Localization of vertex lesions seen on CT scan. A simple method is presented for localizing the anatomical site of vertex lesions seen on a computerized tomography (CT) brain scan, using the patient's plain lateral skull film.


Angiotomography of intacranial aneurysms. Analysis by a new method of angioautotomography. The authors have developed a new method of angioautotomography by the use of a special head-swing apparatus. They have studied 70 intracranial aneurysms by this method and have found that it was more useful in clearly detecting the stalk of aneurysms than conventional angiography. The authors conclude that the method is also superior to conventional magnification angiography. Magnification angiotomography performed by this method offers more precise details.


Quantitative assessment of ventilation-perfusion mismatch by radioxenon imaging of the lung. By the use of xenon-133 and a scintillation camera with digital data storage and processing system, a topographic relationship between ventilation distribution (V) and perfusion distribution (Q) was examined quantitatively in two groups of normal nonsmokers and one of older smokers, all healthy. In addition, subjects with a variety of cardiopulmonary disease were tested. The fractional regional ventilation (VR) and regional perfusion (QR) were plotted against the V/Q ratio on a logarithmic abscissa for the normal subjects; both were distributed log-normally with a narrow standard deviation, and were dissociated slightly from each other. However, with smoking and with increasing age, the s.d. and the dissociation became wider, suggesting an impairment of gas exchange as estimated by alveolar-atrial gas-pressure differences (A-aD), which were calculated by putting these topographic relationships into a gas-exchange program in a computer. In various cardiopulmonary diseases a good correlation was found between the estimated A-aDO2 thus obtained and the actual A-aDO2 derived from analysis of the blood gases.


Ultrasonography of the testis--correlation with radiotracer perfusion. Ultrasonic study of testicular disease and paratesticular masses was carried out in 20 cases. In eight of these, comparison was made with pertechnetate perfusion studies performed concurrently. Testicular torsion was well revealed by both techniques. Acute orchitis, in the early stages, was shown more clearly by radiotracer, unless there was associated epididymal swelling or hydrocele. Chronic complications of inflammation, particularly abscess formation, were seen best by ultrasonography. Paratesticular masses could be studied only by ultrasound. These included both solid and cystic masses due to chronic epididymitis.


Indium-111-labeled autologous platelets for location of vascular thrombi in humans. Twenty-two patients suspected of having either venous or arterial thrombi were studied with In-111-labeled autologous platelets. Whole-body scans were performed 3, 24, and 48 hr following i.v. injection. Twelve patients studied with saline-washed platelets had unsatisfactory 15-min recovery and biologic half-time. When the labeling was carried out in plasma, these values compared favorably with normal values reported for Cr-51-labeled autologous platelets. Of ten patients studied using platelets labeled in plasma, three had normal scans, six had abnormal scans, and one had an equivocal scan. All six abnormal scans were confirmed with corresponding positive findings in either the venogram, arteriogram, or lung scan. J Nucl Med 19: 626-634, 1978.


ECAT: a new computerized tomographic imaging system for positron-emitting radiopharmaceuticals. The ECAT was designed and developed as a positron imaging system capable of providing high contrast, high resolution, quantitative images in two-dimensional (2-D) and tomographic formats. The flexibility in its variety of imaging problems. High (HR), medium (MR), and low (LR) tomographic resolutions are 0.95 +/- 0.1, 1.3 +/- 0.1, and 1.7 +/- 0.1 cm FWHM; high, medium, and low resolutions in 2-D images are 0.85 +/- 0.1, 1.3 +/- 0.1 and 1.7 +/- 0.1, depending on resolution mode employed. ECT system efficiency is 30,100, 15,900, and 9,200 c/sec/muCi/cc with a 20-cm diameter phantom at LR, MR, and HR. Because of the geometric, detector, electronic and shielding design of the system, count-rate capability and linearity are high, with minimum detection of scattered radiation and random coincidence. Measured error agrees well with theoretical statistical predictions down to a level of 1.4% standard deviation. The redundant sampling scheme of this system significantly reduces errors caused by motion and detector instability. Scan times are variable from 10 sec to several min/slice and multiple levels are automatically performed by computer control of patient bed. A variety of human studies illustrate image quality, resolution, and efficiency of both ECT and 2-D imaging mode. Examples of the noninvasive study method have been made possible through development of ECT.


A new method of multiplanar emission tomography using a seven pinhole collimator and an Anger scintillation camera. A new method of multiplanar emission tomography is described; it uses a wide-field Anger scintillation camera (37.5 cm crystal diameter) and a seven-pinhole collimator. The pinholes (5.5 mm) acquire data simultaneously from the emissing source and project the data onto seven independent regions of the camera crystal. Multiple planes are reconstructed from the initial seven-view data acquisition through the use of a computerized addition-multiplication algorithm and variation of the superposition relationships among the projected views. These planes are then altered iteratively by a least-error criterion following ray-sum comparison with the original views. Planar resolution (full-width-half-maximum) is 1.0 cm and depth resolution is 1.5 cm. In 42 patients with angiographically demonstrated coronary-artery disease, studies of myocardial Tl-201 perfusion, under exercise, have shown improved detection sensitivity in comparison with scintigraphy using parallel-hole collimation.


Clinical evaluation of Tc-99m-diethyl-IDA in hepatobiliary disorders. N,alpha(2,6-diethylacetanilide)-iminodiacetic acid is a new Tc-99m-labeled radiopharmaceutical primarily excreted through the biliary tract. Its high concentration in the bile allows the imaging of the biliary tree and the gallbladder. Scintigraphic studies were performed in 20 normal subjects and 42 patients suffering from various hepatobiliary disturbances. In normal subjects, the early liver uptake was followed by the accumulation of the tracer in the intrahepatic bile ducts and the gallbladder before its discharge into the duodenum. In cases of hepatocellar damage, the hepatic accumulation of the tracer was clearly depressed. Any acute or subacute disorder of the gallbladder was clearly demonstrated by Tc-99m-diethyl-IDA. In cases of asymptomatic cholelithiasis, we observed delayed visualization of the gallbladder associated with its decreased accumulation of the tracer. The intrahepatic bile ducts were distended in cases of incomplete obstruction of the hepatobiliary ducts, whereas they were never visualized when there was severe hepatocellular damage or complete obstruction of the biliary tree.


Kinetics of the human thyroid trap: a compartmental model. Thyroidal pertechnetate was measured continuously in normal subjects for 40 min after i.v. injection, using a multicrystal camera. Digital counts (1-min increments) were read directly from the magnetic tape and summed for the thyroid area and for adjacent neck background. The net thyroidal data were used as the basis for development of a compartmental model of the thyroidal trap, using the SAAM program. Input to the trap in the model is plasma pertechnetate radioactivity, measured frequently during the study and fitted to a multiexponential equation. Best fit of the thyroid data was achieved with a model in which the trap is described by two compartments, a fast ("follicular cell") compartment and a slower ("colloid") compartment. Iodide blockade, administered either during the study or 1 hr before its initiation, rapidly blocked the trap at the point of input from plasma into the follicular cells. Iodide did not affect the other parameters of the model.


Clinical comparison of cardiac blood pool visualization with technetium-99m red blood cells labeled in vivo and with technetium-99m human serum albumin. Technetium-99m red blood cells (Tc-RBC) labeled by an in vivo technique were compared with two preparations of Tc-99m human serum albumin (HSA) for cardiac blood-pool imaging. Relative distribution of the tracers was analyzed on end-diastolic frames of gated blood-pool studies and on whole-body (head to mid-thigh) anterior pinhole images. The Tc-RBC demonstrated greater relative percentage localization in the cardiac blood pool, higher target-to-background ratios in the left ventricle, and less liver concentration. For cardiac blood-pool imaging, Tc-RBC labeled by the in vivo approach appears to be superior to the two Tc-HSA preparations studied.


Tc-99m human serum albumin: a suitable agent for plasma volume measurements in man. In 16 patients we have carried out simultaneous plasma-volume measurements with human serum albumins tagged with Tc-99m (Tc-99m HSA) and I-131 (I-131 HSA). The correlation coefficient was 0.987. Tc-99m HSA, prepared from kits that predictably yield high labeling efficiency (and thereby negligible amounts of TCO4-), is clearly a superior agent for repeat plasma volume determinations, because of its shorter half-life and the reduced radiation dose to the subject.


Technetium-labeled heparin: preliminary report of a new radiopharmaceutical with potential for imaging damaged coronary arteries and myocardium. Heparin has been labeled with [99mTc] pertechnetate and its ability to image damaged coronary vessels and myocardium during and following myocardial ischemia has been studied in experimental animals. The data obtained indicate that Tc-99m heparin localizes in damaged myocardium and coronary vessels in canine models of temporary myocardial ischemia and reperfusion and in damaged myocardium during fixed coronary occlusion. Scintigraphic detection of damaged myocardium was possible in both models, but the highest levels of Tc-99m heparin in damaged myocardial tissue were found in those dogs with temporary coronary occlusion and reflow. The data suggest that Tc-99m heparin may be of value as a positive imaging agent when coronary arteries or myocardium are injured and either reperfusion is allowed and/or significant blood flow persists in the damaged area.


Chemical and biological characterization of different Tc complexes of cysteine and cysteine derivatives. The labeling of cysteine and its derivatives (penicillamine, N-acetylcysteine, cysteine ethyl ester) with 99Tc (99mTc) was studied as a model for the radiopharmaceutical preparation of Tc-99m mercaptide complexes. After the use of TcO4-, TcOCl52-, and TcBr62- as labeling agents for the Tc oxidation states VII, V, and IV, respectively, complexes of Tc(V) and Tc(IV) were prepared and characterized. The biologic behavior of these complexes was studied in rats. The substitutions in cysteine are responsible for substantial changes of net charge and lipophilicity in the Tc complexes, and the consequences on the excretion patterns in Wistar rats are discussed.


A new approach to the smoothing of dynamic nuclear medicine data: concise communication. A weighted three-dimensional digital filter that smooths data in both space and time has been developed for use with dynamic nuclear medicine studies. This smoothing algorithm allows a large improvement in signal-to-noise ratio without unacceptable degradation of spatial and temporal resolution. The initial results of using this smoothing algorithm suggests that it is superior to a standard nine-point smoothing function used on dynamic data. This is particularly encouraging since the parameters of the digital filter have not been optimized. The quality of the processed digital images is at least equivalent to that of analog images, and the digital images may be of more diagnostic value. The new algorithm also appears useful in preparing dynamic dynamic data for other manipulations such as the creation of parametric images or the extraction of quantitative measurements.


