Effects of a zinc deficient diet upon fluid intake in the rat. Zinc deficient rats demonstrate an increased intake of sodium chloride (NaCl) containing solutions as compared to normal rats, presumably related to decreased taste acuity. The purpose of this study was to determine if zinc deficient rats would show altered intake of other solutions since changes in NaCl intake may be reflective of serious pathophysiologic processes not related to taste. Eight littermate pairs of inbred Fisher CDF rats, 29 days of age, were divided into two groups and individually housed in stainless steel cages. One group was pair-fed a zinc deficient diet supplemented with ZnSO4, 100 ppm, while the second group was fed the zinc deficient diet, ad libitum. Using a two-bottle preference test, the rats fed the zinc deficient diet showed significantly increased preferences for 5 X 10(-2), 1.5 X 10(-1) and 3 X 10(-1) M NaCl as compared to controls, supporting previous observations. In addition, they showed significantly increased mean preferences for 3.0 X 10(-2) M sucrose, 1.3 X 10(-6) M quinine sulfate and 2.5 X 10(-3) M hydrochloric acid. Analysis of the individual water and fluid intakes showed that the altered preferences were generally the result of increased fluid intake with variable differences observed in water intake. The results demonstrate that zinc deficient rats exhibit altered intake of several different chemical compounds, and support the hypothesis that zinc deficient animals may have alterations in taste acuity.


Hepatic 3-hydroxy-3-methylglutaryl coenzyme-a reductase of rats fed semipurified and stock diets. Rat hepatic 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase) was found to be lower in rats fed a semipurified diet of sucrose, casein, and cellulose with a mixture of safflower oil and stripped lard than those fed a stock diet: 0.115 versus 0.447 nmoles mevalonic acid formed/minute/mg microsomal protein. Efforts were made to find the substances in the stock diet responsible for the higher enzyme activity. Neither the addition of small amounts of cholesterol or plant sterols to the semipurified diet, nor the substitution of corn oil or the lipids extracted from the stock diet for the safflower oil-stipped lard mixture, significantly raised the enzyme level. Replacement of sucrose by starch also had no effect on the enzyme activity. The substitution of soybean protein for the casein did increase the specific activity of the enzyme from 0.115 to 0.247, still well below the 0.447 level response to stock rat diet ingestion. Substitution of the safflower oil-stripped lard fat mixture for the extracted fat of the stock feed had no significant effect on the response of the rats to the stock feed. However, substitution of part of the cellulose in the semi-purified diet with citrus pectin resulted in HMG-CoA levels of 0.553, approximately equal to that produced by the stock diet. In the latter study, the total fecal bile acids of the rat fed the stock, semipurified-cellulose, and semipurified-pectin diets were 2.34, 1.28, and 2.22 mg/g feces respectively, and the total fecal neutral sterols 1.86, 1.50, and 2.42 mg/g feces. Thus, the constituent nonutritive fiber appears responsible for differences in steroid excretion and elevated hepatic HMG-CoA levels, possibly by binding bile acids and increasing the turnover rate of blood and liver cholesterol.


Formation of oxalate in pyridoxine or thiamin deficient rats during intravenous xylitol infusions. Glucose, fructose, sorbitol and xylitol were assessed as precursors of oxalate in normal rats and rats deficient in thiamin or vitamin B-6. Urinary excretions of oxalate, glyoxylate and glycine were increased significantly in vitamin B-6 deficient rats infused with xylitol when compared with all other groups. Using [U-14C]xylitol, oxalate was shown to be derived directly from this polyalcohol in vitamin B-6 deficient rats. These results suggest that vitamin B-6 deficiency may be a factor contributing to oxalate crystal deposition seen in some patients infused with xylitol.


Effects of dietary fiber and salt mixtures on the cholesterol metabolism of rats. The isotopic dilution method, which permits the in vivo measurements of the rates of the processes involved in cholesterol turnover, has been applied to rats fed a commercial stock diet or a basal semipurified diet in which either the nature and proportions of the source of dietary fiber or the salt mixture were changed. The cholesterolemia was about 100 mg/100 g in rats fed agar-agar, cellulose, bran or the stock diet. Pectin addition (5%) lowered significantly the plasma concentration of cholesterol (70 mg/100 g). Changes in the source of dietary fiber or salt mixture have moderate effects on the absorption coefficient of dietary cholesterol (range 58.2%-82%). In comparison to agar-agar, cellulose at 2.3% in the diet significantly lowered this coefficient, but larger amounts of cellulose (6.8% or 12.3%), or pectin (5%) were without effect, while bran addition (10%) tended to slightly decrease cholesterol absorption. Hence, high levels of cellulose in the diet increased the absorption coefficient in comparison to a low cellulose diet. A decrease of this coefficient was also observed when the calcium content of the diet was increased. Cholesterol biosynthesis and fecal excretion were inversely correlated to the absorption coefficient of dietary cholesterol in rats fed all of the semipurified diets indicating, as previously shown, that the intestine was the major source of biosynthesized cholesterol diverted into the plasma. However, feeding a commercial stock diet greatly increased the cholesterogenesis and the fecal elimination of bile acids, suggesting a high hepatic cholesterogenesis.


Effects of selenite and selenomethionine on glutathione peroxidase in the rat. The activity of glutathione (GSH) peroxidase (EC 1.11.1.9) decreased in tissues of rats fed a diet deficient in selenium. A single dose of 300 mug selenium by stomach tube increased GSH peroxidase activity within 48 hours. The effects of selenite and selenomethionine on GSH peroxidase activity were roughly similar. This study provides evidence that selenium from both selenite and selenomethionine is readily available for synthesis of the selenoenzyme GSH peroxidase in rat tissues.


Iron binding substances in the intestinal mucosa of neonatal piglets. Fifty piglets from birth to 14 days of age were used to investigate iron binding substances of neonatal intestinal mucosa, and to evaluate the effects of these substances in neonatal iron absorption. 59Fe-labeled ferric citrate with a molecular weight of 1,500 was injected directly into the ligated duodenum. Approximately 65% of radioiron in the whole homogenate of scraped intestinal mucosa was precipitate by centrifugation for 30 minutes at 10,000 X g. Over 70% of the radioiron of the supernatant applied to Sephadex G-200 column was eluted and separated into three radioiron fractions. These iron binding substances were identified as ferritin, transferrin and a low molecular weight form by elution characteristics on chromatography and by immunological technique. Although ferritin radioactivity was the major fraction of peak 1 (73%), transferrin activity was only 54% of the whole radioiron of peak 2. The sodium dodecyl sulfate (SDS) extract of saline insoluble particles from the mucosa applied to Sepharose 4B column eluted as a single peak near the point corresponded with the ferritin peak. Although the ferritin peak contained a higher percentage of the 59Fe than the transferrin peak at birth, the percentage of ferritin decreased and percentage of transferrin increased with age. A SDS soluble iron binding substance was found in the insoluble particles of mucosa of newborn as well as nursing piglets. Since SDS, as well as saline soluble, iron binding proteins were detected in the newborn intestinal mucosa, neonatal cell membrane and cytoplasma may have an active iron transfer system. Thus, it seems likely that neonatal mucosal cell has two active iron transport mechanisms: endocytosis and transport across the plasma membrane.


Effects of arginine-devoid diets in chronically uremic rats. There is evidence that the kidney has a major role in the formation of the arginine used for extrahepatic protein synthesis. The effects of arginine-free diets were studied, therefore, in female Sprague-Dawley rats made uremic by partial left-renal artery ligation and contralateral nephrectomy. Uremic and sham-operated control rats were fed diets with amino acids proportioned as in casein or similar isonitrogenous diets in which the arginine was replaced by glutamic acid and alanine. Weight gain and the food efficiency ratio were determined, and 6 weeks after nephrectomy, a pulse dose of 14C-guanido arginine was administered. The rats were killed 2 hours later, and the radioactivity of proteins in various tissues was determined. Free arginine levels in tissues were also measured. Control rats fed diets devoid of arginine had reduced growth and a low food efficiency ratio. Free arginine levels in tissues and 14C-arginine incorporation into tissue protein in these rats were not different from controls receiving arginine except that 14C-incorporation into brain protein was decreased. Uremic rats fed an arginine-containing diet had a reduced growth rate as compared to control rats, and 14C-incorporation into brain protein was less. In uremic rats, when arginine was removed from the diet, there was no further effect on weight gain but the plasma arginine level was decreased and the incorporation of 14C-guanido arginine into protein of muscle and of kidney was reduced. Hence, the effects of an arginine-free diet appears to be different in chronically uremic as compared to control rats.


Re-evaluation of effects of meal feeding on lipogenic activation by glucose in rats. Based upon analyses of epididymal fat pads, gorging rats have been reported to synthesize fatty acids from glucose carbon 200 times faster than nibbling rats. This contrasts with our earlier study in mice in which no such adaptation was found in gorgers. Three methods were used to re-evaluate lipogenesis from glucose carbon in fasted-refed nibbling and gorging rats. Two methods in which [U-14C]glucose was injected intraperitoneally before or after different test-meals confirmed an apparent 100- to 200-fold increase in lipogenesis (14C incorporation into fatty acids) in epididymal fat pads of gorgers; however, incorporation of 14C into total fatty acids in the whole body of gorgers was only five times greater than in nibblers. Quantitative tracer techniques (intravenous and oral [U-14C]-glucose) were used to evaluate glucose carbon flux (22-hour fasted) and lipogenic activation following the ingestion of a labeled glucose test-meal. Glucose carbon conversion to total fatty acids (whole rat) increased from 2.7 (24-hour fasted) to 11 microng C/minute/200 g body weight, a fourfold activation, within 15 minutes after feeding the test-meal to nibbling rats. The corresponding increase in gorging rats was from 3.7 to 53 micrgong C/minute/200 g body weight, a 14-fold activation. These data indicate a species difference exists between rats and mice during adaptation to a gorging food-intake pattern.


Effects of cellulose added to diets of low and high fiber content upon the metabolism of calcium, magnesium, zinc and phosphorus by man. Addition of 10 g of cellulose dispersed in 150 g of apple compote to the daily diet with a low fiber content for a 20-day period caused the fecal excretion of calcium and zinc of three men to increase significantly. Balances of both metals became negative and their concentrations in plasma decreased. Magnesium balances became negative in two subjects while phosphorus balance changed to negative in one. In a similar experiment in which the cellulose was added to a fiber-rich diet, fecal excretions of calcium and zinc increased significantly in each of two men and excretion of magnesium in one. Previously negative balances became more negative, and calcium and zinc concentrations decreased in plasma. The dependence of fecal dry weight upon fecal fiber content measured by the acid-detergent method was confirmed. However, increments of dry matter per g of fiber were less fecal fiber concentrations were high. Fecal calcium content correlated significantly with fecal fiber in two subjects, and fecal fiber and zinc in one. No correlations were demonstrated in the subject who apparently digested fiber most effectively. Our findings indicate that high intakes of fiber can explain to a considerable extent the impaired utilization of zinc, calcium, and magnesium among villagers in rural Iran.


