Properties of Venezuelan Equine Encephalomyelitis Virus Accompanying Attenuation In Vitro

Virus obtained during serial plaque passage of the virulent parent egg seed (PES) of the Trinidad strain of Venezuelan equine encephalomyelitis (VEE) virus produced only large plaques during either 3 serial plaque passages in chick fibroblasts or 10 plaque passages in L cells, and was lethal for mice by the intraperitoneal route. Virus showing these characteristics was designated the stable large-plaque (Ls) type. In contrast, virus obtained during serial plaque passage of the attenuated 9t strain in chick fibroblasts formed only very small plaques and was not lethal for mice by the intraperitoneal route. Virus showing these properties was designated the stable small-plaque (Ss) type. Under other passage conditions, however, large-plaque virus that yielded about 90% large and 10% small plaques was obtained; this virus was designated the unstable large or Lu type because it differed from the Ls type, which yielded only large plaques. The Lu type continued to yield the same ratio of large to small plaques for several plaque-to-plaque passages. In addition, small-plaque virus that yielded both large and small plaques and that showed a reduced capability to infect mice was also recovered. This virus was designated the unstable small or Su type because it differed from the Ss type in its higher level of virulence and in its plaque-forming properties. Thus, based upon the properties of virulence for mice and plaque size, four viral types could be discerned. The evidence suggests that serial passage in cell culture imposed environmental pressures that sequentially selected the following viral types: Ls, Lu, Su, and Ss.     

Ventricular septal defect with bidirectional shunting: Mathematical considerations

Previously proposed formulae for the quantitative estimation of bidirectional shunts across ventricular septal defects require determination of the oxygen contents of mixed venous, pulmonary artery, pulmonary venous, and aortic blood. Because these formulae do not take into account the mixing of oxygenated with unoxygenated blood within the ventricles, their use must result in underestimation of shunt flows in each direction. A mathematical model for a ventricular defect is examined, in which it is assumed that mixing of blood occurs in each of six sites in the venae cavae or right atrium, right ventricle, pulmonary artery, left atrium, left ventricle, and aorta. A total of fourteen streams of blood can flow from one to another of these mixing sites. As long as complete mixing occurs in the six specified mixing sites, any degree of mixing or non-mixing of the various streams is permitted. From the equations characterizing the model, formulae are derived in which the shunt flow in each direction is expressed in terms of the oxygen contents in the six mixing sites and the fractions of blood which enter the shunt from either side without prior mixing in a ventricular mixing site. The previously reported formulae, which apply when no ventricular mixing is allowed to occur, lead to theoretical minimum values for the shunt flows in each direction. At the opposite extreme where all the shunting blood is required to mix in a ventricle before entering the shunt, formulae for maximum possible shunt flows are also obtained. The absolute values for the left-to-right and right-to-left shunt flows, which must lie somewhere between the theoretical maximum and minimum values, cannot be computed from blood gas data alone. This work was supported in part by grant HE-07563 from the National Heart Institute of the National Institutes of Health and grants-in-aid from the American and North Carolina Heart Associations and the Life Insurance Medical Research Fund. Work completed during tenure as U.S.P.H.S. post-doctoral fellow.     

The Plasma Phenolsulfonphthalein Index (PSPI) of Renal Function: I. Theoretical Considerations and Investigative Studies

A simple method is described for the assessment of renal function, without collection of urine. Phenolsulfonphthalein (PSP) is injected intravenously in a dosage of 1 mg./kg. body weight, and blood samples are taken at timed intervals. Only one venepuncture is required. The index is based on the rate of decrease in concentration of PSP in the plasma 15 to 35 minutes after injection, during which time this rate is exponential. The methodology and normal range, and the influence of dose, urine flow rate, age and body surface are defined. The extrarenal component of the PSP index and the distribution of PSP in body fluids are discussed.     

Studies of Male Survivors of Myocardial Infarction: VI. The Electrocardiogram

Electrocardiograms of 101 men who survived myocardial infarction for at least three months and were free of hypertension, heart failure and other significant disease were analyzed. Within the range of 30 to 70 years, age had no apparent influence on the ECG. Six ECGs were borderline, 79 were abnormal and 16 had returned to normal. Of those with the pattern of infarction, 56 were transmural and 22 nontransmural. For all cases, posterior involvement was somewhat more common than anterior (46 to 32), but it was less common in non-transmural infarction. Ventricular premature beats, always unifocal and few in number, were the only abnormality in rhythm. Atrial fibrillation was conspicuously absent. There were four instances of complete left bundle-branch block. No evidence of left ventricular hypertrophy was seen. The clinical significance of these observations is briefly discussed.