[Myasthenia, thymoma and hypophyseal tumor associated with heterogenous adenomatous proliferation and ganglioneuroma of the sella turcica]. The authors report a case of myasthenia gravis in which a tumour of the sella turcica, without clinical symptoms, was discovered on X-ray examination of the skull and was removed with success. Histological study showed endocrine and neural type cells with cells of intermediate type. Subsequent thoracic surgery was performed with removal of a thymoma which was not visible on X-ray examination of the chest. The first operation on the sella turcica had no effect on the myasthenia but after the second on the thymoma a definite improvement was noted. The association of myasthenia, thymoma and ganglioneuroma of the sella turcica is unknown. In order to explain this, the authors hypothesize a common origin in the neural crests of both tumours.


Cerebro-hepato-renal syndrome. Report of a case with histochemical and ultrastructural observations. A new case of the cerebro-hepato-renal syndrome is being reported. The neuropathologic changes consisted of developmental abnormalities of cerebral and cerebellar cortex and of the inferior olives. In addition, there were metabolic changes in the central nervous system, indicated by an accumulation of lipid within histiocytes of free in gray and white matter, deficiency in myelination and gliosis of the white matter, and marked proliferation of protoplasmic astrocytes in the gray matter. A unique feature of this case was the presence of numerous clusters of lipid-filled macrophages and occasional cholesterol crystals in the molecular layer of the cerebellum. The histochemical reactions and ultrastructural appearances of the lipid deposits are suggestive of accumulation of several different types of lipids.


Neonatal neuronal loss in rat superior cervical ganglia: retrograde effects on developing preganglionic axons and Schwann cells. Beginning prenatally and during the first week after birth, there is normally a loss of axons in rat cervical sympathetic trunk. To test the hypothesis that this spontaneous axonal loss represents a natural process whereby an excessive number of immature preganglionic axons in the cervical sympathetic trunk adapts to the neuronal population in the superior cervical ganglion, the number of nerve cells in the superior cervical ganglion was reduced in newborn rats by administration of nerve growth factor antiserum, 6-hydroxy-dopamine or postganglionic anxotomy. Quantitative ultrastructural studies of these animals at later stages of development revealed that, with each method, the number of preganglionic axons and Schwann cells was reduced to nearly one-third of normal. These findings indicate that the superior cervical ganglion plays an important role in the development of the cervical sympathetic trunk. Removal of ganglionic cells causes a retrograde loss of preganglionic fibres. This process probably represents an exaggeration of the normal mechanism for elimination of redundant axons. Because the changes in axonal numbers are associated with similar reductions in the number of Schwann cells, it can also be concluded that postnatal Schwann cell proliferation is influenced by axonal populations.


The altrastructure of Auerbach's plexus in the guinea-pig. I. Neuronal elements. The ultrastructural features of nerve cell bodies and axon profiles within Auerbach's plexus in the stomach, ileum, caecum and colon of the guinea-pig have been examined. Nerve cell bodies have been tentatively classified into nine different types according to their size, distribution of organelles, location and relationship to satellite cells. Except for cell size, no attempt has been made to correlate ultrastructual with light microscopical observations. On the basis of vesicular size, shape and content, eight morphologically distinct types of axon profile have been identified as well as two profile types which are thought to reflect different physiological conditions. The axons contained various populations of small, mostly granular vesicles; small, round agranular vesicles; small, flattened vesicles; large flattened or elongated vesicles; and three types of large vesicle with granular contents distinguished by size. Some correlation between types of axon profile and two types of nerve cell body was recognized. However, more than one type of axon profile usually formed synapses with one type of cell body, and a precise correlation was not determined.


The ultrastructure of Auerbach's plexus in the guinea-pig. II. Non-neuronal elements. The ultrastructural features of non-neuronal cells associated with Auerbach's plexus in the stomach, ileum and colon of the guinea-pig have been examined. Apart from Schwann, mast and interstitial or fibroblast-like cells, two other cell types are described that do not appear to have been reported previously. Of these two cell types, one was found external, but close to, the plexus and contained large granular vesicles. The other cell type contained numerous glycogen-like granules, was situated close to or within axon bundles and had processes that extended within and peripheral to nerve bundles as well as being close to smooth muscle cells. Although axon varicosities were opposed to both the processes and cell body of the second type of cell, synaptic-like contacts were not observed.


Organization of crustacean neuropil. I. Patterns of synaptic connections in lobster stomatogastric ganglion. The stomatogastric ganglion of the lobster consists of about thiry neurons, mainly large monopolar cells, which have been well characterized physiologically. This paper presents an anatomical description of this ganglion, emphasizing synaptic connections in the neuropil. The neuron cell bodies are located on the dorsal surface of the ganglion. They send processes into the underlying neuropil mass. The neuropil is differentiated into two regions: a core of coarse neuropil consists of large heavily ensheathed processes; a surrounding region of fine-textured synaptic neuropil consists of smaller unsheather processes. Synapses are found only in synaptic neuropil, not in the core of coarse neuropil. Synaptic contacts, about one million in the entire neuropil, are easily recognized by a set of criteria including presynaptic vesicles and pre- and postsynaptic membrane specializations. Most synaptic contacts invole at least three neural processes, usually one pre- and two postsynaptic elements. Synapses are clustered onto irregular swellings or varicosities on neural processes. These varicosities make both pre- and postsynaptic contacts. Three differenty types of presynaptic profile are recognized. Pyloric dilator, ventricular dilator and lateral posterior gastric neurons belong to type A with clear irregular synaptic vesicles. Lateral pyloric, pyloric, anterior median and dorsal gastric neurons belong to type B with larger clear round vesicles. Many unidentified fibres, presumably stomatogastric nerve afferents, blong to type C with both small clear irregular vesicles and also large dense-core vesicles. The synaptic vesicle types are tentatively correlated with neurotransmitter: type A with acetylcholine, type B with an unknown transmitter, possibly glutamate, and type C with dopamine. The distribution of synaptic contacts on the processes of identified neurons reconstructed from serial section is presented in the following paper.


Carbohydrates as potential diagnostic tracers for brain tumors. Currently available diagnostic tracers for brain tumors are not specific. Tumor-specific tracers would improve the detection of brain tumors by gamma encephalography. Glucose is an important substrate for tumor metabolism and is known to be taken up in large amounts. The authors have studied five labeled carbohydrates in an attempt to find a tumor-specific tracer: three were tritiated (L-galactose-1-3H, L-fucose-3H, and 4,6-dideoxy-xylo-hexose-3H) and two were radioiodinated (methyl-6-125I-6-deoxy-D-glucoside and 6-125I-6-deoxy-D-glucose). The uptake of these tracers by a transplantable mouse ependymoblastoma after intravenous injection was determined by liquid and well scintillation counting. The highest tumor-to-brain ratio was 7.1 to 1 for the tritiated tracers and 6.2 to 1 for the radioiodinated tracers. Although these ratios are not high enough for gamma encephalography, one of the iodinated tracers may be useful for enhancement of contrast in computerized axial tomography.


Body position and cerebrospinal fluid pressure. Part 1: clinical studies on the effect of rapid postural changes. Cerebrospinal fluid (CSF) pressure was recorded in 149 patients and arterial blood pressure (BP) in 11 patients while moving between lateral and sitting positions. Rapid tilting initiated waves in BP and CSF filling pressure. The postural CSF pressure wave manifested itself either as a transient or as a stationary wave similar to a plateau wave. When patients sat up, transient waves had amplitudes up to 550 and stationary waves up to 1000 mm H2O. When they lay down, transient waves had amplitudes up to 800 mm H2O. Stationary waves were found only among patients with elevated intracranial pressure and a diseased brain. The waves were mainly caused by changes in cerebral blood volume probably reflecting the postural BP wave and brain autoregulation. Most patients with stationary and large transient waves also manifested clinical symptoms. These symptoms were aggravated when a craniospinal block developed in the sitting position, and were reduced or avoided when the tilting was performed slowly over 2 to 3 minutes.


Body position and cerebrospinal fluid pressure. Part 2: clinical studies on orthostatic pressure and the hydrostatic indifferent point. Lumbar cerebrospinal fluid (CSF) pressure was recorded in 116 adult neurosurgical patients in the lateral and sitting positions. The level of zero CSF pressure while in the sitting position (ZPS) and hydrostatic indifferent point (HIP) for lateral and sitting positions were determined and referred to the craniospinal axis. In control patients ZPS was located mainly at the upper cervical region, and showed nearly the same variation and frequency distribution as CSF pressure in the lateral position when efforts were made to reduce sources of error and there was no orthostatic change in CSF filling pressure. Under these circumstances ZPS may be used as a variable comparable from one subject to another. In control patients the HIP was located between C-6 and T-5. In 25 hydrocephalic patients, shunting resulted in a mean caudal shift of ZPS of 244 mm, and a mean pressure fall of 126 mm H2O in the lateral position. This difference was due to a caudal shift of HIP on shunting. A caudally located ZPS was found in patients with complete cervical subarachnoid block. Prevention and treatment of CSF leakage cranial to HIP is discussed.


Microvascular bypass surgery. Part 1: anatomical studies. Microvascular anatomical studies were performed to ascertain the most suitable cortical vessel for extracranial-intracranial arterial bypass (EIAB). The three most commonly used cortical areas (the tip of the frontal lobe, the tip of the temporal lobe, and the area at the angular gyrus) were examined in detail. Because of their accessiblity and size, the cortical arteries in the area of the angular gyrus offer the most suitable location for creating an EIAB.


Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury. Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (C1-) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in C1- levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury.


