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Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 ± 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol.Neither treadmill exercise duration (7.7 ± 2.3 versus 7.3 ± 2.7 min) nor peak oxygen consumption (18.7 ± 3.7 versus 18.4 ± 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = −0.64, p < 0.05). At maximal treadmill effort, heart rate (138 ± 16 versus 141 ± 21 beats/min), oxygen pulse (10.3 ± 2.1 versus 9.9 ± 2.2 ml/beat), ventilation (40.3 ± 10.6 versus 42.0 ± 10.8 liters/min) and ventilatory equivalent (29.4 ± 4.8 versus 31.5 ± 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 ± 23.1 versus 153.2 ± 25.3 mm Hg, p < 0.05).Left ventricular ejection fraction at rest (32 ± 12 versus 29 ± 12) and maximal cycle work load achieved (75 ± 32 versus 75 ± 28 W) were not affected by glycoside treatment, but ejection fraction and systolic blood pressure at maximal effort were both higher during digoxin than during placebo therapy (32 ± 8 versus 27 ± 9, p < 0.05. and 177 ± 25 versus 165 ± 21 mm Hg, p < 0.05, respectively). The change in peak treadmill oxygen consumption and the change in peak ergometric left ventricular ejection fraction induced by digoxin were not related (r = −.035, p = NS).Therefore, in ambulatory patients with coronary artery disease and chronic, predominantly mild to moderate heart failure, systolic left ventricular dysfunction and sinus rhythm, maintenance digoxin treatment did not elicit an increase in aerobic capacity despite improvement in left ventricular performance during exercise. Nevertheless, the inverse relation between the peak oxygen consumption during placebo administration and the change in this variable elicited by digoxin suggests that exercise testing with respiratory gas analysis may provide a rational basis for identifying ambulatory patients with heart failure who are likely to benefit from maintenance digoxin therapy.

Three cases involving renal scans that showed both severe photopenia and also increase in uptake in a rim surrounding the renal graft are presented. As previously mentioned in the literature, the bad prognostic import of photopenia is confirmed. The increased rim of activity has been rarely mentioned in the literature in the past and its possible causes are discussed.

Several doses of chlordiazepoxide (45, 100, 200 mg) were administered to dogs while they were subjected to a Sidman nondiscriminated avoidance schedule which contained seven conditioned stimuli-unavoidable shock (CS-US) pairings. The drug reliably reduced baseline response rate and significantly inhibited the amount of urinary cortisol excreted during the experimental sessions. Facilitation of heart, response, and activity rates normally noted during the aversive CS were unaffected by administration of the drug. In addition, over-all heart rate showed no consistent pattern of results in response to drug administration. These results suggest that under this schedule of reinforcement only the baseline response rate and urinary cortisol measures were sensitive to the antianxiety effects of chlordiazepoxide.

1. The relative validity of C14-labeled fat and I131-labeled fat in measuring fat absorption was checked in subjects with Neomycin-induced mal-absorption syndrome.

Serum arginase concentration was measured in 28 acutely intoxicated alcoholic males at the time of admission and one week later. Results were compared to measurement of serum LDH, SGOT, serum bilirubin values and to bromsulphalein retention. In 22 of the 28, serum arginase was significantly elevated, which was as high a percentage of abnormals as with any of the other tests of liver function. Arginase concentrations correlated better with BSP retention than with serum albumin, bilirubin, SGOT or LDH. One surprising finding was that during convalescence serum arginase rose in ten patients. This raised the interesting hypothesis that serum arginase concentrations may be related to repair as well as injury.

1. Administration of 12 gm. daily of neomycin for 5 days was followed by an average fecal fat loss of 21 gm. per day. Fecal fat loss became abnormal in 9 of 10 patients.

Previous work by the authors (1) showed that in the high-lipid-fed rat, clofibrate (CPIB) lowered the deposition of cholesterol in the aorta and kidney. The possibility was raised that CPIB might mobilize cholesterol from these organs. This possibility was also raised by Tolman et al. (2) in their paper. Kritchevsky et al. (3) raised another possible explanation for the production of lower tissue cholesterol levels produced by CPIB when they showed that mitrochondria from CPIB-fed rats had an increased ability to oxidize labeled cholesterol in vitro . In the following experiment an attempt was made to prove or disprove the thesis that CPIB had a cholesterol mobilizing effect from tissue.

The ability of the standard ECG to identify myocardial infarction (MI) involving primarily the left ventricular (LV) apex is controversial. Therefore, the ECGs of 62 consecutive patients with acute infarction and isolated akinesia or dyskinesia of the LV apex on gated blood pool scintigraphy performed at rest 9 +/- 4 days after MI, were reviewed. The following distribution of Q waves was found: none, 26%; inferior leads only, 23%; anterior leads only, 32%; inferior + 1 or more V leads, 13%; lead I and/or aVL + 1 or more V leads, 6%. Only 12 patients (19%) demonstrated one of the "combination" Q-wave patterns thought to indicate apical infarction. Although the 20 patients with a history of MI did not differ in age or ejection fraction from those with a first MI, the combination of inferior and anterior Q waves was present in 6 of them (30%), vs only 2 of the remaining 42 patients (5%) (p less than 0.02). The 24 patients with apical dyskinesia had a lower ejection fraction (36 +/- 14 vs 48 +/- 12, p less than 0.001), a lower prevalence of isolated inferior Q waves (8 vs 32%, p less than 0.05) and a greater prevalence of isolated anterior Q waves (46 vs 24%, p = 0.09) than those with akinesia. Thus, in patients with recent MI localized to the LV apex on radionuclide ventriculography, pathologic Q waves are commonly confined to the anterior or inferior leads or absent altogether. The insensitivity of the various proposed criteria for the electrocardiographic diagnosis of apical MI emphasizes the value of imaging techniques in detecting this common clinical entity.

