Undernutrition and the developing cerebellar cortex in the rat. Undernutrition of the newborn rats, produced during the first 3 weeks by increasing the litter size and restricting the mother's diet, resulted in reduction of the body and brain weights of the experimental animals. One group of undernourished animals showed especially severe reduction of body and cerebellar weights. These animals, on the 10th postnatal day, had an immature cerebellar cortex corresponding to that of the 7th day postnatal control animals. The external granular layer persisted in the cerebellar cortex of the underweight animals until the 23rd day, while it disappeared by 20th day in the control animals. Mitotic activity was evident until the 21st postnatal day in these animals while it stopped in the normal animal by 16th postnatal day. There was no marked difference in the fine structure of the various cell types in the control and undernourished animals. Midsagittal tracings of the cerebellar cortex showed a reduced surface area in the undernourished animals, while the thickness of the external granular layer and molecular layer did not show any significant difference when compared to that of the control animals, thus showing a reduction in total cell number, but not per unit area. The normal morphological appearance of the cerebellar cortex in the underfed animals of higher weight probably indicates that these animals are adequately nourished in spite of the reduction in weight when compared to the control animals, which probably are overfed.


Three dimensional analysis of unmyelinated fibers in normal and pathologic autonomic nerves. The technique of serial-section electron microscopy and diagrammatic three dimensional reconstructions has been used to assess normal and pathological unmyelinated nerve fibers from a peripheral autonomic nerve: the rat cervical sympathetic trunk. Within this predominantly unmyelinated nerve, there is a complex arrangement of axons into longitudinally oriented bundles brought together by chains of Schwann cells. Each bundle is subdivided into smaller components by the cytoplasmic processes of Schwann cells; such subdivisions, which are basal lamina-enclosed masses of Schwann cell cytoplasm, when viewed on cross-sectional electron micrographs, are termed Schwann cell units. The size and shape of each Schwann cell unit varies along the length of fibres, but the diameter of individual axons shows little variation over the segments studied. Axonal branching was not observed in normal unmyelinated nerves. Crush injury and x-irradiation produces different patterns of alteration in the axon-Schwann cell relationships of unmyelinated nerves. Following crush injury, Schwann cell processes increase in diameter and contain numerous small diameter axonal sprouts. Many of the regenerating axons remain thin while others reacquire a normal diameter. X-irradiation affects Schwann cells leading to retraction of their processes and the appearance of naked axonal segments.


Membranous bodies in the cerebral cortex of aging rats: an electron microscope study. Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuoles, and they occur within dendrites which must expand to accomodate them. Some of these bodies measure 9 mu X 13 mu although the median size is about 6 mu in diameter. The membranes which make up the bulk of the complex bodies are assembled into sheets. These sheets are composed of 4 to as many as 100 layers and form undulating circular profiles within dendrites. The individual trilaminar membranes are about 60 A thick and exhibit a distinct tendency to pair within the sheets they form. The source of this great volume of membranes is not known since one finds neither a visible continuity with membranous organelles nor early stages in the formation of these membranous bodies.


Ultrastructure of the axon reaction in the immature rat thalamus. The axon reaction was studied using immature rats aged 4 or 14 days at the time of unilateral removal of the cingulate cortex. After survival times of one to 5 days they were sacrificed and the anterior thalamic nucleus was examined using ultrastructural methods. The degree of degenerative change was much more intense in the 4-day group where the center of the reactive area was characterized by pronounced lysis of the neuropil and the loss of most neurons. Dark neurons were observed in both groups but mitochondrial proliferation was restricted to the 14-day group. Evidence for microglial formation from pericytes was observed in the 4-day group while reactive astrocytes were observed in both groups. It was concluded that a rapid maturation of the thalamic injury response occurs between the 4th and the 14th day in the rat so that by the 14th day the response is similar in many respects to that of mature animals.


Tolosa-Hunt syndrome: one cause of painful ophthalmoplegia. The author reports 12 cases of Tolosa-Hunt syndrome, a benign steroid-resistant cryptogenic granuloma that presents as painful ophthalmoplegia. This syndrome is differentiated from other causes of painful ophthalmoplegia including tumors, aneurysms, collagen disease, specific infections, mucoceles, and benign granulomas of unknown etiology. These other conditions should be excluded by appropriate tests. Surgical exploration is not necessary if there is a prompt remission on steroid therapy.


Lateral microsurgical approach to intraorbital tumors. The authors describe their microsurgical lateral orbital approach to intraorbital tumors. In seven patients ultrasonic scanning, computerized axial tomography, polytomography, orbital venography, and arteriography have allowed precise intraorbital tumor localization relative to the optic nerve. The authors believe that circumscribed tumors superior, lateral, or inferior to the optic nerve can be safely and completely removed through a 30-35-mm lateral skin incision with microsurgical dissecting techniques. A combined neurosurgical-ophthalmological team approach is emphasized.


Metastasis via ventriculoperitoneal shunt in patients with medulloblastoma. The authors have routinely inserted a ventriculoperitoneal shunt in all patients with a posterior fossa tumor and hydrocephalus some 7-10 days prior to craniotomy. Forty-one patients with medulloblastoma were treated in this fashion and of these, four metastasized through the shunt and died of systemic metastases without evidence of recurrent tumor in their central nervous system. A millipore filter  which can be incorporated in the shunt has been used by the authors during the past 18 months in an effort to prevent metastatic spread through the shunt.


