Renal intracortical blood flow distribution, function, and sodium excretion in unanesthetized dogs following vena caval ligation. We studied the renal function and the intrarenal blood flow of nine dogs whose thoracic inferior vena cava had been previously ligated (caval dogs) and nine other dogs. Following preparative surgery which included placement of a left atrial catheter, a femoral artery catheter, and bilateral ureteral catheters, the caval dogs gained an average of 2.1 kg of fluid weight, whereas the normal dogs gained no weight. Although neither the caval dogs' blood pressure (114 plus or minus 7 vs 120 plus or minus 4 mm Hg) nor their inulin clearance (0.64 plus or minus 0.06 vs. 0.79 plus or minus 0.06 ml/min g-1 kidney weight) was significantly reduced, their estimated renal blood flow (Cpah/[1-hematocrit]) was considerably lower (2.30 plus or minus 0.24 vs. 3.25 plus or minus 0.15 ml/min g-1). During the clearance study, the caval dogs' excretion of sodium (79 plus or minus 18 vs. 158 plus or minus 17 muEq/min) and their fractional clearance of sodium (2.0 plus or minus 0.4 vs. 3.4 plus or minus 0.5%) were reduced. Studies with microspheres failed to demonstrate a selective decrease in blood flow. However, comparison studies of nine other dogs (five caval and four normal) demonstrated that microsphere results were less reproducible in caval dogs than they were in normal dogs. We have concluded taht reduced blood flow is the only consistent alteration of renal function in this edematous animal model and that previous suggestions of altered distribution are not supported by these studies.


Permeability of connective tissue linings isolated from implanted capsules; implications for interstitial pressure measurements. Quantification of the permeability of connective tissue linings isolated from implanted capsules was achieved by two types of experiments. The objective of the first type was to determine the restriction offered by the lining to diffusion of 125I-labeled human serum albumin. The restricted diffusion coefficient of albumin with respect to the connective tissue lining the luminal capsule surface (internal lining) averaged 3.0 times 10-7 plus or minus 0.4 times 10-7 cm2/sec in ten experiments indicating that the rate if migration of albumin across the structure was 35% of its free diffusion rate in water. In contrast, the albumin diffusion coefficient obtained for the abluminal (external) lining suggested that diffusion of albumin through this structure was 73% of the free diffusion rate in water. The objective of the second type of experiment was to determine solute reflection coefficients for inulin, serum albumin, and gamma-globulin with respect to the internal and external linings. For the internal lining, the reflection coefficients were: inulin 0.07, albumin0.23, and gamma-globulin 0.53. The external lining showed greater leakiness as evidenced by its lower reflection coefficient for a given molecule and its higher hydraulic conductivity. An equivalent pore calculation resulted in a calculated pore radius of 250-350 angstrom for the internal lining and a calculated pore radius of 500-600 angstrom for the external lining. The ineffectiveness of the leaky capsule lining in transmitting oncotic pressure suggests that under normal conditions the capsule measures interstitial hydrostatic pressure rather than oncotic pressure.


Pulmonary parenchymal tissue volume measurements in graded degrees of pulmonary edema in dogs. We investigated the accuracy and the sensitivity of a modification of the acetylene inhalation technique for the determination of lung tissue volume (Vt) during various grades of hemodynamic pulmonary edema in 23 dogs. After base-line acetylene measurements were obtained, intravascular driving force (pulmonary wedge pressure minus intravascular  colloid osmotic pressure) was varied between -8 and +71 mm Hg by the inflation of an intra-aortic ballon and the infusion of isotonic saline. After 30 minutes at this new driving force, four timed acetylene samples were again collected. Vt (when factored by alveolar volume, VA) increased from base line to 0.23 plus or minus 0.07 ml/ml between a driving force of 0 and  + 17 mm Hg. This same change in Vt/VA was accompanied by an increase in the lung wet weight-dry weight ratio from 3.84 plus or minus 0.31 to 5.2 plus or minus 0.25. Vt was 271 plus or minus ml compared with an actual lung wet weight of 288 plus or minus 57 g; Vt tended to overestimate lung wet weight in severe pulmonary edema. Alloxan-induced pulmonary edema (6 dogs) tended to parallel these data. We conclude that the acetylene method may ve a relatively accurate noninvasive method for the determination of increasing lung water in pulmonary edema.


Contractility in mammalian heart muscle; calcium and osmolality. The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, Lmax, at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the Lmax preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at Lmax preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially unaltered by either sucrose or NaCl, except for the high Ca concentrations (above 5 mM) at the higher osmolalities (above 370 mosmoles) especially with sucrose.


Anoxia-induced release of prostaglandins in rabbit isolated hearts. We investigated the relationship between prostaglandin release and the coronary vasodilation evoked by anoxia. Isolated rabbit hearts were perfused via the aorta with Krebs-Ringer's solution. The coronary effluent was bioassayed continuously in terms of prostaglandin E2 for prostaglandinlike substance which was present (at less than 1 ng/ml) in 60 of 66 hearts. This basal release was abolished by the prostaglandin synthetase inhibitor, indomethacin (1-2 mug/ml), a result which adds further to the identity of the prostaglandinlike substance as a prostaglandin. Anoxia increased coronary flow sometimes by 100% and evoked prostaglandin release shortly thereafter. Ablolition of prostaglandin synthesis by indomethacin pretreatment did not affect nor did infusion of exogenous prostaglandin mimic the anoxia-induced flow increment; thus, we conclude that prostaglandin release cannot account for the anoxia-induced vasodilator response. Furthermore, the failure of indomethacin to alter resting coronary blood flow suggests that a local prostaglandin release is not responsible for either the maintenance or the modulation of coronary flow in this preparation.


Motion of the tricuspid valve annulus in anesthetized intact dogs. Phasic variations in the size, position, and geometry of the tricuspid valve annulus during the cardiac cycle were studied in five normal anethetized dogs 2-6 weeks after 8-11 lead beads had been sutured on the endocardial surface of the valve ring during cardiopulmonary bypass. Field-by-field measurements from biplane videoangiograms were used to assess changes in valve ring size and shape during control hemodynamic conditions and during increased heart rates. In addition, the percutaneous production of a complete atrioventricular block in two dogs enabled us to observe the effect of isolated atrial contractions on the valve annulus. During normal sinus rhythm, progressive narrowing of the annulus  during atrial and ventricular contractions reduced its area by 20-39% of the maximal valve circumference during diastole; approximately two-thirds of the total ring narrowing was associated with atrial systole. These findings suggest that one of the functions of atrial contraction is the reduction in size of the atrioventricular valve orifices prior to the onset of ventricular systole.


Papillary muscle shortening in the intact dog; a cinderadiographic study of tranquilized dogs in the upright position. Shortening of the anterior papillary muscle of the left ventricle was demonstrated in six intact, tranquilized dogs. Two small metal markers that had been surgically implanted 3-50 months earlier were cineradiographically photographed during approximately ten sequential cardiac cycles in each of two orthogonal positions. Distances between markers were plotted for successive frames. The resulting curves were used to obtain maximum velocities of papillary muscle shortening and lengthening: 1.08 plus or minus 0.29 muscle lengths/sec and 1.39 plus or minus 0.48 muscle lengths/sec, respectively. From the two orthogonal planes, the average maximum spatial distance and the average minimum spatial distance between the markers were calculated. The mean percent shortening of 22.8 plus or minus 6.5% was surprisingly large: it approximated the distance from the foot to the peak of the ascending limb of the myocardial length-tension curve derived from isolated muscle studies. Mechanical studies on isolated papillary muscle have consistently shown reduced shortening with increasing loads. Since the in vivo dog papillary muscle has been reported to be under considerable tension during systole, there appears to be some contradiction between the degree of shortening found in the present study and the shortening observed in isolated papillary muscle studies.


Intimal injury and regrowth in the rabbit aorta; medial smooth muscle cells as a source of neointima. The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied serially for up to a week, when neointima formation had provided a virtually complete cover. In en face preparations, the early neointimal cells appeared in random locations; they did not develop in apposition to residual, healthy endothelium. The possibility of blood cell colonization was explored by inserting killed aortic homografts. Since these homografts showed neointima formation only close to the site of junction with the normal aorta and as a direct extension of healthy endothelium, the likelihood of significant blood cell colonization was deemed small. Histologic and electron microscopic sections provided evidence that the early neointimal cells in the healing aorta were derived from medial smooth muscle cells. Healing of the injured arterial intima was accompanied by thickening instead of prompt restoration to normal, and the thickened intima resembled an arteriosclerotic plaque. The present study thus supports the concept that arteriosclerosis is a disease involving proliferation of medial smooth muscle cells.


Effect of hemodilution on the distribution of renal blood flow. We evaluated the effects of hemodilution, expansion of intravascular volume, and expansion of interstitial volume on the distribution of cortical renal blood flow, utilizing the microsphere technique. Hemodilution without volume expansion (saline exchange) produced an increase in fractional blood flow in zone 1 (outermost zone) of the cortex from 34 plus or minus 1% to 43 plus or minus 2% and a decrease in fractional blood flow in zone 4 (innermost zone) from 16 plus or minus 2% to 13 plus or minus 2%. Hemodilution without volume expansion or a decrease in plasma protein concentration (isoncotic exchange) produced a similar redistribution in blood flow in zone 1 from 34 plus or minus 2% to 41 plus or minus 2% and in zone 4 from 14 plus or minus 2% to 10 plus or minus 1%. Hemodilution with intravascular volume expansion (hyperoncotic albumin infusion) also produced a superficial shift; blood flow in zone 1 increased from 27 plus or minus 1% to 30 plus or minus 1% and that in zone 4 decreased from 19 plus or minus 2% to 15 plus or minus 1%. Previous studies have demonstrated a redistribution to the juxtamedullary area after saline expansion. Our data demonstrate that hemodilution causes flow to redistribute to the superficial rather than the deep cortex. This superficial shift appears to be secondary to decrease hematocrit rather than to dilution of plasma proteins or expansions of intravascular volume. The deep shift in cortical blood flow which occurs during saline loading is presumably a consequence of expansion of interstitial volume.


Static and dynamic components in the vascular myogenic response to passive changes in length as revealed by electrical and mechanical recordings from the rat portal vein. The effects of static and dynamic passive stretch and shortening on electrical activity and active force were analyzed in the isolated rat portal vein. Static stretch by 40% of muscle length evoked moderate excitatory effects with enhanced mechanical activity and an average increase in spike discharge of 12% above the control value of 55 plus or minus 2.6 spikes/min. The dynamic responses studied at various rates of length change (dL/dt) over the range between minus 12 and plus 12 mm/min, i.e., minus 3 and plus 3% muscle length/sec, were much more pronounced. Active force and spike activity showed graded increases with increasing rates of stretch. The electrical activity reached a value of 180 spikes/min (approximately equal to 325% of control) at 5 mm/min; this frequency was then maintained for stretch rates up to 12 mm/min. Mechanical activity during stretch was further reinforced by the shift along the length-tension diagram. Passive shortening at rates from minus 1 to minus 12 mm/min caused graded decreases in mechanical and electrical activity below the control levels, complete inhibition being observed at the latter dL/dt. Blockade of alpha and beta receptors indicated that the responses were myogenic in nature. The findings seem to provide direct support for the myogenic hypothesis of vascular tone and responses to stretch of the vascular wall, but they indicate that emphasis should be placed on the dynamic characteristics of the stimulus rather than its static nature. This emphasis constitutes a new concept in the myogenic control of the peripheral circulation.


In vivo electrophysiological effects of lidocaine in canine acute myocardial infarction. Lidocaine was administered as a rapid intravenous bolus injection followed by a constant-rate intravenous infusion to nine dogs with 2-hour-old myocardial infarctions. Bipolar electrograms were recorded from and effective refractory periods were determined in the infarcted and normal zones of the heart. Intervals (Q-EG) were measured from the onset of the QRS complex in a standard electrocardiogram limb lead to the major deflection of the recorded electrograms from the normal and infarcted zones. QRS duration and serum lidocaine concentration were also determined. At serum concentrations considered to be therapeutic, lidocaine prolonged the Q-EG intervals in the infarcted zones of the heart 17-26% at peak effect (P less than 0.01), but it had no effect on the Q-EG intervals in the normal zone except for a slight (1.5%) prolongation shortly after the initial intravenous bolus injection. Lidocaine also had no effect on QRS duration. Similarly, lidocaine prolonged the effective refractory period of the infarcted zone 23% (P less than 0.01) at peak effect but had no effect on the effective refractory period of the normal zone. Prior to lidocaine administration, the mean effective refractory period of the normal zone was 26 msec longer than that of the infarcted zone, but at peak drug effect the disparity in refractoriness was reduced to 1 msec. The present study thus shows that lidocaine has different effects in infarcted and normal zones of the heart. In delaying activation and prolonging the effective refractory period of the infarcted zone of the heart, lidocaine has local anesthetic actions which might explain its effectiveness in curtailing ventricular arrhythmias after acute myocardial infarction.


A mechanism for the electrocardiogram response to left ventricular hypertrophy and acute ischemia. A proposed mechanism for explaining the electrocardiographic response in left ventricular hypertrophy and in subendocardial and epicardial acute ischemia was incorporated in a mathematical model of electrical heart activity. The model of hypertrophy was simply an increase in cell size, and the principal effect on the computer-generated 12-lead electrocardiograms (ECGs) was an increase in R-wave amplitude and ventricular activation time and a flattening or polarity reversal of the T wave. The model of acute ischemia was a reduction between plateau and resting potential of the transmembrane action potential. The principal effect on the computer-generated 12-lead ECGs was an S-T segment displacement up or down depending on the location of the lesion. This shift was linearly proportional to the severity of the ischemia, i.e., the reduction in electrical activity of the ischemic cell, and for a lesion of given severity the S-T segment shift was a measure of the area, not the volume, of ischemic tissue. Therefore, this model suggests that a direct correlation does not necessarily exist between volume-measuring tests such as serum enzyme values in the case of necrosis and S-T segment shifts.


Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets. Fibrous proteins were measured in five arterial beds in adult cynomolgus monkeys after administration of atherogenic and regression regimens. Atherosclerosis was induced by feeding the monkeys a hypercholesterolemic diet containing 1.2% cholesterol for 17 months. A low-fat, cholesterol-free regression diet was then given for 60 days, 200 days, and 20 months. In atherosclerosis, collagen concentration (mg/g dry weight) and collagen content (mg/cm length of artery) both increased. At 200 days of regression the collagen concentration, but not the collagen content, was higher than it was in atherosclerosis. In late regression (20 months), the collagen content was lower than it was in atherosclerosis, although in the five arterial beds considered together the collagen concentration was not significantly lower. Both the elastin concentration and the elastin content rose in atherosclerosis and decreased in regression. These mass data suggest that fibrous proteins are lost from the arterial wall during a regression regimen. Correlative evidence suggests that younger intimal fibers may be chiefly susceptible to fibrolytic activity, leaving dense intimal scars characteristic of regressed arteries.


Diminished inotropic response of aged myocardium to catecholamines. The effect of advanced age on the response of active tension, maximal rate of tension development (dT/dt), and contraction duration to catecholamines and to calcium was evaluated in isometric trabeculae carneae from young adult (6-month-old), middle-aged (12-month-old), and aged (25-month-old) rats. Control values were not age dependent except for that for contraction duration which was prolonged in the aged group. At a norepinephrine concentration of 8 times 10-5M, dT/dt increased to 163.8 plus or minus 5.3% of control in the young adult group and to 125.9 plus or minus 6.3% of control in the aged group (P smaller than 0.001). Active tension increased to 121.3 plus or minus 4.0% of control in the young adult muscles but did not increase in the aged muscles (P smaller than 0.01). Contraction duration shortened proportionately in both age groups. Similar results were obtained with isoproterenol. In contrast to the response to catecholamines, there was no age difference in the response of active tension and dT/dt to increasing concentrations of calcium. It is concluded that the intrinsic inotropic response to catecholamines is diminished in the aged myocardium. This finding does not appear to result from differences in tachyphylaxis, tissue uptake of catecholamines, or the ability of the contractile proteins to respond to increasing concentrations of calcium but instead may result from a decreased ability of catecholamines to increase the intracellular calcium available for contraction.


Influence of carotid baroreceptors on vascular responses to carotid chemoreceptor stimulation in the dog. The modification by the carotid baroreceptors of the vascular responses to chemoreceptor stimulation was studied in anesthetized, artificially ventilated, vagotomized dogs. The carotid bifurcations were vascularly isolated and perfused with blood at constant pressures of 134, 215, and 51 mm Hg to cause intermediate, maximal, and minimal inhibition, respectively, of the vasomotor center. At each pressure, stimulation of the carotid chemoreceptors was achieved by perfusion with hypoxic hypercapnic blood. With intermediate inhibition, the chemoreceptor stimulation increased the aortic pressure by 50% and decreased the hind-limb and kidney blood flow (perfusion at constant pressure) by 59% and 19%, respectively. At carotid sinus pressures of 215 and 51 mm Hg, the effects of chemoreceptor stimulation were absent or markedly attenuated. With intermediate sinus pressure, chemoreceptor stimulation decreased the perfusion pressure of the saphenous vein by 27% (perfusion at constant flow). When the sinus pressure was increased to 215 mm Hg, the tone of the vein did not change, but chemoreceptor stimulation was without effect. The present study indicates a central interaction (which may be presynaptic) between the chemoreceptor and baroreceptor inputs such that the vascular responses to chemoreceptor stimulation are inhibited when the carotid sinus activity is maximal or minimal.


Calculations of pulsatile flow through a branch: implications for the hemodynamics of atherogenesis. Numerical simulations of pulsatile blood flow through a symmetrical branch modeling the aortic bifurcation were carried out to assess several hemodynamic theories of atherogenesis by comparing the distribution of hemodynamic variables with that of early lesions in arterial branches. Considerable spatial and temporal variations in wall shear were found when the flow was pulsatile; the highest values occurred at the convex corner on the outer wall of the branch and in the neighborhood of the flow divider tip, and the lowest shears were experienced by the outer wall of the daughter vessel a short distance distal to the corner. Transient flow reversal occurred almost everywhere in the branch, and a transient separated region was found corresponding to the low-shear region in the daughter vessel. The shear profiles and the calculated separated region were influenced to some degree by the extent of flow development at the branch inlet and markedly by the branch area ratio. All of the proposed hemodynamic promoters of atherosclerosis that were examined--high shear, low shear, and separation--were found at sites in the branch where lesions commonly develop. Comparisons with a steady-flow calculation at the same mean flow rate showed that the severity of all of these proposed hemodynamic determinants was increased by pulsatility.


Functional and hemodynamic adaptation to progressive renal ablation. Removal of renal tissue stimulates functional and anatomical adaptation in the remaining renal parenchyma. Since recent studies have demonstrated no apparent limitation in compensatory growth following progressive surgical ablation, experiments were performed to determine the changes in glomerular filtration rate and renal blood flow. After removal of 50% of the renal mass mean nephron glomerular filtration rate increased 60%, and after ablation of 75% of the renal tissue it increased 150%. These changes paralleled the increases in renal growth under the same conditions. In comparison, mean glomerular blood flow rose 90% and 240% after 50% and 75% nephrectomy, respectively; these changes in relation to the changes in glomerular filtration rate resulted in a progressive fall in the filtration fraction. Intrarenal blood flow distribution was examined with labeled microspheres. The marked increase in renal blood flow after surgical ablation was characterized by a disproportionate rise in blood flow to the inner cortex. The present investigation, therefore, described the remarkable functional changes that occur as overall glomerular filtration rate declines and provides further insight into the mechanism responsible for maintaining water and electrolyte homeostasis after loss of functioning renal mass.


Sphingomyelin and other phospholipid metabolism in the rabbit atheromatous and normal aorta. Hypercholesterolemia induces atheroma formation, and the concentration of sphingomyelin is increased compared with that in the normal aortic intima-media. The aortic intima-media sphingomyelin concentration appears to increase exponentially with time on the cholesterol diet. Moreover, the entry rate of serum sphingomyelin into the aortic wall also appears to increase exponentially with time on the cholesterol diet and with the extent of aortic exposure to hypercholesterolemia. 32P-Phosphate incorporation into sphingomyelin and other phospholipids in the perfused rabbit aorta does not increase with atheromatosis, but the rate of sphingomyelin entry increases 27-fold during approximately the same period of atheroma formation and can account for all of the increase in sphingomyelin concentration in the intima-media.