The effect of moderate amounts of alcohol in rats on a high lipid diet were studied. It was found that alcohol tended to lower the cholesterol in the serum, kidney and liver and raise the triglyceride in the serum and aorta.

Several doses of chlorpromazine (6.25, 12.5, 25.0 mg) were administered to dogs while they were subjected to a Sidman nondiscriminated avoidance schedule which contained 7 conditioned stimuli-unavoidable shock (CS-US) pairings. The drug consistently reduced baseline response rate and enhanced shock rate. Facilitation of heart, response, and activity rates normally noted during the aversive CS were unaffected by administration of the drug. In addition, the over-all heart rate, urinary volume, and urinary Cortisol measures showed no consistent pattern of results in response to drug administration. These results suggest that under this schedule of reinforcement only baseline response rate was sensitive to the anxiolytic effects of chlorpromazine.

We studied 166 hospitalized male patients to determine the clinical importance of tolerance-test-determined "lactose intolerance," assumed to affect most of the world's adults. Abnormal lactose tolerance tests were found in 81% of 98 blacks, 12% of 59 whites of Scandinavian or Northwestern European extraction, and three of nine non-European whites. Seventy-two per cent of the "lactose-intolerant" subjects had previously realized that milk drinking could induce abdominal and bowel symptoms. Two hundred and forty milliliters of low-fat milk produced gaseousness or cramps in 59% of 44 "lactose-intolerant" men, and 68% were symptomatic with the equivalent amount of lactose. None of 18 "lactose-tolerant" men noted symptoms with milk or lactose. Refusal to drink 240 ml of low-fat milk served with meals correlated significantly with "lactose-intolerance": 31.4% versus 12.9% among "lactose-tolerant" patients. "Lactose intolerance" is common in adults and is a clinically relevant problem.

In rats on a high lipid diet a study was done on the effect of glucagon injections on cholesterol and triglyceride levels in plasma, liver, kidney, heart muscle, and aorta. There was little effect on the concentration of triglycerides and cholesterol in the liver or in the diaphragm. However, the level of these lipids was significantly decreased in the kidney, aorta, and serum. Possible explanations for the findings are offered.

1. 1. The effects of glucagon alone and glucagon plus stress on lipid levels in various organs were studied. 2. 2. Stress added to glucagon produced no significant change in cholesterol levels of the kidney, liver, and aorta. There were also no significant changes in the triglyceride levels of liver, aorta and serum. 3. 3. Stress did raise the level of diaphragm and serum cholesterol. 4. 4. Stress lowered kidney and diaphragmatic triglyceride in glucagon treated animals. 5. 5. The significance of these results are discussed.

A double-blind study of 537 patients evaluated the relative efficacy of four drugs—chlordiazepoxide, chlorpromazine, hydroxyzine, and thiamine—commonly used in treating alcohol withdrawal symptoms, specifically to prevent delirium tremens and convulsions. Of the 55 patients who developed these symptoms, two percent were in the chlordiazepoxide group; the incidence ranged from ten to 16 percent in the other treatment groups. The authors conclude that chlordiazepoxide appears to be the drug of choice among those tested.

The effects of saturated fat feeding as contrasted with unsaturated fats were studied in rats. The rats on unsaturated fat had lower serum cholesterol and less cholesterol deposition in the aorta, kidney, and liver than those on saturated fats. The animals on unsaturated fat had less deposition of orally fed 14C-cholesterol and iv Na-Ac in these organs than those on saturated fat. Evidence was adduced that the kidney is more efficient than the aorta in removing cholesterol on saturated fat diets.

Rats fed a high lipid diet and also exposed to unavoidable and unpredictable grid shock for 2 and 8 days showed higher levels of accumulated chemical cholesterol in aorta, kidney, liver and serum as compared to control rats fed only the high lipid diet. Thirty days of shock stress produced similar results except that kidney tissue revealed lower and nonsignificant levels of accumulated cholesterol. A differential cholesterol clearing mechanism for the various tissues is postulated to explain the relative vulnerability of aorta, liver and kidney to stress-induced cholesterol deposition.

To the Editor:— Pruritus without objective evidence of skin disease is not commonly thought of as a feature of hyperthyroidism. Occasionally this may be the presenting manifestation in hyperthyroidism. My interest in this subject was aroused by the following case: Report of a Case:— A 43-year-old woman was seen in May 1962 in the Dermatology Clinic of the Johns Hopkins Hospital because of severe pruritus. In addition, in the preceding six months the patient had noted marked hair loss. The serum protein bound iodine (PBI) level was 10.7μg/100 cc. Because of the elevated value, she was referred to the Endocrine Clinic. In response to specific questioning, the patient gave a history of diminished heat tolerance during the preceding year and of poor appetite and a drop in weight from 170 to 159 lb in the preceding six months. The pertinent finding on physical examination was slight diffuse enlargement of the

1. 1. A study was done on the effect of stress on cholesterol deposition in various organs of pair-fed rats. 2. 2. There was an increased amount of cholesterol with aortas, livers, and serum of the stressed animals as compared to the control. 3. 3. There was only a transient elevation in the kidneys of the stressed animals. 4. 4. Evidence is presented that the kidney possesses a better mechanism for clearing cholesterol than the aorta.