Aortic dissection fifteen years after surgical repair of aortic coarctation. A case of fatal dissection of the aorta fifteen years following successful surgical repair of aortic coarctation is reported. Histologic secretions of the wall of the proximal aortic segment showed significant thickening and degenerative changes in the media which were not present in the distal aortic segment. This suggests that irreversible structural changes may have occurred prior to surgical repair of the coarctation and supports the view that early surgical repair of this condition is desirable.


Youthful hypercholesteremia: its associated characteristics and role in premature myocardial infarction. Hypercholesteremic medical students were different from their normocholesteremic classmates in a variety of ways. When students are grouped by cholesterol level in medical school, gradients across the means of biological, physiological, physical, and psychological characteristics are found. The hypercholesteremic students were older, shorter, and heavier, with younger mothers, less depression, less anxiety and less overall nervous tension under stress. Compared with their normocholesteremic classmates, youthful hypercholesteremics were more than 30 times as susceptible to episodes of acute myocardial infarction occurring 13 to 21 years after the high cholesterol levels were measured. Ten male medical students who subsequently sustained a myocardial infarction, most of whom were known to have had hypercholesteremia in youth, were significantly different at the outset from their 103 hypercholesteremic classmates who have not had such an episode. On the average, the precoronary individuals in medical school were shorter in stature, were older, had more overall nervous tension under stress, were more tired on awakening and had lower academic standing. The combination of hypercholesteremia and a personality profile denoting sensitivity and vulnerability to stress best characterizes this group of ten subjects who sustained a myocardial infarction at an early age. These findings suggest that it may be possible to differentiate young hypercholesteremics who are highly susceptible to myocardial infarction from their hypercholesteremic peers with relatively low susceptibility on the basis of personality profile.


Diarrheagenic effect of volume expansion: intestinal fluid secretion without mucosal adenyl cyclase stimulation. Rapid intravenous saline infusion causes secretion of isotonic fluid by the canine duodenum. The duodenal fluid secretion is not accompanied either by increased adenyl cyclase activity in the mucosal epithelial cells or by widening of the "tight junctions" between epithelial cells. These data clearly indicate that the diarrheagenic effect of volume expansion is not mediated by the adenyl cyclase system. Furthermore, these data provide support for the concept that, when increased mucosal adenyl cyclase activity is associated with gut fluid secretion, the adenyl cyclase stimulation is a primary event, and is not secondary to the transmucosal isotonic fluid movement.


Active and passive immunization to angiotensin in experimental acute renal failure. A number of studies support, and others fail to support, the concept that the renin-angiotensin system plays a key role in the pathogenesis of acute renal failure. This study, employing active and passive immunization against angiotensin II, was designed to examine the primacy of circulating angiotensin as a mediator of this syndrome. Neither mode of immunization significantly affected the degree of azotemia or the marked reduction of inulin clearance expected in rats subjected to glycerol-induced myohemoglobinuria. Twenty-four hours after challenge, inulin clearance (Cin) in actively immunized rats fell to 3.2% of control and that of unimmunized rats given the same dose of glycerol was 2.5% of control. Although there was some variation among groups of passively immunized rats, Cin of one group being 18% of control, Cin of the other groups was less than 3% of control. The dose and binding capacity of the immune globulin used here were essentially the same as those reported in another study in which immunization was thought to be of prophylactic value in rats subjected to s.c. administered glycerol injections. Technologic differences unrelated to immunization are suggested to have caused the difference in results in the two studies, and it seems doubtful that circulating angiotensin plays a key role in the pathogenesis of myohemoglobinuric acute renal failure in the rat.


Nephron functional heterogeneity in the postobstructive kidney. The purpose of this study was to determine the distribution of nephron filtration rates between superficial and juxtamedullary nephrons (S/J ratio) in kidneys studied immediately after relief of 24 hr total obstruction (acute) and after relief of prolonged partial obstruction (chronic). Injection of 14C-ferrocyanide and microdissection (modified Hanssen's technique) was used to provide an index of superficial and deep nephron glomerular filtration rate (GFR), and standard clearance determinations were done. In normal kidneys S/J ratio of 14C content (nephron GFR) was 0.73 plus or minus 0.03, a value similar to those obtained by other workers. After relief of acute obstruction, nephron GFR was too low for accurate measurement in 22% of superficial and 13% of deep nephrons. The mean S/J ratio of 14C content was similar to control, being 0.67 plus or minus 0.07, with only three of seven kidney showing loss of the normal S/J ratio. Since redistribution of nephron GFR was an inconsistent finding, while marked diuresis and natriuresis occurred in all rats, it appears that redistribution of nephron GFR is not an important factor in the phenomenon of postobstructive diuresis. After relief of chronic obstruction, diuresis and natriuresis were less marked but the mean S/J ratio of 14C content was 0.95 plus or minus 0.11, and in the majority of kidneys (six of eight), there was loss of distinction between superficial and deep nephron GFR. This redistribution of nephron function after relief of chronic, rather than acute, obstruction may be due to the more severe structural damage to the renal medulla of such kidneys and, although not responsible for postobstructive diuresis, it may be important in the diminished capacity of the chronically hydronephrotic kidney to conserve salt and water.


The effect of ischemia on renal blood flow in the dog. Renal blood flow (RBF) and the distribution of cortical blood flow (microspheres) were measured in the dog after 90 min of total unilateral renal ischemia. RBF was 21% greater than control 2 min after release of the renal artery occlusion, and returned toward control 60 min later. At 2 min after release there was a small but significant increment in deep cortical blood flow which reverted to control by 60 min. When renal artery occlusion was maintained for 180 min, return of blood flow was blunted at 2 min after release of the occlusion, but was not significantly different from control within 10 min after release. Clearance rates of inulin and para-aminohippurate (Cin and Cpah) were 81 and 82% below control after release of occlusion. These data demonstrate that in the dog there is prompt and complete return of blood flow to or above control levels after complete renal artery occlusion. There was no evidence for the "no-reflow" phenomenon.


Lanthanum permeability of tight junctions along the collecting duct of the rat. The permeability of the tight junctions (zonulae occludentes) was evaluated along the entire length of the collecting duct of the rat using a lanthanum tracer technique. Nine rats with hereditary hypothalamic diabetes insipidus were studied using standard micropuncture and clearance techniques. Glomerular filtration rate (GFR) estimated from inulin clearance, urine and plasma osmolality (U/Posm) and urine flow rate (V) were determined in eight of nine animals. During either sustained diuresis (five animals) or vasopressin-induced antidiuresis (four animals), individual surface convolutions of distal convoluted tubules or early cortical collecting ducts were preserved for ultrastructural examination by intraluminal microperfusion with a glutaraldehyde-formaldehyde fixative followed by a second microperfusion with a lanthanum tracer. Mean GFR during diuresis was 6.31 plus or minus se 0.63 ml/min/kg of body wt and v=797 plus or minus se 108 mul/min/kg or 13.6 plus or minus se 2.2% of the filtered load of water. After administration of exogenous vasopressin, V fell to 311 plus or minus 157 mul/min/kg or 5.2 plus or minus se 3.8% of the filtered load of water and U/Posm rose from 0.658 plus or minus se 0.043 to 2.124 plus or minus 0.454. Tight junctions of cortical and outer medullary segments of the collecting duct resisted lanthanum penetration. Tight junctions of the inner medullary and papillary segments of the collecting duct were freely permeable to lanthanum suggesting the presence of a paracellular shunt pathway for solute and water movement. The results were independent of the presence or absence of vasopressin. Physiological studies have previously demonstrated that cortical and outer medullary segments of the collecting duct have a low urea permeability while inner medullary and papillary segments of the collecting duct have a relatively high urea permeability. The possibility is suggested that urea movement across the inner medullary and papillary segments of the collecting duct may occur, at least in part, via a paracellular pathway formed by the nonoccluding tight junction and the lateral intercellular space.


Whole kidney volume/pressure relationships. We measured changes in kidney volume and intrarenal pressure produced by step-wise, steady state increases and decreases in ureteral pressure (UP). The purpose of such maneuvers, termed exercises, was to examine the relationship between changes in kidney volume and the changes in intrarenal pressure responsible for those in kidney volume. Changes in kidney volume were assessed from directly measured changes in kidney weight. Changes in the intrarenal pressure distending the renal capsule (renal subcapsular pressure [RSCP]) were measured by a strain guage diaphragm-type microtransducer placed between cortex and capsule. We measured these whole kidney volume/pressure events before and after saline loading and examined their relationship to changes in renal function following saline loading. We found that after four "exercises", the kidney became more complaint, i.e., occupied a larger volume at any given UP or RSCP, and that the compliance of the kidney was further increased following saline loading. However, about one hour after saline loading, RSCP returned to or below pre-saline loading levels and renal volume returned to pre-saline loading levels; nevertheless, the natriuresis persisted. Thus, an increase in renal volume is not necessary to sustain increased sodium and water excretion in post-saline loading. Finally, we found evidence that the renal capsule provides the major force opposing expansion of outer cortex when intrarenal pressure is increased.


The ultrastructural identification of tissue basophils and mast cells in Hodgkin's disease. Numerous basophils were identified ultrastructurally in a tumorous lymph node from one of 10 patients with Hodgkin's disease. The tissue basophils displayed the same morphologic characteristics as peripheral blood basophils and differed ultrastructurally from mast cells in the same specimen. Large numbers of mast cells were occasionally seen in tumor tissue of patients with Hodgkin's disease. Many of the mast cells in Hodgkin's tumor revealed structural alteration of granules as well as evidence of degranulation when compared with mast cells in tumor-free lymph nodes of patients with Hodgkin's disease. These results indicate that basophils and mast cells may play a role in the inflammatory response in Hodgkin's disease.