Bone scan in dental diseases.

Bone scan in dental diseases. Bone images of the jaws and related dental structures were obtained in 25 patients undergoing skeletal surveys. The upper and lower jaws were divided into eight quadrants to facilitate comparisons between scintigraphic image findings and the results of dental examination. Fourteen of these 25 patients had at least one jaw quadrant with a positive image. The areas of positive uptake correlated well with dental examination findings, which included healing extraction sites and common dental diseases, such as pulpal and periodontal infections and irritations from ill-fitting dentures. The potential usefulness of bone imaging as an adjunct in dental diagnosis is discussed.


Iodine heterocycles: [125I] and [131I] ortho-iodosophenylphosphoric acid. Since organic molecules tagged with radioiodine are often subject to dehalogenation, techniques are needed for "protecting" the iodine. A suggested approach was the incorporation of iodine directly into a heterocyclic compound as one of the ring's heteroatoms. Such a compound, orthoiodosophenylphosphoric acid, was synthesized with I-125 and I-131. Upon i.v. administration to dogs and rabbits, most of the radiolabel was excreted in the urine. There was no evidence of the appearance of free iodide. The renal elimination of orthoiodosophenylphosphoric acid was contrasted with the biliary excretion of another iodine heterocycle, diphenyleneiodonium. Iodine heterocycles, with appropriate substituents, may represent a useful class of compounds for biologic studies.


Cassette videotape recording of computer images. Direct videotape recording of images from computer display terminals is often not possible because of the nonstandard outputs of these systems. A video-sync mixer is described that permits black-and-white recording on standard 3/4-in. videotape cassettes.


Semi-automated T3 uptake test that uses magnetic albumin microparticles. We describe a T3 uptake test that uses magnetic albumin microparticles to separate free from bound [125I] T3. The test uses 0.1 ml serum in a total assay volume of 1.1 ml, and is performed in barbital buffer of pH 7.6, ionic strength 0.2. The accuracy of the test is not affected by the following ranges: volume, 1-3 ml; incubation time, 15-120 min; and incubation temperature, 4-35 degrees C. We describe a magnetic separator device that allows simultaneous handling of 100 assay tubes with minimum manipulation. The intra-assay and interassay coefficients of variance were 2.87% and 5.20%, respectively.


Factors affecting methionine toxicity and its alleviation in the chick. Young male crossbred chicks were fed crystalline amino acid diets containing excess L-methionine or DL-homocysteine to evaluate factors causing methionine toxicity. Chicks were fed diets containing graded levels of excess methionine from 0% to 2.0%. Rate of gain was reduced at all levels of excess methionine, but the magnitude of depression was greater between 1% and 2% than between 0% and 1% excess methionine. Methionine accumulated in plasma of birds fed excess methionine, but plasma levels of homocysteine, cystathionine and cystine remained essentially unchanged. Spleen iron levels increased linearly and blood hemoglobin decreased linearly when chicks were fed diets containing greater than 1% excess methionine, a level equivalent to about 3 times the chicks' requirement. Chicks fed 1.36% homocysteine had reduced gain and gain:feed values, but spleen iron and hemoglobin levels were unchanged. 3-Methylthiopropionate, a possible metabolite in a proposed alternate pathway, caused a precipitous increase in spleen iron levels. Various methyl sources (betaine, choline, methyl acetate) when fed in excess failed to increase spleen iron levels. Methyl mercaptan and methyl mercaptoacetate likewise did not result in an increase in spleen iron deposition. Both the hemosiderosis condition and the reduced food utilization caused by excess methionine were reversed by supplemental glycine plus threonine.


Circadian rhythms of urea formation and argininosuccinate synthetase activity in rat liver. The circadian rhythms of the urea concentrations in urine, serum, and liver and their generation mechanism were investigated. When rats were allowed to eat freely, the urea concentration and the total urea content of the urine were higher during the night than during the day-time. Consistent with these findings, the urea concentrations in the liver and serum had circadian rhythms with the highest values at 0200 hours and the lowest values at 1400 hours. The amplitude of the rhythm increased with increase in the dietary protein (casein) content. Of the five urea cycle enzymes in the liver, only argininosuccinate synthetase showed fluctuation in activity, and this had the same pattern as the circadian rhythms of urea concentrations. These findings suggest that the circadian rhythm of argininosuccinate synthetase in the liver might be directly responsible for the rhythms of change in urea concentrations in the liver, blood and urine. The circadian increase in enzyme activity was inhibited by cycloheximide, but not by actinomycin D.


Effect of dietary amino acids on jejunal sucrase and leucineaminopeptidase activities in rats. The effect of dietary amino acids on jejunal sucrase (EC 3.2.1.26) and leucineaminopeptidase (EC 3.4.11.1, LAPase) activities in rats was studied. Rats were force-fed a 10% complete amino acid diet or valine-free diet. The sucrase and LAPase activities in rats force-fed the valine-free diet for 2 days were significantly lower than those in rats force-fed the complete amino acid diet, although the specific activities of these enzymes in the isolated brush border fragment were 10 times higher than those in the mucosa, and most of the activities of these enzymes in the mucosa were localized in the isolated brush border fragment. Results of experiments undertaken to investigate the effects of dietary amino acids during the initial period after the dietary alteration on the sucrase and LAPase activities showed that decreases in the activities of these enzymes in rats force-fed the valine-free diet appeared by 26 hours after the first feed administration; whereas, incorporation of dietary 14C-amino acids administered in the first feed administration into the mucosal protein was significantly lower in rats receiving the valine-free diet than in rats receiving the complete amino acid diet by 7 hours following the first feed administration. These results suggest that decreases in availability of dietary amino acids in the valine-free diet for protein formation in the small intestinal mucosa during the initial period caused the decreases in the sucrase and LAPase activities localized in the brush border membrane.


The toxic level of sodium selenite in the diet of laying chickens. Female chickens were fed graded levels of sodium selenite to determine at what level a selenium toxicity occurred. In the first experiment a basal diet was supplemented with 0, 0.1, 1.0, 3.0, and 5.0 ppm of selenium. These levels had no effect on egg production, egg weight or fertility of the eggs. Hatchability of fertile eggs was significantly decreased by 5 ppm of dietary selenium. In the second experiment a basal diet was supplemented with 0, 5.0, 7.0, and 9.0 ppm of selenium. Egg weight and hatchability were significantly decreased by 7 and 9 ppm, and egg production was decreased by 9 ppm of selenium in the diet. When selenite was added to the diet, there was a lag of 2 to 3 weeks before the selenium content of the egg reflected the content of the diet. As long as the selenium content of the diet remained the same, egg selenium remained the same. When selenium was no longer supplemented, egg selenium content decreased. Two weeks after cessation of selenite supplementation, egg selenium was markedly reduced. Four weeks after cessation of selenite supplementation, egg selenium levels approached those of birds fed a basal diet continuously.


Influence of a liquid diet and meal pattern on body weight and body fat in rats. Rats weighing 110 to 150 g or 250 g initially were utilized in five experiments to determine the effect of the form of the diet (dry versus liquid) and the pattern of feeding (meal-feeding, force-feeding, nibbling, or ad libitum) on body weight gain and on body fat. A high-carbohydrate, 20% casein or 20% lactalbumin diet was fed for 4 to 8 weeks. Consumption of a diet mixed with an equal weight of water increased weight gain in one of three experiments. Body fat content of the rats was not influenced by addition of water to the diet. Neither force-feeding nor meal-feeding influenced body fat gain provided the respective control rats were pair-fed during the initial adaptation period. Likewise, when rats were pair force-fed to ad libitum fed rats without an initial adaptation meal frequency did not influence body fat gain. When meal-fed rats were switched to ad libitum intake their food intake increased to equal that of rats which had been continuously fed ad libitum; however, the rats which had been switched gained more body fat than did rats continuously fed ad libitum. These results suggest that meal frequency may have a minimal influence on body fat accumulation, but that a shift to a higher level of food intake may cause an increased food efficiency and greater rate of fat deposition than in rats continuously fed the higher level of intake.


Pathology of the vitamin C deficiency syndrome in channel catfish (Ictalurus punctatus). Channel catfish fingerlings fed purified diets devoid of vitamin C showed reduced growth rate, deformed spinal columns, external and internal hemorrhages, erosion of fins, dark skin color and reduced bone collagen content after 8 to 12 weeks, whereas fish fed a diet containing 30 mg/kg of vitamin C had none of these anomalies after 22 weeks. A dietary level of 30 mg of vitamin C per kg was insufficient to prevent distortion of gill filament cartilage, although 60 mg of vitamin C per kg was sufficient. Vertebral collagen percentages of 25 or below and liver ascorbic acid levels of 30 microgram/g or below appeared to be indicative of vitamin C deficiency in channel catfish fingerlings. Epidermis and dermis were almost completely healed and extensive collagen fiber formation had commenced in the somatic muscle, in experimentally inflicted wounds after 10 days in fish fed the vitamin C-free diet. Skin and muscle at the wound site were almost regenerated to normal after 10 days in fish fed 60 mg of vitamin C per kg of diet.


Body collagen nitrogen in protein-deficient adult rats. Four groups of 10 young adult male rats of the Wistar strain were fed on a protein-free diet ad libitium for periods of 7, 28, 56, and 84 days. Control groups were fed a purified 20% casein diet. Food intake and body weights of rats were measured. Hemoglobin and plasma protein levels, weight, total nitrogen, and collagen nitrogen of skin, carcass, muscle, and liver were determined. Protein-deficient rats lost body weight and had low plasma protein concentrations, but hemoglobin levels remained normal until day 56 of deficiency. The liver lost weight and nitrogen more rapidly than the other organs; the severity of nitrogen depletion in the organs increased with time fed the protein-deficient diet. When protein deficiency was severe, collagen nitrogen concentration increased in organs and carcass. This was not due to an actual increase of collagen nitrogen content; comparisons among malnourished groups showed that the total amount of collagen nitrogen in carcass, liver, and muscle was maintained and that the amount in skin diminished as periods of protein deprivation increased. In control rats, results indicated that the amount of collagen nitrogen in skin, muscle, and carcass increased during growth. These results indicate that protein restriction in adult rats affects collagen metabolism, with skin collagen being more markedly affected than that of other tissues.


Oxalic acid metabolism in the rat.

