Levels of prostaglandin F (PGF) in bovine endometrium uterine venous, ovarian arterial and jugular plasma during the estrous cycle (38789). Prostaglandins F (PGF) were measured in uterine vein, ovarian artery, and jugular vein plasma and in the endometrial tissues at various times during the bovine estrous cycle, and were compared to peripheral plasma progesterone levels. Four groups of heifers at days 1-5, 10-14, 15-17 and 20-0 of the estrous cycle were studied. Low levels of PGF (48 plus or minus 12 ng/g dry tissue were measured in the endometrium on days 1-14 of the cycle. Higher values (131 plus or minus 9.0) were found at days 15 until the day of estrus (p less than 0.001). Similarly, very low levels of PGF were observed in the uterine vein plasma at days 1-14 (0.162) plus or minus 0.044) ng/mlM plus or minus S.E.), whereas on days 15 until the day of estrus the levels ranged from 1.5 to 3.0 ng/ml. The increases in uterine vein PGF on day 15 occurred even while peripheral plasma progesterone levels were still high. However, PGF was not elevated in either the ovarian artery or the jugular vein at any time during the cycle, even when uterine vein levels were greatly elevated. No differences in PGF content were detected in endometrial tissue from uterine horns adjacent or opposite to the functional corpus luteum.


Levels of lutenizing hormone, estradiol and progesterone in serum during the estrous cycle and pregnancy in the beagle bitch (38491). Levels of luteinizing hormone (LH), estradiol-17 beta and progesterone were determined by specific radioimmunoassays in sera obtained from Beagle bitches during proestrus, estrus and diestrus. Concentrations of LH (expressed as NIH-LH-SI equivalents) were 2.8 plus or minus 0.1 ng/ml in proestrus, 35.5 plus or minus  10.0 ng/ml during early estrus and 2.2 plus or minus 0.1 ng/ml in early diestrus. Peak levels of estradiol-17beta (68.9 plus or minus 11.0 ng/ml)  were detected 24 hr prior to the LH peak, declined rapidly and reached basal levels (17.8 plus or minus 6.3 ng/ml) by five days following the LH peak. Levels of progesterone were 1.7 plus or minus 0.3 ng/ml during proestrus, 3.5 plus or minus 0.3 ng/ml during early estrus and 23.3 plus or minus  2.8 ng/ml on day 5 after the LH peak . Progesterone levels remained elevated through day 28 of diestrus and pregnancy. A significant decrease (p smaller than 0.05) in levels of prosgesterone occurred between day 28 of pregnancy and one day prior to shelping (3.3 plus or minus 1.2 ng/ml, with a further decrease on the day of whelping (1.1 plus or minus 0.2 ng/ml). Levels of estradiol-17beta and LH did not change significantly (p smaller than 0.0k) during diestrus or pregnancy.


[Formation of organic acids by the fungus Cladosporium resinae in media containing n-alkanes]. The so-called fungus Cladosporium resinae that often occurs in oil fuels ane increases their acidity grows well at the expense of n-alkanes from C11 to C16.  On the n-alkane containing media the fungus grows slowly and only under the stationary conditions.  During the fungal cultivation on the media containing n-dodecane or kerosene the culture liquid shows acetic acid and other fatty acids, ketoacids (pyruvic and alpha-ketoglutaric) as well as citric and isocitric acids that dominate among nonvolatile acids.  Upon nitrogen deficiency in the medium and comparatively good aeration the content of citric acids increases.  The culture liquid of the fungus devoid from the mycelium and nonutilized n-alkanes can be used a a nutrient medium for different microorganisms.


Route of prostaglandin F2alpha injection and luteolysis in mares (38519). Nine groups of pony mares (3/group) were used in a 3 times 3 factorial experiment. The factors were dose of PGF-2 alpha (0, 0.25 of 1.25 mg and route of administration (im, iu or il). Mares were laparotomized and treated on day 7 postovulation. Jugular blood was collected for progesterone RIA at 0 (pretreatment) and 1,6,12,24,48, and 72 hr posttreatment. In mares given either 0.25 mg or 1.25 mg PGF-2alpha, progesterone concentrations were not significantly different among the three routes at any of the posttreatment times studied except at 6 hr posttreatment. In mares given 0.25 mg, progesterone concentrations at 6 hr was less (p less than 0.05) for mares injected im than for mares injected iu. Compared to pretreatment progesterone values, PGF2-alpha (0.25 mg and 1.25 mg groups combined) administration significantly decreased progesterone concentration by 12 hr posttreatment in mares injected im and 24 hr in mares injected iu or il. In the iu group, a significant increase in progesterone concentration occurred between 1 and 6 hr followed by a significant decrease at 12 hr posttreatment. There were no significant differences among the three routes for intervals from treatment to estrus or ovulation, length of posttreatment estrus or length of interovulatory interval. Injection of either 0.25 mg or 1.25 mg PGF-2alpha significantly shortened the interval from treatment to estrus. Although 0.25 mg tended to shorten the interval from treatment to ovulation and interovulatory interval, these two end points were significantly shortened only in mares given 1.25 mg PGF-2alpha. Results indicated that local administration (iu or il) did not improve the luteolytic efficacy of PGF-2alpha over systemic administration (im).


[Catecholamine concentration and metabolism in old age]. As shown by examination in apparently healthy persons aged from 20 to 100 years and in experiments on 1--28-month-old albino rats there was a significant change with the progress of age in the content and ratio of catecholamines in the blood, various organs and the urine.  The blood noradrenaline level fell considerably; Na/A coefficient also dropped sharply.  Catecholamine content in the organs changed irregularly: in the kidneys it increased, in the skeletal muscles--remained unchanged, in the adrenal glands, the heart, the spleen and the liver--decreased.  There was a significant reduction with the progress of age of the urinary excretion of adrenaline, noradrenaline, DOPA and vanilyl-amygdalic acid.  Elemination of the intravenously injected noradrenaline from the blood of old rats was markedly delayed in comparison with that in the young animals.  Depression of the COMT activity did not alter the noradrenaline level in the heart of adult and old rats.  Administration of ipraside caused an increase in noradrenaline content in the heart of old rats, but failed to alter it in adult animals.  It is suggested that in the catecholamine metabolism of old animals prevalence is given to the processes of oxidative desamination.


Mammary gland growth in the hypophysectomized pregnant rat (38522). Sprague-Dawley-Rolfsmeyer rats were hypophysectomized on days 11, 12 or 15 of pregnancy and sacrificed on day 20 to determine the extent of mammary development, as assessed by determination of nucleic acid content. The DNA of six abdominal-inguinal glands in the hypophysectomized groups was not significantly different from that in the sham-operated pregnant or intact pregnant control groups. All groups maintaining pregnancy had significantly higher DNA contents in mammary glands than virgin control or hypophysectomized aborted groups. In order to determine the minimal numbers of placental-fetal units required to maintain pregnancy  and  mammary gland growth, fetuses and placentas were removed on day 12 of pregnancy in addition to the pituitary so that only one fetus and one placenta remained in the uterus of a group of 6 rats with other groups having 2, 3, 4, 5 remaining. Pregnancy was maintained with only one placental-fetal unit, but mammary gland proliferation was significantly lower than the control group on day 20 of pregnancy. Three to five conceptuses supported mammary proliferation during the  latter half of pregnancy at a level not significantly different from intact or sham-operated control groups. Removal of placental units on day 12 in rats having pituitaries intact resulted in no mammary DNA change when 1-5 units remained. Removal of pitutaries on day 12 and placental-fetal units on day 14 also resulted in no change in mammary DNA with as little as two placentas (minus all fetuses),while only one placenta remaining resulted in a significantly lower mammary DNA than in groups wtih 2 or more placentas.


[The effect of aminazin on thyroid gland function and lactation in goats]. The authors showed that cholrpromazine diminished the accumulation of radioactive iodine in the thyroid gland of lactating goats, and at the same time increased the milk yield and richness.  This can be attributed to the influence of chlorpromazine on the hypothalamic centres, leading to reduction of thyrotropic hormone secretion and an increase of prolactin synthesis.  Rhythmic changes in the thyroid gland function are seen during lactation.  During milking or kid nursing there occurred an increase in the thyroid gland function and more catecholamines were secreted; the activity of the thyroid gland diminished and there was an increase in prolactin secretion after milking.


Injectable selenium: effect on the primary response of mice (38472). Sodium selenite administered to mice ip (ca.5 mug Se) enhances the primary immune response to the sheep red blood cell angigen. Enhancement of the primary immune response is greatest when Se is administered prior to or simultaneously with the sheep red blood cell antigen.


[Pregnanediol excretion in the sexual cycle dynamics of white rats guinea pigs and hamsters]. A study was made of pregnandiol excretion with the 24-hour urine of albino rats, guinea pigs and hamsters at various phases of the esteral cycle.  Excretion of metabolities of the principal hestagens (progesterone and 20-alpha progesterone) in the form of alpha- and beta-isomers of pregnandiol proved to be definitely cyclic in character.  The periodicity of pregnandiol excretion in the three types of experimental rodents reflected the course of the synthesis and secretion of hestagens, with a delay for a cycle phase.  The maximal excretion of both pregnandiol isomeres with the 24-hour urine was abserved in albino rats during the estrus and metestrus, and in guinea pigs and Cricetus auratus W.--during the estrus and diestrus.


Effects of subchronic steroid therapy on vitamin E-deficient rats (38480). Experiments were carried out to determine the effectiveness of steroid therapy in vitamin E-deficiency, as measured by autohemolysis of isolated RBC's body weight gain, serum creatine phosphokinase activity, and stabilization or labilization of isolated hepatic lysosomes. Results of such experiments would indicate whether triamcinolone acetonide could supplant vitamin E in vitamin E-deficiency states via its ability to stablize various membranes. Autohemolysis induced by vitamin E-deficiency could not be prevented by daily administration of triamcinolone. Daily dosages of 0.1 and 0.4 mg/kg (ip) triamcinolone given concomitantly with replacement vitamin E (at sufficient dosages to reverse the autohemolysis) resulted in an increased autohemolysis. No changes in lysosomal membrane fragility were noted when hepatic lysosomes were obtained from vitamin E-deficient rats with triamcinolone resulted in a greater attenuation of body-weight gain. Creatine phosphokinase levels were not augmented in vitamin E-deficient rats. Vitamin E-deficient rats supplemented with vitamin E  and treated with triamcinolone, manifested an increase in creatine, phosphokinase. It was therefore concluded that although triamcinolone and vitamin E possess a common ability to stablize membranes and proteins, their mechanisms must be different since triamcinolone could not substitute for vitamin E in a deficiency state. Indeed, triamcinolone was found to be more toxic in the absence of vitamin E.