Effects on platelet function of removal of platelet sialic acid by neuraminidase. A number of investigators have implicated sialic acid on the surface of platelets in platelet function. In this study we have quantitated the amount of sialic acid removed by purified neuraminidase from the surface of washed platelets of man, rabbit, or pig and examined the effects of this removal. Purified neuraminidase did not induce the release of platelet granule contents. Platelets were pre-labeled with 14C-serotonin for measurement of the release reaction or with 51Cr for determination of adherence to a collagen-coated surface or damaged aortic surface, and for in vivo platelet survival studies. Washed, neuraminidase-treated platelets were resuspended in Tyrode's solution containing 0.35 per cent albumin or in citrated platelet-free plasma from the same species. Both resuspending fluids contained apyrase. Aggregating agents tested were ADP, acid-soluble collagen, thrombin, ristocetin (with human platelets), polylysine, and serotonin (with rabbit platelets). With all of these agents except polylysine, aggregation of neuraminidase-treated human or rabbit platelets was slightly enhanced compared with control platelets; aggregation of pig platelets was unchanged. When release-inducing agents were used, neuraminidase-treated platelets released more of their 14C-serotonin than control platelets. The extent to which rabbit platelets adhered to a collagen-coated surface or to the damaged surface of everted rabbit aorta was unchanged by pretreatment of platelets with neuraminidase. Therefore it seems unlikely that sialic acid is involved in platelet adherence to collagen. When more than 15 per cent of total sialic acid had been removed from rabbit platelets, they were completely cleared from the circulation within 1 hour of their injection into rabbits. When 8 to 10 per cent of total sialic acid had been removed, the platelets were not cleared immediately from the circulation but were cleared more quickly than control platelets. Thus, although removal of up to 65 per cent of platelet sialic acid has only a slightly enhancing effect on platelet aggregation and release in vitro, removal of as little as 8 to 10 per cent results in the recognition of platelets as "foreign" in vivo.


Acid phosphatase demonstrated ultrastructurally in mast cell granules altered by pinocytosis. Rat peritoneal mast cells concentrate colloidal gold particles from the peritoneal fluid in subsurface vacuole-like spaces from which the particles are pinocytosed into small vesicles, into cytoplasmic granules that appear smaller than the specific granules and possess in homogeneous content, and into the specific cytoplasmic granules. Acid phosphatase activity was not consistently or unequivocally demonstrated in the specific granules of mast cells unexposed to colloidal gold. However, mast cells pinocytosing gold exhibited strong activity almost exclusively in the infrequent specific granules which contained gold particles, further indicating that these granules function as heterophagic secondary lysosomes. The pinocytic vesicles and small granules containing endocytosed gold spherules lacked acid phosphatase and apparently derived from an exogenous rather than a Golgi source. The small gold-laden granules appeared, therefore, not to represent an immature or precondensation stage of the specific cytoplasmic granule.


Acute cholestasis induced by lithocholic acid in the rat. A freeze-fracture replica and thin section study. Sodium lithocholate (LCA) was continuously infused intravenously (0.1 or 0.2 mumole per minute per 100 gm. body weight) in Wistar rats with a bile fistula for up to 4 hours. The higher dose induced complete cholestasis within 2 to 3 hours, whereas the low dose reduced the biliary output to less than 10 per cent of the preinfusion level by the 3rd hour. Ultrastructural changes which were primarily localized to the bile canaliculi and the pericanalicular region were seen 30 minutes after the onset of bile acid infusion. Dilation of the bile carnaliculi, loss of canalicular microvilli, prominence of the pericanalicular ectoplasm, and a characteristic lamellar transformation of the canalicular membrane developed, which became more prominent and widespread with progression of time. A freeze-fracture replica study revealed that the canalicular microvilli became transformed through widening and flattening into multilamellar foldings. Intramembranous granules of the canalicular membrane appeared to have become redistributed, being few or absent in the "transformed" regions. In addition, a sharply angulated, crystalline material was seen in occasional bile canaliculi. This material appeared as a negative image in thin sections, indicating its solubility in organic solvents which were used for dehydration. With the lower dose of LCA, subcellular changes were similar to, but less severe and which accompany an acute cholestasis induced by LCA is attributable to the accumulation of this compound in the bile canaliculus and its vicinity. LCA presumably causes an asymmetric perturbation in the molecular organization of the canalicular membrane which results in ultrastructural alterations and failure of fluid transport. In addition, precipitates of LCA appear to form in the bile canaliculi and may contribute to cholestasis.


Anatomy and histology of aorta of White Carneau pigeon. On the basis of anatomical and histologic studies, four distinct zones of the aorta of the atherosclerosis-prone White Carneau pigeon were defined. From its origin to about 1 cm. above the level of the celiac artery (the elastic zone), the aorta had a media composed of alternating lamellae of smooth muscle cells and fibroblasts with elastic plates between them. Distal to the elastic zone was the transitional zone, which was about 1 cm. long and ended at the level of the celiac artery. At this level there was an intimal cushion of longitudinally arranged smooth muscle cells that was present at birth but increased in thickness with age; an occasional lymphocyte-like cell was also present in the cushion. Typically, the atherosclerotic lesion originated in the smooth muscle cell cushion. In the transitional zone the media had an elastic architecture in the lateral third, the remainder being predominantly muscular. The segment of aorta from the celiac artery to the ischiadic arteries (hybrid zone) had a hybrid architecture with a thick muscular anterior wall and a thin elastic posterior wall. The structure distal to the ischiadic arteries was purely muscular (muscular zone). The presence of intimal smooth muscle cells in the transitional zone at birth, in the precise location where the "classic" atherosclerotic lesion develops months later, suggests that atherosclerosis develops within preexisting smooth muscle cell cushions which apparently represent a normal histologic feature of this area.


Studies on liver regeneration. Deoxyribonucleic acid synthesis in the isolated perfused liver after in vitro and in vivo partial hepatectomy. A new method for studying liver regeneration has been introduced. In the isolated perfused liver partial hepatectomy has been performed and -3H-thymidine incorporation into DNA was observed. The short term incorporation observed in vitro was comparable to that observed in vivo under similar conditions. The results suggest that similar regenerative mechanisms are operating in vivo and in vitro, and that the liver is at least one source of the regenerating stimuli.


Scanning electron microscopy of human and rhesus monkey kidneys. Human kidney biopsies fixed by immersion fixation and a rhesus monkey kidney fixed by vascular perfusion were critical point-dried and studied by scanning electron microscopy. The surface morphologies of the parietal and visceral epithelial cells and cells lining the uriniferous tubules are described. Many instructive views of these cells as well as some new nephronal features are presented. This study demonstrated that both scanning and transmission electron microscopy may be undertaken on the same biopsy sample. In view of these results, the possibility of using scanning electron microscopy for routine diagnosis of human biopsies is discussed.


Pathology of the liver in Reye's syndrome. A study of six patients with Reye's syndrome indicated that, by light microscopy, inflammation and necrosis of liver cells are especially prominent in fatal cases. Contrary to previous reports, electron microscopic examination indicated that, aside from loss of matrix dense granules, alterations in mitochondrial structure were minimal or absent. Although an increase in the number of liver cell microbodies has been reported, no such increase was apparent in the present study. The most unusual ultrastructural change in microbodies in the present study was the appearance of noncrystalline cores in the matrix. No ultrastructural features served to distinguish patients who died from those who survived. Although derangement of mitochondrial function may be important in the pathogenesis of Reye's syndrome, such derangement is not necessary reflected in the ultrastructure of mitochondria.


Alterations of rat liver lysosomes and somooth endoplasmic reticulum induced by the diazafluoranthen derivative AC-3579. III. Mechanism and site of action. To elucidate the mode of action of AC-3579, a diazafluoranthen derivative, the effects of the drug were tested, in incubations with rat liver homogenates on three phospholipases: the endogenous microsomal phospholipase A and the exogenous phospholipases A2 and C. The rates of hydrolysis of phosphatidylcholine and phosphatidylethanolamine, the main liver phospholipids, were significantly decreased in liver of treated animals. This inhibition was more marked in experiments with exogenous phospholipase A than with phospholipase C. For phospholipid the difference observed may be due to the decrease in activity of endogenous phospholipase A in livers of treated rats. On the other hand, the addition to the incubation media of AC-3579 or of homogenates of AC-3579-treated rat livers did not modify the action of the three phospholipases on phospholipids from normal rat liver homogenates. It is concluded that AC-3579 forms with the hydrophobic moiety of the phospholipids of smooth endoplasmic reticulum a reversible complex less accessible to the activity of phospholipase A. This mechanism accounts for the decrease in phospholipid catabolism, previously observed in vivo, which leads to hypertrophy of smooth endoplasmic reticulum and to the formation of lamellate cytosomes.


The aortic tunica media of the developing rat. I. Quantitative stereologic and biochemical analysis. The tunica media of thoracic aortas from female rats in age from newborn to 12 weeks were analyzed quantitatively by using stereologic techniques in the electron microscope. Collagen, elastin, smooth muscle, myofilaments, Golgi apparatus, ergastoplasm, and surface to volume ratios were among those components quantified. These parameters were correlated with measurements of medial thickness, blood pressure, and tangenital tension in the wall and with biochemical estimates of collagen and elastin. A progressive increase in morphologically recognizable collagen in the media was in parallel with the increasing tangenital wall tension. Biochemical analysis indicated the presence of much soluble collagen in the early stages of development. Elastin was the major component contributing to increasing wall thickness. The elastin laminae were completely formed by 4 weeks of age, but further elastin was laid down as branches extending between medial cells in the aortas of animals between 2 and 12 weeks of age. Smooth muscle cells were ovoid in young animals and contained large amounts of ergastoplasma and Golgi apparatus, but very few myofilaments. With advancing age, these cells became irregular in outline, and their surface to volume ratios doubled. The myofilament volume increased greatly during development, associated with a decrease in "undifferentiated" cytoplasm, ergastoplasm, and Golgi apparatus. The maximal development of the latter two organelles was coincident with large increases in the connective tissue components.


The aortic tunica media of the developing rat. II. Incorporation by medial cells 3-H-proline into collagen and elastin: autoradiographic and chemical studies. Four-week-old rats received intraperitoneal injections of 3-H-proline, and their thoracic aortas were removed at various times after injection. Autoradiography at the electron microscopic level was carried out on this tissue, together with isolation and chemical analysis of tritiated proline and hydroxyproline from procollagen, and elastin fractions. Autoradiograpic results were expressed in terms of tissue component volumes as calculated by morphometry. Autoradiographic grains were concentrated over medial cells 15 minutes after injection of label. By 30 minutes after injection some extracellular label was present as well; at 3 hours postinjection, large numbers of grains were found overlying cell surfaces, as well as over collagen and elastic fibers. Most grains were present over collagen and elastic tissue 10 hours after injection, although some intracellular labeling persisted. On a grain per unit volume basis, intracellular label steadily decreased over the time interval studied. Collagen showed maximal labeling at 3 hours, but elastic tissue labeling increased up to 10 hours postinjection. Chemical isolation of 3-H-proline and 3-H-hydroxyproline from the three fractions showed that incorporation of label into collagen and elastin is, on a time basis, consistent with autoradiographic labeling and that the labeling products are, in fact, these proteins, to the exclusion of nonspecific labeling.


Striated membranous structures in renal glomerular tufts. An electron microscopy study of 340 human renal biopsies. Striated membranous structures are membranes 200 plus or minus 20 A thick. They are very common in both normal and pathologic human glomeruli, since they were found in 221 of 340 renal biopsies studied. Their appearance varies according to the plane of the section: on cross-section they resemble a pile of plates or double longitudinal bands. On tangential section they have an areolar appearance. Striated membranous structures are located in the basement membrane, mesangial matrix, or extracellular pathologic deposits such as amyloid or "immune" deposits. These membranes, probably double layered, are of unknown origin. They might derive from the focal or total lysis of cellular elements included within basement membrane-like material or extracellular deposits.


Hepatic lesions in mice after continuous inhalation exposure to 1,1,1-trichloroethane. Male CF-1 mice (24 to 34 gm.) were exposed to either 250 p.p.m. or 1000 p.p.m. of 1,1,1-trichloroethane in air continuously for 14 weeks. Control mice were exposed to room air. Serial sacrifice of exposed and control mice from 1 to 14 weeks demonstrated significant changes in the centrilobular hepatocytes of animals in the 1000 p.p.m. group. Moderate liver triglyceride accumulation was evident in the 1000 p.p.m. group and peaked at 40 mg. per gm. of tissue (wet weight) after 7 weeks of exposure. Partial recovery was indicated by a decrease in the hepatic triglyceride level of 16 mg. per gm. by 14 weeks of exposure to 1000 p.p.m. Electron microscopic evaluation revealed that cytoplasmic altertions were most severe in centrilobular hepatocytes in the 1000 p.p.m. group and were mild to minimal in the 250 p.p.m. group. These alterations consisted of vesiculation of the rough endoplasmic reticulum, with loss of attached polyribosomes, increased smooth endoplasmic reticulum, microbodies, and triglyceride droplets. Some cells had ballooned cisternae of the rough endoplasmic reticulum. Necrosis of individual hepatocytes occurred in 40 per cent of the mice exposed to 1000 p.p.m. for 12 weeks. This necrosis was associated with an acute inflammatory infiltrate and hypertrophy of Kupffer cells. Comparison of these findings to the results obtained by other investigators studying dichloromethane indicates that the pathologic alterations observed with 1,1,1-trichloroethane were similar to those observed with dichloromethane, except for different time courses of the effects and different degrees of recovery. The toxic effects of 1,1,1-trichloroethane were of a type similar to those produced by carbon tetrachloride, but they appeared to be much less severe.


The effects of acute cadmium administration in the liver and kidney of the rat. Light and electron microscopic studies. A single injection of cadmium acetate givenintravenously to rats produced, at 16 hours, liver damage but no observable kidney changes. Ultrastructure of the liver revealed more profound changes in parenchymal cells than in Kupffer cells. The most prominent changes were single parenchymal cell necrosis, deterioration of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, autophagocytosis, and mitochondrial degenerative changes. Lesions of Kupffer cells were not prominent, although occasional areas of cytoplasmic degradation and increased vacuolation were observed. Dewquamation of these cells appears also to be a frequent finding in cadmium intoxication. Accumulation of platelets, cellular debris, inflammatory cells, and fibrin in the sinusoids may be the cause of the occasionally observed focal necrosis. Although the present experiment does not simulate any known clinical situation, these composite studies provide a morphologic basis for hepatic dysfunction following acute cadmium administration as well as an ultrastructural basis for thebetter understanding of the synergistic actionof cadmium with other substances such as endotoxins.


Ultrastructure of skeletal muscle in patients with Parkinson's disease and upper motor lesions. Ultrastructural studies of muscle biopsies from the vastus lateralis of the quadriceps in seven patients with Parkinson's disease and six patients with upper motor lesions are presented. All patients showed varying degrees of mitochondrial changes. Loss of outer membranes or abnormal inner membranes were observed alone or in combination. A reduced number of mitochondria was also noted in some cases. A disorder of filaments was seen. It is assumed that the mitochondrial changes are connected with the altered oxidative capacity previously observed in these patients.


Cost-benefit analysis of two decision criteria for spondee threshold measurements. Normal-hearing subjects were tested and retested using two spondee threshold criteria: a strict 50 percent correct rule and a 50 percent or 75 percent correct (or both) rule. The 50 percent criterion produced lower thresholds at the cost of poorer test-retest reliability and longer test durations. Both decision rules gave lower threshold SPL values and required less testing time during the second trial. A proposed benefit-cost ratio model indicated that the 50 percent or 75 percent (or both) decision rule gives a better return on the investment of clinical effort.


Pantomime recognition in aphasics.

Pantomime recognition in aphasics. A pantomime recognition test was developed to study the extent of impairment of pantomime recognition and the relationship between pantomime recognition and verbal deficits in asphasics. This test requires no verbal instructions to the subject and only a simple pointing response. A description and rationale for the test are presented. This new test and three tests of verbal abilities (Verbal Recognition Test, Naming Test, and the Porch Index of Communicative Ability) were administered to four groups of subjects: aphasics, right-hemisphere damaged, subcortically damaged, and normals. Results indicate (1) greater impairment of pantomime recognition ability in aphasics than the other groups of subjects and (2) high correlations between impairment of pantomime recognition and impairment of verbal abilities in aphasics. Our findings are consistent with previous clinical reports and experimental data showing that aphasics commonly demonstrate impairment in gesture and pantomime. We conclude that aphasia is best understood as a general impairment of symbolic communication that includes nonverbal as well as verbal deficits.


Intraoral air pressure as a feedback cue in consonant production. The effects of oral-sensory deprivation on the production of consonants was studied using narrow phonetic transcriptions and measurements of intraoral air pressure and duration. The speech materials were 20 bisyllabic words produced both in isolation and in sentences, and sentences that included words with 34 stop variants. These utterances were produced by four normal talkers and by the same talkers when deprived of oral sensation. The state of oral-sensory deprivation was induced by a series of mandibular, infraorbital, and palatal injections of 2 percent xylocaine. The talkers also scaled levels of effort used to produce the syllables /pa/ and /ba/, both with and without the anesthetic. In general, after the administration of the anesthetic, the characteristic tongue carriage of the talkers was shifted posteriorly, the rate of speech was slower, and there were minor imprecisions in articulation consisting primarily of alterations in lip and tongue activity. In addition, consonants were produced with slightly greater intraoral air pressures and longer durations. The talkers had no difficulty in scaling levels of effort in either the normal or the anesthetic conditions, and maintained a linear relationship between effort and intraoral air pressure in both conditions. The results suggest that the talkers used more effort in producing speech in the anesthetic condition and are untenable with the idea that intraoral air pressure constitutes an important feedback parameter in controlling articulation. The speech produced by the talkers while anesthetized (that is, while without sensation in the mouth) was reasonably precise and must be postulated to have been under the control of a pressure-sensing system other than a closed feedback loop.


Acoustic-reflex response to sustain signals. Acoustic-reflex activity was observed for 10 normal-hearing young adults using three sustained activating signals: 500-Hz tone, 4000-Hz tone, and broad-band noise. Reflex activity was observed over a period of three to five minutes at activator levels of 5, 10, and 15 dB above individual acoustic-reflex thresholds. General findings were that (1) acoustic-reflex adaptation was present to some degree for all three activating signals, (2) the amount of reflex adaptation varied with the spectrum of activating signals (reflex adaptation was greatest for the 4000-Hz activator, less for the noise activator, and least for the 500-Hz activating signal), (3) the rate of reflex adaptation differed with activator spectrum (reflex-adaptation rate was relatively rapid for the 4000-Hz activator, slower for noise, and much slower for the 500-Hz activating signal), and (4) reflex adaptation did not appear to vary systematically with activating-signal level except for the 500-Hz activator, in which case reflex adaptation appeared to begin earlier in time and to be of greater magnitude as the activating-signal level was increased.


Articulatory inconsistencies in the speech of normal children. The spontaneous speech of three children about three years old was recorded and transcribed into CnV syllabic units. Cn represents any number of consonants preceding a vowel and is not lexically constrained. Inconsistent production of /s/ and /z/ was found to be related to motor sequencing constraints independent of word boundaries. The results support a model of speech physiology as well as theoretical formulations of child speech production within an adult phonological system.


Measuring in-the-ear gain of hearing aids by the acoustic reflex method. The gain of hearing aids is conventionally measured in a hard-walled 2-cc coupler. It has become increasingly apparent, however, that many interacting variables can affect the aid's behavior in an individual ear quite significantly. Therefore it is desirable that any departure from coupler response be known. A number of methods have been used to measure real-ear gain, some of which require expensive or nonstandard instrumentation. An alternative method is described, based on measurements of aided and unaided acoustic reflect thresholds that appears to have certain advantages over other methods. Sound-field intra-aural reflex thresholds for six one-third-octave noise bands were determined for 20 subjects using a postauricular aid under three conditions--unaided, aided/ear occluded, and aided/ear nonoccluded. Real-ear gain was defined as the difference in decibels between aided and unaided thresholds. Results showed wide individual differences in real-ear response. Average occluded real-ear gain was about 5 dB greater at 1.6 k Hz, and about 5 dB less at 3.15 k Hz, than the gain in the artificial ear. When the aid was coupled to the open ear, average real-ear response was down at all frequencies relative to the 2-cc coupler, although relative to the closed-ear response frequencies above 1.6 k Hz were emphasized. It is argued that real-ear response can be expected to vary considerably depending on the location and orientation of the microphone of the aid on the head or body. It is suggested therefore that real-ear measurements be part of every aid selection procedure, especially for persons with a reduced dynamic range. Response modifications might then be possible to enable the critical speech frequencies to be heard at a comfortable level.


Memory for speech and speech for memory. Thirty kindergarteners, 15 who substituted /w/ for /r/ and 15 with correct articulation, received two perception tests and a memory test that included /w/ and /r/ in minimally contrastive syllables. Although both groups had nearly perfect perception of the experimenter's productions of /w/ and /r/, misarticulating subjects perceived their own tape-recorded w/r productions as /w/. In the memory task these same misarticulating subjects committed significantly more /w/-/r/ confusions in unspoken recall. The discussion considers why people subvocally rehearse; a developmental period in which children do not rehearse; ways subvocalization may aid recall, including motor and acoustic encoding; an echoic store that provides additional recall support if subjects rehearse vocally, and perception of self- and other- produced phonemes by misarticulating children-including its relevance to a motor theory of perception. Evidence is presented that speech for memory can be sufficiently impaired to cause memory disorder. Conceptions that restrict speech disorder to an impairment of communication are challenged.


Some statistical characteristics of voice fundamental frequency. Two experiments are reported in which the magnitude of sampling errors associated with estimates of the mean, median, and standard deviation of voice fundamental frequencies (fo) during oral reading is investigated as a function of sample size. In one experiment, voices are sampled with fixed time windows. In the other experiment, results of fo analysis are compared for single-sentence voice samples and paragraph voice samples. Overall shape of fo distributions as well as interrelationships among various distributional measures are discussed.


Lip and jaw motor control during speech: responses to resistive loading of the jaw. Resistive loads were applied to the jaw during speech production. Loads were initiated during the jaw closing movement associated with the production of bilabial stops, creating a situation in which bilabial closure would be disrupted if motor control were independent of peripheral feedback. Three subjects were observed during control and experimental conditions. In all utterances in which a load was appropriately introduced, closure of the lips was achieved and the bilabial stop was adequately produced. To assess the nature of this control, displacement of the upper lip, lower lip, and jaw, in the inferior-superior dimension, were recorded along with EMG from medial pterygoid, anterior temporalis, masseter, and orbicularis oris superior muscles. Based on observation of these variables, it appears that the muscles of the lips and jaw are capable of on-line compensatory motor reorganization.


Expectancy as basically a short-term process. Expectancy in stuttering is investigated under conditions that approximate more closely than in previous work the circumstances and mode in which expectancy is purported to operate. The results indicate that the currently accepted explanation of the expectancy phenomenon is inadequate and misleading. An alternative explanation more consistent wwth existent data is offered.


A comparative computer content analysis of the verbal behavior of institutionalized and noninstitutionalized retarded children. Previous studies have indicated structural language differences favoring the noninstitutionalized retarded when compared to matched institutionalized retarded children. In this study, a sociological and psychological deficit hypothesis for institutional retardates was explored by using a verbal content analysis system. Unstructured speech samples from 20 institutionalized and 20 noninstitutionalized retarded children were employed using the computerized General Inquirer System and the Harvard III Psychosociological Dictionary. Differences were found between the groups but all except two were negated or attenuated by additional extended manual analysis treatments. The findings of this study do not support a psychological or sociological deficit hypothesis for institutionalized educable retardates as measured by this content analysis system.


Diplacusis associated with bilateral high frequency hearing loss. Seven normal-hearing subjects and seven subjects with mild bilateral high-frequency sensorineural hearing losses were studied to explore the presence of diplacusis. A tracking procedure of psychophysical method of adjustment-limits was used for pitch judgments rather than the traditional method of adjustment. Each subject was presented with a standard 4000-Hz tone for 500 msec and alternately a variable tone for 500 msec. Subjects were instructed to adjust the variable tone upward or downward in pitch to bracket the pitch sensation of the standard tone. Two intra-aural and two interaural listening conditions were studied. A graphic representation of the subjects' adjustments of the variable tone was obtained for each condition. The resulting tracing indicated frequency correlated to the pitch adjustments from which excursion width and constant error were calculated. Some hard-of-hearing subjects and one normal-hearing subject were found to have diplacusis. Subjects with hearing losses exhibited larger excursion widths for intra- and interaural listening conditions. Subjects with hearing losses tended to be less consistent in pitch judgments than normal-hearing subjects. These findings were interpreted to mean that bilaterally symmetrical hearing losses increase the incidence of pitch aberrations.


Deaf and hearing children's use of language describing temporal order among events. Six experiments are described in which deaf and hearing subjects decided the temporal order of events in picture series and in sentences. The deaf subjects, eight and 11 years old, performed as well as hearing children on a nonverbal picture seriation task. Both deaf and hearing subjects also described most picture series in the natural left-to-right order in which they were shown, and identified the left-hand picture in most series as happening first and the right-hand picture as happening last. In most respects, the deaf children's linguistic performance resembled that of much younger hearing children. Two major results were that deaf children generally used a sequence of simple sentences to describe the events shown in a picture series, and responded to most multiple-clause sentences presented as though the events being described had occurred in the order they were mentioned.


Pursuit auditory tracking of dichotically presented tonal amplitudes. In pursuit auditory tracking tasks subjects match a continuously varying pure tone presented to one ear with a second tone presented to the other ear and controlled by unidimensional movements of part of their motor system. In previous studies in which tonal frequency was varied, performance was significantly better when the tone controlled by a speech articulator (tongue, jaw) was presented to the right ear, rather than the left, but not if the tone was hand controlled. In this study tonal amplitude was varied in mandibular and manual tracking by 30 normal right-handed subjects. Small right-ear advantage was found for both tracking modes although it did not reach statistical significance. Frequency modulated stimuli may more effectively differentiate speech from nonspeech tracking because we may, as a result of speech experience, possess a more developed lateralized auditory-sensorimotor algorithm for frequency-motor relationships involving the mandible than for amplitude-motor relationships. Testable consequences of this hypothesis are outlined.


Language performance of educable mentally retarded and normal children at five age levels. The present study comprised an analysis and comparison of the language performance of educable mentally retarded and normal children at mental age levels six through 10 years. Both syntactic and functional performance variables were investigated. The results indicate language performance differences between the two groups with the primary discriminators being hesitation phenomena (false starts, filled pauses, and repeats) and clausal constructions (relative and subordinate clauses), resulting in a higher sentence elaboration level for normal children.


Acoustic redundancy and the perception of time-compressed speech. An experiment is reported in which time-compressed sentences were heard spoken either in normal intonation or in intonation patterns that conflicted with their underlying syntactic structure. Although there was an overall decrement in intelligibility with increasing compression, sentences heard in normal intonation were significantly better able to withstand the debilitating effects of compression than those with anomalous intonation. An error analysis of subject responses suggests that intonation normally operates to supply supplemental cues for determining syntactic structures as a step in the perceptual coding of heard speech.


Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols. Five heparin protocols, representative of about 30 presently used throughout the country, were analyzed. The adequacy of anticoagulation during and the precision of protamine neutralization at the conclusion of extracorporeal circulation were studied. In each of 50 patient's age, height, weight, or surface area was of no help in predicting heparin kinetics. The study group consisted of the 2 patients with the longest and the 2 patients with the shortest heparin half lives, as well as the 2 patients who showed the greatest sensitivity to heparin and the 2 who showed the least. By computer simulation, each was managed according to the five protocols and by a monitoring procedure. The protocols failed to provide safe anticoagulation or precise protamine neutralization, whereas the simplified monitoring approach was uniformly successful.


Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. Because the administration of heparin and protamine according to a set protocol will fail to anticoagulate safely or neutralize appropriately a significant number of patients, a method of monitoring heparin therapy during cardiopulmonary bypass is presented. A dose response curve relating heparin dosage to its effect on the activated coagulation time (ACT) can be determined with sufficient accuracy for clinical purposes from three ACT's. Preparation of such a curve makes it possible to maintain anticoagulation in a safe range during bypass and minimizes the number of monitoring tests of coagulation required. At the conclusion of bypass, this curve can be used to predict the precise amount of protamine needed for neutralization. Freed from the confusing effects of hyperheparinemia or protamine excess, the physician can diagnose and treat postoperative bleeding problems much more readily.


The surgical anatomy of pulmonary atresia with ventricular septal defect: pseudotruncus. This is a study of 172 heart specimens with pulmonary atresia and ventricular septal defect (VSD)--pseudotruncus. These are divided into simple and complicated types. In the simple type the following may be of importance from the surgical standpoint: (1) the size of the pulmonary arteries, (2) the origin of the aorta, (3) the amount of pulmonary flow, (4) the size of the left side of the heart, (5) the presence of bronchial and/or abnormal systemic supply to the lungs, (6) the coronary circulation, and (7) the presence of intra- and extracardiac associated abnormalities. The following factors may be important in the complicated types: (1) Complete transposition may accompany the complex; (2) instead of the VSD there may be a common atrioventricular (AV) orifice; (3) the pulmonary atresia with VSD may be associated with tricuspid or mitral atresia or with common or single ventricle; (4) the entity may be associated with abnormal position of the entire heart or some of its component chambers.


Pseudoaneurysm of the left ventricle after myocardial infarction: A curable form of myocardial rupture. Rupture of the myocardium following an acute infarction is occasionally compatible with survival. In such cases, pre-existent pericardial adhesions confine the bleeding to a limited space within the pericardial sac and produce a  chamber which communicates with the left ventricular cavity. The chamber gradually enlarges and forms a pseudoaneurysm. Two cases are described in which the diagnosis was made preoperatively and the pseudoaneurysm was surgically resected. Twenty-one previously reported cases are reviewed, as well. The condition's progressive nature leading to death from heart failure or rupture of the pseudoaneurysm, and its amenability to surgical cure make it imperative that the diagnostic features be well known. The diagnosis should be suspected in cases of progressive heart failure developing shortly after the acute phase of myocardial infarction, in which chest roentgenograms show an enlarging heart shadow characterized by a distinct posterior or lateral bulge. The diagnosis can be confirmed by left ventriculography, which should be performed immediately in all suspected cases.


Effects of acid-base imbalance on myocardial pacing thresholds. The effects of acid-base imbalance on ventricular pacing thresholds were studied in anesthetized dogs with complete heart block with the use of an oscilloscope and current probe. Acidosis (base excess-15) and alkalosis (base excess + 15)both resulted in significant increases in threshold voltage and current requirements at all stimulus durations tested. Chronaxie, however, was not significantly affected by shifts in acid-base balance. Abnormalities of acid-base status may adversely affect the accuracy of threshold values obtained during evaluation of different electrode designs and during electrodes implantation for clinical cardiac pacing.


The pulmonary outflow tract in classically corrected transposition. Twenty-one specimens of classically corrected transposition have been studied in order to elucidate the morphology of the pulmonary outflow tract and the nature and origin of structures which obstruct it. The tract is an oblique channel wedged deeply between the inverted mitral and tricuspid valves. As a consequence of septal malalignment, the pulmonary valve ring overrides the muscular ventricular septum. In most specimens, the left wall of the tract is patent owing to incomplete formation of the interventricular portion of the membranous septum. This permits communication of the pulmonary artery with the left-sided morphologic right ventricle. Obstruction to the pulmonary outflow tract may be valvular or muscular or may result from the presence of fibrous tissue tags. Obstruction or atresia was present in 12 specimens (57 per cent). Fibrous tags were the most common cause, and these originated from the intact or perforated membranous septum, the inverted tricuspid valve, or the pulmonary valve. The unusual anterior relationship of the cardiac conducting tissue to the outflow tract in the anomaly is emphasized.


Closed aortic valvotomy and simultaneous correction of associated anomalies in infants. A small infant with severe congenital aortic stenosis presents a difficult therapeutic problem. Both operative and nonoperative treatment are hazardous--especially when other cardiovascular anomalies are present. This report describes a simple, effective technique for dilating the stenotic aortic valve and simultaneously repairing certain associated defects. The procedure has been used successfully in 3 infants with a postoperative follow-up of 6 months to 4 years. There were no deaths, and the functional results have been excellent. This technique is presented as an alternative to the more hazardous approach to open valvotomy and/or stage correction of associated anomalies.


Double prosthetic aortic valve. Case report. A 55-year-old man underwent insection of a Hufnagel valve into his descending thoracic aorta for aortic valve insufficiency 18 years ago. He remained asymptomatic for 16 years. Because of progressive left ventricular failure his incompetent aortic valve was replaced with a De Bakey carbon ball aortic valve prosthesis 2 years later. Currently, 21 months after the operation, he is doing well with two aortic valves. Review of the literature suggests that he is the first patient reported with two aortic valves functioning concomitantly and one of the longest surviving patients with a Hufnagel valve.


First-degree atrioventricular block: a cause of false malfunction of a mitral disc-valve prosthesis. Case report. Malfunction of a prosthetic mitral disc valve was clinically suspected on the basis of absent valve closing sound and an early opening click in a patient with first-degree atrioventricular (A-V) block. Premature closure and opening of the prosthetic valve was demonstrated by echocardiography. All abnormal auscultatory, phonocardiographic, and echocardiographic findings disappeared promptly upon spontaneous restoration of normal A-V conduction. The possible hemodynamic mechanism is discussed, and attention is drawn to this conduction abnormality as a cause of erroneous diagnosis of prosthetic mitral valve malfunction.


Radical surgical treatment of esophageal stenosis due to epidermolysis bullosa. Stenotic lesions of the esophagus in epidermolysis bullosa are a rare cause of dysphagia. Even though 50 cases have been reported in the literature, only recently has surgical treatment been suggested for these patients. In our patients, who had an annular stenosis just distal to the pharyngoesophageal juncture, resection of a mucosal cylindrical segment with reanastomosis through a longitudinal esophageal myotomy was successful. This method of treatment is suggested for patients in whom the stenosis is localized.


Pulmonary insufficiency induced by oleic acid in the sheep: a model for investigation of extracorporeal oxygenation. Most previous studies of the efficiency of bypass techniques for respiratory support have been conducted in hypoxic but otherwise normal animals. However, mechanisms of improved oxygenation by partial venoarterial bypass in the presence of acute respiratory insufficiency can be better studied with an appropriate pathophysiologic model; for this purpose, acute hemorrhagic pulmonary edema was induced in sheep by injection of oleic acid into the right atrium. The model presented a 3 hour period of elevated pulmonary shunting with stable hemodynamics. This preparation is being employed to the study of the mechanisms of extracorporeal oxygenation.


Traumatic avulsion of the trachea associated with cricoid fracture. A 15-year-old girl sustained a cricoid fracture, avulsion of the trachea, and bilateral cord paralysis in a automobile injury. An airway was established by intubation, and primary repair was performed on the day of injury. A postoperative stricture was successfully managed by endoscopic dilatation and injection of triamcinolone into the stricture. Function of one vocal cord appears to be returning 6 months after the injury, and the patient is leading an active life.


Dissimilar metals in a rib spreader a surgical electrical hazard. A case is presented and electrochemical theory is discussed in a situation in which a battery was produced between two dissimilar metals in a Finochietto rib spreader. The problem developed in the thorax of a patient undergoing transthoracic cervical sympathectomy and resection of the first rib. Caution is advised in the use of dissimilar metals in patients undergoing surgery.


Mononeuritis multiplex: a complication of open-heart surgery. A prospective examination of all patients undergoing cardiopulmonary bypass in one unit revealed that a number of peripheral nerve lesions occurred during the postoperative period. These were documented over a period of 20 months with follow-up of those patients so affected.


Malignant tracheoesophageal fistula secondary to Hodgkin's disease. Successful surgical treatment with free fascia-muscle graft and left colon bypass. A case of malignant tracheoesophageal fistula due to Hodgkin's disease at the mediastinum and mid-third of the esophagus is reported. The fistula developed after x-ray therapy (2,000 rads) to the medistinum. In another hospital, she had undergone two unsuccessful attempts to close the fistula surgically with muscle flap grafts, following tracheostomy and feeding gastrostomy. The third operation, performed successfully 2 months later at The Roosevelt Hospital, included division of the esophagus above the fistula with cervical esophagostomy. A free muscle graft was used to close the fistula in the trachea. One month later, subcutaneous antiperistaltic left colon bypass was performed in one stage to connect the cervical esophagus with the lower stomach. At the same time, distal closure of esophagus at the cardia, pyloroplasty, and splenectomy were done. These operations allowed that time, recurrence of the fistula necessitated a fourth operative repair. This time, a 2 inch square piece of fascia and its underlying muscle from the gluteus medius were used to reinforce the closure. The fistula remains closed to date.


Anomalous right ventricular muscle bundle. Repair through the right atrium. Anomalous muscle bundles within the right ventricle may cause obstruction to blood flow at the level of the outflow tract. This condition is usually associated with a ventricular septal defect. Although complete correction is usually approached through a right ventriculotomy, the anatomic configuration makes repair through a right atriotomy more suitable. The advantages of this approach are discussed and a case report is presented.


Recurrent ulcer of the thoracic stomach penetrating the heart. Report of a case and review of the literature. Recurrent and severe gastrointestinal bleeding caused the death of a 67-year-old man who had had resection of carcinoma of the cardiac end of the stomach. The hemorrhage was eventually found to be due to perforation of the wall of the left ventricle by a benign ulcer in the region of the esophagogastric anastomosis. At first, resection of the ulcer appeared to be successful, but recurrence of the penetrating ulcer caused fatal hemorrhage 4 1/2 months later. In our review of the literature, we found only one other instance in which an ulcer on an anastomosis perforated the heart. There were reports of 24 other cases of benign ulcers of the stomach or esophogus which penetrated the heart.


Results of emergency surgical management of hemorrhagic duodenal ulcer. The results of emergency surgical operations carried out on 61 patients with massively beleding duodenal ulcers between the years 1960 and 1969 were reviewed. The most useful diagnostic tool was gastric roentgenography. However, celiac axis arteriography was not in use during this period. The basic procedure carried out was either gastric resection or vagotomy and pyloroplasty. The mortality between the two groups was similar. However, patients more than 60 years of age had a much greater morbidity after gastric resection. Complications were more likely to occur in patients who had a history of chronic ingestion of aspirin prior to the bleeding episode or in whom bleeding from their duodenal ulcer developed while they were recovering from some other surgical procedure.


Decreasing prevalence of tophaceous gout. Retrospective analysis of newly diagnosed gout cases seen at the Mayo Clinic from 1949 through 1972 shows a progressive decline in tophaceous gout, from 14% to 3%. Gout diagnoses remained stable in a range of 1.5 to 2.2/1,000 patients seen.


Biliary bile acid composition in Wilson's disease. Biliary bile acid composition and pattern of bile acid conjugation with glycine or taurine were found to be within normal limits in six patients with documented Wilson's disease. Four patients had previous biopsy evidence of cirrhosis (three with active hepatitis), but most conventional liver function tests gave normal results at the time of the study. Serum levels of conjugates of cholic acid, measured by radioimmunoassay, were not increased. However, plasma disappearance if intravenously injected glycine conjugate of cholic acid was significantly delayed in all subjects, suggesting that this is a more sensitive test of hepatic excretory function and may be of value for assessing hepatic function in patients with this rare genetic disorder. No evidence of a primary disturbance in bile acid metabolism was found in these patients.


The clinical significance of Bence Jones proteinuria. The detection of monoclonal light chains in the urine by the Bence Jones heat test is a useful adjuvant to the diagnosis of myeloma and other related diseases. The test is particularly helpful when no serum spike is noted. Overall, it is positive in approximately half of all patients with myeloma. In order to assess the accuracy of the test, we reviewed the records of all patients with a positive heat test for Bence Jones proteinuria during a single calendar year. Myeloma accounted for 68%, but patients with amyloidosis, the adult Fanconi syndrome, and others also had positive results. One-fifth of the results were false positive in that urine protein electrophoresis showed no spike and immunoelectrophoresis, no monoclonal protein. This group consisted largely of patients with connective tissue diseases, chronic renal failure, or nonplasmacytic malignancies. We also have seen patients who had monoclonal light chains in their urine but failed to show positive results to the heat test and were thus considered false negative. Although the heat test for Bence Jones proteins is a useful clinical test, one must be aware of both false-positive and false-negative results. Electrophoresis and immunoelectrophoresis of concentrated urine are the methods of choice for detection of a monoclonal light chain in the urine.