Infections complicating the use of external ventriculostomy. The use of external ventriculostomy at our institution has been retrospectively analyzed to determine the incidence of cerebrospinal fluid sepsis. Placement of 65 ventriculostomies over a 2-year period resulted in three cases of complicating meningitis and ventriculitis (4.5%). Duration of ventriculostomy placement did not seem related to the rate of infection but the method of placement, the prophylactic antibiotics used, and the monitoring and collecting system employed may be important.


Cerebrospinal fluid shunt infections with anaerobic diphtheroids (Propionibacterium species). The clinical and laboratory findings in six cases of anaerobic diphtheroid infection of cerebrospinal fluid shunts are described. These organisms have been infrequently reported as a cause of shunt infections but our data indicate that such infections may be more common than currently appreciated. Propionibacterium species are common contaminants of cerebrospinal fluid specimens, but when isolated from the spinal fluid of a patient  with a shunt who has symptoms and signs compatible with infection, the organism should not be dismissed as a contaminant. Fever was a constant finding frequently accompanied by signs of central nervous system dysfunction. Spinal fluid pleocytosis was usually limited to 1 to 200 cells and protein and sugar values were variable. The organisms grow slowly, therefore spinal fluid cultures should be held for at least 14 days before they are reported as negative.


Cerebral arterial spasm. Part 4: in vitro effects of temperature, serotonin analogues, large nonphysiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions.


Cerebral arterial spasm. Part 5: in vitro contractile activity of vasoactive agents including human CSF on human basilar and anterior cerebral arteries. In vitro experiments were performed with a small volume chamber to determine the contractile activity of various vasoactive agents on human basilar and anterior cerebral arteries. Cumulative log-dose response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar to curves previously obtained with canine cerebral arteries. It was concluded from these similarities that canine cerebral arteries are a good in vitro model for studying human cerebral arterial spasm. It was also demonstrated that human cerebrospinal fluid, collected up to 17 days after a subarachnoid hemorrhage from patients with clinical and angiographic evidence of cerebral arterial spasm, would cause large, dose-dependent contractions in human anterior cerebral arteries.


Unoperated subdural hematomas. Long-term follow-up study by brain scan and electroencephalography. The authors report nine patients selected from over 100 patients with subdural hematomas successfully treated without surgery. These patients were followed for as long as 5 years. All had angiographically demonstrated subdural hematomas. Electroencephalograms (EEG) documented well the clinical improvement of the patient, but were poor guides to the true size of the hematoma, since EEG returns to normal early in the patient's course. Static scans are a better guide to the presence of a subdural hematoma, but they lag behind clinical improvement and usually remain abnormal for considerable periods of time after a major portion of the hematoma has been reabsorbed, and the patient is asymptomatic.


Brain and bone scans in primary Ewing's sarcoma of the petrous bone. The authors present a case in which primary Ewing's sarcoma of the right petrous pyramid in a 9-year-old girl showed no uptake on a 99mTc-pertechnetate nuclide angiogram. Intense uptake was present on a 99mTc-polyphosphate bone scan, but a static brain scan was only minimally abnormal. The diagnosis and treatment of Ewing's sarcoma are reviewed.


Parietal intradiploic encephalocele. Case report. An unusual case is presented of an intradiploic encephalocele surrounding a cerebrospinal fluid cyst. The relationship of this developmental anomaly to the more commonly encountered midline encephalocele and isolated reports of temporal bone encephaloceles are discussed.


Moyamoya disease as a cause of subarachnoid hemorrhage in a Negro patient. Case report. The authors describe a case of subarachnoid hemorrhage secondary to moyamoya disease in an adult Negro. To the authors' knowledge, this is the first such case reported. Moyamoya, the Japanese word for "puff of smoke," describes the characteristic angiographic appearance of the collateral arterial network associated with internal carotid artery occlusion. The cause is unknown. Treatment consists of supportive care; the prognosis is variable.


Evaluation of an integrated 133Xe regional pulmonary-function analyzer. An integrated system for diagnostic, quantitative, static and dynamic, regional pulmonary-function analysis--both ventilation and perfusion--using 133Xe has recently been developed by Ohio-Nuclear. This paper considers this equipment in a clinical setting and describes the results obtained from 50 normal subjects. Functionally, the analyzer was found to be satisfactory and its operation simple and easy to learn. Patient discomfort is minimal and the complete ventilation-perfusion analysis can be performed and reported in less than 30 min. The results from normal subjects were comparable with published results.


Technetium-99m-glucoheptonate as a brain-scanning agent: critical comparison with pertechnetate. Delayed 99mTc-glucoheptonate and pertechnetate scans were evaluated in a paired study for their ability to detect brain lesions. Glucoheptonate was found to be superior in eight of 17 cases of brain tumor and in two of ten patients with cerebral infarction. In addition, early (30 min) 99mTc-glucoheptonate brain scans were compared with delayed studies: the former were inferior in 48% of the cases. We conclude that 99mTc-glucoheptonate is a promising agent for delayed brain scanning, offering better lesion detection than pertechnetate.


Stasis of 111In-DTPA in the posterior fossa in patients with cerebellar degeneration. Prolonged stasis of 111In-DTPA was noted in the poterior fossa in two patients during cisternography. Both patients had clinical signs of cerebellar dysfunction and pneumoencephalographic evidence of marked cerebellar degeneration. Cisternography may be a useful adjunct in evaluation patients with suspected cerebellar atrophy.