Oxalic acid metabolism in the rat. Feeding experiments indicated that approximately 15% of dietary oxalate is adsorbed in the rat intestine and that dietary oxalate accounts for about one third of the oxalic acid normally excreted in rat urine. Oxalate excretion increased by about 40% when a low calcium diet was fed, decreased by 65% when a low protein diet was fed and increased by 100% when a high protein diet was fed. Fasting for 24 hours resulted in a fall in calcium excretion but phosphate and creatinine excretion increased. Oxalate excretion also tended to increase. Between 60% and 70% of activity was recovered in the urine, faeces and body tissues after 14C-oxalic acid had been administered intraperitoneally. Recoveries of 14C-labeled compounds as urinary 14C-oxalic acid decreased in the following order: glyoxylic acid greater than ascorbic acid greater than citric acid greater than glycollic acid greater than tryptophan greater than hydroxyproline greater than glycine. It is suggested that conversion of citrate to oxalate in the rat may occur via the "glyoxylate cycle." It is concluded that a higher proportion of dietary oxalate is absorbed in the rat intestine compared with man, and that dietary oxalate accounts for a higher proportion of urinary oxalate in the rat than in man. Intestinal secretion and bacterial degradation of oxalate also appear to be proportionately greater in the rat than in man.


Dietary fat and cholesterol metabolism in adult rats undergoing rapid tissue repletion. An experimental model in which adult rats underwent rapid rates of tissue repletion after dietary restriction served to explore the influence of dietary fat on cholesterol metabolism. Adult rats severely restricted in protein and energy were refed either 8 or 24 hours per day for 10 days. Refeeding diets contained approximately 0% or 20% fat by weight as safflower oil or beef tallow and 4% or 17% protein on an energy basis. Concentration or source of dietary fat did not significantly influence either serum or hepatic cholesterol concentrations. Inclusion of dietary fat increased incorporation of 3H-acetate into digitonin precipitable sterols although type of fat did not influence this parameter. Specific activities of serum and hepatic cholesterol were identical for rats fed with diets containing safflower oil and beef tallow, but an elevation in acidic 14C-steroid excretion per g diet consumed occurred with safflower oil as compared with beef tallow. The data suggest that, in the absence of exogenous cholesterol, high levels of polyunsaturated fat may influence cholesterol metabolism primarily by increasing synthesis and excretion of bile acids.


The branched-chain amino acid antagonism in chicks. The effects of dietary supplements of branched-chain amino acids on growth, food consumption and metabolism in chicks were investigated. When an adequate diet contained 1.20, 1.60, 2.25, 3.75, or 5.00% leucine, increasing leucine content caused reduced food consumption and weight gains, coupled with impaired efficiency of food utilization. When the diet deficient in branched-chain amino acids contained 0.98, 1.46, 2.25, 3.75, or 5.00% leucine, increasing leucine resulted in increased food consumption and reduced efficiency of food utilization when levels of leucine up to 3.75% were fed. Excess leucine depressed plasma concentrations of isoleucine and valine. Excesses of isoleucine or valine caused smaller depressions of concentrations of the other two branched-chain amino acids. All these effects were seen during the first 8 days of experiment, after which they diminished or disappeared. Muscle branched-chain amino acid aminotransferase (BCAT) (L-leucine:2-oxoglutarate aminotransferase, EC 2.6.1.6) activity was increased in chicks fed excess leucine but not in those fed excess isoleucine or valine. Hepatic alpha-ketoisocaproic dehydrogenase (KADH) (2-oxoisocaproate:lipoate oxidoreductase, EC 1.2.4.3) activity and muscle polyribosomal aggregation were unaffected by diet. When chicks were fed diets containing either 0.98 or 2.25% leucine, production of 14CO2 from [1-14C]isoleucine and [1-14C]valine was increased in chicks fed the higher level of leucine. The increase was small in both cases, representing approximately 2% of consumed isoleucine and valine. Increased production of 14CO2 was observed within 12 hours of feeding excess leucine; however, BCAT increased only after 2 to 4 days. No differences were seen in excreted 14C or in the relative distribution of 14C along the small intestine. We conclude that the chick is able to adapt in part to excesses of dietary leucine and that the branched-chain amino acid antagonism may involve increased catabolism of the limiting branched-chain amino acids.


The neurotoxicity of valine deficiency in rats. When valine, an essential amino acid, was withdrawn from the diet of weanling rats, the animals rapidly developed a unique pattern of neurological symptoms characterized by head retraction, staggering and aimless circling. At necropsy degenerative changes were most prominent in the neurons of the red nuclei, brain stem structures which modulate motor function. To explore the pathogenesis of the neurotoxicity associated with valine deficiency, we fed rats purified diets deficient in valine alone or in valine plus other branched chain and neutral amino acids, and we examined brain tissues by light microscopy. Motor disfunction and red nuclei damage occurred only in rats fed diets lacking valine alone and not in rats fed diets lacking all three branched chain amino acids. These results suggest that the neurotoxicity of valine deficiency results from amino acid imbalance rather than from lack of dietary valine per se.


Vitamin B-6 activity for rats of epsilon-pyridoxyllysine bound to dietary protein. The biological activity of protein bound epsilon-pyridoxyllysine residues in a phosphopyridoxyl-bovine serum albumin (PP-BSA) preparation was evaluated. Previous studies have demonstrated that pyridoxal phosphate may bind to food proteins as epsilon-pyridoxyllysine complexes during processing and storage. The present research, employing PP-BSA as a model, was initiated to determine the nutritional consequences of epsilon-pyridoxyllysine formation in foods. The concentration of epsilon-pyridoxyllysine residues in the PP-BSA was determined spectrophotometrically and chromatographically. Rat bioassay of the PP-BSA revealed that epsilon-pyridoxyllysine exhibited 60% activity relative to the molar potency of pyridoxine. These results suggest the partial release of bound vitamin B-6 possibly by in vivo enzymatic hydrolysis of epsilon-pyridoxyllysine. The presence of PP-BSA in a test diet containing 0.25 microgram added pyridoxine per g of diet inhibited the utilization of approximately half of the free pyridoxine by the rats. It is postulated that the observed inhibition resulted from an antivitamin B-6 effect of intact epsilon-pyridoxyllysine. This effect requires further investigation.


Effects of penicillamine on distribution of B6 vitamens in rat urine. The antivitamin B6 effect of DL- and D-penicillamine has been studied in rats. A considerable elevation in the urinary excretion of vitamin B6 activity (pyridoxal and its thiazolidine derivative) has been shown as a parameter of B6 antagonism. Both DL- and D-pencillamine have been shown to have an antivitamin B6 effect in rats, although that induced by the DL-form is considerably greater, as would be expected from previous studies. We suggest that B6 supplementation should be included in any long term penicillamine therapy, regardless of the isomer that is employed.


Role of lipids in stabilizing red cells in rats. The causes of osmotic fragility of red cells were studied in rats. Osmotic fragility of red cells in vivo changed after removal of the spleen or induction of experimental splenomegaly by repeated intraperitoneal injections of methyl cellulose (MC): in splenectomized rats, the red cells showed reduced osmotic fragility and an increase in diameter as well as in contents of phospholipids and cholesterol. Conversely in rats with splenomegaly, the cells showed increased osmotic fragility and a decrease in diameter and in lipid contents. Results confirmed that increase in the phospholipid content resulted in decreased fragility and that increase in the cholesterol content brought about decreased spherocytosis. The activity of lecithin cholesterol acyltransferase (LCAT) in the plasma varied inversely with the cholesterol content of the red cells. The above results show that the fragility of red cells is influenced by their lipid content and shape, and that LCAT activity in the plasma influences the membrane content of cholesterol and spherocytosis.


Effects of exogenous retinol and retinoic acid on the biosynthesis of 14C-mannose labelled glycolipids and glycoproteins in rat liver. Studies were conducted to investigate the in vivo and in vitro effects of retinol and retinoic acid on the synthesis of mannolipids and mannopeptides in rat liver. The incorporation of 14C-mannose into glycolipids and glycoproteins showed a decrease in vitamin A-depleted rats as compared with vitamin A-fed rats. By means of DEAE-cellulose, silicic acid and thin-layer chromatography, the mannose-containing lipids were separated into mannosyl retinyl phosphate (MRP, Rf 0.2) and dolichyl mannosyl phosphate (DMP, Rf 0.4), respectively. A rapid increase in the synthesis of labelled MRP was observed, exhibiting a peak between 25 and 60 min after intraperitoneal administration of retinol to vitamin A-depleted rats. Similarly, administration of retinoic acid brought about elevation of 14C-mannolipid (Rf 0.2) synthesis with a peak at 60 min after injection. On the other hand, the incorporation of 14C-mannose into DMP (Rf 0.4) remained unchanged by such treatment. In vitro addition of retinyl phosphate, but not retinoyl phosphate, markedly stimulated the synthesis of 14C-mannolipid (Rf 0.2), using crude membrane of rat liver and GDP-14C-mannose as the donor. These findings strongly suggest that not only retinol but also retinoic acid plays an important biological role in mannosyl transfer reaction in rat liver. However, the molecular participation of a metabolite of retinoic acid in the formation of a mannolipid and the structure of such a metabolite remain to be established.


Light propagation in twisted anisotropic media: application to photoreceptors. The propagation of light through a slowly twisting anisotropic medium is described by a coupled-mode theory; expressions are derived for the electric field for the case of a birefringent dichroic medium with a constant rate of twist. The method provides a simple and intuitive means for determing the effect of twisting on the linear birefringence and dichroic absorption of the medium, particularly when the light is initially linearly polarized. The theory is well suited to the analysis of light absorption in twisting insect photoreceptors, such as found in bees and ants. We provide full expressions and useful approximations for polarization sensitivity and the initial direction of polarization to give maximum absorption for several types of photoreceptors.


Effect of chromatic uncertainty on detectability of a visual stimulus. The detectability of a brief color shift towards red or towards green of a foveally viewed yellow target is less by 25% if the observer is uncertain as to the direction of the color shift. This result matches a prediction of the theory of signal detectability: When signal parameters become uncertain, detectability declines.