Bilirubin binding to hepatic Y and Z protein (ligandin): tissue bilirubin concentrations in phenobarbital treated Gunn rats (38466). NaP treatment significantly reduced plasma bilirubin levels in the (jj) Gunn rat. It is suggested that NaP significantly increased extravascular bilirubin binding in the liver by induction of the synthesis of Y anion binding protein. The changes in bilirubin concentration of blood and other tissues subsequent to NaP treatment were consistent with the establishment of a new tissue bilirubin equilibrium.


Significant differences in the degradation of pro-leu-gly-nH2 by human serum and that of other species (38484). The acyclic C-terminal tripeptide of oxytocin, H-Pro-Leu-Gly-NH-2, is not degraded upon incubation with human (male,female or pregnant female) plasma or serum for 1hr at 37 degrees. However, the sera of other species tested, including rat, chicken and carp, degrade this tripeptide 100%, 4% and 30%, respectively, in 1 hr, as determined by quantitative amino acid analysis of released products. Among the species studied there seems to exist a correlation between the anatomic development of the pars intermedia and the ability of the serum to hydrolyze H-Pro-Leu-Gly-NH-2, which has been proposed to be a MSH-release-inhibiting factor. The only identified degradation products are Pro, Leu and H-Gly-NH-2 with no detectable levels of H-Leu-Gly-NH2. The dipeptides H-Leu-Gly-NH-2 and H-Pro-Leu-OH are each cleaved at similiar rates in either human or rat serum, although the rate of hydrolysis of both peptides is lower in human than in rat. Thus, it does not appear that the dipeptide, H-EU-Gly-NH-2, can accumulate as one of the breakdown products of the tripeptide. The arylamidase present in rat serum has different characteristics from the enzyme in rat brain which can degrade H-Pro-Leu-Gly-NH-2.


Effect of dietary Ca and Cd level of pregnant rats on reproduction and on dam and progeny tissue mineral concentrations. Pregnant Sprague-Dawley rats were used to determine the effects of the addition of 200 ppm of Cd (as CdCl2) to the diet factorially with two levels of dietary Ca (0.07% and 0.96%) on reproductive performance, concentrations of Cd, Cu, Fe, Zn, Ca and Mg in dam liver and kidney and in newborn progeny. High Cd significantly increased liver and kidney Cd, Zn and Ca and decreased liver Fe. High dietary Ca partially protected against accumulation of Cd in liver and kidney but had no effect on concentration of other elements. Number of live or stillborn pups per litter was not significantly affected by diet but high Cd significantly reduced pup birth weight. No grossly abnormal pups were noted. Concentration of Cd in bodies of newborn pups was increased approximately 8.6-fold by high Cd in the diet of dams fed the 0.07% Ca-diet and 3.8-fold by high-Cd in the diet of dams fed the 0.96% Ca diet. Pup, Zn, Cu and Fe contents were significantly decreased and Ca was significantly increased by high-Cd in the maternal diet whereas pup Mg content was unchanged. Maternal Ca intake had no effect on concentration of Zn, Cu, Fe or Ca in newborn pups. The biological importance of the alteration in maternal and fetal tissue concentration of Zn, Cu and Fe by high-Cd maternal diets is unknown.


Factors involved in the intestinal feedback regulation of pancreatic enzyme secretion in the rat. Further studies on the feedback regulation of pancreatic enzyme secretion by trypsin were conducted in conscious rats, surgically prepared so that pancreatic juice could be collected or returned. Suppression of enzyme secretion by trypsin as well as its stimulation by SBTI occurred only in the upper part of the small intestine, where the hormone CCK is known to be released. Over a limited range, trypsin suppression of pancreatic secretion was proportional to the dose of trypsin. Higher concentrations had no further effect, suggesting "saturation" of the intestine. Trypsin which had its active center blocked by DFP did not suppress enzyme output. These results supported the concept that only trypsin (or chymotrypsin) with an exposed active center suppressed pancreatic enzyme secretion in the rat by somehow suppressing the release of CCK from the intestinal cell. Presumably CCK is released from the intestine following "removal" of trypsin from the intestine either by diverting the juice or by feeding SBTI which binds the enzyme. All of the evidence supported the view that the effect of trypsin or SBTI on pancreatic secretion was mediated at the intestinal level and not in the blood as has been suggested.


Free amino acids in plasma and tissue of rats born to underfed dams. Amino acids were determined in plasma, muscle, and liver tissues of adult male rats born of mothers on restricted or nonrestricted diets during pregnancy and lactation. The concentrations of plasma alanine, glutamic acid, glycine, proline, arginine, and valine were significantly lower in the progeny of restricted mothers as compared to non-restricted mothers. Similar changes were observed in liver tissues. The concentrations of free amino acids in muscle of the perinatally malnourished progeny, however, did not differ significantly from those of the controls. The differences determined in this study are of special significance in view of the fact that the animals studied had been maintained on an adequate diet  since weaning. The demonstrated effect of the maternal diet on the plasma aminogram of the off-spring some months later must be considered when interpreting plasma aminograms in studies of malnourished children.


A-type particles in placentas of four mouse strains. A-type particles have been detected by electron microscopy in placentas from four strains of mice: AKR, Balb/c, C3H, and DBA/2N. Complete structures were observed within rough endoplasmic reticulum cisternae of the placental labyrinth cytotrophoblasts. A marked prevalence of such particles was observed in the DBA/2 N mice. Similar particles were also found in small cytotrophoblastic elements of the junctional zone (located between labyrinth and maternal decidua) of all mouse strains studied. The numbers of junctional zone particles in all four strains were roughly equivalent.


The effect of uremic serum on normal human and guinea pig lymphocytes. Incubation of normal 51-Cr-labeled human and guinea pig lymphocytes with uremic serum or guanidinosuccinic acid did not cause an increase in 51-Cr release. Electron microscopic examination of these lymphocytes revealed no abnormalities. It is suggested that the lymphocytopenia of uremia is not due to increased destruction of cells but may be a result of redistribution to other body compartments.


Effect of heat and milk yield on bovine plasma glucocorticoid levels. This study indicates that at 15 degrees higher producing cattle (milk yield) have higher plasma glucocorticoid concentrations compared to lower producing cattle with glucocorticoid levels appearing to be positively correlated with lactational intensity. Short term thermal (30 degrees) exposure for 18 hr resulted in glucocorticoid levels being markedly lower in high producing cattle compared to low producers. This shift at 30 degrees (after 18 hr) is possibly due to different time sequence of glucocorticoid response to thermal exposure between high and low producing cows. These data support the concept that glucocorticoids assist the animal in efficiently meeting the greater energy demand of lactation and further studies should be undertaken to denote free plasma levels and their utilization by dairy cattle at various levels of milk production.


Isotope inequilibrium of glucose metabolites in intact cells and particlefree supernatants of Ehrlich ascites tumor. With an enzyme degradative technique, isotope inequilibrium of glucose metabolites was demonstrated in intact cells and particlefree supernatants of Ehrlich ascites tumor using 1-14C-glucose as tracer. Inequilibrium was found between glucose and glucose-6-phosphate, glucose and fructose-6-phosphate, glucose and 6-phosphogluconate, while glucose-6-phosphate were found to be in near-equilibrium within the incubation time investigated. Glucose and lactate were found to be in near equilibrium after 8 min in intact cells. Calculations based on the equilibrium levels found, showed that these inequilibria could not be explained by the effects of the pentose cycle.


Congenital transposition of the scrotum and penis. A case of penoscrotal transposition is presented. A corrective surgical prodedure isdescribed.


Awe and premature efaculation: a case study. The analysis of a man suffering from premature ejaculation is described.  As is typical of a large group of men who ejaculate prematurely, he was passive and masochistic in his marriage and obsessive-compulsive in his character.  Analysis of his affect of awe led first to a deeper understnding of his self-representations and object relationships, and later, with the discovery of the specific unconscious fantasies associated with the feeling of awe, to the alleviation of his symptom of premature ejaculation.


Reversal of ECS-induced amnesia by post-ECS injections of amphetamine. Water deprived rats were trained to drink from a water spout within an apparatus on each of 2 days. On the third day, passive avoidance of the spout was induced by giving the animal a 0.3 sec, 5 mA footshock after 1 lick at the spout. A test for retention of the avoidance learning was given 48 hr following training. ECS administered through cortical electrodes at 15 sec following the footshcok impaired retention. The amnesia was attenuated when amphetamine (1 mg/kg) was injected immediately but not at 6 hr following the ECS. In a second experiment, attentuation of amnesia by amphetamine was not found when the ECS occured at 4 sec instead of 15 sec following the footshock. The results are interpreted in terms of reactivation by amphetamine of a consolidation process that was interrupted by ECS.


Puromycin's suppression of memory in mice as affected by caffeine. It has previously been shown that expression of maze-learning in mice is blocked for long periods of time by puromycin injected intracerebrally one or more days after the training experience. Treatment with caffeine after training has now been found to reduce greatly the amnestic effects of puromycin. With a high dose of caffeine (200 mg/kg) this reduction is evident 6 days after treatment with puromycin. With a lower dose of caffeine (25 mg/kg) the effect becomes evident only after a more extended period of time. In view of control experiments, we suggest that caffeine modifies factors necessary for the expression of memory and that this alteration makes puromycin relatively ineffective in blocking memory.


Antagonistic effect of cyproheptadine on neuroleptic-induced catalepsy. The influence of cyproheptadine on the neuroleptic-catalepsy in rats was studied. Cyproheptadine antagonized dose-dependently the catalepsy induced by spiroperidol, pimozide, fluphenazine and reserpine. The anticataleptic effect of two antiparkinsonian drugs, L-DOPA or amantadine was potentiated by cyproheptadine.


Inhibitory effects of pre- and posttest drugs on mouse-killing by rats. Mouse-killing in rats was gradually inhibited by repeated posttest injections of d-amphetamine (1.5 mg/kg), l-amphetamine (1.5 mg/kg) or pilocarpine (7.5 mg/kg), but not by control substances. Of these drugs, only d-amphetamine inhibited killing when given prior to a mouse-killing test. Further experiments suggested that anorexia per se did not contribute to drug-induced inhibitory effects, but that changes in internal state were important to the development of inhibition. Pretest injections appear to inhibit predatory killing by a direct pharmacological action on some target site or sites, while posttest injections produce a learned aversion to predatory killing.


The experimental reproduction of thrombocytopenic purpura in piglets. Two gilts, non-affected members of a litter which had been affected with thrombocytopenic purpura were mated to a boar which was an affected member of the same litter. During pregnancy the gilts were injected with pure thrombocyte suspensions from the boar. Antibodies to the boar's thrombocytes were demonstrated in the sera of both gilts and also in samples of their colostrum at each parturition. The piglets produced from these matings had normal thrombocyte counts at birth but a proportion of them developed thrombocytopenia and purpura similar to that seen in natural cases within a few hours of receiving colostrum. However, despite the fact that this condition was observed in three litters from each of the gilts, a secondary thrombocytopenia at 10 to 14 days of age, characteristic of the naturally occurring condition, was only observed in two piglets in one litter.


The significane of Nematodirus helvetianus eggs which have survived on a pasture throughout the winter in the transmission of infection to calves. A field experiment was carried out to determine the significance of Nematodirus helvetianus eggs which had survived throughout the winter in the transmission of infection to calves turned on to a pasture in the early summer. The calves became infected but did not exhibit symptoms of clinical disease. It was concluded that eggs which survive the winter are unlikely to be associated with outbreaks of disease.


Snuff dippers keratosis (snuff-induced leukoplakia). Patients with chronic snuff-induced keratosis associated with mucosal ulcerations were treated with topically applied vitamin A acid. In each case, after a marked, local inflammatory response initially, topical vitamin A acid showed a definite beneficial effect in promoting healing and involution of the precancerous snuff-induced leukoplakic keratosis. In one patient there was distinct involution of the oral lesions with complete healing and restoration of a normal-appearing mucosa within five weeks after beginning of treatment. In four patients there was healing of superficial ulcerations and regression in the size of the luekoplakic lesions.


Number of cells in diapausing silkworm embryos with different ploidies. The number of cells in diapausing silkworm embryos of different ploidies was determined. Thermal activation was shown to lead to a decrease in the number of cells in parthenogenetic embryos in comparison with normal, zygotic development. The number of cells in the embryo is a direct function of egg volume and a reciprocal function of embryo ploidy and is affected by the maternal genotype.


Study of the nature of the growth-inhibiting factor in embryos of mice of the mutant line brachypodism-H. An extract from 13-day embryos of mice homozygous with respect to the bp-H gene contains a growth-inhibiting factor (GIF), which inhibits the growth of normal bones in vitro. The activity of the GIF depends on the concentration of the extract in the culture medium. The sensitivity of the GIF to heating and proteolytic enzymes is an indication of its protein nature. The precipitation of the GIF from the embryonic extract with ammonium sulfate, followed by fractionation on columns with Sephadex G-200 and DEAE-Sephadex gave a 400-fold degree of purification. The active growth-inhibiting preparation obtained is represented by three proteins, which migrate slowly in electrophoresis in polyacrylamide gel. The molecular weight of the basic component is 76,000.


The frequency and detection of serious postoperative thromboembolic disease. A safe, sensitive and convenient technique using 131-I fibrinogen for detecting deep venous thrombosis in postoperative patients has been developed. A total of 47 volunteers over age 40 years about to undergo major operation were studied prospectively. Neither in 20 patients given heparin as part of the surgical procedure or for prevention of superficial phlebitis in the arm during intravenous therapy nor in the 27 others not given anticoagulants before, during or after operations was there evidence of venous thrombosis in the leg or pulmonary embolism either by the 131-I fibrinogen scan nor by clinical course. A retrospective review of hospital records confirmed the relative rarity of pulmonary embolism as a cause of identified morbidity and mortality in surgical patients. Of 54, 183 adult patients discharged from the University Hospitals of Cleveland during 1972 and 1973, 197, or 0.4 per cent, were diagnosed as having pulmonary embolism, and of these only 32, or 16 per cent, occurred in postoperative surgical patients. A review of the autopsy records of the same institution for the same time also revealed a low incidence of deaths due to pulmonary embolism among the surgical population, only 180, or 0.8 per cent, of the 22, 449 adult surgical admissions. Although feasible to perform, the value of the radiofibrinogen method of detecting deep venous thrombosis in postoperative patients as a routine measure is questioned.


Reconstruction of intrahepatic bile ducts in congenital biliary atresia. Macroserial reconstruction of the main intralobular bile ducts was made in 7 cases of biliary atresia; 2 cases of type I, 1 case of type II and 4 cases of type III according to Kasai's classification. From the results of these reconstruction studies, it was confirmed that the main interlobular bile ducts are usually patent through the liver regardless of the type of atresia of the extrahepatic bile ducts. A microserial reconstruction of bile ducts and ductules of a small portal tract performed in one case disclosed that a number of ductules make a network around the main duct and have some communications with the main duct. These results were compatible with the fact that active excretion of bile was obtained in many postoperative patients with biliary atresia. As observed in one case of the present series, postoperative complication of severe ascending cholangitis seemed to be an important cause of destruction or disappearance of intrahepatic bile ducts, which has also seen in older infants with this disease without complicaion of cholangitis. In view of these facts the operation of an early stage of life is recommended in biliary atresia.


Comparative studies of the growth promoting effects of ascitic or pleural effusion from patients with malignant tumors, human serum and fetal calf serum on human cells cultured in vitro. Twelve specimens of ascitic and pleural effusion (APE) from patients with malignant diseases were examined quantitatively for growth promoting effect on three human cell lines and one human cell strain, by four different assay procedures. Simultaneously, healthy human serum (HS) and fetal calf serum (FCS) were also examined for comparison. When the activity per mg protein of the test specimen was evaluated, the value of APE on an average was somewhat greater than that of HS in three out of four different assays, although FCS gave a higher average value than either APE or HS did in two of the three assays. However, a portion of APE specimens were found to have a unique promoting activity responsible for increase in number of cell colonies.


Effects of amethopterin (methotrexate) on the evolution of pregnancy in rats. Amethopterin (4-amino-N-10-methyl-glutamic acid) was given to pregnant rats in varying doses at different periods of gestation to evaluate its effects upon both the mother and the fetoplacental unit. The maternal organism is more sensitive to this drug at days 14 to 17 than at a larger stage of gestation. When administered to rats from day 14 to day 18 of pregnancy the drug is capable of inducing a series of deleterious effects: maternal weight loss, resorption, abortion or hypotrophy of fetuses. Day 16 appears to be a critical moment in the evolution of rat pregnancy, after which injection of amethopterin does no longer impair fetoplacental growth. Before this date, the drug directly inhibits fetal weight gain, whereas the sensitivity of the placenta is only transient at day 16 resulting in maximum weight decrease of this organ 24 h later. Its action on rat pregnancy follows a direct dose-effect relationship reflecting increasing damage to the products of conception (resorption, abortion and hypotrophy).


New approach to the study of hormone-protein interaction using the microcalorimetric method. Binding enthalpies of various hormones to bovine serum albumin (BSA) and human serum albumin (HSA) in 50 mM phosphate buffer, pH 7.4, at 37 degrees C have been determined by direct microcalorimetry. The observed enthalpies of binding of progesterone, testosterone, dihydrotestosterone, corticosterone and estriol to BSA were found to be -13.24 plus or minus 0.11 -10.31 plus or minus 0.02, -2.37 plus or minus 0.46, -17.64 plus or minus 0.32 and -17.14 plus or minus 0.36 kcal/mol of hormone, respectively. under the same experimental conditions the enthalpies of binding of progesterone, testosterone, dihydrotestosterone, corticosterone and estriol to HSA were found to be -23.94 plus or minus 0.32, -18.88 plus or minus 0.49, -11.14 plus or minus 0.02, -9.88 plus or minus 0.14 and -20.85 plus or minus 0.39 kcal/mol of hormone, respectively.


Radioimmunoassay of estradiol-17beta in bovine peripheral plasma with and without chromatography. An assay of estradiol-17beta (E217beta) in bovine peripheral plasma is described. The plasma is incubated with an antiserum to E217beta-BSA and the gamma-globulin fraction precipitated with ammonium sulphate. After extraction with diethyl ether E217beta in the precipitate is estimated by radioimmunoassay using a specific antiserum against E217beta-6-BSA. Plasma concentrations of E217beta during the normal estrous cycle determined by this method and by a method involving Sephadex LH-20 chromatography range from 4 to 23 pg/ml.


Urinary gonadotropins in management and prognosis of testicular tumor. Ninety-three cases of germinal testicular tumors with urinary gonadotropin (HCG) values, estimated by biologic or radioimmunoassay techniques, were reviewed. Preoperative values of HCG and subsequent postoperative values were related to response to treatment and prognosis. Twenty-five patients (26.9 per cent) comprised the seminoma group, and 68 patients (73.1 per cent) the nonseminomatous groups of germinal neoplasms. High HCG values were observed in the nonseminomatous group pre- and postoperatively by both assay procedures. Most significant was the high HCG values postoperatively (p smaller than 0.05, x2 equals 5.21 and p smaller than 0.05, x2 equals 5.23) for the biologic assay and radioimmunoassay, respectively, with high HCG values being associated with a poor cumulative 24 per cent two-year survival rate. Urinary HCG assay is of prognostic value in the ongoing management of testicular neoplasms. In the future, serum HCG assays may be of additional benefit.


Transpubic repair of vesicourethrovaginal fistula. A patient with recurrent urinary vaginal fistula involving bladder, bladder neck, and urethra was treated by transpubic approach. This afforded excellent exposure for careful repair of the urologic defects. Difficulty with ambulation during the first few weeks postoperatively may be related to removal of larger segment of pubic bone than is usually reported.


Urethral pressure profile.  Standardization of technique and study of reproducibility. The different methods utilized for measurement of urethral resistance were critically reviewed.  Using dogs, experiments were done to standardize the pressure profile measurement.  A catheter with eight side holes measureing 0.34 mm. each was found to give the best results.  The various parameters which can influence the procedure were analyzed.  Strict specifications are proposed to be utilized for such a procedure.


Choriocarcinoma and bilateral renal metastases. A case of choriocarcinoma presenting with metastases to both kidneys is reported.  The epidemiologic and pathologic aspects of gestational choriocarcinoma are briefly discussed.  Prior reports of renal metastases with choriocarcinoma are reviewed, and the fairly typical clinical presentation for this entity is emphasized.


Neurofibrosarcoma of spermatic cord.

Neurofibrosarcoma of spermatic cord. The first report of a neurofibrosarcoma arising within the spermatic cord is presented.  The light and electron microscopic features are discussed.


Suprarenal neurilemoma.