Studies of the dimensions of oligopeptides by singlet-singlet energy, transfer and theoretical calculations. I. Influence of glycine on the dimensions of tetrapeptides. The efficiency of energy transfer between a fluorescent donor, L-tyrosine, and a fluorescent acceptor, L-tryptophan, has been determined in R'-L-Trp-L-Ala-L-Tyr-R", R-L-Trp-L-Ala-L-Ala-L-Tyr-R", and R'-L-Trp-Gly-L-Ala-L-Tyr-R" in ethanol solution. The protecting groups R' and R" were respectively tert-butyloxycarbonyl and methyl ester. A conformational theoretical analysis of molecules studied has been performed in parallel on the basis of semiempirical conformational potential energy function. In the theoretical models all the side chains have been represented by a methyl group. From the distribution of distances between chromophores obtained theoretically, transfer efficiencies have been computed assuming a random orientation of the chromophores (k-2 equals 2/3). The comparison of calculated efficiencies with the values determined experimentally for the same value of k-2 has been used as a check for the theoretical model. Both experimental and theoretical studies have been shown that the glycyl residue procudes a reduction of dimensions when it replaces in a tetrapeptide a residue with a beta-carbon atom such as the L-alanyl residue. However, only a qualitative agreement between experimental and theoretical values of the efficiencies has been obtained.


Small-bowel obstruction secondary to endometriosis. Though endometriosis is a frequent finding in females, it rarely causes obstruction of the small bowel. However, 11 patients with such obstruction were seen at the Mayo Clinic in the years 1950 through 1970. Their ages ranged from 27 years to 51. A portion of involved bowel had to be resected in every case, but most of the lesions were single. Generally the obstructions were subacute and did not produce surgical emergencies. But because the symptoms were neither specific nor acute, the diagnosis seldom was established prior to laparotomy and the majority of the resections were performed without bowel preparation. Nevertheless, morbidity was minor in most cases and there was no mortality. Small-bowel obstruction has not recurred. Endometriosis of the small bowel tends to be limited to the serosa and the muscular coats, not penetrating the mucosa; and obstruction is due to fibrosis and kinking of the bowel. The obstructed segment usually must be resected. If pelvic endometriosis is minimal, no further surgery is necessary. But if the pelvic lesions are extensive, or if multiple sites in the small and large intestines are involved, then more radical resection and bilateral oophorectomy are indicated.


Side-chain interactions and conformation in alpha-helical poly(gamma-phenacyl L-glutamate). Aggregation in dilute solutions. The behavior of alpha-helical poly(gamma-phenacyl L-glutamate) (PPLG) has been studied by hydrodynamic, optical rotation, dielectric, and nmr measurements in different solvents. Special attention has been paid to side-chain interactions which depend on the ease of solvation of the phenacyl chromophore. Thus, in hexafluoro-2-propanol the circular dichroism spectrum is very similar to that usually observed for an alpha helix, and hydrogen bonding was shown to occur between the solvent and phenacyl CO group. In other heliocogenic solvents, side chain-side chain interactions occur. In dimethylformamide and pyridine they give rise at low temperature and low concentrations to an aggregation phenomenon whose molecular mechanism implies a molecular weight dependent folding of the molecules. Models for the side-chain conformation are proposed for the polymer in the solid state on the basis of infrared dichroism.


Microcirculatory obstruction in focal cerebral ischemia. Relationship to neuronal alterations. The cerbral microcirculation in squirrel monkeys was studied by the carbon perfusion technique after middle cerebral artery occlusion. No filling impairment was detected with 90 minutes of ischemia, and only slight impairment was detected with 3 hours of ischemia. Severe microcirculatory obstruction  was found after ischemia longer than 3 hours. The obstruction appeared to be at the capillary level and seemed partly the result of narrowing of cappillary channels by perivascular glial swelling and developing cerebral edema. The relationship between the developing microcirculatory obstruction and the distribution and severity of the neuronal alterations was studied. The results of this investigation using the same experimental model suggest that obstruction of parenchymal vessels does not play a major role in the production of an infarct in areas of acute focal ischemia.


Drug-induced malabsorption.

Drug-induced malabsorption. Pharmacologic agents of diverse types may alter gastrointestinal absorption of nutrients and other substances. Mechanisms underlying drug-induced absorptive defects that have been documented include: (1) a direct toxic effect causing morphologic changes in the mucosa of the small intestine; (2) inhibition of mucosal enzymes with or without morphologic evidence of mucosal damage; (3) binding and precipitation of micellar components, such as bile acids and fatty acids; and (4) alteration of the physicochemical state of another drug or dietary ion. The malabsorptive effect generally is dose-related, rather than an idiosyncratic reaction, and usually involves multiple nutrients. Certain clinical states, such as in the malnourished alcoholic may predipose the gastrointestinal tract to a drug-induced absorptive defect. For this review we discuss in detail nine commonly used drugs or types of drugs that cause malabsorption of dietary nutrients or other medications.


Carotid endarterectomy. Complications and preoperative assessment of risk. A system of grouping patients according to preoperative evaluation of risk of carotid endarterectomy is presented. The primary complications of this surgical procedure were myocardial infarction and residual mild to severe neurologic deficit. Neurologically stable patients without medical or angiographically determined risk factors (group 1, 129 patients) have a risk of 1%. Neurologically stable patients without medical risk but with angiographically determined risk (group 2, 56 patients) have a risk of 2%. Neurologically stable patients with significant medical illness and with or without angiographically determined risks (group 3, 76 patients) have a risk of 7%, primarily related to cardiac disease. Neurologically unstable patients (group 4, 70 patients) have a 10% risk for a neurologic deficit.


Familial hemiplegic migraine.

Familial hemiplegic migraine. Ten members of one family had hemiplegic migraine. The typical attack was sterotyped from member to member. Three of the 10 members had hemiplegic migraine attacks associated with minor head trauma. One patient suffered premanent neurologic deficit. Therapy of hemiplegic mirgaine is briefly discussed.


Congenital hypertrophic pyloric stenosis. Surgical experience. Of 132 infants who underwent surgery for congenital hypertrophic pyloric stenosis during a 13-year period, 83% were males and 31% were firstborn males. Ninety-one percent of the patients presented with projctile vomiting after feeding, and an "olive" was palpated in 92%. Upper gastrointestinal studies were not obtained in 73%. Twenty patients had positive family histories. For the entire 13 years under review, the average total hospital was 6.14 days, and the average postoperative stay was 4.45 days. For the later period 1970 to 1974, the hospital stay was 5.2 and 3.7 days, respectively. Intravenous fluids were not used in 77% of the patients and were used but not needed from a surgical standpoint in 9%. No deaths resulted from the procedure for pyloric steonsis, but there were five complications. Only 13 patients had no vomiting after operaion, whereas 105 (79%) had modest regurgitation of mild vomiting. Specific preoperative, operative, and postoperative care is important in every case.


Mesenteric angiofollicular lymph node hyperplasia (lymphoid hamartoma) with nephroitc syndrome. In an 18-year-old woman who presented with the nephrotic syndrome and an abdominal mass, removal of a benign mesenteric lymphoid tumor was associated with remission of the nephrotic syndrome without further recurrence (30 month follow-up). Biopsies of both kidneys showed  a minimal-change glomerular lesion. Clinical and pathologic characteristics of angiofollicular lymph node hyperplasia and its possible relationship to the nephrotic syndrome are discussed.


Open-angle glaucoma associated with topical administraion of flurandrenolide to the eye. Intraocular pressure was elevated in both eyes and a glaucomatous field defect developed in one eye of an 18-year-old Caucasian man after prolonged topical use of flurandrenolide. Spontaneous remission occurred in one eye, the eye with least drug exposure, within a few weeks. The other eye continued to show evidence of elevated intraocular pressure and further field loss developed over 4 years after discontinuation of the steroid. The most serverly affected eye became myopic. This case strongly suggests that chronic application of flurandrenolide into the conjuctival sac can produce corticosteroid-induced glaucoma in susceptible individuals. Although both eyes were normal before exposure to the steroid and elevations of the same level developed in both eyes at the peak of the disease, the eye with the least drug exposure underwent complete and spontaneous remission whereas the eye exposed more frequently appeared to show irreversible changes in the aqueous humor outflow pathway with subsequent loss of visual field.


Microscopic and baceriologic analysis of expectorated sputum. Samples of expectorated sputum were examined grossly and microscopically to determine their suitability for bacterial cultures. Microscopically, specimens were categorized according to the number of leukocytes and squamous epithelial cells (SEC) observed under low-power (times 100) in a Gram-stained smear. The mean number of species isolated was greater than 4 from specimens with more than 10 SEC per field, 2.7 from specimens with fewer than 10 SEC per field, and 2.4 from transtracheal aspirates. Oropharyngeal flora was isolated from nearly all of the specimens with more than 10 SEC per field, and potential pathogens were found in less than 15% of such specimens. The bacterial flora of specimens with fewer than 10 SEC per field closely resembled that of transtracheal aspirates.


Glutamine transport in dog kidney mitochondria: a new control mechanism in acidosis. Experiments performed with isolated mitochondria from dog renal cortex provide evidence for a carrier for glutamine located in the inner mitochondrial membrane. This carrier transfers glutamine to glutaminase located in the inner membrane or matrix space and provides a site for regulation of glutamine metabolism and ammoniagenesis. Examination of glutamate formation by the carrier-glutaminase system in mitochondria and in submitochondrial preparations from acidotic and alkalotic dogs shows enhanced glutamate formation without accompanying alteration in glutaminase levels in preparations form acidotic animals. These findings suggest that the increased renal ammonia formation from glutamine during metabolic acidosis results from an adaptive increase in transport of glutamine by the inner membrane carrier.