Hypothermic arrest and potassium arrest: metabolic and myocardial protection during elective cardiac arrest. Hypothermic arrest, potassium arrest, and ischemic arrest, either singly or in combination, with or without coronary perfusion were studied in an isolated perfused rat heart preparation. Procedures that permitted the maintenance of high cellular levels of adenosine triphosphate (ATP) and creatine phosphate during arrest, e.g., coronary perfusion with hypothermic solutions or solutions containing 16.0 mM potassium, produced a fully reversible arrest with complete cardiac recovery. Cardiac arrest and coronary flow were related to the degree of hypothermia and the concentration of potassium in the coronary perfusate, and the minimum conditions required to induce complete cardiac arrest were ascertained. The effects of hypothermia and potassium were additive; total cardiac arrest could be obtained by combining small evaluations of potassium with moderate hypothermia. Under these conditions, cellular high-energy phosphates were maintained, and complete recovery was possible. Under conditions in which arrest was obtained without maintaing coronary perfusion, e.g., ischemic arrest, cellular high-energy phosphates declined rapidly, and the hearts exhibited poor recoveries. Some protection could be afforded to the ischemic myocardium by topical hypothermia or by combining the ischemia with potassium arrest. In both instances, ATP and creatine phosphate were maintained at higher levels, and improved recoveries were observed.


A one-dimensional viscoelastic model of cat heart muscle studied by small length perturbations during isometric contraction. To develop a model of heart muscle, we studied cat papillary muscle contracting in a quasi-isometric condition under a fixed inotropic state. The properties of resting muscle were determined by using a step stretch of less than 1.2% of Lmax for initial lengths from 85 to 100% Lmax. The passive force response suggested the model of the passive branch (Fig. 1). All five parameters were small at muscle lengths below 95% of Lmax but increased markedly at longer lengths. The properties of contracting muscle were studied with a sinusoidal length change (amplitude less than 0.15% of Lmax, frequency 0.1-35.0 Hz). The frequency response of active (total minus passive) stiffness suggested the model of the active branch (Fig. 1). We determined the dependency of the elastic elements (K, Ks) and the viscous element (C) on length and time by recording the frequency response at various combinations of length and time Ks varied linearly with active force (FA). K and C exhibited time courses that paralleled FA up to 0.6tmax, and they maintained their values until 1.4tmax. K then fell toward zero, whereas C exhibited a secondary rise before it fell toward zero. K was dependent of length up to 95% of Lmax and then began to decline, but C varied in proportion to muscle length.


Continuous inhibition of renin release in dogs by vagally innervated receptors in the cardiopulmonary region. Inhibition of the release of renin by vagal afferents from the heart and lungs was studied in 14 dogs with their aortic nerves cut and their carotid sinuses vascularly isolated. The release of renin from one kidney was calculated from the venous-arterial difference in plasma renin activity (radioimmunoassay) and the renal blood flow (electromagnetic flowmeter). Renin release was determined before and during temporary interruption of afferent vagal nerve traffic (bilateral cooling of the cervical vagi). With carotid sinus pressure maintained at 40 mm Hg, vagal cooling increased mean aortic blood pressure (24%), decreased renal blood flow (19%), and increased renin release (241%). With sinus pressure maintained at the mean aortic blood pressure existing during the control period, vagal cooling caused a lesser increase in mean aortic blood pressure (12%), little decrease in renal blood flow (7%), and a marked increase in renin release (522%). The changes in renal blood flow and renin release with vagal cooling were prevented by renal denervation. Thus, vagal afferents from the cardiopulmonary region exert a tonic restraint on the release of renin; this restraint occurs in circumstances in which these afferents cause little change in total renal blood flow.


Baroreceptor reflex effects on transient and steady-state hemodynamics of salt-loading hypertension in dogs. Intact dogs were compared with barorecptor-denervated dogs to determine the extent to which the baroreceptor reflexes delay the onset and offset transients and alter the final steady-state levels of salt-loading hypertension. Two months after their renal mass had been reduced to about one-third of normal, hypertension was produced in both groups of dogs by continuous intravenous infusion of isotonic saline (190 ml/kg day-1). Major hemodynamic variables were recorded continuously 24 hours/day throughout the experimental period. Both groups of dogs had similar control 24-hour arterial blood pressure values: intact dogs averaged 112 plus or minus 4.1 (SE) mm Hg, and denervated dogs averaged 110 plus or minus 4.3 mm Hg. Both groups reached the same average plateau of elevated arterial blood pressure: intact dogs averaged 142 plus or minus 4.8 mm Hg, and denervated dogs averaged 142 plus or minus 8.7 mm Hg. After the start of salt loading, the denervated dogs reached their plateau level of arterial blood pressure in an average of 8 hours compared with nearly 24 hours for the intact dogs. Cardiac output also rose more rapidly in the denervated dogs and reached a maximum elevation of 26% above the control level in an average of 7.4 hours compared with a maximum elevation of 40% above control in the intact dogs in 18 hours. Total peripheral resistance fell below the control level during the entire first day of infusion in the intact dogs but was somewhat elevated in the denervated dogs. When the saline infusion stopped, arterial blood pressure in both groups returned to control levels within 24 hours. The results indicate that the major action of the baroreceptor reflexes on the onset of salt-loading hypertension is to slow the development of hypertension by modifying the total peripheral resistance; the final steady-state level of hypertension is unaffected by the baroreceptor reflexes.


Arterial lysosomes and connective tissue in primate atherosclerosis and hypertension. The cellular events that occur in the vessel wall consequent to changes in endothelial permeability result in the progression of vascular disease, particularly atherosclerosis. Female rhesus monkeys were fed an atherogenic diet or were made hypertensive for 6-8 months; and their vessels were then compared with vessels from control monkeys. Length-defined segments of coronary vessels, the thoracic aorta, and the abdominal aorta showed significant increases in total connective tissue in the atherosclerotic and hypertensive groups; pulmonary vessels did not. The diseased aortic segments had increased levels of two lysosomal enzymes, acid phosphatase and beta-N-acetylglucosaminidase; pulmonary vessels were not diseased and did not show these changes. Coronary vessels from the atherosclerotic and hypertensive groups did not show an increase in enzyme levels on biochemical measurements, but focal accumulations of lysosomes were identified by cytochemical techniques. In atherosclerotic lesions, a doubling of cholesterol and more than a tenfold increase in cholesterol ester were found. These connective tissue and lysosomal changes are early features of primate vascular disease and may result from the accumulation of excessive substrate (cholesterol ester) in the lysosomes of vascular smooth muscle cells.


A forty-year review of bacterial endocarditis in infancy and childhood. A retrospective review of 149 episodes of bacterial endocarditis (BE) in 141 patients under 25 years of age, at The Children's Hospital Medical Center from 1933 through June of 1972, demonstrates increasing survival and a distinct change in the frequency of underlying congenital heart disease and rheumatic heart disease (RHD). Certain forms of congenital heart disease such as tetralogy of Fallot, small ventricular septal defect, and aortic stenosis are at particular risk for BE. Following BE, patients with ventricular septal defect and tetralogy of Fallot have less morbidity and higher survival rates than children with aortic outflow lesions. over the entire time period, alpha Streptococcus is the most common pathogen and Staphylococcus aureus, second most frequent organism. Surgical correction in patients with congenital heart disease may offer the best form of prevention.


Diastolic vibration of the interventricular septum in aortic insufficiency. The echocardiograms of 46 patients with aortic insufficiency which manifested typical high frequency vibrations of the anterior mitral valve leaflet were reviewed.  All patients had overt clinical evidence of aortic insufficiency which was confirmed by angiography in 17 cases.  In 17 cases (eight of whom underwent catheterization and angiography), high frequency diastolic vibrations of the interventricular septum of similar frequency to those on the anterior mitral leaflet were observed.  This finding was not seen in 100 control echocardiograms from patients without clinical evidence of aortic insufficiency, and represents a previously undescribed echocardiographic manifestation of this lesion.


Clinical measurement of myocardial infarct size.  Modification of a method for the estimation of total creatine phosphokinase release after myocardial infarction. A modified method for the measurement of total creatine phosphokinase release from venous blood samples taken four-hourly after myocardial infarction has been used in 43 patients admitted to a Coronary Care Unit.  The fractional decay rate (Kd) of enzyme activity has been measured by a standardized method in each patient, and accuracy of the calculation of total enzyme release has been improved by allowance for individual variations in decay rate, and discarding of data from which decay rates cannot be measured within confidence limits of less than plus or minus 15 per cent.  Total enzyme release was greater in cases of transmural infarction than in patients with subendocardial infarction, and showed a good positive correlation with clinical indices of the extent of myocardial damage.  As noted by previous workers, this method allows for the measurement of the rate as well as the extent of enzyme release, and so should prove useful in the clinical evaluation of therapeutic agents which might accelerate or retard the rate of myocardial necrosis in patients with acute myocardial infarction.


The effect of hypoglycemia on myocardial ischemic injury during acute experimental coronary artery occlusion. To determine the effect of hypoglycemia on myocardial ischemic injury following coronary artery occlusion epicardial electrograms were recorded 15 minutes after two 20-minute coronary artery occlusions in seven anesthetized dogs. The first occlusion was a control (blood glucose 85 plus or minus 5(sd) mg per cent). Before the second occlusion hypoglycemia was induced (blood glucose 40 plus or minus 5 mg per cent) by the intravenous administration of insulin (2 units/kg). The average ST-segment elevation in leads during control was 3.5 plus or minus 1.0 mV which rose to 6.1 plus or minus 1.4 mV during the second occlusion (P smaller than 0.05). The number of sites showing ST-segment elevation exceeding 2 mV increased from 7.6 plus or minus 1.6 during control to 10.6 plus or minus 1.4 (P smaller than 0.05) during the occlusion with hypoglycemia. In other dogs, a coronary artery was occluded for 24 hours. Epicardial ST-segment elevations were compared to creatine phosphokinase (CPK) activity and histological appearance from the same sites. CPK activity in sites with normal ST segments (0-2 mV) was 33.1 plus or minus 6.0 IU/mg protein. Six additional dogs received insulin following the 15 minute epicardial map and blood sugar was maintained at a level of 46 plus or minus 6 mg per cent for the 24 hours. These dogs showed more myocardial necrosis than predicted by the ST-segment elevation prior to insulin administration. Forty-six percent of sites, which in control dogs would have been expected to have normal CPK and histological appearance, showed depressed CPK activity and histological evidence of early myocardial necrosis. Thus, hypoglycemia increases myocardial damage, as reflected by enzymatic and histological analyses.


Persistence of MB isoenzyme of creatine phosphokinase in the serum after minor iatrogenic cardiac trauma. Absence of postmortem evidence of myocardial infarction. The specificity of serum CPK-MB for acute myocardial infarction was examined by retrospective analysis of 401 consecutive patients admitted to Coronary Care Unit over a three and one-half year period with suspected infarction in whom the isoenzyme was subsequently detected.  Four patients (1 per cent) who died during the hospital admission had no autopsy evidence of acute myocardial infarction.  All four had experienced mild iatrogenic cardiac trauma, following which serum CPK-MG persisted for at least 24 hours.  In one patient, a permanent pacemaker had been inserted by the transmediastinal approach.  Two patients had been subjected to closed chest cardiac massage and intracardiac puncture, and one to external cardiac massage alone.  The findings suggest that persistent identification of serum CPK-MB, although specific for myocardial necrosis, cannot be regarded as diagnostic of myocardial infarction.  The implications of this are important to treatment of patients after cardiopulmonary resuscitation and operative trauma to the heart.


Thallium-201 for myocardial imaging.  Relation of thallium-201 to regional myocardial perfusion. Following intravenous administration, the myocardial concentration of tracer thallium-201, potassium-43, and rubidium-81 were determined in mice; thallium was present in the greatest concentration in the myocardium (2.08% compared 1.25% for potassium and 1.15% for rubidium at 10 minutes). The regional myocardial distribution of thallium-201 was determined in dogs under conditions of normal flow, and total occlusion, and compared with potassium-43 (r=0.97). The regional distribution of thallium-201 was compared to microspheres under conditions of partial occlusion and reactive hyperemia (r=0.97). Thallium-201 was evaluated in a series of phantom scans, which demonstrated that the low energy X-ray of thallium was suitable for imaging. These results suggest that thallium-201 can be used for the evaluation of the distribution of regional myocardial perfusion.


Primary T wave abnormalities caused by uniform and regional shortening of ventricular monophasic action potential in dog. We correlated primary T wave changes with the changes of monophasic action potentials (MAP) recorded with suction electrodes from the ventricular surface of the dog heart following systemic or intracoronary infusions of small doses of isoproterenol (ISP). The portions of the heart perfused with ISP were excised and weighed to determine the mass of perfused tissue. ISP shortened the ventricular MAP by an average of 12-18 msec in the entire ventricular mass following systemic administration, in 34 plus or minus 6 per cent of the ventricular mass after injection into the left circumflex coronary artery (LCA), in 8.5 plus or minus 2.6% of the ventricular mass after injection into a branch of LCA and in 17 plus or minus 8 per cent of the ventricular mass after injection into the right CA. The MAP changes induced by ISP were similar to the transmembrane action potential changes recorded with microelectrodes from papillary muscles excised from the same dogs. The most important results of this study showed that: 1) the early and the late effects of ISP administration produced opposite effects on the T wave polarity. The early T wave change was associated with nonhomogeneous and the late change with homogeneous MAP shortening; 2) the T wave change was greater after infusion into LCA than after systemic administration, 3) the T wave change was greater after infusion into LCA than after infusion into LCA branch apparently because of greater mass of the ISP-perfused myocardium; 4) the T wave change was greater after infusion into LCA branch than after infusion into RCA, apparently due to the unequal regional repolarization contribution to the T wave; 5) the ventricular gradient did not always reflect the magnitude of the primary T wave change. Our study helps to identify factors contributing to high sensitivity and low specificity of T wave abnormalities.


The evaluation of left ventricular function in man.  A comparison of methods. Comparisons of the sensitivities of parameters for assessing left ventricular performance in man were made in 38 patients. The parameters compared were the ejection fraction, ventriculographic contraction patterns, the left ventricular end-diastolic pressure, and the contractile indices including the contractile element velocity at 10 mm Hg (Vce 10) and maximal contractile element velocity (Vmax). The contractile indices were obtained by catheter tip manometry, utilizing developed pressure (DP) to calculate the velocity of contractile element shortening (Vce) from the formula: dp/dt divided by 32 DP. Vce 10 was measured directly and Vmax was derived by linear manual extrapolation of the pressure-velocity plot to 0 mm Hg. Vmax values derived from linear manual extrapolation were compared with values obtained by computer least squares fitting of the Vce and developed pressure data points to single and double exponential equations. The Vce and developed pressure data points fit the single exponential equation better than the double exponential equation but the use of either equation resulted in slightly higher values for Vmax than obtained with linear manual extrapolation. The effect of heart rate on myocardial contractility was eliminated by making comparisons at both a basal and atrial paced rate of 100. Utilizing all methods, 24 patients were identified to have ventricular dysfunction. The contractile indices were significantly less sensitive than any other parameter (P smaller than 0.05) and identified seven patients while the left ventricular end-diastolic pressure, ejection fraction, and presence of asynergy identified 15, 15, and 12 patients, respectively. The use of a common atrial paced rate of 100 did not increase the sensitivity of the contractile indices. Since there was only partial overlapping between parameters in the identification of left ventricular dysfunction, the combination of different parameters was more sensitive than any single parameter alone. It is concluded that several methods are required to identify all patients with left ventricular dysfunction and that the contractile indices are the least sensitive indicator of left ventricular dysfunction.


Serum digitoxin concentrations in infants and children. Serum digitoxin levels were measured in 18 infants (under two years) and in 23 children (aged 2-13 years) receiving maintenance therapy. Digitalization was carried out because of heart failure in 17 infants and 13 children and for control of dysrhythmia in one infant and 10 children. Mean maintenance dosage for infants was 0.0042 plus or minus 0.0008 (sd) mg/kg/day and for children was 0.0031 plus or minus 0.0012 mg/kg/day. The mean serum digitoxin level was not significantly different in infants (30 plus or minus 10 ng/ml, range 14-58) from that found for children (34 plus or minus 11 ng/ml, range 19-61). Both values were significantly different (P smaller than 0.001) from those determined in this laboratory for adults (mean 24 plus or minus 7 ng/ml, range 5-39). In four infants with electrocardiographic or other evidence of toxicity, the mean serum level was 71 plus or minus 2 ng/ml (range 68-72), and in four children with electrocardiographic or other evidence of toxicity, the mean serum level for digitoxin was 72 plus or minus 14 ng/ml (range 53-84). The data suggest that infants and children tolerate a higher serum digitoxin concentration without any evidence of toxicity and may require more digitoxin (mg/kg) for therapeutic effect than do adults. Serum digitoxin levels may serve as an important guide in determining the adequacy of digitalization and in the recognition and management of digitalis toxicity.


The course of the conduction system in single ventricle with inverted (L-) loop and inverted (L-) transposition. The conduction systems of three hearts with single ventricle and inverted (L-) loop and inverted (L-) transposition were studied by serial section.  The course of the conduction system was similar in all three hearts.  The regular (posterior) atrioventricular (A-V) node was rudimentary and did not form the bundle of His.  An accessory (anterior) A-V node was present in the roof of the right atrium.  This node pierced the connective tissue adjacent to the right side of the pulmonary annulus to form the bundle of His.  The bundle proceeded into the main ventricular chamber lying on the septum between this chamber and the small outlet chamber.  It bifurcated a varying distance from the defect in this septum.  The right bundle branch proceeded through the septal wall to the trabeculae of the outlet chamber.  The left bundle branch proceeded to caudad on the anterior wall of the main ventricular chamber.  An unusual feature in one case was the splitting of the anterior node into two parts, one forming the bundle of His, and the other giving off Mahaim fibers to the ventricular myocardium.  The surgical importance of avoiding the right side of the pulmonary annulus and the region adjoining the defect is stressed.


Congenital mitral valve disease in transposition of the great arteries. A spectrum of mitral valve disease was noted in 71 per cent of 163 specimens with transposition of the great arteries.  At one end of the spectrum were hearts with normal mitral valve, except that the free margin of the anterior leaflet was shortened; at the other end were specimens with underdevelopment of the space between or behind the papillary muscles of the left ventricle.  In additional specimens the anterior leaflet was indented and attached by chordae tendineae to the ventricular septum.


Reduced baroreceptor sensitivity in borderline hypertension. The sensitivity of the baroreceptor reflex in nine patients with borderline hypertension (mean age 19.1 plus or minus 0.2 years) was compared to that in six normal subjects of comparable age (mean 18.8 plus or minus 0.3 years) and that in 14 patients with established hypertension (mean age 48.3 plus or minus 3.1 years). The sensitivity of the baroreceptor reflex was assessed by determining the slope of the regression line relating the rise of systolic pressure to the prolongation of the R-R Interval during the transient rise of arterial pressure induced by an intravenous injection of phenylephrine. The average baroreceptor slope in nine patients with borderline hypertension was 9.1 plus or minus 0.8 msec/mm Hg, which was significantly less than that in six normal subjects (16.0 plus or minus 2.0; P smaller than 0.01), but was greater than that in 14 patients with established hypertension (4.9 plus or minus 0.7; P smaller than 0.01). The significant negative correlation was found as the baroreceptor slope was related to the mean arterial pressure in patients with borderline hypertension and normal subjects, all of whom were 20 years old or less. Attenuation of the baroreceptor sensitivity may influence the maintenance of raised arterial pressure in borderline hypertension.


Catheter positions in congenital cardiac malformations. Biplane cineangiocardiograms were examined from a population of patients with diverse forms of congenital heart disease and examples were selected to illustrate catheter positions which may help define and elucidate the anatomy of simple and complex cardiac lesions.  Familiarity with the appearance of these typical and atypical catheter positions may be of considerable aid in the course of hemodynamic study and in the evaluation of cineangiocardiograms.  The editors suggest that each figure be evaluated as an unknown before reading the caption.


Enzymatic determination of serum urea on the surface of silicone-rubber pads. An enzymatic, fluorometric method is described for determination of serum urea on silicone-rubber pads. In this method, the reagents are lyophilized on the surface of the pads, NADH on one side and a mixture of urease, glutamate dehydrogenase, and alpha-ketoglutarate on the other. The rate of disappearance of NADH fluorescence at 460nm (excitation wavelength, 340 nm) is monitored and related to serum urea concentration. The calibration curve is linear to 250 mg of urea per liter. The method affords a rapid, simple, and inexpensive means for urea assay, the results of which correlate well with automatic diacetyl monoxime method (correlation coefficient, 0.998).


Thin-layer chromatographic detection and identification of methaqualone metabolites in urine. A procedure for detecting methaqualone and identifying methaqualone metabolites in urine by thin-layer chromatography is described and evaluated. Urine is hydrolyzed with HCl or NaIO4, adjusted to pH 9.5, and extracted with chloroform. The chloroform extract is evaporated, reconstituted in methanol, applied to fluorescent silica-gel plates, and developed with ethyl acetate:methanol:ammonium hydroxide (28%) (85:10:5 by vol). Methaqualone use is detected by a pattern of four metabolites, which can be seen under ultraviolet light or are made visible by acidified iodoplatinate reagent. Synthetic methaqualone metabolites are used for identification and to compensate for procedural variables. More than 250 positive urine specimens were correctly identified by this method. Hydrolyzed natural and synthetic metabolites were identical by several criteria.


Radioimmunoassay of drugs subject to abuse: critical evaluation of urinary morphine-barbiturate, morphine, barbiturate, and amphetamine assays. Radioimmunoassays for morphine-barbiturate (MOR-BARB), morphine, barbiturate, and amphetamine were evaluated by a direct comparison with differential elution extraction thin-layer chromatography, the "enzyme multiplied immunoassay technique," and XAD-2 resin extraction thin-layer chromatography for the detection in urine of drugs subject to abuse. Statistically significant (Psmaller than 0.01) concentrations for detection were: 50-100 mug/liter for MOR-BARB; 5 Mug/liter for morphine, 10 mug/liter for barbiturate, and 100 mug/liter for amphetamine. Unconfirmed and unaccounted-for radioimmunoassay positives (false) were: 0% for morphine in the radioimmunoassay for MOR-BARB and that for morphine alone; 2.8% for barbiturates in the MOR-BARB assay and that for barbiturates alone; 0-6% when a combination of these drugs was present in the MOR-BARB, morphine, or barbiturate assay; and 2.4% in the amphetamine radioimmunoassay. Less than 1% of all radioimmunoassay-negative samples were unconfirmed (false). Cross-reactivity was observed with drugs of a similar chemical structure in each of the radioimmunoassays tested. All the radio-immunoassays were easy to use, highly sensitive, and extremely reliable for detecting drug use or abuse.


Binding of 63Ni (II) to ultrafiltrable constituents of rabbit serum in vivo and in vitro. Binding of 63Ni(ll) to ultrafiltrable constituents of rabbit serum was studied (a) after in vitro incubation (2 h, 37 degrees C) of rabbit serum with 63NiCl2 (10-100 mumol/liter), and (b) at intervals (0.25-2 h) after in vivo administration of 63NiCl2(40-160 mumol/kg body wt,i.v.). Serum ultrafiltrates were fractionated by thin-layer chromatography, and the separated compounds made visible by autoradiography and by ninhydrin staining. Severel (congruent to 5) ultrafilitrable 63Ni-complexes were demonstrable as distinct radiodense 63Ni-bands with chromatographic mobilities corresponding to those of ninhydrin-positive bands. Unbound 63Ni(ll) was not detected in serum ultraviltrates in either the in vitro or in vivo experiments. In sera (n equals 10) incubated in vitro with 63Ni(ll) (10 mumol/liter), the mean percentage of ultrafiltrable 63Ni was 36% (range equals 33-38) of total serum 63Ni. In contrast, in sera (n equals 10) obtained 2 h after i.v. injection of 63Ni(ii) (40 mumol/kg), the mean concentration of total serum 63Ni was 10.8 mumol/kg), the mean concentration of total serum 63Ni was 10.8 mumol/liter (ranger equals 6-14), and the mean percentage of ultrafiltrable 63Ni was 15% (range equals 9-21) of total serum 63Ni. The disparity between the percentages of ultrafiltrable 63Ni obtained in vitro and in vivo was obviated when the in vivo experiments were performed in rabbits bilaterally nephrectomized, with ligated common bile ducts. This investigation confirms the existence of several nickel receptors in serum ultrafilitrates and substantiates the role of ultrafiltrable complexes in the excretion of nickel.


Micro-scale blood lead determinations in screening: evaluation of factors affecting results. The Delves micro-scale technique for blood lead analysis is an accurate method for screening capillary blood specimens, obtained by fingerstick, for lead intoxication.  Results are affected by the age of cup, loop, and hollow-cathode tube and by the spatial relationship between optical tube and cup.  Because the glass in many commercially available capillary tubes (used in specimen collection) contains lead and cannot be decontaminated, a lead-free glass tube must be used.  A solution of citric acid in ethanol (20 g/liter) effectively cleanses the puncture site.  A double-blind study of 207 specimens gave a mean value of 276.6 plus or minus 105.8 mug/liter (1SD) for the micro-scale method vs. 273.2 plus or minus 99.0 for a macro-scale method.  The mean coefficent of variation for the micro-scale method was 5.75 percent plus or minus 1.9 (SD).  We conclude that values of 480 mug/liter or below are not "toxic" (i.e., are significantly less than 600 mug/liter, the value at which therapy is begun).  The method is shown to be satisfactory as a screening procedure and for confirming lead analyses done by other methods.


Effect of zinc deficiency and repletion on thymidine metabolism. We studied the effect of zinc deficiency on thymidine metabolism in intact and wounded rats. Zinc deficiency was associated with significantly decreased incorporation of [methyl-3H] thymidine into skin DNA of both intact and wounded rats, as shown by liquid scintillation counting and autoradiography. With wounding, proliferation--as gauged by the labeling index--increased to about twice normal for zinc-supplemented rats, but 3.5-fold for zinc-deficient rats. However, despite the increased proliferation rate, wound-healing in deficient rats was always slower than in zinc-supplemented animals. Incorporation of 3H-labeled thymidine into spleen DNA at 2 and 4 h, and liver DNA at 4 h was also significantly less in zinc-deficient rats than in zinc-supplemented rats. Conversely, DNA synthesis was enhanced in the thymus gland of zinc-deficient rats. Further studies showed that significantly higher percentages of [methyl-14C] thymidine were oxidized by zinc-deficient rats. The specific involvement of the methyl group of thymidine was indicated by the observation of normal oxidattions of [2-14C] thymidine. These findings support the view that zinc directly regulates DNA synthesis.


Intercomparison program of lead, mercury, and cadmium analysis in blood, urine, and aqueous solutions. Sixty-six European laboratories participated in an intercomparison program of lead, mercury, and cadmium analysis in blood, urine, and aqueous solutions.  The experimental protocol was designed in such a way that the effect of precision, experience, and analytical method could be evaluated.  For all the analyses, the scatter of the reported results is important.  The major factor influencing the variability of the results is the intralaboratory variation.  Analytical methods and degree of experience do not seem to have a significant influence.  However, with the exception of mercury determination in urine, a satisfactory intralaboratory precision is not sufficient to make the interlaboratory variation acceptable.  It appears that systematic errors are responsible for the high interlaboratory variation observed between "precise" laboratories.


Micromethod for lead determination in whole blood by atomic absorption, with use of the graphite furnace. I describe a micro-scale method for determining lead in whole blood by utilizing a graphite furnace.  Sample pretreatment consists of fivefold dilution with a dilute surfactant.  The method is directly calibrated with lead standards prepared in dilute HNO3.  To eliminate a small, nonspecific absorption signal from the blood matrix, simultaneous background correction is used.  Interlaboratory comparison with a flame atomic absorption technique that requires extraction yielded high correlation (r equal to 0.98).  Within-run precision (coefficient of variation) ranged from 2 to 4 percent.  Lead in blood can be accurately measured in as little as 20 mul of blood, hence the method is suitable for routine laboratory use and for pediatric screening.


Technique for determining nickel in blood by flameless atomic absorption spectrophotometry. We describe a technique for determining nickel in serum by flameless atomic absorption, with use of dimethylglyoxime.  The procedure permits a greater number of analyses per technician at a relatively low cost, yet provides acceptable accuracy and reliability.  After the sample is evaporated and dry ashed in a muffle furnace at 560 degrees C for 5 h, the residual salts are dissolved in hydrochloric acid (1 mol/liter).  Sodium citrate and dimethylglyoxime are then added for complexation of iron and nickel, respectively.  The pH is adjusted to 9 with ammonia and the nickel dimethylglyoxime is extracted with methyl isobutyl ketone.  The determination is carried out by injecting 50 mul of the organic phase into the graphite furnace, where the sample is dried at 120 degrees C and ashed at 1200 degrees C, respectively.


Serum and tissue enzyme activity and trace-element content in response to zinc deficiency in the pig. Zinc deficiency is associated with poor growth and development.  It has been postulated that a deficiency of the various zinc metalloenzymes results from the lack of dietary zinc.  From present study, an examination of some aspects of this postulate, we conclude the following about zinc deficiency in pigs: (1) Of the tissues studied, it results im diminished zinc content only in liver, kidney, and pancreas.  (2) It is associated with tissue abnormalities of various trace elements other than zinc.  (3) Histochemical enzyme assays are satisfactory for qualitative but not quantitative determination of zinc metalloenzymes.  (4) Deficiency of various tissue zinc metalloenzymes is difficult to demonstrate, even in severe zinc deficiency.  (5) It is associated with decreased activity of hepatic leucine aminopeptidase and ornithine transcarbamylase, and decreased serum cholesterol concentrations.  Our findings are consistent with the postulate that alterations in a number of trace elements may occur in the entity called zinc deficiency.