Suprarenal neurilemoma. Retroperitoneal neurilemomas are rare tumors. They are usually asymptomatic, grow to a large size, and generally undergo cystic degeneration before they are discovered. There may be a palpable flank mass. Almost invariably excretory urography shosw renal or ureteral deviation, and arteriography usually reveals an avascular mass. We present a brief review of the literature and 2 case reports of suprarenal neurilemoma, a site of occurrence not previously reported. One suprarenal neurilemoma occurred in a two-year-old child. The other was removed from a fifty-two-year-old man, and in this case a thoracoabdominal approach was helpful.


[The effect of N-nitrosomethylurea on organ cultures of human embryonal lung tissue]. The character of blastomogenic action of 7,12-dimethylbenz(a)anthracene on the stomach in its parenteral administration was studied on different lines of mice. Under the same conditions DMBA distribution was investigated in the proventriculus and gastric glandular tissues. In DMBA application on mice skin in the dosage of 0.5 mg per animal in 0.1 ml of acetone proventricular tumors developed in 34% of mice of line CC57Br, in 10% of mice of line CC57W, and in 11% of mice of line C3HA, and in 19% of white nonpedigree mice. In intraperitoneal injection of DMBA in the dose of 0.5 mg per mouse in 0.2 ml of saline solution proventricular tumors appeared in 56% of CC57Br mice (in 9 of 16) and in one of five mice of CC57W line. Whereas, in application of DMBA onto mice skin in the dose of 0.5 mg per mouse in 0.1 ml of acetone the DMBA content in the proventriculus was 13 times higher than that in gastric glandular tissues.


[The effect of N-nitrosomethylurea on organ cultures of human embryonal lung tissue]. A direct effect of NMU (0.05 mg/ml) on human embryonal pulmonary tissue (22-24 week old fetuses) has been studied in various duration of cultivation: from 3 to 33 days. During the first period of the experiment the NMU action produced marked dystrophic changes and death of a considerable number of experimental cultures, as compared with the corresponding intact control cultures. Starting from the 10th day the survival of cultures under experiment was higher, in general, than in the control. Moreover, hyperplastic changes developed in them, which frequency rising from 7.7% to 39.1%. These were absent in control series.


Generalized calcification of the liver in advanced schistosomiasis japonica--a case report. A generalized calcification of the liver was seen in a plain abdominal radiograph of an old male with schistosomiasis japonica and a myeloma.  Autopsy disclosed advanced fibrosis of the liver, and histologically, numerous calcified ova with calcification of the surrounding tissue were seen in the thick fibrous bands.  Calcification of schistosoma ova so intense as to exhibit a generalized hepatic calcification has never been described in the literature.  It is not clear whether the number of ova and the period of their presence are the only factors that determine the degree of liver calcification.


Influence of formula concentration on caloric intake and growth of normal infants. Fifteen fullterm female infants were enrolled in each of two feeding groups and all but one completed the proposed period of observation to age 112 days. Formulas prepared from the same ingredients (fat-free milk solids, a mixture of corn and coconut oils, lactose, vitamins and minerals) were fed ad libitum to both groups. Formula concentration was 54 kcal/100 ml for one group and 100 kcal/100 ml for the other. A limited selection of commercially prepared strained foods was permitted after 28 days of age. Weighed intakes of food were recorded for each day of study. During the internal 8 through 41 days of age, the infants fed the 54 kcal/100 ml formula consumed a considerably greater quantity of food but fewer calories than did those fed  the 100 kcal/100 ml formula. Those fed the 54 kcal/100 ml formula also gained less weight. These differences between feeding groups were statistically significant. After 41 days of age, mean caloric intakes (kcal/kg/day) and rates of gain in weight were similar for the two feeding groups. The data provide a basis of speculation on the possible difference in allocation of calories to growth and non-growth in the two groups.


Exchange transfusions with concentrated ACD-blood. I. Effects on the infant's red cell volume, plasma volume and haemoglobin mass. During ten exchange transfusions, the infant's gain or loss of haemoglobin, and of the volumes of red cells and plasma were studied quantitatively The gain or loss of haemoglobin was found to be closely correlated to the difference between the haemoglobin concentration of the given blood and that of the infant before the exchange transfusion. The standard ACD-blood used was hypo-osmolar (NIH sol. B) and its red cells overhydrated. During the exchange, the cells returned to normal and released water, about 10 ml per kg of the infant's bodyweight. Haematocrit readings therefore are unsuitable for the judgement of the ACD donor blood's oxygen transport capacity. As a rule, less plasma was given than removed. However, if the above-mentioned water, released from the red cells, was included in the "given" volume, the latter became almost equal to the volume removed.


Estrogen stimulation of conjugase activity in the uterus of ovariectomized rats. Recent observations have indicated that uterine folic acid conjugase (pterolypolyglutamyl hydrolase) undergoes rhythmic variation during the reproductive cycle of the rat. In the present study conjugase activity and ratios of "total" folate to "free" folate were determined in uterine homogenates of ovariectomized rats, with ane without estrogen stimulation. An increase in conjugase levels and a relative increase in the "free" folate component occurred in castrated animals 12 to 18 hours following injection of 10 mug of estradiol-17beta.


Cerebrospinal fluid lactic acid dehydrogenase activity. Levels in untreated and partially antibiotic-treated meningitis. High levels of cerebrospinal fluid (CSF) lactic acid dehydrogenase (LDH) activity were found in 23 cases of bacterial meningitis, but significantly lower levels of CSF LDH activity were observed in 11 patients with viral meningitis and in 13 patients with no central nervous system infection. No correlation was found between levels of CSF LDH activity and specific agents or the amounts of CSF white blood cell, protein, and glucose. The number of meningitis cases of unknown cause that could be classified as probably bacterial or viral was increased by determination of the level of CSF LDH activity. The level of CSH LDH activity is useful in differentiating bacterial from viral meningitis and, along with determination of the CSF blood cell counts and protein and glucose levels, aids in classification of meningitis before culture results are available.


The effect of acute ethanol treatment on lipid-reesterifying enzymes of the rat small bowel. The acute effects of intraduodenal administration of ethanol, 5 g/kg body weight, on intestinal activities of lipid-reesterifying and disaccharidase enzymes of the small bowel were studied. Results were compared to those produced in controls receiving isocaloric amounts of glucose by the same route. Acyl-CoA:monoglyceride acyltransferase, acyl-CoA synthetase (acid:CoA ligase (AMP) EC 6.2.1.3), sucrase, and lactase assays were performed on jejunal samples; acyl-CoA synthetase assay was performed on ileal samples. Ethanol produced greater activities of the lipid-reesterifying enzymes in the jejunum than did glucose. Ileal specific activity of acyl-CoA synthetase was also increased in the experimental group. No effect of ethanol on jejunal disaccharidase enzyme activities was noted. It is concluded that ethanol given acutely has a specific stimulating effect on intestinal enzymes involved in lipid absorption.


Carcinoembryonic antigen in patients suffering from ulcerative proctocolitis. Carcinoembryonic antigen (CEA) has been measured by radioimmunoassay in samples obtained from all patients suffering from ulcerative proctocolitis and seen within a four-month period. The characteristics of this group of patients have been compared with reported epidemiological studies in this disease, and have been found to have a similar sex ratio and age of onset, but a more limited disease. Among 59 patients, 11 were found to have elevated circulating CEA values. One of the 11 had a colonic carcinoma and another was pregnant. Excluding these two patients, an overall prevalence of elevated CEA levels of 17.5% was found. The prevelance in ulcerative proctitis was 7.1%, and in colitis was 19.9%. The patients in whom elelvated plasma CEA values were found were compared with the remaining patients in relation to factors known to be associated with an increased propensity for the development of colorectal carcinoma complicating ulcerative colitis. There was no difference in mean age of the patients at disease onset, nor was there any difference in disease duration, extent, and control. A significant correlation was found between elevated plasma CEA levels and the severity of the initial attack. One patient with premalignant changes in the rectal mucosa had consistently normal concentrations of plasma CEA. There was no significant correlation between elevated plasma CEA values and disease activity. The mean age of the two groups of patients was similar. No carcinoma has manifested in any patient during follow-up periods of at least 18 months.


Tetanus and diphtheria antitoxin levels following a hospital-based adult immunization program. A hospital-based program to immunize adults against tetanus unless specific contraindications to immunization are present has been in effect at Parkland Memorial Hospital since 1959. Adsorbed tetanus toxoid was used from 1959 to 1970, and was replaced at that time by adult type adsorbed combined tetanus/diphtheria toxoid. In the present survey, the titers of diphtheria and tetanus antitoxins were determined in sera from 97 adults admitted to the Medical Service. Titers of diphtheria antitoxin less than 0.0125 units per ml were found in only seven patients and less than 0.0125 units per ml of tetanus antitoxin in only 17 patients. This high prevalence of immunity especially to tetanus appears to reflect our practice of routine immunization of adults. Although the recommended frequency of tetanus boosters has recently been reduced for adults who have completed a full primary immunization series, susceptibility to diphtheria or tetanus or both is not uncommon among adults in the US. Unless contraindications are present, we therefore urge routine immunization of all adults seeking medical care and of all hospital personnel as a means of diminishing the risk of diphtheria and tetanus in those adult populations with a significant incidence of susceptibility to these diseases.


The pharmacy college as a pharmacy service "corporation". A program of providing contract pharmaceutical services to health care facilities by a college of pharmacy is described.  Services are provided to ten facilities: five hospitals, three mental health centers, a free-standing cancer clinic and a primary care center.  The initial development of the concept, the lines of authority between the college and the facilities, the nature of the contractual agreements, and the benefits of the program are discussed.  Among the benefits are the development of advanced drug distribution systems and clinical services, secure positions for clinical faculty members, the availability of the college's resources to the health care facilities, training and employment opportunities for students, and the good will created by improved health services.


Diphenylhydantoin-induced serum sickness with fibrin-platelet thrombi in lymph node microvasculature. In this 16 year old boy a syndrome, characterized by high fever, generalized lymphadenopathy, splenomegaly, diffuse skin rash, facial and periorbital edema, neutropenia, thrombocytopenia, elevated serum glutamic oxaloacetic transaminase (SGOT) levels and transient electrocardiographic changes, appeared 2 weeks after the institution of diphenylhydantoin therapy. Lymph node biopsy, performed at the height of the illness, revealed widespread subendothelial fibrin exudation and fibrin-platelet thrombi in the lymph node microvasculature, a finding most consistent with thrombotic thrombocytopenic purpura. Although many types of abnormal lymph node histology have been described with diphenylhydantoin, this appears to be the first instance of this histologic picture. This syndrome may be related to a serum sickness-like illness which triggered an episode of localized coagulopathy.


Thrombotic thrombocytopenic purpura in four siblings. A family is described in which four members of a sibship of seven suffered from a hematologic and systemic disorder whcih has been fatal in three and has been proved at  autopsy to have been fatal in three and has been proved at autopsy to have been thrombotic purpura. The fourth member has probably suffered the same disorder. The clinical laboratory and genetic features of the family are discussed at length. No cause of the disorder has been determined.


Maternal psychological stress and fetal asphyxia: a study in the monkey. Fifteen pregnant rhesus monkeys near term were anesthetized with pentobarbital. Catheters were placed into the right femoral arteries of the mother and fetus, the fetuses being retained in utero. After repair of all incisions, the mothers were placed on their sides and allowed to recover from anesthesia. As they awakened, their fetuses regularly developed blood chemical and, frequently, vital signs changes indicative of deepening asphyxia. In eight cases, anesthesia was reinstated with intravenous pentobarbital, 30 mg. per kilogram. This caused an immediate and significant improvement in oxygenation of the fetus in all instances. The remaining animals were transferred to restraining chairs where the blood chemical and cardiovascular statuses of the mothers and fetuses were followed over the next 3 to 72 hours. During this time, the mothers, fully awake, were subjected to both "contrived" and "incidental" episodes of psychological stress stimulation. In the majority of instances, these periods of stress to the mothers caused episodes of bradycardia and hypotension in their fetuses. These induced vital signs changes of the fetuses appeared regularly about 50 seconds after the beginning of the periods of stress stimulation of the mother. Similarly, the vital signs changes frequently began returning toward more normal values with 1 to 2 minutes after the alleviation of maternal stress. Blood samples drawn in single cases before, during, and after recovery from bradycardia identified an associated increase in asphyxia of the fetuses. These episodic aggravations of the already existent fetal asphyxia of the fetuses. These episodic aggravations of the already existent fetal asphyxia brought about by stress stimulation of the mother are interpreted as resulting from activation of the maternal sympathetic nervous system causing vasoconstriction throughout the abdominal viscera and an accompanying retardation in intervillous space perfusion.


Placental transfer of glutamate and its metabolites in the primate. When radioactive glutamate was infused into pregnant rhesus monkeys, 69 to 88 per cent of radioactivity in the maternal plasma remained in association with glutamate while 10 to 22 per cent was converted to glucose. In the fetal plasma, glucose and lactate accounted for more than 80 per cent of radioactivity, with less than 2 per cent of the label found in glutamate. Maternal glutamate infusions resulting in a ten- to twenty-fold increase in maternal plasma glutamate levels (60 to 100 mumoles per 100 ml.) had no effect upon fetal glutamate levels. Infusions producing maternal glutamate levels 70 times normal (280 mumoles per 100 ml.) did result in some transfer of glutamate to the fetal circulation. Labeled glutamate administered to the fetus at 1.5 to 2.4 Gm. per kilogram of fetal weight did not result in glutamate transfer to the maternal circulation. Infusion of glutamate to the fetus at 5 Gm. per kilogram of fetal weight increased fetal plasma glutamate levels to 2, 000 mumoles per 100 ml. and resulted in some transfer of glutamate to maternal circulation. Glutamate metabolites (lactate and glucose) were readily transferred across the placenta in either direction. These studies indicate that the primate placenta is virtually impermeable to glutamate unless extreme elevations of plasma glutamate are induced.


Amenorrhea and galactorrhea: results of therapy with 2-Brom-alpha-ergocryptine (CB-154). Administration of Brom-ergocryptine (CB-154) has a dramatic effect on breast secretion. Inhibition of lactation occurs within three to four weeks in women with amenorrhea and galactorrhea. Resumption of normal ovulatory function was documented by serum progesterone levels, as well as pregnancy, in three of four women attempting to conceive. Serum prolactin levels become normal following initiation of Brom-ergocryptine. Discontinuation of Brom-ergocryptine was found to result in a return of both inappropriate lactation and elevation of serum prolactin in this study. No deleterious side effects of Brom-ergocryptine have been found in any of the volunteers either clinically or on the basis of sequential laboratory studies.


Serum amylase changes during pregnancy.

Serum amylase changes during pregnancy. Study of the behavior of serum amylase activity in 200 preganant women in various stages of pregnancy indicated that: (1) serum amylase rises gradually during pregnancy until the twenty-fifth week and thereafter falls slightly; (2) serum amylase values may be found in normal pregnant women during the second and third trimesters that exceed those in normal men and nonpregnant women; (3) during the second trimester of pregnancy there may be an alteration in the relative distribution of the pancreatic and salivary-type isoamylases with the salivary type tending to dominate. Knowledge of these changes is of importance in the clinical assessment of serum amylase values in pregnant women complaining of abdominal pain and other symptoms suggestive of complicating acute pancreatitis. An explanation for the observed changes is not readily available and further study is required.


Sequential therapy for advanced ovarian adenocarcinoma: operation, chemotherapy, second-look laparotomy, and radiation therapy. In an attempt to improve the survival rates in women with advanced ovarian adenocarcinoma (abdominal spread), they were treated with sequential therapy. This consisted of operation followed by chemotherapy, second-look exploratory laparotomy, and finally whole-abdomen irradiation. Only those patients who had a complete clinical response to chemotherapy and subsequently underwent a second operation and irradiation were evaluated. Seventy-five per cent of the patients had recurrent cancer within the treated area after sequential therapy was completed. Morever, of four patients with no gross residual cancer after the second operation, three had cancer recurrences within the treated area. It is concluded that methods of treating advanced ovarian adenocarcinoma other than sequential therapy must be found.


Ocular effects of a 325 NM ultraviolet laser. Corneal exposures were made on 100 eyes of anesthetized rhesus monkeys with a continuous wave HeCd ultraviolet laser at a wavelength of 325 nm. The ED-50 corneal damage probability point was determined to be 0.8 joules of energy. This is higher than the levels for damage reported for noncoherent ultraviolet sources. However, the endpoint used here was a well-defined circumscribed lesion as contrasted to the appearance of granules used for the broad band, wide-beam, noncoherent studies. The granules were not seen with the narrow band, small beam laser irradiation. Exposures made with 6.5 joules of energy produced lens damage, i.e., cataracts. This represents permanent damage as compared to the corneal damage which at threshold levels is completely reversible in 24-48 hours.


Free amino acids of sex organs of the mouse: regulation by androgen. Male mice were castrated at 2 mo and a pellet of testosterone propionate was implanted subcutaneously 2 wk later. Mice were killed after 11 days and tissue extracts were analyzed. All the common 20 amino acids were present in widely varying concentrations. Castration uniformly increased the concentration of all free amino acids of the seminal vesicle, excepy proline, cystine/2, and tryptophan; androgen restored values to normal. These changes were not entirely due to changes in quantity of seminal vesicle fluid. Concentrations of amino acids of the prostate were not significantly changed by castration or testosteronepropionate. Fifteen other ninhydrin-postive compounds were detected. Hypotaruine, taurine alpha-aminobutyric acid, and cysteic acid in seminal vesicles were greatly decreased and several other compounds were slightly decreased by castration and restored tp normal by testosterone propionate. In the prostate, hypotaurine, alpha-aminobutyric acid, cysteic/cysteinessulfinic acids, glycerophosphoethaniomine, cystathionine, and phosphoethanolamine were decreased and alpha-amino-n-butyric acid was increased by castration and restored to normal by testosterone propionate. Concentrations of taurine and 5 other compounds were not affected. Epidiymis and testis also contained appreciable pools of amino acids and the other compounds. Amino acids concentrations were lower in cauda than in caput epididymis; in the testis values were intermidate, with much higher concentrations of glutamic and aspartic acids. Taurine concentrations were twice as great in cauda as in caput epidiymis; concentrations of hypotaurine and the other sulfur-containing compounds were similar in both parts of the epidiymis. The most striking result in the testis was the high concentration of reduced glutathione.


Effects of acute and chronic ethanol administration on isoflurane requirement in mice. Inspired isoflurane concentration for anesthetizing 50 percent of adult albino mice (ED50) was 1.33 percent (1.20 to 1.47, 95 percent confidence interval). Ethanol anesthetizing dose was 5.09 (4.74 to 5.47) gm./kg. intraperitoneally (I.P.). Twenty, 39, and 79 percent of this ethanol anesthetic dose reduced isoflurane ED50 by 0, 8, and 70 percent, respectively. Thus, acute combinations of ethanol and isoflurane are more effective than either alone but less than the expected sum. Mice receiving no other fluid than 10 percent alcohol developed cross-tolerance to isoflurane. After 10 days of continuous alcohol ingestion, isoflurane ED50 increased to 1.54 (1.36 to 1.75) and after 20 days to 1.69 (1.55 to 1.84) percent. Combined with 2 and 4 gm./kg. of alcohol I.P., isoflurane ED50 in these mice decreased to 1.34 (1.26 to 1.42) and 0.73 (0.62 to 0.85) percent. Cross-tolerance acquired by these alcohol-consuming mice persisted through 55 days after stopping alcohol (ED50 1.65 percent), but returned to control values after 80 days (1.32 percent).


Use of the pulse-wave monitor as a measurement of diagnostic sympathetic block and of surgical sympathectomy. Changes in skin blood flow in a digit following sympathetic denervation were determined by use of a photoelectric digital plethysmograph (pulse-wave monitor). Results in 20 cases of diagnostic sympathetic block, surgical sympathectomy, or both, are discussed. Pulse-wave changes were seen 3 to 5 minutes after block and 1/2 to 1 minute after sympathectomy. Use of a pulse-wave monitor permitted limiting the dosage of local anesthetic, usually to 5 to 10 ml. of 0.5 percent lidocaine for lumbar sympathetic block and 1 to 2 ml. of 0.5 percent lidocaine for stellate ganglion block. Pulse-wave monitoring was found to be simple and rapid.


Adverse effects of increased succinylcholine dose following d-tubocurarine pretreatment. Changes in serum potassium (K+) and serum creatine phosphokinase (CPK), incidence of heart rate slowing, junctional rhythm, and postoperative myalgia were determined in patients receiving intravenously (I.V.) either 1 mg./kg. of succinylcholine (SCh) or 0.04 mg./kg. of d-tubocurarine (dTc) as pretreatment, followed 3 minutes later by 2 mg./kg. of SCh. The incidence of heart rate slowing (15 percent less than the control heart rate), junctional rhythm, and postoperative myalgia was less in pretreated patients. Serum CPK and serum K+ elevations were similar with or without pretreatment. Increasing SCh dosage with pretreatment apparently did not accentuate adverse effects, and in some instances was associated with fewer such effects, than after lower-dose SCh injections without pretreatment.


Minimizing emergence phenomena: subdissociative dosage of ketamine in balanced surgical anesthesia. Three hundred twelve patients, ranging in age from 14 to 89 years and undergoing various major and minor surgical procedures, were anesthetized by oxygen, nitrous oxide, and ketamine in sequence. Anesthesia was induced with thiopental (5.8 mg./kg.). The first 212 patients received an initial dose of ketamine of 1.6 mg./kg. lean body mass; 100 other patients, an initial (subdissociative) dose of ketamine of 0.4 mg./kg. body weight. Subsequent doses of ketamine, one-half the initial dose, were given 20 to 40 minutes apart, as needed. Postoperative subjective reactions were limited to slight confusion on emergence, with some disorientation to time, and occurred in 10 patients (5 percent) in the first group and 4 (4 percent) in the latter group. No psychotomimetic reactions were noted in either group. The latter group unanimously found the anesthetic technic acceptable for future use.


Pyridostigmine as an antagonist of d-tubocurarine-induced and pancuronium-induced neuromuscular blockade. In an evaluation of the clinical effectiveness of pyridostigmine as an antagonist of d-tubocurarine-induced and pancuronium-induced neuromuscular blockade in patients anesthetized with a neurolept-nitrous oxide (N2O) technic, 60 adults received either d-tubocurarine (dTc) (N equals 30) or pancuronium (N equals 30). The pancuronium-dTc potency ratio with neurolept-N2O anesthesia is 4.85:1. The mean doses of pyridostigmine necessary for 50 percent recovery of control twitch height and sustained tetanus were 5.72 plus or minus 0.45 (S.E.) mg. and 11.6 plus or minus 0.88 mg., respectively, for dTc, and 4.05 plus or minus 0.24 mg. and 8.27 plus or minus 0.41 mg., respectively, for pancuronium. There was no correlation between the amount of pyridostigmine necessary for relaxant antagonism and the total dose of relaxant used. In 24 patients, neuromuscular blockade was reversed by an intravenous injection of pyridostigmine and either 0.6 mg. or 1 mg. of atropine. Within 2 minutes, patients given 1 mg. of atropine had a significantly faster heart rate than those given 0.6 mg of atropine (p smaller than 0.0001). There was no correlation between control heart rate and maximum changes in heart rate. No cardiac arrhythmia or bronchospasm was observed in patients with either pancuronium or dTc following atropine-pyridostigmine mixtures. The cardiac muscarinic effects of pyridostigmine could be modified by simultaneous administration of 1 mg. of atropine.


Awake endotracheal intubation: a review of 267 cases. During a 3-month period, 267 "awake" endotracheal intubations, representing 35 percent of all preoperative intubations, were performed with small doses of amnalgesic drugs given intravenously. Of 249 patients interviewed postoperatively, 86 percent reported complete amnesia for the procedure and only 3.5 percent recalled the event as being "quite unpleasant".


Correlation between specific immunity to a metabolite of halothane and hepatic lesions after multiple exposures. A correlation between the use of halogenated anesthetic agents and liver necrosis is not yet established in man. In an attempt to resolve this dilemma, guinea pigs were immunized with a complex of guinea-pig albumin and trifluoroacetate (TFA), a common metabolite of halothane and fluorexene, and then exposed to halothane on multiple occasions. Histology and liver-function tests showed no difference in the incidence of liver damage between groups of animals immune to TFA with cellular immunity and untreated control animals. However, a difference in the liver enzyme levels was seen between controls and animals showing humoral immunity.


Anesthesia orientation for the medical student. Exposure of all medical students to selected anesthesiology-related subjects provides better acquaintance with the procedures and practices of the specialty. Airway management, methods of cardiopulmonary resuscitation, and patient monitoring are among the anesthesiologist's technics that have widespread applicability to all areas of medicine. The pharmacology of the many drugs, not only anesthetic agents, used in anesthesia may be discussed and demonstrated to advantage. The scope of the specialty, including preoperative and postoperative patient evaluation; the values and shortcomings of modern anesthetic agents, the role of anesthesia in postsurgical morbidity; and the anesthesiologist as a consultant, can be emphasized. Even a brief exposure to the specialty should enable the student to understand the place of the anesthesiologist and anesthetic agents in patient management.


Squamous metaplasia of tracheal epithelium associated with high-volume, low pressure airway cuffs. The tracheas of 12 patients, intubated from 2 hours to 20 days with tracheal airways equipped with the newer style, high-volume, low-pressure (HVLP) cuffs, were examined at autopsy. The type and severity of iatrogenic damage to the epithelium and submucosa was determined and compared to that seen in a previous study of 54 patients, who had been intubated with the older-style low-volume, high-pressure (LVHP) cuffed airways. The tracheal epithelial and submucosal damage due to intubation with the HVLP cuffed airways was considerably less than that with LVHP cuffs. The submucosal glands were often spared, and some of the tracheal epithelium even survived 20 days of exposure to the "soft" cuffs. However, the pseudostratified ciliated epithelium, which normally lines the trachea, was often replaced by stratified squamous epithelium. If such a zone of nonciliated epithelium remains in the trachea of a long-term survivor, its detrimental effect on the removal of particulate matter from the tracheobronchial tree may have to be considered.


Sickling dynamics of red blood cells and other physiologic studies during anesthesia. Nineteen patients with electrophoretically proven sickle cell diseases were studied prospectively at intervals, using halothane, methoxyflurane, cyclopropane, and fluroxene. Simultaneous venous and arterial samples were taken from the same arm in heparinized syringes at the sampling intervals and analyzed for blood gases, hematocrit, and percent sickle cells. Measurements of blood pressure, pulse, temperature, tidal volume, minute ventilation, and other significant data were recorded. There were no anesthetic deaths, and the morbidity seen was an extension of pre-existing pathology. Sickling was found to be greatly reduced in both arterial and venous blood during anesthesia, with the greater reduction in venous blood. Following anesthesia, sickling returned toward, but often did not reach, pre-anesthetic levels. Blood-gas measurements reflected the slightly increased ventilation and considerably increased inspired oxygen during anesthesia. Other measurements were not remarkable.


Interscalene cervical plexus block: a single-injection technic. A review of the anatomy of the cervical plexus and surrounding structures suggests a single-injection technic which simplifies anesthesia of the cervical plexus and increases the margin of safety in this procedure. Used by the authors, the technic has been successful in 97 percent of over 100 cases.


Alterations in ventricular fluid pressure during ketamine anesthesia in hydrocephalic children. We studies ventricular fluid pressure changes in 26 hydrocephalic children following administration of ketamine. The increase in VFP previously found with intravenously administered ketamine was compared with changes after ketamine given intramuscularly, and the possible alteration of this increase with sedative premedicants was studies. Changing the route of administration did not change the time to peak VFP changes or the duration of pressure elevation. There was no demonstrable alteration of the increase in VFP by premedication with secobarbital, dorperidol, or diazepam in clinical dosage. We feel that acute rises of VFP may affect areas of marginal cerebral blood flow and may increase the risk of herniation of brain tissue.


Anesthetic problems with aspirin-intolerant patients. Sixty-seven aspirin-sensitive asthmatic patients underwent a total of 89 operative procedures. Wheezing with induction, intraoperative tachycardia and arrhythmias, and postoperative wheezing were the major problems in their anesthetic course. Wheezing was encountered despite various induction technics. Preoperative steroids, aminophylline, and ephedrine appeared necessary for surgical preparation, but the presence of aminophylline and ephedrine predisposed to tachycardia under anesthesia. The appearance of mild preoperative wheezing allows the prediction of postoperative wheezing in a significant number of patients.


Pulmonary edema and wheezing after pulmonary embolism. A young, pregnant woman with angiographically proved pulmonary emboli developed pulmonary edema and wheezing without evidence of left ventricular failure. This cast study points out the unusual association of pulmonary embolism with pulmonary edema, wheezing, and hyper-reactive airways in a patient with a positive family history of allergy, but no antecedent history of bronchospasm. Mechanisms for the occurrence of noncardiogenic pulmonary edema and wheezing after pulmonary embolism are reviewed.


Doxapram antagonism of meperidine-induced respiratory depression. The intramuscular injection of meperidine (1 mg./kg.) alone causes significant respiratory depression, and doxapram (2 mg./kg.) alone causes significant respiratory stimulation, as evidenced by their ability to shift the carbon dioxide (CO2) response curve to the right and left, respectively. When given together, the mixture of the two drugs does not cause any significant respiratory depression, as indicated by the absence of a significant shift in the CO2 response curve to the right. This mixture has possible clinical usefulness in providing postoperative analgesia without respiratory depression.


Regional anesthesia in children.

Regional anesthesia in children. Regional anesthesia employing the spinal, epidural, or caudal approach was used to anesthetize 200 children, varying in age from 17 days to 15 years. Lidocaine in concentrations varying according to age was used. Ketamine (1 to 2 mg./kg.) was given in the majority of cases to ensure a quiet patient prior to block. No major anesthetic complications or deaths were attributable to the anesthetic technic. The caudal approach proved easiest.


Effects of anesthetic doses of morphine on renal function in the dog. Renal effects of anesthetic doses of morphine (2 mg./kg.) administered intravenously (I.V.) were determined in 15 mongrel dogs before and after addition of 50 percent nitrous oxide (N2O). Morphine significantly increased urine osmolarity and decreased urine output, free-water clearance, and arterial blood pressure, but did not affect inulin or para-aminohippurate (PAH) clearances. Addition of N2O did not significantly change arterial blood pressure and inulin clearance but did decrease urine osmolarity and osmolar and PAH clearances. These data demonstrate that, in contrast to man, anesthetic doses of morphine have significant antidiuretic properties in the dog.


Erythema gyratum atrophicans transiens neonatale. An unknown dermatosis was observed in an infant girl. During the newborn period, she had a generalized, patchy, erythematous eruption of about 60 round erythematous patches on the trunk, thighs, head, labial mucosa, and palate. After a few weeks, the lesions became whitish, atrophic, and depressed, and they were surrounded by an erythematous and slightly infiltrated border, which was occasionally lobulated. Histologically, the lesions demonstrated a thin epidermis overlying an edematous dermis. Around the border of the lesions the collagen bundles were infiltrated with mononuclear cells. Granular deposits of IgG, C'3, and C'4 were found at the dermoepidermal junction and around the superficial capillaries. The lesions healed completely and spontaneously within a year.


