摘要:

The ability to alter human tumour cells geneticallyin vivoprovides a variety of new opportunities to selectively destroy malignant cells.The herpes simplex thymidine kinase gene (HS-tk) confers a sensitivity to the antiherpes drug ganciclovir. Insertion of HS-tk into tumours and subsequent treatment with ganciclovir has successfully eliminated tumours in experimental animal models, despite a less than 100% gene transfer efficiency. This phenomenon, the ‘bystander effect’, allows the destruction of neighbouring tumour cells not transduced with HS-tk. Since there is no gene transfer method that is 100% efficient, the bystander effect makes the possibility of using gene therapy for the treatment of brain tumours a reasonable approach in patients with recurrent or metastatic CNS tumours.Human experimentation with this approach began in December 1992. Results from an initial trial have shown that the HS-tk/ganciclovir system can selectively destroy tumour cells with minimal toxicity. Despite the bystander effect, the magnitude of the antitumour effect is currently limited by insufficient gene delivery. Since the HS-tk system is a potent method for tumour cell destruction that is not limited by toxicity, further improvements in gene transfer efficiency may allow the development of a clinically useful therapy for the treatment of CNS malignancies.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Tuberculosis meningitis is the most serious extrapulmonary complication of tuberculosis and the commonest cause of death in childhood as a result of tuberculosis. Appropriate treatment must be started as soon as a diagnosis of tuberculosis meningitis is suspected.The main aims of the drug treatment of tuberculosis meningitis are the eradication of the causative organismMycobacterium tuberculosis, the control of raised intracranial pressure, and modulation of the immune processes causing cerebral vasculitis and the associated exudate at the base of the brain.Isoniazid, rifampicin (rifampin) and pyrazinamide are essential drugs in the treatment of tuberculosis meningitis in dosages of 20 mg/kg/day, 20 mg/kg/day and 40 mg/kg/day, respectively. Lower dosages of isoniazid (10 mg/kg/day) and rifampicin (10 mg/kg/day) can be used if infectious hepatitis is a recognised problem in a particular geographical area, but a reduction in the dose of rifampicin may compromise its sterilising capacity. If it is possible that the disease is caused by drug-resistant organisms, the above regimen should be augmented by ethionamide 20 mg/kg/day or streptomycin 20 to 40 mg/kg/day. Treatment must be continued for a minimum of 6 months, but should be extended to 9 or 12 months if rifampicin cannot be used throughout and if pyrazinamide cannot be used for the first 2 months of treatment.Hydrocephalus and raised intracranial pressure frequently complicate stage II and stage III tuberculosis meningitis. In the presence of communicating hydrocephalus, confirmed on air encephalogram by the appearance of air in the ventricles, furosemide (frusemide) 1 mg/kg/day and acetazolamide 100 mg/kg/day given in 6- or 8-hourly divided doses will expedite the normalisation of intracranial pressure in the majority of cases. Ventriculo-peritoneal shunting should be undertaken immediately in those children with non-communicating hydrocephalus, demonstrated on air encephalogram by the presence of air at the base of the brain but not in the ventricles, and in those children who do not respond satisfactorily to medical management.Corticosteroids, in the form of prednisone or dexamethasone, have been shown to improve both morbidity and mortality in tuberculosis meningitis. These drugs should be given for the first month of treatment.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Trichotillomania is a psychiatric condition characterised by chronic hair pulling, which is often associated with considerable comorbidity. Typically striking during critical developmental periods in childhood or early adolescence, the disorder tends to follow a chronic course.Trichotillomania is currently classified in DSM-IV as an impulse control disorder. However, phenomenological observations, neurobiological investigations and pharmacological responsivity have suggested similarities between hair pulling and affective states, compulsions, tics, and displacement activities involving excessive grooming. These findings indicate that the classification and theories of the aetiology of trichotillomania may need to be reconsidered.Few pharmacological treatment studies have been conducted for trichotillomania, and among those that have been published several discrepant results have been noted. Nonetheless, certain clinical guidelines can be offered. The usual recommended pharmacological approach is to initiate treatment with an antidepressant that has serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibiting properties. This should be administered for 8 to 12 weeks. Depending on the clinical context, augmentation with anxiolytics, thymoleptics, antipsychotics, topical corticosteroids and other agents may be useful.Behavioural treatment is also an important treatment approach and should be considered either as the initial intervention or in concert with medication.Although rational options for the treatment of trichotillomania can be recommended based on the currently available literature, further controlled studies of pharmacological and nonpharmacological interventions are clearly needed.