[Changes in the contractile function of the myocardium in various methods of excluding the heart from the circulation during the surgical correction of acquired heart defects]. Changes in myocardial contractile function were studied during 46 operations with extracorporeal circulation on patients with acquired heart diseases; the operations were performed with the use of cold cardioplegia and electrical fibrillation of the heart. The dependence of the decrease in myocardial contractilicy on the method of cardioplegia, the duration of the heart arrest, and the parameters of extracorporeal circulation is analysed. The results obtained are evidence that it is necessary to improve the method for protecting the myocardium during operations with extracorpeal circulation.


[Trauma to the blood during assisted circulation]. Trauma inflicted to blood in different method of assisted circulation was studied in experiments and in the clinic. Morphological disturbances of red blood cells and changes in their aggregation properties were revealed. Left ventricular shunt and aorto-aortic counter-pulsation are attended with increased aggregation properties of blood platelets. Aorta-aortic counter-pulsation causes a greater damaging effect than shunting of the left ventricle. Counter-pulsation by means of a balloon pump is attended with least hemolysis.


[Basic courses of approach to the surgical treatment of postinfarct defects of the interventricular septum]. The authors studied 20 patients with postinfarction ventricular septal defects; among them 9 had been operated on and 2 of these patients died. Eleven patients did not undergo operation, 10 of them died. All patients subjected to operation had severe circulatory insufficiency; in 3 the septal defect was of nor more than one month's duration. Patients whose condition was particularly severe were subjected to intubation, catheterization of the heart, left ventriculo- and coronarography, and after the operation has been planned they were operated on on the same day. Some patients who could move about but who also suffered from circulatory insufficiency were operated on according to the planned schedule. In 10 patients who had died without being operated on the anatomy of the defect and the condition of coronary circulation were examined. The authors contend that before undertaking an operation it is necessary to assess the patient's condition and the possibility of operating on him and determine the role of the ventricular septal defect and the hemodynamic disturbances consequent upon the infarction; all cardiac lesions should be corrected during the operation. Besides closure of the defect and resection of an aneurysm 2 patients also underwent operation for aorticocoronary shunt.


[Sympathetic-adrenal and enterochromaffin systems and homeostatic indices in open-heart surgical operations under morphine anesthesia]. Catecholamine, serotonin and histamine metabolism and the level of acid metabolites and the activity of the enzymes lactate dehydrogenase and catalse in blood were studied in patients with congenital heart disease who were operated on under conditions of extracorporeal circulation and morphine anesthesia. The results obtained were compared with the values of acid-base balance, haemodynamics and volume of diuresis. It wwas found that the period of morphine induction was marked by a significant increase in the blood plasma noradrenalin content in the absence of essential changes in the other biochemical and hemodynamic indices studied. No significant changes were noted in the systems of neurohumoral and tissue regulation, indices of the redox processes and renal excretion in the most traumatic periods of the operation. The data obtained allow morphine to be accepted as an anesthetic which provides adequate protection of the organism from operative trauma.


[Use of correlation analysis of clinical biochemical indices for a study of the pathogenesis of acute arterial obstruction]. The role of serotonin, histamine, and the kallikrein-kinin system in acute arterial occlusion during ischemia was studied from the standpoint of multivariate correlation analysis. The mechanisms of their participation in the genesis of pathophysiological disorders in the organism in acute arterial occlusion are discussed. The important role of serotonin and the kallikrein inhibitor in this pathological condition is shown.


[Effect of auxilliary orthograde perfusion on lesser circulation hemodynamics]. The causes of disorders of the venous return of blood to the heart in development of acute experimental cardiovascular insufficiency were studied. It was established that grave hemodynamic disturbances in pulmonary circulation are the consequence but not the cause of the sharp decrease of venous blood return to the heart with the development of acute cardiovascular insufficiency.


[Behavioral factors in the problem of treating arterial hypertension]. The paper deals with the role of the psychological factors in the control of arterial hypertension in the population. The attitude of the population towards their own health and possible medical intervention--these are the factors. It is proved that the negative attitude can low down the efficiency of the public health effort in the revealment and systematic management of hypertensives. Special attention is paid to the discussion of the role of the psychological factors in the pathogenesis of the essential hypertension. Personality traits of the patients with different forms and course of arterial hypertension (symptomatic included) are considered. Strategy and psychological intervention methods in essential hypertension control in order to increase the treatment efficiency are also discussed. The importance of the multidisciplinary approach which envisages routine hypertensive drugs, beta-blocker, psychotropic agents and relaxatiion technique, causal-pathogenetic psychotherapy methods, psychosocial intervention is stressed.


[Nature of the reaction of blood plasma steroid hormones in hypertension to various types of stimulation]. Fifteen healthy persons and 31 patients with essential hypertension whose ages ranged from 18 to 45 were examined. The basal level of three steroid hormones (progesterone, aldosterone, and cortisol) in blood plasma and their level after loading (walking, furosemid and rest, furosemid and walking) were studied by the radioimmune method. It is shown that in comparison with healthy individuals, patients with essential hypertension are marked by a change in the ratio of the pressor (aldosterone, cortisol) to the depressor (progesterone) hormones in blood plasma during loading. In different types of loading, no direct correlation was found, on the whole, between the degree of the reactions of aldosterone and renin in healthy individuals and in patients with essential hypertension.


[Clinical aspects of hypertensive crises]. Hypertensive crises were studied in 80 patients. In severe cases the ECG provided evidence of systolic overloading of the left ventricle with intensification of coronary circulation and development of acute myocardial ischemia. Phase analysis showed prolongation of the mechanical systole with increase of the myocardial index. In more complicated cases there was a more evident hypodynamic syndrome with marked myocardial insufficiency. Hemodynamic disturbance were marked by a sharply increased peripheral resistance with a heterogenous reaction of the cardiac output. Blood supply to the cerebral tissue reduced sharply with an increase in the resistance of cerebral vessels. Renin activity was directly related to the severity of the crisis. A sharp onset of cerebral and cardiac ischemia was marked by changes in the antigen albumin. Timely diagnosis and differentiated treatment made it possible to avoid vascular complications in hypertensive crisis.


[Fluorescein angiographic studies of the fundus oculi in the malignant arterial hypertension syndrome]. Fluorescein-angiographic examination of fundus oculi in 33 patients with the syndrome of malignant hypertension made it possible to recognize for the first time changes in the choriocapillary layer, which in 29 patients were displayed by choroidal retention; ischemic zones were seen in 20 patients. It is suggested that the discovery of ischemic zones in the choriocapillary layer may be an early diagnostic criterion of malignant hypertension.


[State of the vascular wall in experimental hypertension induced by the administration of indomethacin in combination with a saline drink]. It is shown that various types of vessels (elastic, musculo-elastic, and muscular) possess initially different capacity for synthesizing and destroying prostaglandins. Under the effect of indomethacin and salt load considerable changes occur in the synthesis and metabolism of prostaglandins and the closely related system of cyclic nucleotides in the vessels of experimental animals. The character of these changes suggests the predominance of constrictive vascular reactions, which was confirmed by the results of functional tests on segments of the aorta and femoral arteries. It was shown also that the walls of small arteries of different organs, the kidneys in particular, undergo marked structural changes resulting in their thickening and narrowing of the lumen. These functional and structural changes may underlie the increase in peripheral vascular resistance and be the principal pathogenic mechanism of hypertension.


[Blood plasma lipoextraction as a method of lipid removal from atherosclerotic lesions of the aorta in rabbits]. The effect of repeated lipoextraction of their own blood plasma on regression of the atherosclerotic process was studied in rabbits with experimental hypercholesterolemia 2 months after they had been fed cholesterol. The blood plasma cholesterol level at the end of the experiment was lower in the experimental animals than in the controls, whereas the results of morphological examination of the aortic areas involved in atherosclerosis showed that repeated removal of lipids from the blood plasma promotes rapid regression of experimental atherosclerosis in the experimental animals.


[Effect of the characteristics of the preinfarct period on the state of patients in the 1st year after a myocardial infarct]. From a follow-up of 496 patients (males aged from 20 to 65 years) the authors analyse their condition during the first year after recovery from myocardial infarction. It is shown that preceding arterial hypertension, a history of myocardial infarction and angina pectoris as well as the patient's elderly age have an unfavourable effect with regard to the possible development of circulatory insufficiency during the first year after myocardial infarction which must, without doubt, be taken into account in planning regimens of motor activity for these patients. An unfavourable prognostication factor with regard to the hazard of a new myocardial infarction developing during the first year is a recurrent affection of the cardiac muscle, and in patients of the 60--65 year group, the existence of hypertension prior to myocardial infarction.


[Functional state of the left ventricle in patients who have had a myocardial infarct according to ultrasonic scanning data]. In most patients who had suffered from myocardial infarction 3 1/2 to 12 months (7.6 months on the average) previously and had no clinical symptoms of circulatory insufficiency, ultrasonic scanning of the heart showed normal stroke volume and stroke index, and normal minute volume and cardiac index against the background of low indices of left ventricular contractility function (ejection fraction, % delta S, VcF) and large end-diastolic and end-systolic left ventricular volumes. Normal stroke ejection was achieved due to an increase of the end-diastolic volume, the decrease in the contractility of the left ventricular was thus compensated for with the participation of the Frank-Starling mechanism.


[Blood hormones in chronic ischemic heart disease and acute myocardial infarct]. The activity of some blood hormones was determined by radioimmune analysis in 58 patients with chronic ischemic heart disease (CIHD), 60 patients with myocardial infarction (MI) and in 24 practically healthy individuals. Increased activity of pituitary hormones (ACTH and TTH) with simultaneous increase in the blood STH content in the absence of essential changes in the FSH and LH content was established. These shifts in the production of pituitary hormones are evidently due both to disorders in the hypothalamo-hypophyseal area and to changes in the activity of systems coordinated to the pituitary gland in patients with CIHD. In patients with MI the activity of these hormones in blood does not differ from that in the control group. In patients with CIHD, the activity of the thyroid is diminished due to a decrease in its thyroxin-producing ability against the background of high activity of the pituitary thyreotropic function. The discussed shifts in the activity of some hormones in CIND and MI are conducive to the advancement of atherosclerosis and changes in myocardial metabolism.


Study of factors which modify the development of norepinephrine-induced acute renal failure in the dog. Previous studies have demonstrated that the fall in inulin clearance which occurs 3 hours after the intrarenal administration of norepinephrine can be markedly attenuated by the prior administration of intrarenal prostaglandin E2 (PGE). Since in the previous studies PGE led to a marked increase in both renal blood flow and solute excretion, we designed the present series of experiments to investigate whether an increase in renal blood flow, solute excretion, or other factors were responsible for the protective effect in the norepinephrine model. Two renal vasodilators, bradykinin and secretin, were evaluated initially. Bradykinin administration prior to norepinephrine administration had a protective effect similar to that previously found with PGE, whereas secretin did not. Both of these vasocilators increased renal blood flow to the same degree, but only bradykinin increased urine flow and solute excretion. The fall in inulin clearance 3 hours after the administration of norepinephrine was also attenuated by two diuretics (mannitol and furosemide) which tended to increase renal blood flow. In contrast, two natriuretic agents, which are also renal vasoconstrictors (chlorothiazide and benzolamide), had no protective effect. Further, chlorothiazide and benzolamide obviated the protective effect of bradykinin. These studies demonstrate that there are several types of pharmacologic agents which can modify the magnitude of renal functional impairment resulting from extreme renal ischemia. Although the mechanism of the protective effects remain unclear, the findings are compatible with the view that the protective effect noted with PGE, bradykinin, mannitol, and furosemide may be related to an increase in osmolar excretion which occurred with administration of each of these agents. This potentially salutory effect (increased osmolar excretion), however, could be overcome by an agent (e.g., chlorothiazide or benzolamide) which also increased renal resistance prior to the administration of norepinephrine.


Effects of fluorocitrate on renal ammoniagenesis and glutamine metabolism in the intact dog kidney. Renal glutamine metabolism was studied in vivo following infusions of fluorocitrate into chronically acidotic and alkalotic dogs. Coincident with a dramatic rise in renal cortical citrate concentrations, there was a significant fall in tissue glutamate in both acid-base states. This was accompanied by a significant increase in total renal ammonia production. Glutamine metabolism and ammoningenesis in alkalotic dogs receiving fluorocitrate simulated that achieved in acidotic dogs. The simultaneous administration of alpha-ketoglutarate and fluorocitrate significantly diminished the fall in tissue glutamate and the rise in ammoniagenesis induced by fluorocitrate alone. These results are compatible with the hypothesis that ammonia production from glutamine is enhanced secondary to increased glutamate deamination. We postulate that this chain of events may be the consequence of impaired alpha-ketoglutarate production from citrate.


Functional characterization of drug-induced experimental papillary necrosis. The functional expression of papillary necrosis was investigated with a model of drug-induced papillary necrosis. Bromoethylamine hydrobromide (BEA) administration to rats uniformly resulted in the development of papillary necrosis. All studies were performed 24 hours after BEA administration with the exception of the electrolyte balance studies, which were performed during the 72 hours after the induction of papillary necrosis. GFR was not different between BEA-treated and sham rats. BEA-treated rats had a significantly lower maximal urine osmolality and free water reabsorption than did sham rats. Renal tissue concentrations of sodium, potassium, and water were not different between BEA-treated and sham rats. During water diuresis, free water clearance was not significantly different between the two groups. During sodium bicarbonate administration, maximal bicarbonate reabsorption and urine-blood Pco2 gradient (at comparable urine bicarbonate concentrations) were not significantly different between the two groups. During sodium sulfate infusion, there was no difference in minimum urine pH, ammonium excretion, and net acid excretion between chronically acidotic BEA-injected and sham rats. In rats on "zero" sodium intake, BEA administration resulted in a significant increase in urine flow and sodium excretion, whereas sham rats remained in sodium balance. In rats with restriction of both sodium and chloride, BEA administration resulted in a significant wastage of sodium, chloride, and calcium. There was no difference in potassium excretion between BEA-treated and sham rats during hydropenia, bicarbonate administration, sodium sulfate infusion, or ingestion of a normal potassium diet. When potassium intake was restricted to "zero," BEA-treated rats developed potassium wastage; when potassium intake was increased to 21 mEq/day, BEA-treated rats had a significantly lower potassium excretion than did sham rats. These findings may result from alterations in collecting duct transport, but damage to deep medullary structures may also contribute.


Effects of hemodialysis on protein-bound calcium. This study evaluates whether hemodialysis alters the affinity of plasma proteins for calcium. We have used a new automated methodology for the determination of the dialyzable calcium fraction. Protein-bound calcium was estimated as the difference between the total and dialyzable calcium fractions. All measurements were made after adjustment of the sample pH to 7.40 +/- 0.02. The calcium fractions were determined in 12 patients before and after hemodialysis. In addition, we added calcium to the predialysis specimens to evaluate the effect of increased ionic calcium on protein binding and corrected the protein-bound calcium in these specimens for the increase in total protein observed in the postdialysis specimens. Hemodialysis significantly increased total, dialysable, and protein-bound calcium. The mean ratio of protein-bound calcium in the postdialysis specimens to the corrected protein-bound calcium in the predialysis specimens with calcium added was 0.97 +/- 0.02. We conclude that (1) the increase in protein-bound calcium to the predialysis specimens, and that (2) the binding affinity of serum proteins for calcium is not altered by hemodialysis.


Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man. The present study was designed to evaluate the spectrum of responses of PRA and plasma aldosterone (PAldo) to a range of oral potassium intakes (0 to 300 mEq of potassium chloride per day) in 20 normal human subjects receiving an electrolyte-free diet. Potassium exhibited a dose-dependent natriuretic effect. The results of the PRA studies indicate that normal dietary amounts (50 mEq/day) of potassium chloride do not prevent the increase in PRA with absolute sodium deprivation and that PRA is maximally stimulated on 150 mEq of potassium chloride per day. The rise in PRA is directly correlated with serum potassium concentration. The results of the PAldo studies indicate that potassium chloride deprivation attenuates PAldo increases due to sodium deprivation and that PAldo is maximally stimulated on 150mEq of potassium chloride per day. The rise in PAldo is directly correlated with serum potassium concentration and with PRA. The administration of 300 mEq/day of potassium chloride caused significant hyperkalemia and blunted both PRA and PAldo increases. Our results suggest that potassium chloride has an important role in the regulation of PRA and PAldo, and that only following potassium chloride deprivation is the PRA/PAldo response dissociated.


Autoradiography of gentamicin uptake by the rat proximal tubule cell. Rats were injected with 25 microCi (14.2 microgram) of tritiated gentamicin and were killed 10 min, 1 hour, or 24 hours after the injection. Renal tissue was preserved by intravascular perfusion of a glutaraldehyde-containing solution. In a preliminary experiment, glutaraldehyde was found to fix gentamicin to bovine serum albumin, and this property probably accounted for the negligible loss of label during specimen preparation. By light microscopy, gentamicin appeared to be confined almost entirely to the proximal tubules. Autoradiographic grains appeared initially over the apical cytoplasm of the proximal tubule cells and, with time, moved progressively into the interior of the cell. Electron-microscopy revealed that the grains were associated with apical vesicles at 10 min and lysosomes at 1 and 24 hours. The specificity of labeling was confirmed by quantitative grain analysis. These results indicate that gentamicin is transported into the proximal tubule cell by pinocytosis and becomes sequestered in lysosomes. This process may account for the accumulation of myeloid bodies in the proximal tubule lysosomes of gentamicin-treated rats, but whether this mechanism contributes the nephrotoxicity of this drug cannot be ascertained at this time.


The connecting tubule: a functional subdivision of the rabbit distal nephron segments. Studies on adenylate cyclase response of the nephron fragments to hormones and drugs have suggested that there is a functionally distinct segment tentatively called the connecting tubule (CNT), which is located between the distal (DT) and the cortical collecting tubule (CCT). The functional significance of these biochemical findings was examined with isolated rabbit renal tubules perfused in vitro. The transepithelial voltage (PDt) of the DT, CNT, and CCT were, respectively, -28.7 +/- 3.24 mV (24), -27.0 +/- 2.69 mV (24), and -3.5 +/- 2.14 mV (11) in the normal rabbits. The PDt of the CCT increased to -32.2 +/- 2.02 mV (33) when rabbits were pretreated for at least 3 days with deoxycorticosterone acetate, DOCA (1 mg/kg/day, i.m.), whereas the PDt of the DT and the CNT remained unchanged. The PDt of the CCT obtained from deoxycorticosterone acetate- (DOCA) treated animals decreased after addition of antidiuretic hormone (ADH) or isoproterenol (ISO) to the bath. The PDt of the CNT also responded to these agents, but the dose required to obtain the same response was quite different: The CNT was 100-fold more sensitive to ISO as compared to the CCT, whereas the CCT was 10-fold more sensitive to ADH than was the CNT. In contrast, the PDt of the DT did not respond to any of these agents, even at a higher concentration. After addition of ADH (200 microU/ml) to the bath, the osmotic water permeability (10(-8) cm2 . sec-1 . atm-1) of the CCT increased from 1.13 +/- 0.83 to 7.46 +/- 2.36, but that of the CNT remained low (0.36 +/- 0.78 in control vs. 0.48 + 0.64 after ADH). These observations support the view that the CNT is functionally distinct from either the DT or the CCT.


Effect of erythropoietin on anemia of peritoneally dialyzed anephric rats. The effect of erythropoietin on anemia was studied in anephric rats undergoing peritoneal dialysis. Both the number of bone marrow red cell precursors and plasma iron turnover were markedly depressed in untreated peritoneally dialyzed anephric animals when compared to peritoneally dialyzed sham-operated control rats. Anephric rats receiving 2 U of erythropoietin per day for 12 days had greater than threefold more bone marrow red cell precursors and a twofold larger plasma iron turnover than did the saline injected anephric rats. There was no significant difference in either bone marrow red cell precursors or plasma iron turnover in the erythropoietin-treated anephric rats when compared to the nonuremic controls. Although the rats receiving erythropoietin for 12 days had a significantly higher hematocrit (29.5%) than the saline injected uremic rats did (19.0%), the hematocrit was significantly lower than that found in nonuremic control animals, either receiving erythropoietin (48.1%) or not receiving erythropoietin (41.6%). Our data suggests that erythropoietin is potentially a useful agent for the treatment of anemia of chronic renal failure.