Comparative study of the pressure of various aneurysm clips. Comparative study of the pressure and the resistance to slippage of several aneurysm clips was done. Knowledge of the physical characteristics of various clips, such as the pressure, maximum opening angle, and width and thickness of the blade is essential for their proper use.


Postirradiation necrosis of the temporal lobe presenting as a glioma. Case report. A patient is reported who presented with manifestations of a space-occupying lesion in the left temporal lobe thought to be a metastasis, but on radiological examination and surgical exploration appeared to be a diffuse infiltrative glioma. Some 21 months earlier he had received a course of fast neutron therapy to a carcinoma of the left parotid gland. Diagnosis by microscopic examination revealed changes characteristic of delayed radiation necrosis.


Sarcoidosis of the spinal cord. Case report. A case of intramedullary sarcoidosis simulating a tumor of the cervical spinal cord is presented. Autopsy showed that the disease was limited to the cervical cord and hilar lymph nodes. The literature is reviewed and six cases of histologically documented spinal cord sarcoidosis are discussed.


Rapid arteriovenous shunting in a spinal cord ependymoma. Case report. A case of ependymoma of the conus medullaris and cauda equina is described in which spinal angiography demonstrated rapid arteriovenous shunting, an angiographic sign which is typical of arteriovenous malformations and which has not been previously reported to occur with ependymomas.


Osteoclastoma of the thoracic spine. Case report. A case of osteoclastoma arising in the body of the T-9 vertebra is presented. Osteoclastoma rarely involves the vertebrae, and treatment, whether by surgery or radiotherapy, seldom results in eradication of the lesion or prevention of recurrence.


Embolization of a traumatic arteriovenous fistula of the scalp with radiopaque Gelfoam pledgets. Case report and technical note. A large traumatic arteriovenous malformation of the scalp was embolized with Pantopaque-saturated Gelfoam pledgets, which made fluoroscopic monitoring of the radiopaque emboli possible. Postembolization angiography demonstrated complete occlusion of the malformation. There is still no clinical or physical evidence of recurrence after an 8-month follow-up period.


Microblock for occlusion of small vessels. Technical note. A small microvascular occluder termed a "microblock" is described. It has the advantages of controlled gentle occlusion and small size.


Brain-cutting device for correlation of brain scan and autopsy sections. Technical note. The authors describe a frame with guides to facilitate accurate correlation of the planes of brain-specimen sections with computerized axial tomography brain scans.


Thallium-201 for myocardial imaging: appearance of the normal heart. Thallium-201 myocardial perfusion images were obtained from 13 healthy adults after tracer administration both at rest and at maximal stress. On the rest-injected scan, tracer was seen in left ventricular myocardium, liver, and spleen. In two subjects with resting tachycardia, the right ventricular myocardium was slightly visualized after tracer injection at rest. When tracer was administered at stress, the left ventricular activity was more nearly homogeneous and the left ventricle was better defined on the scan. The left-ventricle-to-lung-background activity ratio increased from 2.4 at rest to 3.4 at stress. The right ventricular myocardium was seen on the stress-injected scan. Phantom studies, performed to define the optimum position for visualization of lesions, showed that small lesions were best defined when seen either en face or in tangent. Scans should be performed at stress whenever possible and multiple views are essential.


Radionuclide venography: significance of delayed washout; visualization of the saphenous system. Venograms were obtained on dogs in which venous thrombosis had been surgically induced. Radionuclide venograms, obtained after injection of 99mTc-labeled microspheres or macroaggregated albumin, showed decreased radioactivity over the areas of venous thrombosis and increased radioactivity over areas of venous stasis. Scintigrams of veins excised after an injection of labeled particles did not delineate thrombi, areas of crush-injured vein, or the venous valves. Delay in the washout of radioactivity on a venogram indicates stasis due to impeded venous flow in the area of thrombosis. A modified technique was developed to obtain simultaneous images of the superficial and deep veins of the leg. Visualization of the superficial veins not only permits detection of superficial abnormalities, but also assists interpretation of the venographic observations of the deep veins.


Compartmental models of cerebral blood flow. Analysis using the 81-keV and 31-keV photons of 133Xe. The clearance of 133Xe from the cerebrum after intra-arterial injection was studied in the pig. A mathematical model, consisting of two exponential terms and a constant, was fitted to decay curves obtained for both the 81-keV and the 31-keV radiation of 133Xe. The corresponding exponential terms for the 31-keV and 81-keV curves were found to differ significantly, implying that the two-compartmental model, based on the paritition of the white and gray matter of the brain, is not adequate to describe the clearance process. Other studies have shown that cerebral blood flow is more heterogeneous than the two-compartment model suggests. The discrepancies found here are interpreted as due to the simplification of representing a multiexponential clearance process by means of a two-exponential model.


A diagnostic strategy using ventilation-perfusion studies in patients suspect for pulmonary embolism. A diagnostic strategy for the assessment of pulmonary embolism was developed using results of scintigraphic examinations in over 100 patients, all of whom had angiographic assessment of their pulmonary vasculature and nearly 50% of whom had combined ventilation-perfusion studies. The highest-probability estimate of pulmonary embolism that could be made in the absence of a ventilation study was 80%. When a ventilation study was added, this probability increased to nearly 100% for patients with multiple large perfusion defects and normal ventilation. For smaller defects with normal ventilation, the probability of pulmonary embolism was only 50%. For perfusion defects corresponding to known radiographic abnormalities, the probability of pulmonary embolism was 25%.


Childhood pelvic osteomyelitis presenting as a "cold" lesion on bone scan: case report. A case of occult pelvic osteomyelitis is presented. The involved portions of the left pubis and left ischium presented as "cold" areas on the original bone scan with 99mTc-diphosphonate. The presumed mechanism for this unusual finding in osteomyelitis is compression of the microcirculation to bone by subperiosteal and intraosseous pus.


Radionuclide angiocardiographic calculation of the ratio of left-to-right heart outputs in a patient with unusual cardiovascular anatomy: case report. The subject of this case report is an unusual patient whose right lung receives blood from the right heart and whose left lung receives blood from the left heart. Due to this unusual anatomy, it was possible to calculate the ratio of the outputs of the left and right hearts using standard techniques.


Focally increased activity on scinticisternography: report of two cases. Two cases where focally increased activity was noted on scinticisternography are reported. One case involves a documented arteriovenous malformation, and the other, documented embolic vascular disease. After a review of the pertient literature, various other pathologic entities associated with similar scan findings are described. Possible causative mechanisms are discussed.


Development of new radiopharmaceuticals based on N-substitution of iminodiacetic acid. A new approach to radiopharmaceutical design is demonstrated, in which small chelating groups capable of binding gamma-emitting radiometals are attached to biologically active molecules, thus producing radiopharmaceuticals based on bifunctional drug and biochemical analogs. The chelating group iminodiacetic acid has been evaluated for this role by examining two N-substituted iminodiacetic acids: methyliminodiacetic acid (MIDA) and N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (HIDA). Radiochemical and biologic studies showed that both agents were obtained in high radiochemical purity, were stable in vitro and in vivo, and possessed biologic distributions governed almost exclusively by the N-substituted group. These characteristics of 99mTc-labeled N-substituted iminodiacetic acids, prepared using an "instant kit" method, provide the basis for a valuable new class of radiopharmaceuticals based on bifunctional drug and biochemical analogs.


Field flood uniformity correction: benefits or pitfalls? Strict quality control of scintillation camera images is increasingly recognized as important in a nuclear medicine laboratory. The field flood uniformity of the camera should be tested daily. A variety of commercially available data systems facilitate the above task. Concomitantly, scintigrams are increasingly being corrected for uniformity, namely, unbalanced photo-multiplier tubes, uniformity correction can occasionally, depending on the scatter fraction, produce clinically significant artifacts. This effect is due to the application of a linear correction factor to a nonlinear phenomenon.


Stability of radiothyroxine plasma disappearance curve despite catharsis and unblocked thyroidal uptake of radioiodide. Plasma radioactivity was measured over 21 days after an intravenous injection of 50 muCi of 125I-T4 in eight normal men. No thyroid-blocking medication was given. Four subjects (castor oil group) received 30 ml of castor oil on each of Days 13, 14, and 15, while the other four subjects (control group) were studied without medication. After A 5-day equilibration period, plasma 125I-T4 was measured on Days 5-13 in order to calculate the disappearance curve for each subject and to derive the mean for each experimental group. The curves were then extrapolated to Day 21. Measured radioactivity did not depart significantly from the extrapolated line, either during the castor oil period (Days 14, 15, and 16) or during the recovery period (Days 17, 19, and 21). The castor oil, therefore, had no observable effect on the clearance of plasma radioactivity. None of the subjects had a late increase in plasma radioactivity to suggest recirculation of radioiodide or buildup of iodoproteins. In normal subjects, radiothyroxine plasma levels up to 21 days are not significantly affected by short-term catharsis or by failure to block thyroidal radioiodide uptake.


Significance of choline synthesis in the oxidation of the methionine methyl group in rats. Experiments were conducted to assess the significance of de novo choline synthesis in the oxidative metabolism of the methyl group of L-methionine in the rat. Comparison of the rates of 14CO2 production by rats fed diets containing equimolar or equal methyl loads of [methyl-14C]methionine, [methyl-14C] choline, [methyl-14C] betaine and [methyl-14C] sarcosine revealed that the methyl groups of choline, betaine and sarcosine were oxidized at rates nearly equivalent to or exceeding that of the methionine methyl group. However, the results of a second series of in vivo experiments using non-radioactive choline or betaine as intermediary trapping pools indicated that little newly formed radioactive choline was released from tissue phospholipid choline during the period of rapid 14CO2 production from [14CH3] methionine. Incorporation of the methionine methyl group into phospholipid choline by incubated liver slices was strongly inhibited by 2-methoxyethanol without a parallel inhibition of methionine methyl group oxidation. Results of these in vitro studies also indicated that the metabolic pathway responsible for the transfer of the methionine methyl group into choline and that responsible for its oxidation to CO2 differ widely in the ease with which they can be saturated by L-methionine. It is concluded that essentially all of the methionine methyl group oxidation in vitro and that occurring during the absorptive period in vivo must depend primarily on pathways other than those leading to the synthesis of choline.