Metabolism of gamma-linolenic acid in essential fatty acid-deficient rats. Female rats were weaned and fed a semipurified diet lacking in essential fatty acids. After 160 days, the deficient diet was supplemented with varying amounts of gamma-linolenic acid. Changes in body weight and feed efficiency were measured. Total liver phospholipid fatty acids were also analyzed. Supplementation with gamma-linolenic acid to the deficient diet for 7 days led to improvements in body weight and feed efficiency of the deficient rats. The liver phospholipid fatty acid composition returned to a normal pattern. There was a reduction of 5,8,11-eicosatrienoic acid and an increase in the arachidonic acid. Thus, there was a fall in the triene: tetraene ratio with increasing dietary supplementation of gamma-linolenic acid. The essential fatty acid potency, the minimum dietary requirement for this fatty acid, and the widely accepted levels of the minimum requirements of dietary essential fatty acids are discussed.


Effect of dietary protein restriction or food restriction on oxygen consumption and mitochondrial distribution in cardiac and red and white skeletal muscle of rats. The effects of food restriction and dietary protein restriction on the oxygen consumption of three types of muscle in the rat were compared. Control rats were fed a diet containing 27% casein. Two groups of protein-restricted rats were fed isoenergy diets containing 15% or 8% casein. Two groups of food-restricted rats were fed either the 27% or 15% casein diets in amounts equivalent to 35% of the intake of energy. Oxygen consumption was measured in papillary muscle and in fibers from the red (high oxidative) and white (low oxidative) portions of the quadriceps with pyruvate and malate as substrates. Control values (micronlO2/g dry wt/min) were 35.2 + 1.5 (papillary), 20.7+/-1.9 (red), and 7.8+/-0.7 (white). Restriction of dietary protein content failed to alter the oxygen consumption of any of the muscle types. In contrast, involuntary food restriction,combined with a reduction in protein content, caused a reduction in the oxygen consumption of papilary and white skeletal muscle, but the metabolism of red skeletal muscle was not affected. No differences were found in the appearance and distribution of mitochondria in cardiac or red skeletal muscle after examination by electron microscopy, but a depletion of subsarcolemmal mitochondria was evident in white muscle from the food-restricted rats.


Effect of a high fructose diet on lipogenic enzyme activities of meal-fed rats. The effect of a high fructose diet on lipogenic enzyme activities in liver, intestine and adipose tissue, and serum immunoreactive insulin level was studied in meal-fed rats. Male and female rats were meal-fed for 5 days with stock diet. After a 45-hour fast, they were meal-fed a high carbohydrate diet composed of fructose, glucose or cornstarch diet for 4 days. The daily food intake was similar within each sex (females 9-11 g/day and males 10-13 g/day). Only males fed glucose consumed significantly more food than any other group (12.9 g/day). Rats fed fructose had the greatest liver weight and total lipid content. The hepatic malic enzyme activity of both sexes was significantly higher in rats fed fructose than in those fed cornstarch. Small intestinal malic enzyme activity was largely unaffected by diet. The serum immunoreactive insulin level of rats fed fructose was the lowest, and the level in females was higher than in males fed fructose or glucose. The above results lead to the conclusion that the effect of feeding fructose compared to glucose is attributable to fructose itself and not differences in food intake.


Serum insulin concentration, insulin release and degradation, glucose tolerance and in vivo insulin sensitivity in cholesterol-fed rats. A series of experiments was conducted to elucidate the mechanism by which cholesterol feeding decreases serum insulin levels in rats and to determine the effect of this reduced insulin level on glucose metabolism. Rats were fed a casein-sucrose-soybean oil basal diet or this basal diet supplemented with 1% cholesterol (dissolved in hot oil) for periods longer than 30 days. Cholesterol feeding resulted in a decrease in serum insulin concentrations, although the decrease was not always significant. Cholesterol feeding did not affect fasting blood glucose levels, glucose tolerance, glucose-induced insulin release, pancreatic insulin content, in vivo insulin sensitivity, or in vitro glucose utilization in diaphragm and adipose tissue, but it significantly elevated the activity of liver glutathione-insulin transhydrogenase. On a per liver basis, the activity of this enzyme was approximately doubled. Results of this study suggest that cholesterol feeding has no significant effect on glucose utilization, but it can lead to a decrease in serum insulin concentration, probably by increasing the rate of insulin degradation in the liver.


Effect of vitamin A deficiency on intestinal cell proliferation in the rat. Cell division kinetics and the biochemical composition of the small intestine of normal and mildly vitamin A-deficient rats have been examined. Thymidine labeling index, growth fraction and the content of DNA, RNA and protein in the jejunal mucosa were not significantly affected by vitamin A deficiency. On the other hand, the duration of the cell cycle of jejunal crypt cells was found to be lengthened by vitamin A deficiency and this increase in generation time was due mainly to a lengthening of the DNA synthesis phase. Furthermore, the labeling pattern of the newly divided crypt cells of the vitamin A-deficient rats was strikingly different from that of the vitamin A-supplemented rats, suggesting an impaired migration of cells out of the crypts. These findings suggest that vitamin A may play a role in the regulation of cell division in the small intestine of the rat.


Effect of dietary protein level on urea synthesis in isolated rat hepatocytes. Urea cycle enzymes of rats were altered by feeding protein-free 15% casein, or 70% casein diets. Cells isolated from the livers of these rats were incubated with 10 mM ammonia and varying levels of ornithine (2 or 10 mM) and lactate (0-10 mM). Conditions providing the greatest rate of urea synthesis depended on the diet consumed and on whether rats were fed or starved 24 hours before cell isolation. Maximum rates of urea synthesis, though not different for the fed and starved groups, increased with the protein content of the diet and were equal to the maximum theoretical rates, as determined by argininosuccinate synthetase activity. This indicates that with optimal conditions, the activity of argininosuccinate synthetase is the rate-limiting factor in the synthesis of urea in isolated hepatocytes.


Postprandial plasma lysine as an indicator of dietary lysine adequacy in infants. Postprandial plasma free amino acids were studied as an index of the level of dietary lysine. Fasting blood was obtained from 11 children who were then fed a meal in which wheat provided 100% of 0.4 g protein and 30% to 50% of 25 kcal/kg body weight. Blood samples were obtained 3 and 4 hours postprandially. Fasting blood samples were obtained from these same children after 9, 18 and 27 (n=6) days of consuming the same diet (2 g protein, 125 kcal/kg/day). Postprandial blood samples were taken from four additional children after consuming a meal containing 25 kcal and 0.75 g protein (0.5 g from wheat, 0.25 g casein)/kg. This meal was expected to provide adequate lysine while still maintaining lysine in lowest concentration among the essential amino acids relative to needs for protein synthesis. After consuming the unsupplemented wheat diet postprandial values showed a significant rise of total amino acids at 3 hours with a return to fasting levels at 4 hours. Total essential amino acids did not change at 3 or 4 hours. Lysine concentration was significantly lower at 3 and 4 hours. The ratio of lysine to total essential amino acids decreased at 3 and, more so, at 4 hours. In 3 of 4 children studied the postprandial decrease of plasma lysine and its molar fraction was not manifest after consuming wheat + casein. The fasting lysine concentration during continued wheat consumption showed no change at 9 days and then a progressive fall at 18 and 27 days. The results with wheat + casein lend support to the concept that a postprandial fall in the concentration of lysine and its molar fraction indicates not merely that lysine is present in lowest concentration but that it is present in inadequate concentration relative to needs for protein synthesis.


Reproduction and lipid composition of rats fed cyclopropene fatty acids. The effect of cyclopropene fatty acids fed in saturated or unsaturated lipid diets on reproduction and lipid composition of progeny was determined in rats. Sterculia foetida oil (50% cyclopropene fatty acids) fed at 0.2% of the diet for three generations and 0.5% fed to first generation rats did not significantly affect breeding. Two percent S. foetida oil fed with 3% corn oil did not appreciably affect conception rate and litter size in the first litters, but reduced pup survival 36% in the first litters and 78% in the second litters. Replacement of the 3% corn oil with 3% animal fat in diet containing 2% S. foetida oil reduced litter rate from 87% to 7% in the first litter. Cyclopropene fatty acids were readily incorporated into the tissue and milk of females. Pups rapidly accumulated cyclopropene via milk from dams. Fetal tissue contained only 10% of the cyclopropene concentration of the females fed a diet containing 2% S. foetida oil and 3% corn oil; however, the level of fetal cyclopropene doubled when animal fat replaced corn oil in the diet. Unsaturated lipid in the diet enabled rats to cope with the effects of moderate levels of cyclopropene fatty acids, but the combination of cyclopropene in saturated lipid diets caused detrimental effects.


Controlling factors in the maintenance of plasma cholesterol concentration in the rabbit. We have investigated factors important in the maintenance of plasma cholesterol concentration in three groups of New Zealand white rabbits fed either a cholesterol-free, commercial stock diet or an atherogenic diet consisting of stock diet supplemented with 0.1% cholesterol and 10% corn oil. When fed stock diet, the plasma cholesterol concentration in female rabbits (164 mg/100 ml) of one strain was significantly greater than plasma cholesterol concentration in males (67 mg/100 ml) of the same strain or in females (62 mg/100 ml) of another strain. Cholesterol absorption and turnover, steroid excretion and tissue cholesterol storage were examined. The percentage of an oral dose of isotopically labeled cholesterol absorbed could not account for group differences in plasma cholesterol concentrations and was not changed by cholesterol supplementation for 3 weeks. Turnover of plasma cholesterol conformed to a two-pool model in rabbits fed stock diet and the atherogenic diet. In rabbits fed the atherogenic diet, the irreversible disposal rate from pool A and total acidic steroid excretion were inversely related to plasma cholesterol concentration. One controlling factor in the maintenance of relatively low plasma cholesterol concentrations in cholesterol-fed rabbits appears to be enhanced bile acid excretion.


Effects of ethanol on growth. Consumption of food, and body composition of weanling rats. Ethanol administered to weanling rats in various concentrations as the sole drinking fluid in conjunction with a semipurified dry diet was consumed at a level of not more than 20% of total energy. Suppression of fluid intake and concomitant reduction of food intake resulted in decreased growth. Analysis of body composition indicated that the difference in weight in rats given 20% solutions of ethanol as the sole drinking fluid and in rats pair-fed diets without ethanol was primarily due to dehydration. With total liquid formulations having good resistance to separation, there were no significant differences in weight gain between rats given 20% or 30% of total energy as ethanol and rats pair-fed diets without ethanol. Ethanol fed at 40% of total energy caused inhibition of growth which could not be ascribed solely to decreased consumption of food and water. These data indicate that the method of administering ethanol to weanling rats affects not only the levels at which ethanol is toxic but also the amount of ethanol voluntarily consumed by the rats. The use of pair-feeding techniques and of homogenous liquid formulations is essential for studies of the metabolic effects of ethanol.


Milk production, nitrogen utilization and glucose synthesis in lactating cows infused postruminally with sodium caseinate and glucose. Four lactating Holstein cows were used in a 4 X 4 Latin Square design to determine the effects of postruminally administering sodium caseinate and/or glucose on milk production, milk composition, nitrogen utilization, amino acid utilization by the lactating mammary gland and glucose turnover rate. An 8.5% increase in milk yield and a 13.3% increase in milk protein production were obtained during infusion of sodium caseinate. No significant production responses were attributed to abomasal infusion of glucose. Arterial concentrations of most essential amino acids were increased during infusion of sodium caseinate. Uptake of phenylalanine, methionine and lysine by the mammary gland most closely paralleled their output in milk. The relative concentrations of methionine, lysine and phenylalanine in arterial plasma were considerably less than their concentrations in milk which resulted in a large percentage extraction of these amino acids by the mammary gland. If the availability of essential amino acids to the mammary gland, per se, was limiting the synthesis of milk protein, methionine, lysine and phenylalanine may have been the three amino acids most limiting. Measurements of glucose entry rate showed a trend toward increased glucose flux when either glucose, sodium caseinate or glucose plus sodium caseinate were infused abomasally. The similarity in glucose entry rates obtained during infusion of glucose and sodium caseinate suggest that the increase in milk production was not due totally to increased glucose flux resulting from sodium caseinate infusion.


Protection against carbon tetrachloride-induced lipid peroxidation in the rat by dietary vitamin E, selenium, and methionine as measured by ethane evolution. Dietary vitamin E, selenium (Se), and methionine were tested for their ability to inhibit carbon tetrachloride (CCL4)-induced lipid peroxidation. Peroxidation, in vivo, was monitored by the evolution of ethane, an autoxidation product of omega-3-unsaturated fatty acids. Weanling rats were fed a basal diet low in vitamin E, Se, and sulfur-containing amino acids, or diets individually supplemented with these factors. After 3 to 7 weeks, the rats were injected with CCL4 (ip) and ethane was collected for 9 hours. Cumulative ethane evolution was increased by CCl4 in all groups. Vitamin E, Se, and methionine reduced ethane evolution from CCl4-treated rats by 82%, 74%, and 60%, respectively. The toxicity of CCl4 was decreased in correlation with ethane evolution. Thus, methionine and Se, probably by maintaining intracellular glutathione and glutathione peroxidase, protected against CCl4-induced lipid peroxidation, as did vitamin E. Substitution of cod liver oil, which is rich in omega-3-unsaturated fat, for lard in the basal diet increased CCl4-induced ethane evolution six-fold. Relative inhibition by the dietary supplements was not changed. Thus, the feeding of cod liver oil greatly increased ethane production which facilitated the detection and measurement of lipid peroxidation in vivo.


Lipid peroxidation in vivo during vitamin E and selenium deficiency in the rat as monitored by ethane evolution. Ethane evolution was monitored from vitamin E and selenium (Se)-deficient rats to determine if lipid peroxidation occurs in vivo when these rats develop fatal organ lesions. Weanling rats were fed a vitamin E and Se-deficient, or supplemented, diet for 40 to 90 days. Each was then prefasted for 4 hours and fasting was continued for 24 to 40 hours while ethane was collected. Approximately 50% of the doubly-deficient rats died as a result of fasting. Pathological signs included hematuria, lung hemorrhage, and liver necrosis. Ethane evolution increased exponentially 10 to 20 hours before death and then declined 2 hours before death. Rats that survived (at least 5 days after ethane collection) evolved 7.4+/-1.3 nmoles ethane/100 g body weight/24 hours compared to 100+/-6 for rats that died. Supplementation of the basal diet with vitamin E (200 IU/kg), Se (0.2 ppm, as Na2SeO3), or both, completely prevented mortality and reduced ethane evolution values to 0.4+/-0.2, 3.1+/-0.4, or 0.2+/-0.2, respectively. These experiments indicate that lipid peroxidation occurs in vivo as a result of vitamin E and Se deficiency, and the peroxidation process greatly accelerates during the terminal phase of the fatal disease.


Dietary-induced variations in urinary taurine levels of college women. Dietary-induced variations in the urinary taurine excretion of healthy college women were investigated. Data were collected in three metabolic studies in which nutritionally adequate diets of constant composition were fed. Variables included isonitrogenous natural food and semi-purified diets; taurine, cystine and meat supplements; and kind and amount of dietary fat. Observed urinary taurine levels were low and ranges were narrower than those reported by other investigators. The low taurine excretion at the completion of the studies was considered evidence that urinary taurine levels in humans is related to the level of body taurine as well as to the level of dietary taurine. Urinary taurine excretion was shown to be related to dietary taurine intake rather than protein (nitrogen) intake. A relationship between kind of dietary fat and taurine excretion is suggested.


Comparative flatulence activity of beans and bean fractions for man and the rat. To evaluate H2 production in the rat after ingestion of legume products as a predictive bioassay of their flatulence activity for man, responses of man and the rat to (1) a bland formula diet, (2) cooked California Small White bean (CSW) solids, (3) 70% ethanol extract of (2), (4) oligosaccharide fraction of (3), (5) non-protein nitrogen fraction of (3), and (6) combination of (4) and (5) were compared. Six human subjects were fed an 800 kcal breakfast of (1) or containing the amount of a test item equivalent to 100 g CSW. Each subject received all items once plus a single replicate of three items at the rate of one per week in random order. Total flatus volume, H2, CO2, and CH4 volumes and breath H2 concentration were measured for the interval 2.5 to 8.5 hours after breakfast. Young rats in metabolic chambers received known amounts of items 2 to 6 mixed with a bland basal diet. H2 trapped in the chambers was measured after 20 hours. Correlation of rat H2 and to human breath H2 measurements and flatus gas volumes were significant and positive except for negative correlation with flatus methane volume. Measurement of hydrogen production in the rat has potential for a predictive bioassay for flatulence in man.


Carbohydrate absorption in the young of protein-deficient rats. The absorption of 3-O-methylglucose (TMG) and of lactose has been studied in the young of female rats fed a protein-deficient diet during pregnancy. Postnatally, these young were suckled by stock diet-fed dams. Intestines of newborn, 4-day and 12-day old pups were infused in situ with 5% TMG or 3.5% lactose. The mean amount retained per enterocyte was measured as well as the mean amount absorbed from the lumen and transferred from the enterocyte. Absorption of lactose was reduced in the enterocytes of newborn prenatally protein-deprived (PPD) young but not postnatally, while TMG absorption was normal at birth and 12 days but reduced at 4 days. The amount of carbohydrates absorbed in total or per unit intestinal weight seemed to vary with changes in the number of absorptive cells. It is suggested that reduced absorption in PPD pups is primarily related to the smaller number of absorptive cells in these young. There is a greater increase in numbers of cells and in absorption per cell between birth and 12 days in PPD young than in controls, indicating that the effect on the intestine of prenatal protein deprived young is at least partially reversible.


Life history and host specificity of Mediorhynchus centurorum Nickol 1969 (Acanthocephala: Gigantorhynchidae). Examination of 1905 arthropods from a swamp and surrounding pasture in sothern Louisiana revealed larval specimens of Mediorhynchus centurorum in 8 of 228 woodroaches, Parcoblatta pensylvanica, but in no other species. The life cycle was confirmed by feeding eggs of M. centurorum to laboratory-reared woodroaches. Cystacanths later recovered from the woodroaches developed into mature worms when pipetted into esophaguses of red-bellied woodpeckers, Centurus carolinius: red-headed woodpeckers, Melanerpes erythrocephalus; yellow-shafted flickers, Colaptes auratus; and a hairy woodpecker, Dendrocopos villosus. Infection was achieved in all woodpeckers fed cystacanths at least 47 days old and the mean prepatent period was 35 days. Cystacanths fed starlings, Sturnus vaulgaris, and red-winged blackbirds, Agelaius phoeniceus, did not produce infections although cystacanths from the same pool were infective to control woodpeckers. Larval development of Mediorhynchus centurorum in woodroaches did not differ significantly from that of M. grandis in grasshoppers. M. centurorum is the only species of the Gigantorhynchidae for which the life cycle has been confirmed by laboratory infections using an intermediate host species known infected nature.


Praesomal musculature of the acanthocephalan genus Mediorhynchus Van Cleave 1916. The praesomal musculature of Mediorhynchus is described. The proboscis is considered to consist of 3 zones: an anterior protoboscis, a median mesoboscis, and a posterior teloboscis. New structures reported are mesoboscis retractor muscles, the formation of 3 ligament strands from the proboscis retractor muscles, a teloboscis inflator muscle, and conduit through the protrusor muscle sheath. Some aspects of the taxonomy of Mediorhynchus are discussed.


Ecology of Capillaria hepatica (Bancroft 1893) (Nematoda). 1; Dynamics of infection among Norway rat populations of the Baltimore Zoo, Baltimore, Maryland. Seventy-five per cent of 845 Norway rats examined in the Baltimore Zoo for Capillaria hepatica were infected. Nearly all adult rats and 65% of juveniles were infected. Only 8% of 299 infected rats were heavily infected. The prevalence and intensity of infection increased with the size of the host. There were no seasonal differences in infection rates among adults, but juveniles collected during spring had higher infection rates than those collected during winter. Prevalence of C. hepatica infection varied from one place to another. No correlation between infection rate, vegetative cover, soil type, monthly rainfall, mean daily temperature, or food habits of rats was found. The dynamics of rat populations are perhaps the most important factors in the maintenance and dynamics of C. hepatica infections. Rapid population turnover contributes to the rapid release of a great number of eggs into the environment and high recruitment rates provide sufficient numbers of susceptible hosts for the parasite to complete its cycle.