Survey of the clinical use of electrocochleography. A questionnaire on the clinical use of electrocochleography (ECochG) was distributed to clinics throughout the world which use this method. The 26 replies comprised 3696 cases with a median age of 22.5 years. The majority (57.1%) were tested with a transtympanic promontory electrode. The risk of any undesirable effect from this electrode placement was negligible (less than 0.1%), but a greater probability (less than 1.0%) of serious complication from general anesthetics was revealed. On the benefit side, ECochG added significant information to the diagnoses of 87.8% of the children and 34.2% of the adults, and in 48.2% of the children and 2.0% of the adults this information was a primary factor in the hearing evaluation and decision on management. The cases for which ECochG was most helpful were predominantly children and neonates with complex neurological or psychiatric problems which interfered with reliable testing by other methods. Comparisons of ECochG with other methods were reported in 63.2% of the cases. The respondents judged 97.4% of those comparisons to reflect favorably on the validity of ECochG.


Maternal protein depletion and small-for-gestational-age babies. It has been established that there is a high incidence of small-for-gestational-age babies among underprivileged urban Africans. This community suffers from endemic malnutrition. Serum albumin studies on mothers of low birthweight babies showed a direct correlation with size of babies for gestational age. Thus maternal protein depletion, and probably therefore malnutrition, was associated with the high incidence of small-for-age-gestational babies.


Benign granular cell tumors of the larynx: a review of 36 cases with clinicopathologic data. The clinical, microscopic, and gross features of 36 cases of benign granular cell tumor arising in the larynx are reviewed and studied. This infrequent lesion, when in the larynx, is found most commonly on the true vocal cord in adults in their third, fourth, and fifth decades; there is no obvious sex predilection. Slowly increasing hoarseness was the primary complaint in our cases. Clinically, the tumors are considered benign. The most common clinical impression was a vocal cord papilloma. The microscopic pattern of the granular cell tumors is uniform and bland, but there may be a marked pseudoepitheliomatous hyperplasia of the over-lying squamous epithelium, often stimulating squamous cell carcinoma. Follow-up information is discussed as is the origin and histogenesis of this lesion.


Eustachian tube ventilatory function in relation to cleft palate. The ventilatory function of the Eustachian tube was assessed in a group of infants and children with cleft palate, some of whom had received palatal repair. Those whose palates had been repaired were better able, in general, to equilibrate applied positive middle ear pressures than were those with open clefts. In many of the patients whose palates had been repaired, the results of Eustachian tube function studies were similar to those in normal subjects. Differences in Eustachian tube ventilatory function are assumed to be related to differences in tubal compliance. Excessive compliance probably results in, or exaggerates, functional Eustachian tube obstruction. Improvement in tubal function following palate repair is probably related to factors resulting in greater tubal stiffness.


A review of echinococcal disease.

A review of echinococcal disease. Echinococcal infestation, although still a rare occurrence in most of the United States, is being seen with increasing frequency. Three cases of hepatic echinococcosis are described. A review of the salient features of the disease is presented along with various aspects of diagnosis and therapy.


A new instrument for surgical exposure of subaortic and subpulmonic stenosis. An instrument for providing adequate visualization of the subvalvular area during repair of intracardiac defects is described. Essentially a type of modified nasal speculum, the instrument has proved helpful in performing resections in both subaortic and subpulmonic stenoses by exposing a wider surgical field.


Human wakefulness and biological rhythms after birth. Both a sleep-wakefulness cycle and a basic rest-activity cycle were observed in 20 normal infants left undisturbed for ten hours following birth. Behavioral wakefulness occurred immediately following delivery and in between sleep periods despite the lack of feeding and other intervention. Medication given to mothers during labor resulted in decreased amounts of infant wakefulness and increased amounts of quiet (non rapid eye movement) sleep.


Male transsexualism in England: sixteen cases with surgical intervention. The syndrome of transsexualism is now regarded as a dinstinct entity separate from transvestism and homosexuality (Benjamin, 1966; Green and Money, 1969). It refers to those patients who since childhood have been convinced of their wrong sex assignment and who wish to attain the sexual characteristics of the opposite sex and to live as a member of that sex. The present report is an initial one referring to the first group of transsexual patients studied at a postgraduate teaching hospital by a multidisciplinary team. Their study has three aims: first, to compare this group of patients with other series; second, to evolve a surgical technique of sex reassignment; and, finally, to assess the success of such surgery in allowing the patients to attain a satisfactory adjustment in their new gender role.


Initial heterosexual behavior of adolescent Rhesus monkeys (Macaca mulatta). This report described the first heterosexual encounters of twelve 3-year-old rhesus monkeys, six of each sex. The subjects were all laboratory-born and were reared in wire cages for the first 8 months of life, accompanied only by their mothers. After these animals were weaned, each was placed in a cage with another animal of the same age and sex. The pairs formed in this way remained intact until the animals were 2 years old. When heterosexual dyads were formed, some of the subjects attached and bit the animal with which they had been paired, while the members of other pairs established almost immediate rapport as evidenced by mutual grooming and adequate sexual behavior. The initial sexual interactions of most pairs were uncoordinated, but all eventually demonstrated qualitatively species-typical patterns of sexual behavior. Despite their immaturity, two of these pairs succeeded in producing offspring, both of which were healthy.


Effects of hypotension on rhesus monkeys. Twenty-one late-juvenile rhesus monkeys were rendered profoundly hypotensive for 0-, 15-, or 30-minute periods by means of infusion of trimethaphan camsylate. Blood pressure was then restored to prehypotensive levels with phenylephrine infusions. Respiratory gas tensions and pH of arterial blood were maintained within their normal limits throughout experimental and recovery periods. Animals either recovered and showed no sequelae or diet 12 to 48 hours later of cardiorespiratory difficulties, often accompanied by brain swelling. Brain injury and death occurred in 64% of cases when arterial blood pressure was maintained at 25 mm Hg for up to 30 minutes. Multifocal myoclonus, depressed electroencephalographic activity, rises in cisternal cerebrospinal (CSF) pressure, respiratory depression, and characteristic changes in serum and cisternal CSF glucose followed episodes of controlled hypotension. Hypoxia and acidosis occurring during insult or recovery periods rather than hypotension itself probably account for neuropathological sequelae described by others.


Snuff-dippers lesion. A ten-year follow-up. A population of over 15,000 snuff users and tobacco chewers were observe for cytological, histological, and clinical evaluation. The original observation was for 5 1/2 years. The same group was observed for an additional 4 1/2 years, bringing the total time to ten years. Of the original group of 1,751 patients showing mucosal change, i was able to follow up 1,550. No patient developed carcinoma or serious mucosal changes. From this ten-year study we concluded that snuff, per  se, or chewing do not act as carcinogens.


Electrolytic lesioning in the cochlea.

Electrolytic lesioning in the cochlea. A method has been developed whereby relatively discrete protions of the organ of Corti can be selectively destroyed with the use of a high-frequency current. The procedure involves passing th current (1 to 3 ma at an approximate frequency of 5 megahertz) between a differential pair of recording electrodes located in the scalae vestibuli and tympani of a particular cochlear turn. Damage patterns progressing from partial to complete outer hair cell lesioning and eventually to the inner hair cells accompanied by progressive decreases in cochlear microphonic sensitivity can be effected.


Open-field behavior in mice: A diallel analysis of selected lines. The open-field behavior of 719 mice resulting from a diallel cross among the six lines of the DeFries selection experiment was assessed.  Results of several analyses employing different models and procedures in open-field activity and defecation among these lines have predominantly additive effects.  Estimates of heritability obtained from these analyses were considerably higher than previous estimates based on familial resemblance or the realized response to selection; thus estimation of heritability from diallel analyses is clearly unwarranted when selected lines are employed and the character of interest has been either directly or indirectly subjected to artificial selection.


The genetics of pheromonally mediated aggression in mice. I. Strain difference in the capacity of male urinary odors to elicit aggression. Castrates scented with urine from intact DBA males elicited greater attack with a shorter attack latency than castrates scented either with male urine from other strains or with water. The results suggest that genetic factors affect pheromonally elicited aggression in mice


Genetic study of the aggressiveness of two subspecies of Apis mellifera in Brazil. IV. Number of stings in the gloves of the observer. Data are analyzed on an aspect of aggressiveness in workers from colonies of Africanized bees (Apis mellifera adansonii), Italian bees (Apis mellifera ligustica), their F1 hybrids, and backcrosses of the F1 to the parental stocks (Rothenbuhler method). The segregation values (3:1) in the backcrosses to the Africanized stock and nonsegregation in the backcrosses to the Italian stock suggest the existence of two pairs of genes (F1/F1; F2/F2 IN THE Italian bees and f1/f1; f2/f2 in the Africanized bees) which control a character defined of the number of stings in the gloves of the observer.


Ballistocardiographic deflections in active rheumatism without valvular defect. A study was carried out on 100 youths (aged 18-23 years, suffering from active rheumatism without a valvular defect. The cases with mild ballistocardiographic deflections prevail. In the greater number of patients, the Bcg normalization sets in 6 months after onset of the disease.


Development of the quantitative ballistocardiographic characteristics in children. Based on the examination of 493 boys and girls of ages 6-19 years, we have tried to express the relationship of quantitative ballistocardiographic characteristics to age. The absolute values exhibit increase which is common up to 13 years of age but is then followed by the steadily enlarged decline of curves. The relative values exhibit decrease with age and the differences between boys and girls get gradually larger, being smaller inrelation to the lean body mass than to the body weight. It bears evidence to the fact that body fat plays a certain role in relative values.


On the role of sialic acid in the rheological properties of mucus. The importance of sialic acid in the rheological properties of mucus has been investigated. Both bovine cervical mucus, which is a gel, and the structural glycoprotein derived from it were studied before and after treatment with neuraminidase which selectively cleaves terminal sialic acid residues. The storage modulus, viscosity and circular dichroism spectrum were all essentially changed after removal of the sialic acid. These results would indicate that removal of sialic acid does not affect the physical structure of the glycoprotein and it is concluded that sialic acid has no significant role in the rheological properties of cervical mucus.