Enzymic synthesis of 1-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine through ethanolaminephosphotransferase activity in the neuronal and glial cells of rabbit in vitro. The transfer of radioactivity from cytidine-5'-diphosphate ethanolamine into 1-alkyl-2-acyl-sn-glycerophosphorylethanolamine of neuronal and glial cells from adult rabbit brain cortex has been investigated in vitro. The synthesis of 1-alkyl-2-acyl-sn-glycerophosphorylethanolamine in both cell populations was stimulated 23-25-fold by the addition of 6 mM alkylacylglycerol. The neuronal cell-enriched fraction was found to possess/unit protein a 1.7-1.8-fold ethanolaminephosphotransferase activity (EC 2.7.8.1), as compared to the glial fraction, when saturating concentrations (6 mM) of alkylacylglycerols were added in the incubation system. The neuronal/glial ratio was 2.6-2.8 in the absence of lipid acceptor or with low concentrations of alkylacylglycerol. Under most favorable conditions, 6.4 and 3.3 nmoles 1-alkyl-2-acyl-sn-glycerophosphorylethanolamine/mg protein/30 min was obtained for neurons and glia, respectively. Various kinetic properties of the 1-alkyl-2-acyl-sn-glycerophosphorylethanolamine synthesizing phosphotransferase activity were found to be similar both in neurons and glia.


Relationship between lipids in plasma and skin secretions of neonatal calf with particular reference to linoleic acid. A study has been made on the lipid composition of the skin secretions and plasma of the neonatal calf. A significant proportion of the skin surface lipids was comprised of triglycerides. Saturated fatty acids comprised the major proportion of the fatty acids of the skin surface triglycerides at birth. Immediately after birth, the proportion of the saturated fatty acids decreased, and there was a concomittant increase in the proportion of 18:1. Some 3-4 weeks after birth, the proportion of 18:2 delta cis-9, cis-12 in the skin surface triglycerides increased to ca. 14 percent, and there was a decrease in the proportion of 18:1. The 18:2 was shown to be confined almost entirely to the 2 position of the triglycerides. During the first 5 weeks after birth, the concentrations of the cholesteryl esters and phospholipids in the plasma increased markedly and were accompanied by a rapid increase in the proportion of 18:2 within these 2 fractions. The results are discussed in relation to the known role of 18:2 in the metabolism of biological systems.


Some unusual fatty acids of Rhizobium.

Some unusual fatty acids of Rhizobium. A number of unusual fatty acids were identified after isolation from Rhizobium. They include 11-methyl-octadec-11-enoic, 12-methoxy-11-methyl- and 11-methoxy-12-methyloctadecanoic, and 11-methoxy- and 13-methoxynonadecanoic acids.


Positional analysis of isovaleroyl triglycerides using proton magnetic resonance with Eu (fod) 3 and Pr (fod) 3 shift reagents: I. Model compounds. The proton magnetic resonance spectra of isomeric triglycerides of isovaleric and palmitic acids in the presence of the downfield and upfield chemical shift reagents Eu(fod)(3) and Pr(fod)(3) were studied. The resonance profiles of the gamma-protons on the isovaleroyl chains are distinctive for each of the four possible triglyceride isomers at low shift reagent/triglyceride ratios. With either reagent, the well defined gamma-methyl isovalerate doublets can be used to identify 2-isovaleroyl and 1,3-isovaleroyl structures and to analyze isomeric mixtures. This technique will be useful for positional analysis of natural cetacean triglycerides containing isovaleric acid.


New application of high pressure reversed-phase liquid chromatography in lipids. High pressure reverse-phase liquid chromatography has been used to separate saturated fatty acids, their methyl esters, polyunsaturated fatty acids, and triglycerides. Rapid separation of fatty acids differing in chain length and number of double bonds has been accomplished. Analysis time was less than 10 min in most cases. The high pressure reverse chromatography resulted in better separations of polyenoic acids than can be accomplished by conventional argentation silicic acid column chromatography. The analyses were carried out on a chemically bonded reverse phase packing, VYDAC reverse phase.


Effect of low methionine, choline deficient diets upon major unsaturated phosphatidyl choline fractions of rat liver and plasma. To see how the metabolism of specific phosphatidyl choline fractions might be affected when only a limited source of methyl groups was available, rats were fed for 7 days a low methionine, choline-deficient diet or one supplemented with either choline or methionine. Prior to killing, they were injected with -14C-methyl methionine and liver and plasma phosphatidyl choline isolated and separated by argentation chromatography into 3 major unsaturated fractions. Fatty acid composition and radioactivity of the fractions were determined. Deficient rats had reduced total liver phosphatidyl choline when compared with the supplemented groups, but the proportions of 20:4 and 22:6 fatty acids in the total phosphatidyl choline were unchanged. Plasma phosphatidyl choline also was reduced sharply by the deficiency, as was its proportion of 20:4 fatty acid. Specific activities of the liver 22:6, 20:4, and 18:2 phosphatidyl choline fractions showed that deficient rats had less radioactivity in their 20:4 and 18:2 phosphatidyl choline than did the supplemented animals. Plasma phosphatidyl choline fractions presented a similar pattern. Feeding methionine or choline nearly doubled radioactive methyl group incorporation into the 20:4 phosphatidyl choline fraction of liver and plasma, while incorporation into the 22:6 phosphatidyl choline was reduced or unchanged. The results suggested that, in the rat, limited availability of methyl groups altered the metabolism of liver and plasma phosphatidyl choline fractions. Methionine, as a source of labile methyl groups, appears necessary for the normal synthesis of certain unsaturated phosphatidyl choline fractions (particularly 20:4 phosphatidyl choline). Transmethylation of phosphatidyl ethanolamine molecular species to the corresponding phosphatidyl choline species may be an important reaction in normal lipid metabolism and transport. Relative affinities for incorporation of the labeled methyl groups into the phosphatidyl choline fractions of either deficient or supplemented rats were: 22:6 less than 20:4 less than 18:2.


Effects of phenobarbital upon bile acid synthesis in two strains of rats. Rats of the Wistar and Sprague-Dawley strains were injected with sodium phenobarbital (100 mg/kg body wt/day) for 8 days. Fecal bile acid excretion was measured on days 6 and 8 of the experiment, and biliary bile acid composition, hepatic microsomal cholesterol, 7alpha-hydroxylase, and 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase were determined at the end of the study. In the Wistar rat, injection of phenobarbital produced a doubling of fecal bile acid output (controls, 5.3 mg/rat/day; treated rats, 10.6 mg/rat/day) and a two-threefold increase in cholesterol 7alpha-hydroxylase. The fecal bile acid output of Sprague-Dawley rats increased 20% in response to phenobarbital (controls, 9,5 mg/rat/day; treated rats, 11.6 mg/rat/day). The activity of cholesterol 7alpha-hydroxylase remained unchanged. In both strains, phenobarbital treatment produced a decrease in the proportion of cholic acid in total bilary bile acids (controls, 85%; treated groups, 65%). This was associated with a decrease of 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase activity by ca. 50%. Biliary cholesterol concentrations were reduced in phenobarbital treated rats of both strains, but liver cholesterol concentrations remained unchanged. The drug produced a 25% increase in liver wt, on the average.


Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat. The incorporation of radioactivity from orally administered linoleic acid-1-14C, linolenic acid-1-14C, arachidonic acid-3H8, and docosahexaenoic acid-14C into the liver and brain lipids of suckling rats was studied. In both tissues, 22 hr after dosing, 2 distinct levels of incorporation were observed: a low uptake (from 18:2-1-14C and 18:3-1-14C) and a high uptake (from 20:4-3H8 and 22:6-14C). In adult rats, the incorporation of radioactivity into brain lipids from 18:2-1-14C and 20:4-3H was considerably lower than the incorporation into the brains of the young rats. In the livers of the suckling rats, the activity from the 18 carbon acids was associated mostly with the triglyceride fraction, whereas the activity from the 20:4-3H8 and 22:6-14C was concentrated in the phospholipid fraction. In the brain lipids, the activity from the different fatty apid fatty acids, some of the activity in the 18:2-1-14C and 18:3-1-14C experiments was associated with 20 and 22 carbon polyunsaturated fatty acids; however, radioactivity from orally administered 20:4-3H8 and 22:6-14C was incorporated intact into the tissue phospholipid to a much greater extent compared with the incorporation of radioactivity into 20:4 and 22:6 in the experiments where 18:2-1-14C and 18:3-1-14C, respectively, were administered. Possible reasons for these differences are discussed. Rat milk contains a wide spectrum of polyunsaturated fatty acids, including linoleate, linolenate, arachidonate, and docosahexaenoate. During the suckling period in the rat, there is a rapid deposition of 20:4 and 22:6 in the brain. The results of the present experiments suggested that dietary 20:4 and 22:6 were important sources of brain 20:4 and 22:6 in the developing rat.


Rate of restoration of cardiolipin and other major phospholipids during liver regeneration in rat. The rate of restoration of liver phospholipids, especially cardiolipin, during liver regeneration after two-thirds partial hepatectomy, was studied. Preoperative content of cardiolipin was not restored during the first week of regeneration, while this was the case for the other major liver phospholipids. The observations are discussed in relation to the morphogenesis of mitochondria during liver regeneration.


Effect of dietary safflower oil upon lipogenesis in neonatal lamb. The effect of dietary safflower oil upon lipogenesis has been investigated in neonatal lambs. Preliminary experiments with lambs suckled by their mothers showed that there was a 10-fold increase in the rate of incorporation of [14-C] from acetate into fatty acids in adipose tissue slices during the first 10 days post partum. Barely detectable rates of [14-C] acetate incorporation into fatty acids were found in liver slices from lambs during the same period. In lambs given cows' milk from birth untill 11 days of age, there was also a 10-fold increase in the rate of lipogenesis in adipose tissue slices. Supplementing the diet of cows' milk with safflower oil (5 ml/lamb/day) resulted in significantly lower rates of lipogenesis in adipose tissue slices from 11 day old lambs. Administration of safflower oil had no effect upon the concentration of unesterified fatty acids, including linoleic acid, in the lamb adipose tissue slices. The data show that lipogenesis in ovine adipose tissue, like that in rodent liver and adipose tissue, is sensitive to dietary polyunsaturated fatty acids, and that, for the neonatal lamb, the effect of polyunsaturated fatty acids upon lipogenesis is not dependent upon an increase in the tissue concentration of polyunsaturated fatty acids.