The 99mTc-DTPA dynamic renal scan with deconvolution analysis. Dynamic renal studies were performed with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). The results were analyzed by the method of mathematical deconvolution in order to obtain the impulse response function of the kidney. Regional analysis of the kidney was attempted by evaluating the independent responses of the renal parenchyma and renal pelvis to a bolus injection of 99mTc-DTPA.


Possible enhancement of 67Ga-citrate imaging by iron dextran. The whole-body retention of 67Ga-citrate was studied in intact and in abscess-bearing rabbits. The abscess-to-muscle ratio was obtained using a data processor. Administration of iron dextran lowers the whole-body retention in both the intact and abscess-bearing animals. The optimum time for administering the iron dextran was 24 hr after the 67Ga-citrate injection. At this time, the abscess-to-muscle ratio was highest and the cathode-ray screen images showed lowered back-ground activity and much better definition of the lesion.


Diagnosis of hepatic hemangioma using multiple-radionuclide and ultrasound techniques. Two cases of heptatic hemangioma are reported in which multiple-radionuclide and ultrasound techniques were combined in the diagnostic process. Blood pool imaging rather than perfusion imaging proved to be the most definitive diagnostic procedure. The application of radionuclide and ultrasound studies in the differential diagnosis of focal lesions of the liver is discussed.


Liver scan in Budd-Chiari syndrome.

Liver scan in Budd-Chiari syndrome. Seventeen liver scans were performed in seven patients with occulsion of hepatic veins: the Budd-Chiari syndrome. When some, but not all liver veins were occluded, markedly diminished uptake over the affected segments was usually seen (absence of uptake may occur in acute infarction and in chronic cases). When all major liver veins are occluded, markedly diminished uptake is seen over the peripheral parts of the right and left lobes with a triangular midline area of normal or excessive activity. The latter effect is probably caused by uptake in segments surrounding the inferior vena cava (frequently the caudate lobe) that have direct venous drainage. This liver-scan appearance is characteristic enough to warrant consideration of the Budd-Chiari syndrome as the first diagnosis. Good correlation existed between selective venography and liver-scan findings. The usefulness of liver scans in the followup after portocaval shunting is illustrated in one patient.


Soft-tissue concentration of 99mTc-phosphates associated with injections of iron dextran complex. An unusual concentration of 99mTc-phosphates appeared in the gluteal area in bone scans of three patients who had recently had intramuscular injections of iron dextran complex. These cases indicate one more cause for extraosseous accumulation of these bone-seeking radiopharmaceuticals.


Arteriographically confirmed focal defect in colloid spleen scan with no gross pathologic lession: case report. A focal avascular defect in an enlarged spleen, clearly shown both by 99mTc-sulfur colloid scanning and by celiac angiography, could not be associated with any gross pathologic abnormality at splenectomy. Vascular lesions can probably produce focal defects on the scan in the absence of infarction.


Combination of renal and adrenal scanning in the diagnosis of renovascular hypertension: case report. Superimposition of an adrenal scan on a renal scan revealed a kidney defect not appreciated on the renal scan alone. The defect proved to be ischemia of the upper pole of the kidney. Resection of the lesion alleviated the patient's hypertension.


Effects of prior administration of Sn(II) complexes on in vivo distribution of 99mTc-pertechnetate. This report evaluates the effect of prior administration of several clinically used Sn(II)-containing agents on in vivo distribution of 99mTc. Abnormal binding of 99mTc to red blood cells can occur after administration of pertechnetate to patients who have previously received tin-containing agents. Increased blood levels of tin from other causes may have similar effects.


New preparation method for 99mTc-phytate. A new method is described in which Pt-Sn or Sn-Sn electrodes are used to activate 99mTcO4-. The 99mTc is incorporated into phytic acid by stannous ion released from a tin anode by the corrosive reaction. The most suitable pH for labeling phytic acid by this method was below 5 and the 99mTc-phytate formed could be precipitatedd with Ca+2 at a pH above 3.5. Though 99mTc-phytate is soluble in aqueous solution, it forms an insoluble species with Ca+2 in vivo and is trapped in the reticuloendothelial system. More than 93% of the 99mTc-phytate localized in the liver of mice; here its biologic half-time is about 112 hr. The 99mTc-phytate prepared by this method promises to be useful as a liver-scanning agent. Since our method does not require an applied electric potential, it appears to be one of the most convenient methods for labeling compounds with 99mTc.


Preparation and use of 123I-labeled highly iodinated fibrinogen for imaging deep-vein thrombi. A method for producing protein-iodination-grade 123I suitable for use with a compact bio-medical cyclotron is reported. The preparation of highly iodinated fibrinogen (25 123I atoms per molecule) is described, and its successful use as a thrombus-imaging agent in experimental animals is reported. This new agent clears from the blood faster than conventional radioiodinated fibrinogen and gives higher thrombus-to-blood activity ratios. Thus, the detection of deep-vein thrombi in areas of large blood pool is enhanced, and images can be obtained sooner after administration of the radiopharmaceutical. Induced 4--8-hr-old femoral-vien thrombi in dogs can be well visualized with a scintillation camera as early as 4 hr and as late as 15 hr after administration of 1 mCi of 123I-labeled highly iodinated fibrinogen.


Collimation for imaging the myocardium.

Collimation for imaging the myocardium. Line-source response functions and modulation transfer functions (MTFs) were used to compare the resolution obtained with four myocardial-imaging agents: 129Cs, 43K, 13N-ammonia, and 81Rb contamination. When an Anger camera with pinhole collimator was used, the order of decreasing resolution was 129Cs, 43K, 13N, and 81Rb. Two techniques were employed to determine the extent to which spatial resolution could be improved. The first, involving the addition of lateral shielding, improved the MTFs for all the agents studied. The second, which utilized a subtraction mode, gave the best overall results. With the second method the MTF curves for 129Cs and 43K became very similar and were superior to both 81Rb and 13N. Both techniques were found useful in improving the spatial resolution of certain myocardial-imaging agents by reducing or eliminating the effects of penetration of the pinhole collimator walls by high-energy photons.


Assay of 32P-sodium phosphate using a commercial dose calibrator. Dose calibrators are not usually used to measure the activity of pure beta-emitting radionuclides. In this work, the activity of 32P-sodium phosphate was accurately measured with a Capintec CRC-2 dose calibrator. Using a calibration knob setting of 012 on the 1-mCi range, the 32P dose (in mCi) could be calculated directly simply by multiplying the instrument readout by 10. The dose calibrator response was found to be linear at this knob setting and moderate alterations in geometry produced no significant changes.


Usefulness of brain scans in metastatic carcinoma of the lung. The usefulness of brain scans for detecting unsuspected cerebral metastasis in patients with carcinoma of the lung was studied in a group of 35 such patients who had had routine brain scans as part of the initial evaluation. Seven (20%) had scans that were positive for tumor, but six of these seven had neurologic deficits corresponding to the brain-scan abnormality. Routine brain scans for evaluation of carcinoma of the lung are not justified if neurologic examination is normal.


Radiation hazards from 241Am sources used in thyroid studies. The neutron and gamma photon doses corresponding to the neck and eye level from an 241AmO2 source used in thyroid studies have been theoretically estimated. The radiation hazard to the patient is found to be not significant.


A simple and rapid radioimmunoassay of triiodothyronine in unextracted serum. A simple, accurate, and rapid procedure for radioimmunoassay (RIA) of triiodothyronine (T3) is described. Serum is denatured by sodium trichloroacetate and the T3 released is allowed to react with 125I-T3-labeled T3 anti-serum. The displaced 125I-T3 is rapidly taken up by an anionic-resin sponge, and this uptake is linearly related to serum T3 concentration. The entire assay procedure was completed in the same tube in about 1 hr. The T3 antibody was specific, and T4-to-T3 conversion in the assay did not occur. Recovery of exogenously added T3 was virtually complete. The mean T3 concentration in 92 euthyroid subjects (142 ng/100 ml) is comparable to the values described in a number of radioimmunoassays for T3.


Diagnosis of cirrhosis and hepatitis by quantitative hepatic and other reticuloendothelial clearance rates. Although methods for measuring colloid clearance rates have been described, they are not commonly used. Rather, most clinicians rely on the relative radiocolloid accummulation in the liver and spleen as estimated by visual inspection of liver scans. This method lacks objectivity, however, and only indirectly reflects the rate of radiocolloid clearance. We have developed a noninvasive kinetic technique for measuring radiocolloid clearance by the liver, spleen, and other reticuloendothelial tissues. The clerance-rate constants obtained by this technique appear to differentiate among cirrhosis, fatty metamorphosis, hepatitis, and normal function. In normal subjects, the mean clearance-rate constants for the liver, spleen, and extrahepatosplenic reticuloendothelial system were 16.0, 1.4, and 3.4 ml/min per 100 ml of plasma, respectively. The mean hepatic clearance-rate constant was normal in hepatitis (16.8 ml/min per 100 ml), reduced in cirrhosis (5.7), and slightly reduced in fatty metamorphosis (10.4). Both the hepatic-to-splenic and the hepatic-to-extrahepatosplenic ratios of clearance-rate constants were reduced in cirrhosis and slightly reduced in fatty metamorphosis and hepatitis. Interestingly, the splenic clearance-rate constants were normal in these three diseases.


Specificity of 99mTc-pertechnetate in scintigraphic diagnosis of Meckel's diverticulum: review of 100 cases. Numerous reports in the recent literature have questioned the value of abdominal scanning with pertechnetate in the diagnosis of Meckel's diverticulum. In an attempt to evaluate further the specificity of pertechnetate in this condition, the clinical data and scintigrams of 100 patients with suspected Meckel's diverticulum were reviewed. The scintigram correctly identified Meckel's diverticulum before operation in seven of eight patients. One false-negative study occurred in 33 patients who underwent laparotomy. Conditions suggested as possible causes of false-positive studies (hydronephrosis, arteriovenous malformations, and intussusception) were found to give negative scans.


Intestinal concentration of 99mTc-pertechnetate into isolated loops of rat bowel. In scanning patients for Meckel's diverticulum, the colon occasionally visualizes more rapidly than would be expected simply from gastric secretion and intestinal transit. To gain a better understanding of the intestinal physiology of pertechnetate and thereby to make a more intelligent interpretation of abdominal scans, segments of the gastrointestinal tract of Sprague-Dawley rats were isolated by transection between double ligations. After abdominal closure, the animals received an intravenous injection of 99mTcO4 and were killed at 30, 45, or 150 min after injection. Technetium concentrations in the stomach, colon, and appendiceal contents increased significantly with time after dosing, and after 30 min technetium could be clearly imaged in the stomach, upper small intestine, appendix, and colon. These results suggest that technetium is actively secreted by the intestinal mucosa. Additionally, the results indicate caution in the interpretation of scans in patients with suspected Meckel's diverticulum since, in the rat and probably in the human, significant amounts of technetium can accumulate in the gut apart from gastric secretion and intestinal transit.