1-deamino-8-D-arginine vasopressin in the treatment of central diabetes insipidus in childhood. The effectiveness of therapy with carbamazepine and clofibrate (oral therapy), intramuscular pitressin-in-oil, and intranasal 1-deamino-8-D-arginine vasopressin has been compared in 15 children with partial or complete central diabetes insipidus. Mean daily urine volume without therapy was 5.4 l and dropped to 1.1 and 1.6 l/day while receiving pitressin and DDAVP, respectively. Oral agents decreased the daily urine volume to 2.2 l in patients with partial DI, with good symptomatic control except for some nocturia. These agents had no effect in patients with complete DI and did not alter pitressin requirements. Duration of pitressin action was 24 to 36 hours with a significant incidence of hyponatremia. The duration of DDAVP effect was 8 to 20 hours, varying in individual patients. Children with partial DI required smaller doses of DDAVP and the duration of action was longer than in those with complete DI. Control of serum electrolytes was excellent using two doses per day and nocturia was eliminated. All patients who had received pitressin had growth hormone antibodies, but continued to grow normally unless there was pre-existing growth hormone deficiency. These antibodies gradually disappeared after approximately one year of therapy with oral agents or DDAVP. DDAVP did not alter growth hormone, cortisol, or prolactin levels during sleep. DDAVP is the antidiuretic therapy of choice in children with either complete or partial DI; to date, no side effects have been demonstrated.


Paroxysmal supraventricular tachycardia during theophylline therapy in a premature infant. An episode of supraventricular tachycardia occurred in an infant born at 31 weeks' gestation after three days of therapy with theophylline 3.5 mg/kg every six hours. The infant had a plasma theophylline half-life of 24.7 hours and a low plasma theophylline clearance of 12.7 ml/kg/hour. The plasma theophylline concentration at the time of the arrhythmia was about 42 mg/l. The extent of drug accumulation with these kinetic characteristics is emphasized. Serious adverse effects due to theophylline may occur with few signs of symptoms of impending toxicity. Plasma theophylline concentration measurements are valuable in avoiding such toxicity.


Hyperthermia as a possible teratogenic agent. Hyperthermia has been shown to be a teratogenic agent in a number of animal species. We have attempted to determine if maternal hyperthermia during early gestation might also be responsible for problems in human development. Eight retrospectively ascertained cases, in which high fever had occurred at four to six weeks' gestation, revealed a similar clinical phenotype in the infants despite the fact that the maternal fever was caused by different infections. The most consistent manifestations were severe mental deficiency, seizures, hypotonia, microphthalmia, midface hypoplasia, and mild impairment of distal limb development. In five patients exposed to hyperthermia at seven to 16 weeks' gestation, predominant features were hypotonia, neurogenic arthrogryposis, and central nervous system dysgenesis. The cause of fever differed in each of these cases; in one, a patient with neurogenic arthrogryposis, the hyperthermia had been induced in a sauna bath. No apparent serious problem in morphogenesis was found following hyperthermia during the latter half of gestation. These findings are similar to those resulting from induced hyperthermia in animals. Further research on the effects of hyperthermia in the developing human being seems warranted.


Demographic factors in the epidemiology of hemophilus influenzae meningitis in young children. To determine the effect of various demographic factors on the incidence of Hemophilus influenzae, type b meningitis, Rhode Island residents with H. influenzae in 1970-1974 were identified by review of data from the State Department of Health, a private health care research organization, death certificates, and hospital bacteriology laboratories. Of the 108 cases of H. influenzae, 99 (92%) occurred in children under five years of age. The disease incidence among black children under five (103.6/100,000/annum) was significantly (P less than 0.0005) higher than that among white children (23.9/100,000/annum). By eliminating the 29 of 185 census tracts in which the total population was greater than 5% black, disease incidence was studied in a virtually monoracial population. In these white census tracts, in which the population was 99.2% white, the occurrence of H. influenzae was not related to family income, education, number of household members, population density, or rate of hospitalization. These findings confirm the increased incidence of H. influenzae in blacks and indicate that socioeconomic factors do not affect the incidence of the disease in white children.


Brain biopsies for neurodegenerative disease in children. Brain biopsies for neurodegenerative disease performed at The Hospital for Sick Children, Toronto, over a 12-year period (1964 to 1976) were reviewed. Of 64 biopsies, major histologic abnormalities with diagnostic or prognostic significance comprised 39% of the total cases, minor abnormalities represented 13%, and 48% appeared normal. The procedure failed to provide prognostic assistance in 41%. With the advent for newer diagnostic techniques (enzyme assays and muscle, skin, peripheral nerve, rectal, and appendix biopsies) for neurodegenerative disease in childhood, a much lower yield is noted (15 to 20%). Only two progressive degenerative childhood conditions remain in which cerebral tissue is necessary for diagnosis--Alexander disease and Canavan spongy degeneration.


Idiopathic hypercalciuria in children: prevalence and metabolic characteristics. A group of 273 children with minor complaints was screened for idiopathic hypercalciuria by measurement of the urine Ca/Cr. Borderline or definitely high levels were noted in 17 of these children, 11 of whom were boys. More intensive metabolic studies were completed on four of these children and on three children who were noted to have symptomatic renal stones associated with idiopathic hypercalciuria. These studies suggest that IH, well recognized in adults, may have its origins in childhood and that appropriate management, if initiated in childhood, may have significant long-term benefits.


Uric acid excretion in normal children.

Uric acid excretion in normal children. Standard values were established for urinary excretion and clearance of uric acid in 95 normal, nonhospitalized children. We found that urinary uric acid excretion and serum uric values increase throughout childhood; that in early childhood, fractional excretion and clearance of uric acid are higher than adult norms; and that despite an increasing filtered load of uric acid, there is a progressive decrease in fractional excretion and clearance of uric acid with advancing age. Some tubular maturational change, either decreasing secretion or increasing reabsorption, must account for the progressive decline in fractional excretion and clearance of uric acid.


Diphenylhydantoin interstitial nephritis. Roles of cellular and humoral immunologic injury. A child with diphenylhydantoin hypersensitivity developed an associated interstitial nephritis. Circulating autoantibody of the IgG class which reacted with normal human tubular basement membrane was linearly deposited along host renal TBM. Cell-mediated immunity to the DPH antigen was also present. In addition, deposits of DPH were demonstrated along the renal TBM. It is suggested that initial alteration of host renal TBM by DPH deposition with secondary immune injury directed at the DPH-TBM antigen may have altered the TBM or uncovered new antigenic sites, rendering it susceptible to further injury on an autoimmune basis.


Anemia in patients with juvenile rheumatoid arthritis. Patients with juvenile rheumatoid arthritis may have an anemia attributable to the chronic disease, to iron deficiency, or to a combination of the two. The contribution of iron deficiency is often difficult to determine by routine laboratory studies. We studied 51 patients with pauciarticular and polyarticular juvenile rheumatoid arthritis with red blood cell counts, indices, free erythrocyte protoporphyrin, and serum ferritin. Fifteen of the 18 who were anemic were restudied after a 3 to 6-month period of iron therapy. Thirteen of the 15 responded by these criteria: a rise in hemoglobin of 1.0 gm/dl or more and an increase in mean corpuscular volume of 3 fl or more; in 11 of these 13, hemoglobin values returned to the normal range for age. These findings indicate that iron deficiency can be a major component of the anemia that is commonly found in patients with active juvenile rheumatoid arthritis.


Sphygmomanometry in the pediatric patient. The indirect measurement of blood pressure in the pediatric population is often difficult or impossible to perform and when values are obtained, they are often unreliable or inaccurate. An accurate measurement of arterial systolic pressure in the upper extremity is obtainable with a properly designed and sized occluding cuff and an ultrasonic device to detect the first Korotoff sound. For the detection of the first Korotkoff sound ultrasonic Doppler devices are superior to the stethoscope. When wider occluding cuffs than usual are applied to the upper extremity, the error of measurement is minimized. A method for accurately measuring end diastolic pressure has yet to be described despite assertions to the contrary.


Pulmonary physiotherapy in neonates: physiologic changes and respiratory management. To investigate physiologic alterations in respiratory function associated with chest physiotherapy, arterial blood gases, respiratory patterns, lung mechanics, and functional residual capacity were measured in 13 neonates (weights 1.25 to 3.20 kg) during the control period, after vibration of the chest and suctioning, after hyperventilation, and two hours after suctioning. Compared to control values, mean PO2decreased significantly after suctioning to 43 mm Hg and increased significantly after hyperventilation to 78 mm Hg. There was a significant decrease in inspiratory resistance and a trend toward decrease in expiratory resistance after suctioning, with return to control levels after hyperventilation. Respiratory rate increased significantly after suctioning. Functional residual capacity, dynamic lung compliance, and tidal volume, as well as PCO2 and base excess, were not changed appreciably throughout the protocol. Because of potentially severe hypoxemia, this study suggests that suctioning and hyperventilation are not warranted on a routine basis in infants recovering from respiratory diseases.


Bronchopulmonary dysplasia: possible relationship to pulmonary edema. The pathogenesis of bronchopulmonary dysplasia is controversial. Oxygen toxicity, mechanical trauma to the lung secondary to respirator therapy, and congestive heart failure with a left to right shunt through a patent ductus arteriosus have all been implicated. Our data suggest that in addition to these three conditions, all of which are edemagenic, infants with bronchopulmonary dysplasia have a significantly greater mean fluid intake in the first five days of life when compared with infants with respiratory distress syndrome or patent ductus arteriosus alone. We suggest that the addition of a fluid load may potentiate the effects of other factors and increase the risk of bronchopulmonary dysplasia in infants with respiratory distress syndrome who require respiratory support.


Acute renal failure in newborn infants.

Acute renal failure in newborn infants. The clinical course and follow-up of 14 neonates who developed acute renal failure are reported. Renal failure in these patients was secondary to major perinatal disorders, e.g., hyaline membrane disease, pneumonia, hemorrhage, or sepsis. Thirteen patients had hypoxia and nine were in shock when renal failure developed. Five patients died during the acute stage of renal failure. Of nine survivors, five patients sustained residual renal damage.


Neonatal circumcision and penile dorsal nerve block--a painless procedure. Circumcision is the only surgical procedure, excluding cord-clamping and cutting, which is routinely performed on normal, healthy newborn infants, usually during the first two or three days of life. Apparently no analgesic technique has been described nor suggested in association with neonatal circumcision. This is the first description of a technique of penile dorsal nerve block in neonatal circumcision. In 52 instances using 0.5 ml of 1% lidocaine (Xylocaine) and a 1.2 cm number 27 gauge needle PDNB was successfully and safely introduced with consistent elimination of pain, rendering NC a painless surgical procedure.