The effect of a nonabsorbable lipid, sucrose polyester, on the absorption of dietary cholesterol by the rat. The absorption of cholesterol from diets containing various proportions of triglycerides and an unabsorbable fat, sucrose polyester (SPE), was determined in rats. Each replacement of 1% dietary triglyceride with SPE resulted in a 1.2% decrease in cholesterol absorption. The SPE was a mixture of the hexa-, hepta- and octa-esters of long chain fatty acids. The physical properties of this material are similar to those of the usual dietary triglycerides. Relative to these studies, cholesterol was found to be equally soluble in triolein or SPE. If water was present as well, the solubility of the sterol was decreased by the same amount in both fats. The distribution coefficients of cholesterol between an oil phase of either triolein or SPE and a micellar phase simulating that found in the lumen of the intestinal tract were identical. These two types of fats differ in that SPE is neither digested nor absorbed. The decrease in cholesterol absorption is attributed to the continued presence of an oil phase of SPE in the lumen of the intestine. Dietary cholesterol distributes itself between this oil phase and the micellar phase. That portion in the oil phase is not absorbed but is egested in the feces.


Isolation of monoferric phytate from wheat bran and its biological value as an iron source to the rat. The objectives of the study were to isolate and chemically characterize the iron in wheat and to determine the biological availability to the rat of the iron as the purified complex(es). Hard wheat bran contained no butanol extractable or water extractable iron, but approximately 60% of the iron was extracted by 1 to 1.2 M NaCl or ammonium acetate solution. This salt extractable iron complex was purified and identified as monoferric phytate. The purified monoferric phytate was soluble in water. Synthetic monoferric phytate was prepared from sodium phytate and ferric chloride and determined to have spectral characteristics and gel filtration chromatography behavior identical to the complex isolated from wheat bran. The butanol-water-salt extracted bran residue contained no detectable phytate and an as yet uncharacterized form of iron. The biological availability of the iron to the rat was determined by a hemoglobin depletion-repletion bioassay. The relative biological value of the iron as monoferric phytate, either isolated from wheat bran or the synthetic product, was equal to the reference compound, ferrous ammonium sulfate. In contrast, the biological availability of the iron in the bran residue was significantly lower and the low biological availability of an insoluble form of ferric phytate was confirmed. It is concluded that the major portion of the iron in wheat is monoferric phytate and has a high biological availability to the rat. Monoferric phytate in bran may be bound to cationic sites of proteins or other cellular components and utilization of the iron may be through solubilization of the monoferric phytate by ion exchange type mechanism rather than by hydrolysis of the phytate as has been postulated.


Prenatal aspects of ascorbic acid metabolism in the albino rat. Transfer of ascorbic acid and/or its derivatives from maternal blood into the fetus was studied during the last week of gestation in the rat. Rats were injected intravenously with [1-14C]-ascorbic acid and the rate of transfer estimated by the concentration and content of label present in placentas and fetuses. At all times studied the concentration of label in the placenta was greater than in the fetus. The highest capacity of the placenta to concentrate label was found on day 15 decreasing to a low at day 19 and again increasing up to day 21. While in the fetuses, the concentration of label per gram of tissue remained remarkably constant throughout the study. The quantity of labeled compounds transferred into the fetus per gram of placental tissue increased between day 15 and day 21 of gestation.


Effect of fluoride on the mobilization of skeletal magnesium and soft-tissue calcinosis during acute magnesium deficiency in the rat. To investigate the effect of fluoride on the mobilization of skeletal magnesium and on kidney calcification during magnesium depletion, male Holtzman rats were fed a magnesium-sufficient diet (400 ppm of magnesium) and drinking water containing either 0, 50 or 100 ppm of fluoride for a 20-day period prior to the initiation of magnesium deficiency. The high fluoride regimen resulted in a 100-fold increase in the fluoride content of the skeleton. On day 20 magnesium depletion was initiated by feeding the animals a diet containing 12 ppm of magnesium. Over a 4-week period of magnesium deprivation, a 26% decrease of the total magnesium in the humeri was observed. Fluoride exerted a significant effect in retarding the mobilization of skeletal magnesium. Four weeks of magnesium deficiency was associated with a decreased rate of skeletal mineral accretion and with an increase in the kidney calcium content. The decreased rate of mineral accretion was accentuated by the administration of fluoride during the deficiency state. While fluoride exerted an initial protective effect on calcinosis of the kidneys, the overall effect of the administration of fluoride during magnesium deficiency was to promote calcification of the kidneys rather than to prevent it.


Influence of dietary selenium on lead toxicity in the rat. An investigation of the influence of dietary selenium (0.015, 0.05, 0.50, 1.0 ppm) on toxicity of dietary lead (0 and 200 ppm) in the young male rat indicated that selenium was mildly protective against the toxic effects of lead, but only up to 0.50 ppm selenium. At the excess selenium dietary level an exaggeration of lead toxicity was observed. Criteria employed to judge the effects of dietary selenium on lead toxicity included tissue lead concentration and urinary delta-aminolevulinic acid excretion. One exception to the exaggeration effect of excess selenium on lead toxicity was the protective effect of selenium on liver delta-aminolevulinic acid dehydratase activity. Since lead depressed kidney selenium concentration, lead may act as an antagonist to selenium metabolism.


Protein quality of some representative Latin American diets by rat bioassay. A study of the protein quality of twelve different food-mixtures common to Latin America, was performed by rat bioassay. The individual foods were cooked and dried and then mixed in the appropriate proportions resembling the original meals. Rats of the Sprague-Dawley strain were used for the bioassays. Special emphasis was given to the methodology of the slope-ratio techniques preconized by Hegsted and his associates who have claimed that classical bioassays overestimate the nutritive value of poor quality proteins. RNV and RPV values were calculated using the slope-ratio technique, with and without use of a non protein control group. PER, NPR, relative NPR and utilizable protein were also calculated using the same data. The amino acid composition was determined and the score against the FAO/WHO 1973 pattern was compared with the bioassays. Protein value of the diets was also calculated from food table data. Agreement was good between all the procedures especially for the calculation of utilizable protein although the poorest diet containing little else but maize was somewhat overestimated in its quality by calculation from food table data. Thus, in general, estimates for protein quality of diets by standard bioassay techniques and even by amino acid scoring procedures gave values comparable to those obtained by the slope-ratio assays. The large scale re-evaluation suggested for all protein quality data prior to the slope-ratio techniques may not in fact be necessary.


The influence of enrichment with cholesterol on the phagocytic activity of rat macrophages. Prolonged treatment of rats with a cholesterol-rich diet induced hypercholesterolaemia and increased free cholesterol content of peritoneal macrophages. A 2-2 times increase in plasma membrane cholesterol was demonstrated in cholesterol-enriched macrophages. These cells showed a significant inhibition of phagocytosis. The inhibition was 37-0% and 81-7% for latex particles or lipid droplets, respectively.


The lymphoreticular response to a transplanted adenovirus 12-induced tumour of CBA mice. The growth and structure of a virus-induced tumour has been studied in normal and immunised animals. Retardation of tumour growth in immunised animals is accompanied by a lymphoreticular infiltrate; macrophages ingest apparently intact tumour cells.


The effect of hyperthermia on the neuroepithelium of the 21-day guinea-pig foetus: histologic and ultrastructural study. Hyperthermia was induced in guinea-pigs on day 21 of gestation by placing them in an incubator set at 42-5 degrees-43-0 degrees C for 1 hr. At intervals thereafter foetuses were removed from the uterus and sections of the telencephalon were prepared for light and electron microscopy. The histologic and ultrastructural appearance of the telencephalon of the normal 21-day guinea-pig foetus was described for comparative purposes. Damage to cells in mitosis characterised by clumping of chromosomes, and dispersal of polysomes in interphase cells were observed immediately after hyperthermia. Breakdown of the network of junctional complexes was apparent at 4 hr and cellular proliferation was inhibited for 6-8 hr. Degenerative changes and cell deaths were observed deep in the venticular zone after 8 hr; the extent of cell death was related to the post-stressing temperature. Proliferation was resumed at 8 hr and damaged and dead cells moved outward toward the intermediate zone. Phagocytosis of debris by large mononuclear cells was a common finding. Cytoplasmic inclusions, some of which were Feulgen-positive, were present in otherwise normal ventricular cells. Occasional dead cells and empty spaces were present in the ventricular zone at 24 hr and by 48 hr the ventricular zone was normal in appearance. It was concluded that previously observed micrencephaly in the offspring of guine-pig mothers which were heat stressed on day 21 of gestation resulted from a temporary cessation of proliferation and partial depopulation of the proliferating neuroepithelium.


Histological effects of ductal ligation of salivary glands of the cat. Forty-two submandibular, 32 sublingual and 31 parotid glands have been examined microscopically after ductal ligation avoiding the nerves for periods from 1 day to 1 yr. After an initial increase in size, there was over-all atrophy in all three glands. In the parotid gland the response was uniform and there was progressive atrophy until most of the acini were extremely atrophic. However, in the submandibular and sublingual glands the response was very variable, and although in some glands most of the acini were extremely atrophic, in other glands there was far less atrophy and most of the remaining acini appeared more or less similar to normal despite prolonged ligation. These results contrast with those of earlier experimental studies on ductal ligation, but have similarities with observations on the behaviour of human salivary glands.


The application of a serum 17OH-progesterone radioimmunoassay to the diagnosis and management of congenital adrenal hyperplasia. Serum concentrations of 17OH-progesterone were studied serially over 24 hours in 13 treated and untreated patients with the C21 hydroxylase form of congenital adrenal hyperplasia. The results were correlated with measurements of plasma renin activity, serum electrolytes, and urinary 17-ketosteroids and pregnanetriol. In 500 healthy subjects from birth to adult life, serum 17OH-pregesterone levels ranged from 5 to 315 ng/dl. In untreated CAH, serum 17OH-progesterone was markedly elevated (2,000 to 80,000 ng/dl). Treatment with cortisol (20 to 30 mg/m2/day in 3 doses) resulted in normal serum 17OH-progesterone levels in both non-salt-losing and salt-losing patients receiving adequate mineralocorticoid. Even slightly inadequate mineralocorticoid therapy (shown by high plasma renin activity with normal serum electrolytes) was associated with elevated 17OH-progesterone (to 65,000 ng/dl) in spite of usually effective doses of cortisol. Some patients showed isolated 17OH-progesterone elevations (usually early morning), a situation which requires only revision of the cortisol dosage schedule without an increase in total dosage. The data confirm the value of 17OH-progesterone assays in both the diagnosis and management of CAH. Taken together with determinations of plasma renin activity, serum 17OH-progesterone assays can permit more exact control of CAH without excessive doses of glucocorticoid.


Hepatic porto-enterostomy or cholecystostomy in the treatment of extrahepatic biliary atresia. A study of 49 cases. Hepatic porto-enterostomy or cholecystostomy (Kasai's procedure) was successful in restoring bile flow in 31 of 49 patients with "noncorrectable" extrahepatic biliary atresia.  However, all but one of the 31 developed acute or chronic complications such as cholangitis, bile peritonitis, or portal hypertension. During a five-year follow-up period, 26 (53%) died while 9 of the 23 survivors continue to manifest chronic or recurrent cholangitis. Thirteen of the 19 survivors who are more than one year of age have developed portal hypertension. These complications limit the prognosis of infants with "noncorrectable" biliary malformations.


The acute and transient nature of idiopathic immune hemolytic anemia in childhood. The records of 22 children with the diagnosis of idiopathic immune hemolytic anemia were reviewed. Fifty per cent of the children had a history of an antecedent infection and 32% had underlying immune deficiency or lymphoproliferative diseases. The majority (77%) of the patients had an acute self-limited disease which was frequently associated with a positive complement or nongamma Coombs test. The anemia was usually severe, and a number of the children had reticulocytopenia at the time of diagnosis. These children responded rapidly to transfusions and corticosteroids and generally remained well on follow-up. Immunosuppressive drugs did not prove useful in two patients refractory to prednisone, but splenectomy was apparently beneficial in three of four patients so treated. Mortality rate was 18%, with most of the deaths related to an underlying disease.


Granulopoiesis in childhood aplastic anemia. The soft agar technique was employed to investigate factors involved in the regulation of granulopoiesis in ten children with aplastic anemia. Children with AA had greatly reduced numbers of granulocytic colony-forming cells in their bone marrow and in their peripheral blood when compared to "control" children. Colony-stimulating activity was decreased in five of the ten children tested. Serum from eight children with AA did not inhibit colony formation when added to normal adult bone marrow cells in culture. The defect in AA residues in the stem cell, with involvement of the CSA-producing cells in some cases. The serum of these patients does not contain an inhibitor of granulopoiesis.


Malabsorption of iron in children with iron deficiency. Inability to absorb oral iron is believed to be an extremely rare cause of therapeutic failure in the treatment of iron deficiency anemia. Six patients who had failed to respond to oral iron therapy were studied by a simple oral absorption test and contrasted with 25 patients with untreated iron deficiency anemia and 10 normal subjects. All six of the patients who were therapeutic failures demonstrated impaired iron absorption in the absence of other clinical evidence of gastrointestinal disease. In the 25 newly diagnosed patients with iron deficiency. 24 demonstrated elevated iron absorptions while 10 ironreplete normal subjects had minimal elevations in their serum iron values following the administration of the test dose of 1 mg of elemental iron per kilogram. When the therapeutic failures were treated with parenteral iron, all had a therapeutic response. In addition, after treatment the impaired absorption of iron improved transiently. All children who absorbed iron readily responded to oral iron therapy.


Hyponatremia in sickle cell disease. A renal salt-losing state. Severe hyponatremia has been observed in three children with sickle cell disease, and mild hyponatremia was noted during 36% of random hospitalizations for sickle crisis secondary to vasoocclusion or infection. Serum and urinary electrolytes were therefore studied in such patients. Hyponatremia was found in 52% of patients hospitalized with pain and/or fever, even though they received large amounts of sodium intravenously. Urine sodium losses were high with frequent negative sodium balance and weight loss. When well, these patients did not demonstrate hyponatremia, although urinary salt losses appeared to be just as high, suggesting compensatory salt intake when the children are well. It is essential to monitor electrolytes and urinary losses to manage sickle crisis properly. Six to 11 mEq/kg/day of sodium is suggested as a usual need of these patients during crisis. Sickle cell disease patients have, in addition to the better known defect in concentration of urine, a functional defect in dilution of urine at least during periods of "crisis".


The significance of focal sclerotic lesions of glomeruli in children. To establish the relationship between the type of focal sclerotic lesion of glomeruli and the development of progressive renal disease, the clinical courses of 20 children with focal segmental and 7 with focal global sclerosis were analyzed. Only five patients, all of them with focal segmental sclerosis, did not have the nephrotic syndrome, although all had proteinuria. Results suggest that patients with focal global sclerosis have a course identical to that of children with the minimal lesion form of nephrotic syndrome: onset in early childhood, response to steroid therapy, and a relapsing, nonprogressive course. Focal segmental sclerosis, in constrast, is characterized by older age at onset, high incidence of nephritic symptoms, lack of response to steroid therapy, and a progressive course with histologic and functional deterioration. Since most published reports have not distinguished between these two entities, a more favorable prognosis in focal segmental sclerosis may be inferred than is actually the case.


Transient neonatal pustular melanosis.

Transient neonatal pustular melanosis. Newborn infants were observed with vesicopustular and pigmented macular skin lesions, which occurred more commonly in black and mature infants and which were distinct clinically and histopathologically from erythema toxicum. Histopathology of skin biopsies of the vesicopustules is characterized by polymorphonuclear infiltration. The lesions often present as, or evolve into, a pigmented macule and persist from three weeks to three months. There are no associated systemic symptoms.


Renal function in respiratory distress syndrome. Renal function wa assessed in 20 newborn infants with idiopathic respiratory distress syndrome and compared to that of 10 neonates without respiratory distress or renal disease. Inulin and PAH clearances were markedly depressed in neonates with RDS as compared to controls (5.9 +/- 0.6 vs 9.3 +/- 0.8 ml/min/m2 (p less than 0.01) and 13.5 +/- 2.0 vs 23.2 +/- 1.2 ml/min/m2 ( p less than 0.01), respectively). The impairment of inulin and PAH clearances correlated with the severity of the pulmonary disease. Improvement of the respiratory distress was followed by a progressive rise of inulin and PAH clearances toward normal values. Intravenous administration of hypertonic mannitol in three patients resulted in an immediate increase in urine flow and inulin and PAH clearances. It is concluded that a state of acute, reversible, renal insufficiency can occur in the acute phase of idiopathic respiratory distress syndrome.


Anxiety, self-concept, and personal and social adjustments in children with sickle cell anemia. The psychologic effect of sickle cell anemia, a life-long chronic illness, on the self-concept, anxiety level, and personal and social adjustments of school-aged children was investigated by using a battery of standard psychologic tests. Two groups of children were evaluated: a study group of 29 children with sickle cell anemia (hemoglobin SS) and a comparison group of 26 black inner city schoolchildren without sickle cell disease or other known chronic illness. The youngsters with sickle cell anemia did not differ from a peer group of schoolchildren in personal, social, and total adjustments. The self-concept scores of the patient group were lower than those of the comparison group. An unexpected finding of the study was the observation that the anxiety scores (measuring acute anxiety) were significantly lower in the study group than those in the comparison group.


Pharmacokinetic analysis of the disposition of intravenous theophylline in young children. The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The man plasma theophylline clearance was 0.100 +/- 0.036 l/kg/hr, kel 0.49 +/- 0.30 hr-1, betat1/2 3.38 +/- 1.11 hr, alphat1/2 0.13 +/- 0.09 hr, and V1 0.25 +/- 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost identical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetic constants predict that a maintenance dose rate for aminophylline of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/1. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement of steady state) have not yet been conducted.


Telephone assessment of illness by practicing pediatricians. Telephone assessment of illness by 40 practicing pediatricians was studied using simulated complaints of cough, vomiting, diarrhea, or rash. Of a possible 370 standardized questions based on the American Academy of Pediatrics "Guidelines for telephone communications," only 194 were used. Crucial questions such as difficulty breathing with cough, the state of hydration in diarrhea, the character of the eruption in rash, or the presence of abdominal pain with vomiting were asked less than 50% of the time. Pediatricians in practice for fewer than five years requested more information and spent more time on the telephone than did those with greater than five years' experience.