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Bipolar affective disorder is a recurrent, long term mood disorder characterised by the presence of both depressive and manic phases. It involves substantial morbidity with a high suicide risk, and frequently causes a variety of psychological and social problems.The primary goals in the management of patients with bipolar disorder are the treatment of acute depressive and manic episodes and the prevention of future affective episodes. Other equally important goals are interepisodic mood stabilisation and the reduction of excess mortality, mostly caused by suicide. Long term treatment of bipolar disorder requires the development of an overall psychiatric management strategy, that addresses many issues such as pharmacotherapy, informing the patient about the course and treatment of the illness, and supportive psychotherapy.Specific drug treatments are the most important tool in the treatment of bipolar disorder. Lithium is regarded as the drug of first choice for prophylaxis against bipolar disorder. In a number of controlled investigations, lithium has been shown to be preventive and mood stabilising by substantially reducing the frequency, duration and severity of future episodes. Carbamazepine is being used increasingly as an alternative to lithium in patients who fail to respond to lithium prophylaxis. Novel pharmacological alternatives for the prophylactic management of bipolar disorder include valproic acid (sodium valproate), highdose thyroxine and specific drug combinations (such as lithium and carbamazepine or valproic acid).Lithium is the drug of choice for the immediate treatment of acute mania, either on its own or in combination with antipsychotics. Alternatives are primarily valproic acid and carbamazepine. The treatment of the depressive phase is often complicated by the potential risk of an antidepressant-induced rapid change to a manic phase. However, the treatment of depression in patients with bipolar disorder does not generally differ from the treatment of unipolar depression.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Clonidine is an imidazoline compound that was originally used as an antihypertensive agent. It has been found to reduce sympathetic tone via an agonist action at central &agr;2adrenergic receptors, as well as agonist effects on central imidazoline receptors. Clonidine has sedative properties, and its use has been explored by both researchers and clinicians in the treatment and investigation of psychiatric disorders that have a pathophysiology that may involve adrenergic mechanisms.Clonidine has been used extensively in a number of psychiatric disorders, including mood, anxiety, substance abuse, childhood-onset and movement disorders, narcolepsy and anorexia nervosa, and as a treatment for the adverse effects of other drugs. However, there have been few double-blind, controlled studies of the drug in any of these conditions.The disorders for which the use of clonidine is most well supported by research are opiate dependence and Gilles de la Tourette's syndrome. It may also play a limited role in the treatment of patients who have certain disorders that are refractory to standard treatments, and as an adjunctive agent in patients with only a partial response to standard agents. In addition, the drug is currently being used increasingly as a probe of the noradrenergic system in patients with anxiety disorders, depression or schizophrenia.Clonidine is generally well tolerated in patients with psychiatric disorders, although its use is limited by dose-dependent sedative and hypotensive effects.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

This review summarises the preclinical and clinical pharmacology of antipsychotics that are on the verge of introduction into clinical practice by juxtaposition of these data with the information that is already available for clozapine and risperidone.The pharmacology of clozapine is characterised by low affinity for and occupancy of dopamine D2receptors. Furthermore, the locus of action of clozapine may lie at a number of other sites, possibly D4or serotonin 5-HT2receptors. Risperidone is characterised by a high D2receptor affinity and occupancy and a particularly high 5-HT2receptor occupancy. Some investigators postulate that the action of these drugs at 5-HT2receptors is responsible for their efficacy against the negative symptoms of schizophrenia and the low incidence of extrapyramidal adverse effects associated with their use.The effects of olanzapine on receptor systems lie between those of classical antipsychotics and clozapine. The behavioural profile of the drug is atypical, and clinical response is associated with low D2receptor occupancy. Quetiapine (ICI-204636; SeroquelTM) is also behaviourally an atypical antipsychotic. Its receptor binding profile is one of broad spectrum and low affinity, but rank potencies are the same as those of clozapine. Sertindole and ziprasidone seem to be high affinity D2and 5-HT2receptor antagonists, and share many of the properties of risperidone.Much of the clinical information on olanzapine, quetiapine, sertindole and ziprasidone is not in the public domain, but early indications are that all these drugs are useful and well tolerated. While the clinical information may not discriminate one from another, their introduction will make the need to resort to classical antipsychotics less justifiable in a wider range of clinical circumstances.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS