high serum testosterone concentrations (hyperandrogenism) and menstrual disorders. These disorders are especially common among women who have gained weight during valproic acid treatment. There are some discrepancies regarding the reported occurrence of reproductive endocrine disorders in women taking valproic acid for epilepsy. However, most studies also including patients receiving valproic acid for other reasons than epilepsy, and studies in different non-epileptic animal models, have shown an association between valproic acid medication and hyperandrogenism and related reproductive endocrine disorders.From a practical point of view, the length of the menstrual cycles and bodyweight should be monitored in women with epilepsy after commencement of treatment with valproic acid. A serum testosterone assay is helpful in following the possible biochemical endocrine changes. Ultrasonography of the ovaries (preferably transvaginal) is indicated if clinical assessment and serum testosterone measurement imply that there is a clinically significant valproic acid-related reproductive endocrine problem. That would be the case if the menstrual cycles were irregular or prolonged (usually >35 days) and serum testosterone levels elevated, especially with associated weight gain.The endocrine effects of the new AEDs have not been widely studied. However, it seems they may offer an alternative if reproductive endocrine problems emerge during treatment with the older AEDs.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Selective serotonin 5-HT3receptor antagonists have proven safe and effective for the management of postoperative nausea and vomiting. Dolasetron, granisetron, ondansetron and tropisetron selectively and competitively bind to 5-HT3receptors, blocking serotonin binding at vagal afferents in the gut and in the regions of the CNS involved in emesis, including the chemoreceptor trigger zone and the nucleus tractus solitarii. Despite their shared mechanism of action, 5-HT3receptor antagonists have different chemical structures and exhibit differences in receptor binding affinity, dose response and duration of effect. Furthermore, although dolasetron, granisetron, ondansetron and tropisetron are all extensively metabolised by the cytochrome P450 (CYP) system, different components of this system predominate in the metabolism of each of these agents. Hence, although these agents are considered equally effective in the overall population, their pharmacokinetic and pharmacodynamic differences may explain the variability in individual responses to these drugs. This review discusses the pharmacological profiles of dolasetron, granisetron, ondansetron and tropisetron, and the clinical implications of differences in their profiles.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Several disease-modifying agents (DMAs) are approved for the treatment of multiple sclerosis, including three interferon (IFN)-β products, glatiramer acetate and mitoxantrone. This article reviews the adverse event profiles of these DMAs based on the pivotal phase III trials, and provides practical guidelines for managing adverse effects. In general, the most common adverse events associated with IFNβ therapy are flu-like symptoms, including fever, chills and myalgias, and headache. The flu-like symptoms typically resolve within 24 hours and may be mitigated by over-the-counter anti-inflammatory agents. Adverse events related to glatiramer acetate therapy include injection-site reactions and a systemic reaction consisting of flushing, chest tightness, palpitation, anxiety or dyspnoea. The systemic reaction is transient (30 seconds to 30 minutes) and self-limited. Mitoxantrone may cause nausea, vomiting, alopecia, amenorrhoea and myelosuppression; isolated cases of acute leukaemia and dose-related cardiotoxicity have been reported in the literature. Longer-term tolerability data on mitoxantrone as a treatment for multiple sclerosis are needed. It is important for physicians to counsel patients on DMA-related adverse effects, most of which are transient and of mild-to-moderate severity. Various strategies that can be employed to prevent or manage these adverse effects and lessen their impact on the patient are discussed.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

The ability to perform paid or unpaid work is integral to an individual’s quality of life. Therefore, we performed a systematic literature review to examine the impact of depression and its treatment on occupational outcomes. This review found absenteeism from work to be markedly higher among depressed employees and productivity to be dramatically undermined by some symptoms of depression. Gaps in the published literature point to the need for future economic and clinical analyses to include work-related outcomes.Published studies showed that antidepressants can enhance work-related outcomes by alleviating affective symptoms. However, the pharmacological properties of antidepressants may produce differential effects that influence work-related outcomes in other ways. For example, TCAs, but not SSRIs, produce sedation and impair cognitive function in ways that could undermine work-related outcomes. Formal analyses are required to quantify whether the improved social functioning, motivation and vigilance that may be associated with some newer antidepressants translate into improved work-related outcomes. Although few published studies have directly quantified the cost benefit of managing depression and associated lost productivity, existing studies that directly assessed work-related outcomes have suggested that treating depression is cost effective.Gaps in the published literature imply that the impact of depression and antidepressants on occupational outcomes has been understudied. This reflects, in part, the fact that antidepressant studies lasting 4 or 6 weeks are unlikely to capture the impact of treatment on work-related measures. In addition, the current evidence base is fraught with other methodological limitations. The effect of depression on non-paid employment also requires further assessment.In conclusion, the efficacy of antidepressants on work-related outcomes should be measured in clinical trials that have an adequate design and a suitable follow-up period, and included in health technology assessments. Until such studies are available, the evidence base supporting the use of antidepressants will remain incomplete.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

▴ Pregabalin, the pharmacologically activeS-enantiomer of 3-aminomethyl-5-methylhexanoic acid, possesses anticonvulsant activity. Pregabalin binds with high affinity and specificity to voltage-gated calcium channel α2-δ proteins. The putative mechanism of action of the drug is reduced excitatory neurotransmitter release caused by binding to the α2-δ protein, resulting in allosteric modulation of P/Q-type voltage-gated calcium channels.▴ In three well designed trials, oral pregabalin as adjunctive therapy in patients with refractory partial seizures was significantly (p ≤ 0.0007) more effective than placebo in reducing seizure frequency when administered at dosages of 150–600 mg/day (as two or three divided doses).▴ Adjunctive pregabalin produced an overall mean 41.3% improvement from baseline in 28-day seizure-free rate in four long-term (maximum exposure 1764 days), open-label studies in 1480 patients.▴ CNS-related effects (e.g. dizziness and somnolence) were the most frequent dose-related treatment-emergent adverse events associated with adjunctive pregabalin therapy.Table. Features and properties of pregabalin (Lyrica®, CI-1008)

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS