Cardiac Monitoring in a Community Hospital—Analysis of 18 Months' Experience

Cardiac monitoring facilities have been present in teaching hospital centers for over five years. A substantial decrease in mortality has been observed in monitored patients with acute myocardial infarction. The community hospital system offers a challenge to effective monitoring since many physicians care for patients and often many kinds of therapy are used.After 18 months of operation mortality from myocardial infarction was only 16.6 percent in a community hospital monitoring unit where the majority of the emergency care and resuscitation was carried out by nurses. Vital to this success was the use of standing orders for nurses, requirement of privilege to practice within the monitoring facility and acceptance of the nurse as a therapist in emergency situations.Fourteen patients were successfully resuscitated and were later discharged from the hospital. Four of them had ventricular fibrillation from digitalis intoxication.Patients with shock and severe congestive heart failure continue to be a major unsolved clinical problem. The results indicate that the potentially viable patient with serious electrical disturbances can almost invariably be salvaged.     

Regulation of Glutamine Synthetase X. Effect of Growth Conditions on the Susceptibility of Escherichia coli Glutamine Synthetase to Feedback Inhibition

The kinetic properties of Escherichia coli glutamine synthetase are markedly influenced by the manner in which the organism is grown. Enzyme obtained from stationary-phase cells grown on glycerol and glutamate is strongely inhibited by each of the eight feedback effectors known to influence this enzyme; however, the enzyme from log-phase cells grown on glucose and growth-limiting concentrations of NH(4)Cl is stimulated by some of these effectors. Of the growth variables examined, nitrogen source and time of harvest were the most important; carbon source and aeration seemed to have no effect. Two purified enzyme preparations have been obtained from cells grown under two different conditions, designated enzymes I and II for convenience. Enzyme I is stimulated by adenosine 5'-monophosphate, histidine, and tryptophan in the transfer assay, whereas enzyme II is strongly inhibited by all effectors tested. Enzyme I has a higher specific activity in the forward assay in the presence of Mg(++) or Co(++), whereas enzyme II is more active in the presence of Mn(++).     

Inheritance of quantitative expression of erythrocyte glucose-6-phosphate dehydrogenase activity in the Negro—a twin study

Studies have been conducted on eight sets of monozygous and nine sets of dizygous female Negro twins, both members of whom were heterozygous for G-6-PD deficiency. Twins were studied both by assay of erythrocytic G-6-PD activity and by the methemoglobin elution test (MET). The MET is a procedure which identifies histochemically cells with appreciable G-6-PD activity and permits accurate determination of the percentage of such cells in heterozygotes. Monozygous twins showed significantly less within-pair variation than dizygous twins with both the MET and G-6-PD assay.Concerning the significantly greater agreement in MET results in monozygous twins than dizygous twins, our present working hypothesis is that X-chromosomal inactivation in the Negro female is genetically controlled, rather than random. However, certain alternate hypotheses allowing for random X-inactivation have not been excluded; these include somatic cell selection after random X-inactivation, and cell exchange between identical twins in utero/it. Studies in nontwin related heterozygotes now underway should help differentiate among these various possibilities.In addition to the studies on 17 pairs of female twins heterozygous for G-6-PD deficiency, 26 pairs of nondeficient female Negro twins have been studied by G-6-PD assay. Within-pair variation in monozygous twins was significantly less than within-pair variation in dizygous twins in all cases. The genetic influences detected with the G-6-PD assay in the female twins could theoretically be due to nonrandom X-inactivation, to genetically determined quantitative differences in enzyme activity (e.g., isoalleles), or to both. By appropriate calculations, based on the MET results, we have factored out the effects of X-inactivation on overall enzyme activity in the heterozygous deficient twins. After removal of the effect of X-inactivation, monozygous twins heterozygous for enzyme deficiency continue to show significantly less within-pair variation than dizygous twins. This finding indicates significant genetic influences on quantitative G-6-PD activity other than X-inactivation and other than the deficiency allele. This conclusion has been strengthened by studies on male twins where X-inactivation is not present.Supported by USPHS research grants AM-09381, HE-17544, AM-09919, and HE-03341, by USPHS Career Development Award 1-K3-AM-7959 (Dr. Brewer) and by U.S.A.E.C. Contract (11-1)-1552.     

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.     

Substructure of membranes in cultivated chick embryo fibroblasts

Summary Electron microscope examination of the plasma membrane of chick embryo fibroblasts cultured in vitro revealed the presence of a single osmiophilic layer about 90 Å thick and a substructure composed of ovoid sub-units associated with an amorphous component. These ovoid sub-units measured approximately 112 Å along the major axis and 75 Å along the minor axis and were composed of a central core, approximately 30 Å by 60 Å, surrounded by a peripheral component.Examination of other membranous components of these cells revealed a similar ovoid subunit structure in a single layered membrane. Differences in thickness and in the sizes of ovoid sub-units were seen in these membranes. The ergastoplasmic membranes, the outer nuclear membranes, the outer mitochondrial and the Golgi membranes were found to be the thinnest.These varied in thickness from approximately 75 Å to 80 Å. The thickest membranes seen were the inner nuclear membranes. These were approximately 100 Å thick. The dimensions of the ovoid sub-units corresponded with differences in the thickness of the various membranes. These findings support the concept of a particulate substructure of cell membranes.This work was aided by Research Grant PH 5593 from the National Science Foundation. Some of the equipment used was purchased with funds from the National Institutes of Health Grant 2TI GM 326. I wish to thank Dr. Robert M. Dougherty from the Department of Microbiology who grew and supplied me with the chick embryo fibroblast cultures used in these studies, and Mrs. Ursula Feller fer her technical assistance.