Metablism of aldosterone in dogs with renovascular hypertension (38476). The rate of metabolism of aldosterone was measured in seven normal dogs, 4 dogs with chronic renal hypertension and five dogs with malignant renal hypertension. Tritiated aldosterone was injected intravenously and the rate of disappearance of authentic aldosterone was determined. The disappearance curves were resolved into two exponential components and the plasma half-life was measured from the slow component which reflects the rate of metabolism of aldosterone. The half-life of aldosterone was essentially the same for the three groups of dogs. It is concluded, therefore, that the rate of aldosterone metabolism is normal in dogs with experimental renal hypertension.


Rhythmic patterns of endogenous LH release in castrate sheep receiving exogenous LH (38477). Exogenous ovine LH was constantly infused during 6-hr experimental sequences in order to determine the effect of elevated levels of plasma LH on the pulsatile discharges of pituitary LH characteristic of ovariectomized sheep. Plasma LH concentrations (exogenous plusendogenous) in sequential 10-min samples continued to fluctuate significantly as did plasma LH (endogenous only) during control periods. The temporal patterns of plasma LH during LH infusion were at least as as rhythmic as they were in the controls. Furthermore, the mean periods for extremely rhythmic frequencies were equivalent in control and LH-infusion sequences. These data refute the original hypothesis that inhibitory short-looped feedback of circulating LH governs the timing of subsequent LH discharges in ovariectomized sheep.


The site of zinc absorption in the rat small intestine (38481). Rats fed a zinc-adequate diet exhibited a nonuniform distribution of zinc in the small intestine. The zinc content of zinc-deficient rat small intestine was reduced, particularly in the duodenum and distal ileum. It is possible that the difference in the intestinal zinc content may reflect the rate of zinc absorption in the tissue. Uptake of 65-Zn by intestinal segments in vitro showed that the pattern of absorption obtained is dependent upon the parameters used for quantitation. This observation could account for the variation between the results obtained by different experimental methods of determining the site and rate of absorption of the nutrient.


Blood volume responses of rats adppted to different barometric pressures (38482). The total blood volume, circulating red cell volume (CRCV), and plasma volume of rats exposed for 30 days to either 480 or 380 mmHg were quite different. At the lower altitude 480 mmHg) total blood volume was similar to that found in sea level controls of a similar weight and age, while CRCV was increased and plasma volume was decreased. However, at the higher altitude CRCV was increased to a much greater extent, with the result that the total blood volume was approximately 44% greater than at 480 mmHg. The differences in response to the two barometric pressures became even more striking when the rats adapted to 380 mmHg were compared with their age- and weight-matched controls. Diet restrictions in the absence of hypoxia resulted in significant decreases in CRCV, plasma volume, and total blood volume. Consequently, when compared to these animals, rats adapted to 380 mmHg had a 100% greater total blood volume due primarily to a higher CRCV, but also to a higher plasma volume.


Studies on an inhibitor of erythropoiesis. II. Inhibitory effects of serum from uremic rabbits on heme synthesis in rabbit bone marrow cultures (38483). The effects of sera from anephric rabbits on the rate of heme synthesis in erythroid cells were studied in vitro in rabbit bone marrow cultures. Sera from nephrectomized rabbits significantly (p smaller than 0.05) inhibited 59-Fe incorporation into heme in normal rabbit bone marrow cultures incubated with erythropoietin (ESF) when compared with the response in control culutres with normal serum and ESF. This inhibitory activity increased exponentially with increasing concentrations of the serum  in cultures suggesting that a higher concentration of the inhibitor is present in uremia and may be the result of the failure to excrete the inhibitor. This suggests that the retention of this inhibitor may play an important role in the mechanism of the anemia of uremia. The inhibitor of heme synthesis is a low molecular weight substance.


The effect of sodium benzoate and taurocholic acid feeding on human bile composition. Four patients were fed sodium benzoate after stabilization following common bile duct exploration. Bile collections revealed no change in the output of glycine conjugated bile acids. Three patients had taurocholic acid added to the regimen after 3 days and demonstrated a significant increase in total and taurine conjugated bile acid output with marked reduction of the G/T ratio. These latter changes are similar to those produced by taurocholic acid feeding alone and therefore no benefit of the combination of drugs on bile salt excretion or conjugation ratio was demonstrated.


Contractility of renal cortex following complete ureteral obstruction. Contractility of strips of renal cortex obtained from rabbit kidneys obstructed by complete ureteral ligation for 8 and 32 days was tested and compared with control tissue.  Concentration-response data were obtained for norepinephrine, angiotensin, and 5-hydroxytrypamine, and were expressed as mg tension/cm of tissue.  Control tissue tested simultaneously revealed minimal responses, but obstructed tissue containing modified interstital cells revealed statistically significant evidence of contraction in response to all three drugs studied.  The response to norepinephrine could be blocked by the alpha adrenergic antagonist, phenoxybenzamine, but this drug did not significantly affect the response to angiotensin or 5-hydroxytryptamine.  The findings are related to similar observations reported in stimulated fibroblasts of granulation tissue and are discussed in terms of the possible role this phenomenon may play in the pathogenesis of renal interstitial injury.


Renin release, an artifact of anesthesia and its implications in rats. In our attempt to find an anesthetic agent which did not influence the renin-angiotensin system in the rat, the effect of widely used injectable and gaseous anesthetics and narcotic agents on renin release was chacterized.  All of the agents studied induced dose- and time-related increases in serum renin activity when administered in anesthetic doses.  Preliminary experiments in anesthetic doses.  Preliminary experiments indicated that cardiovascular effects were highly variable, giving little insight into the relationship between renin release and cardiovascular changes.  Propranolol impaired most of the anesthesia-induced renin release and impaired aldosterone release with the one agent (urethane) studied.  Renin release by two anesthetic agents (ketamine and urethane) appeared to be mediated premarily through the beta-adrenermediated primarily through the beta-adrenergic receptor mechanism, but equivocal results were obtained with other agents (pentobarbital and morphine).  It is possible that other anesthetics, as with urethane, may induce aldosterone release by way of renin release.  This anesthesia-induced renin release and the extensive biologic activities of angiotensin and aldosterone suggest a potential for influencing many investigations, particularly those involving cardiovascular and endocrine systems.


Rabbit muscle triosephosphate isomerase: activity and inactivation by sulfhydryl reagents as affected by enzyme concentration. Progressive increase of enzymatic activity with time occurs after dilution of a crystalline suspension of rabbit muscle TIM. The concentration of p-MB required to inhibit the enzyme is higher the greater the concentration of enzyme. With the lowest concentrations of mercurial that are ultimately inhibitory to the enzyme in dilute solution, there is a lag period before inactivation begins. With higher concentrations of mercurial, some degree of inactivation occurs almost immediately, and enzymatic activity thereafter decreases at a slower rate. With an enzyme concentration of 32 ng/ml, a low concentration of p-MB decreases Vmax without change KM. A higher concentration of mercurial also increases KM. With an enzyme concentration of 1 mg/ml, iodoace begins to inactivate it only after a lag period. In enzyme solutions containing 8 ng/ml, inactivation by iodoacetate progresses without significant initial lag. Discrepancies between the present work and that of other authors can probably be accounted for by differences in the concentrations of enzyme used. It is suggested that the conformation of rabbit muscle TIM in solution is dependent on its concentration. In more dilute solutions the enzyme assumes a conformation in which it is catalytically more active and in which its sulfhydryl groups are more accessible to chemical attack.


Metabolic effects of exercise.  I. Effect of exercise on serum lipids and lipogenesis in rats. To evaluate the metabolic effects of exercise, three groups of exercised male rats were compared to their sedentary controls at the end of 10 wk of voluntary exercise in rodent activity cages.  Exercises rats consumed more food than sedentary rats but had greater weight gain only at the higher levels of activity.  Exercised rats had significanlty lower serum triglycerides and higher values of adipose tissue alpha-glycerophosphate dehydrogenase activity.  At higher levels of physical activity, the exercised rats enhibited larger adrenal glands and lower values of hepatic glucose-6-phosphate dehydrogenase.  It is concluded that specific levels of voluntary exercise are needed to achieve specific metabolic effects.


Metabolic effects of exercise.  II. Residual metabolic effects of exercise in rats. This report described the duration of changes in serum lipids, adrenal weight and hepatic G-6-PD activity in rats following the termination of 10 weeks of voluntary activity in a revolving drum. Exercised rats had lower weight gain, larger adrenal glands, lower serum cholesterol, lower serum triglycerides and lower liver glucose-6-phosphate dehydrogenase (G-6-PD) activity than the sedentary controls. The differences between exercise and control rats in adrenal gland weight, body weight and G-6-PD tend to disappear within 3 wk after termination of the exercise. These experiments provide evidence that exercise can affect lipid metabolism and have a beneficial effect on the lowering of serum lipids. It also shows that this effect will persist for up to 3 wk after the exercise is terminated, under the experimental conditions of this study.


Comparative response of castrate and intact male rats to diethylstilbestrol. Treatment of castrate and intact male rats with DES in the feed was used to note its comparative effect on feed intake vesicle, testicle, spleen and liver weights, and DES similarly reduced gain and feed efficiently in both castrate and intact male rats. Thus, there appears to be a basic difference in the response of rats to DES, compared to cattle and sheep, that does not depend on whether they are intact or castrate males.


Effect of arginine deficiency on normal and dystrophic chickens. Normal and genetically dystrophic chickens were fed diets deficient in arginine or further aggravated by the addition of lysine. Growth of dystrophic chicks is depressed less by a deficiency of arginine than that of normal chicks. Muscular ability of dystrophic chicks was improved by feeding them an arginine deficient diet but this effect may be related to the size of the bird. The total creatinine content of the pectoral muscle of dystrophic chicks was reduced more with a deficiency of arginine than was that of normal chickens.


Vascular and extravascular volume changes due to elevated venous pressure. Abrupt elevation of venous pressure causes an initial rapid and a secondary slow increase in total tissue volume (plethysmography).  Changes in total tissue volume and blood conductivity from the isovolumetric state were determined to assess what factors determined the two components of the tissue volume change.  The initial component of the plethysmograph record would appear to be 90% vascular volume change and 10% extra-vascular  volume change.  Since the two techniques measured identical amounts of capillary filtration during the second component of the recording there would seem to be no slow component of vascular volume increase following venous pressure elevation.  Evidence that elevation of venous pressure causes myogenic closure of precapillary vessels isolating a segment of the microvasculature is presented.