A reclassification of the genus Aplodontopus (Acari: Sarcoptiformes) with a description of Aplodontopus micronyx sp. n. from the thirteen-lined ground squirrel, Spermophilus tridecemlineatus, in Indiana, USA. The genus Aplodontopus is transferred from the family Glycyphagidae to the family Chortoglyphidae and a new species Aplodontopus micronyx is described. The new species is from the tail-hair follicles of Spermophilus tridecemlineatus in Indiana, USA; deutonymphs and a female are described.


Gruiformes, a new host group for pterodectine feather mites (Acarina: Analgoidea). Pterodects ralliculae sp. n. (Proctophyllodidae, Pterodectinae) is described from Rallicula f. forbesi (Rallidae) from Papua New Guinea. This is the first record of a proctophylloid species from Gruiformes.


A new species of Plutarchusia oudemans 1904, with a key to the species (Analgoidea: Syringobiidae). Plutarchusia brachytarsa sp. n. is described from Thalasseus sandvicensis (Laridae), Yucatan. P. pseudochelopus Dubinin 1956, and P. longitarsa (Mégnin and Trouessart 1884) are reported for the first time from the New World. A key to the genus is provided.


Plasmalemmal modifications of Entamoeba histolytica in vivo. We used electron microscopy to study Entamoeba histolytica trophyozoites in rectal and liver lesions. The amebal surface had bleblike structures. Also noted were subplasmalemmal vacuoles and plasmalemmal extensions generally similar to the "surface lysosome" and "trigger" previously described. We found on serial sections that the plasmalemmal extensions were dendritic complexes enfolding the membrane of the subplasmalemmal vacuole and extending to contact host tissue. We postulate that membrane-bound cytotoxic hydrolases enter the plasmalemmal extension via the translocation of the subplasmalemmal vacuole membrane and thus are available to act at contact sites. The small blebs may provide an alternate method for membrane-bound hydrolase activity.


Lipids of Plasmodium lophurae, and of erythrocytes and plasma of normal and P. lophurae-infected Pekin ducklings. A lipid analysis was performed on the avian malaria parasite Plasmodium lophurae, freed from duckling erythrocytes by immune hemolysis, and on the erythrocytes and plasmas of normal and P. lophurae-infected ducklings. Major lipids of normal erythrocytes were: phosphatidylcholine (40% of total lipids), phosphatidylethanolamine (20%), cholesterol (20%), sphingomyelin (11%), and glycosphingolipids (5%). Major fatty acids of erythrocyte total phospholipids (74% of total lipids) were 16:0 (22%), 18:2 (n-6) (21%), 18.1 (n-7, n-9) (18%), 18:0 (9%), 20:4 (n-6) (9%), 22:6 (n-3) (5%). Erythrocyte phosphatidylcholine was greater than 90% the diacyl form, while phosphatidylethanolamine was approximately 44% alkoxy forms and phosphatidylinositol approximately 11% alkoxy forms. Major fatty aldehydes of phosphatidylethanolamine were 16:0 (47%), 18:1 (23%), 18:0 (14%), and 14:0 (12%). The lipid composition of P. lophurae (plus the parasitophorous vacuole membrane) was qualitatively and quantitatively different from that of the duckling erythrocyte in a number of respects. Major lipids were phosphatidylcholine (40%), phosphatidylethanolamine (36%), cholesterol (8%), phosphatidylinostol (4%), 1,2-diacylglycerols (3%), sphingomyelin (2%), and glycosphingolipids (2%). Diphosphatidylglycerol (approximately 1%) was also detected. The major fatty acids of parasite total phospholipids (86% of total lipids) were more saturated than those of the erythrocyte, and octadecenoic acids were notably elevated: 18:1 (33%), 16:0 (26%), 18:0 (16%), 18:2 (12%), 20:4 (3%), and 22:6 (3%). Parasite phosphatidylcholine and phosphatidylethanolamine were greater than 93% the diacyl form and phosphatidylinositol was approximately 25% alkoxy forms. Major fatty aldehydes of the phosphatidylethanolamine were 14:0 (62%), unidentified long chain forms (24%), 16:0 (7%), 18:0 (4%), 18:1 (3%). The lipid composition of the infected erythrocyte reflected the separate contributions of the erythrocyte and parasite. The major lipids of normal duckling plasma were phosphatidylcholine (33%), triacylglycerols (22%), cholesterol esters (20%), cholesterol (12%), phosphatidylethanolamine (5%), and sphingomyelin (2%). The fatty acids of plasma total lipids were 18:1 (26%), 16:0 (26%), 18:2 (12%), 20:4 (12%), 18:0 (9%), 22:6 (3%). Plasma phosphoglycerides were remarkably lower in C18 unsaturated fatty acids and higher in 20:4 than the erythrocyte phosphoglycerides. Infection of ducklings with P. lophurae caused increases in plasma unesterified fatty acids, triacylglycerols and cholesterol esters, and a notable rise in the 18:1 content of all fatty acid-containing plasma neutral lipids. These findings are compared with those reported for other species of Plasmodium infecting other avian and mammalian hosts.


Degeneria halosauri (Bell 1887) gen. et comb. n. (Digenea: Gorgoderidae) from the deep-sea telost Halosauropsis macrochir. The earliest reported trematode from a deep-sea fish, Distomum halosauri Bell 1887 collected by the H.M.S. Challenger expedition, is redescribed from fresh material taken from the type host in the northwest Atlantic. The species is assigned to Degeneria gen. et comb. n. Distinguishing characteristics are the combinaion of a pharynx, cirrus pouch with internal seminal vesicle, disposition of the uterus into the forebody, large eggs, and location in the excretory system of the host. The relationship of Degeneria to other gorgoderids is discussed.


Lectin binding by trypanosoma equiperdum. Agglutination studies with 6 plant lectins indicated that the unaltered surface coat of Trypanosoma equiperdum isolated from rat blood lacks the carbohydrate molecules preferentially bound by these proteins. However, trypsin, pronase, chymopapain, or papain treatments exposed the binding sites for Concanavalin A and the phytohemagglutinins M and P and trypsinized cells were attached to Concanavalin A immobilized on agarose beads. Lipolytic, amylytic, and other proteolytic enzymes or other agents did not reduce or induce lectin agglutination and wheat germ, Anti A, and Anti H lectins did not clump the trypanosomes under any of the conditions employed. Carbohydrate residues resembling D-mannose or n-acetyl-D-galactosamine are therefore within the surface coat of T. equiperdum or on the cell membrane underneath it. The results are contrasted with the lectin induced agglutination of other parasite species and mammalian cells.


Schistosoma mansoni: effects of zinc on cercarial and schistosomule viability. The effects of ZnCl2 on the viability and morphology of cercariae and schistosomules of Schistosoma mansoni were examined. The longevity of cercariae was inversely proportional to the zinc concentration from 0.05 to 5 micronM. Zinc caused body-tail separation and crenation of bodies but not of tails of cercariae, as well as alteration of the staining of cercariae in the indirect immunofluorescence test. Zinc was also effective in reducing penetration of cercariae into mice in a brief (10 min) exposure period. Although the effects on schistosomule morphology were not as conspicuous as with cercariae, 5mM ZnCl2 also affected this stage of the parasite.


Effects of stressful conditions on the development and movement of reproductive cells in Schistosoma mansoni. Adult S. mansoni exposed to 3H-thymidine to label reproductive cells were cultured in vitro, maintained intraperitoneally, and transplanted to the hepatic portal vein of hamsters in unisexual infections. Daily samples were taken, processed for autoradiography, and observed for abnormal morphological and development characteristics. Males cultured in vitro did not produce labeled sperm and the testes exhibitied necrotic changes by the 5th day. Vitelline cell formation was normal for the first 5 days, but after that time both vitellaria and ovary showed degenerative changes. Males and females were still alive after 18 days of culture. Worms transferred to the peritoneal cavity were dead after 3 days, and no signs of reproductive development occurred during that time. Most males and a few females were encapsulated by cells thought to be of host origin. Males transplanted into hamsters in unisexual infections produced sperm in the normal time period and showed no morphological deterioration after 8 days. Females similarly handled were degenerating by day 3 and dead by day 6. Development and movement of reproductive cells was not detected in these females.


Aploparaksis borealis sp. n. (Cestoda: Hymenolepididae) from passeriform and charadriiform birds in Chukotka and Alaska. Aploparaksis borealis sp. n. (Cestoda: Hymenolepididae), from the long-tailed jaeger, Stercorarisu longicaudus Vieillot, on the Seward Peninsula, Alaska, and from the red-throated pipit, Anthus cervinus (Pallas), and the Lapland longspur, Calcarius lapponicus (Linnaeus), in Chukotka, northestern Siberia, is described. This cestode is distinguished by the structure of the cirrus and other morphologic characters from other species of Aploparaksis Clerc 1903 in which there are 10 rostellar hooks and the vitelline gland is aporal to the ovary. A. borealis is the first species of Aploparaksis to be reported from birds representing 2 orders (Passeriformes and Charadriiformes).


Bilateral Duane's syndrome.

Bilateral Duane's syndrome. Two cases with bilateral Duane's Syndrome are presented. Both showed immediate large angle exotropia following bilateral medial rectus recession for esotropia. In both cases, the forced duction test was then found to be positive in adduction and negative after disinsertion of the lateral rectus. It is suggested that both the medial rectus muscles and lateral rectus muscles are tight in bilateral Duane's Syndrome and that seemingly simultaneous recession of the medial and lateral rectus muscles would be indicated.


The necessary resection of the levator muscle of the upper eyelid in the operation for congenital blepharoptosis. The authors comment on the excellent postoperative results obtained in 22 eyes operated on according to the Blaskovics method for congenital blepharoptosis. They discuss the length of the resected part of the levator muscle of the upper lid, the length depending in each case on the degree of the ptosis and on the functional ability of the levator muscle. They arrive at the conclusion that the shortening of the levator muscle must be considerably greater than heretofore advocated by the classical view.