Influence of myocardial infarction on serum manganese, copper, and zinc concentrations. Reportedly, serum manganese concentrations increase after myocardial infarction, closely correlated with increased serum aspartate aminotransferase activity.  However, these conclusions are apparently based on analyses of contaminated samples.  Serum manganese concentrations after myocardial infarction have been re-investigated by neutron activation analysis, and no significant increase could be demonstrated.  Because serum copper and zinc could be determined simultaneously, analyses for these trace elements are also reported, which confirm the findings of others.  After myocardial infarction a statistically significant (0.02 smaller than P smaller than 0.05) increase in serum copper and a statistically significant (0.001 smaller than P smaller than 0.01) decrease in serum zinc were observed.


Zinc deficiency in sickle cell disease.

Zinc deficiency in sickle cell disease. Clinical similarities between patients with sickle cell anemia and zinc-deficient subjects suggested a secondary zinc deficiency in sickle cell anemia.  Zinc was assayed in various biological fluids and tissues by atomic absorption spectrophotometry.  Zinc in the plasma, erythrocytes, and hair was decreased and urinary zinc excretion was increased in anemia patients as compared to controls.  Erythrocyte zinc and daily urinary zinc excretion were inversely correlated in the anemia patients (r equal to minus .63, P smaller than 0.05), suggesting that hyperzincuria may have caused zinc deficiency in these patients.  Carbonic anhydrase, a zinc metalloenzyme, correlated significantly with erythrocyte zinc (r equal to plus 0.94, P smaller than 0.001).  Plasma RNase activity was significantly greater in anemia subjects than in controls.  We administered zinc sulfate, 660 mg per day, orally, to seven men and two women with sickle cell anemia.  Two 17-year-old males gained 5 cm and 7 cm in height during 49 and 42 weeks of zinc therapy, respectively.  All but one patient gained weight (0.5 kg to 4.1 kg).  Five of the males showed increased growth of pubic, axillary, facial, and body hair, and in one a leg ulcer healed in six weeks on zinc and in two others some benefit of zinc therapy on healing of ulcers was noted.


Effect of the matrix of the standard on results of atomic absorption spectrophotometry of zinc in serum. Zinc in pooled human serum, diluted 10-fold with demineralized water, was determined by flame atomic absorption spectrophotometry.  Recoveries of zinc added to the serum were calculated by use of standards prepared in water, physiological saline, synthetic serum, or dilute HNO3 (10 ml/liter).  The flow rates were essentially the same (9.1 to 9.3 ml/min) for water, diluted synthetic serum or actual human serum, and diluted nitric acid.  The mean apparent percentage recoveries (plus or minus SD) were the best (102.6 plus or minus 2.5) when the standards were prepared in nitric acid; the values obtained when standards in water were used were too high (111.5 plus or minus 3.9); those with standards prepared in physiological saline (92.0 plus or minus 3.2) or synthetic serum (92.3 plus or minus 2.5) were too low.


Some aspects of specimen collection and stability in trace element analysis of body fluids. Analyses for trace elements in biological fluids are uniquely susceptible to extreme errors unless special precautions are taken during collection, storage, and analysis.  The integrity of the specimen may be compromised before it is analyzed, by contamination during collection and processing or by attenuation of the analyte concentration during storage.  If this happens, determined values are not valid even though the method of analysis is extremely sensitive and highly accurate.  Obstacles to obtaining precise and accurate analytical data arising from these factors are discussed.  We consider control procedures applicable at all stages for ascertaining the sources of error and eliminating them.


Trace elements in hair, as related to exposure in metropolitan New York. Previous studies have revealed that trace element concentrations in hair can reflect exposure in cases of frank poisoning and deficiency.  This study reports significant correlations within a single metropolitan area between trace-element content of hair and exposure (as measured by analyses for the corresponding elements in dustfall or housedust) for Ba, Cr, Pb, Hg, Ni, Sn, and V.  Age, sex, hair color, and smoking habits were factors included in the statistical evaluation.  Several metals increase and decrease together in the hair specimens, in agreement with trends reported for other human tissues.


Retention of fluoride with time in man.

Retention of fluoride with time in man. Fluoride retention is high during fluoride supplementation and increases with increasing fluoride intake.  When large amounts of fluoride were given for several months the retention of fluoride was about the same as in the initial phase of fluoride supplementation, whether the supplemental dose of fluoride was 10, 20, or 45 mg per day.  The rapid return of the fluoride balance to control values after the high fluoride intake was discontinued indicates that there is not only a tendency for continued retention of fluoride during the high fluoride intake but also after large amounts of fluoride have already been retained.


Effect of carbon cup aging on plasma zinc determination by flameless atomic adosorption spectrometry. Determination of zinc in blood plasma by flameless atomic absorption spectrometry is discussed, with particular reference to the protocol required for the successful use of the Varian-Techtron Carbon Rod Atomizer.  Cup aging is shown to be an important factor in limiting the precision of this analytical technique and ways of minimizing the problem are described.  Matrix problems have also been encountered, which precluded the use of aqueous standard curves and the method of standard additions.  We propose the use of plasma in preparing standard curves, the values for which are corrected for inherent plasma zinc, as a possible solution to the problem.


Associated congenital malformations in retinoblastoma. A complete family investigation was made for 598 cases of retinoblastoma and details of any associated congenital malformations were recorded. Associated malformations were found in seven cases, four of which were cleft palate. There was a highly significant difference between the frequency of cleft palate in our cases with retinoblastoma and the frequency in the general population. This result supports the hypothesis that cases of retinoblastoma with associated congenital malformations are caused by germinal mutations.


Frequency of phenylketonuria in Norway.

Frequency of phenylketonuria in Norway. By January 1973, a total of 146 homozygotes (born between 1875 and 1972) for phenylketonuria (PKU) had been identified in Norway. This is an incomplete total, particularly in respect of PKU cases born before 1950, because of the PKU mortality rate. Between 1951 and 1972, the observed incidence of PKU was unchanged at 0.07 plus and minus 0.01 per 1000 live births. Haematological screening of about one-third of all births in Norway between 1966 and 1972 indicated an incidence of 0.07 plus and minus 0.02 per 1000 liveborn screened. As expected, this was well below the observed incidence of 0.11 plus and minus 0.01 per 1000 from screening data from Denmark, and considerably higher than the observed value of 0.03 plus and minus 0.01 per 1000 screened in Sweden. In comparison, indirect estimates, using the inbreeding coefficent of parents of PKUs and that of the general population in Norway in the corresponding years (1874-1972), suggested a fall in incidence of PKU in Norway from 0.14 plus and minus 0.15 per 1000 live births in 1918, to 0.08 plus and minus 0.08 per 1000 in 1941, and to 0.06 plus and minus 0.06 per 1000 live births in 1972. The present level of inbreeding in Norway (obtained from the Medical Registration of Bith) is discussed and compared with information in the 1891 census, with the parish registers between 1889and 1902, and with the parochial lists for the years 1903-1941.


Early childhood development of four boys with 47, XXY karyotype. In an epidemiological study, infants identified at birth as having sex chromosome anomalies are enrolled in a voluntary, long term evaluations program. Case histories are presented of the first four boys in the series to have a 47,XXY karyotype. They have been followed from birth for 6 to 9 years, with physical and psychological evaluations. Parents were informed in general terms of the child's genetic defect, and were offered continuing support and encouragement throughout the study. Close cooperation with the families was maintained. So far, the development of all these children has fallen clearly within the normal range and a reasonable healthy dpattern has been secured. Minor deviations in motor, speech and emotional development suggest a common underlying pattern, but four cases are too few on which to establish a relationship between karyotype and phenotype. The data suggest that the symptomatology reported in selected children with a 47,XXY karyotype may be strongly dependent on factors other than the chromosomal constitution, and that an appropriate familial and environmental situation may minimize elevated risks due to the marked genetic defect.


The pediatrician and the prevention of adolescent pregnancy. Some unplanned adolescent pregnancies may be averted through education and preventive servies provided by the teen-ager's physician. This paper discusses the need for such services, and reviews the current literature concerning issues surrounding adolescent contraception--professional acceptability, legality, public attitudes, morality, and appropriateness to the pediatrician's role. The authors conclude that recent developments make the pediatrician's involvement in adolescent sexuality counseling entirely feasible.


A follow-up study of the Preschool Readiness Experimental Screening Scale (the PRESS). A follow-up study of the Preschool Readiness Experimental Screening Scale (the PRESS) was conducted to determine whether the PRESS is a valid indicator of school readiness. Teacher ratings and Metropolitan Readiness Tests (MRT) scores were obtained at the end of kindergarten for 170 children who had been administered the PRESS before entering kindergarten. When the PRESS scores were compared with the teacher ratings and the MRT scores, the PRESS seemed a valid indicator of school readiness. A modified rating system for interpreting PRESS scores is also proposed.


Prophylaxis in rheumatic and nonrheumatic mitral insufficiency. Clinical, epidemologic, and experimental findings suggest that acquired mitral insufficiency should not invariably the attributed to rheumatic fever. In this series of childhood cases, more than 50 per cent of the instances of "pure" mitral insufficiency did not have an acceptable past history of rheumatic fever in terms of the Jones Criteria for the diagnosis of rheumatic fever. The authors therefore recommend that daily antibacterial prophylaxis should be limited to those children with valvular heart disease who have had at least one of the major manifestations of the Jones Criteria. But all cases or acquired valvular heart disease should remain under continued clinical observation, and be given antibacterial therapy to prevent bacterial endocarditis of the damaged valves whenever indicated.


Utilization of a hospital rotation system in an offic practice. Easing the burden of nighttime and office practice. A four-man pediatric group in private practice instituted a rotation system whereby one of the four worked entirely in the hospital for a week at a time. That physician also took all emergency nighttime calls. The program was evaluated for patient acceptance and for income production.


Fractures of the mandible in motor vehicle accidents. Motor vehicle accidents are a common cause of fractures of the mandible and are the most common cause of serious and multiple fractures. The usual mechanism of injury is outlined. The common fractures that occur are through the anterior alveolar process, condylar necks, or edentulous areas of the body and symphysis. There is high incidence of other injuries associated with jaw fractures in these patients. Treatment of the mandibular fracture must wait until the patient's general condition is stabilized. Obstruction of the airway demands emergency treatment by keeping the tongue forward and repeated suction of blood and mucus from the mouth and nasopharynx. Emergency tracheostomy is rarely necessary because of mandibular fractures. The methods for immobilizing a fractured jaw are outlined. The majority of accident victims are young and therefore have teeth. When there are teeth that occlude immobilization of the mandible must include intermaxillary fixation by wiring the teeth into occlusion. Interosseus wiring is used to support unstable fragments. Intramedullary Kirschner wires are a simple and effective method for immobilizing fractures through the body and symphysis of edentulous patients.