Techniques for positron scintigraphy of the brain. Positron scintigrams were obtained in normal subjects and in patients with intracranial tumors and cerebral vascular disease, using a multicrystal positron camera. The radiopharmaceuticals were 68Ga complexed with adenosine triphosphate (68Ga-ATP), 13N-ammonia (13NH3), and 15O2. Six clinical cases are described to illustrate the different cerebral distributions of intravenously administered 68Ga-ATP, 13NH3, and inhaled 15O2. The possible value of these agents in the study of cerebral metabolism and in differential diagnosis of intracranial disease is discussed.


Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. II. Particles. When various radioactive particles are incubated and tumbled in concentrated suspensions of blood phagocytes at body temperature for 1 hr, they bind to the phagocytic cells with a labeling yield of 30-40%. In vitro experiments show that, for some radioactive colloids, a sizeable fraction of the total cellular binding results from nonspecific surface adsorption to other cells and from reversible surface adsorption to phagocytes without engulfment. No completely satisfactory in vitro methods have been found for separating leukocytes with completely engulfed particles from those with surface-adherent particles; nonetheless, surface adherence can be partially reversed by 20% acid citrate dextrose (ACD) solution or by an excess of nonradioactive colloid. Gelatinization of colloidal particles tends to increase their binding to phagocytic cells but also increases the degree of nonspecific adherence to other cells. Technetium-99m-millimicrospheres, 0.5-2 mum in diameter, are optimal in size for phagocytosis by neutrophils, and their non-specific adherence to other cells is minimal. Because of the microspheres' poor stability in aqueous suspension, however, it is technically difficult to separate free from phagocytosed radioactivity after cell incubation. The highly stable small-particle colloids (less than 0.1 mum), such as 198Au-colloid or 111In-colloid without iron carrier, are phagocytosed poorly or not at all by neutrophils, although they are engulfed by mononuclear cells.


Design and performance characteristics of a whole-body positron transaxial tomograph. A whole-body positron-emission transaxial tomograph (PETT III) is described in detail and evaluated in terms of resolution, accuracy, and efficiency. The PETT III utilizes annihilation coincidence detection to provide spatial resolution; high sensitivity is achieved by using 48 Nal(tl) detectors set in a hexagonal array with a multiple-coincidence logic. The assumptions and approximations made in the reconstruction and their effect on image quality are discussed. Phantom studies shows the depth-independent resolution and response of PETT III, as well as its ability to recover activity distribution quantitatively in the cross section measured. Images obtained with patients and normal volunteers show the potential clinical utility of PETT III.


Influence of dietary peroxides, selenium and vitamin E on glutathione peroxidase of the gastrointestinal tract. The influence of dietary peroxides, vitamin E and selenium on glutathione peroxidase (GSH-Px) activity in the gastrointestinal tract of the rat was investigated. Feeding 7% oxidized stripped corn oid (peroxide value 1,000) in a diet adequate in selenium and vitamin E increased the specific activity of GSH-Px  in the stomach mucosa. Feeding oxidized oil produced an increase in the wet weight of the intestinal mucosa which was associated with a decrease in the specific activity of the enzyme. Total GSH-Px activity in the intestinal mucosa was unchanged or moderately increased. These changes were unaffected by the presence of vitamin E in the diet. Dietary peroxides had no effect on GSH-Px activity in the plasma or in the perirenal and paraepididymal adipose tissues. Subacute vitamin E deficiency had no consistent effect on the activity of the enzyme in several tissues examined. In rats fed a Se deficient diet glutathione  peroxidase activity decreased markedly in most tissues but only slightly in the intestinal mucosa. The moderate decrease in the intestine may be explained by the accessibility of residual dietary Se to the mucosal cells. The role of Se in the detoxification of peroxides in foods and the response of gastrointestinal GSH-Px to dietary peroxides are discussed.


Free amino acid patterns and the distribution of 14C from [U-14C]-L-Leucine, [U-14C]-L-Lysine, and [U-14C]-L-Alanine in the tissues of young adult rats. In studies designed to evaluate the role of the liver and muscle in modifying the plasma amino acid response, three levels of dietary amino acids, 3.6%, 4.8% and 6.0% were fed to three groups of young adult male rats for 2 weeks. After fasting, either [U-14C]-L-leucine, [U-14C]-L-lysine or [U-14C]-L-alanine was administered intragastrically with a portion of diet. After a 4.5 hour fast, rats were killed. Distribution of radioactivity was evaluated in trichloroacetic acid (TCA) supernatants and lipid-extracted precipitates of plasma, liver and gastrocnemius muscle, and in expired CO2. Free amino acids were measured and specific activities of amino acids were determined. Rats fed 6.0% or 4.8% amino acids lost less weight than those fed 3.6%. A high percentage of radioactivity from 14C-leucine and 14C-lysine was recovered in the lipid-extracted precipitate. TCA supernatants from rats fed 14C-leucine contained low levels of radioactivity. A large percentage (60%) of the radioactivity from 14C-alanine was expired in 14CO2. The percentages of alanine found in TCA precipitates were very low. Significant increases in concentration associated with increments in dietary amino acids occurred in plasma free isoleucine, leucine, valine and tyrosine; liver free histidine; and muscle free leucine and threonine. Concentrations of many amino acids were depressed in the muscle of rats fed 4.8% amino acids whereas they increased in response to 6.0%. Protein and free amino acid specific activities indicated no change in rates of protein synthesis. Data from this type of experiment may assist in interpreting the role of the liver and muscle in modifying the plasma amino acid response to dietary amino acids.