Neurogenic influence on pulmonary surface tension and cholesterol in cats. Previous work showed that stress involving the sympathetic nervous system via mechanical head injury and hyperbaric oxygen results in a decreased lung compliance and altered alveolar surfactants. Similar changes were associated with sympathetic nerve stimulation via the stellate ganglion. In view of reports that the minimum surface tension attained by lung wash fluid is increased by very small amounts of cholesterol content of the alveoli. The results show a nearly 200% increase in intra-alveolar cholesterol as well as high minimum surface tensions following sympathetic nerve stimulation. Such changes developed in the absence of any increase in lung wet wt/dry wt ratios. The results from the present study suggest that the previously reported decreased lung compliance and increased minimum surface tension associated with sympathetic stimulation may be due at least in part to contamination of the alveolar surfactants with large amounts of cholesterol.


Hematologic observations on the yak.

Hematologic observations on the yak. The uak has two hemoglobins sharing a common globin chain.  Hb slow appears unique to the yak among the ruminants studied.  It is not known if Hb slow is important in high altitude adaptation, but physilogic rather than hematolgoic adjustments may be more important agter acute blood loss, as 2,3-DPG remains nit and no disproportionate hemolgoin production occurs.


Histochemical measurements of rat kidney hexokinase. HK has been measured in substructures of the developing rat nephron.  Reactions were carried on samples dissected from freeze dried kidney and assayed in 1 mul reaction volume utilizing the "oil-well" technique.  Samples from 4 days prenatal to 44-day adult were analyzed.  Activity during development decreased in G, PCT, and it increased in ALH.  There was little change in PRT, DCT and CT.  Activity in small arteries decreased.


A model for ultracentrifugal quantification of (35-S) bromosulphthalein-binding to plasma proteins in the presence of radioimpurities. Sloutions of (35S)bromosulphthalein ((35S)BSP) in heparinized canine plasma, in the proportions established in vivo after injecting BSP intravenously to test liver function, were ultracentrifugated at 226,000 g for 24 hr at 5 degrees.  Protein-free supernatant was replaced by Krebs-Ringer buffer (pH 7.40), the protein sediment resuspended, and the mixture recentrifugated.  That process was repeated several times, and the radio-activity of each resulting supernatant was measured. Since (35-S)BSP could not be adequately purified, supernatant radioactivities reflected both (35-S)BSP and radioimpurity.  Therfore, a model was derived that (i) interpreted the rapid decrease in supernatant radioactivities of initial centrifugations and the gradual fall therafter; and (ii) allowed us to determine picomoles of non-protein-bound (35-S)BSP. Results indicated that only 0.053% (SD .0013%) of BSP in our system was not protein-bound.


Renin and distal tubule Na during stop flow in dogs. Using radioimmunoassay techniques, arteria (A) and renal venous (RV) plasma renin activities were measured in sodium pentobarbital-anesthetized dogs during clearance and stop-flow periods. Changes in RV-A renin were used to estimate changes in renin secretion. RV-A renin increased during stop flow from its average value during clearance periods, whether 10% mannitol in 0.15 M NaCl or 10% mannitol in 0.1 M Na2SO4 was being administered intravenously. However, RV-A renin during mannitol + NaCl stop-flow periods was significantly greater than during mannitol + Na2SO4 stop-flow periods. Distal tubular fluid Na concentrations as indicated by stop-flow analysis were higher during the latter. These observations suggest that a macula densa stimulus, Na concentration, and/or load, may control renin secretion during ureteral occlusion.


Environmental lighting and human salivary gland function. Three experiments were conducted to (a) determine the effect of light deprivation on submandibular flow, (b) test for accommodation in darkness-induced parotid flow-rate depression, and (c) evaluate the effects of lights of widely varying intensities on parotid flow. Light deprivation decreased submandibular flow rate from 0.146 ml/min to 0.045 ml/min, a decrease of 69%. It is suggested that photic input through the retina provides stimulation to the salivary glands in the human through the superior cervical ganglion in a system similar to that present for the pineal. This implies that the sympathetic nervous system functions in the regulation of a component of the resting flow from both the parotid and submandibular glands. Series of parotid saliva samples collected in darkness did not reveal a pattern suggestive of accommodation to darkness. The effect of darkness on flow is as strong in the first sample as in those collected later under darkness. Reinstitution of light brings immediate restoration of the routine level of unstimulated salivary flow. A light intensity as low as 0.1 fc is sufficient to maintain the usual level of resting parotid flow. Increasing intensity up to 150 fc did not significantly increase this rate of flow.


Adrenal rhythmicity in the immature pseudopregnant rat. A daily rhythm of serum corticosterone persists in 31 day old immature female rats in which pseudopregnancy has been induced by means of 25 IU pregnant mare's serum gonadotrophin (PMS) given at 26 days of age. There is, in addition, a daily rhythm of progesterone in 31-day old controls with a rise during the day and a fall during the dark portion of the photoperiod. PMS-injected rats had a much higher level of progesterone but no rhythm.


Effect of blood volume expansion on tubule sodium transport in the isolated dog kidney. Nonrecollection end-proximal tubule micropuncture technique and the microsphere method for estimating fractional distribution of renal cortical blood flow were applied to further define the mechanism of the natriuresis in the isolated dog kidney in response to volume expansion with equilibrated blood. Following volume expansion sodium excretion increased +79 plus or minus 24 muEq/min (P less than 0.01) in the face of significant decreases in inulin clearance (C IN) and renal blood flow (RBF) and in the absence of changes in renal perfusion pressure, plasma protein concentration or packed cell volume. (TF/P)IN of end-proximal tubular fluid decreased from 1.65 plus or minus 0.03 to 1.53 plus or minus 0.04, P less than 0.025, and proximal tubule absolute reabsorption decreased from 36 plus or minus 3 to 29 plus or minus 2 nl/min, P less than 0.05. The decrease in absolute reabsorption, however, was balanced by a decrease in single nephron GFR (SNGFR) so that no increase in distal delivery of fluid (V TF) out of the proximal tubule was detected. SNGFR/C-IN remained constant. No change in fractional distribution of RBF was detected. The data indicate that volume expansion with equilibrated blood depresses proximal tubule fractional and absolute reabsorptive rates in the isolated kidney but since V-TF did not increase, they imply that the natriuresis derives from a decrease in sodium transport along more distal nephron segments.


Polycythemia induced in rats by intrarenal injection of nickel sulfide Ni3S2. In rats, injection of nickel sulfide (5 mg) into each pole of one kidney, unlike intramuscular administration, elicits a plethoric condition a few weeks later.  The resulting hematologic changes (increased hematocrit, hemoglobin, erythrocytes and circulating erythrocyte mass with normal plasma volume) indicate that the plethoric condition is due to polycythemia, which is not associated with alterations in the 2,3-diphosphoglyceric acid content of erythrocytes.  Removal of the treated kidney, following the development of the polycythemia, as well as the tumor growth and expansion in the renal parenchyma, reverse the plethoric condition, suggesting that the erythropoietic changes derive from nickel-induced renal lesions.  Further studies are required to elucidate the nature and mechanisms of the cellular alterations.


Differential binding to Sepharose-Con A of B12-binding proteins from human gastric juice. Human gastric juice was found to contain at least two vitamin B-12 binding substances.  One of the proteins which formed a complex with B12 was found to bind to a column containing Sepharose-ConA.  Since the protein which bound to Sepharose-ConA was absent in the gastric juice of pernicious anemia patients it was concluded that this protein was intrinsic factor.  The ability of intrinsic factor to bind to Sepharose-ConA offers a potential means by which intrinsic factor could be separated from other B-12 binding proteins in gastric juice.  The ConA binding properties of intrinsic factor might be exploited in the development of a diagnostic test for pernicious anemia.


Radioimmunoassay for GH-release inhibiting hormone. The synthetic growth hormone release inhibiting hormone (GH-RIH) was conjugated with human serum globulin using glutaraldehyde and administered to rabbits. An antiserum thus generated 70% of 125I-Tyr1-GH-RIH. The binding was inhibited by unlabelled GH-RIH and the inhibition was dose-related, enabling us to establish a radioimmunoassay method for GH-RIH. The minimum detectable dose was 4 pg. A linearity was demonstrated for immunoreactive GH-RIH of extracts of rat and pig hypothalami, indicating that they contained substance(s) indistinguishable from GH-RIH. Various hypothalamic and pituitary hormones did not interfere with the radioimmunoassay, but considerable cross-reaction was observed for linear GH-RIH and the ring portion of GIH-RIH, suggesting that the antigenic determinant involved the amino acid sequence from position 3-14 of GH-RIH or part of it. Plasma protein appears to contain substance(s) immunologically indistinguishable from GH-RIH or to interfere, in a nonspecific manner, with the radioimmunoassay system for GH-RIH.


Aging and ovarian delta5-3beta-hydroxysteroid dehyrogenase in rats. Ovarian delta5-3beta-hydroxysteroid dehydrogenase activiety and protein content were determined in long-evans rate 1-24 mo of age.  Activity of the enzyme per miligram of protein was maximal between 2 and gram of protein was maximal between 2 and 4 mo of age and declined theragter.  Ovarian enzyme activity of the 24-mo old rat was significantly less than that of the prepubertal animal.  Total ovarian enzyme acitivity was maximal in 4-mo old rats.  A decline in ovarian protein was noted between 4 and 24 mo of age.


The use of 51Cr for sheep red blood cell survival studies. The red blood cell half-life as determined by 51Cr-labelled autologous cells in five adult sheep was 13.7 days.  In contrast, the red blood cell life span measured by cohort 59Fe-labelling in six adult sheep was 111.7 days.  The rapid loss of 51Cr-activity from the circulation appears to result from rapid elution of the label from the circulating red cells.  51Cr does not appear to be a suitable isotope for erythrokinetic studies in sheep.


Platelet recovery after induction of acute thrombocytopenia. After mild thrombocytopenia (about 50-100% of control platelet level), induced by injection of antiplatelet serum (APS), platelets increased at a fairly constant and moderate rate for about 4 days and reached a maximum count, greater than pretreatment levels, on the fifth day. After moderate to severe thrombocytopenia, an early moderate rate of platelet increase was succeeded within 2 days by a second more rapid rate that persisted for about 3 days. The maximum overshoot of the platelet count was usually less than twice the pretreatment level. After the largest doses of APS, the platelet count remained depressed for several days. Platelet response after acute thrombocytopenia induced with antiserum is therefore variable, depending on the level and duration of thrombocytopenia.