Trematodes of marine fishes from South Australia. I. Paraneocreadium australiense gen. et sp. n. (Lepocreadiidae). Paraneocreadium australiense gen. et sp. n. (Lepocreadiidae) is described from Psilocranium nigricans (Richardson) from the Aldinga Reef of South Australia. Paraneocreadium is most similar to Neocreadium Howell 1966 from Geniagnus in New Zealand and Neolepocreadium Thomas 1960 from Trachinotus in Ghana. It differs from both genera in being ovoid rather than elongate, in having a coiled rather than saccate internal seminal vesicle, and having no viteline follicles between the gonads. It differs further from Neocreadium in lacking lymphatic vessels and in the position of the genital pore.


Comparison of the effects of the growth factor produced by Spirometra mansonoides and growth hormone in diabetic-hypophysectomized rats: lipid composition. The effects of bovine growth hormone and the growth factor produced by plerocercoid larvae of the tapeworm, Spirometra mansonoides, on body growth and lipid composition in diabetic-hypophysectomized rats were compared. The diabetic-hypophysectomized control rats gradually lost weight throughout the experiment but both growth hormone and plerocercoids stimulated marked weight gains. Growth hormone treatment resulted in a loss of depot fat from the epididymal fat pads and caused a reduction of liver and serum cholesterol concentrations but had no effect on triglyceride concentrations of either liver or serum. However, plerocercoid infection resulted in increased weights of the epididymal fat pads and increased liver and serum triglyceride concentrations. Serum cholesterol was slightly increased but liver cholesterol was decreased in the plerocercoid-infected rats. Therefore, in the absence of pituitary hormones and insulin, these growth factors had similar effects on body growth but distinctly different effects on lipid metabolism.


Comparison of the effects of the growth factor produced by Spirometra mansonoides and growth hormone in diabetic-hypophysectomized rats: lymphoid tissue. Growth and development of the thymus is dependent on secretions from the anterior pituitary, presumably growth hormone. Diabetes mellitus is known to reduce immunological competence. These studies compare the effects of bovine growth hormone (bGH) and the growth factor produced by plerocercoid larvae of the tapeworm, Spirometra mansonoides, on metabolism of lymphoid tissue, thymus and spleen, in hypophysectomized rats made diabetic with a single intraperitoneal injection of alloxan. Whereas the control diabetic-hypophysectomized rats gradually lost weight throughout the experimental period, both bGH and plerocercoid infection caused significant weight gains during the experimental period. The diabetic-hypophysectomized rats treated with bGH had significantly heavier thymuses and spleens than controls. Plerocercoid infection also caused significant increases in thymus weights. Both bGH and plerocercoids stimulated the metabolic activity of thymocytes isolated from treated rats and tested for their ability to incorporate 3H-thymidine into DNA in vitro. Thus, these growth factors have similar effects on the lymphoid tissue of diabetic-hypophysectomized rats which are apparently independent of normal insulin levels. Whether this anabolic effect is direct or mediated by somatomedin remains to be determined.


Scanning electron microscopic observations of Cysticercus fasciolaris (=Taenia taeniaeformis) after treatment of mice with mebendazole. The time-related topographical changes in mature cysticerci of Taenia taeniaformis induced after medication of infected mice with 250 ppm of mebendazole are described. The changes included the gradual disappearance of microtriches and progressive degeneration of the tegment resulting in an irregular surface with grooves, holes, and craterlike structures. Host cells adhered to the altered areas and the number of these cells increased when more severe changes became apparent. Finally the necrotized cysticerci, which lost their tegument completely, were almost entirely covered with adhesive host cells. A difference in the time sequence of the reported changes occurred between the scolex, the pseudoproglottids, and the bladder. This difference in susceptibility towards the drug between the three parts of the parasite in relation to the morphology of their microtrichous covering is discussed.


Estimation of the coupling coefficient for glucose and sodium transport in Hymenolepis diminuta. Bidirectional fluxes of 3H-glucose and 22Na+ in Hymenolepis diminuta were examined. Pulse-chase techniques involving 2-min incubations with 3H-glucose or 22Na+ followed by 15-sec post-incubations with unlabeled glucose and Na+, were used to estimate efflux rates of the labels after cell penetration. Effect of Na+ concentration (10 and 50 mM) on the efflux rates was determined. Efflux of 3H-glucose in the 15-sec postincubations was unaffected by Na+ concentration and appeared to occur by diffusion. 22Na+ efflux, on the other hand, was markedly greater in 50 mM Na+ than in 10 mM Na+ and appeared to occur by countertransport. This finding suggested that a coupling coefficient (22Na+ influx/3H-glucose influx) might be underestimated at a 22Na+ concentration of 50 mM because of the 22Na+ exchange phenomenon. The loss of 22Na+ due to exchange was minimized by decreasing the incubation time from 2 min to 15 sec; 22Na+ efflux in 15 sec relative to influxes of both 10 and 50 mM 22Na+ were negligible. Using 15-sec incubations we obtained coupling coefficients of 2.09, 2.24, and 1.89 in Na+ concentrations of 5, 25, and 50 mM, respectively, suggesting that the coupling process is not dependent on the Na+ concentration in the ambient medium.


Survival of Trichinella spiralis larvae in sewage sludge anaerobic digesters. The survival of some bacteria, viruses, protozoans, and helminths through the sewage digestion process has been a question of considerable concern among researchers throughout the world. Among the most resistant organisms are some of the pathogenic roundworms and tapeworms. Encysted larvae of Trichinella spiralis are sometimes present in animal tissues discarded as waste from slaughterhouses, restaurants or other sources. In experimental anaerobic sewage digesters, encysted larvae of T. spiralis, in rat muscle, were able to survive a maximum of 96 hr in a "batch" digester. In a digester "fed" daily with small numbers of encysted larvae, "draw-off" remained infective for white rats throughout a 16-day experimental period. Potentially infective material could be present when there is continuous "draw-off" from the anaerobic digesters.


Trypanosoma brucei-cultivation in vitro of infective forms derived from the midgut of Glossina morsitans. Infective forms of Trypanosoma brucei derived from the midgut of Glossina morsitans, have been propagated in vitro for 61 days on a bovine embryonic spleen (BESP) feeder layer using RPMI 1640 medium. It was reproducibly shown that only parasites cultured from the midgut of tsetse flies 12-14 hr after feeding on infected animals could be established in vitro. Cultures thus established were infective to rats and tsetse flies. Only midgut vector types of the parasites were identified by light and electron microscopic techniques.


Development of Nuttallia danii (Protozoa: Babesidae) within tick salivary glands cultured in vitro. Development of the protozoan parasite Nuttallia danii was observed in salivary glands which were extirpated from Hyalomma anatolicum excavatum nymphs, fed as larvae on infected gerbils and held in organ culture. At 34 C the parasite continued developing in the cultured glands at a rate similar to that observed under normal conditions. Development also occurred in culture at 25 degrees C, but at a somewhat slower rate.


Ultrastructure of the foveal glands of the ticks, Dermacentor andersoni Stiles and D. variabilis (Say). The foveal glands of Dermacentor variabilis appear to consist of 2 cell types. The outer cells (Type I) are active, with large areas of abundant finely granular material, apparently precursors of the mature secretory granules. The inner cells (Type II) are apparently storage cells. They are highly vacuolated and contain coarsely granular material as well as presumably mature secretory granules. The foveal glands of D. andersoni contain only Type II cells with extensive accumulations of presumably mature secretory granules.


Discriminating violent individuals by means of various psychological tests. Attempted to clarify the 43/4-8(8-4) controversy and further research the relationship between assaultiveness and other non-MMPI measures. Sixty-one male adolescent prisoners divided into four groups according to Race and Level of Assaultiveness served as subjects for this study. Each prisoner was administered the MMPI, the Buss-Durkee Hostility Scale and the Rotter I-E scale. The results suggest that the 4-3 code type is not an accurate predictor of violence; that elevations of F4897&6 describe the offender population (with) 8-4 describing the violent profile type); and that the Buss-Durkee Hostility scale may be valuable in assessing the violent personality.


A measure of autonomy.

A measure of autonomy. This article reports the development of a measure of indicidual differences in autonomous rule compliance. The autonomy scale (a short, easily administered CPI based test) was developed within the framework of a multidimensional, role-theoretical model of moral development. Five samples were used in the construction of the scale. Two of the samples (total n = 111) were used to derive the autonomy scale. The items for the scale were derived through the sequential use of two common item selection stategies: criterion keying and factor analysis. An initial set of 55 CPI items were derived using an "ideal" autonomy Q-sort profile as a selection criterion, and an Alpha factor solution was used to reduce this initial pool to a final set of 25 items. Several analyses were conducted using three additional samples (total n = 245) to estimate the reliability of the scale and determine its validity. The results of these analyses provide initial evidence for the content, criterion-realted, and construct validity of the scale and indicate that the measure has an adequate reliability.


Adjective correlates for women on the CPI scales: a replication. In a replication of a ten-year-old study by Gough, peer-rated adjectives from the Adjective Check List were correlated with scores on the 18 standard scales of the California Psychological Inventroy (CPI) for 95 college sorority members. For each scale, the ten most positively and negatively correlated adjectives were selected for comparison with Gough's results. The absolute magnitude of the correlations, the qualitative content of the adjectives, and the degree of correspondence with Gough's findings were used to assess the extent to which each CPI scale achieved its stated objective.


Locus of control and effects of failure on perfomance and perceived competence. Reactions to related performance feedback of 117 internal and external eighth-grade children were investigated under conditions which made denial of personal responsibility for outcomes difficult. Both internals and externals were equally pleased by success feedback and displeased by failure and their competence judgement was influenced by the feedback received. However, internals exhibited more effective coping with failure than did externals. They improved their performance following failure feedback relatively more than after success and no external feedback conditions, and their percieved competance did not decrease in comparison with externals.


Dysmenorrhea and personality.

Dysmenorrhea and personality. The experiment examined whether reliable personality differences exist between (a) women who suffer from spasmodic and congestive dysmenorrhea and (b) women who experience dysmenorrhea and women who do not. A sample of 12 congestive dysmenorrhea sufferers, 12 spasmodic dysmenorrhea suffers, and 24 nonsufferers obtained from a larger sample of university women, completed the Menstrual Symptom Questionnaire, Minnesota Multiphasic Personality Inventory, Tennessee Self-Concept Scale, and Personality Research Form. Results indicated that congestive sufferers differed from spasmodic sufferers only in their level of impulsivity. However, dysmenorrhea sufferers differed significantly from nonsufferers in that dysmenorrhea sufferers were more similar to a neurotic sample, were depressed, anxious and introverted, and less independent, playful, satisfied with themselves, positive about their physical and social selves than nonsufferers. In spite of these differences, standard scores from the personality measures suggested that dysmenorrhea sufferers were not maladjusted.