Hemodynamic changes during sequential ultrafiltration and dialysis. Seven patients on regular dialysis were studied to elucidate the hemodynamic changes during ultrafiltration and dialysis, performed sequentially, the period of ultrafiltration (1 hour) either preceding or following dialysis (3 hours). During dialysis ultrafiltration was prevented by applying positive pressure in the dialysate compartment. Cardiac index (dye dilution: indocyanine green), heart rate, stroke volume index, blood pressure, and total peripheral vascular resistance index were measured. During ultrafiltration, cardiac index and stroke volume index decreased, but heart rate was not significantly changed. Total peripheral vascular resistance increased, resulting in unchanged blood pressure. During dialysis, the total peripheral vascular resistance decreased, but cardiac index and heart rate increased. BP decreased when the increase in cardiac index was insufficient to compensate for the decrease in total peripheral vascular resistance. PRA increased during ultrafiltration due to hypovolemia and decreased during dialysis, presumably due to decreased sympathetic activity which may also be a cause of dialysis-induced vasodilation.


Recovery from postischemic acute renal failure in the rat. To define the pattern of recovery from postischemic acute renal failure (ARF), we performed clearance and micropuncture studies at intervals of 1, 2, 4, and 8 weeks following 60 min of complete unilateral renal artery occlusion in the rat. At 1 week, the inulin clearance (CIn) of the postischemic kidney was less than 2% of normal. The presence of marked preglomerular vasoconstriction was indicated by the reductions in renal blood flow (RBF), and stop-flow (SFP) and estimated glomerular capillary hydrostatic pressures (GCPe). In additon, there was evidence of tubular obstruction. Proximal intratubular pressures (PITP) were elevated, and intratubular casts could be seen in vivo and on histologic sections. At 2 weeks CIn had increased more than tenfold. This change occurred in the absence of any significant elevation in RBF, SFP, or GCPe. PITP had fallen, however, to normal values, and histologic sections revealed a marked reduction in the extent of intratubular casts. Ipsilateral urinary recovery of 3H-inulin microinjected into proximal convolutions was complete. At 4 and 8 weeks, there were further but more gradual rises in CIn, which were associated with progressive increases in RBF, SFP, and GCPe. These observations indicate that recovery from postischemic ARF occurred in a biphasic pattern. The initial rise in CIn was associated with the relief of intratubular obstruction, whereas subsequent rises in CIn occurred in association with progressive renal vasodilation.


Tissue resistance to insulin stimulation of amino acid uptake in acutely uremic rats. Peripheral tissue resistance to insulin-mediated glucose uptake occurs in uremia. A similar resistance also may exist to insulin-mediated amino acid uptake. The present study examined the effect of insulin on the uptake or distribution ratios (DR) of alpha-aminoisobutyric acid (AIBA) attained in the tissues of rats made acutely uremic by bilateral nephrectomy. Both uremic and control rats concentrated equally AIBA in the gastrocnemius muscle in the absence of insulin (DR = 2.82 +/- 0.39 in controls, 2.52 +/- 0.40 in uremics). Compared to control rats, the diaphragm and liver of uremic rats, in the absence of insulin, had higher concentrations of AIBA. Insulin had the expected effect of increasing the uptake in the gastrocnemius, diaphragm, and liver of control rats but had no effect on uptake in the gastrocnemius muscle of uremic rats (DR = 5.82 +/- 0.78 in controls, 3.07 +/- 0.60 in uremics). The effect of insulin on the distribution ratio of AIBA in diaphragm and liver or uremic rats was less than it was in control rats. Uremia is associated with inhibition of insulin-mediated amino acid uptake as well as peripheral resistance to glucose utilization.


Effects of gastrointestinal hormones on transport by peritoneal dialysis. Because the gastrointestinal hormones are known to dilate the splanchnic vasculature, their effects on transport of water and solutes during peritoneal dialysis were studied in an experimental model, the rabbit. In unanesthetized rabbits, dialysate volume was calculated by isotope dilution, and clearances were estimated by dialysate/plasma concentration ratio factored by minute volume. With isotonic dialysis solution, the mean increment in dialysate volume per minute of intraperitoneal dwell was 0.19 ml/kg/min, and mean clearances of creatinine and urea were 0.71 and 0.90 ml/kg/min, respectively. When administered intravenously, secretin significantly augmented osmotically induced water flux, but not when given intraperitoneally. Neither glucagon nor cholecystokinin affected dialysate volume. Intravenously, but not intraperitoneally, glucagon increased peritoneal clearances of creatinine and urea to more than 150% of control values. Neither cholecystokinin nor secretin augmented significantly peritoneal mass transport when given by either route. The data suggest that the site of acton is the endothelial surface of the membrane, that the mechanisms of augmenting transport involve increased permeability and/or surface area, and that agents which combine an increase in mass transport and capillary filtration coefficient may be clinically useful.


Reversal of renal cortical actions of angiotensin II by verapamil and manganese. Experiments were performed on 19 euvolemic Munich Wistar rats to examine the role of calcium in the action of angiotensin II(AII) on the glomerular microcirculation. Intravenous infusion of a mildly pressor dose of AII(N = 7 rats) led to a significant rise in mean glomerular capillary hydraulic pressure (PGC) and significant decines in glomerular plasma flow rate (QA) and the ultrafiltration coefficient (Kf). Because of these offsetting effects, single nephron GFR (SNGFR) and total kidney GFR failed to change significantly. Both afferent and efferent arteriolar resistances (RA and RE) increased during AII infusion, on average by approximately 40% and 75%, respectively. Despite continued AII infusion, addition of verapamil led to return of values for PGC, QA, Kf, RA, and RE essentially to pre-AII levels. In 7 other rats, verapamil infusion alone failed to exert significant influences on these indices. Likewise, no significant changes in these measures were observed when this same dose of AII was infused into verapamil-pretreated animals. Moreover, intrarenal arterial injection of a nonpressor dose of AII into 6 other rats also resulted in changes in PGC, QA, Kf, and RE similar to those seen during intravenous infusion, and addition of manganese abolished these effects. Since verapamil and manganese are both known to interfere with excitation-contraction coupling of smooth muscle, perhaps by inhibiting transcellular calcium transport, the present results suggest that the calcium ion may be an important cofactor required for the expression of AII action on the glomerular microcirculation, by affecting mesangial and efferent arteriolar smooth muscle contractility.


Synergism of dopamine plus furosemide in preventing acute renal failure in the dog. The protective effects of a combination of dopamine and furosemide were studied in dogs during the initial phase of acute renal failure (ARF) induced by intravenous uranyl nitrate (10 mg/kg). Fifteen minutes after injection of the nephrotoxin, and infusion of dopamine (3 micrograms/kg/min), furosemide (1 mg/kg/bolus followed by 1 mg/kg/hr), or both drugs simultaneously were given for 6 hours. Exogenous creatinine clearance was measured for 6 hours, and the intrarenal blood flow was measured with radioactive microspheres before and 3 hours after the induction of ARF. Treatment with both dopamine and furosemide produced renal vasodilatation, high urine flow rate, and attenuation of the fall in GRF seen in untreated animals. In contrast, single use of dopamine or furosemide was totally ineffective in producing renal vasodilation, a diuresis, or the maintenance of the GFR. These data indicate that dopamine plus furosemide have a synergistic effect in preventing the early pathophysiologic changes associated with ARF in this animal model. Maintenance of a high GFR correlated best with the enhancement of solute excretion and urine flow rate. Potential protective effects of dopamine plus furosemide in other models of ARF deserve careful investigation.


[The immune competence of patients with Crohn's disease (author's transl)]. The cell-mediated and humoral immune responses were assessed in 15 patients with Crohn's disease and in 28 age-matched control subjects by means of several in vivo and in vitro methods. The disease activity in most patients was absent or moderate. Studying cellular immunocompetence we investigated the skin reactivity to various recall antigens (Candida, Trichophytin, Mumpsantigen, Streptokinase-Streptodornase, PPD), the primary immune response to Dinitrochlorobenzene (DNCB) and Keyhole Limpet Hemocyanin (KLH), and the lymphocyte transformation induced by mitogens (Phytohemagglutinin, Concanavaline A, Pokeweed Mitogen) and specific antigens. Humoral immunity was studied by measuring immunoglobulins, isohemagglutinins, and the antibody response to KLH. In addition, complement components and (in 10 patients) the proportions of T- and B-lymphocytes in the peripheral blood were evaluated. Cutaneous responsiveness to Candida, Mumps-antigen, SK-SD, and DNCB as well as the cellular immune response to KLH were impaired in patients with Crohn's disease (significance was reached for SK-SD, DNCB, and the mean area of induration). The lymphocyte transformation test with PHA, ConA, and PWM revealed normal results. For specific antigens (PPD, SK-SD, KLH) a good correlation could be demonstrated between delayed hypersensitivity and the in vitro lymphocyte responsiveness. Humoral immunity was not unequivocally impaired in Crohn's disease. Five patients with Crohn's disease proved constantly decreased total absolute lymphocyte counts in peripheral blood. The proportions of T- and B-lymphocytes and the complement-levels were corresponding to those in normal controls. No correlation was found between immunological and clinical parameters. In conclusion, patients with Crohn's disease exhibited a partial impairment of the cellular immune response, whereas humoral immunity was not affected. However, it remains to be elucidated whether this immune defect represents a basic pathogenetic factor in the onset of the disease.


New type of hepatic porphyria with porphobilinogen synthase defect and intermittent acute clinical manifestation. In two young patients with acute hepatic porphyria syndrome and persisting paralyses, which increased in intensity during intermittent occurring crisis, the activity of erythrocyte porphobilinogen synthase (delta-aminolevulinic acid dehydratase) was found to be considerably diminished, below 1% of the value of normal control persons. In contrast, the activity of uroporphyrinogen synthase was normal. Both patients have been excreting high quantities of delta-aminolevulinic acid and porphyrins in urine for years. Lead intoxication has definitively been excluded. Since the relatives also show lower activities in porphobilinogen synthase, the disease of these two patients is probably a new enzymatic type of inherited acute hepatic porphyria, the excretion profile of which is qualitatively completely different from those of the known acute porphyrias. The discovery of this porphyria confirms the theory of overlapping transition in the biochemical and clinical symptoms and analogies among acute hepatic porphyrias.


Aldosterone 18-glucuronide excretion determined with and without chromatography in human hypertensives. 24 h-urine excretion of aldosterone-18-glucuronide was determined with and without preceding paper chromatography in patients with essential hypertension (n = 50). Radioimmunoassay was performed with a highly specific antibody against aldosterone. Urine specimens determined without chromatography gave significantly higher values than aliquots which were estimated at the same time with chromatography. A highly significant correlation was found between the two methods (r = 0.91, p less than 0.0001). Without chromatography, mean over estimation in samples with concentrations in the low and middle range was on average 32 and 24% respectively, whereas aldosterone concentrations in the upper range showed a 14% over estimation. The RIA procedure for aldosterone without chromatography as here described is suitable for hypertension screening programmes to exclude known forms of primary hyperaldosteronism in which elevated aldosterone excretion rates have to be differentiated from values lying within the normal range.


[Circulating platelet aggregates during haemodialysis]. In eight chronically haemodialysed patients a significant increase of circulating platelet aggregates (method of Wu and Hoak) was observed immediately after starting haemodialysis. The number of aggregates decreased at the end of haemodialysis reaching the starting values after 360 min. The platelet interaction with the dialysis membrane surface might cause this phenomenon. Anticoagulation with heparin alone was insufficient in preventing aggregate formation during haemodialysis.


Hemodilution (HD) in patients with ischemic skin ulcers. In 25 patients with arterial occlusive disease in the clinical stage IV according to Fontaine a hemodilution down to an average hematocrit value of 0.31 +/- 0.02 was performed. Eighteen patients had peripheral ulcers of the lower limbs and 3 patients had ulcers of the upper ones. Four patients had tissular lesions both at the level of the feet and toes and hand and fingers. The average age of the patients was 43. Hemodilution was achieved by repeated withdrawals of approx. 500 ml blood, followed by reinfusion of the autologous plasma associated with infusion of substitutive solutions of low-molecular weight dextran to avoid hypovolemia. In all patients with peripheral ulcers of the upper limbs, with no exception, a good to a very good clinical effect was obtained ranging from extended to complete healing. The healing tendency of lesions in the feet and toe region was on the whole less marked and depended basically on the total number of vascular impediments found in one patient. The rheological and hemodynamic mechanism of the therapeutic effect of hemodilution, the preliminary criteria for indicating this therapy and its observed complications are discussed.


[Application of the mechanical oscillator technique for the measurement of blood density and hematocrit (author's transl)]. Density measurements were performed with an accuracy of 0.01 g/l by means of a density meter based on the "mechanical oscillator technique", on human whole blood, on plasma, and on erythrocyte concentrates. A highly significant correlation between blood density and hematocrit was found. If plasma and red cell densities are known, hematocrit can be estimated more precisely than using the centrifugation method. This fact is important if small variations of the hematocrit are to be determined. Such variations can be produced, e.g., by alteration of the transcapillary filtration equilibrium. Furthermore, the statistical distribution of plasma and erythrocyte densities allows to determine the range of variation of blood densities for certain hematocrit values and vice versa.


[Polyvinylpyrolidone-fixed hemoglobin as an oxygen carrying blood substitute (author's transl)]. The development of blood substitute oxygen carriers has branched off into several directions: stroma-free hemoglobin solutions, modelling of hemoglobin by fixation of heme or hemopeptides to polymers, filling of microcapsules with hemoglobin solution, crosslinking of hemoglobin. However, the application as blood replacement fluids in patients has not been possible so far because of several disadvantages. In this paper synthesis and properties of an oxygen carrying blood substitute are described in which the hemoglobin molecule is covalently bound to polyvinylpyrrolidone. In aqueous solution the preparation fulfills some basic requirements such as high solubility, only slightly increased oxygen affinity, and low viscosity. Normothermic perfusion experiments with isolated pig kidneys demonstrate that the solution provides an adequate oxygen supply to the organ, has no toxic side effects on kidney function, and has a significantly lower elimination rate compared to an unmodified hemoglobin solution.


[Haemodynamic studies on the blood pressure-raising effect of mineralocorticoids (author's transl)]. The effects on systemic haemodynamics of long-term administration of high mineralocorticoid doses were studied in six healthy volunteers. The subjects received the synthetic steroid fludrocortisone in a daily oral dose of 0.8 mg. Central venous and arterial pressures were recorded directly, and cardiac output was determined by dye dilution method before as well as after 1 and 6 weeks of steroid application. Within the first week of steroid administration, mean arterial pressure rose by 5.6 +/- 4.6 (+/- S.D.) mm Hg (p less than 0.025). Body weight increased by 2.5 +/- 1.1 kg (p less than 0.01), and central venous pressure by 1.3 +/- 1.4 mm Hg (p less than 0.05). An increase in cardiac index was observed in all subjects, the average increase was 0.72 +/- 0.47 1/min.m2 (p less than 0.01). Heart rate decreased. After the 6th week of steroid administration, blood pressure had risen in all subjects, the average increase in mean arterial pressure was 17.8 +/- 6.0 mm Hg (p less than 0.001). This pressure rise was the consequence of an increase in total peripheral resistance by 267 +/- 125 dyn.cm-5.s (p less than 0.01) on the average. At that time cardiac index was even lower than at the first study in five of the six subjects. Compared to the second study, heart rate had decreased further, central venous pressure had increased further, and body weight had not changed significantly. This data show that the mineralocorticoid-induced blood pressure rise is initially due to an increase in cardiac output and in its chronic phase due to an elevated peripheral resistance. The mechanism of the increase in peripheral resistance remains unclear.


[Influence of hydroxyurea on DNA synthesis of human bone marrow in vivo (author's transl)]. Four patients, who suffered from malignant, disseminated tumors but had a morphologically intact bone marrow, where given a peroral Hydroxyurea (HU) infusion in a concentration of about 5 x 10(-4) mol over a period of 10 h. As indicator of the DNA synthesis the 3H-TdR-incorporation of bone marrow, gained by puncture before, during, and/or after HU application, was measured. While using HU, the DNA synthesis was extensively inhibited. Fourteen to 16 h after discontinuing the HU it increased by the factor 1.5 to 2 of the initial value, i.e., before treatment. This is interpreted as a partial synchronization of bone marrow cells where effects of cell depletion and recruitment are not to be entirely excluded, Toxicity, such as the decrease of peripheral blood cells or nausea, did not occur.


Three variations of hairlessness associated with albinism in the laboratory rat. The relationship of three variants of hairlessness, or hypotrichosis, in laboratory rats were examined morphologically, genetically and histologically. The results indicated that the recessive gene causing the fuzzy characteristic in Wistar Furth rats and genes responsible for two other hypotrichotic coat variants in albino rats were the same gene or closely linked genes. The genes were in Linkage Group I of the Norway rat and were closely associated with the albino gene (c), with a recombination percentage of approximately 18%. The hypotrichotic animals had fewer and smaller hair follicles, smaller hair shafts, and a reduction of medullated hair shafts.


Environmental and biological effects of propoxur-impregnated strips within a laboratory animal room. Rats were exposed to propoxur-impregnated strips in a conventional laboratory animal room. The air in the room was monitored for the pesticide, and erythrocyte acetylcholinesterase activity was determined periodically. Air concentration of the pesticide never exceeded 0.8 microgram/m3, and no significant change in enzyme activity was observed.


Protein requirement of hamsters fed a natural diet. The dietary protein requirement for growing hamsters was studied in two 5-week feeding trials using 52 weanling hamsters in the first trial and 37 in the second. Diets prepared primarily from natural ingredients supplied protein from four sources and contained 13.7, 16.7 and 19.7% protein in the first trial and 10.6, 13.7 and 16.7% protein in the second. Mean daily body weight gains of 2.04, 2.04 and 1.99 g/day, respectively, in the first experiment were not significantly different. In the second trial, daily gains of 1.55, 1.79 and 1.93 g/day were significantly improved when the dietary protein was increased from 10.6 to 13.7 and 16.7%. The maintenance requirement for protein by the adult hamster was evaluated in two nitrogen balance studies using four adult males fed a diet with 7.8% protein and seven fed 5.6%. The mature males remained in positive nitrogen balance and gained a slight amount of weight with both levels of protein.


True pregnancy toxemia (preeclampsia) in the guinea pig (Cavia porcellus). In this study, normal nonpregnant, normal full-term pregnant, fasting ketotic and spontaneous pregnancy toxemic guinea pigs were compared to define the mechanism of this disease. In addition to conventional clinical, laboratory and pathologic studies, arterial blood pressure (thoracic and abdominal aortic) measurements and angiography were used. The results showed that in spontaneous cases of pregnancy toxemia, there is an aortic compression just caudal to the renal arteries. This compression reduced the aortic diameter by 22% of prerenal level as compared to 10% for fasting ketotic and normal pregnant guinea pigs. The aortic compression also resulted in a 30% postcompression reduction in blood pressure. No pressure differences were seen in the other groups. The postulated etiology for true toxemia of pregnancy in guinea pigs is, therefore, similar to that of man where aortic compression produces uterine ischemia and the resultant syndrome.


Selected biological values of the African white-tailed sand rat (Mystromys albicaudatus). Forty-three female and 44 male, sexually mature normal African sand rats (Mystromys albicaudatus) provided serum and urine for determining normal ranges of selected serum chemistry and electrolyte determinations and for routine nonfasted urinalyses. Serum chloride and serum glucose levels were greater and serum sodium levels lower for female rats. An unusually high physiological level of urine protein was detected, and it was determined that standard dipstick methods for determining urine protein levels in this species gave artificially high results. Ketouria and glycosuria were more common in males than in females, but these determinations were not correlated to blood urea nitrogen or to serum glucose levels. No association was found between body weight and any of the serum chemistry, electrolyte or urinalysis variables examined.


Cardiopulmonary, hemocytologic and biochemical effects of xylazine in goats. Intramuscular administration of xylazine at the rate of 0.22 mg/kg body weight caused a significant reduction in respiratory rates. Mean arterial blood pressure and rectal temperature were not altered. Preadministration of atropine did not affect the depth and pattern of respiration; however, the heart rate increased. A significant reduction in pH and arterial oxygen tension and an increase in carbon dioxide tension was observed after xylazine and xylazine following atropine treatment. Hemocytologic changes included a decrease in total erythrocytes, leukocytes, hematocrit and hemoglobin concentration and a rise in neutrophils with relative decrease in lymphocytes. Biochemical changes included a slight rise in potassium and a decrease in sodium concentration. Glucose level was significantly increased at maximum depth of sedation. The changes in hemocytologic and biochemical parameters returned to near preadministration level in 24-72 hours. No alteration was observed in the electrocardiogram. Xylazine was well tolerated, and the sedation was rapid in onset and lasted for about 30 minutes. The recovery was uneventful.


Idiopathic megaesophagus in a rat (Rattus norvegicus). Necropsy and histopathologic examination of a rat (Rattus norvegicus) revealed megaesophagus and gangrenous bronchopneumonia. The esophageal dilitation, mural atrophy with persistence of neural structures, regurgitation and bronchopneumonia seen in this case were similar to findings in other animals with megaesophagus.


A restraining cage for instrumented rats. A rectangular restraining cage for chronically instrumented rats was constructed of acrylic plastic. The cage allowed connections between implanted instrumentation and external recorders through a slot in the top cover. The cage was easy to load and unload through a removable cover plate, and the sidewall was adjustable to accommodate rats of diverse sizes. The cage was easy to dissemble for cleaning, and it was inexpensive.


The fabrication of plastic cages for suspension in mass air flow racks. A cage for suspension in mass air flow racks was constructed of plastic and used to house rats. Little or no difficulty was encountered with the mass air flow rack-suspended cage system during the 4 years it was used for the study of trace elements.


A plastic restraining device for rodents. A simple device was fabricated from a single piece of plastic to restrain several different species of rodents. The device served as a useful adjunct for numerous research, medical and teaching applications.


Congenital entropion in a litter of rabbits. Conjunctivitis and blepharospasm were observed in a litter of four, 2-week-old New Zealand white rabbits. Corneal opacity and neovascularization of the cornea and entropion of the upper eyelids were observed when the rabbits were examined 10 weeks later. Conjunctival cultures of these rabbits yielded normal bacterial flora. Treatment with a steroid-antibiotic ophthalmic ointment did not alter the ocular abnormalities. Surgical correction of the entropion resulted in a complete regression of all clinical signs.


The restraint of rabbits in a special sling. A special sling for the restraint of rabbits was developed for the investigation of the effects of continuous motion on the healing of intraarticular injuries. Studies of over 200 rabbits have demonstrated the sling restraint system to be effective and humane, with a restraint related mortality of less than 10%.


Fin damage in captured and reared squids. Fin damage was a major factor in the mortality of wild-caught squids kept in the laboratory. Infection of abraded fins by opportunistic bacterial pathogens impaired swimming and led to death. Serious skin abrasions were especially common in trawl-caught squids. Dipnets and jigs inflicted minimal trauma and were preferred for squid capture. Fin damage also occurred during transportation and during maintenance of squids in onshore tanks. A successful aquarium system with recycled sea water was used for squid maintenance. Hatchling, juvenile and adult loliginid squids remained healthy in closed-system aquaria for periods ranging from 1 to 16 weeks.


A technique for barium esophagram in the opossum. Single and double contrast barium esophagram examinations were performed on 42 opossums. Each animal was anesthetized with pentabarbital sodium, a catheter was placed in the esophagus, and barium or barium and air were injected into the esophagus. Two radiographs per second for 7 seconds were taken. The radiographs were reproducible and of high quality.


Adjustable metabolism units for swine.

Adjustable metabolism units for swine. A swine metabolism unit was constructed which permitted separate quantitative collection of urine and feces. The unit was built of wood and proved to be reliable. It was adapted for studies with goats, sheep and young cattle.


Anesthesia for prairie dogs.

Anesthesia for prairie dogs. The combination of 20 mg xylazine/kg of body weight and 100-150 mg ketamine/kg of body weight provided satisfactory levels of anesthesia in 63 prairie dogs, and the combination was tolerated well with a mortality rate of 3.2%.


Body temperature changes in sows during the periparturient period. Deep body temperatures were monitored with an implanted radiotelemetry device from 2 to 4 days prepartum to approximately 12 days postpartum in sows. The mean prepartum temperature of five normal sows was 38.6 degrees C, with a range of 38.3--38.9 degrees C. An increase in body temperature (1.4 degrees C) was associated with parturition. The increase in body temperature began about 12 hours before the first pig was born, peaked 1-2 hours after delivery of the last pig, and decreased during the first day postpartum but did not reach the prepartum values. Two days postpartum, the mean body temperature was about 1 degree C higher than it was during the prepartum period. The mean body temperature increased an average of 0.06 degrees C per day during the 12-day postpartum period. A diurnal pattern was evident in the body temperature variations.


Microbiological evaluation of a biological safety cabinet modified for bedding disposal. A biological safety cabinet modified for bedding disposal was tested to determine the cabinet's ability to protect operators and experiments from aerosol exposure during routine microbiological and cage cleaning procedures. Stringent test conditions were provided by modifications of standardized protocols in addition to simulated cage dumping procedures, both of which utilized bacterial aerosols as challenges. Results of standardized test procedures (with no operator present) indicated good performance in protecting both operators and experiments. Procedures involving the dumping (by an operator) of contaminated bedding within the unit showed that the cabinet was able to contain 99.96% or greater of the total particles generated.


A device for milk collection from mice.

A device for milk collection from mice. Approximately 14 days after SHN, SLN and C3H/He strains of mice gave birth, their pups were removed. After 14--16 hours away from their pups, the dam was anesthetized, injected with oxytocin and milked. The milking device consisted of a rubber-stoppered centrifuge tube containing a stainless steel catheter and polyvinyl chloride tube. It was operated by vacuum.


Orbital venous anatomy of the rat.

Orbital venous anatomy of the rat. Ten rats were embalmed, the veins of the head latex-injected, and the heads were dissected. Five rats were used to prepare corrosion casts of the venous structures of the head. It was found that the rat has an orbital venous plexus rather than an orbital venous sinus as seen in the mouse and hamster. The orbital venous plexus was formed by the external dorsal ophthalmic vein, the external ventral ophthalmic vein and numerous anastomoses between these veins. Of major interest was a large anastomotic vein located in the caudaldorsal area of the orbit. The anastomotic vein joined the orbital venous plexus and the superficial temporal vein.


Harderian gland dacryoadenitis in rats resulting from orbital bleeding. Localized necrotizing inflammation of the Harderian gland was a sequela to obtaining blood samples from rats by the orbital bleeding technique. The lesion affected a few adjoining lobules that were adjacent to ocular muscles, in contrast to the widespread inflammation of the Harderian gland which results from sialodacryoadenitis virus infection. Lesions resolved in 4 weeks by atrophy of acini in affected lobules with associated mononuclear cell inflammation and fibrosis.


Frequency of hydronephrosis in Wistar rats. Kidneys from 1806 Wistar rats were examined grossly for hydronephrosis and ureteral dilation. Hydronephrosis was seen more often on the right side (11%) than the left (0.3%). Overall frequency of hydronephrosis in males (181/1305) was greater than in females (23/501), and the frequency was statistically greater in male rats aged 5,6,8 and 9 weeks than in age-matched females.


A latex-sponge collar for partial-body plethysmography using anesthetized rodents. A latex-sponge sandwich collar was used for sealing rodents in a partial body plethsymograph. This collar formed a leak-free seal between an aerosol inhalation exposure unit and the plethysmograph. Respiratory frequency was compared in anesthetized rats and hamsters using this collar and other types of collars. The newly designed collars did not hamper breathing patterns and reduced the incidence of deaths observed using collars of another design.


Cryptosporidium cuniculus in the rabbit (Oryctolagus cuniculus). Cryptosporidium cuniculus was identified by light and electron microscopy in two apparently healthy rabbits. Organisms were firmly attached at the brush borders of intestinal epithelial cells. Cellular alterations were minimal, consisting of elongation and shortening of microvilli adjacent to the attachment sites of organisms. Various developmental stages of cryptosporidium were identified by electron microscopy.


Fecal cup for collection of feces in male rats. A cup was designed which fits around the tail of male rats. The cup was used to collect feces and made it possible to separate urine and feces completely from each other. The cup was easy to apply, remove, empty and replace, and its use did not cause noticeable stress to the animal.


Toe-clipping procedure for individual identification of rodents. A simple, easily readable system for permanent individual identification of rodents was accomplished by clipping off selected toes according to a code. Up to 10,000 animals could be consecutively numbered using this system.


A safe and simple technique for obtaining cerebrospinal fluid from rabbits. A safe and simple method for obtaining cerebrospinal fluid from the anesthetized rabbit was accomplished by cannulating the fourth ventricle. Cerebrospinal fluid (1.5--2.0 ml) was obtained for laboratory analysis. The procedure could be repeated at 2--3 day intervals without  detrimental effects.


Bile acid metabolism in the cirrhotic rat. Bile acid metabolism was studied in rats with cirrhosis induced by carbon tetrachloride (CCl4). Although the typical histologic features of cirrhosis were seen, cholestasis was not present in these animals as evidenced by a normal total serum bilirubin concentration and by a normal hepatic capacity to remove taurocholate infused intravenously. The cirrhotic rats also secreted taurocholate into bile at a normal rate. The total bile salt pool size in the cirrhotic rats was not significantly different from the pool size in normal rats (10.59 +/- 1.19 mumoles per gm. of liver (+/- 1 standard error of the mean) and 10.43 +/- 0.92 mumoles per gm. of liver, respectively). When the bile was drained externally through a chronic bile fistula, the normal rats increased the bile salt synthetic rate approximately 3-fold after 48 hours of drainage. However, the cirrhotic rats failed to significantly increase the synthetic rate for bile salts in response to biliary drainage. The normal rats also had a significant increase in cholic acid synthesis at the maximal synthetic rate, whereas the cirrhotic rats did not. These findings indicate that (when feedback inhibition is removed) CCl4 cirrhotic rats lack the ability to normally increase the activity of 7 alpha-hydroxylase and 12 alpha-hydroxylase, rate-limiting enzymes in the synthesis of bile salts.


Morphologic observations on experimental corneal vascularization in the rat. The morphologic evolution of the early events of corneal vascularization in the rat cornea induced by silver nitrate cautery were followed by light and electron microscopy. An initial acute inflammatory response occurred within the first 6 hours after cautery as evidenced by vascular dilation, diapedesis of leukocytes, and an increased vascular permeability, as manifested by distended lymphatics and the presence of extravascular fibrin. At 24 hours after injury, the hypertrophy and the prominence of nucleoli and the presence of abundant polyribosomes were the initial suggestion that vascular endothelial cells and pericytes had entered the mitotic cycle. Nine hours later, at 33 hours after cautery, the first new vessels were observed as sprouts from the capillary arcade and postcapillary venules. The experiments reemphasize the association of acute inflammation and corneal vascularization in this model and underscore the early occurrence of vascular endothelial cell replication.


Autopsy study of small cardiac scars in Japanese men who lived in Hiroshima, Japan and Honolulu, Hawaii. Japanese men long resident in Honolulu, Hawaii have significantly more ischemic heart disease but significantly fewer small cardiac scars than men in Hiroshima, Japan. These scars occur in three forms:(1)small scars in the mural myocardium which account for the difference in frequency of small lesions in the two cities and are of uncertain etiology; (2)areas of diffuse fibrosis in the papillary muscles. These are equally frequent in the two cities and are associated with advancing age and sclerosis of papillary muscle arteries; and(3)focal scars in the papillary muscles. These are more frequent in Honolulu than Hiroshima. They are healed infarcts due to ischemic heart disease and are associated with a severe degree of extramural coronary artery atherosclerosis. Small mural myocardial scars, when present, are usually found in multiple sites. Their increased frequency in Hiroshima is not explained by differences in age or heart weight. They are more common in the presence of sclerosis of intramural small arteries, but this association also fails to explain the intercity difference. It is supected that the excess of these small cardiac scars in Hiroshima males reflects past privation. There is no evidence that is is related to A-bomb radiation exposure.


Assessment of Dharmendra antigen. II. Standardisation of the antigens. Dharmendra antigen with different bacterial counts (16, 12.5, 10, 7.5, 5 and 2.5 million/ml) have been utilized for determination of skin delayed hypersensitivity in leprosy patients. It has been noted that antigen with 10 million acid fast bacilli (AFB)/ml mounts a standard early (24 hrs) as well as late (3 weeks) reaction in patients. Lepromatous patients do not show any skin reaction with this dilution. Thus, a standard Dharmendra antigen has been prepared using a considerably smaller number of organisms as compared to the International standards for Mitsuda antigen.


Assessment of Dharmendra antigen. III. Comparative study with Mitsuda antigen. Four fractions each from Dharmendra and Mitsuda antigen have been obtained by step-wise centrifugation and sonication of the antigen. These fractions have been assessed for their capacity of inducing skin delayed hypersensitivity response. While, it has been noted that all fractions of both types of antigens can induce a good early reaction, the late skin reaction is only mounted by intact bacilli of both types of antigen. When compared at a constant bacillary concentration, Dharmendra antigen has produced better early skin reaction than Mitsuda antigen, whereas the intensity of late skin reaction is almost equal with both the antigens. The hypothesis has been put forward that the early, as well as the late reaction are produced by the same antigen and this antigen is located in the protoplasm of M. leprae.


Ulnar nerve decompression by medial epicondylectomy of the humerus and a method of assessing muscle power status by totalling the muscle grading. This paper advocates the principle of ulnar nerve decompression by medial epicondylectomy of the humerus in leprosy patients presenting with ulnar nerve neuritis and early muscle weakness of ulnar nerve supplied muscles. 16 medial epicondylectomies were done on 14 patients and a follow up showed relief of nerve tenderness and an improvement in the motor power status of the muscles as shown by total grading.


Activity and effective serum level of repository sulphones (DADDS) in lepromatous leprosy. 35 cases of lepromatous leprosy were studied to evaluate the effective blood level and long depot action of acedapsone (DADDS). It was revealed that serum level of this drug is maintained well above the minimum inhibitory concentration upto 60 days following single intramuscular injection. No significant untoward effects of the drug were encountered except one case of Erythema Nodosum Leprosum and six patients with mild reactional symptoms in the form of fever and arthralgia.


A study of platelet adhesiveness in leprosy. Platelet adhesiveness was studied in fifty patients of leprosy and fifteen healthy individuals who served as control group. Platelet adhesiveness as determined by glass bead apparatus showed a trend towards elevation in patients of leprosy, being maximum in reactional phase, statistically also the increase being highly significant (p value less than 0.001). The observed increase in platelet adhesiveness may be due to marked tissue destruction and vasculitis seen in leprosy patients.


Effects of speech materials on the loudness discomfort level. Clinicians have used speech stimuli when measuring the loudness discomfort level (LDL) to determine the upper intensity limit for test stimulus presentation, and to select the saturation sound pressure level for an individual's hearing aid. Because little research has investigated the effects of speech stimuli on the LDL, this study was undertaken to compare LDLs using six commercially available speech materials on 120 normally hearing listeners. Our comparisons showed no significant differences between the mean scores for any of the speech stimuli. These findings suggest that any differences in the mean LDLs among studies probably are not attributable to the speech stimuli. The intrasession reliability of LDL measurement was also assessed using a modified method of limits procedure with 2-dB increments and instructions stressing initial discomfort. It was concluded that examiners probably could attain a high degree of reliability by simply averaging the results of two ascending trials, because 95% of these test/retest differences did not exceed 6 dB. Our findings were integrated with previous studies in terms of: (1) test stimuli; (2) listener experience; (3) instructional set; and (4) psychophysical method. This discussion points to many unanswered questions and concludes that the LDL should be interpreted very cautiously. Moreover, it is suggested that the stimuli selected for LDL measurement should reflect the examiner's purpose.


Aspects of phonological acquisition during articulation training. Acquisition of correct /s/ over time was studied in five misarticulating children and compared to data reported for younger children during normal phonological development. Changes in production of /s/ as the children were learning to produce /s/ were examined in untrained syllables session by session. These longitudinal data were explored for patterns reported to occur in normal acquisition. It was found that the misarticulating children typically shifted their responses from correct to incorrect during the acquisition period; this may be attributed to competing rules operating during the early stages of acquisition similar to the rules proposed to be operating during morphological acquisition. The children varied in the time required to acquire correct production which is comparable to the variability reported in normal acquisition. Individual learning strategies were noted in the children's productions of consonant clusters which correspond to the proposed stages of development in normal phonological acquisition.


Level of aspiration in female stutterers: changing times? In a study designed to cross-check a previous finding that females who stutter suffer from markedly low self-esteem and low levels of aspiration, 21 female stutters and 35 female controls were compared on the Rotter Level of Aspiration Board. For the female stutterers, the mean D score was +1.46, while for the female nonstutterers, it was +3.11 (t = 2.75; p less than 0.005). It was concluded that females who stutter do indeed suffer from low self-esteem, as reflected in their greater reluctance to bid for scores promising higher achievement. Comparison of the 1979 sample with a 1955 sample indicated that female stutterers may be making some generational gains in self-esteem perhaps reflecting improved status of females in our society.


Effects of listener uncertainty on articulatory inconsistency. This investigation determined the effects of listener uncertainty on articulatory inconsistency. Subjects were 15 children between three and five years of age. Each subject was tested to find a set of 45 pictures to which articulatory responses would contain sound errors on: /f,v,th,s,ts,dz/. After one week, articulatory responses to these 45 stimuli elicited by traditional picture naming techniques were compared to productions of the same words elicited in an experimental communication setting. The number of sound errors decreased significantly (p less than or equal to 0.01) in the experimental communication setting when the listener pretended to be uncertain of what the speaker said. This finding was interpreted to mean that listener uncertainty may increase the effectiveness of articulatory remediation procedures if included in treatment programs.


A child with Noonan syndrome.

A child with Noonan syndrome. The speech, language, and hearing characteristics of a child with Noonan syndrome are described in this report. The physical characteristics of this disorder are presented. Also included is a description of a pragmatic language analysis completed to provide a description of social-linguistic communication and a basis for treatment.


Planning and self-assessment in articulatory training. Children misarticulating the /r/ or /s/ speech sounds or both were identified, and assigned randomly to one of two groups. Each group received speech lessons that were similar. However, during response acquisition training, Group 1 was requested to plan articulatory movements mentally, produce the target sound, and assess the production. Group 2 practiced the training units without using the planning and assessment procedures. Group 1 exceeded Group 2 on generalization measures when the planning and assessment training was in effect.


Isovowel lines for the evaluation of vowel formant structure in speech disorders. This report describes a system of isovowel lines in the F1-F2 and F2-F3 planes and demonstrates how these linear approximations to vowel formant frequencies for a diverse sample of speakers can be used to evaluate the vowel formant structures of individuals with speech disorders. The application to disordered speech is illustrated with data for dysarthric adults, deaf adolescents, and young children with developmental errors of: Formula: (See Text) production.


A comparison of the NU-6 and W-22 speech discrimination tests for assessing sensorineural hearing loss. The Auditec recordings of the CID W-22 and NU-6 word lists were administered to 30 adults having sensorineural hearing losses. Speech discrimination scores for both tests were obtained at 16, 24, and 32 dB sensation level. Results suggest that both tests differentiate sensorineural-impaired subjects from normal listeners, although scores were significantly better for the W-22 word lists at all sensation levels. Implications for the clinical use of these measures are discussed.


SSW and dichotic digit results pre- and post-commissurotomy: a case report. A 19-year-old right-handed male with normal peripheral hearing bilaterally, was tested on the SSW and dichotic digits before and after commissurotomy. SSW results showed a definite deficit for words presented to the left ear in both the competing and noncompeting conditions. Dichotic digit results showed complete inability on the part of the subject to report the digits presented to the left ear. These findings are similar to other dichotic test results previously reported on split-brain patients.


A systematic investigation of measurement parameters of acoustic-reflex adaptation. Acoustic-reflex adaptation was assessed in 49 normal ears. Acoustic reflexes were elicited by the use of contralateral stimulation at four frequencies and five sensation levels. The results displayed the effects of stimulus frequency and sensation level on the amount of acoustic-reflex adaptation. Suggestions are presented for clinical procedures for obtaining contralateral acoustic reflex adaptation measures.


Variables influencing phonemic discrimination performance in normal and learning-disabled children. Twenty-five learning-disabled and 25 normal first-grade-age children took a phonemic discrimination test that manipulated word-pairs systematically according to degree of phonetic difference, position of phoneme contrast, and lexical familiarity. Results indicated that (1) the significantly lower performance of the learning-disabled to children as a group was due to the impaired performance by a small subgroup, (2) all three stimulus variables had significant effects on performance, (3) all combinations of stimulus variables interacted significantly, and (4) discrimination performance did not correlate with measures of receptive vocabulary or reading achievement for either group.


Static acoustic-immittance measurements. The basic principles of deriving static acoustic-immittance measurements in human ears are presented. Problems caused by differences in instrumentation, computations, and measurement technique are discussed in terms of the utility and comparisons of static acoustic-immittance measurements. Data are provided regarding the short- and long-term variabilities inherent to static measurements. Although our subject pool was relatively small, certain patterns were apparent in the short- and long-term variability inherent to static acoustic-impedance measurements. The intra-event variability about the mean static acoustic impedance was small and varied inversely with probe-tone frequency. Standard deviations were less than 50 acoustic ohms for a 220-Hz probe tone and less than 25 acoustic ohms for a 660-Hz probe tone. Session-to-session variability in static measurements varied little within subjects but varied greatly across subjects. There was little correlation between the mean and standard deviation for within-subject measurements. Standard deviations across subjects approximate a relatively constant proportion (30-40%) of the mean static value. The need for large population studies of static acoustic-immittance measurements is noted.


Prediction of hearing levels from acoustic reflex thresholds in persons with high-frequency hearing losses. This study examined the precision of the bivariate method in subjects with high-frequency sensorineural hearing loss. The current bivariate data effectively separated normal hearing subjects from those with pure tone averages of greater than 32 dB HL, in a manner consistent with the results of Popelka and Trumpf (1976) and Margolis and Fox (1977b). However, for persons with high-frequency losses the prediction of hearing levels from acoustic reflex thresholds (ARTs) appears to be complicated. Moderate hearing losses involving 500, 1000 and 2000 Hz ("speech frequencies") as well as higher frequencies were identified on the basis of elevated average ARTs for 500, 1000 and 2000 Hz. Normal ears (pure tone averages of less than 30 dB HL) were isolated from others on the basis of position on the bivariate graph. Those with (1) normal hearing in the "speech frequencies" and a high-frequency loss and (2) a mild loss in the "speech frequencies" and a high-frequency loss, could be separated from those with normal hearing by location on the bivariate graph, and from those with moderate (or worse) losses on the basis of average ART for tones. Consideration of these findings is useful in the evaluation of patients at risk for high-frequency loss, such as patients with noise exposure, and is particularly useful in cases of suspected functional impairment within this population. A modification of the bivariate method is suggested which extends its application to patient populations with a large incidence of high frequency sensorineural hearing loss.


Intonation and intelligibility of time-compressed speech. Supplementary report: English vs. French. Comparative data are reported for the intelligibility of English and of French time-compressed speech when heard spoken either in normal intonation or in intonation patterns conflicting with underlying syntactic structure. Within an overall decrement in intelligibility with increasing compression, both French and English show similar superiority functions for sentences heard in normal intonation. Results suggest a role of prosodic features in perceptual processing of French comparable to that previously reported for English.


The effect of psychophysical method on the loudness of continuous and interrupted pure tones. Using the Bekesy tracking method for loudness judgement tasks such as most comfortable loudness (MCL) and recalled loudness (RL) measurements, normal listeners have tracked continuous (C) tones at lesser intensities than interrupted (I) tones. The resulting continuous/interrupted (C/I) separations have ranged up to 22 dB. Explanations of the unexpected C/I separations have not been in agreement. The purpose of this study was to investigate whether psychophysical method has a significant effect on the C/I separation. Subjects were six normal-hearing adults, each of whom participated in three practice and ten test sessions of one hour each. Thirty-six experimental conditions were presented. The test signals were C tones, 200/200 msec I tones and 200/800 msec I tones, all at 1 kHz. The reference intensities wer 20, 50 and 80 dB SPL. The four methods were Bekesy tracking method (BTM), method of adjustment (MAdj), method of limits (ML) and method of constant stimuli difference (MCSD). Mean values for Point of Subjective Equality and C/I separation were calculated. C/I separations obtained with the BTM were significantly larger than C/I separations obtained with any other psychophysical method. These results demonstrate that C/I separations obtained during suprathreshold Bekesy tracking tasks by normal hearers are largely caused by the measurement method itself rather than by differences in C and I tone loudness. Time order errors could explain the BTM effect.


Phone rate and the effective planning time hypothesis of stuttering. Effects on syllable disfluency and phone rate (duration of phones spoken per minute) were compared in 19 adult stutterers under three reading rate conditions: control; slow normally-spoken-word-syllable timed (WS); and phone-prolongation (PP) matched to WS in syllable rate. Both phone rate and syllable disfluency were progressively reduced from control to WS to PP conditions. These results strongly support the discoordination hypothesis that any condition which facilitates initiation of phonation in coordination with articulation and respiration will reduce stuttering. A broader hypothesis is that effective planning time for voice onset coordinations is the common element that explains the power of retarded phone rate, reduction of phonatory complexity, and rhythm virtually to eliminate stuttering.


Effects of hemodialysis on pure-tone thresholds and blood chemistry measures. Eight adults suffering from end-stage renal disease and undergoing hemodialysis were subjected to pure tone audiometry before and after each of five consecutive hemodialysis treatments. In addition, pre-treatment and post-treatment blood chemistries were analyzed. Computer statistics for these audiometric and physiologic variables indicated that these subjects, as a group, did not exhibit significant differences in threshold before and after hemodialysis, although individual differences did appear. No trend regarding the direction of change was evident. However, threshold shifts did occur which might reflect transient imbalance in the labyrinthine system produced by hemodialysis.


A note on patterns of comprehension and recovery in global aphasia. Two tests of auditory comprehension (one probing knowledge of geographical locations, the other probing knowledge of familiar objects) were administered on two occasions to global aphasic patients. In addition to words drawn from the relevant lexical domains, nonsense words and words from inappropriate syntactic categories also were presented to the patients. The aphasic subjects attained more success rejecting nonsense words and words drawn from inappropriate syntactic categories than in comprehending the target words; in addition there was a consistent and surprising superiority in making correct localizations on a map as contrasted to localizing correctly familiar objects in a room. Similarly, patients' improvement across administrations was more pronounced in their heightened ability to reject the inappropriate terms rather than in increased capacity to make more accurate localizations of the target words. Overall, improvement was modest and virtually equivalent on the two measures of auditory comprehension.


Articulatory effects of monaural and binaural masking in normal speaking adults wearing palatal appliances. Ten normal speaking adults (five male, five female) performed three speaking tasks during conditions of monaural and binaural masking with and without complete palatal appliances. Significant effects on the subjects' articulation were found for the factors of masking type, palatal appliance and speaking task. No significant effects were found for monaural right- versus monaural left-ear masking or sex of the speakers. The findings are similar to previous results using binaural masking and indicate that the disruptive effect of monaural masking on the articulation of adult subjects is approximately midway between the effects of no masking and binaural masking. It is suggested that the lack of a significant effect for right-ear versus left-ear monaural masking may be due to the high degree of automatization which subjects possessed for the stimuli used in the speaking tasks.


A further evaluation of the speech of stutterers during chorus- and nonchorus-reading conditions. The claim that stutterers change their customary way of speaking during chorus-reading conditions was assessed in a single subject experimental design on the speech of three stutterers. A number of pairs of speech samples of identical prose were obtained from chorus- and nonchorus-reading conditions for each stutterer. Observers judged whether the pairs were composed of samples drawn from same (chorus/chorus or nonchorus/nonchorus) or different (chorus/nonchorus) oral reading conditions. The findings aligned with those obtained in an earlier group study. They indicated that there may be changes in the speech pattern of some stutterers during chorus-reading conditions, but this change may not occur in the speech pattern of all stutterers who respond to chorus reading conditions.


Vocal shadowing under conditions of normal and altered laryngeal sensation. Five adult male subjects vocally matched the pitches of tones in a steady-state tone matching task (SSTMT) and vocally shadowed frequency changes in a frequency modulated tone matching task (FMTMT). Matching was done in both a normal condition and a condition of topical anesthesia of the laryngeal mucosa. Pitch matching accuracy was not seriously altered in the anethesia condition, but anesthetized subjects required more time and had slower velocities in effecting transitions between tones on the FMTMT, as compared to normal. In both conditions there was a direct proportionality between interval size and each of the time and velocity variables examined, while frequency lowering was generally faster than frequency raising. Analysis of subject response strategies on the FMTMT revealed recurring patterns, described here as Overshoot, Undershoot, Oscillate and Hit. Fewer Hit, and more Oscillate, patterns were observed for the anesthesia condition as compared to normal. It was concluded that the FMTMT, as compared to the SSTMT, required finer and more rapid laryngeal control to coordinate respiratory driving pressures and glottal resistance, and hence was more susceptible to impairment of the laryngeal mucosal reflexogenic system. Implications of the data for modeling certain mechanical and physiological aspects of laryngeal control are discussed.