Effects of several antianginal agents on pacing-induced S-T Segment depression in the atherosclerotic rabbit. Several agents used clinically in the treatment of angina pectoris were studied in an atherosclerotic rabbit model previously shown to be useful in differentiating antianginal drug activity.  Intravenously administered isosorbide dinitrate afforded protection against pacing-induced S-T segment depression in a dose-related manner.  Drugs with no protective effect included pentaerythritol tetranitrate, chromonar, and papaverine.  Propranolol also did not prevent pacing-induced S-T segment depression, due in part to the overriding of the beneficial negative chronotropic effect of this drug by pacing.


The effect of mineralocorticoid deficiency on renal concentrating and diluting capacity. To examine the effect of mineralocorticoid deficiency on sodium transport by the ascending limb of the loop of Henle, free water clearance and reabsorption were measured in the same six dogs under conditions of aldosterone deficiency and mineralocorticoid sufficiency.  Aldosterone deficiency was induced by bilateral adrenalectomy with dexamethasone replacement.  H2O/100 ML GFR ranged from 4.0 to 19.5 in the aldosterone deficient dogs and 4.5-18.6 in the mineralocorticoid sufficient dogs.  H2O/100 ML GFR plotted against V/100 ML GFR showed no significant difference between the two groups.  H2O/100 ml GFR ranged from 1.2 to 6.5 in the mineralocorticoid sufficient group and 2.4-8.5 in the mineralcorticoid sufficient group and 2.4-8.5 in the aldosterone deficient group. TC-H2O/100 GFR plotted against Osm/100 ml GFR revealed no significant urine concentration in the mineralocorticoid sufficient group was 1356 mOsm/kg plus or minus 254 (SD) and 1386 mOsm/kg plus or minus 331 (SD) for the aldosterne deficient group; the difference is not significant.  This study failed to demonstrate any effect of aldosterone deficiency on renal concentrating and diluting capacity and thus provides inferential evidence against an effect of aldosterone on ascending limb sodium reabsorption.


Effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) on Friend leukemia virus infections in mice. Ribavirin, when administered intraperitoneally to mice infected with Friend leukemia virus, significantly inhibited development of the disease as determined by inhibition of virus-induced splenomegaly and viable virus titers in the spleen and plasma of the infected animals.  The drug was effective whether administered ip in multiple daily treatments, treatments every three days, or single injection.  Greatest efficacy was seen when therapy began early in the infection, presumably while the virus was in its eclipse phase.


Placental transport of creating in the rat. Pregnant rats near term were injected iv with creatine-1-14C or creatinine-1-14C and the distribution of radioactivity was studied in maternal and fetal blood as well as in the visceralyolk sacs and chorioallantoic placentae. After injection of creatine-1-14C into the dam, the level of radioactivity in fetal blood was somewhat higher than that inmaternal blood at 30 min, reached maximal levels after 30 min, and remained essentially constant for at least 4 hr. The radioactivity in the labyrinth and junctional zone portions of the chorioallantoic placenta and the yolk sac was maximal after 30-6- min and was always considerably higher than that in the fetal and maternal blood. Furthermore, the level of radioactivity in the labyrinth was several times higher than that in the junctional zone portion of the chorioallantoic placenta and the yolk sac in which the radioactivity remained essentially constant after 1 hr. On the other hand, the radioactivity in the labyrinth declined rapidly after the first hour and reached levels which were about one-third of the maximal value after 4 hr. When labeled creatine was injected into the dam, 90% of the radioactivity present in the fetal blood and chorioallantoic placenta was found in free creatine as shown by paper chromatography in three different systems. Ancillary studies showed that the creatine concentration in fetal blood was several times higher than that in the maternal blood on the 21st-22 day of gestation. Creatine concentration in both portions of the chorioallantoic placenta as well as the visceral yolk sac was higher than that in the fetal blood, indicating that a downhill concentration gradient existed between creatine in placental tissues and that in the fetal circulation. When creatinine-1-14C was injected iv into pregnant rats, the level of radioactivity in fetal blood rose to a maximum after 5-15 min, but the radioactivity in the maternal blood was considerably higher than that in either the fetal blood or the chorioallantoic placenta and yolk sac. These studies indicate that creatine is actively accumulated and released by the placental unit to the growing rat fetus, while creatinine is passively transported from mother to conceptus across the placentae, at least during the later stages of rat gestation.


The effect of hyperbaric exposure of 20 atmospheres-absolute (He-O2) on sphingoglycolipids of rat tissues. The effect of hyperbaric exposure of helium-oxygen at 20 atmospheres-absolute (ATA) on sphingoglycolipids of rat liver, kidney, lung and spleen was studied.  No changes were found in the total lipids of the tissues of rats held in ambient air, helium-oxygen mixtures at 1 ATA and 20 ATA.  The amounts of three glycolipids in the spleen and the monoglycosyl ceramide in the lung were decreased in the stressed animals.  There were changes in the fatty acid profiles of glycolipids between groups of animals held in ambient air and He-O2 at 1 ATA. Greater changes were observed in the amount of glycolipids from liver and kidney of animals held at 1 ATA and 20 ATA, providing additional evidence that helium can affect cellular metablism at ambient pressure.  Chain elongation of fatty acids was observed in glycolipids of liver, kidney and spleen of rats exposed to helium-oxygen at 20 ATA compared to animals held in helium-oxygen at 1 ATA.


Antiprostatic effects of a nitrogen mustard of estriol. The chemical ester of a nitrogen mustard with estriol was tested for its antiprostatic effects in dogs and rats.  The E33-mustard was shown to interfere with the uptake of labeled estriol in the dog prostate and by the ventral prostate of the rat; and to increase the uptake of the radioactivity associated with testosterone in the dog prostate.  The weights of the ventral and dorsolateral prostates of the rat were significantly reduced following the administration of E3-mustard for 2 days.  The results are interpreted to be very similar to those obtained with the mustard of E (Estracyt) and the effects are probably a combination of the actions of the released estrogen (D) and/or mustard, either adding individually or in concert.


Accumulation of 3H-estradiol in the vaginas and pituitary glands of mice of inbred strains. The sensitivity of the vaginal epithelium of ovariectomized mice of the A and C57 strains to estradiol differ approximately fivefold.  The vaginas of the more sensitive C57 strain did accumulate more 333H-E2 at 1 hr in two or three experiments but the retention at 6 and 12 hr was not significantly different.  The pituitary accumulation of H-E2 by the pituitary-tumor susceptable C57 mice, although not significantly greater than that of the nonsusceptable A strain mice at 1 hr was higher at 6 and 12 hr after the injection.  Most of the toluene extractable radioactivity from pituitary glands and vaginas was estradiol with no strain differences.  The accumulation of H-E2 in other tissues was not significantly different in mice of the two strains.


Effects of vitamin E deficiency on GSH-induced swelling of rat liver  mitochondria. Liver mitochondria from alphatocopherol deficient rats swell more rapidly, both spontaneously and in the presence of GSH, than those from control animals.  The increased swelling of deficient mitochondria induced by GSH was completely eliminated when mitochondria were left longer than two hours at 0 degrees in the suspending medium. GSH-induced swelling of liver mitochondria from alpha-tocopherol deficient rats is reversed by ATP, polyvinyl pyrrolidone (PVP) and by oral administration alpha-tocopherol (2 mg/day per rat).  Swelling of mitochondria in the above system was completely inhibited by the respiratory chain inhibitor, cyanide (.001 M), and partially by azide (0.001 M).  We suggest that the swelling tendency of liver mitochondria from alpha-tocopherol deficient rats might be associated with an altered respiratory mechanism and/or an alteration in membrane permeability.


Effect of relaxin on mammary gland growth and lactation in the rat. Mammary DNA, RNA and RNA/DNA were measured in groups of 10 ovariectomized rats treated for 20 days with relaxin (R) in doses of 20 and 90 guinea pig units (GPU) alone or in combination with 1 mug estradiol benzoate (EB) or EB plus 3 mg progsterone (P).  No treatment, EB only, and EB plus P served as control groups.  Twenty GPU R alone significantly increased DNA over the no treatment group while 90 GPU did not increase DNA  any higher.  Although DNA values for the EB group were higher than no treatment and EB plus P higher than EB, R was not effective in increasing DNA in combination with either EB or EB plus P.R alone at either level did not change RNA from the no treatment group, but 90 GPU R in association with EB and both levels of R in association with EB plus P significantly reduced RNA in relation to the approiate control groups.  Relaxin acts synergistically with estrogen and progesterone to develop the mammary apparatus and at the same time to suppress lactation.  Removing the inhibitory effects of relaxin at parturition may be an important prelude to lactogenesis.


Improved hatch rate in helium-oxygen by reducing shell diffusion area. For eggs incubating in a He atmosphere (79% He/21% O2), covering approximately 50% of the shell with melted paraffin improves hatch rate to control values (from 20% to 74%) and decreases egg weight loss to control values (from 17% to 9%). In air (79% N2/21% O2) the same paraffin treatment depresses hatch rate. The role of the inert gases in incubation appears to be an indirect one related to their modification of the rate of gaseous flux across the shell with the adverse effects of He due to excessively rapid diffusion.


Inhibition of estradiol-induced intranuclear inclusions by an anti-estrogen (nafoxidine) in mammotrophs of the Mongolian gerbil. Nafoxidine, an anti-estrogen, inhibited the induction of intranuclear inclusions by estradiol in mammotrophs of the male Mongolian gerbil. No inclusions were observed with inhibitor alone or in control-injected gerbils. Estrogen may well act directly on mammotrophs in induction of nuclear inclusions.


Factors affecting the initial extraction of ovine gonadotropins. The method of tissue homogenization as well as the solvents used for extraction influenced the protein yield, the specific activity of the oLH and oFSH, and the total units of each hormone recovered. Use of the Tekmar homogenizer (Method 2) produced a fivefold increase in the total yield of oLH per Kg glands (2390 units, Method 2; 474 units, Method 1) and the relative potency of this partially purified LH from the 80% ethanol precipitate was increased (0.16 times NIH-LH-S18, Method 2). By combining the aqueous extraction--ammonium sulfate precipitation with a subsequent ethanolic acetate extraction (Methods 3 and 4) the combined yields provided a 2.4-fold increase in oLH and 1.4-fold increase in oFSH. Thus the total units recovered of oFSH and oLH can be increased simply by changing the methods of homogenization and extraction.


Effects of magnesium deficiency and thyroparathyroidectomy on calcium active transport by rat duodenum. Mg deficiency was produced in rats by feeding a Mg-free diet. Ten days of dietary Mg depletion led to an increase in active duodenal Ca absorption in sham-operated animals, but this increase was abolished by thyroparathyroidectomy (TPTX). In addition, TPTX reduced Ca absorption in control aminals fed a Mg-containing diet. More prolonged Mg deficiency was produced by feeding sham-operated animals the Mg-free diet for 19 days. This condition resulted in more marked hypomagnesemia and a depression of Ca transport rates to the level observed in the TPTX groups. These results are consistent with the concept that adaptation of duodenal Ca transport in response to Mg deficiency occurs through an increase in parathyroid hormone (PTH) secretion; however, direct blood PTH measurements will be required to prove this point.


Effect of chronic ethanol ingestion on mitochondrial protein synthesis in Sinclair(S-1) miniature swine. The effect of chronic ethanol ingestion on hepatic mitochondrial protein synthesis in miniature swine was investigated. After 3 wk on test, there was no decrease in the rate of amino acid incorporation between livers of control and ethanol consuming pigs. After 6 wk on test, there was a 33% decrease in rate of hepatic mitochondrial membrane protein synthesis in livers of experimental pigs, as compared with controls. When analyzed by SDS-gel electrophoresis, a decrease in labeling of the 40,000 mol wt peak, from both whole membrane protein and proteolipid protein profiles, was observed for livers from ethanol consuming pigs as compared with controls.


Different responses of two mouse strains to 650 rads and protection by surgical stress. Radiation survival of C57B1/6J mice after 650 rads improved from 1.7% to 66% when mice were stressed surgically one week before irradiation. Surgical stress one or three weeks before irradiation increased endogenous CFUs and decreased exogenous CFUs in C57B1/6J and DBA/1J mice. Survival may be related to the proportion of stem cells in different phases of the cell cycle, which was abnormal in C57B1/6J mice and compensated for by a greater number of nucleated cells per femur.


Alleviation of silver toxicity by selenite in the rat in relation to tissue glutathione peroxidase. Dietary Se (0.5 ppm Se supplied as sodium selenite to a casein-based diet containing 0.02 ppm Se and lacking in vitamin E) prevented the growth depression observed in rats receiving 76 ppm Ag in the water supply and markedly improved growth and survival of those given 751 ppm Ag. The Ag concentration of liver and possibly of kidney was increased by Se. Liver glutathione peroxidase activities from rats fed 0.5 ppm Se and given 76 and 751 ppm Ag for 52 days in their water were, respectively, 30% and 4% of those from control rats fed 0.5 ppmSe without Ag. In rats fed a diet, adequate in vitamin E (100 IU/kg) and Se (0.5 ppm as sodium selenite), administration of 751 ppm Ag in the water for 15 wk reduced liver GSH-Px activity to 5% of that from control rats receiving no Ag. GSH-Px activity of erythrocytes and kidney was decreased by Ag to 37% and 38%, respectively, of control values. It is concluded that in vivo administration of Ag dramatically decreased liver GSH-Px in rats fed Se-supplemented diets with or without vitamin E. Furthermore, supplemental Se (0.5 ppm) prevented the growth depression and mortality caused by Ag in rats fed a diet lacking vitamin E, while increasing the Ag concentration of liver and kidney.


Prolonged production of ovarian progesterone in pseudopregnant hamsters bearing deciduomata. Decidual tissue in pseudopregnant hamsters prolonged ovarian progesterone release by one full day. The terminal decline in circulating progesterone occurred abruptly overnight in experimental and control animals and was synchronous with termination of hyperemia. During the hours immediately preceding luteal regression the mean progesterone level was significantly higher in hamsters with decidual tissue.


Rat immunoglobulins in serum and secretions: comparison of IgM, IgA and IgG in serum, colostrum, milk and saliva of protein malnourished and normal rats. Immunoglobulin levels in colostrum and milk of normal and protein malnourished rat dams and in serum and saliva of their offspring were quantitated by radial immunodiffusion employing purified anti-rat alpha, gamma and mu. In general, no significant difference was observed in the level of colostral IgA in malnourished as compared to normal rat dams or in the level of serum IgA and IgM and salivary IgA and IgG2a of their offspring. On the other hand, malnourished mothers demonstrated approximately twofold lower levels of colostral IgG2a than normal mothers throughout the entire period of lactation. In addition, at every interval tested, the level of IgG was approximately 1.5- to 2-fold less in malnourished as compared to normal offspring.


Germ-free status and colon tumor induction by N-methyl-N'-nitro-N-nitrosoguanidine. Female germfree and conventional rats of 50 days of age were injected intrarectally with MNNG for 20 wk (total dose, 48 mg/rat) and autopsied 30 wk after last injection. The colon adenomas induced by MNNG were doubled in germfree rats compared to conventional animals. However, germfree status had no effect on the incidence of adenocarcinomas. It is concluded that pharmacodynamics and metabolism of carcinogen play a role greater than the immune status of the animal in the action of carcinogens such as MNNG.


Phytohemagglutinin committed lymphocytes: the mitotic activity of the phytohemagglutinin stimulated lymphocytes. The purpose of these experiments was to find out why there was a decrease in the mitotic activity in the prolonged PHA stimulated lymphocyte cultures. The present observations suggested that the decrease in the mitotic rate in the prolonged PHA-stimulated lymphocytes was not due to a deficiency in the essential material in the culture medium to sustain a maximum mitotic response, nor was it due to an accumulation of the metabolites that might inhibit the lymphocytes to undergo further division. However, the results obtained suggest that there may be a limitation in the number of generation cycles in which the T lymphocytes can be stimulated with the PHA. They also suggest that a second dose of PHA may stimulate some of the original noncommitted lymphocytes to undergo mitosis thus attempting to maintain the in vitro lymphocyte population.


Control of cell division in the cornea of rats II. Age-dependent effects of dexamethasone upon circadian mitotic activity. Data are presented here which verify that immature rats exhibit no circadian fluctuation of mitoses in the corneal epithelium prior to the third week of life. These data indicate that dexamethasone administration induces age-dependent alterations in the circadian mitotic pattern of the corneal epithelium. Nine day old animals still revealed no rhythmic component in circadian mitotic activity after dexamethasone treatment. Eleven-, 12- and 13-day old animals treated with dexamethasone exhibited circadian cycles which looked qualitatively like the circadian rhythm of the 15-day old animal. Fifteen-day old animals responded with a synchrony of mitotic activity at 0700 hr and a generalized decrease in mitotic activity. The possible dependence of these responses upon existing circadian mitotic activity and maturation of the central nervous system and/or the glucocorticoid target tissue is discussed.


Metabolic studies in eviscerated rats with functional livers. A new technique is described for evisceration in the rat in which liver function is preserved. These animals lack all known sources of glucagon and insulin and are capable of active gluconeogenesis, urea formation and ketone body production by the liver. Measurements of blood levels of the metabolites of the caloric substrates showed that, unlike the classical eviscerate preparation, these animals maintain high blood glucose, urea and ketone body levels for up to 72 hr as contrasted with the profound decrease in these constituents in the absence of the liver. Survival time is also significantly extended from about 6 hr in rats lacking liver function to 72 hr or more when the liver is viable. This new surgical preparation is a valuable tool for studying the role of the liver in absence of the known gastroentero-pancreatic hormones. It would also be utilized as a model of "acute" diabetes.


Effects of indomethacin on furosemide-induced changes in renal blood flow. The effects of indomethacin on furosemide induced changes in renal blood flow were determined in dogs. Furosemide alone caused an increase in total renal blood flow while indomethacin alone decreased renal blood flow. When furosemide was administered to animals pretreated with indomethacin the increase in renal blood flow was blocked. Changes in intrarenal blood flow distribution were also measured using radioactive microspheres. The pattern of blood flow distribution after furosemide was modified in some of the animals pretreated with indomethacin. Stimulation of renin secretion occurred after furosemide in indomethacin-treated animals. The data suggest that the changes in renal blood flow produced by furosemide may be modulated by the prostaglandin system.


Metabolic response after isoproterenol-induced myocardial infarction in arteriosclerotic breeder vs nonarteriosclerotic virgin intact and gonadectomized male rats. Male, nonarteriosclerotic (virgin) intact and castrated, Sprague-Dawley rats and male, arteriosclerotic (breeder) rats were subjected to an acute and massive myocardial infarct, by treating them with two large, subcutaneous doses of isoproterenol, spaced 24 hr apart. Serum insulin and glucose rose abruptly after the first injection of isoproterenol, but not after the second injection. Free fatty acids rose, most markedly, in the intact, nonarteriosclerotic rats, less in the arteriosclerotic breeders, and least in the castrates. These changes in free fatty acids coincided with numerical survival, i.e., greatest number of survivors in castrates. The castrated males also manifested the least amount of congestive heart failure and showed the greatest capacity to affect myocardial repair. It is suggested that reduced androgen levels may have an ameliorative effect on the usual pathogenesis of isoproterenol-induced myocardial infarction in rats.


Aortic histomine syntesis in experimental neurogenic hypertension. Aortic histamine synthesis of normotensive rats has been compared to that of rats rendered hypertensive via production carotid sinus ischemia and to animals additionally subjected to bilateral adrenalectomy. Results indicate that the aortic histamine-forming capacities (HFC's) of rats sacrificed 24 hr after surgical treatment were elevated 83% and 103% for hypertensive rats and those additionally subjected to adrenalectomy, respectively. At an 8-day postoperative interval, the respective aortic HFC's were elevated over control by 33% and 45%, although at this time interval animals were not considered hypertensive. This study thus offers suggestive evidence that hypertension causes increased vascular permeability by increasing the histamine-forming capacity of the vessel wall.


Release of transcobalamin II by canine organs. The output of vitamin B12 transport proteins by canine tissues was determined from isolated, perfused organs. Transcobalamin II as identified by four techniques was released by the spleen, heart, liver, and kidney. When related to perfused weight, the greatest output occurred from the kidney.