Endogenous uveitis in Indian children: analysis of 94 cases. Out of 1086 cases of endogenous uveitis registered in the uveitis clinic of Irwin Hospital, New Delhi, India, over a period of 10 years from 1963-1972, 94 cases (8.6%) were within the pediatric age group 0-15 years. These cases have been analyzed in detail and the data on age, sex distribution, clinical types, course, complications, various etiological factors, and associated conditions have been tabulated. There were 29 cases within the age group 0-10 years. The youngest was six weeks old. Brief clinical data were: boys, 61.7%; bilateral cases, 45.8%, anterior uveitis, 40.4%; posterior uveitis, 47.9%; generalized uveitis, 11.7% and chronic cases 81.9%. Complicated cataract was the most frequent complication (25.5%) followed by band keratopathy (10.6%). The etiology could be determined in 52.1% of the cases. Tuberculosis was the commonest cause (31.9%) followed by toxoplasmosis (10.6%). There was one case of Behcet's disease where the ocular lesions preceded oral and genital lesions by two years. The series is conspicuous by the notable absence of sarcoidosis as a cause of uveitis. Comparative data on the incidence of childhood uveitis and its various etiological factors as reported by other workers have also been tabulated.


Steroid treatment of an orbital or periocular hemangioma. Orbital hemangiomas may cause deviation of the visual axis with amblyopia and loss of fusion in the infant as a result. Prior methods of treatment include radiation, injection of sclerosing solutions, surgery and ligation of feeding vessels and systemic steroids. A case is presented of an infant treated at five months of age with systemic prednisone over a six-week period with rapid resolution of an orbital hemangioma.


A new approach to congenital posterolateral diaphragmatic hernia. The theory is advanced that increased pulmonary vascular resistance, resulting in a state of fetal circulation, with right-to-left shunting through the ductus arteriosus, is the main reason that many patients do not survive after repair of a diaphragmatic hernia. Three patients are presented (who, by Raphaely's criteria, were destined for a fatal outcome) in whom the ductus was ligated, and vasodilator drugs were infused into the pulmonary artery. All three demonstrated definite improvement in oxygenation. Two expired after 6 days, one of whom was found at autopsy to have intestinal volvulus and gangrene, and the other multiple plumonary emboli. One case, so managed, survived. The suggestion is made that pulmonary hypoplasia is not the main reason for the high mortality rate after diaphragmatic hernia repair, and that additional laboratory and clinical investigation of the pulmonary circulation may lead to significant improvement in results.


Peripherally located congenital arteriovenous fistulae in infancy and childhood. Significant macrofistulae between arteries and veins of congenital origin may result in the extremes of life-threatening hemorrhage or simply a cosmetically displeasing mass. The most helpful diagnostic aid is that of adequate arteriography both to determine the size, location, and extent of the fistulae. After adequate clinical and angiographic evaluation, therapy should be conservative enough to afford optimal function and radical enough to prevent death due to hemorrhage. This report includes eight patients who underwent angiographic evaluation and surgical therapy for arteriovenous malformation. Of the six living patients, five are known to have residual arteriovenous shunting.


A new method for investigating regional lung function in children with localized lung disease. Lung function studies using 13Nitrogen have been used to determine regional and total lung function in 16 children suspected of having localized lung disease amenable to surgery. This method is simple, requires no active co-operation on the part of the child and gives a radiation dosage of about one-third of that for a bronchogram. The studies provided information about the severity and localization of the disease, and in addition, information about the remaining lung areas.


Surgery of megaureters--modification of Hendren's operation. It was Hendren's contribution to introduce an aggressive restorative procedure for the entire urinary tract in children with the megaureter syndrome. Our own experience in applying this method enabled us to more critically assess its value and prompted us to introduce some modifications. Instead of longitudinally resecting the dilated ureter we applied a method in which the dilated ureter wall is folded. This prevents injury to the ureter wall and its necrosis. We have given up excessive shortening of the elongated ureter, since the elongation proved to be spurious. We have also given up reconstruction of the upper part of the ureter.


Bilateral congenital anophthalmos. Report of two cases. Two cases of bilateral congenital anophthalmos in Nigerian children are reported. Both cases are sporadic, and belong to the primary type of anophthalmos. The first case has associated polydactyly of both hands. There is no history of ingestion of any teratogenic drugs during pregnancy in the two cases.


The management of portal hypertension in cystic fibrosis. We have found that with proper selection and preoperative preparation, a major portosystemic shunt can be done with considerable safety in a majority of cystic fibrosis patients and thus provide them with significant palliation and improved quality of life.


Microphthalmos with orbital cyst: a clinicopathological report. The clinical and histopathological findings in a case of microphthalmos with orbital cyst is described. The clinical interesting feature of this case was the bilateral coloboma which represented interference in the development of the eye at different stages of embryonic life.


Rectoplasty with posterior triangular colonic flap--a radical new operation for Hirschsprung's disease. Rectoplasty with posterior triangular colonic flap was devised as a new operation for Hirschsprung's disease with the purpose of eliminating the anastomotic leakage that was encountered in rectal myotomy with colectomy, retaining the original intent of the operation. The procedure was carried out on 15 patients. Postoperative function of the anorectum was clinically assessed as excellent in 12, fair in one, poor in another. The remaining patient was too young for clinical assessment of function.


Colitis in children with the hemolytic-uremic syndrome. The hemolytic-uremic syndrome consists of hemolytic anemia, renal failure, and thrombocytopenia. Submucosal hemorrhage with "thumbprinting" on roentgenographic examination of the colon with barium was demonstrated in four patients, prolapse of the rectum in two patients, and pseudomembranous enterocolitis and toxic megacolon in one. These lesions are not generally associated with hemolytic-uremic syndrome. The presence of these lesions in a child with bloody diarrhea should suggest hemolytic-uremic syndrome as a possible diagnosis. Sigmoidoscopy and roentgenographic examination of the colon with barium should be done in selected patients with hemolytic-uremic syndrome to evaluate the degree of colonic involvement and the need for surgery.


Surgical management of esophageal stricture due to recessive dystrophic epidermolysis bullosa. Esophageal stricture may occur as a complication of the dystrophic recessive form of epidermolysis bullosa. Mechanical dilatation by bougienage may cause more severe esophageal injury. The fourth reported case of esophageal replacement by colonic interposition for this condition is presented. Central venous total parenteral alimentation was a helpful adjunct in the surgical management of this patient. Colonic replacement is preferred over local resection of an esophageal stricture because in most instances there is extensive inflammatory involvement of the entire esophagus.


Intramural tracheoesophageal fistula (TEF) associated with esophageal web. This is a report of the fourth known case of intramural TEF with diaphragmatic esophageal atresia. These patients present clinically as a typical esophageal atresia with tracheoesophageal fistula, but in effect have the following unusual features: 1) high TEF entering the trachea in the neck; 2) diaphragmatic-type atresia of the esophagus with uninterrupted muscular coat; 3) the location of this diaphragm is at the level of the carina producing in effect a long intramural fistulous tract. It is believed that faulty recannulization of a segment of the esophagus in association with H-type TEF may explain this uncommon anomaly.


Diagnosis and surgical management of "H-type" tracheoesophageal fistula in infants and children. By means of the new rod lens telescopic endoscopes, the diagnosis of H- or N-type tracheoesophageal fistula in infants and children can now be made definitively without the difficulties and complications previously described, and the numerous methods recommended in the literature, all of which have their inconsistensies, failures, errors, and dangers. Using these advanced endoscopes the fistula is demonstrated by bronchoscopy, a small Fogarty catheter is threaded through the opening in the trachea under direct view of the telescope and passed through the fistula into the esophagus. The balloon is inflated and the bronchoscope removed, leaving the catheter in place. A proper incision is then made in the neck or chest, depending on the location of the lesion, and the fistulous tract is quickly located by palpation of the balloon and catheter. Then with minimal and accurate dissection, correction is carried out.


Levator repair and posterior suspension for rectal prolapse. An operative procedure for the management of rectal prolapse is described. It has the advantanges of simplicity, relative safety, short hospitalization, and lack of recurrence in the four patients presented.


Infraumbilical entry into the peritoneal cavity through a small incision for the identification and cannulation of an umbilical artery. An infra-umbilical entry into the peritoneal cavity through a small incision, without anesthesia, for the identification and cannulation of an umbilical artery was employed for monitoring and therapy in five prematurely born neonates. The extra-peritoneal approach to umbilical artery identification and cannulation had been unsuccessful in all of these cases. The operations were carried out in the neonatal intensive care unit under strict surgical asepsis. Microsurgical techniques with 2.5 times magnification and microsurgical instruments were employed and found to be quite useful. In all five cases, an umbilical artery was readily identified and cannulated and there were no postoperative complications attributed to this approach.


Giant craniopharyngioma evaluated by computerized axial tomography. The advent of computerized axial tomography (CAT scan) has augmented the neurologic diagnostic armamentarium dramatically. The ability of the CAT scan to differentiate and accurately locate various intracranial densities in a noninvasive manner makes it a very valuable method of investigating craniopharyngiomas. Because they are often composed of cystic, solid, and calcified portions, craniopharyngiomas are very well demonstrated, with the same CAT scan revealing ventricular size as well. A recent and representative case is reported demonstrating the correlation between the CAT scan and the operative findings.


Retroperitoneal fibrosis with hydronephrosis as a complication of the Dwyer procedure. The first reported urological complication of Dwyer Instrumentation for scoliosis is presented. This patient demonstrated ureteral obstruction secondary to retroperitoneal fibrosis temporally associated with this procedure. Routine IVP following surgery is recommended for early detection of urinary complication.


Male homosexual psychodynamics and the Rorschach test. A review of contradictory findings regarding Wheeler's Rorschach content signs of male homosexuality suggested that negative findings may have resulted from a focus on homosexual populations characterized by minimal arousal of underlying unconscious conflicts. It was hypothesized that activating these unconscious psychodynamics would enhance the discriminative power of the Wheeler signs. Inkblot protocols obtained in an earlier study from matched groups of homosexuals and heterosexuals under two experimental conditions -- involving subliminal exposure of either an incest-related or a neutral control stimulus -- were scored for Wheeler signs. The incest condition brought about a significantly greater incidence of the signs in homosexual records only, suggesting that the intensification of unconscious incest wishes stimulates homosexual reactions, consonant with psychoanalytic formulations.


The effects of surgery-induced stress on anxiety as measured by the Holtzman Inkblot Technique. Form A of the Holtzman Inkblot Technique (HIT) was administered to 45 subjects approximately 24 hours prior to a surgical operation and Form B of the HIT was administered after surgery. A-State and A-trait were monitored by the State-Trait Anxiety Inventory (STAI) pre- and postsurgery. STAI A-State scores declined and STAI A-Trait scores remained stable from pre- to postsurgery. Among selected HIT variables, only Barrier scores remained stable and correlated (negatively) with STAI A-Trait scores. No HIT variables changed across periods and were correlated with STAI A-State scores obtained concurrently. Employing a multiple regression approach, a three-variable prediction model was derived for A-State and six-variable model was derived for A-Trait. In addition, the implications of the high number of rejected cards obtained in this study were discussed in terms of the possible inappropriateness of the HIT as an assessment tool under conditions of high situational stress.