The measurement of assertiveness and aggressiveness. The Bakker Assertiveness-Aggressiveness Inventory is a 36-item self-report inventory designed to measure two separate aspects of what has previously been subsumed under the rubric "assertiveness", namely, (a) defensive, responsive behaviors which protect territory and privileges, and (b) initiating behaviors which augment the person's territory or status. Assertiveness scores increases significantly above aggressiveness scores in a class which focused on the defensive, responsive aspects of behavior. Aggressiveness was found to correlate with occupation level and amount of schooling sought, while assertiveness did not correlate with either of these. Normative, reliability and validity data are presented.


Correlates of self-consciousness.

Correlates of self-consciousness. Examined the relationship between the three subscales of the Self-Consciousness Scale and a variety of other personality dimensions, including measures of reflectivity, self-regulation, and social desirability. Data from six geographically diverse samples (total N = 1395) were presented. In general, both the construct validity and discriminant validity of the subscales were supported. First, private self-consciousness significantly correlated with the Guilford-Zimmerman Thoughtfulness Scale and the Paivio Imagery Scale. Second, all of the self-consciousness subscales were shown to be relatively independent of the social desirability response set. Third, less than 6% of the variance in each self-consciousness subscale was shared with scores on the Self-Monitoring Scale. Finally, the minimal relationships between the self-consciousness subscales and measures of emotionality and test anxiety reported by Carver and Glass (1976) were in general replicated. The low magnitude of the correlations obtained was interpreted as supporting the distinctive contribution of the Self-Consciousness Scale to personality assessment.


Developing a measure of loneliness.

Developing a measure of loneliness. Research on loneliness has been hindered by the lack of a simple and reliable assessment technique. The development of the UCLA Loneliness Scale, a short, 20-item general measure of loneliness is reported. The measure has high internal consistency (coefficient alpha = .96) and a test-retest correlation over a two-month period of .73. Concurrent and preliminary construct validity are indicated by correlations with self-reports of current loneliness and related emotional states, and by volunteering for a "loneliness clinic."


The utility of two Wechsler Adult Intelligence Scale short forms with prisoners. Previous research has suggested that the Pauker (1963) and Satz and Mogul (1962) short forms of the WAIS have been efficacious in estimating the standard form. While there is a growing need in correctional settings for quicker evaluation procedures, the lack of WAIS short form research with prisoners prohibits their use with such populations. Hence, this study employed 126 young adult male inmates to test the comparability of the above cited short forms and the standard WAIS across a variety of evaluative criteria. The results generally suggested the superiority of the Pauker (1963) form in estimating the standard WAIS. However, because the current study employed only black and white young male offenders it is suggested that the current findings not be generalized to other age groups, races, or women inmates until these findings are cross-validated on such samples.


Personality assessment and insurance reimbursement. A contract between APA and OCHAMPUS has committed APA to developing a national peer review capability for the review of out-patient psychological services. This paper describes the review criteria which apply to personality assessment and psychological testing.


Structure-activity studies of barbiturates using pattern recognition techniques. The relationship between molecular structure and duration of depressant effect for barbiturates was investigated. A data set of 160 5,5'-disubstituted barbiturates with various acyclic substituents was coded using 47 numerical descriptors including fragments, substructures, environmental descriptors, and molecular connectivity indexes. All descriptors were derived directly from the connection tables of the barbiturates. Using an interactive error-correction feedback algorithm, linear discriminant functions were developed that could dichotomize the data set with respect to several thresholds separating longer from shorter acting compounds. Feature selection was used to focus on the relatively few structural descriptors sufficient to support linear separability. For three specific thresholds, nine, 11, and nine descriptors were sufficient. The importance of these descriptors and the utility of the technique are discussed. Predictive abilities of approximately 94% were obtained for known barbiturates of the same general molecular types.


Spectrofluorometric determination of alkoxy-substituted benzylimidazolidinones in biological fluids. Sensitive and specific spectrofluorometric assays were developed for the determination of d, 1-4-(3,4-dimethoxybenzyl)-2-imidazolidinone and d,1-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone in blood and urine. Each compound is selectively extracted from buffered blood or urine and oxidized with alkaline permanganate to its respective fluorescent benzoic acid derivative, which is quantitated in acetic acid in ethanol (1:99). The method was applied to the determination of blood levels and urinary excretion in the dog following the administration of single intravenous and oral doses of each compound.


Studies on drug metabolism by use of isotopes XX: Ion cluster technique for detection of urinary metabolites of 1-butyryl-4-cinnamylpiperazine by mass chromatography. An ion cluster technique and mass chromatography were used for the structural elucidation of several unidentified urinary metabolites of 1-butyryl-4-cinnamylpiperazine (I) in mice and guinea pigs. The urinary metabolites in guinea pigs and mice receiving a single 100 mg/kg dose of an equimolar mixture of 1-butyryl-4-[aromatic-d(5)]-cinnamylpiperazine (I-d(5)) hydrochloride and I hydrochloride (I:I-d(5)) were purified and subjected to trimethylsilyl derivatization with bis(trimethylsilyl)acetamide, followed by GLC-mass spectrometry-computer analysis. Appropriate fragment and molecular ions of unidentified metabolites were selected based on the major mass fragment ions appearing in the mass spectra of the previously identified metabolites of I to provide the mass chromatograms. The presence of ion clusters as doublet peaks in the mass chromatograms indicated that the corresponding total ion peaks originated from the administered I:I-d(5). The mass spectra of selected scans from the total ion chromatogram were plotted, and the structures of unidentified metabolites were readily determined by the presence of ion clusters separated by 3-5 mass units and by the shift of the fragment ions. By using this technique, six previously unidentified metabolites were identified in the urine of guinea pigs and two were identified in the urine of mice.


Effect of salicylamide and acetaminophen on dextromethorphan hydrobromide metabolism: possible pharmacological implications. The effect of salicylamide and acetaminophen on the metabolic fate of dextrorphan, the primary metabolite of dextromethorphan, was studied in vivo in the rat. Plasma dextrorphan levels were measured at 5-min intervals up to 20 min and at longer intervals up to 2 hr after dextromethorphan hydrobromide was administered orally either alone or in combination with salicylamide and acetaminophen. The combination gave rise to higher plasma dextrorphan levels than did dextromethorphan hydrobromide alone at most sampling times. Conjugation of dextrorphan was inhibited almost quantitatively by salicylamide and acetaminophen at the 5-min sampling time. Salicylamide alone increased the plasma dextrorphan levels when it was coadministered with dextromethorphan, but the differences were not statistically significant. The antitussive activity of dextromethorphan hydrobromide in the unanesthetized dog was faster in onset, greater in intensity, and longer in duration when it was coadministered with salicylamide and acetaminophen. It is suggested that salicylamide and acetaminophen may inhibit the metabolic inactivation of dextrorphan, thereby improving the coughinhibiting potential of dextromethorphan hydrobromide.


Bioavailability of erythromycin stearate: influence of food and fluid volume. The influence of various test meals and coadministered water volumes on erythromycin stearate bioavailability from orally dosed film-coated tablets was studied in healthy human subjects. Serum erythromycin levels were uniformly reduced by all test meals, with the reduction in mean peak serum levels varying from 47 to 60%. Serum erythromycin levels also were reduced significantly in fasted individuals when the accompanying water volume was reduced from 250 to 20 ml. The apparent drug absorption rate constant was not influenced by treatments. This result is probably due to rapid degradation of solubilized, unabsorbed drug in the GI tract. Higher and more uniform serum erythromycin levels are obtained when erythromycin stearate tablets are given on an empty stomach together with an adequate water volume.


Quantitative crystallinity determinations for beta-lactam antibiotics by solution calorimetry: correlations with stability. The solution calorimetry method is based on the observation that amorphous forms are normally significantly higher in energy than are crystalline forms. The utility and validity of the calorimetric method were investigated for cephalothin sodium, cefazolin sodium, cefamandole nafate, and cefamandole sodium. Amorphous, partially crystalline, and crystalline forms were prepared and characterized by X-ray diffraction (powder), by solution calorimetry, and, for cephalothin sodium, by the thermal decomposition rate at 50 degrees. Qualitatively, there was a good correlation between calorimetric crystallinity and the (less precise) crystallinity derived from X-ray data. The energy and structure of the amorphous state depend on the history of the sample; even samples of the same crystalline polymorph, containing no amorphous phase, may differ in energy. Thus, the absolute value of the crystallinity (X-ray or calorimetric) depends on the choice of amorphous and crystalline standards. The heat of solution is a precise (+/- 1%) and unambiguous measure of the relative crystallinity; and provided amorphous and crystalline standards are appropriately chosen, the calorimetric crystallinity correlates well with chemical stability.


Interaction of doxorubicin with phospholipid monolayers. The energies of interaction of doxorubicin hydrochloride and sodium 1,2,4-trihydroxy-9,10-dioxo-3-anthracenesulfonate with dipalmitoylphosphatidylethanolamine and dipalmitoyllecithin monolayers spread at the air-water interface were estimated from the increase in surface pressure with increasing concentrations of the subphase-injected compound. Their orders of magnitude were consistent with those of the energies of interaction of doxorubicin and acridines with double-stranded DNA, which suggests that the same type of van der Waals forces are operative.


C-NMR spectroscopy of tropane alkaloids. The natural abundance 13C-NMR spectra of tropine, atropine, scopolamine, cocaine, atropine methonitrate, and dl-tropic acid were determined at 22.63 MHz. With the aid of proton decoupling techiniques and by comparison with analogous simpler compounds, it was possible to make self-consistent and unambiquous assignments of all carbon resonances for these alkaloids. Some important chemical shift trends were observed and should be useful in the identification of similar systems.