Effects of thrombin on washed, human platelets: changes in the subcellular fractions. Pressure homogenization and subcellular fractionation has been performed on washed, human platelets and platelets treated with thrombin to undergo the so-called release reaction. Electron microscopy revealed that the particulate zones obtained from the control sample corresponded to membrane vesicles (B), small storage granules (D) as well as mitochondria and larger storage granules (E). Only a few storage granules could be observed in the particulate zones isolated from thrombin-treated platelets. Visual comparison of the sucrose gradient patterns revealed that one granule fraction (D) had disappeared from the thrombin-treated sample. Sodium dodecysulfate-polyacrylamide gel electrophoresis showed a major protein band (mol. wt 145 500 plus or minus 1000) in the extracellular phase (supernatant after removal of the platelets) of the thrombin-treated sample and in the granule fractions (D and E) of the control (mol. wt 147 000 plus or minus 1000). Incubation of whole, washed platelets with thrombin for 5 min at 37 degrees C followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis of the isolated membrane fraction revealed no reproducible differences in the protein band pattern compared to membranes isolated from control platelets. However, after treatment with thrombin for 30 min, a protein band (mol. wt 183 000 plus or minus 3500) had disappeared. The distribution of protein and beta-N-acetylglucosaminidase activity among the subcellular fractions were measured. Both were mainly recovered in the soluble fraction (greater than 77%). The granule fractions, D and E of the control contained 3.0% plus or minus 0.8% and 6.4% plus or minus 1.3% of the total amount of beta-N-acetylglucosaminidase in the gradient. Fraction E of the thrombin-treated cells contained 3.3% plus or minus 1.0% of total while fraction D was lacking.


HL-A W27 in psoriatic arthropathy.

HL-A W27 in psoriatic arthropathy. Forty subjects with psoriatic arthritis (PA) underwent HL-A tissue typing. HL-A W27 was significantly increased in psoriatic spondylitis (35%), whereas statistical significance was not reached in patients with peripheral arthritis alone, although W27 was present in a frequency greater than in controls. Psoriatic spondylitis (often asymptomatic) occurred in 57% (23 of 40) of our PA patients. Of interest, psoriatic spondylitis was more often W27 negative than W27 positive; nevertheless, W27-positive and W27-negative spondylitis was clinically and radiographically indistinguishable except that W27-positive disease occurred exclusively in males and the duration of the psoriasis.


Adrenal catecholamines content in fetal and newborn rats. The adrenal epinephrine content of newborn rats delivered by caesarian section on day 21.5 of gestation and maintained at thermal neutrality (37 degrees C) did not decrease over the 6 h following birth in spite of a transient phase of hypoglycemia. Cold exposure (30 or 24 degrees C) of the newborn rats immediately after birth did not decrease their adrenal epinephrine content. A decrease in adrenal epinephrine content is observed in 21.5-day-old rat fetuses after insulin-induced hypoglycemia for 4 h, after 2-deoxy-D-glucose injection or after anoxia. In 20.5-day-old rat fetuses, insulin-induced hypoglycemia for 4 h or 2-deoxy-D-glucose did not decrease the adrenal epinephrine content of the fetus. No variation was observed in norepinephrine content of the adrenal gland in all these situations. It is concluded that spontaneously occurring hypoglycemia or cold exposure are not sufficient stimuli to induce adrenal epinephrine depletion. It is suggested that hypoxia is perhaps the physiological stimulus for epinephrine secretion in newborn rats.


Developmental changes of tissue enzyme patterns in the bovine fetus with gestational age. The activities of aspartate aminotransferase (GOT), alanine aminotransferase (GPT), alkaline phosphatase (alkP), creatine kinase (CPK), and ornithine carbamoyltransferase (OCT) were determined in liver, heart, skeletal muscle, brain, kidney, lung, spleen, adrenals, pancreas, thyroid, thymus, and red cells of 56 bovine fetuses varying in gestational age from 115 to 255 days. The tissue aminotransferase activities were the most variable with gestational age. The GPT activity of liver, kidney, spleen, and red cells and the GOT activity of red cells decreased with fetal age. The GPT activity of heart, brain, and skeletal muscle and the GOT activity of adrenal, brain, and skeletal muscle increased with fetal age. Increasing activities were also described for adrenal and brain alkP and for brain and skeletal muscle CPK. In contrast, the OCT activities were fairly constant for each tissue as a function of gestational age.


Variations in human aortic fatty streaks among geographic locations. Histologic features of aortic fatty streaks were examined in male subjects aged 10-39 from Guatemala, Jamaica Negro, Durban Bantu, New Orleans Negro, New Orleans white, Lima and Santiago. These groups were selected from the 19 available in the IAP (International Atherosclerosis Project) because they represented the greatest contrasts between the exten of fatty streaks in the young and raised lesions in the elders. Among these seven groups the extent of raised lesions in the older subjects was significantly but weakly correlated with the type of fatty streaks in the young as measureed by lesion thickness, content of demonstrable lipid, numbers of foam and spindle cells. The severity of leukocytic infilitration and prevalence of foci of necrosis in fatty streaks however, correlated strongly with raised lesions (rank r equals 0.90). We interpret this to imply that the presence  of leukocytes and of foci of necrosis in the fatty streak marks its propensity to progress into raised lesions. If this formulation is correct, then the presence of both features in the histology of fatty streaks could be used as a marker in future studies of factors bearing upon the emergence of raised lesions out of fatty streaks.


The use of critical levels of birth weight and "free bilirubin" as an approach for prevention of kernicterus. Free bilirubin (FB) and total bilirubin (TB) were determined in 154 samples of blood taken from 112 jaundiced newborns: 51 prematures without hemolysis (19 of these with RDS); 26 full terms presenting ABO incompatibility; 35 newborns (both prematures and full terms) presenting rhesus incompatibility. Kernicterus was observed in seven cases and only three occurred in the TB group above 20 mg/100 ml; 57 cases had FB equal to or above 0.1 mg/100 ml and all kernicterus fell into this category. In the other 55 cases in which FB was less than 0.1 mg/100 ml no kernicterus was observed. In the group of healthy full-term newborns presenting ABO incompatibility, 15 had FB above or equal to 0.1 mg/100 ml ranging between 0.1 and 0.4 mg/100 ml; however no kernicterus was observed during the neonatal period. On the contrary, in the group of prematures a little more than half of the cases had a FB ranging from 0.1 to 0.4 mg/100 ml whereas four macroscopic kernicterus cases were observed. The difference between the two groups compels us to consider other factors than those acting on the albumin-bilirubin binding especially those acting on the blood-brain barrier and on the fixation of the pigment by the neurons. A second series of 605 consecutive autopsies, on a period of 10 years, on prematures excluding light-for-dates and cases of hemolysis, evaluates the distribution of 40 kernicterus as a function of birth weight. On this second series kernicterus appears with maximal frequency for birth weight between 1,000 and 1,250 g, with a nonnegligible frequency at 1,500 to 2,000 g and was absent between 2,000 and 2,500 g. 13 kernicterus were observed for a peak TB below 12 mg/100 ml. These results seem to justify a systematic determination of FB in the premature weighing less than 2,000 g from the 24th hour of life whether he has jaundice or not.


Effects of ddt homologs administered to female rats during the perinatal period. The administration of estrogen to female rats during the perinatal period induces a masculine pattern of hypothalamic differentiation resulting in persistent vaginal estrus (PVE) and anovulation. 10 mg day of the estrogenic homologs o,p-DDT, o,p-DDE, and dda, as well as allegedly nonestrogenic forms of the pesticide, p,p-DDT and o,p-DDD, were given by gavage from days 15-19 of pregnancy. 1-mg doses of the homologs were also given SQ daily to female rats on the second, third, and fourth days of life. Vaginal opening was delayed by 2 days in rats derived from the dams gavaged with o,p-DDD. Periodic examination of estrous cycles in the rats treated neonatally with o,p-DDD revealed PVE by 209 days of age, and absence of corpora lutea by 258 days of age. Prior to 4 months of age, estrous cycles were normal in these animals. The remaining pesticide homologs tested, regardless of the mode of administration, had no significant effect on the estrous cycles or on endocrine gland weights.


Umbilical blood flow and glucose uptake in lamb fetus following single umbilical artery ligation. Umbilical blood flow (UBF) and fetal glucose uptake were measured in 5 lamb fetuses 4-20 days following single umbilical artery ligation (SUAL). The ligation was performed at 108-119 days gestation (sheep pregnancy = 145-150 days), and the blood flow and glucose uptake studies were performed as chronic preparation at 120-137 days of gestation. In comparison with 9 control subjects at matched gestation, the SUAL fetuses had significantly lower UBF (mean plus or minus SEM, 735 plus or minus 70 vs. 475 plus or minus 24 ml/min, p less than 0.01) and fetal glucose uptake (2190 plus or minus 1.6 vs. 14.8 plus or minus 1.9 mg/min, p less than 0.05). When the values were expressed per kilogram fetal weight, the UBF decreased with increasing gestational age in SUAL fetuses. In the control fetuses, the UBF increased with increasing gestational age. The fetal glucose uptake (FGU), when expressed per kilogram fetal weight, was essentially similar to that of the control subjects. The glucose gradients across the placenta were similar in both groups of fetuses. These data suggest that in lamb fetuses with placental vascular insufficiency induced by SUAL, the reduction of UBF and FGU may account for growth retardation in utero. It was also suggested that placental transfer of substrate other than glucose may also be impaired as a result o


The offset of morphine tolerance in rats and mice. 1. In rats and mice made tolerant to morphine by pretreatment with the drug, the shift to the right of the log dose/analgesic response line for in naive animals occurs without significant change in slope provided that sufficient time is allowed for elimination of pretreatment drug. 2. Responsiveness to the analgesic effects of morphine, given together with cycloheximide to prevent reinforcement of tolerance, was measured in rats (paw pressure method) and mice (hot plate method) at intervals during 1-23 days following cessation of a variety of regimens of tolerance-inducing drug treatments. 3. A biphasic pattern of recovery of responsiveness was observed, which was independent of the regimen or the drug (morphine, methadone or diamorphine) used to induce tolerance. Estimates of the rates of the first, fast phase are imprecise but the rate of the second phase of offset, from 4th day after cessation of pretreatment had, in rats, a mean half-time of 13.2 plus or minus 0.53 days-for all pretreatments combined, there being no significant differences between the various pretreatment regimens employed. In mice, similarly, a biphasic recovery of analgesic responsiveness was seen after morphine pretreatment, the mean half-time of the slower phase being 17.4 days. 4. Precipitation of an acute withdrawal syndrome in rats by naloxone HCl given 6 h after the final injection of a tolerance-inducing treatment with morphine did not affect the subsequent rate of recovery from tolerance. 5. During the period following a tolerance-inducing pretreatment with morphine in mice, the rate of attenuation of the naloxone-evoked jumping response was faster than the rate of offset of tolerance.


Diurnal variations in radiosensitivity of mouse intestine. Crypts in the mouse small intestine show a diurnal rhythm in radiosensitivity and are most sensitive in the middle of the dark period, when mitotic activity in the crypt is high. Analysis of crypt survival on a cellular basis shows that the changes in cryptogenic cell radiosensitivity are dose-modifying between 1,000 and 1,450 rads gamma rays such that the DO value varies between 85 rads and 140 rads.