Black Thematic Apperception Test stimulus material. A factorial design was used to test variations of the TAT based on racial characteristics. The subjects consisted of 135 black Southern males divided into three test groups of 45 subjects each. The M-TAT, T-TAT, or an experimental version of the TAT for blacks was group administered to each test group of 45 subjects. Each of the three test groups were further divided into three age groups of 15 subjects each designated as residents, college students or high school students. Subjects' responses to the racial characteristics and needs content across tests and age groups were examined. The data revealed: (a) subjects could distinguish the racial characteristics of black and white TAT material, (b) subjects indicated that black TAT material facilitated the writing of their stories, (c) subjects viewed the black TAT characters as more like "people in general," (d) both figure and background stimuli are important to subjects, and (e) content differences on need for achievement was found between age groups.


The Rorschach test and the assessment of object relations. The study attempts to demonstrate a structurally-based consistency to subjects' object relations as measured across various independent ratings. Particular interest was aimed at the capacity of the Rorschach to tap developmentally crucial aspects of the structure of patients' object relations. A scale was developed to measure the degree to which relationships between figures on the Rorschach were perceived in terms of a mutuality of autonomy. These Rorschach ratings were then correlated with independent measures of this mutuality of autonomy dimension which were obtained from a written autobiography, and ratings by ward staff. Based on a sample of 40 inpatient subjects, the resulting intercorrelation among measures proved to be highly significant.


Reflections of personality functioning in psychological testing of disadvantaged three to five year olds. Psychological assessment with preschool children provides a unique opportunity to observe developmental conflicts before the defensive organization of the personality is fully formed. Specific sub-tests of the WPPSI and Merrill-Palmer Scales have been observed to evoke behavioral expression of phase-specific conflicts. Clinical observations of a disadvantaged inner-city population suggest that what is being tested is the child's experience with adults in the sphere of object relations, and not cognitive functioning per se.


Second order factors in the California Psychological Inventory. In order to further specify the structure of the California Psychological Inventory (CPI), correlations among the first order factors of the CPI were factor analyzed, yielding two second order factors. These factors were described, and were named General Adjustment and Social Sensitivity, respectively. The second order configuration of CPI scales appeared to be consistent with other research done on the scales. It was suggested that, like the 16PF, second order factor scores for the CPI could have some utility.


Sex differences on the Personal Orientation Inventory. Differences on the Personal Orientation Inventory (POI) between 816 male and 408 female entering freshmen were examined. Females scored consistently and significantly more in the purported self-actualizing direction on the POI scales and subscales than males in this study. Special emphasis was placed upon the pattern of significant scale differences in an effort to derive the meaning of such male-female differences for these and other data. One interpretation is that females may be seeking a college education for more self-actualizing purposes than males. It is suggested that the consistency of such differences be further explored and that sex differences on the POI be considered in future studies of self-actualization.


Extraversion, neuroticism and different aspects of self-reported aggression. Sixty-two male, and 57 female university students were administered tests of extraversion, neuroticism and aggression. Different forms of aggression were found to have different personality correlates, and the correlation matrices of the male and female samples were largely dissimilar. The direction of sex differences in subtest scores seemed to depend on the type of aggression measured. Socioeconomic class was not significantly related to any of the aggression scales.


Affective guilt states in women and the Perceived Guilt Index. Two experiments were conducted to examine the determinants of affective guilt states, and to examine the interrelationships among one measure of dispositional guilt, and two measures of affective guilt. In study 1, women who were high in affective trait guilt had higher guilt states after being required to make sexual responses to sexual double-entendre words. In study 2, high affective trait guilt women had higher guilt states after being told they would be required to make sexual responses, but before they actually made any responses. The hypothesized relationship between a measure of dispositional guilt and a measure of affective state guilt was not found in either experiment.


Ego-delay and vocational behavior.

Ego-delay and vocational behavior. Two hypotheses derived from ego analytic vocational theory were tested using neuropsychiatric patients referred for vocational rehabilitation procedures. Subjects who obtained higher ego-delay scores derived from a time estimation technique were found to obtain higher vocational aptitude scores and higher levels of vocational readjustment following disability. Issues for counseling and further research are discussed.


The effects of self-esteem and evaluator demandingness on effort expenditure. The self-esteem of subjects was temporarily either raised or lowered by giving them false feedback on an alleged personality test. Subjects then participated in what they believed was a second, separate experiment in which they would engage in problem solving. Half the subjects in each self-esteem condition were led to believe that the evaluator of their problem-solving performance was difficult to please; the remainder, that he was easy to please. Subjects then committed themselves to expending effort in preparation for the problem-solving exercise. Based on a self-enhancement perspective derived from attributional principles, an interaction was predicted: High self-esteem subjects would plan to exert greater effort when the evaluator was demanding than when he was undemanding, whereas low self-esteem subjects would exert greater effort when the evaluator was undemanding. The results supported the hypothesis and are discussed with respect to consistency theory, as well as in the context of self-enhancement ideas.


Effects of communication about interpersonal process on the evolution of self-disclosure in dyads. In an earlier investigation, like-sex partners in an acquaintance exercise were found to match their mean levels of intimacy. This "consensus" was achieved through the adoption of asymmetric roles, whereby one partner would consistently set the pace with respect to intimacy, and the other would reciprocate. It was proposed that such unilateral control of the dyad's evolution would be replaced by shared control if partners were encouraged to discuss the problem of how intimate to be with one another. As predicted, role asymmetry gave way to role symmetry when such communication took place. In addition, partners were able to match their mean levels of intimacy during the exercise without recourse to matching on a moment-to-moment basis. In place of a monotonic increase in intimacy, dyads followed a curvilinear course marked by an accelerated increase and a subsequent tapering off or decrease in intimacy level. The findings are discussed in relation to the more general question of how consensus is achieved in the social construction of an encounter or relationship.


Observers' focus of attention in the simulation of self-perception. This research was designed to assess the effects of a manipulation of observers' focus of attention--from a focus on the actor to a focus on the actor's situation--upon observers' attributions of attitude to an actor in a simulation of a forced-compliance cognitive dissonance experiment. Observers induced through empathy instructions to focus attention on the actor's situation inferred less actor attitude positivity than did observers given no specific observational set. In addition, situation-focused observers inferred that the actor's attitude was directly related to reward magnitude, whereas actor-focused observers inferred that the actor's attitude was inversely related to reward magnitude. An extension of self-perception theory, offered as an interpretation of these and other results, suggested that motivation attribution made by actors and observers in dissonance and simulation studies are dependent on focus of attention. The attributions made by actor-focused observers simulate those of objectively self-aware actors and are based upon perceived intrinsic motivation; the attributions of situation-focused observers simulate those of subjectively self-aware actors and are based upon perceived extrinsic motivation.


Sexual arousal and aggression by males: effects of type of erotic stimuli and prior provocation. Eighty-five undergraduate males participated in an experiment designed to investigate the impact of various types of erotic stimuli upon aggression. On the basis of previous research, it was hypothesized that exposure to mild erotic stimuli would tend to inhibit subsequent aggression, while exposure to more arousing stimuli of this type would facilitate such behavior. In order to examine this hypothesis, male subjects were first angered or treated in a more neutral manner by a confederate of the experimenter and then provided with an opportunity to aggress against this person by means of electric shock. Before aggressing, participants were exposed to one of five different types of stimuli: nonerotic pictures of furniture, scenery, and abstract art; pictures of seminude females; pictures of nude females; pictures of couples engaged in various acts of lovemaking; or explicit erotic passages. Results offered partial support for the major hypothesis. Exposure to mild erotic stimuli inhibited later aggression, while exposure to more arousing sexual materials neither facilitated nor inhibited such behavior.


The effects of failure and depression on subsequent aggression. Two experiments assessed the effects of repeated failure on subsequent aggressive responses to increasing attack. In the first experiment, male subjects who had been assigned randomly to a treatment involving failure at a task evidence smaller increments in aggressive responses to attack than did those who succeeded at the initial task. In the second experiment, prior failure inhibited the aggressive increments to escalating attack on the part of depressed male subjects but faciliated the aggressive increments of nondepressed male subjects. The results are discussed in terms of learned helplessness theory and a belief in the ability to control the consequences one's behavior.


Lack of control as a determinant of perceived physical symptoms. Two experiments were conducted to investigate the role of lack of control in determining the extent to which individuals report experiencing physical symptoms. In Experiment 1, subjects who had little control over a noise burst subsequently reported a higher incidence of physical symptoms than did subjects who could control the noise burst. Unfortunately, degree of failure may have been confounded with degree of control in Experiment 1. Thus, Experiment 2 was designed to determine if differential perceptions of control would produce differences in reported symptoms when degree of success was held constant. Greater symptoms were again reported by subjects in the no-control condition. Experiments 1 and 2 also explored questions concerning the mechanism underlying the effects of lack of control on reported physical symptoms. Both experiments failed to find evidence that subjects reported symptoms for ego-preserving reasons. Other data suggested that the symptoms reported by subjects were not related to their past experience with physical symptoms, nor were symptoms reported as a function of perceived or actual physiological arousal.


Predictive conversion of in vitro drug dissolution data into in vivo drug response versus time profiles exemplified for plasma levels of warfarin. A mathematical approach to computing the in vivo drug response profiles (such as plasma level, pharmacological response, and urinary recovery versus time curves) corresponding to observed in vitro dissolution of drug dosage form versus time profiles is described. The method is exemplified for warfarin tablets,for which observed in vivo plasma level profiles are compared to corresponding predicted profiles computed from in vitro dissolution data. The potential of the method is demonstrated; approaches to its improvement, as well as its limitations, are discussed.


Pattern recognition II: Investigation of structure--activity relationships. A simple form of pattern recognition is successfully used to classify a set of structurally diverse therapeutic agents. By using only organic structural information, the major pharmacological classes present were correctly identified and the pharmacologically unrelated compounds were separated out. One technique of factor analysis--principal component analysis--is shown to be readily adaptable in preprocessing the data. Simple graphical representation of the results enables their direct interpretation.