Serum vitamin B12- binding proteins in neutropenia. Serum unsaturated vitamin B12-binding capacity (UBBC) has been shown to fluctuate with neutrophil levels and has been reported to correlate with TBGP in normal and hyperleukocytic states. However, the present report demonstrates that the above relationship is not present in neutropenia, suggesting that some of our concepts regarding UBBC may have to be reexamined, since factors other than TBGP appear to be operative. There was a wide scatter of UBBC values among the 39 neutropenic subjects studied, the mean being significantly above normal. There were few low values. High UBBC was primarily confined to subjects with transient neutropenia. Normal values were generally seen in steady neutropenia. The difference in UBBC was primarily due to Transcobalamin I, the other serum binders being similar in both groups. No other significant diagnostic pattern of UBBC was found. Recovery from neutropenia was accompanied by a rise in UBBC in all cases except in four patients whose UBBC was initially very high and fell with recovery. No discernible pattern of serum B12 levels existed, although subnormal levels without evidence of B12 deficiency were found in three of the seven patients with aplastic anemia. Serum B12 levels did not change with recovery in approximately half of the neutropenic subjects, change being variable in the others. Neither serum B12, UBBC, total B12-binding capacity, or any of the three serum B12 binders correlated with neutrophil count, bone marrow findings, TBGP, or granulocyte turnover rate.


Chromosomal instability in cell lines derived from patients with xeroderma pigmentosum. The chromosomes of four cell lines derived from skin biopsies of four patients with xeroderma pigmentosum (XP) were studied and compared with corresponding controls. In the early passages, all XP lines had normal chromosome constitution with rates of polyploidy and chromosome aberrations within the range found in the controls. In the later passages, the XP cell lines had higher levels of chromosome abnormalities. The degree of abnormalities varied greatly among the XP lines; two lines had very high level of polyploidy (up to 50%) and cells with chromosome aberrations (up to 79%), the other two XP lines had a normal level of polyploidy and a slightly higher incidence of cells with chromosome aberrations than normal. The most common type of aberration was dicentrics.


Cardiovascular and platelet responses in the dog to the monoenoic prostaglandin precursor dihomo-gamma-linolenic acid. The monoenoic prostaglandin precursor, dihomo-gamma-linolenic acid (DGLA), in a single dose intravenously (2.0 mg/kg) in dogs, produced a biphasic alteration in systemic arterial pressure (SAP) with a predominant and marked depressor effect. This SAP response is approximately equidepre-sor to the effect of PGE1 5 mug/kg. DGLA had a positive inotropic effect, causing a greater increase in myocardial contractility than PGE1 in an equidepressor dose. The effect of DGLA on MC was not altered by ganglion blockade or beta-adrenergic blockade. Aspirin blocked the sustained depressor response to DGLA but not an initial drop in SAP and increase of MC of very short duration. Aspirin had no effect on PGE1 or PGF1 alpha responses. DGLA caused no thrombocytopenia, but caused a decrease in sensitivity to platelet aggregation. Control fatty acid injections produced variable effects with no resemblances to DGLA responses. It is concluded that DGLA produces direct depressor and positive inotropic responses as well as responses which may be due to conversion to an endoperoxide formed in the biosynthesis of prostaglandins. In contrast, in equidepressor doses, arachidonic acid (AA), the bisenoic prostaglandin precursor, produces a delayed, single-phase depressor effect which may be due to endoperoxide formation alone. Further, the effect of AA on MC is reflex and is blocked by hexamethonium.


Kaluresis and cardiac sensitivity to hyperkalaemia in intact and adrenalectomized rabbits. Rabbits K loaded by infusion of 2 meq KCl/kg/hr excrete over 55% of the administered K in the urine and do not develop prelethal ECG  changes until mean serum K attains to 14.9 meq/liter, i.e., 11.8 meq/liter above the average preinfusion level. Four hours after bilateral adrenalectomy there is a profound diminution of urinary K loss in K loaded rabbits--less than 7% of the infused K is excreted. There is, however, no significant change in cardiac sensitivity to hyperkalemia. K loaded dogs lose only about 20% of infused K in the urine and develop prelethal ECG  changes at similar to 10.2 meq/liter, i.e., 5.6meq/liter above the mean of the preinfusion levels. After adrenalectomy, urinary K loss is only moderately diminished (12%  of infused K is still found in the urine), but cardiac sensitivity to K is markedly increased: prelethal ECG changes appear at a serum K level of similar to 7.6 meq/liter--about 2.9 meg/liter above the preinfusion value.


Concentration of serotonin in intestine and factors affecting its release. The concentration of serotonin in the female chicken intestine (10.79 mug/g wet tissue) was significantly higher than in the male (7.98 mug/g). The release of serotonin from an isolated perfused intestine was studied. The intestine continually releases serotonin at the rate of 10 ng per g/min. A number of substances, including glycine, epinephrine, and acetylcholine, caused a significant release of serotonin, with acetylcholine having the greatest effect. Histamine or electrical stimulation did not affect the release of serotonin.


Renal clearance of human and rat albumins in the rat. Experiments were done to investigate whether molecular discrimination occurred in the renal handling of two species of serum albumin. Human albumin, 40 mg,  was infused into rats; it was removed from serum (t1/2 equal to 15.8 hr) more rapidly than previously reported measurements of removal of endogenous rat albumin (t1/2 equal to 46 hr). Human albumin was cleared by the rat kidney at a constant rate of 0.0026 mul/min--a value virtually identical to that of rat albumin (0.0020 mul/min). In rats with proteinuria following the single iv injection of puromycin aminonucleoside, human albumin was removed from serum with a half-life of 17.6 hr. During the development of the nephrotic syndrome, the renal clearances of human and rat albumin increased proportionately. Despite the difference in the serum concentration and rates of removal of the two species of albumin, renal handling of the two species was similar. Thus the kidney did not appear to discriminate in its handling of these two proteins.


Discriminative stimulus properties of mescaline: mescaline or metabolite? The purpose of this study was to investigate possible similarities in the interoceptive stimuli produced by mescaline and its metabolites. Rats were trained in a 2 lever operant chamber to discriminate between the drugged state (mescaline 25 mg/kg) and the nondrugged state (saline). Following acquisition of discriminative response control the rats were pretreated with either saline, aldehyde dehydrogenase inhibitors or amine oxidase inhibitors and tested stimulus generalization produced by i.p. injections of 3, 4, 5-trimethoxyphenylethanol (TMPE), 3, 4, 5-trimethoxyphenylacetaldehyde (TMPA), N-acetylmescaline, mescaline or saline. The results indicated that both aldehyde dehydrogenase and amine oxidase inhibitors enhanced the effects of mescaline, while TMPE, TMPA and N-acetylmescaline failed to exhibit generalization to the mescaline state, regardless of pretreatment. These findings do not indicate the role of a metabolite in the interoceptive cue produced by mescaline.


Dilutional hyponatremia due to diazoxide-produced polydipsia. Subcutaneous injection of diazoxide every 3 hr for a total of 5 doses in 15 hr produced a state of elevated drinking and antidiuresis in rats resulting in a massive, positive, self-imposed water load. Dilutional hyponatremia was present, but not serum hyposmolality, owing to the increased serum glucose and BUN. The mechanism by which diazoxide produces a polydipsia even in the presence of an accumulating water load may illuminate the genesis of other pathophysiological dilutional states.


Relation of rat brain acetylcholine levels to duration of self-stimulation and escape behavior. Total brain acetylcholine (ACh) was assayed in groups of animals after various periods of operant responding maintained by electrical stimulation of the lateral posterior hypothalamus or of escape behavior induced by electrical stimulation of the midbrain tegmentum. Different groups of trained rats were placed in identical Skinner boxes for periods of 1 to 24 hr. The following groups were studied: controls, self-stimulators receiving electrical stimulation, escapers from brain stimulation or peripherally applied aversive stimulation, self-stimulators not receiving electrical stimulation prior to decapitation, tubocurarine-paralyzed respired rats with electrodes in the posterior-lateral hypothalamus not receiving stimulation, and a group of tubocurarine-paralyzed, respired rats receiving electrical stimulation automatically. It was found that brain stimulation decreased total brain ACh, regardless of whether the stimulation was positive, as during self-stimulation behavior, or negative, as during escape behavior. Animals that receivied positive stimulation while being paralyzed showed similar decreases in total brain ACh, but the change in ACh was smaller. No changes occurred in animals that were paralyzed that recieved no electrical stimulation. It is concluded that brain usage produced by electrical stimulation of discrete functional pathways causes a reduction of total ACh, but this is unrelated to the specific motivational properties of the electrical stimuli.


Time course for plasma 11-hydroxycorticosteroid elevation in rats during stress. The time course of plasma 11-hydroxysteroid elevation was studied in two stress situations: regular unsignalled foot shock which produces an intermediate steroid elevation and irregular signalled foot shock with the possibility of escape, which produces an extreme steroid elevation. The initial time course for steroid elevation followed a similar pattern for both treatment groups with the exception that in the irregular signalled group the plasma steroid elevation was more pronounced and there was an indication of biphasic response. The results are discussed in terms of possible inhibitory feedback pathways.


A method of direct chemical brain stimulation in behavioral studies using microiontophoresis. A method of microiontophoresis for direct chemical brain stimulation in chronic, awake animals for behavioral studies is described. Carbachol-induced drinking was employed to test the method. Fluid-filled micropipettes (tip diameters: 5-15 mu) were stereotaxically implanted in the region of the nucleus of the diagonal band. Up to 3 weeks after recovery, ions could be ejected directly into the brain of awake animals by passing a direct current through the pipette. Iontophoretic ejection of carbachol in doses as low as 0.05 mug elicited drinking. This effect could be blocked by intraperitoneal injection of 0.5 mg/kg scopolamine. Passage of choline ions produced no detectable effect. The microiontophoretic technique allows direct chemical brain stimulation in chronic, awake animals without major changes in tonicity or volume that can occur with crystalline or fluid implants through cannulae. Additionally, the technique allows precise localization, precise control of dosage, and minimal damage at the site of stimulation.


Alterations in brain monoaminergic functioning associated with septal lesion induced hyperreactivity. Thirty male albino rats, individually housed and receiving food and water ad lib were rated on 3 consecutive days for reactivity to handling. The animals were then assigned to behaviorally equivalent groups and received either bilateral septal lesions or a sham operation. Following two days of recovery, all animals received an additional behavioral testing session. Immediately following this last test, norepinephrine (NE) and dopamine (DA) levels, instantaneous rate constants (k), turnover times (TT) and utilization rates (K) as well as the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the hypothalamus, limbic system, cortex and pons-medulla were determined fluorometrically. Postoperatively, animals with septal lesions were significantly more reactive to handling, while the behavior of sham-operated controls remained essentially unchanged. Significant reductions in hypothalamic NE and DA and limbic DA were observed in the septal lesion animals. Catecholamine levels in other brain parts were unaffected as were 5-HT and 5-HIAA levels in all brain areas. Ratios of NE/5-HT in the limbic system were significantly reduced in animals which received septal lesions. Measures of catecholamine dynamics (k, TT, K) were unaltered by septal lesions. These results support the hypothesis of a catecholaminergic involvement in affective behavior but do not demonstrate any alteration in the functional dynamics of the brain monoamines associated with the hyperreactivity induced by septal lesions.


