A Case of Juvenile Pernicious Anemia: Study of the Effects of Folic Acid and Vitamin B12

Observations on a 4-year-old boy with Addisonian pernicious anemia havebeen presented. Noteworthy clinical features included the onset of glossitisat the age of 4 months, followed by anemia severe enough to require hospitalization at the age of 1 year. Relapse occurred in the absence of specific therapywith vitamin B₁₂ and was completely unaffected by the administration of folicacid.

Studies with radioactive vitamin B₁₂ demonstrated that almost all of thecompound administered by mouth was unabsorbed and was recovered in thestools. When the vitamin was given simultaneously with a concentrate of intrinsic factor, however, approximately 70 per cent was absorbed. Furthermore, the child’s gastric juice, when mixed with radioactive vitamin B₁₂ andfed to an adult with pernicious anemia in relapse, failed to enhance the latter’s absorption of the vitamin. The failure of our patient to absorb the vitaminalone, but his ability to do so when it was administered with intrinsic factorconcentrate, was also confirmed by the "Schilling test," in which a proportion ofthe absorbed radioactive vitamin was "flushed" into the urine by parenteralinjection of one milligram of conventional vitamin B₁₂.

Of special interest was the occurrence in the urine of an unidentified derivative of tetrahydrofolic acid, derived from orally administered pteroylglutamicacid. The presence of this compound in the urine was demonstrated chromatographically when the patient was critically ill with his disease prior to treatment with vitamin B₁₂. Subsequent to therapy with vitamin B₁₂, while theadministration of folic acid was continued, the abnormal metabolite of folicacid could not be found in the urine. Similarly, the administration of folicacid did not lead to the appearance of this metabolite in the urine at a timewhen, after more than two years without specific therapy, a hematologicalrelapse occurred that was much less severe than that previously observed. Theimplications of these observations, with respect to the metabolic interrelationships of folic acid and vitamin B₁₂, are discussed.

Of further interest were the findings of strongly acid gastric juice containingmuch mucus and free hydrochloric acid. A fairly normal gastric mucosa wasdemonstrated by biopsy. The meaning of these unusual findings is discussedand an hypothesis to account for them is offered. The probable sequence ofevents in these patients from childhood to the development of anemia, usuallyin later life, is set forth.

Submitted on October 26, 1960 Accepted on February 9, 1961     

THE CYCLING OF COMBINATION ANTIRHEUMATIC DRUG THERAPY IN RHEUMATOID ARTHRITIS

In this open pilot study a combination of hydroxychioroquine,prednisolone and alternating months of treatment with sulphasalazineor oral weekly pulse methotrexate has been investigated in 16patients with rheumatoid arthritis (RA) refractory to a totalof 67 disease suppressive medications. Results at 3 months indicatedsignificant improvements in visual analogue score for pain,joint count, Ritchie index, scale of disability related to activitiesof daily living, ESR, rheumatoid factor and C-reactive protein.This degree of improvement, however, was not maintained 6 and12 months after commencement of treatment. Pain score, Ritchieindex and ESR were the only parameters demonstrating significantimprovement at 12 months. Therapy was terminated in eight patients,half due to lack of efficacy and half because of side effects. KEY WORDS: Arthritis, Treatment, Methotrexate, Sulphasalazine, Antimalarials, Corticosteroids     

Clinical Electrophysiological Effects of Intravenous Recainam: An Antiarrhythmic Drug Under Investigation for the Treatment of Ventricular and Supraventricular Arrhythmias

This open-label, multicenter study was designed to assess the electrophysiological properties of intravenous recainam, an investigational Class I antiarrhythmic agent. In 25 patients undergoing electrophysiological studies for the evaluation of arrhythmias, recainam was administered intravenously in a loading infusion (0.1 mg/kg/min) for 40 minutes, followed by a maintenance infusion (0.02 mg/kg/min) until the completion of the study. Electrophysiological measurements were obtained at baseline, 30 minutes after initiation of the loading infusion, and 30 minutes after termination of the infusion during washout. Conduction intervals, refractory periods, and sinus node recovery times were measured during sinus rhythm and during atrial or ventricular pacing. Vital signs were obtained and recorded before, during, and after recainam infusion. The results showed no change in mean arterial pressure, but heart rate increased slightly by 4 beats/min following recainam infusion. Recainam produced a generalized slowing of intracardiac conduction. The mean intraatrial conduction time, measured at an atrial paced cycle length of 600 msec, increased during recainam loading infusion by 44%, from 38.8% +/- 2.8 to 53.0 +/- 5.4 msec; intranodal conduction time increased by 10%, from 102.0 +/- 5.5 to 112.1 +/- 5.2 msec; and infranodal conduction time increased by 31% from 53.1 +/- 3.0 to 70.7 +/- 3.8 msec. Slowed conduction persisted during washout. The mean right atrial effective refractory period was significantly prolonged (+7% at 600 msec cycle length and +8% at 450 msec cycle length, P less than 0.05 and P less than 0.01, respectively) during recainam loading and remained so during washout.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Preloads of Differing Energy and Macronutrient Content on Eating Behavior in Bulimia Nervosa

Evidence suggests that bulimics demonstrate blunted satiety possibly due to repeated episodes of overeating. This suggestion was tested further by comparing responses to yogurt preloads differing in carbohydrate and fat relative to a lower energy control yogurt in 12 bulimics and 12 age- and weight-matched controls. Participants were tested on three occasions at lunchtime. On each occasion, appetite and mood were rated before and after receiving a lunch of raspberry yogurt (350 g). Covert manipulation of energy and nutrient content was achieved by matching the yogurts on sensory properties and formulating a control yogurt (161 kcal), a high-fat version (357 kcal: 65% calories from fat), and a high-carbohydrate version (357 kcal: 81% calories from carbohydrate). Although there were no differential effects of the preloads on intake of anad libitumtest meal given 5 hr later in either the control or bulimic groups, there were significant differences in test meal energy intake between groups. On average and with all conditions combined, bulimics ate significantly fewer calories (775±167 kcal) than controls (1182±94 kcal) and consumed a greater percentage of calories from carbohydrate than controls. Bulimics restricted their intake relative to controls, and chose foods low in fat. This study provides further evidence of restricted eating in bulimia nervosa when the opportunity to purge is not available. Furthermore, the present study suggests that intake by bulimics is not influenced by nutrient contentper sebut by consideration of the caloric value of foods and the consequences of eating certain foods for weight control.