Stability of (pyrrolidone-5-hydroxamato)iron (III) chelates. Overall stability constants of mono-, bis-, and tris(pyrrolidone-k-hydroxamato)iron(III) chelates were determined in aqueous solutions at 25 degrees as log beta1=1.49, log beta11=1.55, and log betaIII=0.21, respectively, where beta1=[Fe(C5H7O3N2)2+][H+]/[F=E3+][HC5H7O3N2], betaII=[Fe(C5H7O3N2)2+][H+]2/[Fe3+][hc5h7o3n2]2, and betaIII=[Fe(C5H7O3N2)3][H+]3/[Fe3+][HC5H7O3N2]3. Stability constants of all three chelates were determined potentiometrically in the 3.00-3.23 pH region. The stability constant of the mono chelate also was determined spectrophotometrically at 25 degrees as log beta1-1.52 by measuring absorbance at 500 nm (absorbance maximum), where the molar absorptivity was epsilon=1124 liters/(mole cm). Biological implications of hydroxamic acid-containing compounds are discussed.


Pharmacokinetics of beta-methyldigoxin in healthy humans II: Oral studies and bioavailability. The pharmacokinetics of orally administered aqueous 3H-beta-methyldigoxin solutions were studied at two dose levels, 0.3 and 0.6 mg, in healthy human subjects. The drug and its metabolites were specifically assayed in biological fluids and compared with results after intravenous doses to the same subjects. No significant dose dependency was observed. The apparent half-life of absorption was 16+/-6 min (SEM). Digoxin was the only metabolite observed in the plasma and comprised 28.6+/-3.7% of the dose in the urine. 3H-beta-Methyldigoxin, renally excreted unchanged, comprised 25.7+/-1.7% (SEM). Water-soluble metabolites in the urine comprised 9.0+/-1.8%. Fecal and urinary excretion accounted for 85% of the dose at 144 hr. The oral absorption of unchanged 3H-beta-methyldigoxin from solution was 59+/-6% by area under the curve methods and 60+/-4% by renal excretion. A total of 73% of the dose in the solution was absorbed as beta-methyldigoxin and digoxin. First-pass metabolism prior to absorption was largely prehepatic and assignable to GI degradation; 21.9+/-2.8% was degraded with 12.8+/-4.0% to digoxin and 9.1+/-4.0% to water-soluble metabolites. From 14 to 18% of the administered oral dose did not reach the systemic circulation. Analog computer fitting of plasma and urine levels of drug and digoxin was consistent with the first-pass premise with a delayed absorption of GI-generated digoxin and other metabolites. There were no significant differences between the oral absorption of a tablet formulation and the solution. Orally administered beta-methyldigoxin solution delivered 97% cardioactivity as itself and digoxin with respect to an equivalent amount of intravenously administered digoxin. This value contrasts to the 140% delivered by intravenously administered beta-methyldigoxin on the premise of pharmacodynamic equivalence of systemically appearing digoxin and beta-methyl-digoxin. Literature reports on the oral bioavailability of solutions and solid dosage forms of digoxin were critically reviewed, but no reliable comparison of the extent and reproducibility of oral absorption of cardioactive agents from administered digoxin or beta-methyldigoxin could be made from the widely variable digoxin studies with nonspecific assays.


Methods for evaluating hermetic closures for screw-capped bottles. With the described method, a large number of sealed bottles can be tested to determine their effectiveness, integrity, and reliability in preserving an inert atmosphere. The method consists of placing milligram quantities of dry ice into the bottles, capping them, and periodically weighing them on an analytical balance; leaky bottles are detected by a loss in weight. This method can be applied to test a large number of bottles with a minimum of effort and manpower and without complicated instrumentation. The data presented are highly reproducible and correlate well with data from other methods and with the physical defects of the bottles.


Quantitative determination of phenacetin and its metabolite acetaminophen by GLC-chemical ionization mass spectrometry. A quantitative GLC-mass spectrometric procedure was developed for the determination of phenacetin and its O-desethyl metabolite, acetaminophen, in human plasma. The assay utilizes selective ion detection to monitor, in a GLC effluent, the MH+ molecular ions of both phenacetin and the methyl derivative of acetaminophen, p-acetanisidine, generated by isobutane chemical ionization. Deuterated analogs of phenacetin and acetaminophen, phenacetin-d3 and acetaminophen-d3, respectively, are added to the plasma before extraction to serve as internal standards. To determine phenacetin and unconjugated acetaminophen, 1.0 ml of plasma is extracted with 5 ml of benzene-dichloroethane (7:3). The extraction solvent is removed, and the residue is methylated with diazomethane. Th solution is again evaporated to dryness, and the residue is reconstituted in ethyl acetate. A portion of this solution is then analyzed by GLC-mass spectrometry, with the mass spectrometer set to monitor m/e 166 (p-acetanisidine), 169 (p-acetanisidine-d3), 180 (phenacetin), and 183 (phenacetin-d3). To determine total acetaminophen, 0.1 ml of plasma is treated with a mixture of beta-glucuronidase and sulfatase, extracted with ethyl acetate, methylated, and analyzed by GLC-mass spectrometry. The procedure has a sensitivity limit of 1 ng of phenacetin/ml and 0.1 mug of acetaminophen/ml. The curves relating the amount of phenacetin and acetaminophen added versus the amount of phenacetin and acetaminophen found for 12 known phenacetin concentrations over the 9.9-246.6-ng/ml range and for 16 known acetaminophen concentrations over the 0.52-13.10-mug/ml range are straight lines with intercepts of nearly zero and with slopes of unity. Analyses of six separate plasma samples, each containing 25 ng of phenacetin/ml and 1.31 mug of acetaminophen/ml, had a precision of +/- ng/ml for phenacetin and +/- 0.08 mug/ml for acetaminophen.


Pharmacokinetics of ampicillin and methoxymethyl ester of hetacillin in dogs. Concentrations of ampicillin and the methoxymethyl ester of hetacillin were measured in plasma, prostatic fluid, and spinal fluid of dogs receiving  ampicillin or the hetacillin ester by continuous intravenous infusion. The ratios of ampicillin in prostatic fluid relative to plasma levels were higher after dosing with the hetacillin ester. Pharmacokinetic parameter values were consistent with urinary excretion characteristics. Ready diffusion of the ester across biological membranes may facilitate eradication of pathogenic organisms in prostatic and spinal fluids.


Serum lipid-lowering properties of 6-chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid. 6-Chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid hydrochloride lowered serum cholesterol, triglyceride, phospholipid, and free fatty acid levels in normal rats. The compound appeared to have a low toxicity and to be well tolerated in mice, adult and neonatal rats, and rabbits. At hypolipidemic doses, it caused a slight hepatomegaly associated with an increase in liver phospholipid and protein content. Liver N-demethylase and catalase activities were increased by the drug treatment. This acid had no in vitro antilipolytic activity and did not affect serum desmosterol-cholesterol ratios. The results indicate that it has a mechanism of action similar to clofibrate.


Spectrofluorometric determination of substituted tetrahydrocarbazoles by a methylene blue sensitized photolytic reaction. A spectrofluorometric method was developed for the determination of 6-chloro-9-[2-(2-methyl-5-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-methanol hydrochloride and its carboxylic acid analog in blood and urine. It involves extraction of both compounds at neutral pH, either from blood into ethyl acetate (the residue of which is dissolved in either) or from urine directly into ether. Both the alcohol and the acid are separated from each other by selective extraction into acid or base, respectively, and then reextracted into either from the respective aqueous medium by appropriate pH adjustment. The residues of the ether extracts containing the compounds are dissolved separately in 0.25 N NH4OH. Methylene blue is added to all samples, which are then exposed to UV energy for 15 min to produce the fluorophores. The fluorescence of the solutions is read at 370 nm, with excitation at 340 nm. The linear range of quantitation of both compounds is 0.02-10 mug/each/ml of final solution. The method was applied to the determination of blood levels and urinary excretion of the alcohol and its acid metabolite in a dog.


GI drug absorption in rats exposed to cobalt-60 gamma-radiation I: Extent of absorption. The extent of absorption of sulfanilamide, bretylium tosylate, sulfisoxazole acetyl, and riboflavin was determined in rats exposed to 850 rad of cobalt-60 gamma-radiation of sham irradiated. The drug were administered orally at 1 or 5 days postirradiation, and the amount of drug excreted in the urine was used as the measure of absorption. Following intravenous drug administration, there was no difference between irradiated and control animals in the amount of drug excreted in the urine. At 1 day postirradiation, the absorption of sulfanilamide and bretylium was not affected by radiation; the absorption of sulfisoxazole acetyl and riboflavin was increased. The fraction of sulfanilamide excreted in the urine as N4-conjugate was increased at 1 day postirradiation. At 5 days postirradiation, there was no detectable difference between irradiated and control animals in the extent of drug absorption. The effects of radiation on the extent of absorption of orally administered drugs were most pronounced immediately following irradiation. Irradiation apparently does not affect the absorption of drugs that are normally well absorbed or poorly absorbed due to slow transport across the GI mucosa. Following irradiation, there may be an increase in the extent of absorption of drugs that are poorly absorbed due to low aqueous solubility or that are absorbed by a saturable transport mechanism.


GI drug absorption in rats exposed to cobalt-60 gamma-radiation II: in vivo rate of absorption. The rate of absorption of sulfanilamide, bretylium tosylate, sulfisoxazole acetyl, and riboflavin was studied in rats exposed to 850 rad of cobalt-60 gamma-radiation either 1 or 5 days before oral drug administration. Polyethylene glycol 4000 was administered with sulfanilamide; its distribution along the GI tract indicated that the gastric emptying rate was reduced threefold at 1 day postirradiation but returned to normal at 5 days postirradiation; the small intestinal transit rate was not detectably altered by irradiation. At 1 day postirradiation, there was a marked decrease in the absorption rate of sulfanilamide, a smaller, although significant, decrease in the absorption rate of sulfisoxazole acetyl and bretylium, and an increase in the absorption rate of riboflavin. At 5 days postirradiation, the drug absorption rate was normal. The changes in the absorption rate of the drugs were due to a radiation-induced reduction in the gastric emptying rate; the permeability of the GI epithelium did not appear to be affected by radiation. The results indicate that, immediately following irradiation, a marked reduction in the gastric emptying rate causes a pronounced reduction in the absorption rate of rapidly absorbed drugs, a less pronounced reduction in the absorption rate of drugs that are absorbed slowly because of slow dissolution or slow diffusion across the GI epithelium, and an increase in the absorption rate of drugs that are absorbed by a saturable mechanism provided the mechanism is not impaired by irradiation.