Self-stimulation and local injections of 6-hydroxydopamine into the rat brain: enhanced behavioral depressive effects of alpha-methylparatyrosine. The effects of intracerebral injections of 6-OHDA on self-stimulation were examined. Small amounts of 6-OHDA were injected either in the area ventralis tegmenti (AVT) or laterally in the pedonculus cerebellaris superior (PCS), then all rats were implanted in the AVT. In spite of marked depletion of brain catecholamines, self-stimulation learning was not altered by PCS 6-OHDA injections, whereas, AVT 6-OHDA injections produced a small perturbance. The administration of low doses of AMPT which had no observable effect in control rats, produced a severe depression of self-stimulation rates in 6-OHDA pretreated rats. The depressive effect of AMPT is always more important in rats injected with 6-OHDA in the AVT than those injected at the level of PCS. The respective role of noradrenergic and dopaminergic neurons in AVT self-stimulation are discussed.


Localization of the antinociceptive action of morphine in primate brain. Microinjections of morphine sulfate (20-40 mu g) were made into various subcortical regions of the rhesus monkey brain. The effects of these injections were evaluated on the nociceptive threshold as defined by the shock titration technique. The results of this preliminary investigation indicate that the region of maximal antinociceptive sensitivity to morphine in the primate is the periventricular-periaqueductal gray matter. It is tentatively suggested that morphine lowers that affective tone or the aversive component of pain by its action on the midbrain central gray and periventricular areas--both important projection and integration areas of the extralemniscal somatosensory system.


A modification of the jump-flinch technique for measuring pain sensitivity in rats. The jump-flinch procedure provides a sensivite alternative to the hot-plate and tail-flick procedures. Analysis of the components of motor responses to increasing intensity of foot shock presentation has allowed the observational discrimination of five reliably elicited categories of unlearned responses to inescapable foot shock. Morphine sulfate differentially altered response category thresholds in rats. Response category thresholds also differed between Wistar and Fisher strain rats in analgesic effects of morphine sulfate.


Efficiency of muscular work: some clinical implications. The concept of mechanical efficiency is briefly reviewed.  Biochemical considerations set a maximum potential efficiency of 25 percent, but, in some instances, storage of energy in elastic tissue may yield a higher apparent efficiency.  Comparisons of efficiency between normal and handicapped individuals can be made in terms of the oxygen cost of specific activities, or, if due regard is paid to the effects of the primary disease, the simpler indexes of pulse rate and ventilation may be used.  Measurements of efficiency can be helpful in improving the working technique of both the healthy individual and the handicapped person,  Useful gains of efficiency can result only if tasks initially have an efficiency substantially below the theoretical ultimate of 25 percent.


Effects of delta-9-THC and a water soluble ester of delta-9-THC on schedule-controlled behavior. delta-9-Tetrahydrocannabinol (delta-9-THC) and one of its water soluble esters (SP-111) decreased the rates of responding by pigeons working under a variable interval 3-min schedule of food presentation, or a multiple fixed-ratio 30, fixed-interavl 5-min schedule of food presentation. delta-9-THC was 3-6 times more potent than SP-111 and had a faster onset of effects on behavior.


Comparison of 2, 5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine for in vivo efflux of catecholamines from rat brain. The neurochemical effects of DOM and d-amphetamine were compared under several conditions in unanesthetized rats implanted with chronic-indwelling push-pull cannulae in a cerebral lateral ventricle. Brain catecholamine storage sites were previously pulse-labelled with 14-C-norepinephrine administered intraventricularly. During the perfusion of the lateral ventricles with artificial cerebrospinal fluid, the animals were injected i.p. with 1.5 mg/kg of DOM, 2.0 mg/kg of d-amphetamine or 1.0 ml/kg of isotonic saline. Analysis of the perfusate in successive samples indicated an increased efflux of 14-C-radioactivity in rats administered DOM or d-amphetamine. Increased proportions of 14-C-norepinephrine and 14-C-normetanephrine were detected in samples of perfusate 15 to 30 min after drug injection. Pretreatment of other animals with 6-hydroxydopamine intraventricularly, which decreased brain levels of both norepinephrine and dopamine, blocked the increased efflux of 14-C-radioactivity induced by DOM or d-amphetamine. Pretreatment of rats with 6-hydroxydopa i.p., which depleted brain norepinephrine selectively, reduced to about half the d-amphetamine-induced efflux of 14-C-radioactivity for all samples during the time course of the effect. However, animals pretreated with 6-hydroxydopa and then tested for DOM effects showed a different pattern of 14-C-radioactivity efflux. The efflux for the initial samples was increased as with the DOM control, but the 6-hydroxydopa pretreatment attuated the DOM-induced efflux for the later samples. The results suggest DOM and d-amphetamine share qualitatively similar effects in releasing and/or blocking the reuptake of catecholamines at brain periventricular nerve terminals. Nevertheless, DOM appears to differ from d-amphetamine in the temporal pattern of net catecholamine release.


Reduction of skin bacterial load with use of the therapeutic whirlpool. Effects of immersion time, water temperature, and three whirlpool treatment techniques on the reduction of bacterial load on the plantar surface of feet were examined.  When cultures were taken before and after treatment, water temperature was found not to be a significant factor when removal of bacteria is the primary objective in a vascularly uncompromised limb.  Maximum reduction of bacterial count in water at 37.7 degrees Celsius appeared to be obtained after immersion about twenty minutes.  Although agitation of the water was significantly better than either spraying or soaking the foot, agitation followed by spraying was significantly better than any single technique in removing bacteria.


Anticonvulsant effects of 6-methoxy-1, 2, 3, 4-tetrahydro-alpha-carboline on audiogenic and electroconvulsive seizures in mice. 6-Methoxy-1, 2, 3, 4, -tetrahydro-beta-carboline (6-MeO-THBC) was tested for anticonvulsant properties against audiogenic seizures in DBA/2J and primed C57BL/6J mice (i.e., mice given a prior auditory exposure) and aginast electroconvulsive seizures in DBA/2J mice. 6-MeO-THBC (100 mg/kg) was found to attenuate both types of behavioral seizures 2 hr after injection as compared to saline controls. In addition, 6-MeO-THBC increased whole brain serotonin and decreased whole brain 5-hydroxyindoleacetic acid 2 hr after injection. These results support previous reports which suggest a serotonergic involvement in behavioral seizures.


Tricyclic antidepressants: effects on extinction and fear learning. Rats trained to run an alley for a food reward were extinguished following injections of different antidepressants. When retested several days later, the animals extinguished following pretreatment with the NE reuptake blocker protriptyline showed faster running speeds than did the other groups. Other rats given electrical shocks following pretreatment with protriptyline avoided the compartment in which they had been shocked less than did animals shocked following pretreatment with other antidepressants. This implies an interferance with some aspect of the learning or consolidation process which is correlated with the degree of NE reuptake blockage. It is hypothesized that NE terminals are deactivated following frustrative nonreward or punishment by the conversion and reuptake of the released NE to an altered extinction molecule.


Neural activity changes correlated with central anticholinergic blockade of cholinergically-induced drinking. In the rat, microinjections of carbachol into the septal area elicited water ingestion and increased multiple unit activity at this site and also the noninjected lateral hypothalamus. Carbachol injection into the lateral hypothalamus also elicited water ingestion, but multiple unit activity did not increase in this structure, although it did in the noninjected septal area. If carbachol was injected into one of these sites and isotonic saline into the other (conditions comparable to those for which drinking has been previously demonstrated), increased multiple unit activity was still found. However, if carbachol was injected into one of these sites and atropine into the other (conditions comparable to those for which the blockade of drinking has been previously demonstrated), the increases in multiple unit activity were blocked. Carbachol-elicited drinking may result from neural activity changes similar to those recorded in this study, and atropine may inhibit carbachol-elicited drinking by inhibiting such neural firing changes.


Characteristics of hospital provisions for continuing education for physical therapists in California. The authors surveyed 197 acute general hospitals in California to determine characteristics of hospital provisions for continuing education for physical therapists.  Most hospitals in California were found to provide continuing education opportunities for physical therapists, but physical therapists in small hospitals and in private-profit hospitals could be at a disadvantage financially if continuing education becomes compulsory for relicensure.  A relatively low proportion of physical therapy departments in hospitals with less than one hundred beds budgeted continuing education, but a relatively high proportion of the same facilities required that therapists take time off without pay or use vacation time and pay their own expenses for continuing education.  Similar circumstances characterized private-profit hospitals.


Anorexigenic effects of d-amphetamine and l-DOPA in the rat. The effect of amphetamine and l-dopa was compared in 22-hr food- and water-deprived rats. Amphetamine produced marked anorexia, and l-dopa significantly reduced food intake at 200 mg/kg. Following pretreatment with RO 4-4602, a decarboxylase inhibitor, 100 mg/kg of l-dopa, a dose that did not significantly affect eating, produced marked anorexia. The anorectic effect of both amphetamine and l-dopa was antagonized by propranolol, a beta adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, potentiated the anorectic effect of amphetamine and l-dopa. Haloperidol (0.1 mg/kg), a dopamine antagonist, failed to prevent the anorexia due to amphetamine but accentuated that due to l-dopa. Methysergide, a serotonin antagonist, also failed to prevent the anorexigenic effect of amphetamine. Finally, the administration of l-dopa with or without peripheral decarboxylase inhibition resulted in more than twice the increase in hypothalamic dopamine levels without significant changes in 5-HT or norepinephrine levels. The data show that the anorexigenic effect of amphetamine and l-dopa are similar and indicate a functional role for both norepinephrine and dopamine neurons in feeding behaviour in the rat.


Electrophoresis of acid soluble proteins from rat liver nuclei and polysomes on large two-dimensional polyacrylamide gels. Increased resolution of 0.4 N H(2)SO(4) soluble rat liver polysomal and nuclear proteins was achieved by initial electrophoresis on 15 percent polyacrylamide disc gels (25 times 0.5 cm) followed by electrophoresis on 16 percent polyacrylamide gel slabs (25 times 15 cm). With this method, it was found that the histones were resolved into 12 spots, the polysomal proteins A1 and A9 were each resolved into two components, and polysomal proteins A1, A1 and A1 with molecular weights of approximately 14,000 were separated from the other proteins by their rapid migration in the first dimension. Moreover, no histones were found in the acid extracts of the polysomes.