Medicolegal aspects of automobile injuries. We have tried to acquaint you with the basic elements of law relevant to the treatment of vehicle-related injury, i.e., the Good Samaritan clause, the definition of liability in surgery, warranty and informed consent. We have listed prophylactic measures to reduce medicolegal problems to a minimum. We have outlined the stepwise development of a court case and your duties to the court. Finally we have detailed special situations that occur in a trial and how to cope with them. In summary, bear in mind that it is natural to be edgy about court appearances. Few of us in medicine, after all, enjoy this kind of thing and to that extent we are truly out of our element. On the other hand, most attorneys, expert though they may be, are out of their element in medicine. That evens the score to a very considerable degree.


Traffic accidents, facial injuries, and psychiatry. The extent to which emotional factors play a direct or indirect role in the causation of traffic accidents has been presented along with the early and late emotional response of individuals to facial injuries as a result of traffic accidents. Illustrated case histories are presented.


Human volunteer and anthropomorphic dummy tests of driver air cushion system. The dynamic impact tests at Southwest Research Institute for the first time exposed human volunteers to production-like driver air cushion system depolyments at impact levels equivalent to a 30 mph barrier crash (48 kph). No significant injury was produced. At no time was it necessary for the secondary restraint systems to be utilized and the entire program schedule was carried out as planned. All tests were conducted under the most safe and controlled conditions possible, and typify only what the air cushions might accomplish in direct, head-on impacts up to 30 mph (48 kph). In comparing the test results, the anthropomorphic dummies' response to impact was conservative compared to the human volunteers. These and other human volunteer tests were run to help understand what might be expected in real world driving conditions. To further understand the value of this new safety system, 1000 1973 Chevrolets were built and places in a high mileage fleet across the couhtry. They now have accumulated 41 millions miles of experience and have had 15 accidents of sufficient severity that the air cushion depolyed. This fleet was followed with 1974 vehicles with air cushions sold to the general public as an option. These cars, combined with the test fleet, have accumulated approximately 60 million miles and have a total of 25 depolyments with 34 occupants in the front seat. There has been one fatality in accidents involving these vehicles, a seven week old baby boy. The child was not restrained in any protective carrier. All other injuries have been classified AIS-1 except for three AIS-2. Facial injuries have been very minimal and there have been no known hearing impairments as a result of these accident situations. To date, the results have been encouraging but caution must be taken in their interpretation. The population of drivers is not to be considered normal. The 60 million miles may appear to be a large number, but only represents 25 minutes of driving time of the total U.S. car population in 1 year.


Facial injury to vehicle occupants associated with traffic crashes. The engineer's viewpoint. The greatest immediate opportunity in automobile safety lies in utilization of what is already available to the motorist-equipment he may already have on hand, belts specifically. Without any further expenditure of money and without any further delay, the motorist can reduce the risk of facial injury.


Automobile accident studies of maxillofacial injuries. The use of the available lap and shoulder belts would between 10,000 and 15,000 fatalities annually, and would significantly reduce the number of injuries, particularly those of the face. By mandatory seat belt usage laws a significant reduction in deaths, disfiguring injuries, and hospital bed-days would be realized.


The biomechanics of maxillofacial trauma. Current advances in vehicle design include nonlacerative windshields and energy-absorbing instrument panels and interior structures. In order to prevent more severe injuries, it may be necessary to accept minor soft tissue trauma and nasal fractures, but it should be possible to prevent almost all other facial trauma at reasonable impact speeds.


Recurrent problems in emergency room management of maxillofacial injuries. Some of the problems that currently plaque emergency rooms are outlined, as well as possible solutions. Steps in the emergency room management of maxillofacial injuries are also presented.


Emergency care of severe facial injuries. In the absence of other life-threatening problems and with the airway adequate and bleeding contained, the emergency phase is now under control. At this point, priorities can be assigned for additional diagnostic procedures and definitive care. Further, as indicated above, one should be able to list precautions necessary in obtaining x-rays, in transporting the patient, or in other necessary manipulations. And finally, before progressing any further in diagnosis and treatment, record the data base of acute care and examination. This document anticipates problems and is essential if the patient's status later changes. Further, since most serious injuries involve liability considerations, the creation of an accurate initial record is totally dependent upon the attending physician. In summary, during the acute or emergency phase of care, the only considerations related to facial injury are airway maintenance, bleeding control, and determining whether more serious problems are present. Then and only then does the face itself merit attention.


Changes in physiological performance of the lower limb after fracture and subsequent rehabilitation. 1. Eight patients who had suffered a fracture of one leg were studied before and after a 7 weeks period of rehabilitation during work with one leg and both legs on a bicycle ergometer. 2. In submaximal exercise minute ventilation for a given carbon dioxide output and tidal volume at a given minute ventilation remained unchanged throughout the period of therapy for both one- and two-leg exercise: oxygen intake for a given work output and cardiac frequency for a given oxygen intake decreased in both the injured and uninjured limb during one-leg work, although in two-leg exercise there was no significant change. 3. Oxygen intake at zero load was subtracted from the maximum oxygen intake measured during loaded exercise to give net values for each limb exercised separately or both legs exercised together. The net maximum oxygen intake thus calculated increased 8-9% (*17 1/min) in the uninjured leg and 17-4% (*29 1/min) in the injured leg during one-leg exercise. In two-leg exercise the increase was 17-2% (*43 1/min), which approximately equals the increase in the two legs measured separately. 4. In both legs there was an increase in leg muscle (plus bone) volume although this was significant in the injured leg only. 5. The maximum oxygen intake attained in two-leg exercise for a given leg volume in the patients at discharge was not significantly different from that found previously in a cross-sectional survey of young healthy (naval) servicemen. Thus the rehabilitation programme investigated appears to be effective, although the spontaneous recovery without a rehabilitation programme is unknown.


Evidence for a significant contribution from central effects of angiotensin in the development of acute renal hypertension in the greyhound. 1. The importance of central vasomotor effects of endogenously generated angiotensin in the acute hypertensive response to renal artery constriction has been investigated in the anaesthetized greyhound. 2. When the central cardiovascular action of angiotensin was abolished by thermocoagulation of the areas postrema, the hypertensive response to renal artery constriction was reduced by half while the increase in plasma renin activity was unchanged. 3. It is concluded that central vasomotor effects of angiotensin play a significant role in renin-dependent hypertension.


Haematological status of middle- and long-distance runners. 1. Haematological investigation and blood volume measurements were carried out on forty male middle and long distance runners and twelve non-athletes. 2. The distribution of haemoglobin concentration, packed cell volume, erythrocyte count, total ironbinding capacity, serum and erythrocyte folate and serum vitamin B12 concentrations were essentially the same in atheletes and non-athletes. The mean serum iron concentration was higher in non-athletes than in athletes. There was no difference in the above measurements between athletes taking iron and/or folate and athletes not taking these supplements. 3. Blood volume and total body haemoglogin were on average 20% higher in the atheletes than in the non-athletes. 4. There was no correlation between haemoglobin concentration and blood volume in athletes. The evidence of this study suggests that haemoglobin concentration and blood volume are independently controlled. 5. 2,3-Diphosphoglycerate concentration in the erythrocytes was higher in the athletes than in the non-athletes; the mean values were 15-9 and 14-2 mumol/g of haemoglobin respectively.


Modifications of plasma post-heparin lipolytic activity and tissue lipoprotein lipase activity induced in the rat by acute administration of ethanol or propan-2-ol. 1. The oral administration of propan-2-ol [isopropanol; 100 mmol (6 g)/kg body weight] or ethanol [130 mmol (6 g)/kg body weight] to starved rats produced no change in plasma post-heparin lipase activity (PHLA) compared with that observed in 154 mmol/1 sodium chloride (saline)-treated rats. 2. An increase of adipose tissue lipoprotein lipase (LLA) and a decrease of heart LLA occurred in isopropanol-treated animals, whereas no significant changes were found in these activities after ethanol administration. 3. Since administration of isopropanol produces hyperglycaemia, observations were also made in rats receiving glucose infusion rather than saline. In these animals a rise in PHLA and adipose tissue LLA, and a fall in heart LLA, occurred. 4. It is suggested that the changes in tissue LLA produced by isopropanol are mediated by the rise in blood glucose.


Stimulation of calcium absorption and apparent increased intestinal 1,25-dihydroxycholecalciferol in rats treated with low doses of ethane-1-hydroxy-1,1-diphosphonate. 1. Ligated intestinal segments from rats treated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at the daily dose of 16 mumol (identical to 1 mg of phosphorus)/kg subcutaneously for 7 days show an increased rate of calcium absorption. 2. This dose of EHDP enhances the intestinal accumulation of a vitamin D3 metabolite with the chromatographic characteristics of 1,25-dihydroxycholecalciferol.


Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods. 1. Three-renin-stimulating methods for detection of low-renin hypertension have been compared. First, renin activity was measured in hospital patients after 5 days of sodium restriction and 3 h ambulation.  Secondly, renin activity was measured after frusemide stimualtion [0.42 mmol (140 mg) in 18 h] and 3 h ambulation. Thirdly, renin activity was measured after 5 days of chlorthalidone treatment [0.3 mmol (100 mg/day]ured after 5 days of chlorthalidone treatment [0.3 mmol (100 mg)/day] and 3 h ambulation. The last two tests were done with the subjects as out-patients without any dietary regimen. 2. In eleven normotensive control subjects and twenty hypertensive patients the results after frusemide were not comparable with those after sodium restriction since the frusemide test did not identify the same renin-suppressed hypertensive subjects as the sodium-restriction procedure. 3. After 5 days of chlorthalidone treatment in the renin values in eleven control subjects as well as in thirty-eight hypertensive patients were significantly higher than after sodium restriction. The values obtained after each procedure were closely correlated. 4. Thus the out-patinet chlorthalidone procedure identified similar sub-groups of patients as having low- or normal-renin hypertension as did the inpatient sodium-restriction test.