Passive euthanasia of defective newborn infants: legal considerations. The recent increase in reporting of passive euthanasia of defective newborn infants has not been accompanied by extensive analysis of the legality of the practice or the appropriateness of current law. There appears to be criminal liability on several grounds for parents, physicians, nurses, and administrators. Such liability may include charges of homicide by omission, child neglect, and failure to report child neglect. Increasing public exposure of the practice increases the probability that such prosecutions may be brought. Individuals involved in such decisions should be aware of their possible legal liability. If existing legal policy is inappropriate, it sould be changed through open discussion and not subverted through private action. Two alternative policies are described: establishment of criteria for the class of infants who can be allowed to die or a better process of decision making. We conclude that a committment to process would be preferable.


Urinary biogenic amines in idiopathic apnea of prematurity. Urinary biogenic amines were measured in 22 preterm infants of less than 36 weeks' gestational age. Fifteen of these infants had idiopathic apnea. Although levels of urinary dopa were not significantly different, dopamine, norepinephrine and epinephrine were all significantly lower in the infants with apena. It is proposed that apnea of prematurity may be related to an immaturity of catecholamine-producing pathways, leading to inadequate physiologic responses to hypoxia, with resulting accentuation of central respiratory depression. Alternatively, urinary biogenic amines may be a reflection of some unrelated process occurring elsewhere in the body or a depletion of catechol stores resulting from the apnea itself.


Amniotic fluid cortisol after premature rupture of membranes. Total amniotic fluid cortisol concentration was studied in 12 patients at 24 to 34 weeks of gestation after premature rupture of membranes of one to eight days duration. Rupture of the membranes of less than 24 hours duration was associated with normal amniotic fluid cortisol concentrations. Rupture of membranes for more than 24 hours was associated in 10 of 12 patients with higher than normal amniotic fluid cortisol levels. The rise in amniotic fluid cortisol concentrations following premature rupture of the membranes may reflect increased fetal or maternal cortisol production or both, and could explain enhanced lung maturation in such infants.


Effect of premature delivery on the maturation of the Hering-Breuer inspiratory inhibitory reflex in human infants. The Hering-Breuer inspiratory inhibitory reflex was studied serially in a group of premature infants and in a group of term infants in the immediate postnatal period. The premature infants had a stronger inspiratory inhibitory reflex than did the term infants at birth; this reflex decreased with maturation of the premature. Development in the extrauterine environment significantly delayed the rate of disappearance of this reflex. This may indicate that premature delivery retards the neurologic maturation of the human infant. The term infant showed no change in the activity of the inspiratory inhibitory reflex in the first five days of life.


Hematologic abnormalities in severe neonatal necrotizing enterocolitis. Serial determinations of the absolute granulocyte and platelet counts were performed in 40 infants with severe neonatal necrotizing enterocolitis. Fourteen of the 38 infants had absolute granulocyte counts less than 1,500 nm3, the mean absolute granulocyte count was significantly lower in the group of infants who died during the acute episode of NEC as compared to that of the infants who survived. Thrity-five of 40 infants had nadir platelet counts less than 150,000/nm3, clinical bleeding occurred in 12 of the thrombocytopenic infants. Fourteen thrombocytopenic infants were evaluated for disseminated intravascular coagulation by additional coagulation studies; six were noted to have laboratory evidence of DIC. We conclude that (1) a low absolute granulocyte count in severe NEC is associated with a poor prognosis and (2) thrombocytopenia is a significant problem in severe NEC and may occur with or without evidence of fulminant intravascular coagulation.


Pharmacologic observations on the neonatal withdrawal syndrome. The relationship between a maternal dose of methadone and the incidence and severity of neonatal signs of withdrawal, placental transfer of drug, and the relationship between maternal and neonatal plasma levels of  methadone were studied in 30 mothers and their infants. Plasma levels of methadone were analyzed using a gas chromatographic method. Our studies demonstrate that the relationship between maternal dose of methadone and the incidence of neonatal withrawal symptoms was closely related to the last maternal dose of methadone. The ratio of neonatal to maternal plasma concentrations of methadone was 2.2:1. Neonatal withdrawal symptoms appear to be related to individual variation in maternal metabolism of the drug, placental transfer of methadone, and most importantly, to the individual variations in the rate of excretion of methadone as reflected in the neonatal plasma t 1/2. At plasma levels of methadone greater than or equal to 0.06 mug/ml, the symptomatic patients appeared to be protected from withdrawal. When the plasma concentration fell below this level, withdrawal symptoms began within 24 hours.


Genetic counseling for congenital heart disease. The genetic knowledge of parents of children with congenital heart disease, who had received genetic counseling, was compared with that of a control noncounseled group attending the same cardiac  clinic. A follow-up questionnaire showed that both groups had excellent knowledge of the nature of their children's heart lesions. The counseled group had significantly more accurate knowledge of their recurrence risks. Inasmuch as the reproductive attitudes of some of these parents were found to be influenced by genetic information, parents of children with CHD should be given a better understanding of recurrence risks for CHD than many of them possess.


Histocompatibility antigens in childhood-onset arthritis. One hundred and twelve well-studied patients with a prior diagnosis of juvenile rheumatoid arthritis were differentiated into seven clinically distinct subgroups, including a group in whom recognizable ankylosing spondylitis had developed by time of follow-up. An apparent increased prevalence of HLA-B27 in the entire series (26%) was clearly related to its increased prevalence in only two subgroups: patients whose disease had progressed to overt ankylosing spondylitis (five of five patients) and boys with pauciarticular arthritis whose disease would be consistent with early ankylosing spondylitis (11 of 18 patients). There were no significant associations of B27 with systemic onset JRA, polyarticular JRA, pauciarticular JRA in girls, or JRA with chronic iridocyclitis. The only other significant alterations found were increased prevalences of HLA-A2 and HLA-BW15 in patients with polyarticular disease without identifiable rheumatoid factor. This study emphasizes that the clinical disorders included under the category of juvenile rheumatoid arthritis represent more than a single disease and that this heterogeneity must be considered in interpreting studies such as those of histocompatibility typing.


Encephalopathy following measles infection in children with chronic illness. Five patients with an unusual encephalopathy, possible secondary to measles virus infection, are described. Features common to these patients are: an existing chronic disease, neurologic deterioration 2 1/2 to 6 months after a measles infection, and death several weeks later. These events occurred when the chronic disease (e.g. leukemia or neuroblastoma) was in remission. That the measles virus was the causative agent is suggested only by finding in brain and extracranial tissues intracytoplasmic and intranuclear inclusions which contained measleslike particles. Additional clinical features seen in each of the five patients were: seizures, hypertension, and the inappropriate secretion of antidiuretic hormone.


Good diabetic control - a study in mass delusion. The terms "diabetic control" and "diabetic management" are not synonymous. Diabetic control implies normal glucose metabolism, typically monitored by periodic determinations of plasma glucose and urine reducing sugar concentrations. A group of 220 diabetic children attending a camp complied 74% of the time with the request to collect and test their urine for URS. Fifty percent of random URS values determined by the children varied from those obtained on the same specimens of urine by laboratory technicians. Good diabetic control defined URS less than 25gm/24 hours was found in 18 of 54 children.


Modular Formula: an approach to management of infants with specific or complex food intolerances. Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.


Congenital hypothyroidism in a young man with growth hormone, thyrotropin, and prolactin deficiencies. A growth-retarded, mentally deficient, young man is described with diminished secretory response of growth hormone, thyrotropin, and prolactin to the pharmacologic stimuli of insulin, arginine, chlorpromazine, and thyrotropin-releasing hormone. Gonadotropin and ACTH functions were normal both basically and upon pharmacologic stimulation. Additionally, the patient was unresponsive to exogenous thyrotropin injections. These data suggest that the hypothyroidism in this patient was due to combined thyroid dysgenesis and pituitary insufficiency, i.e., primary and secondary hypothyroidism.


Interrupted aortic arch in infancy.

Interrupted aortic arch in infancy. Data from 30 infants with interrupted aortic arch in the New England Regional Infant Cardiac Program, 1968 to 1974, were reviewed. All patients had major associated cardiac abnormalities: approximately one third had ventricular septal defect with patent ductus arteriosus, one third had complex ventricular septal defect with left ventricular outflow obstruction, and one third had complex intracardiac lesions incompatible with survival. Twenty-one of the patients had either palliative or reconstructive surgery, with a hospital mortality rate of 76%. Nine patients did not have surgery; eight of them died at a median age of four days. One-stage primary repair of interrupted aortic arch including the associated cardiac defects, using deep hypothermia and circulatory arrest, is proposed as the current method of treatment in such infants.


Craniosynostosis, midfacial hypoplasia and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred. An unusual spectrum of craniofacial and foot abnormalities has been detected within a large midwestern Amish kindred. Enlarged great toes and craniofacial abnormalities suggested Pfeiffer acrocephalosynadactyly type V; however, thumb abnormalities were not present. Eighty-eight affected individuals were observed and another 50 were reliably reported to be affected. An autosomal dominant inheritance pattern was observed associated with variable expressivity. All affected individuals had some clinical or radiologic abnormality of the feet. The phenotypic expression was so variable that the entire spectrum of dominantly inherited craniofacial dysotoses-acrocephalosyndactylys (except the typical Apert syndrome) was seen within this kindred.