Osmotic pressure variations used to elicit oscillations and changes in stiffness of muscle fibers. By observing diffraction spectra produced by passing a laser beam through stimulated muscle fibers, the magnitude of sarcomere length change and the relative rate of filament sliding were found to decrease in hypertonic solutions. The first order diffraction for both resting and stimulated muscle fibers faded and then returned to its original intensity as the bathing solution was changed from isotonic to hypertonic and then back to isotonic. This is explained as being due to a change in optical contrast between the A and I bands. 7 Hz oscillations were detected at 4 degrees C during stimulation as the fibers equilibrated in hypertonic solutions. The stiffness of resting muscle in the hypertonic solutions increased while the stiffness of stimulated muscle decreased until at a concentration of 3.10 R they were equal. All processes were reversible.


Biochemical profiles of cancer cells: I. Computerized analysis of mouse leukemic cellular RNA on polyacrylamide gels. Recent studies in this laboratory have been directed at investigating the cellular and subcellular metabolism of RNA in leukemic cells which have been characterized with respect to their degree and type of sensitivity/resistance to specific chemotherapeutic agents. In the present report, electrophoretic patterns on several types of SDS-polyacrylamide gels are presented using total cellular RNA preparations from a subline of L1210 mouse leukemia found to be resistant to cytosine arabinoside (L1210/Ara-C). These studies have been facilitated by using a computerized-spectrophotometric system for quantitative and qualitative comparisons of these profiles. The results suggest that patterns of RNA metabolism may be a useful biochemical test in leukemia.


Effect of alpha-tocopherol on the rate of photohemolysis of human erythrocytes. The results of this study demonstrate that alpha-tocopherol has a significant ability in vivo to prohibit the production of cholesterol hydroperoxide in the erythrocyte membrane, and also significantly reduce the degree of cell membrane deformation upon exposure of the blood to light and oxygen (photooxygenation conditions). This study suggests that alpha-tocopherol prohibits the production of cholesterol hydroperoxide in the membrane which if produced leads to a weakened membrane observed as a "budded" cell in the electron micrographs.


A potent new mesodermal growth factor from mouse submaxillary gland. A quantitative, comparative study with previously described submaxillary gland growth factors. A new growth factor with potent growth stimulating effects on connective tissue cells of the cornea has been isolated and partially purified from mouse submaxillary glands. A computerized image analysis system has been used to quantitate the growth responses of connective tissue fibroblasts to this new growth factor and to compare its activity with that of four previously described growth factors [nerve growth factor (NGF), epidermal growth factor (EGF), mesodermal growth factor (MGF), and thymocyte-transforming factor (TTF)] also obtained from mouse submaxillary glands. The new factor is as potent a growth stimulator as the previously described MGF. All five of the growth factors possessed esteropeptidase activity (trypsin-like) and general proteolytic activity. There was no correlation between the degree of growth stimulation of the connective tissue cells and either the esteropeptidase or general proteolytic activities of any of the growth factors.


A variation of the Biesenberger technique of reduction mammaplasty. A variation of the Biesenberger technique of reduction mammaplasty is presented. The medial and lateral blood supply is preserved in a "cut as you go" technique. The results in 68 widely varying cases have been most satisfactory.


Xeroradiography examinations in orbitonasal surgery. Preliminary report. The use of xeroradiography for graphic visualization of both the bony and soft tissue structures of the head is presented. The advantages and indications are discussed.


Intracranial use of a breast prosthesis to temporarily stabilize a reduction cranioplasty. We present a method of correcting cranial vault collapse after total reduction cranioplasty.


The etiological significance of the primal scene in perversions. The etiological significance of the actually observed primal scene in fetishism and other perversions is discussed.  The impact of the primal scene on the pathology of part object relationships, self and object image, and on the development of superego structures in perversion is stressed.


Evaluation of progress in supervision.

Evaluation of progress in supervision. Evaluation is an ongoing process in psychoanalytic education and is most active during supervision.  Here we formulate five learning objectives relevant to evaluating competence in analyzing that can be used by both supervisor and candidate to assess progress throughout the supervisory experience.  Session-by-session evaluation produces the core material for periodic progress reports.


Some observations on transitional object and infantile fetish. Observations of a girl's development are presented to demonstrate the role of the transitional object in coping with the normal strains implicit in the separation-individuation thrust and in the anal-urinary and early sexual stages of development.  When at eighteen months a separation experience led to a serious preoedipal castration reaction, the transitional object no longer was capable of serving its ordinary function and was replaced by a fetishistic object.


Idosophobia: a form of pregenital conversion. The origins of idrosophobia (profuse sweating) in a young man are traced to his oedipal resolution and his pathological regressions and defenses.  Idrosophobia, which resembles erythrophobia, is described as a syndrome of pregenital conversion.


The square left ventricle: an angiographic and radionuclide sign of left ventricular thrombus. The association of mural thrombus with left ventricular aneurysm is well documented, though angiographic documentation of left ventricular thrombus can be difficult. The authors describe the unique appearance of the left ventricular cavity in 5 patients. In all cases, ventriculograms obtained in the right anterior oblique position showed a squared apex. In 2 patients this phenomenon was also demonstrated by radionuclide angiocardiography. All 5 patients were found to have left ventricular thrombus at operation or autopsy.


Diffuse idiopathic skeletal hyperostosis (DISH): Forestier's disease with extraspinal manifestations. The extraspinal manifestations of Forestier's disease are described in 21 consecutive cases; diffuse idiopathic skeletal hyperostosis (DISH) is suggested as a more appropriate description of this ossifying diathesis. Characteristic roentgen abnormalities of the spine were present in all individuals and associated with significant axial clinical complaints. In extraspinal locations, hyperostosis at ligament attachments usually occurs in the pelvis, calcaneus, tarsal bones, ulnar olecranon and patella, and is occasionally associated with clinical signs and symptoms requiring surgery. The radiographic appearance in the peripheral skeleton is frequently distinctive and allows the radiologist to suggest the correct diagnosis, even in the absence of axial radiographs.


Pneumoperitoneum, pneumomediastinum and pneumopericardium following dental extraction. Pneumoperitoneum, pneumomediastinum, pneumopericardium and subcutaneous emphysema developed in a patient following simple dental extraction. Other causes of this unusual complication, such as pneumatosis cystoides intestinalis, insufflation of fallopian tubes, pulmonary-peritoneal fistula, post-partum knee-chest exercises, laparotomy, paracentesis and peritoneal dialysis should be considered when peritoneal signs are absent so that unnecessary laparotomy can be avoided.


Gallstone in the lung.

Gallstone in the lung. A gallstone was found in the lung in a 70-year-old woman. The authors suggest that it perforated the gallbladder, subsequently penetrating the diaphragm and eroding into a right-lower-lobe bronchus.


Bilateral renal-cell carcinomas.

Bilateral renal-cell carcinomas. The incidence of 5 cases of bilateral renal-cell carcinomas and one case of possible bilateral angiomyoliposarcomas over a period of 16 years suggests than these entities may be more frequent that previously thought. One patient successfully underwent surgery via the "workbench" technique, in which the tumor was dissected from one kidney which was then reinserted as an autograft. It is suggested that renal angiography should always be performed bilaterally when attempting to diagnose or exclude renal masses.


Percutaneous management of renal cysts: results of a four-year study. A standardized technique for percutaneous therapeutic management of renal cysts is described. After partial aspiration of the cyst fluid, the fluid is replaced with Pantopaque, Renografin 60 and air. Fifty-six renal cysts so treated were followed at intervals of up to four years and 68% showed a 50% or more decrease in cyst volume. Only 13% of a control group of 15 renal cysts which were percutaneously punctured but did not have Pantopaque instilled showed a 50% or more decrease in cyst volume. The results suggest that instillation of Pantopaque into a renal cyst can alter the natural history of the cyst by causing it to decrease in size.


Venous angiography of hemodialysis fistulas. Experience with 52 studies. The authors describe a simple outpatient venous angiographic method of delineating arteriovenous fistulas constructed for chronic hemodialysis, and variations of the basic technique are offered to solve the problems of overlapping vessels and obscured anastomoses. A normal fistula produces enlargement of the involved artery only, but there may be enlargement of multiple veins in the extremity in which the fistula is constructed. Stenoses, occlusions, surgical variations, aneurysms, functional abnormalities in the direction and quantity of flow, and inadequate positioning of the dialysis needles are discussed.


The columnar epithelial-lined lower esophagus and its association with adenocarcinoma of the esophagus. Four cases of columnar epithelial-lined lower esophagus are presented. The condition can be complicated by esophagitis, ulceration, perforation, and adenocarcinoma of the esophagus. When the squamocolumnar junction is involved by peptic esophagitis, the area of mucosal transition appears as a tapered, strictured segment or a ring-line constriction some distance proximal to the muscular esophagogastric junction. Hiatal incompetence with massive gastroesophageal reflux was evident in 1 case. A deep penetrating ulcer may occur anywhere along the columnar epithelium, identical to peptic gastric ulceration. The columnar-lined lower esophagus should probably be considered a premalignant condition. Two of these patients had associated esophageal adenocarcinoma.


The diagnostic accuracy of barium studies of the stomach and duodenum--correlation with endoscopy. Radiologic and endoscopic diagnoses were compared in 240 patients. In 175 patients examined by a standard barium contrast technique there were 39 radiological errors (22%). The most common causes of error were failure to detect an abnormality on the radiograph and prominent mucosal folds which could either mask or simulate small lesions. In 65 patients examined by a formal double contrast technique using effervescent pills and a thick barium suspension, there were 4 radiological errors (6%). In addition, superficial gastric erosions were demonstrated in 7 patients. Double contrast radiography appears to offer the potential for significant improvements in diagnostic accuracy.


Fluoroscopy of the upper gastrointestinal tract by the radiological technologist. A pilot program was established to train an experienced radiological technologist to perform fluorescopy of the upper gastrointestinal tract. Patients were prescreened and films reviewed by a staff radiologist. The quality of the films obtained by the technologist equaled that of the department's resident radiologists.


Pedunculated malignant colonic polyps with superficial invasion of the stalks. Malignant colonic polyps on substantial stalks were seen in 3 patients. In each case the base of the pedicle was free of tumor. The author suggests that these were initially benign adenomatous polyps but subsequently became malignant. These findings suggest that initially benign colonic polyps can become malignant over a period of time and that the presence of a substantial stalk may not always be pathognomonic of benignity.


