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1 A search for patient variables relevant to digoxin dose requirements was made in forty-three patients with a wide range of renal and hepatic function. The daily dose of digoxin to achieve a mean serum concentration of 1.5 ng/ml, the standardized dose, was calculated for each patient. 2 The standardized dose correlated significantly with the following variables, in descending order of correlation coefficient; creatinine clearance, serum creatinine concentration, body weight and serum albumin concentration. An equation containing the two independent variables, creatinine clearance and serum albumin concentration, had a significantly stronger correlation with standardized dose than creatinine clearance alone. 3 Attempts were made in each patient to predict the standardized dose using both empirical prescribing methods and the published nomograms. Although a maximum of 70% of the variance of the standardized dose was explained, this corresponded approximately to one patient in three having a predicted dose outside the 95% confidence limits for the standardized dose. 4 There remain important sources of individual variation in digoxin dose requirements yet to be identified. Future application of empirical prescribing methods, such as multiple linear regression and Bayes' theorem, to prescription for large, defined patient groups may improve dose prediction for individual patients.

THE USE OF HISTOPATHOLOGY IN LEPROSY DIAGNOSIS AND RESEARCH The way we think and talk about leprosy, using the terms 'tuberculoid' and 'lepromatous', is histopathologically orientated. In the most widely used system of leprosy classification-the Ridley-Jopling classification-histology plays the major role.' In clinical practice, there is no doubt that the histological assessment by an experienced pathologist of a representative skin (and/or nerve) biopsy and enumeration of bacilli provides information as significant as that derived from the clinical examination of a patient. Only a small proportion of the estimated 10+ million patients with leprosy have been biopsied. The current uses of tissue biopsy fa ll into two broad categories: diagnosis of leprosy and leprosy reactions; and research into inflammatory processes. Some aspects, particularly those with practical applications, are discussed here. Diagnosis of leprosy-early disease Early diagnosis of leprosy is a prerequisite for control as well as for effective therapy. Epidemiologically, the total number of cases of leprosy needs to be established for a region, and much underestimation may ensue from the poor detection of early cases. There is no independent 'gold standard' for the diagnosis of leprosy. Neither serological nor skin tests have sensitivity and specificity high enough to be useful in confirming or eliminating all suspect cases of leprosy. How useful is histopathology? The two cardinal histological fe atures of leprosy are appropriate patterns of inflammation involving certain sites in skin (e.g. nerves), and the demonstration of acid-fast baciUi (AFB) in appropriate sites. The degree of confidence that individual pathologists place in a diagnosis of early leprosy is variable. The importance of accurate histological assessment is emphasized by the widespread poor performance of slit-skin smear bacteriology: low densities of AFB in skin are underestimated or missed entirely, so that cases are missed as well as being misclassified.2 Only one systematic study has been published on the performance of pathologists on leprosy. Three experienced histopathologists examined the same 143 skin biopsies from leprosy suspects in Malawi, where 95% ofleprosy is paucibacillary.3 The results appear disturbing. The proportions of biopsies classed as showing strong or definite evidence of leprosy ranged from 39% to 58%. The proportions of biopsies thought to be 'possibly leprosy' ranged from 11•5% to 38'5%, reflecting an unexpectedly large variation in degree of uncertainty. Nonetheless, considering only the 82 cases that were clinically thought certain to be leprosy, the histopathologists did agree in 63% to 83% of cases.4 Much of the discrepancy in diagnostic certainty derived from differences in the interpretation of nerve involvement by granulomatous or nongranulomatous inflammation. AFB were uncommonly detected in the biopsies from this population.