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Because of an error in the manufacture of digoxin tablets a large number of patients took tablets that contained 0·20 mg. of digitoxin and 0·05 mg. of digoxin instead of the prescribed 0·25 mg. of digoxin. The symptoms are described of 179 patients who took these tablets and suffered from digitalis intoxication. Of these patients, 125 had taken the faultily composed tablets for more than three weeks. In 48 patients 105 separate disturbances in rhythm or in atrioventricular conduction were observed on the electrocardiogram. Extreme fatigue and serious eye conditions were observed in 95% of the patients. Twelve patients had a transient psychosis. Extensive ophthalmological observations indicated that the visual complaints were most probably caused by a transient retrobulbar neuritis.

In a titrated dose cross-over trial of debrisoquine and methyldopa in 38 hypertensive patients neither drug was superior in lowering supine or standing diastolic pressure with a minimum of side effects. Methyldopa caused significantly greater reduction of supine (P

Plasma levels of tricyclic antidepressant drugs vary considerably between individuals receiving the same amount of drug. The bearing of this variation on the occurrence of subjective side effects was investigated in 40 psychiatric inpatients with depressive disorders. Plasma levels were determined before and during four weeks of treatment with nortriptyline 50 mg. three times a day and patients were rated for subjective side effects, the assessors being unaware of the plasma levels of the drug.Plasma levels varied widely between individual patients, but in any given patient the plasma level tended to be constant over a period of time. The side effects of nortriptyline diminished significantly with time and were in most cases absent during the fourth week of treatment. There was a significant positive correlation between plasma level of nortriptyline and subjective side effects.The steady-state plasma level of a drug which is metabolized is usually a more important determinant for its effect than dosage, since it reflects the amount of drug available for biological action. Very high plasma levels of nortriptyline should presumably be avoided, since there is no evidence that they are needed for therapeutic effect and they are potentially harmful.

Use of the midnight dexamethasone suppression test showed that the plasma 11-hydroxycorticosteroid (11-O.H.C.S.) level did not undergo its normal reduction in 14 out of 27 patients with severe depression. Resistance to dexamethasone suppression correlated with the clinical rating of the severity of depression, while recovery from depression was associated with return of normal responsiveness to dexamethasone. The explanation of these findings is unknown.

The clinical effects of transient elevation of serum tyrosine level were evaluated in a group of premature infants. Neurologic performance was measured at 15 to 29 months of age using the Bayley Infant Scale of Mental Development. There were no differences in either motor or mental development as measured by this test between infants with high and low serum tyrosine levels. The neonatal course in infants with elevated serum tyrosine levels was compared to that in two groups of infants with low serum tyrosine levels: one group with and one without supplemental ascorbic acid. The only difference in the occurrence of maternal or neonatal complications was in the group with high tyrosine levels, which had significantly greater incidence of symptoms similar to those in infants with neonatal sepsis and characterized by lethargy, poor feeding, and failure to gain weight.