Gastric bullae. An early roentgen finding in corrosive gastritis following alkali ingestion. In most cases of alkali ingestion, the stomach is protected from injury by its contents and gastric acidity, so that the esophagus is usually the main site of injury. The authors describe a case of severe corrosive gastritis following ingestion of a large amount of alkali. Huge gastric bullae, an unusual manifestation, were an early roentgen finding. As healing occurred, the stomach was reduced to a shrunken, aperistaltic pouch.


Nonsurgical treatment of arteriovenous malformations of the trunk and limb by transcatheter arterial embolization. Two patients with large arteriovenous malformations (AVM) were successfully treated by transcatheter selective arterial embolization with Gelfoam. An extensive lumbar retroperitoneal acquired AVM was markedly reduced, eliminating any clinical evidence of a persistent left-to-right shunt. A large localized congenital AVM of the thigh in the second patient completely disappeared. Transient post-procedure fever developed in the first patient. Prolonged fever and pulmonary infarction complicated the second case with complete recovery in three weeks. The advantages of Gelfoam as an embolizing agent are discussed. The technique appears to be a reasonable alternative to extensive and sometimes mutilative surgery.


Popliteal cysts: presentation as thrombophlebitis. Synovial-lined cysts in the popliteal space associated with rheumatoid arthritis or meniscal tears may compress the popliteal vein and produce signs and symptoms suggestive of thrombophlebitis. Because of a presumptive diagnosis of thrombophlebitis, venography may be performed initially and demonstrate compression of the popliteal vein by an extrinsic mass. The correct diagnosis of a popliteal cyst can easily be made with B-mode ultrasonography, and, if desired, confirmed by arthrography. Four cases are presented which emphasize these features.


Validity of the sesamoid index in the diagnosis of acromegaly. Sesamoid indices of 100 control and 10 acromegalic subjects were determined and the results compared with previous studies. It was found that a substantial overlap of values exists between the two groups and that the range of values for both groups is substantially wider than previous studies have indicated.


Lymphatic visualization during hip arthrography. Lymphatic visualization at arthrography has been reported previously in patients with rheumatoid arthritis. The authors describe this phenomenon in 4 patients undergoing arthrography of the hip following prosthetic surgery, only one of whom had a history of rheumatoid arthritis. It is suggested that lymphatic visualization is not a reliable indicator of any specific type of arthritis, but rather an ancillary sign of inflammation, and that it may occur whenever lymphatic hyperplasia or increased synovial membrane permeability is present.


Radiographic manifestations of Japanese acupuncture. The radiographic manifestations of Hari, a peculiar type of acupuncture currently practiced in Japan, are described. This acupuncture method consists of inserting multiple fine gold needles through the skin into the subcutaneous tissue. The needle is cut off at the skin surface and left in the subcutaneous tissue for the life of the patient. These multiple needles present curious, frequently unsuspected findings on radiographs obtained for reasons unrelated to acupuncture.


Some new angiographic observations in patients with Chiari type I and II malformations. Angiographic abnormalities of the lower hindbrain seen in 13 cases of Chiari Type I and Type II malformations are described. Previously reported findings are assessed, particularly deformities of the posterior inferior cerebellar artery (PICA). Caudal displacement of the cerebellar tonsils without other angiographic localizing signs of an expanding intracranial mass suggest a Chiari malformation. In such cases it is helpful to demonstrate a low cephalic loop of the PICA, reflecting caudal displacement of the fourth ventricle. Associated angiographic demonstration of significant intraspinal localization of the brainstem is pathognomonic of Chiari malformation.


Compression of superior sagittal sinus by neonatal calvarial molding. Compression of the superior sagittal sinus may result from overlapping of the parietal and occipital bones in the newborn infant. Such compression has been documented angiographically and the resultant decreased blood flow confirmed with a Doppler ultrasound probe. This compression may increase intracerebral venous pressures and thereby contribute to the high incidence of intracerebral hemorrhage in premature infants with respiratory distress syndrome.


Venous channels within the intracranial dural partitions. Complete dura maters exclusive of their midline basilar attachments were obtained by autopsy from persons of all age groups. Vinylite casts of the venous channels in the diaphragma sellae, falx cerebelli, falx cerebri, and tentorium cerebelli were made by injecting a mixture of Vinylite and acetone, after which the specimens were fixed in formalin and subsequently corroded with concentrated hydrochloric acid. Studies showed that the size and position of the channels within the diaphragma sellae were quite constant. Large venous lakes were present in the falx cerebelli and contiguous suboccipital dura mater, and venous pools were also seen connecting the caudal end of the inferior sagittal sinus and the superior sagittal sinus. A great variety of channels were observed in the tentorium cerebelli.


Cerebral angiographic changes associated with tuberous sclerosis. Two patients with tuberous sclerosis were examined angiographically. In one, direct left carotid angiography showed a contralateral shift of the anterior cerebral artery and lateral displacement of the middle cerebral artery. On the lateral series, increase in the sweep of the anterior cerebral artery as well as stretching of the opercular branches of the middle cerebral artery were noted in the early arterial phase. In the later arterial phase, there was marked hypervascularity, with the contrast substance temporarily pooling in small, rounded collections. In the mid-arterial phase of the second case, pooling of the  the contrast medium within the tumor and many small, berry-like outpunchings were noted. There was no evidence of early venous drainage in either case.


Traumatic vertebral artery pseudoaneurysm following chiropractic manipulation. A vertebral artery pseudoaneurysm accompanied by serious neurological injury was seen in a 42-year-old woman who had undergone chiropractic manipulation of the neck. Such manipulation is a potential cause of neurological injury due to trauma to the cervical spine and the major vessels of the neck. The arterial pattern in this case was similar to that of angiodysplasia except for narrowing and irregularity of the vertebral artery.


99mTc-pertechnetate thyroid scintigraphy in patients predisposed to thyroid neoplasms by prior radiotherapy to the head and neck. Histories, physical examinations and 99mTc-pertechnetate imaging were used to evaluate 1,452 persons who had had x-ray therapy to the neck region for benign conditions 18 to 35 years previously. Thyroid abnormalities were found in 301 patients (21%) and thyroid malignancy was found in 29% of 193 patients with abnormal studies who were explored surgically. Thyroid imaging detected 96% of these abnormalities, 40% of which would not have been unequivocally established by physical examination alone. Nuclear imaging could not distinguish benign from malignant lesions.


Detection of craniosynostosis by bone scanning. Growth patterns of the cranial sutures were studied by bone scanning in 29 children, 13 of whom had craniosynostosis. Primary craniosynostosis was initiated by localized bony fusion across a suture, associated with an abnormal accumulation of bone-seeking radiopharmaceuticals. As the abnormal fusion process extended along the suture, there was a corresponding spread of radionuclide. With complete fusion, uptake diminished. In addition to calvarial scanning, three abnormal sutures were scanned following surgical excision, which allowed direct comparison in vivo and in vitro. Calvarial bone scanning is helpful in the early detection of primary craniosynostosis.


Decompression hyperostosis: cranial hyperostosis mimicking bilateral subdural hematoma on brain scintigraphy. Scintraphic findings suggestive of bilateral subdural hematoma developed after successful decompression of communicating hydrocephalus. These findings were secondary to cranial hyperostosis. The similarity of brain scintigraphic findings in the two disorders is pointed out, and the necessity of correlating brain scintigraphs is stressed.


Ultrasonic diagnosis of hypernephroma extending into the inferior vena cava. Extension of hypernephroma into the inferior vena cava was demonstrated by ultrasound. When a solid renal lesion is encountered, it is suggested that the inferior vena cava be scanned. The possible significance of gray scale scanning as a more precise diagnostic tool and its use in tumor staging are discussed.


Scintigraphic findings in primary amyloidosis. An analysis of 7 cases. Images of 7 patients with primary amyloidosis revealed organomegaly with regions of decreased tracer accumulation due to infiltration and replacement of normal tissue by the amyloid complex. These scintigraphic changes in the clinical setting of multisystem disease should suggest amyloidosis as a possible diagnosis.


Analysis of sites and causes of failures of irradiation in invasive squamous cell carcinoma of the intact uterine cervix. An analysis of the records of 916 patients who received radiotherapy for invasive squamous cell carcinoma of the intact uterine cervix from January 1964 through December 1969 revealed that 94% of the central and regional failures will occur within 3 years of treatment. Survival rates were as follows: Stage I, 91%; Stage IIA, 82%; Stage IIB, 65%; Stage IIIA, 54%; and Stage IIIB, 40%. The incidences of central and regional failures in Stages I through III are: Stages I and IIA; central 2% and regional 4.5%; Stage IIB; central 5% and regional 13%; Stage III: central 14% and regional 19%. In stages IIB, IIIA, and IIIB, the main cause of failures, either centrally or in the parametria, is the presence of massive disease.


Radiation therapy of brain tumors in children. The case histories of 124 children irradiated for brain tumors were reviewed to determine survival rate and functional prognosis, with special reference to somatic growth. Five-year survival rates (29% of 97 patients with gliomas and 70% of 27 patients with non-gliomatous tumors) were approximately the same as in our adult series, despite the differences in histology and predilection. Although 70% of 42 long-term survivors had active, useful lives, stunted growth was observed in 15 of them. More attention should be directed to the growth of children irradiated for brain tumors.


Early and late radiation changes following a second course of irradiation. The effect of two 10-fraction courses of irradiation separated by intervals varying from 1 to 10 months on both the early skin reaction and late deformity of the leg was studied in mice. It was found that the "memory" of the first course was much greater for the late end point (deformity) than for early skin reactions at all intervals between the two courses. The extent of the late deformity reaction following a second course was predicted fairly well from the Ellis formula for decay of partial tolerance, but it also appeared to be more complex than is evident from the formula. Evaluation of early vs. late reactions showed that the extent of the deformity is not governed entirely by the level of the early skin reaction; rather, it depends critically on the previous radiation history of the tissue.


Detail enhancement in prints of radiographs. Use of a linear radial transmission filter. A simple, inexpensive technique using a linear radial transmission filter for selectively enhancing fine detail when making prints from radiographs is described. Fine detail is often better on the enhanced print than on the original radiograph.


Reducing the operating temperatures of thin viewboxes. Several manufacturers' thin viewboxes operate at excessively high temperatures. The measured equilibrium ballast temperature was 95 degrees C in a 25 degrees C room. Canadian standards limit ballast surface temperatures to 90 degrees C. The ballast cover plate reaches 47 degrees C. Temperatures were reduced to 67 degrees and 37 degrees C by substituting a more efficient ballast and painting the outer surface of the polished metab cover plate.