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methylmalonic acid was first isolated from pooled human urine in 1957 by Thomas and Stalder and convincing evidence has since been obtained to show that in man the isomerization of l‐methylmalonyl‐Co A to succinyl‐Co A is dependent on the B12 coenzyme dimethylbenzimidazolyl cobamide (White, 1962). Indeed, Cannata, Focesi, Mazumder, Warner and Ochoa (1965) showed recently that l‐methylmalonyl‐Co A mutase bears two molecules of cobamide coenzyme firmly attached to its molecule. In a series of 30 patients Cox and White (1962) detected excessive methylmalonic acid in the urine of all patients with serum vitamin B12 levels below 140 pg./ml., their lower limit of normal. Patients with normal serum B12 levels excreted up to 4 mg. of methylmalonic acid in 24 hours. Their series included six patients who were treated with intramuscular hydroxocobalamin (1000 μg.). In five of these, excretion fell to normal within 3 days, and on the fifth day after injection in the sixth patient. Barness, Young, Mellman, Khan and Williams (1963) reported one vitamin B12 deficient patient in whom the urinary excretion of methylmalonic acid reached 500 mg. in 24 hours. Recently Khan, Williams, Barness, Young, Shafer, Vivacqua and Beaupre (1965) have described seven out of nine patients with pernicious anaemia in whom methylmalonic acid excretion persisted for some months after the institution of B12 therapy. This occurred despite full clinical and haematological remissions and in four patients, normal serum vitamin B12 levels. The present study was undertaken to determine the value of urinary methylmalonic acid excretion as a screening test for vitamin B12 deficiency. The estimation of methylmalonic acid was carried out by a rapid thin layer chromatographic technique, suitable for routine laboratory use. Normal controls and patients suffering from general haematological and medical disorders were screened as well as patients suffering from megaloblastic anaemia. In several patients the excretion of methylmalonic acid was followed for a short period after B12 therapy.

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To elucidate further the clinical significance of the anticentromere antibody (ACA), 32 Australian-born Caucasian patients with scleroderma (SD) or CREST (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) were reclassified as ACA-positive (19 patients) or ACA-negative (13 patients). The clinical features of the two groups were compared. Mean disease duration was 11.7 years for the ACA-positive group and 1.1 years for the ACA-negative group. No ACA-positive patient had generalized skin SD, whereas all ACA-negative patients with disease duration greater than 6 months had moderate or severe proximal scleroderma. Only one ACA-positive patient had serious extra-oesophageal internal organ involvement, excluding primary biliary cirrhosis (three patients) which is itself associated with ACA. Three ACA-negative patients had serious extra-oesophageal internal organ involvement. No ACA-positive patient had been treated with penicillamine or captopril compared with 11 ACA-negative patients. Thus ACA appears to be a favourable prognostic indicator. Analysis of individual CREST manifestations in ACA-positive patients revealed that most had 'incomplete CREST', lacking one or two of the five features. The classification of SD patients as ACA-positive or ACA-negative is suggested.

In a randomized double-blind prospective between-patients trial in patients presenting with primary anxiety, atenolol significantly improved mean values on the Hamilton rating scale at two and four weeks when compared with placebo. There was also a significant improvement in affective symptoms at 28 days for atenolol when compared with placebo.