Changes in diet and patterns of feeding activity of developing rats. The purpose of this study was to determine the amount of milk and stock diet consumed by rats during postnatal development and the extent to which they feed in circadian rhythms when weaned naturally by their dams or when separated from their dams at age 21 days. One approach used in several experiments was to record feed bin weight losses at circadian intervals. The second approach was to analyze the stomach contents of rats killed at circadian intervals at representative ages. Contents were inspected, freeze-dried, weighed and assayed for fat by extraction with solvent. The difference in fat between rat milk solids and stock diet was the basis for estimating proportions of stock diet and milk. The results indicate that 1) natural weaning occurs progressively from 14 to 30 days after birth, with an accelerated phase between 18 and 25 days; 2) pups up to 8 days old and their dams feed mostly by light and darkness, respectively; 3) circadian variations in feeding are weak and inconsistent in 10 to 20 day old pups and their dams; 4) at 21 days pups and dams begin to feed mostly in darkness; 5) the proportions of food consumed by light and darkness approach those of the adult by age 29 days when rats are weaned naturally, and by 25 days when weaned at 21 days; and 6) progression into the nocturnal feeding pattern may be disturbed if larger litters are not provided with sufficient space.


Alteration of glucose tolerance by dietary L-tryptophan in rats. L-Tryptophan is known to have pharmacological effects on carbohydrate metabolism. In a scrutiny for possible physiological relationships, intravenous glucose tolerance was measured in rats fed various diets of defined L-tryptophan-content. Within 14 days, animals which had been fed a tryptophan-deficient diet diet removed excess glucose from their blood at a reduced rate. This decreased tolerance to glucose was dose dependent to dietary L-tryptophan and the intolerance was reversed by feeding a complete diet. The intolerance was not dependent on dietary protein source, not reversed by added niacin or vitamin B-6, not a necessary consequence of decreased food consumption and growth, and not duplicated by a lack of dietary lysine. The results suggest  that dietary L-tryptophan is active in physiological regulation of carbohydrate metabolism.


Nitrogen metabolism and reproductive response of gravid swine fed an arginine-free diet during the last 84 days of gestation. Based upon nitrogen retention and urinary excretion of orotic and citric acid, previous experiments have shown that the gravid gilt does not require a dietary source of arginine during late gestation. This experiment was designed to evaluate effects of feeding an arginine-free diet for a major portion of gestation. Three diets, 0% L-arginine, 0.38% L-arginine and a fortified corn-soybean meal control, were fed to two litter-mate trios from day 30 of gestation until parturition. The experimental diets contained crystalline amino acids as the sole source of nitrogen and provided 12.6% crude protein equivalent. All gilts received 2 kg of diet daily and were housed throughout the 84-day feeding period in metabolism crates. Nitrogen retention tended to increase with advancing pregnancy, but was uninfluenced by dietary treatment. Averaged across all three gestational trimester periods, nitrogen retention was 11.2, 9.7 and 12.0 g/day for the 0% arginine, 0.38% arginine and cor-soybean meal diet, respectively. Urinary excretion of orotic acid was not significantly affected by arginine intake. Moreover, number and weight of pigs at birth and weaning were unaltered by dietary treatment. Thus, it is evident that satisfactory reproductive response can be achieved with gravid swine fed an arginine-free diet during the last 84 days of pregnancy.


Metabolism of D- and L-tryptophan in dogs. The metabolism of D- and L-[benzene ring-U-14C]tryptophan by dogs was studied. The distribution of label from each isomer in urine, feces, CO2 and various tissues was determined. Thirteen different urinary tryptophan metabolites were isolated by ion exchange cellulose chromatography. D-[14C]Tryptophan was poorly converted to 14CO2 relative to the L-isomer, while giving rise to nearly three times as much urinary 14C as did the L-isomer. The major urinary metabolites of D-tryptophan were unchanged D-tryptophan via indolepyruvic acid appeared to be the major fate of ingested D-tryptophan, with renal excretion of the unchanged D-isomer the next most important fate. The dog apparently utilizes D-tryptophan more efficiently than does the human but much less efficiently than does the rat. The dog appears to be a reasonable animal model for the human in studies of D-tryptophan metabolism.


Protein requirements of man: obligatory urinary and fecal nitrogen losses in elderly women. Eleven health elderly women, ranging in age from 67 to 91 years, were given an essentially protein-free diet for 8 to 10 days, to determine obligatory urinary and fecal nitrogen losses. Body cell mass (BCM) was calculated from whole body 40K, and basal metabolic rate was determined by indirect calorimetry. Urine was analyzed daily for nitrogen and creatinine, and fecal N was measured in pooled samples. Urinary N output reached a relatively stable-state level by day 6; the average of the last four daily measurements was taken as an estimate of obligatory urinary N loss. The obligatory urinary N was: 24.4 +/- 5.2 mg N/kg body weight; 89.5 +/- 17.1 mg N/kg BCM; 1.44 +/- 0.14 mg N/basal kcal; and 2.11 g N/g creatinine. Obligatory fecal N was 9.8 mg N/kg body weight. Comparison of these results with published data for young adults indicates that obligatory urinary N losses in elderly women are similar to those for young women when expressed per unit body weight but higher than young women and men when expressed per unit creatinine excretion and per unit BCM.