Verbal training to improve explanations of conservation with aphasic adults. Recent research has indicated a need to study the relationship between the language of the adult aphasic and his attempts at cognitive processing. Nine aphasic adults who demonstrated a minimal ability to explain conservation (as defined by Piaget), a cognitive task which they understood, were given verbal model training to improve their explanations of weight and liquid conservation. Each subject was given a pretest, an experimental condition during which explanations for weight conservation only were trained, a control condition during which subjects named pictured common objects, and a posttest. Order of presentation of the experimental and control conditions was varied. As a result of training, a greater number of explanations (quantitative improvement) and a greater number of explanatory concepts (qualitative improvement) were expressed for both the trained and nontrained conservation tasks. It is suggested that the improvement in conservation explanations is the result of "response facilitation effects" as described by Bandura. Furthermore, the improvement in conservation explanations is supportive of Schuell's concept of impaired linguistic retrieval mechanisms in aphasia.


Harmonic levels and vowel roughness.

Harmonic levels and vowel roughness. In this study the effects of vowel roughness on the level of harmonics in test vowel spectra were investigated. Twenty normal-speaking adult males sustained productions of each of the vowels (formula: see text) first normally and then with simulated abnormal vocal roughness, at one intensity. A tape recording of each production was rated for roughness on an equal-appearing intervals scale by 11 judges and was also analyzed to obtain its 3-Hz bandwidth amplitude-by-frequency acoustic spectrum. The median roughness rating, the level of the first five spectral harmonics, and the f0 of each production were obtained. It was found that the level of the first three harmonics for each test vowel diminished with an increase in roughness (as was hypothesized from earlier results), but the higher harmonics of /u/ and /i/ showed some reversals. A moderately large negative correlative relationship was shown between lower-harmonic levels and median vowel roughness. A possible explanation of the higher-harmonic reversals was offered. The results suggest that spectral noise level measurements may provide a more reliable acoustic index of vowel wave aperiodicity and vowel roughness than measurements of harmonic level.


Syntactic and phonological influences on children's articulation. The effects of syntactic and phonological structure on the consonant articulations of children with phonological deficits were investigated. Three structural variables were studied: syntactic structure (noun phrase, declarative sentence and passive sentence), work structure (monosyllable and disyllable) and word position (initial and final). Syntactic structure and word structure significantly affected the accuracy of articulation and the degree of word simplification. Structural complexity may contribute to overall hierarchial complexity, in turn causing children to simplify their speech.


Loudness discomfort level and acoustic reflex threshold for speech stimuli. Loudness discomfort level (LDL) and acoustic reflex threshold (ART) measurements were obtained from subjects with normal hearing using several speech stimuli, as well as broad-band and speech-spectrum noise. The purpose of the investigation was to determine the LDL for a variety of representative speech samples, and to determine the relationship between the LDL and ART for selected speech and noise stimuli. For all stimuli, LDL measurements were relatively constant, but ART measurements decreased significantly for wide-band noise stimuli as compared with the speech stimuli. Mean differences between the two measures were consistent, but individual subject data were characterized by wide variability precluding accurate prediction of the LDL from ART measurements.


Chest wall movements prior to phonation. Movements of the chest wall during the interval between an acoustic stimulus and the subject's vocal response were examined and timed in eight normal males. The reaction-time interval was divisible into two phases, a latency period with duration independent on chest wall status at the time of stimulus and an adjustment period during which the rib cage and abdomen usually moved oppositionally to achieve a prephonatory postural set. The time required for this adjustment varied significantly with lung volume, but was independent of the ventilatory phaze previously in progress.


Relationship between loudness discomfort level and acoustic reflex threshold for normal and sensorineural hearing-impaired individuals. The relationship between loudness discomfort level (LDL) and acoustic reflex threshold (ART) was determined by comparing the ART to the LDL obtained by the psychophysical method of constant stimuli. Randomly presented stimuli of 1000 Hz, 2000 Hz, and a multi-talker speech noise were presented to normal and sensorineural hearing-impaired listeners. The listener's task was to judge whether the stimulus was at a level that was: (1) too loud or uncomfortably loud; or (2) not too loud or not uncomfortably loud. Prior to the judgement of the subject acoustic reflex threshold were determined. Both LDL and ART were found to be significantly higher for the hearing-impaired group. For the pure tone stimuli, LDL for the hearing-impaired group was at or below the ART. Significant differences were shown to exist between LDL and ART for each group. A multiple regression analysis indicated significant correlations between LDL and ART. Ranges of prediction error were selected to investigate the ability of ART to predict LDL. Both pure tone and speech ART successfully predicted LDL within +/- 10 dB for a high percentage of the subjects.


Comparison of the major polypeptides of the erythrocyte nuclear envelope. The three most abundant nonhistone polypeptides (molecular weights 75,000, 71,000 and 61,000) of the avian erythrocyte nucleus have previously been isolated in the nuclear envelope fraction. They have been separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis and peptide-mapped after limited enzymatic digestion. Three enzymes -- chymotrypsin, papain and Staphylococcus aureus protease -- were used. Results obtained with each enzyme indicate strong similarities between the three nuclear envelope polypeptides. The amino acid compositions of the two most abundant polypeptides (P75 and P71) have been determined and found to be similar. Further, they readily yield large fragments upon brief alkaline hydrolysis. For both P75, and P71 the degree and the pattern of alkaline fragmentation are almost identical. A 61,000-dalton polypeptide which appears to be P61 is obtained from P75 and P71 by mild acid hydrolysis. These results establish the close chemical similarity of these predominant polypeptides in the erythrocyte nucleus and suggest that they serve related functions.


Tubulin rings: curved filaments with limited flexibility and two modes of association. Tubulin rings have been previously identified as composed of linear polymers of tubulin subunits, equivalent to a protofilament in the microtubule wall but in a curved rather than a straight conformation. We have examined and measured a number of different ring structures obtained under different conditions. The preferred curvature is indicated by a single ring of 380 A outside diameter. Radially double rings consist of two coplanar rings of 460 A and 350 A outside diameter, held together by a pattern of eight identical contacts between the 40 A subunits in the inner and outer rings. In some circumstances a larger ring, 570 A diameter, can be added to the outside, or a smaller ring, 240 A diameter, may be added to the inside of the radially double ring, in both cases repeating the pattern of eight radial contacts. The distortion of the filament from its relaxed 380 A diameter curvature apparently can be made without disrupting the longitudinal bond between subunits in the filament, but must be stabilized by the energy of the radial contact. All of these rings (single and radially double and triple) are observed to associate axially to form pairs or in some cases larger stacks. The radially double rings or an axially associated pair of these (quadruple ring) may also associate to form crystals. These are thin plates, up to 100 micrometers in extent and several micrometers thick which have been of limited use so far in diffraction studies because of irregularities in the packing of adjacent rings.


Dram shop liability and the prevention of alcohol-related problems. Aspects of dram shop imposed by 27 states and the District of Columbia are described, with emphasis on recent developments in California. Recommendations include broadening the focus of dram shop liability to include the prevention of alcohol-related problems.


Ethanol, tobacco and laterality effects on simple and complex motor performance. Tobacco had no effect on knob turning, hand tapping, foot tapping and pursuit rotor tests in 24 right-handed men, but ethanol influenced left-hand performance more than right.


A multivariate evaluation of the MAST.

A multivariate evaluation of the MAST. Five factors underlying the Michigan Alcoholism Screening Test reflect specific problem areas, while total scores classify patients along a continuum according to degree of alcohol misuse. For most purposes, a simpler unit weighting method of scoring may be used in place of differential weights.


Psychometric properties of the MAST and two briefer versions. The discriminative value and internal consistency of items of the MAST, MAST-10 and MAST-13, as well as the predictive validity of the MAST-10 and MAST-13, are examined in the scores of 200 motorists arrested for driving while intoxicated.


Self-regulation and sense of competence in men alcoholics. Although alcoholics' performance on three measures of self-regulatory competence was markedly inferior to that of nonalcoholics, alcoholics' overestimates of their ability and underestimates of their limitations were greater than those of nonalcoholics.


Drinking as conformity; a critique of sociological literature on occupational differences in drinking. Research on occupational differences in drinking has focused on deviant drinking. The deficiencies of this perspective are discussed, and a subcultural theory is proposed.


A note on the effects of changes in alcohol control policies in the Canadian North. Of three communities changing their alcohol control policies, only Frobisher Bay, the most isolated, experienced a noticeable decrease in arrests for assault and public drunkenness.


Characteristics of detoxication of patients referred to alcoholism treatment programs. An attempt to predict referrals to an alcoholism treatment program from a general detoxication population was largely unsuccessful, suggesting that referrals are made on a subjective basis.


Drinking behavior of children in Santiago, Chile. Eighty per cent of the 9-year-old children studied had consumed alcohol, usually a beverage that was sweet and of low alcohol content; 28% drank once a week, 23% twice a week and 9% every day.


Gastrointestinal hormone profile in renal insufficiency. Fasting serum gastrin, cholecystokinin, glucagon, and gastric inhibitory polypeptide concentrations were simultaneously measured in normal subjects and in patients with different degrees of renal failure. Values of gastrin, cholecystokinin, gastric inhibitory polypeptide, and glucagon were significantly higher in all patients with serum creatinine concentrations greater than 3 mg/dl than in controls (P less than 0.01). The degree of renal insufficiency was significantly correlated (P less than 0.05) with serum concentrations of each hormone, but no significant linear correlation existed among the serum concentrations of different gastrointestinal hormones in individuals. Hemodialysis did not significantly alter predialysis serum gastrin, cholecystokinin, or glucagon concentration, but the serum gastric inhibitory polypeptide concentration decreased by 30% (P less than 0.01) after hemodialysis. The disproportionate increases of hormones with antagonistic actions may alter gastrointestinal function in renal insufficiency.