Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies.

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon but distinctive clinicoradiological entity comprising of headache, seizures, visual disturbance, and altered mental function, in association with posterior cerebral white matter edema. With appropriate management, RPLS is reversible in the majority of cases. Previous reported associations of RPLS include hypertension, eclampsia, renal failure, and use of immunosuppressive drugs; reports in the adult hematology setting are rare. We report two cases of adults undergoing treatment for hematological malignancies who developed RPLS, and we emphasize the importance of early recognition and institution of appropriate management in reducing the risk of development of permanent neurological disability.

Clinical features of Fabry's disease in Australian patients.

BACKGROUND: Anticipating the prospect of specific treatment, we studied a large group of Australians with Fabry's disease. AIMS: We aimed to: (i) document the clinical features of Fabry's disease in Australian patients, (ii) test the hypothesis that clinical features vary with specific mutation and blood group and (iii) assess small-fibre peripheral nerve function. METHODS: A questionnaire was forwarded to all Australian patients known to us. Patients were invited to attend for clinical, renal cardiac, ophthalmological and neurological assessment. RESULTS: Sixty-seven patients (29 men and 38 women) from 18 families participated. Diagnosis in index cases was delayed by > or = 10 years in nearly all families. Common clinical features are: (i) episodic acroparaesthesia (100% of hemizygotes; 53% of heterozygotes), (ii) anhydrosis (93%; 1%), (iii) characteristic rash (93%; 13%), (iv) renal disease (69%; 21%), (v) ischaemic heart disease (28%; 26%), (vi) palpitations (62%; 29%), (vii) mitral valve murmurs (37%; 23%) and (viii) premature cerebrovascular disease (31%; 5%). Ophthalmic findings of cornea verticillata (96%; 76%) and anterior cataract (48%; 14%) were common. Findings were variable within and between families. In women, anhydrosis reliably predicts the presence of significant Fabry's renal disease. Small nerve fibre testing using quantitative sensory testing was clearly abnormal in 95% of male patients, and in those female patients with paraesthesiae. CONCLUSIONS: Symptoms of anhydrosis, acroparaesthesiae, rash and renal disease suggest diagnosis of Fabry's. Women are commonly symptomatic, and the advent of therapy highlights the practical advantage of earlier diagnosis.

The clinical use of plasma clozapine levels.

OBJECTIVE: This review examines the evidence supporting the proposition that a threshold clozapine plasma level can predict clinical response. In addition, it provides a brief overview of the pharmacokinetics, side effects, drug interactions and assay methodology of clozapine. METHOD: A comprehensive search of relevant literature was made with respect to the above criteria. The findings were collated and analysed to produce an overview of the usefulness of using clozapine levels in clinical practice. RESULTS: Most researchers find that, although the correlation between dose of clozapine and clinical effect is not high, a threshold plasma level of 350-420 ng mL-1 of clozapine is associated with an increased probability of a good clinical response to the drug. Results vary, however, with the study design. CONCLUSIONS: The data reviewed present a case for increasing the dose of clozapine in non-responsive patients to achieve a plasma level of at least 350-420 ng mL-1. Non-response at these levels, however, should not preclude a further upward titration of dose. This should occur unless (i) clinical response is obtained at a lower dose, (ii) intolerable side effects occur, or (iii) a daily dose of 900 mg is reached.