Influence of different levels of dietary pyridoxine on certain parameters of developing and mature brains in rats. The influence of different levels of dietary pyridoxine-HC1 (1.2, 2.4, 4.8, 9.6, 19.2, 38.4, 76.8 and 153.6 mg/kg diet) fed to dams on certain parameters of developing and mature brain was studied in rats. Brain weights and alanine aminotransferase (ALAT) activities (initial and following in vitro addition of pyridoxal phosphate, PLP) were significantly reduced in brains of 12-day-old pups of dams fed the lowest level of pyridoxine compared to other treatments; in vitro addition of PLP significantly stimulated the activities of glutamic acid decarboxylase (GAD) and ALAT. Vitamin B-6 concentrations in brain were higher for 2-day-old pups of dams fed 38.4 or 76.8 mg vitamin/kg diet and for 12-day-old pups of dams fed 2.4 to 153.6 mg compared to the 1.2 mg groups; at weaning, values were greater in groups fed 76.8 or 153.6 mg compared to the 1.2 mg group. As brain developed during the suckling period, the content of bitamin B-6 and protein increased in all groups, except the 1.2 mg group in which values remained the same. The vitamin and protein content in brain had not reached chemical maturity at weaning as evidenced by greater concentrations of each in brains of dams as compared with values for 21-day-old progeny. As brain developed, ALAT activity increased about 30 times from age 2 to 21 days when activities were similar to those observed in mature brains of dams. Activity of GAD in brain increased about four times from age 12 to 21 days.


Influence of dietary zinc on lead toxicity in the rat. An investigation of the influence of dietary zinc (8, 35, 200 ppm) on the toxicity of dietary lead (0, 50, 200 ppm) in the young male rat in a seven week period indicated that as dietary zinc increased, the severity of lead toxicity decreased. Evidence included decreased lead concentration in blood, liver, kidneys, and tibias; decreased excretion of urinary delta-aminolevulinic acid; decreased accumulation of free erythrocyte porphyrins; decreased inhibition of kidney delta-aminolevulinic acid dehydrase activity; and a decrease in apparent lead absorption. Infected zinc did not afford protection against lead toxicity. The data indicate that the protective effect of zinc on lead toxicity is largely mediated by an inhibition of lead absorption at the intestinal level.


Effect of litter size on weight gain in rats. Male rats, placed in litters of 2, 4, 8, 12 and 16 on the first postnatal day, were weighed at 3-day intervals and killed at days 21 or 58. The carcasses were assayed for total protein, DNA and lipid. Animals raised in litters of 16 were significantly smaller than any of the others at all times examined, and their carcasses contained significantly less protein, DNA and lipid. In contrast, animals raised in very small litters exhibited no persistent significant differences in body weight or composition from animals raised in standard-sized litters of 8 or 12.


Effect of selenium on rat growth, growth hormone and diet utilization. Female rats were fed a selenium-deficient diet composed of Torula yeast, sucrose, vitamins (including tocopheryl acetate) and minerals from weaning and during breeding, gestation and lactation. The offspring were used to study the effects of selenium on growth, diet utilization and growth hormon status. The Torula yeast diet containing 200 IU dl-alpha-tocopheryl acetate was fed alone or supplemented with 0.025 or 0.1 ppm of selenium as selenite. Rats fed the selenium-supplemented diets grew significently faster and consumed significantly more diet than rats fed the unsupplemented diet. Anterior pituitary weights were lower in selenium-deficient rats, but if expressed per unit of body weight, were similar to pituitary weight of selenium-supplemented animals. Total growth hormone in the anterior pituitary was reduced in selenium-deficient rats. A metabolism study indicated that rats allowed ad libitum access to supplemented diets consumed more diet and obtained more metabolizable energy from the diet than rats fed the deficient diet. It the intake of rats fed the supplemented diets was limited to that of rats allowed ad libitum access to deficient diet, growth of rats was similar. However, metabolizable energy content of the diet increased quadratically and nitrogen digestibility increased linearly as thelevel of selenium increased. Selenium deficiency reduced growth primarily by decreased diet consumption, but also reduced the utilization of energy and nitrogen.


Gluconeogenesis from lactate in liver of stress-susceptible and stress-resistant pigs. In vitro rates of lactate conversion to glucose and oxidation to CO2 were determined in livers of stress-susceptible (SS) and stress-resistant (SR) pigs because we hypothesized that livers of SS pigs had a lower capacity than livers of SR pigs to remove lactate from blood. Stress-susceptibility was determined by reaction to halothane at 7 weeks of age. At approximately 9 weeks of age, pigs were assigned to one of three experimental diets. Pigs weighing 95 kg were slaughtered immediately after stress, and liver samples were obtained. Incorporation of lactate into glucose in liver of SS pigs was 38% of that in SR pigs. Addition of either vitamin C or vitamins C and E plus magnesium oxide and collagen extract to a corn-soy diet did not alter lactate conversion to glucose, but depressed lactate oxidation to CO2. No differences were detected in either activities of lactate dehydrogenase, HAD-malate dehydrogenase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase or concentration of glycogen in livers of SS and SR pigs. Our data indicate that livers of SS pigs possess a lower capacity to incorporate lactate into glucose and to oxidize lactate to CO2; maximal activities of enzymes measured in this study are not the cause of these differences. Reduced capacity of lactate metabolism in livers of SS pigs seems a part of the etiology of the porcine stress syndrome.