The role of plasma volume in the increase of aldosterone secretion rate during sodium deprivation. 1. 24 h aldosterone secretion rates (ASR) have been measured in six normal volunteers while recumbent all day and while standing for 12 h, on 200 and 10 mmol/day sodium diets and after salt-poor albumin infusions (75 g in 150 ml), which significantly expanded plasma volume. 2. The mean ASR on the 10 mmol/day sodium diet, both without and with the salt-poor albumin infusion, was highly significantly increased above the mean ASR on the 200 mmol/day sodium diet, both in the recumbent and in the upright posture. 3. There was no significant difference between the mean ASR values on the 10 mmol/day sodium diet alone and after the infusion of albumin either in the recumbent or in the upright posture. 4. The above abservations su;gest that sodium deprivation raises ASR by a mechanism or mechanisms unrelated to plasma volume.


Mechanisms of post-obstructive diuresis in the solitary hydronephrotic kidney of the rat. 1. In order to clarify further the phenomenon of post-obstructive diuresis, clearance and micropuncture experiments were done before and after relief of partial ureteral obstruction in rats with a solitary hydronephrotic kidney. 2. Glomerular filtration rate, urine flow and sodium excretion increased markedly, whereas surface nephron glomerular filtration rate increased only slightly and intratubular pressure, proximal and distal tubular water reabsorption did not change significantly. Decreased tubular reabsorption in deeper nephrons and collecting ducts appeared to be of major importance in the post-obstructive diuresis after relief of chronic obstruction. 3. In order to examine further the distinctive functional characteristics of the chronically hydro-nephrotic kidney, the results were compared with control rats having a solitary normal kidney or a solitary remnant kidney with an intact renal medulla. Urine flow rate and sodium excretion were higher and urine osmolality was lower (P less than 0-01) in post-obstructive kidneys when compared with either control group. There were no differences in glomerular filtration rate or surface nephron function which could account for the greater diuresis and natriuresis from the hydronephrotic kidney, thus confirming the importance of an abnormality in deep nephron or medullary function in post-obstructive diuresis. 4. There was a greater diuresis in post-obstructive rats with a marked increase in blood urea concentration. Water reabsorption in the distal nephron was decreased in such animals, as well as in urea-loaded rats with a remnant kidney, indicating the probable mechanism by which urea diuresis potentiates the phenomenon of post-obstructive diuresis.


Resin column perfusion with whole blood or plasma separated by the continuous flow celltrifuge. 1. The aim of this study was to define the factors influencing plasma separation from the continuous flow celltrifuge and to evaluate plasma as an alternative to whole blood for perfusion of exchange resins as part of a system of artificial liver support. 2. Studies in vitro showed the importance of packed cell volume, centrifugal force and duration of centrifugation on the degree of plasma separation. From these data it was possible to calculate plasma flow rates likely to be obtained from the celltrifuge when used in vivo. These predicted values correlated closely with plasma flow rate obtained in twenty-six studies in dogs. 3. Comparison of whole blood perfusion with plasma perfusion of exchange resins in another series of dog experiments showed that with whole blood perfusion there was often a considerable rise in pressure across the resin column but that this did not occur with plasma perfusion. 4. Measurements of platelet losses in the same series of experiments showed a 50% reduction of arterial platelet counts over a 31/2 h period of perfusion when whole blood was perfused. Although the fall was lower with plasma perfusion, the difference was not statistically significant. 5. Use of the celltrifuge provides a means of resin perfusion free of the mechanical difficulties of whole blood perfusion, but platelet losses still remain a problem.


Monitoring of intrapartum phenomena.

Monitoring of intrapartum phenomena. We have discussed in the first part of this paper the place of labor monitoring in the delivery of health care to the pregnant woman and the fetus. We have shown that monitoring is only practical and realistic in centers which are equipped to welcome high risk patients. Adequate personnel and facilities should be available on a 24 hr basis. The collaboration of the pediatrician and of the neonatal nursery is essential to the success of the operation. A great part of successful attempts to decrease perinatal mortality and morbidity has to do with prevention. Our population has to be educated during childhood and adolescence about reproduction. The second part of the paper describes the measurement of intrauterine pressure and fetal heart rate and the value of data interpretation. The advantages and limitations of the techniques are outlined. The problems which the doctors and engineers encounter during these procedures are briefly reviewed. It is concluded that monitoring of labor is still in an early developmental stage. Man power and technical innovations22 are necessary to assure a reduction of 15 per cent of the total perinatal mortality with the use of this technique.


Fetal monitoring techniques.

Fetal monitoring techniques. It is seen that there are several possible techniques for monitoring the fetus during labor. In addition to those described above, one can take microblood samples from the fetus and analyze for blood gases and pH. The latter is usually the only parameter measured and often is helpful in assessing the fetus. Yet even with spot checks of this chemical determination added to the monitored data, the overall value of fetal monitoring in definitively diagnosing the onset of significant fetal distress must be questioned. Further work and new monitoring techniques and parameters are clearly needed to improve the care of the high risk mother and fetus during labor and delivery.


Duration of effect of treatment of menopausal symptoms by oestrongen fraction. A follow-up study of 17 menopausal patients receiving piperazine oestrone sulphate (Harmogen), the efficiency measured by the effect on plasma oestradiol levels, was conducted in two groups of patients. The first group had undergone an artificial menopause. Clinical relief of symptoms again correlated with the effect of the oestradiol levels, the duration of the effect exceeding the period of therapy by 3 months.


Comparison between the bronchodilator and cardiovascular effects of inhaling 0.5 mg. rimiterol ('Pulmadil') and 0.2 mg. salbutamol. A comparison between the acute effects of rimiterol (0.5 mg) and salbutamol (0.2 mg.) has been made using metered dose aerosols. In this dosage it was found that the peak effect of the two drugs was the same but that the effect of rimiterol was less prolonged than that of sulbutamol. No increase in blood pressure occurred and heart rate changes were minimal after both drugs. Rimiterol is an acceptable alternative to the short-acting isoprenaline but lacks the cardiovascular effects of isoprenaline and is an alternative to salbutamol where very prolonged action is unnecessary.


Anabolic agents in kidney disease: the effect of formebolone on protein synthesis in patients with renal insufficiency or nephrosis. The anabolic activity of formebolone was studied in 7 patients with nephrosis or renal insufficiency by measuring the amount of 14C-leucine incorporated into plasma proteins as an index of protein synthesis. The data demonstrate that the incorporation of label into the plasma albumin fraction was significantly increased after formebolone administration.


Psycho-sexual disorders and their treatment: Part II. In a previously published part of this review the historical and aetiological aspects of sexual inadequacy were considered and an account given of vaginismus. The main problems found in patients with erective and orgasmic dysfunction were also discussed. In this second part, the author considers the conditions of premature ejaculation and ejaculatory incompentance as well as discussing erective and orgasmic incompetence in more detail. Behavioural and other psychotherapeutic measures are considered and a brief review is made of the use and value of drug therapy in patients with sexual dysfunction.


Management of arterial hypoxemia induced by fiberoptic bronchoscopy. Twenty patients undergoing fiberoptic bronchoscopy (FOB) (bronchofiberscopy) were studied with serial arterial blood gas analyses. Ten patients were managed using a 40 percent Venturi mask with a 2-cm opening cut out for the FOB; there were ten other patients, with this opening modified by a thin rubber diaphragm with a slit for insertion of the FOB. Both masks decreased the extent of hypoxemia after bronchoscopy, but the mask with the diaphragm provided significantly higher PaO2 values. A significantly higher mean FIO2 was found at the carina in the group using the diaphragm-modified mask. This study suggests that declines in PaO2 after bronchoscopy can be avoided in most patients undergoing diagnostic FOB by using a diaphragm-modified 40 percent Venturi mask during and after the procedure. However, patients with a PaO2 below 60 mm Hg before bronchoscopy may require other measure to avoid potentially hazardous degrees of hypoxemia after bronchoscopy.


The effect of bronchofiberscopic examination on oxygenation status. Arterial blood gases were measured in 62 patients, none of whom was critically ill, to determine the effect of transnasal fiberoptic bronchoscopy on oxygenation status. Blood samples were obtained at regular intervals during the procedure. Thirty-four patients who were bronchoscoped while breathing room air had a significant drop in the arterial P02 following saline solution lavage. Twenty-eight patients who were given 28 percent oxygen via a Ventimask during the procedure were protected from this hypoxemia. Simultaneously measured arterial pH and Pco2 were unchanged during the procedure. Premedication alone resulted in a minimal but insignificant drop in PaO2 in 7 patients. These observations suggest that if the initial PaO2 is less than 70 mm Hg on room air, bronchoscopy by the transnasal approach is best performed with the administration of oxygen through an appropriate mask. If the patient is at risk of developing hypercapnia with supplemental oxygen, a 28 percent Ventimask should be utilized to prevent significant hypoxemia without causing hypercapnia.


Hemodynamic effects of edrophonium chloride (Tensilon) infusion. The hemodynamic effects of a 10 mg bolus of edrophonium chloride followed by a continuous infusion of 0.25 to 1.0 mg per minute, were determined in unanesthetized patients with significant myocardial disease. The effect on heart rate of the drug was negated by studying a group of nine patients with complete heart block and permanently implanted ventricular pacemakers. After the 10 mg bolus, two of the nine patients experienced dizziness, nausea and abdominal cramps associated with a mild decrease in peripheral vascular resistance. There was no significant change in cardiac index, mean blood pressure, brachial artery upstroke time, corrected ejection time, or left ventricular systolic ejection time. This study demonstrated that the continuous infusion of 0.25 to 1.0 mg per minute of edrophonium chloride following a 10 mg loading dose, had no significant effect on myocardial function.


Immediate operative treatment for massive hemoptysis. A series of 15 patients with life threatening, massive hemoptysis is reported. Thirteen of these patients underwent immediate operative treatment with only three deaths. One died after bronchoscopic identification of the bleeding site while awaiting elective thoracotomy. The other patient left the hospital against medical advice. Immediate identification of the site of bleeding by bronchoscopy followed by thoracotomy with resection of the bleeding source, is the preferred method of managing such patients, except when there are specific contraindications to resection.