A neurologic comparison of pre-term and full-term infants at term conceptional age. There are currently no neurologic examinations designed for pre-term infants with sufficient data to determine neurologic deviance at various gestational or conceptional ages (gestational age plus age from birth). In this study a neurologic examination standardized for full-term newborn infants was administered to 97 full-term newborn infants was administered to 97 full-term newborn infants and 97 pre-term infants at their expected date of birth, 40 weeks' conceptional age. The pre-term infants had more weak responses than did the full-term infants despite being at a higher level of activity state throughout the examination. The pre-term infants also had more asymmetric responses. There was no correlation between gestational age and the incidence of weak responses in the pre-term infants, but the pre-term infants of lowest birth weight at all gestational ages had the greatest number of weak responses. The latter may be because pregnancy and neonatal problems contribute more to the neurologic findings than does the length of gestation.


Complexity and measurement of hypnotic susceptibility: a comment on Coe and Sarbin's alternative interpretation. Coe and Sarbin's claim that a single role skill dimension accounts for individual differences in hypnotizability is not supported by an empirical analysis. We suggest that current measures of hypnotic susceptibility are not only factorially complex but contain a sizable nonhypnotic variance component. Implications for the assessment of "true" hypnotic susceptibility are discussed.


The Honi phenomenon revisited: factors underlying the resistance to perceptual distortion of one's partner. An individual being viewed in an Ames room usually appears considerably altered in physical size to an observer. However, some married persons perceive less size distortion of their spouses than a stranger. This instance of selective perceptual distortion, known as the Honi phenomenon, could perhaps reflect differential familiarity and/or emotional involvement toward these stimulus persons. Using heterosexual couples as subjects, we investigated familiarity (i.e., length of the relationship), type of relationship (i.e., dating, engaged, or married), and positive cathexis (i.e., love, liking, and trust of one's partner) as possible mediators of this effect and also explored the impact of some judgemental variations. Neither familiarity nor type of relationship influenced relative perceptual distortion of partner versus stranger. Rather, selective perceptual distortion was directly related to the strength of positive cathexis, principally among females. Only women high in positive cathexis exhibited the Honi phenomenon and perceived a stranger as being more distorted than their partners. In contrast, size judgements by men were affected only by the sequence in which stimulus persons were observed. Implications and interpretations of these findings are discussed.


Self-disclosure: an attributional perspective. This experiment examined the effect of timing of an intimate disclosure and assignment of responsibility for the event disclosed on interpersonal attraction. Subjects were induced to interact with a confederate who in all cases revealed something quite personal about himself. The disclosure occurred either early or near the end of a 10-minute conversation. The confederate accepted responsibility for the event disclosed, did not mention responsibility, or assigned responsibility to external factors. Negative traits were assigned to the early disclosure, and he was liked significantly less than the late discloser. The results are explained in terms of differential attributions made to early and late disclosures. The results for the assignment of responsibility variable were surprising: The confederate who accepted responsibility for the event disclosed elicited more negative reactions than the confederate who blamed other factors or who did not mention responsibility. Some possible reasons for this unexpected finding are discussed.


Multidimensional locus of control in sociopolitical activists of conservative and liberal ideologies. Three studies were conducted to examine the relationship between a multi-dimensional measure of locus of control and sociopolitical activism, controlling for the effects of political ideology. In Study 1, 98 male college students completed a measure of conservatism-liberalism. Kerpelman's Activism scale, and locus of control scales designed to differentiate between two types of externals: belief in powerful others versus belief in chance forces. In Studies 2 and 3, female college students (Ns=26 and 40) who differed in the extent of their participation in leftist political activities or feminist causes responded to the multidimensional locus of control scales. As predicted, results from analyses of variance and trend analyses indicate that for liberals, increases in expectancies of control by powerful others are positively associated with increases in activism, while for conservatives, there is a negative relationship. The importance of controlling for ideology and the implications of the differentiated view of externality for understanding social action are discussed.


Biographical determinants of achieved eminence: a multivariate approach to the Cox data. Ranked eminence of creators and leaders was hypothesized to be a function of both substantive (developmental and productive) variables and methodological artifacts. Cox's sample of 301 geniuses was reexamined using multiple-regression techniques. The results indicated that ranked eminence is (a) a curvilinear inverted-U function of education for creators but a negative linear function for leaders, (b) a positive linear function of versatility for leaders only, and (c) a curvilinear U-shaped function of life span for creators but a "backwards-J" function for leaders. Although creators are more intelligent than leaders, the correlation that Cox found between intelligence and ranked eminence was shown to be an artifact of data reliability and, especially, a timewise sampling bias. It was also shown that father's status has no direct impact on ranked eminence.


Aggression and heat: the influence of ambient temperature, negative affect, and a cooling drink on physical aggression. Two experiments were conducted to examine the influence of ambient temperature upon physical aggression. In the first, male subjects received either a positive or negative evaluation from a confederate and were then provided with an opportunity to agress against this person by means of electric shock. On the basis of previous research, it was predicted that high ambient temperatures (92-95 degrees F) would facilitate aggression by those receiving positive evaluations but actually inhibit such behavior by those receiving negative assessments. Results confirmed both of these predictions and also indicated that more moderate but still uncomfortably warm temperatures (82-85 degrees F) produced similar effects. The second experiment employed procedures similar to the first and examined the suggestion that administration of a cooling drink would reduce the impact of high ambient temperatures upon overt aggression. This prediction, too, was confirmed. The possible mediating role of negative affect with respect to the influence of ambient temperature and other environmental factors upon aggression was discussed.


Causal priority of social desirability over self-concept: a cross-lagged correlation analysis. The study examined the causal relationship between social desirability (SD) and self-concept (SC). Two self-report instruments--Crandall's Children's Social Desirability Scale and the Piers-Harris Children's Self-Concept Scale--were administered before and after a 9-month therapeutic treatment designed to enhance self-concept. Subjects were 57 upper elementary pupils in a laboratory research school. Three hypotheses were proposed: (a) There is a positive correlation between SD and SC; (b) SD is more stable across time than SC; and (c) SD is causally prior to SC. Cross-lagged panel correlation analysis supported all three hypotheses. Discussion centers on a causal explanation of the distorting effect of SD upon SC scores.


Achievement and morality: a cross-cultural analysis of causal attribution and evaluation. A recent study by Weiner and Peter has considered the emergence of  certain patterns of attribution and evaluation in achievement and moral situations. According to their analysis, judgments should generally follow a Piagetian sequence in which younger children are influenced more by the outcome of an episode and older children by the intent of the protagonist. With a sample of U.S. subjects they found overall support for this analysis. A major of the present study is to determine how sociocultural factors may influence the judgmental patterns outlined by Weiner and Peter by essentially replicating their study in the manifestly different cultural context provided in Iran. Important discrepancies with Weiner and Peter were found which can be attributed to sociocultural factors. However, the cognitive-developmental framework proved generally valuable in working toward a comparative understanding of socialization patterns extant in the two cultures.


Externality in the nonobese: effects of environmental responsiveness on weight. The study considered whether external responsiveness in normal weight people would predict changes in eating behavior and weight following major alteration of environmetnal food cues. Normal weight children were tested for externality on measures of eating, slide recall, and extremity of affective responsiveness during the first week of a summer camp, and were weighed biweekly thereafter. There was a significant correlation between externality and weight change, indicating that the more externally responsive the children were, the more weight they gained. The implications of this finding for theories about the development of obesity were considered.


Effects of nonverbal dissimulation on emotional experience and autonomic arousal. Three studies are reported that examine the relationship between the nonverbal display of emotional affect and indices of the emotional state. Subjects were asked either to conceal or to exaggerate the facial display associated with the anticipation and reception of painful shocks that varied in intensity. Both self-reports of shock painfulness and skin conductance measures of emotional response showed significant changes paralleling the changes induced in expressive behavior; that is, the suppression of expressive responses decreased the magnitude of phasic skin conductance changes and subjective reports of painfulness as compared to the free expression or exaggeration of pain-related expressive response. The effects were obtained for shocks of varying intensities and for both male and female subjects. The findings support theories of emotion that assume that expressive responses serve a self-regulatory as well as a social-communicative function, and further suggest that the self-regulation is mediated neurally, rather than via a process of self-attribution. Finally, the results highlight the need for research on dissimulation in social interaction to consider the effects of acting upon the actor, as well as its effects upon the inferences of observers.


Psychometric, diurnal, and electrophysiological correlates of activation. Several studies were performed using Thayer's Activation-Deactivation Adjective Check List (AD-ACL). Factor analysis of college students' scores identified a single activation factor representing a continuum ranging from sleep through wakefulness. Next, changes over the diurnal cycle in activation factor scores were demonstrated. One-week test-retest reliability was also investigated. Finally, activation scores were related to pulse rate, respiration rate, and skin resistance level under passive and active conditions. Correlations between factor scores and electrophysiological measures were higher than were intercorrelations of electrophysiological measures, indicating that scores on this revised activation factor represent a valid measure of phenomenological bodily activation level.


The perception of self and others: acquaintanceship, affect, and actor-observer differences. Three studies were designed to examine how people perceive themselves versus others. The main finding was that people were seen as causing positive behaviors, and situational factors were regarded as causing negative behaviors (positivity effect). This positivity effect was found to operate most strongly for perceptions of intimate others, such as spouse and friends, and less strongly for strangers and liked and disliked acquaintances. There was little support for the actor-observer difference that people view their own behavior more situationally than they do other people's behavior. It was concluded that both cognitive and motivational factors must be considered in predicting how people perceive and describe others.


Egotism and attribution.

