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use of sensitive assays of digoxin in body fluids." This knowledge has recently been reviewed in detail by Smith and Haber.'2 Digoxin in serum is only 230' protein bound and is excreted primarily in the urine in unchanged form or as small amounts of metabolites which are both cardioactive and immunoreactive. Urinary excretion is directly proportional to the glomerular filtration rate, and serum levels in the elimination phase decline exponentially with an average serum half time of 36 hours in patients with normal renal function. Daily maintenance treatment without a loading dose results in a steady-state plateau concentration after four or five half lives or about seven days in patients with normal renal function. 13 Impairment of renal function is associated with higher serum digoxin concentrations at any dose level.Clearly, therefore, consistent differences in glomerular filtration rate in patients with thyroid disease, of the order observed in our patients, would influence comparative serum digoxin concentrations. In a recent review of renal function in patients with thyroid disease'4 inulin clearance was found to be raised (145-5±5-6 ml/min in 36 hyperthyroid patients reported by seven groups of workers), and in 17 hypothyroid patients G.F.R. fell to 71±+43 ml/min and then rose towards normal in six out of seven patients who received replacement therapy. In view of the close correlation between digoxin and creatinine clearance the finding of a short digoxin half time and lower serum concentrations of digoxin in the hyperthyroid patients was not unexpected. A similar interpretation is implicit in Doherty's data; mean digoxin clearance was 158 ml/min and 83 ml/min in hyperthyroid and hypothyroid subjects respectively. 5 Undoubtedly a difference in tissue distribution space for digoxin exists in patients with changed thyroid status, but this difference is not relevant to the serum concentrations after achievement of a steady-state plateau in clinical therapeutics.Serum digoxin concentrations in hyperthyroid subjects could also be low secondary to decreased absorption or increased metabolism or faecal excretion of the drug, factors which might explain our discrepant findings. The demonstration of a relative increase in cumulative urinary digoxin excretion in two hyperthyroid patients despite low serum concentrations argues against an important role for these alternative routes of metabolism or excretion.A rapid ventricular response to atrial fibrillation refractory to digitalis treatment is common in hyperthyroidism. Chamberlain's finding of a correlation between slowing of the ventricular rate in patients with atrial fibrillation and serum digoxin levels' 5 suggested that this apparent refractoriness may be partly due to the lower serum concentration in the hyperthyroid patient. Many clinical studies have established the correlation between serum digoxin levels and therapeutic or toxic effects of the drug, and our findings indicate that ideal digitalization of patients with altered thyroid function requires me...

A patient with Whipple's disease has been studied to examine the effect of antibiotic therapy on the immune status of the patient, and the specific immune response to a cell wall deficient form of an alpha-haemolytic streptococcus (alpha HS) isolated from this patient. T lymphocyte numbers were reduced, and cutaneous anergy was present. Autoantibodies directed against smooth muscle and mitochondria were detected. These abnormal parameters became normal following antibiotic therapy. The specific immune response to the alphaHS was characterised by IgA antibody and lymphocyte sensitisation. The latter was detected as antigen-inducedd lymphocyte stimulation and antigen-induced leucocyte inhibition factor (LIF) production. Antibiotic therapy was associated with a fall in antibody titre and reduced LIF production. No defect in neutrophil function was found. These results are most consistent with the postulates that (i) immunological abnormalities in Whipple's disease are secondary to infection and (ii) the primary abnormality is an unusual pathogenic bacterium.

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