Colorimetric determination of catecholamines by 2,3,5-triphenyltetrazolium chloride. A convenient spectrophotometric method was developed for the determination of epinephrine, levarterenol, isoproterenol, and methyldopa by reduction of 2,3,5-triphenyltetrazolium chloride and subsequent measurement of the formazan at 485 nm. With absolute alcohol as the solvent, maximum color absorption was attained in 30 min at 25 degrees in the presence of 0.1 N KOH. Evidence is provided to account for the reduction of the tetrazolium salt at the expense of the epinephrine catechol moiety. In addition to the considerably high values of the molar absorptivities of the chromogen formed, ideal adherence of the color absorption to the Beer-Lambert law permitted a sensitive microdetermination of these catecholamines in both pure forms and pharmaceutical formulations. The tetrazolium interaction was selective. No interference was encountered from common catecholamine antioxidants, adjuvants, or noncatechol degradation products.


Extraction of daunorubicin and doxorubicin and their hydroxyl metabolites: self-association in aqueous solution. The extraction of daunorubicin and doxorubicin and their hydroxyl metabolites daunorubicinol and doxorubicinol was studied using chloroform-1-pentanol (9:1) as the organic phase. Because of differences in acid dissociation constants, the pH for optimum extraction varied from 8.0 to 8.6 for the different compounds. Self-association in the aqueous phase significantly influenced the distribution ratio. Constants for the formation of dimers and tetramers in aqueous solutions were about 10(4.5) and 10(12), respectively.


Relationship between steroid permeability across excised rabbit cornea and octanol-water partition coefficients. Permeability rates were determined across excised rabbit corneas for 11 steroids. Permeability coefficients for each steroid were calculated, and their logarithms were plotted against their respective log octanol-water partition coefficients. A parabolic relationship resulted, with an optimum log permeability and coefficient observed at a log Po of 2.9. From these experimental results, an improvement in ophthalmic bioavailability of dexamethasone acetate as compared to dexamethasone is predicted and correlates with literature results.


Effect of formulation factors on penetration of hydrocortisone through mouse skin. The effect of formulation factors on the steady-state flux of hydrocortisone through mouse skin was evaluated. The flux of hydrocortisone from solutions containing propylene glycol as a cosolvent varied inversely with the propylene glycol concentration. Solutions containing 2-propanol gave flux values higher than those obtained from propylene glycol solutions and independent of the 2-propanol concentration. Addition of polysorbate 80 to 2-propanol-water solutions produced an increase in flux at low surfactant concentrations that reached an apparent limiting value at higher concentrations. The penetration flux was the same from solutions and gels. The role of vehicle-skin interactions in penetration is emphasized.


Rapid blue tetrazolium procedure for analysis of corticosteroids in pharmaceutical preparations. A rapid quantitative analysis of nine selected corticosteroids and corticosteroid esters at room temperature is described. The procedure is similar to the official blue tetrazolium reaction for corticosteroids, except that methylene chloride instead of alcohol USP is used as a solvent and the reagents are dissolved in or diluted with nonaqueous solvents. These two modifications reduce the medium polarity, which increases the reaction rate. The reactions are complete in 7-18 min, and the formazans are stable for at least 90 min. The results from 15 different pharmaceutical formulations, 12 containing hydrocortisone and three containing prednisolone acetate, show that the proposed method gives results that compare favorably with those obtained by the official blue tetrazolium, isoniazid, and phenylhydrazine procedures.


Preferential localization of radiolabeled liposomes in liver. Liposome formulations were studied to achieve an efficient entrapment procedure for the production of liposomes of 99mTc-pentetic acid. The entrapment efficiency was studied by separation of the product using column chromatography. The particle-size range of the prepared liposomes was evaluated using electron microscopy. Entrapment techniques and separation procedures led to a liposome preparation with particles in the colloidal size range (0.001-0.5 micron). Dramatic differences in the organ distribution of the liposome preparation in mice were produced when different particle-size ranges were injected. Liposomes eluted in the first fraction after the void volume led to a maximum uptake by the liver and spleen 10 min after intravenous injection. Liposomes from pooled fractions provided less than half of the activity in the liver, as did the narrow size range liposome preparation.


Cobaltous choride-induced hypothermia in mice I: effect of pretreatment with anticholinergic drugs. The hypothermic response following intraperitoneal doses (6.25, 12.5, and 25 mg/kg) of cobaltous chloride was investigated in Swiss albino mice. The magnitude and duration of rectal temperature depression were dose related. In each case, maximal hypothermia was evident within 30 min after injection. Body temperature depression was noted 30 min after oral, subcutaneous, intraperitoneal, intravenous, and intracerebral administration of cobaltous chloride. Cobalt was most active when administered intracerebrally, suggesting a central component to the thermolytic response. Rectal temperature depression following cobaltous chloride was dependent on the ambient temperature. The time course of the effect of cobaltous chloride on rectal and cutaneous tail temperature was noted. Cutaneous tail temperature depression occurred throughout the rectal temperature response, suggesting that cobalt may decrease heat production. Pretreatment with atropine sulfate, hexamethonium bromide, or nicotine failed to modify the temperature response to cobalt. Chlorpromazine hydrochloride pretreatment resulted in a partial antagonism of cobalt-induced hypothermia, presumably through a mechanism other than cholinergic blockade.


Quantitative GLC determination of cis- and trans-isomers of doxepin and desmethyldoxepin. A GLC method for the simultaneous quantitative determination of the cis- and trans-isomers of doxepin and desmethyldoxepin in human plasma was developed. The method involves the use of a capillary column for efficient separation of the four compounds and the internal standards, amitriptyline and nortriptyline. A high sensitivity is obtained with a nitrogen detector, enabling quantitation of the compounds in plasma of humans treated chronically with doxepin. Confirmation of the identity of the cis- and trans-isomers of doxepin and desmethyldoxepin in biological samples was carried out by selected ion monitoring.


Simple, rapid, and micro high-pressure liquid chromatographic determination of plasma griseofulvin levels. A rapid high-pressure liquid chromatographic assay is described for the quantitative determination of griseofulvin in plasma. An aliquot (25--10 microliter) of plasma was deproteinized by a simple procedure involving the addition of 2.5 volumes of acetonitrile, vortex mixing for a few seconds, and centrifugation for 1 min. The clear supernate, 50 microliter, was injected into the high-pressure liquid chromatograph. A reversed-phase column was used with a mobile phase of distilled water-acetonitrile (1:1) at a flow rate of 2 ml/min and was operated at ambient temperature. A fluorescent detector with an excitation wavelength of 260 nm was employed to monitor the column effluent. Griseofulvin had a retention time of 3.8 min. This procedure yields reproducible results with high sensitivity; plasma concentrations as low as 50 ng/ml can be measured. Several commonly used drugs do not interfere. Analysis of plasma samples collected from a rabbit injected with griseofulvin indicated that the procedure is suitable for pharmacokinetic studies and clinical monitoring of plasma concentrations in patients. Assay turnaround time is less than 6 min. For clinical monitoring of plasma griseofulvin concentrations, a sample volume as small as 10 microliter can be used.


Stability of furosemide in aqueous systems. A stability-indicating assay for furosemide based on high-pressure liquid chromatography was developed. The method is sensitive, accurate, and precise. The standard deviation based on six injections of the standard solution was +/- 1.37%. This method was used to study furosemide stability in various aqueous solutions and dosage forms. Stability tests were conducted at room temperature as well as at higher temperatures (45, 65, and 85 degrees) at various pH values and with different vehicles. Some decomposition products were identified.


Quantitation of cocaine and its principal metabolite, benzoylecgonine, by GLC-mass spectrometry using stable isotope labeled analogs as internal standards. A quantitative GLC-mass spectrometric assay was developed for the determination of cocaine and its principal metabolite, benzoylecgonine, in human urine. The assay utilizes selective ion focusing to monitor in a GLC effluent the molecular ions of cocaine and benzoylecgonine generated by electron-impact ionization. Cocaine-d(3) and benzoylecgonine-d(3) were the internal standards. The assay can measure 2 ng of cocaine/ml and 5 ng of benzoylecgonine/ml with about 5% precision. The curves relating the amounts of cocaine and benzoylecgonine added versus the amounts found over a large range of cocaine and benzoylecgonine concentrations were straight lines with nearly zero intercepts and slopes of 0.98 +/- 0.01 and 0.97 +/- 0.01, respectively. The method was used for the analysis of urinary cocaine and benzoylecgonine in cocaine addicts. Assay specificity was confirmed by complete identity of the mass spectra of cocaine and benzoylecgonine with those of authentic materials.


Thiamine whole blood pharmackinetics in rats using both a specific S-thiamine liquid scintillation assay and the thiochrome fluorescence assay. The study of factors altering the CNS and GI absorption of thiamine in rats required the development of a specific assay for thiamine from 100-microliter samples of blood and plasma and small quantities of tissue. The specific thiochrome fluorescence assay for thiamine was modified to handle microsamples and to use S-thiamine. This sensitive and specific radioassay using S-thiamine gave pharmacokinetic parameters for 4-mg/kg iv doses of thiamine in rats equivalent to those using the less sensitive thiochrome fluorescence assay. The new assay, because of its lower limit of detection, allowed the study of the time profile of thiamine after a 1-mg/kg iv dose in rats. Such a time profile could not have been followed using the standard thiochrome fluorescence assay.


Simultaneous multicomponent drug determinations with a vidicon spectrometer. A vidicon spectrometer, useful for absorption spectrophotometry over the 210-800-nm spectral region and capable of scanning a portion of this region at repetition rates of 250 scans/sec, was applied for the simultaneous determination of multicomponent drug formulations without a separation. Results are reported for two drug preparations containing two and four active components. The average of ratios of determined to expected values for the six active components contained in both formulations was 99.2% based on the specified tablet contents. Relative standard errors for the analyses were less than 3%. Other potential applications of the vidicon spectrometer are discussed briefly.


Fluorometric TLC determination of free and conjugated propranolol, naphthoxylactic acid, and p-hydroxypropranolol in human plasma and urine. Sensitive, specific, and reproducible TLC methods are described for the determination of propranolol and its major metabolites in humans, conjugated propranolol, free and conjugated naphthoxylactic acid, and free and conjugated p-hydroxypropranolol. The drug or metabolites are extracted from plasma or urine with ether and applied to TLC plates of silica gel or microcrystalline cellulose. After development, the plates are scanned in a spectrodensitometer equipped to measure fluorescence in the UV and blue regions of the light spectrum. Quantitation is achieved by comparing the areas under the peaks obtained from the unknowns to those obtained from standards applied to the same plate. Limits of quantitation in plasma are: free propranolol, 2 ng/ml; free p-hydroxypropranolol, 10 ng/ml; conjugated propranolol, 15 ng/ml; total (free and conjugated) naphthoxylactic acid, 25 ng/ml; and conjugated p-hydroxypropranolol, 50 ng/ml. These methods were used to obtain plasma level data in a volunteer after one single dose of propranolol and in patients under propranolol therapy. The Rf values of some known metabolites of propranolol obtained in various TLC developing systems are also presented.