Brain free fatty levels in rats sacrificed by decapitation versus focused microwave irradiation. Values are presented for whole brain free fatty acid levels of rats sacrificed by decapitation vs focused microwave irradiation. Free fatty acids were quantitated by specific colorimetric analysis. Within ca. 1 min of sacrifice by either decapitation or microwave, rat whole brain free fatty acid concentrations ranged from ca. 80-100 mug/g fresh tissue. If the brain remained in the head for a total of 5 min after decapitation, free fatty acid levels increased by over 100%. The free fatty acids at this time were enriched with arachidonic acid. The increase in free fatty acid levels following decapitation was completely absent in rats sacrificed by the microwave irradiation. This microwave technique could be a valuable tool in determining free fatty acid and other heat stable compounds in brain tissue.


Fatty acid and aldehyde composition of major phospholipids in salt gland of marine birds and spiny dogfish. The lipophilic components of choline phosphoglycerides and ethanolamine phosphoglycerides obtained from the salt gland of herring gull and eider duck and from the rectal gland of spiny dogfish were investigated by means of thin-layer chromatography, gas chromatography, and gas chromatography-mass spectrometry. All phospholipids analyzed were shown to contain small amounts of plasmalogens, and mainly C16, C18, and C18:1 aldehyde was detected. The fatty acids were composed of saturated, unsaturated, straight chain, and branched chain types, ranging between 14-22 carbon atoms. The lipophilic composition of the rectal gland phospholipids showed a higher degree of unsaturation and the presence of more branched chain fatty acids than that of the birds, possibly related to body temperature.


Incorporation of oxygen-18 into secondary alcohols of grasshopper Melanoplus sanguinipes. Incorporation of 18-O2 and H2-18-O into the secondary alcohol moiety of wax esters in the grasshopper Melanoplus sanguinipes was determined by mass spectrometry. Results of this study show that oxygen-18 from 18-O2 was incorporated into the secondary alcohol, whereas no incorporation of oxygen-18 from H2-18-O was detected. The data suggest that the reaction, which hydroxylates n-alkanes at or near the center of the carbon chain, involves a mixed function oxidase type enzyme.


Fluorescent pigments from uterus of vitamin E-deficient rats. Spectrophotofluorometric analyses of the extracts of uterus from sterile rats maintained on a vitamin E-deficient diet for a prolonged period of time indicated that the brown ceroid-like pigments present were highly fluorescent, having characteristics typical of products formed during lipid peroxidation in vivo. The aqueous-methanol layer of the uteral extract from vitamin E-deficient animals had higher fluorescence than the corresponding chloroform layer, indicating the presence of more polar water-soluble pigments than those found in most other tissues so far examined.


Use of internal vial for determining quench correction in scintillation counting of heterogeneous media. An insert vial situated at the center of the counting medium and containing a standard count has been used for quench correction in the liquid scintillation counting of gels containing suspensions of silicic acid scrapings from thin layer chromatoplates. The method has provided a simple and direct means of routine count correction for a range of 14-C-labeled lipid classes following separation on thin layer chromatoplates. The use of insert vial provides several advantages over other methods for the count correction of these suspensions.


Inhibition of glyceraldehyde 3-phosphate dehydrogenase by plasma and serum ultrafiltrates due in part to a low-molecular-weight, nonpeptide material. In an attempt to verify the existence in the blood of a diabetogenic peptide (somantin) derived from growth hormone, ultrafiltrates from plasma and serum from normal and diabetic subjects were prepared. The freeze-dried residues of these ultrafiltrates inhibited glyceraldehyde 3-phosphate dehydrogenase as somantin is claimed to do. However, the behavior of the inhibitory material on gel filtration on Sephadex G-10 indicated a molecular weight well below 700, rather than the considerably larger size claimed for somantin. The inhibitory material did not adsorb to Dowex 50W cation exchange resin at pH 2.5, while over 95 percent of ninhydrin-positive material was retained. Acid hydrolysis of the inhibitory material did not abolish its activity. Because of the presence of this low-molecular-weight, nonpeptide inhibitory material, inhibition of glyceraldehyde 3-phosphate dehydrogenase by a simple ultrafiltrate of plasma or serum is probably not a definitive measure of somantin.


Development of the obese-hyperglycemic syndrome in mice with a growth hormone deficiency. By mating mice heterozygous for the recessive gene, obese (ob/+) (+/+), with mice homozygous for the recessive gene, dwarf (+/+)(dw/dw), and subsequent mating of the offspring, mice homozygous for both the obese and dwarf gene were obtained. It was established that the genes for obese and dwarf mice belong to different linkage groups. The homozygous obese dwarf mice develop obesity and hyperinsulinemia. The degree of hyperglycemia developed by these homozygotes is not significantly different from that of nonobese dwarf mice. Because homozygous dwarf mice are deficient in growth hormone production, it was concluded that obesity and hyperinsulinemia can develop under conditions of extreme growth hormone deficiency.


Relationships of the renin-angiotensin-aldosterone system and sodium balance to blood pressure regulation in chronic renal failure of polycystic kidney disease. In 5 patients with polycystic kidney disease and creatinine clearances ranging from 4 to 40 ml/min, relationships between changes in blood pressure, sodium balance, body fluid compartments, plasma renin activity (PRA), urinary aldosterone excretion, and plasma aldosterone concentrations were studied during periods of low, medium, and high sodium intake. Total body water (TBW), total exchangeable body sodium (TEBS), and extracellular volume (ECV) were measured by isotope dilution techniques, plasma volume with Evan's blue dye, and PRA and aldosterone by radioimmunoassay. Low sodium intake reduced kidney function, blood pressure, and serum sodium, while PRA reached its highest levels. Subsequent increases in sodium intake improved kidney function and increased blood pressure. Plasma volume increased slightly and ECV markedly, while PRA dropped to 15 percent of the value noted after the low sodium intake. TBW and TEBS showed inconsistent changes. Aldosterone changes correlated closely with PRA. Blood pressure showed a negative correlation with PRA, but a positive one with body weight and cumulative sodium balance, and with plasma and extracellular volumes.it is suggested that whereas renin and aldosterone are involved in the maintenance of circulatory homeostasis during sodium loss, sodium retention causes an increase in blood pressure by concomitant changes in body fluids.


Relationship between local and total bone mass in osteoporosis. The relationship between total body calcium (TBC) and local bone calcium mass (BCM) was studied in a group of osteoporotic patients (12 females and two males) with a wide range of body size. Two methods were used to estimate BCM: photon absorptiometry and radiographic morphometry. TBC was estimated by total-body neutron-activation analysis. Since 99 percent of TBC is located in the skeleton, it was assumed that TBC was essentially a measure of total skeletal (calcium) mass. TBC ranged from 482 to 1076 g. High correlations with r values from 0.84 to 0.94, p less than 0.001, were found between TBC and BCM measured by absorptiometry at six different sites of radius, ulna, and humerus. Additionally, high correlations with r values from 0.89 to 0.95, p less than 0.001, were found between BCM at the distal tenth of the radius and BCM at the five other sites. A high correlation was also found between body height and TBC, but partial correlations indicated that this accounted for very little of the correlation between TBC and BCM. In contrast to the above, correlations between BCM determined by radiographic morphometry and TBC were weak or nonsignificant. When TBC and BCM were expressed as percent of their mean value, the slopes of the estimating equations, describing the relationships between TBC and BCM, were essentially the same, but significantly less than one, which is the value of the slope expected if TBC and BCM had changed at the same relative rate. From these relationships, we conclude (1) that the rate of change in BCM was similar in the six sites examined, and (2) that the rate of change in these six sites was relatively more rapid than the change in total body calcium. Whether the change in rate of BCM was related to rate of increase during attainment of maximum BCM or subsequent rate of loss of BCM or both remains to be determined.


Sympathetic control of hepatic glycogenolysis during glucopenia in man. Liver glycogen stores may be mobilized during hypoglycemia by release of adrenomedullary catecholamines, by release of norepinephrine from sympathetic nerve endings and by release of glucagon. To clarify the nature of peripheral sympathetic control of hepatic glycogenolysis during glucopenia in man, 2-deoxy-d-glucose (2 DG), a competitive inhibitor of glucose metabolism, was infused intravenously (50 mg/kg) to nine normal volunteers and four adrenalectomized patients for 20 min. In normal volunteers, the initial elevation of free fatty acids (FFA) and growth hormone (HGH) correspond with the rise in total catecholamines, with maximal levels attained at 60 min; lactate and cortisol rose at a slower rate, no change in IRI was noted. Plasma glucose levels were 148 percent of preinfusion values by 120 min and remained elevated. In adrenalectomized subjects, despite no change in plasma FFA, lactate, catecholamines and glucagon, glucose rose 20 percent by 150 min; the growth hormone and insulin responses were similar to normals; A significant increase in glucose response from 60 min onward was found in the 2 DG infusion studies when compared to cortisone administration, alone. Thus, during glucopenia, plasma glucose rose in spite of unchanged adrenomedullary catecholamine and glucagon levels. The findings indicate that the sympathetic neurotransmitter, norepinephrine, contributes to counter-regulatory events during 2 DG-induced glucopenia presumably via its release from hepatic sympathetic nerve endings,


Effects of ethanol ingestion on glucose tolerance and insulin secretion in normal and diabetic subjects. To investigate the effect of ethanol on carbohydrate homeostasis in circumstances in which food and ethanol are usually ingested, ethanol was administered hourly in the afternoon prior to the ingestion of a glucose load at 5:00 p.m. in a group of normal subjects and in mild diabetics. In both groups the blood glucose levels following the glucose load were 30-80 mg/100 ml lower and the early insulin secretory response (15-45 min) was 35 percent-40 percent higher after ethanol ingestion. In contrast, ethanol intake had no effect on the glucagon response to glucose ingestion; These data suggest that ethanol enhances glucose-stimulated insulin secretion. The dampened blood glucose rise observed with ethanol may be related to the augmented insulin response or to decreased gastrointestinal absorption of glucose. In mild diabetic patients, moderate intake of ethanol is without acute deleterious effects on carbohydrate homeostasis and may in some instances improve the blood glucose response to ingested carbohydrate.