Application of gluconolactone in direct tablet compression. Gluconolactone was evaluated as an excipient for tablets prepared by direct compression using various drugs known to be difficult to compress. The physical properties of the tablets were evaluated after compression and after storage and were satisfactory. Comparative studies were conducted between gluconolactone and anhydrous lactose, a common direct compression diluent, for development of static charges during blending, flow, drug distribution, drug stratification, color distribution, compressibility, and preservation against mold growth. Gluconolactone possesses those properties necessary to produce high quality tablets by the direct compression process. Separate powdered mixtures of aspirin USP with gluconolactone, anhydrous lactose, spray-dried lactose, mannitol, and sorbitol were stored at various humidities and temperatures for specified periods and tested for the integrity of aspirin. Gluconolactone contributed least to the degradation of the drug as compared to other excipients studied. A preliminary in vivo study also was conducted on the bioavailability of aspirin from separate and similar mixtures with gluconolactone, anhydrous lactose, and starch. Gluconolactone did not show any inhibitory effect on aspirin absorption.


Electron-capture GLC determination of nanogram to picogram amounts of isosorbide dinitrate. A GLC method for the determination of plasma isosorbide dinitrate using electron-capture detection is described. The organic nitrates are especially suited for electron-capture detection if the detector temperature is optimized for maximum sensitivity, e.g., 175 degrees. Proper maintenance of the detector and column assures reproducible data in the low nanogram range. The extraction procedure described is simple, efficient, and expedient for processing large numbers of samples. The method was used to study plasma levels in four human volunteers after a single dose of a 5-mg chewable isosorbide dinitrate tablet. Concentration levels of isosorbide dinitrate as low as 0.5 ng/ml of plasma can be measured by this procedure.


Quantitative assay of physostigmine in human whole blood. A quantitative assay for measuring physostigmine in human whole blood is described. Blood samples are maintained at 37 degrees, and cholinesterase activity is measured periodically. The time required for enzyme reactivation is related to physostigmine concentration. The precision of the method is within +/- 4% over a physostigmine concentration range of 0.5-5.0 x 10(-7) M.


Pharmacokinetics of delta9-tetrahydrocannabinol in dogs. The pharmacokinetics of intravenously administered 14C-delta9-tetrahydrocannabinol and derived radiolabeled metabolites were studied in three dogs at two doses each at 0.1 or 0.5 and 2.0 mg/kg. Two dogs were biliary cannulated; total bile was collected in one and sampled in the other. The time course for the fraction of the dose per milliliter of plasma was best fit by a sum of five exponentials, and there was no dose dependency. No drug was excreted unchanged. The mean apparent volume of distribution of the central compartment referenced to total drug concentration in the plasma was 1.31 +/- 0.07 liters, approximately the plasma volume, due to the high protein binding of 97%. The mean metabolic clearance of drug in the plasma was 124 +/- 3.8 ml/min, half of the hepatic plasma flow, but was 4131 +/- 690 ml/min referenced to unbound drug concentration in the plasma, 16.5 times the hepatic plasma flow, indicating that net metabolism of both bound and unbound drug occurs. Apparent parallel production of several metabolites occurred, but the pharmacokinetics of their appearance were undoubtedly due to their sequential production during liver passage. The apparent half-life of the metabolic process was 6.9 +/- 0.3 min. The terminal half-life of delta9-tetrahydrocannabinol in the pseudo-steady state after equilibration in an apparent overall volume of distribtuion of 2170 +/- 555 liters referenced to total plasma concentration was 8.2 +/- 0.23 days, based on the consistency of all pharmacokinetic data. The best estimate of the terminal half-life, based only on the 7000 min that plasma levels could be monitored with the existing analytical sensitivity, was 1.24 days. However, this value was inconsistent with the metabolite production and excretion of 40-45% of dose in feces, 14-16.5% in urine, and 55% in bile within 5 days when 24% of the dose was unmetabolized and in the tissue at that time. These data were consistent with an enterohepatic recirculation of 10-15% of the metabolites. Intravenously administered radiolabeled metabolites were totally and rapidly eliminated in both bile and urine; 88% of the dose in 300 min with an apparent overall volume of distribution of 6 liters. These facts supported the proposition that the return of delta9-tetrahydrocannabinol from tissue was the rate-determining process of drug elimination after initial fast distribution and metabolism and was inconsistent with the capability of enzyme induction to change the terminal half-life.


Synthesis and in vivo antimalarial evaluation of isopropyl [(4-chlorophenyl)amino]iminomethylcarbamimidate. Isopropyl [(4-chlorophenyl)amino]iminomethylcarbamimidate was synthesized as a potential antimalarial agent. Biological activity was evaluated against Plasmodium lophurae in turkeys. The activity of this compound was compared to its nitrogen isostere, chloroguanide.


GLC determination of opium alkaloids in papaveretum. A GLC method for the determination of the opium alkaloids in papaveretum, based on the formation of the acetyl derivatives of morphine and codeine, is described. The analytical results are compared with those obtained by the official method. The proposed method is fast and accurate and is particularly suited to the analysis of the raw material.


Quantitative high-pressure liquid chromatographic determination of epinephrine in pharmaceutical formulations. A quantitative high-pressure liquid chromatographic method, using a cationic exchange resin column and an aqueous phosphate buffer as the mobile phase, was employed for the determination of epinephrine in liquid pharmaceutical preparations. The method is stability determining and can differentiate epinephrine in the presence of oxidative and other degradation products.


Complement fixing site of human IgG1.

Complement fixing site of human IgG1. A number of chemical modifications were made to purified human IgG1. The effects of these modifications on the complement activity of the immunoglobulin were studied using aggregation on latex and measuring the consumption of the complement by CH50-quantitation. Tryptophan and tyrosine are implicated in the complement fixing site of this human immunoglobulin, and an arginine moiety probably provides a binding site for the complement.


Determination of oxamniquine in serum.

Determination of oxamniquine in serum. A method for the analysis of oxamniquine in serum (or plasma), sensitive to 10 ng/ml, was developed. Oxamniquine and a close structural analog as the internal standard were extracted from serum with ether. After derivatization with N,O-bis(trimethylsilyl)acetamide, oxamniquine was determined as its trimethylsilyl ether derivative by GLC using an electron-capture detector. The method was developed to study serum concentration profiles of different dosage forms of oxamniquine.


Survival of pleomorphic sarcoma-37 transplanted virgin female DBA/2J mice: hyperthermia and hyperglycemia, alone and in combination with drugs. Sarcoma-37 (S-37) transplanted DBA/2J mice were submitted to a controlled whole body hyperglycemic-hyperthermic ("double attack") treatment. A single exposure to the 3-hr 400-500-mg% blood glucose level coupled with 1 hr of whole body 40.0 degrees warming was safe and extended longevity by 40% over the nontreated controls. This increase suggests that additive or potentiated effects follow the two-parameter procedure. The treatment safety and resultant increased longevity were not enhanced by single-dose chemotherapy with doxorubicin and/or dacarbazine.


IR spectrophotometric assay of carbachol solutions. Carbachol ophthalmic solutions can be assayed by evaporating a measured volume, dissolving the residue in methanol, and scanning the carbonyl stretching frequency in an IR spectrophotometer using a cell with calcium fluoride windows. Methylcellulose and other formulation vehicle components do not interfere. The method is stability indicating with respect to hydrolysis. It affords a recovery of 99.5+/-0.51% (RSD).


Anomalies of disparity detection in the human visual system. 1. Oculomotor and psychophysical depth responses were investigated in thirty individuals by use of briefly exposed disparities in the range from 0-6 to 4-6 degrees (1-8 centrads). 2. The results substantiate a previous finding which reported the common occurrence of specific types of stereoanomalies within a sample from the normal population. However, arguments are presented to suggest that these forms of stereoanomalies are limited to coarse stereopsis and spare mechanisms concerned with fine disparity, high resolution stereopsis. 3. A relatively high proportion of individuals were found to manifest deficiencies of vergence eye movement under these stimulus conditions. These vergence-anomalies are characterized by a marked reduction, or absence, of neither convergent or divergent eye movements to briefly exposed stimuli. 4. The vergence-anomaly is not detrimental under normal seeing conditions since it can be present in persons with adequate binocular vision and normal fine stereopsis. 5. The presence of vergence-anomaly was always associated with the occurrence of stereoanomaly; however, the converse was not true. 6. The results are taken as evidence to show how disparity information is organized prior to its influence upon the processes of coarse stereopsis and vergence initiation.


Ballistic contractions in man: characteristic recruitment pattern of single motor units of the tibialis anterior muscle. 1. Single motor units were recorded with highly selective electrodes from intact tibialis anterior muscle in the adult man. A detailed parametric analysis was made of the discharge patterns during voluntary isometric contractions of different peak forces carried out at various rates of force development. 2. During the smooth tracking of a ramp force, the different motor units recorded from a given muscle site were recruited in a consistant order, each unit becoming active when the muscle developed a certain level of force. The threshold of some of the units in such slow ramp contractions exceeded 8 kg. By contrast, in brisk ballistic contractions reaching a peak force of 12 kg in less than 0-15 sec, the same motor units discharged in a transient burst which largely preceded the muscle force production. 3. In slow tracking ramp contractions, the instantaneous frequency of single motor units was initially rather low (5-15/sec) and it increased as the ramp force augmented. By contrast, in (strong) ballistic contractions, the same units discharged at an unusually high instantaneous frequency (60-120/sec) early in the burst and the firing frequency decreased thereafter. Such hitherto unknown pattern appears characteristic of ballistic contractions and it was not found in even fast tracking ramp contractions achieving 12 kg in only 0-4 sec. 4. The potentials of the different motor units activated are rather crowded at intervals of a few msec in the early burst of a strong ballistic contraction and observations on the rank activation of the different motor units do not provide reliable data for the analysis of the recruitment order of units in ballistic contractions. 5. A new method is described for estimating ballistic force threshold of single motor units. When a large series of brisk ballistic contractions with peak forces ranging from 0-05 to 12 kg was carried out any given motor unit only became active when the ballistic peak force exceeded a certain reproducible value. A detailed analysis of the recruitment order based on these ballistic force thresholds showed it to be virtually identical to the recruitment order of the same units in slow tracking ramp contractions (correlation=0-95). 6. Ballistic contractions are graded in force both by the recruitment of additional motor units in stronger contractions, and by an increase in their rate of firing. These gradation mechanisms are discussed.