Determination of indoprofen in physiological fluids by reversed-phase liquid chromatography. A rapid, sensitive, reversed-phase high-performance liquid chromatographic procedure was developed for the quantitative analysis of indoprofen in plasma and urine. Minimal sample preparation is required for the analysis of unconjugated urinary or plasma drug levels. The method provided quantitative results for indoprofen levels of 0.5-50 microgram/ml of plasma and 0.5-200 microgram/ml of urine and had a lower detection limit of 1 ng. Total urinary indoprofen levels required enzymatic hydrolysis of the conjugated drug prior to analysis. Results are presented for the plasma and urinary excretion levels of indoprofen for a patient receiving a single oral dose.


Determination of phytonadione in elemental diets by TLC-spectrophotodensitometry. The quantitative analysis of phytonadione in several elemental diet formulations at levels ranging from 90 to 150 ppb is described. After extraction with petroleum either, the sample is cleaned up by silica gel column chromatography and separated on a TLC plate; phytonadione is determined by reflectance densitometry. Recovery data show that the method is accurate (X = 97%) and has a precision (RSD) of +/- 6%.


Difference spectrophotometric determination of p-hydroxybenzoic acid in presence of its esters. A difference spectrophotometric analytical method was developed for the selective determination of p-hydroxybenzoic acid in the presence of its alkyl esters without prior separation. Based on the spectral shift to a shorter wavelength accompanyint carboxyl dissociation, the procedure measures as little as 2% of this acid in mixtures with the alkyl ester preservatives and has an accuracy of 2% mean relative error over the 0.16-12.0 microgram of p-hydroxybenzoic acid/ml range.


Simultaneous determination of procainamide and N-acetylprocainamide in plasma by high-performance liquid chromatography. A sensitive, specific, high-performance liquid chromatographic procedure is described for the simultaneous determination of procainamide and its metabolite, N-acetylprocainamide, in plasma. Basic plasma (2.0 ml), containing pheniramine maleate as an internal standard, is partitioned with methylene dichloride. The organic extract is concentrated to between 0.3 and 0.5 ml, and 100-microliter aliquots are chromatographed on a microparticulate silica gel column using 0.1% acetic acid-20% 0.1 M ammonium acetate in acetonitrile as the mobile phase. With a fixed-wavelength (254-nm) UV detector, both compounds can be quantitated in the 0.1-8.0-microgram/ml of plasma range.


Noninvasive polarographic measurement of drug dissolution. Polarographic analysis was applied successfully to dissolution studies and content uniformity assessment of both capsules and tablets, using a dropping mercury electrode with the modified Levy beaker method. The described noninvasive technique places the polarographic sensor probe directly into the dissolution flask and thus simplifies dissolution measurement by eliminating transfer lines and pumps typically required with the invasive (sampling) mode of analysis. A continuous sampling flowcell with polarographic detection was also evaluated for invasive measurements. Continuous dissolution profiles and content uniformity were determined for chlordiazepoxide, trimethoprim, ornidazole, and isoniazid, using the invasive and noninvasive sampling modes. Results obtained for these drugs showed excellent precision with both sampling techniques. In addition, excellent correlation to UV spectrophotometric data was obtained.


Functional group contribution of bile salt molecules to partitioning of a quaternary ammonium N,N-dimethyl derivative of propranolol. A quaternary ammonium N,N-dimethyl derivative of propranolol was extracted from pH 7.4 phosphate buffer into 1-octanol as ion-pairs with 12 different bile salts. The binding number, n, and the extraction constant, Ke, were determined. To obtain group contribution values of the bile salt molecule from the ion-pair extraction data, multiple linear regression analysis by the Free-Wilson technique was applied. The results showed that the fundamental premise of the functional group's contribution to the ion-pair extraction is valid. The functional groups of counterions contribute to the partitioning of the ammonium compound independently and additively in this system.


Hydrolysis and subsequent cyclization of etazolate hydrochloride and related compounds in aqueous solutions: application of PMR and mass spectrometry in accelerated stability studies. The hydrolysis of etazolate hydrochloride, an inhibitor of cyclic nucleotide 3',5'-monophosphate phosphodiesterase that degrades cyclic adenosine 3',5'-monophosphate (cyclic AMP) to adenosine 5'-monophosphate, and related compounds was studied by PMR and mass spectrometry. The compounds underwent reversible acid-catalyzed hydrolysis in aqueous solutions at 60 degrees, followed by cyclization to a major and a minor product formed by independent pathways. Under the experimental conditions, the minor product was stable. The formation rate of the major product, 6-ethyl-1,6-dihydrodipyrazolo [3,4-b:3',4'-d] pyridin-3(2H)-one, was considerably greater than that of the minor component, 3-ethoxy-6-ethyl-1,6-dihydrodipyrazolo [3,4-b:3',4'-d] pyridine. For the 6-methyl analog of etazolate, the rate of methyl deuteration was considerably slower than the rate of cyclization.


Solubilization of napthalene by sodium cholate and pattern of self-association of sodium cholate in 0.15 M sodium chloride. Naphthalene solubility was determined in aqueous 0.15 M NaCl containing sodium cholate in the 0-0.05 M concentration range at 25 +/- 0.1 degrees. Sodium cholate tends to self-associate in aqueous solutions. Most often, the association pattern has been described in terms of a monomer-micellar model in which it is assumed that no association occurs below the critical micelle concentration. By comparison of the experimental solubilization curve with curves calculated on the basis of the monomer-micellar model, it was shown that this model is inappropriate for the self-association pattern of sodium cholate. The solubility data were consistent with a model that assumes that sodium cholate associates to form dimers, trimers, and higher aggregates with an average aggregation number of 7.63. Model calculations suggest that naphthalene is solubilized by dimers and higher aggregates. Solubilization of naphthalene by trimers appears to be negligible.


Secondary disulfonamides and secondary tetrasulfondiamides as proposed new biological alkylating agents. Secondary disulfonamides and secondary tetrasulfondiamides were prepared for antineoplastic activity testing. For the disulfonamides, one alkyl series (n-butyl), three aralkyl series (benzyl, phenethyl, and phenpropyl), and one diaralkyl series (diphenpropyl) were prepared. Two series of tetrasulfondiamides were made from diamines, one in which the central methylene chain was varied from four to six and another using the tetrasubstituted sulfonyl derivative of xylylenediamine. Thirteen final compounds were synthesized. Ten of these compounds and four intermediates have not been reported previously. Preliminary screening results for the final compounds are given.


Synthesis of antifungal 2-substituted phthalimidines. An improved synthesis of phthalimidine is reported. Two N-substituted phthalimidines were synthesized by alkylation of the parent compound, and they showed complete inhibition of Microsporum and Trichophyton species at 10-100 microgram/ml in an agar dilution test. Both compounds were inactive against Candida albicans at 100 microgram/ml or Aspergillus niger at 250 microgram/ml.


Comparative pharmacokinetics of coumarin anticoagulants XXXV: Examination of possible pharmacokinetic interaction between (R)-(+)- and (S)-(--)-warfarin in humans. The elimination kinetics and anticoagulant effect produced by single 1.5-mg/kg doses of (R)-(+(-, (S)-(--)-, and racemic warfarin were determined in 10 healthy men. The results obtained in experiments with the individual enantiomers were used to predict the elimination kinetics and anticoagulant effect of racemic warfarin, assuming that there is no interaction between the two enantiomers. These predictions were compared to experimental results, and no significant differences were observed. This finding suggests that there are no pronounced pharmacokinetic or pharmacodynamic interactions between single large doses of (R)-(+)- and (S)-(--)-warfarin in humans.


Rapid and micro high-pressure liquid chromatographic method for simultaneous determination of procainamide and N-acetylprocainamide in plasma. A rapid and simple high-pressure liquid chromatographic method was developed for the simultaneous determination of plasma levels of procainamide and its major metabolite, N-acetonitrile, and the supernate was chromatographed on a cation-exchange column. The assay can be carried out on as little as 20 microliter of plasma and requires only about 7 min for each sample. No interference was found in plasma samples from cardiac patients receiving procainamide. This method is simple, fast, and useful for routine therapeutic monitoring and for pharmacokinetic studies procainamide and its metabolite.


Constant blood withdrawal method for area under plasma concentration-time curve. The area under the plasma concentration-time curve (AUC) was measured after an intravenous injection of sodium salicylate and after intragastric administration of aspirin, using either an intermittent sampling and the trapezoid rule (AUC-trapezoid) or the recently introduced constant blood withdrawal method (AUC-integrated concentration). Six dogs were used in each study. The AUC-integrated concentration was significantly higher than the AUC-trapezoid. The difference between the two methods was more significant after the intravenous infusion than after the intragastric administration. The higher AUC-integrated concentration was attributed to the inclusion of the initial plasma levels, which is an inherent advantage of the constant blood withdrawal method.


Constituents of Cannabis sativa L. XIII: Stability of dosage form prepared by impregnating synthetic (--)-delta 9-trans-tetrahydrocannabinol on placebo Cannabis plant material. Synthetic (--)-delta 9-trans-tetrahydrocannabinol impregnated on placebo Cannabis decomposed only 6.3% after being stored for 1 year at --18 degrees. Storage at 5 degrees and room temperature under various conditions led to severe decomposition. The amount of cannabinol observed when (--)-delta 9-trans-tetrahydrocannabinol decomposed indicates that cannabinol is not the only decomposition product.


Metabolism and excretion of normorphine in dogs. Normorphine metabolism was studied in dogs given 20 mg of normorphine hydrochloride/kg sc. Free and (onjugated normorphine excreted in the urine over 144 hr represented 32 and 32%, respectively, of the administered dose. Eighty percent of the urinary excretion of the drug occurred within 9 hr. One percent of the administered dose was excreted as free normorphine in the feces. The urine was chromatographed on a column. Evaporation of the washing and methanolic effluent yielded a residue, which was purified by crystallization from aqueous methanol. Results of UV and IR studies, elemental analysis, and determination of normorphine and glucuronic acid content established the identity of this metabolite as normorphine 3-glucuronide. Dihydronormorphine and dehydronormorphine were detected with GLC-mass spectrometry as minor metabolites.