Egotism and attribution. Egotism is defined as the tendency to make attributions that put oneself in the best possible light, for example, the attribution of good outcomes to one's skill rather than to luck. An experiment was designed to demonstrate egotism. To rule out alternative explanations, the experiment compared the attributions of actors and observers for both good and bad outcomes. Theoretical considerations suggested that egotism might be especially likely at the conclusion of competition. Hence, subjects competed, won, or lost and then made attributions for their own and their opponents' outcomes. Evidence for egotism was clear. In addition, subjects made predictions of their opponents' attributions, which often turned out to be fairly accurate.


The coronary-prone behavior pattern and the suppression of fatigue on a treadmill test. A study was conducted to test the hypothesis that Type A (coronary-prone) individuals would show greater suppression of subjective fatigue than Type B (non-coronary-prone) individuals in order to persist at a tiring but challenging task. Type A and Type B college students completed a Balke treadmill test (at a walking pace) while rating their fatigue at 2-minute intervals. Each subject also completed another treadmill test (at a running pace) that was designed to assess maximum aerobic capacity. Subjects' aerobic capacities and their aerobic performance levels attained on the Balke test were determined by analysis of expired air. Each subject's walking performance was scored as a proportion of his maximum aerobic capacity. Analysis of the resulting percentage values indicated greater effort among A's than B's. Moreover, the subjective fatigue ratings of A's were lower than those of B's. The results were discussed in terms of fatigue suppression as an instrumental response for attaining mastery over the environment. consideration was also given to the role of fatigue in the onset of coronary heart disease.


Interpersonal attraction and rewarding aspects of disclosure content and level. The relationship between self-disclosure and interpersonal attraction was viewed within the context of theories of social penetration and social exchange. The effects of similarity of disclosure level and similarity in content of disclosure on interpersonal attraction were assessed. Specifically, 24 high-self-disclosing subjects and 24 low-self-disclosing subjects were presented with four bogus inventories manipulated on the variables of agreement in content and amount of disclosure. The reward potential of various factors within the disclosure process were measured by the subject's attraction to these four hypothetical strangers. Results indicated that along with amount of disclosure, similarity in the content of the disclosed material and similarity between the subject's and another's level of disclosure had a positive influence on attraction.


Effects of prior destructive behavior, anonymity, and group presence on deindividuation and aggression. Three of Zimbardo's deindividuation input variables (group presence, anonymity, and arousal) were manipulated in laboratory experiment, and their effects on aggression and deindividuation were measured. Only arousal produced a significant increase in aggression (p less than .05), while group presence produced a significant decrease in aggression (p less than .01). Anonymity had no significant effect on subjects' aggressiveness. Deindividuation per se was measured on a postsession questionnaire that assessed subjects' memory for their own aggressive behavior, self-consciousness, concern for social evaluation, and memory for central and peripheral cues. Only arousal condition participants showed deindividuation changes, but a factor analysis revealed that the deindividuation changes did not comprise a unified factor. Also it did not appear that the internal changes caused aggressive behavior, since the correlation between the two was low.


Learned helplessness, depression, and the attribution of failure. Depressed and nondepressed college students received experience with solvable, unsolvable, or no discrimination problems. When later tested on a series of patterned anagrams, depressed groups performed worse than nondepressed groups, and unsolvable groups performed worse than solvable and control groups. As predicted by the learned helplessness model of depression, nondepressed subjects given unsolvable problems showed anagram deficits parallel to those found in naturally occurring depression. When depressed subjects attributed their failure to the difficulty of the problems rather than to their own incompetence, performance improved strikingly. So, failure in itself is apparently not sufficient to produce helplessness deficits in man, but failure that leads to a decreased belief in personal competence is sufficient.


Personal space invasions in the lavatory: suggestive evidence for arousal. The hypothesis that personal space invasions produce arousal was investigated in a field experiment. A men's lavatory provided a setting where norms for privacy were salient, where personal space invasions could occur in the case of men urinating, where the opportunity for compensatory responses to invasion were minimal, and where proximity-induced arousal could be measured. Research on micturation indicates that social stressors inhibit relaxation of the external urethral sphincter, which would delay the onset of micturation, and that they increase intravesical pressure, which would shorten the duration of micturation once begun. Sixty lavatory users were randomly assigned to one of three levels of interpersonal distance and their micturation times were recorded. In a three-urinal lavatory, a confederate stood immediately adjacent to a subject, one urinal removed, or was absent. Paralleling the results of a correlational pilot study, close interpersonal distances increased the delay of onset and decreased the persistence of micturation. These findings provide objective evidence that personal space invasions produce physiological changes associated with arousal.


Effects of control and predictability on the physical and psychological well-being of the institutionalized aged. It was hypothesized that some of the characteristics frequently observed among the aged--such as feelings of depression and helphlessness, as well as accelerated physical decline--are at least in part attributable to loss of control. A field experiment in which institutionalized aged were randomly assigned to one of four conditions was carried out to assess the effects of increased control and predictability upon the physical and psychological well-being of the aged. Individuals in three of the four conditions were visited by college undergraduates under varying contingencies, while persons in the fourth condition were not visited and served as a baseline comparison group. Subjects in the control condition could determine both the frequency and duration of visits they recieved. A second group of subjects (predict) was informed when they would be visited and how long the visitor would stay, but had no control over these details. A third group (random) was visited on a random schedule. It was found that predictable and controllable positive events have a powerful positive impact upon the well-being of the institutionalized aged.


Ares and Babbitt in the classroom: effects of competition and reward on children's aggression. In many competitive situations, aggression is one of several instrumental behaviors that can produce reinforcing consequences. Despite the fact that aggression precipitated by competition for valued resources is an increasingly important social problem, there is little evidence of a causal relationship. In a factorial experiment, dyads of 64 kindergarten and first-grade males played a game in a face-to-face setting that yielded a prize for the winner only. It was predicted that high levels of competition and high levels of reward magnitude would produce more aggressive behavior than lower levels of these variables. Additionally, children rated by their teachers as high in dispositional aggressiveness were anticipated to behave most aggressively in the game. Each of these predictions was confirmed on three different measures of aggression: verbal, interference, and physical. Furthermore, the data suggested that constructive action was sometimes abandoned in attempts to harm an opponent. Since competition for desirable objects is a social reality, it was concluded that conditions inhibiting aggression in these situations should be investigated.


Effects of a stimulus associated with a victim's pain on later aggression. Male college students participated in an experiment designed to associate a neutral stimulus with a victim's pain and then to assess the impact of the paired stimulus on their aggression. The subjects were either provoked or not provoked by a confederate's shock evaluation. They then observed a flashing white light that was associated with either their former evaluator's pain or an irrelevant, affectively neutral event. The subjects then administered electric shocks to a different confederate, with whom they had not interacted previously, at the flash of both the familiar white light (the conditioned stimulus) and a novel blue light. Results supported the prediction that provoked subjects would give more intense shocks to the conditioned stimulus when it had been associated with their evaluator's pain. Unprovoked subjects were found to give less intense shocks to the light that had been associated with their evaluator's pain.


Evidence of stress as a function of experimentally altered appraisal of stimulus aversiveness and coping adequacy. The present study examined the effects of initial appraisal of stimulus aversiveness and coping adequacy on subsequent evidence of stress. Results indicated that level of appraised coping efficacy had the most pronounced effect during stressor exposure and that the pattern of this effect was dependent on whether the source of the appraised coping resources was "personal" (the subject's own resources) or "environmental" (a bogus technique donated by the experimenter). In addition, information about personal resources reduced the pre- to poststressor increment in state anxiety and lessened cognitive avoidance of stressor-related stimuli. Results were discussed with respect to differential sensitivity of components of stress response to variation in environmental versus personal sources of coping efficacy, and the specific aspects of cognitive structuring associated with variation in physiological reaction (muscle tension) were noted. The importance of factors associated with appraised coping efficacy was clearly supported, but factors involving the objective (in contrast to defensive) aspects of appraised stressor potency required further investigation, and suggestions for such future research were made.


Person perception and the Berkowitz paradigm for the study of aggression. Three experiments in person perception were conducted to investigate the conditions under which naive observers label an actor as aggressive and to ascertain how this label affects the reactions of the observers to the actor. These studies were performed by exposing subjects to written descriptions of Berkowitz's much-used paradigm for the study of aggression in order to additionally demonstrate that naive observers do not label in the same way as do research psychologists. In Experiment 1 the hypothesis was confirmed that harm-doing behavior is labeled as aggression only when it is antinormative. When harm doing was justified by the instigation or attack of another person, its use did not lead to the actor being labeled as aggressive. In Experiment 2 it was found that violation of the limits imposed by the experimenter on the number of shocks that could be used by actors led observers to characterize them as aggressive even when their action was justified by the prior instigation of the other party. Violation of two norms led to a more aggressive rating of the actor than did the violation of only one norm. Experiment 3 showed that actors who are labeled as aggressive are disapproved of and avoided by observers. The results of these studies are discussed in terms of the ecological validity of Berkowitz's research paradigm and metatheoretical implications for the scientific study of harm-doing behavior.


Collective coping with stress: group reactions to fear, anxiety, and ambiguity. A review of studies examining the fear-affiliation relationship revealed that none had ever observed groups in interaction while awaiting a fearful event. It was predicted that such groups would, consistent with individual member's previously studied affiliative preferences, spend more time interacting in the service of social comparison needs than would groups facing anxiety or ambiguity. This prediction was strongly supported, and in addition, it was found, as expected, that groups in the fear condition developed a relatively high degree of cohesiveness as measured by intragroup attraction ratings. The implication of these results for the interpretation of the functional relationship between stress and cohesiveness was discussed.


Effects of self-esteem and expected duration of interaction on liking for a highly rewarding partner. Psychological theories predicated on the assumption of human selfishness and theories based on principles of equity may lead to conflicting predictions about when a person will like his partner. Of special interest are a person's reactions to receiving uncommonly high rewards. The present study addressed this issue by examing the development of same-sex liking in 40 female college students. It was hypothesized that subjects with lowered self-esteem, having a great need for interpersonal rewards, would react favorably to the receipt of such rewards, even if underserved. Subjects with raised self-esteem, on the other hand, having had their need for rewards met, should respond unfavorably to the receipt of high rewards, desiring a more equitable distribution of reward. These effects should be strong only when continuing dyadic interaction is expected (i.e., as issues of stability and reciprocity become salient). The predictions were confirmed.


Arbitrary norms and social change in high- and low-authoritarian societies. Following Jacobs and Campbell's methodology for replacing confederates and naive subjects over 11 successive generations, this study considered the impact of authoritarianism on the rate of social change of arbitrary norms in laboratory societies. Subjects were 116 college students scoring high and low on the California F scale who participated in an autokinetic experiment either with no confederates (control), confederates who made estimates in a range of 9 to 15 inches (22.86-38.10 cm) (moderately arbitrary), or those who estimated in a range of 15 to 21 inches (38.10--53.34 cm) (extremely arbitrary). Results indicated: (a) High-F societies perpetuated arbitrary norms (both 9-15 and 15-21) for more generations than low-F societies; (b) in low-F societies, the 9-15- and 15-21-inch norms rapidly declined; and (c) in high-F societies, the 15-21-inch norms gradually declined, while the 9-15-inch norm declined very little. Overall, the results suggested that an interaction model would better described social change than do presently existing theories of social change.


A renewed look at Miller's conflict theory of aggression displacement. The present study is the first to examine Miller's theoretical assumptions of displaced aggression using human subjects. Subjects in the present study either served as nonangered controls, were angered by the experimenter's confederate, or were both angered by and led to fear the confederate. All subjects were then able to three targets: the confederate, a person described as a friend of the confederate, and a person having no association with the confederate. Targets received the most intense aggression from angered subjects. The difference between the aggression gradients for high-anger-low-fear and control subject. Frightened subjects gave their most intense aggression to the displaced targets. Results also support the suggestion that direct aggression is most likely if the aggressor can first extinguish some of his fear by attacking more indirect targets.


Trait salience in the spontaneous self-concept. A discrimination theory of selective perception was used to predict that a given trait would be spontaneously salient in a person's self-concept to the exten that this trait was distinctive for the person within her or his social groups. Sixth-grade students' general and physical spontaneous self-concepts were elicited in their classroom settings. The distinctiveness within the classroom of each student's characteristics on each of a variety of dimensions was determined, and it was found that in a majority of cases the dimension was significantly more salient in the spontaneous self-concepts of those students whose characteristic on thedimension was more distinctive. Also reported are incidental findings which include a description of the contents of spontaneous self-comcepts as well as determinants of their length and of the spontaneous mention of one's sex as part of one's self-concept.


Verbal imagery and connotation as memory-induced mediators of aggressive behavior. Three studies investigated the effects of an information-processing variable (imagery-concreteness) on susceptibility to aggressive stimulation. Study 1 (n=83) results indicated that subjects' rating of imagery level and aggressive connotation for words can be manipulated independently. In study 2 (n=64), manipulations of verbal connotation and verbal imagery indicated that imagery level but not aggressive connotation significantly influenced the delayed recall of the verbal material. In Study 3 (n=60), males in a 2 X 2 between-subjects factorial design first learned lists of words varying in imagery (high or low) and verbal connotation (aggressive or neutral). Next, subjects were given the opportunity to shock their partners as part of a sham learning task. To induce arousal, all subjects learning high-imagery-aggressive word lists delivered significantly more intense shock to their partners. The results were interpreted as supporting an information-processing (memory) analysis of the effects of exposure to aggressive material.


Information about the model's unconditioned stimulus and response in vicarious classical conditioning. Four groups with 16 observers each participated in a differential, vicarious conditioning experiment with skin conductance responses as the dependent variable. The information available to the observer about the model's unconditioned stimulus and response was varied in a 2 X 2 factorial design. Results clearly showed that information about the model's unconditioned stimulus (a high or low dB level) was not necessary for vicarious instigation, but that information about the unconditioned response (a high or low emotional aversiveness) was necessary. Data for conditioning of responses showed almost identical patterns to those for vicarious instigation. To explain the results, a distinction between factors necessary for the development and elicitation of vicariously instigated responses was introduced, and the effectiveness of information about the model's response on the elicitation of vicariously instigated responses was considered in terms of an expansion of Bandura's social learning theory.


Machiavellianism in patients and their children. The role of the family in the development of Machiavellianism was examined in this study. High- and low-Machiavellian sixth graders played a bluffing game. Their parents completed Machiavellian belief measures. The Machiavellianism of fathers and mothers was positively related to their children's success at deceiving others but not at seeing through others' attempts at deception. In addition, fathers' Machiavellianism was positively related to their children's Machiavellian beliefs. These data support a modeling hypothesis for the development of Machiavellianism. Unexpectedly, the children's own behaviors and beliefs were unrelated. This pattern of results suggests that a child's manipulative behaviors and beliefs are learned separately and only become consistent over time.


Controlled drug release from polymeric delivery devices IV: in vitro--in vivo correlation of subcutaneous release of norgestomet from hydrophilic implants. The in vitro and in vivo releases of norgestomet from hydrophilic implants were found to follow a matrix-controlled (Q - t1/2) process. The sorption of drug onto the implants was observed to obey the same mechanism but with a much smaller magnitide of the Q/t1/2 value. The effect of the extent of cross-linking on the magnitude of drug release (Q/t1/2) profiles was analyzed both theoretically and experimentally. The release of norgestomet from hydrophilic implants was found to be an energy-linked process. Two energy terms were calculated; the activation energy for matrix diffusion was 7.71 kcal/mole, and the heat of drug crystal solvation was 25-28.6 kcal/mole.


Modification of diffusion rates of benzocaine from topical vehicles using sodium salicylate as complexing agent. The release of benzocaine from various topical vehicles containing benzocaine, alone and in the presence of a complexing agent, sodium salicylate, was measured at 37 degrees using dialysis through a cellulose membrane. Sodium salicylate had a marked effect on the release of benzocaine, depending upon the the type of vehicle, with the largest increase observed for the water-miscible base, polyethylene glycol (macrogol ointment BPC). The amount of drug released from preparations containing 1% (w/w) and 2% (w/w) benzocaine in this vehicle depended upon the sodium salicylate concentration. Results are discussed in terms of the differing physical properties of the complexes formed.


Release and elimination of 14C-fluphenazine enanthate and decanoate esters administered in sesame oil to dogs. The rates of release of 14C-fluphenazine enanthate and 14C-fluphenazine decanoate were compared in two groups of five male dogs. Each dog was given a single dose (2 mg/kg im) of either the enanthate or decanoate ester in sesame oil. The times required to attain maximum concentrations of radioactivity in plasma were 3.8 +/- 0.5 days (+/-SE) for the enanthate ester and 10.6 +/- 1.1 days for the decanoate ester (p less than 0.001); maximum concentrations of radioactivity in the plasma at these times were 16.7 +/- 1.1 and 11.1 +/- 1.2 ng/ml, respectively (p less than 0.01). However, 35 days after dosing, the concentrations of radioactivity in plasma were greater for the decanoate ester than for the enanthate ester. The times required for 50% of the dose to be excreted in the urine and feces were 7.8 +/- 0.5 days for the enanthate ester and 22.6 +/- 4.4 days for the decanoate ester (p less than 0.05). The total amounts excreted in 35 days were 85.4 +/- 1.8 and 68.8 +/- 6.6% of the dose for the enanthate and decanoate esters, respectively; the average half-times for the rates of release of radioactivity from depot and body, as calculated from the data for total excretion, were 5.55 days for the enanthate ester and 15.4 days for the decanoate ester. Thirty-five days after dosing, the amount of the dose present in the injection site was 4.6 +/- 1.6% for the enanthate ester and 18.6 +/- 5.7% for the decanoate ester. Two groups of six dogs each were protected against the emetic effects of apomorphine more than twice as long by the decanoate ester than by the enanthate ester after the subcutaneous administration of single 8-mg/kg doses of either drug in sesame oil (p less than 0.05). Based on measurements of total radioactivity, it was concluded that the decanoate ester was released from the depot at less than one-half the rate of the enanthate ester.


Analysis of butaclamol in serum by fluorescence induction. A sensitive TLC-fluorometric method was developed for the analysis of butaclamol, a benzo[6,7]cyclohepta[1,2,3-de]-pyrido[2,1-a]isoquinoline derivative, in serum. The method involves cyclohexane extraction of serum samples followed by TLC of the concentrated extracts. The developed TLC plates were sprayed with an oxidizing reagent and heated at 110 degrees. Highly fluorescent spots were produced for butaclamol, which was well separated from metabolites and serum components. Fluorometric densitometry permitted quantitation with a sensitivity of 10 ng/spot application.


Bioavailability assessment under quasi- and nonsteady-state conditions II: study designs. The flexibility of bioavailability assessment at quasi-and nonsteady state is demonstrated by systematically removing experimental constraints from the study design. Mathematical expressions are derived to describe each design variation. From the resultant solutions, it is evident that the proposed method can accommodate nonuniformities in dose, dosage interval, dosage regimen, dosing cycle, sampling interval, plasma half-life, washout period, and protocol adherence. Nominal requirements for the method are linear kinetics and mean plasma concentrations estimated over time intervals beginning and ending in the log-linear region.