Effect of spatial frequency on the visibility of unstructured patterns. Threshold measurements have been made on random patterns that  have been computer filtered to contain only certain spatial frequencies. The dependence of threshold on the spatial-frequency distribution of the energy in the patterns was measured. The results indicate that the visibility of an unstructured pattern is dependent on the spatial-frequency content of the pattern. Near threshold, narrow-band noise is much more visible than wide-band noise. The narrow-band noise visibility is caused by the presence of structure in the pattern, some of which is rotation sensitive. For wider-band noise, the modulation transfer function is circularly symmetric. The visibility of very-wide-band noise near threshold depends only on the luminance variations concentrated within a one-octave spatial-frequency band.


Interference with line-orientation sensitivity. Sensitivity for inclination detection of a foveally seen line is exceedingly high. It is shown that appropriately structured visual stimuli can interfere with the inclination detection threshold, presumably by inhibiting some neural signals before they are channeled to interact with others of their ensemble. The parameters of this inhibition, and by implication those of the sensitivity of the involved neural elements, are outlined: spatial location, time course, movement sensitivity, dichoptic nature, nonrecurrent characteristics, and position rather than orientation dependency.


Visual sensitivity of the eye to infrared laser radiation. The foveal sensitivity to several near-infrared laser wavelengths was measured. It was found that the eye could respond to radiation at wavelengths at least as far as 1064 nm. A continuous 1064 nm laser source appeared red, but a 1060 nm pulsed laser source appeared green, which suggests the presence of harmonic generation in the retina.


On corneal transparency and its loss with swelling. The cornea is the clear front covering of the eye through which we see and is composed of collagen fibrils embedded in an optically homogeneous ground substance. It has long been recognized that these fibrils scatter light and that transparency results from interference effects due to an ordering in the spatial arrangement of the fibrils about one another. The nature of this ordering and of its disruption in abnormal corneas is of great current interest. The present study reviews experimental light scattering and electron microscopic evidence relevant to this problem. This evidence suggests that theoretical attempts to model and understand corneal transparency and its loss during swelling, in terms of ultrastructure, must account for a short-ranged ordering of fibrils in normal healthy corneas and for the formation of regions void of fibrils in swollen corneas.


An ultrahistochemical study of the distribution of acid and alkaline phosphatases in placentae from normal and complicated pregnancies. The subcellular localisation of acid and alkaline phosphatase has been studied in the trophoblast of placentae from both normal and complicated pregnancies. In placentae from uncomplicated pregnancies the number of trophoblastic acid-phosphatase-containing organelles decreases progressively as gestation proceeds whilst alkaline-phosphatase activity, although abundant at term, could not be demonstrated during the early stages of pregnancy. The acid-phosphatase-containing organelles are of two types; one is a small round body which is probably a lysosome whilst the other is a multivesicular body. The alkaline phosphatase is distributed mainly on the syncytial microvilli and plasma-membrane. It is suggested that the marked lysosomal activity during early pregnancy is related to the architectural refashioning of the placenta during this period and that there are two phosphatase-linked transfer systems in the trophoblast, one dependent upon acid-phosphatase-containing multivesicular bodies and being utilised during early pregnancy and the other reliant upon alkaline phosphatase and dominating during the second half of gestation. In placentae from prolonged pregnancies there is a further decrease in trophoblastic acid phosphatase and, usually, a continuing increase in alkaline-phosphatase activity. In placentae from babies of low birth weight this trend is sometimes reversed and alkaline-phosphatase activity either disappears or its reaction product diffuses throughout the syncytium; this is usually accompanied by a marked increase in the number of acid-phosphatase-containing multivesicular bodies. Placentae from women with pre-eclampsia show no loss of alkaline-phosphatase activity but are characterised by an increased number of lysosomal bodies.


The influence of the thymus on multinucleate giant cell formation. Glass coverslips were implanted in nude athymic mice and normal controls and the development of multinucleated giant cells on the implant investigated. Although the percentage of the surface area of the coverslip covered by cellular exudate was reduced in older implants (12 days or more) in athymic mice, the proportion of nuclei within syncytia was the same as in normal controls. It is concluded that the multinucleated giant cells in this type of inflammatory lesion are not thymus derived nor is the efficiency of fusion between their precursor mononuclear phagocytes thymus dependent. The number of exuded mononuclear phagocytes on the other hand may be influenced directly or indirectly by the thymus.


The effects of pure and micellar solutions of different bile salts on mucosal morphology in rat jejunum in vivo. The effects of pure and micellar solutions of different bile salts on mucosal morphology have been investigated in rat jejunum using a closed-loop technique; the effects of an anionic dihydroxy steroid antibiotic, fusidic acid, have also been studied. Mucosal changes were assessed by light-microscopical appearances and quantified by determining surface to volume ratios (c/1h). The unconjugated dihydroxy bile salts, chenodeoxycholate and deoxycholate (DC), produced similar and gross structural changes at concentrations of 2-5 to 5 mM, as judged by mucosal appearances, but not at 1 mM; the unconjugated trihydroxy bile salt cholate and a variety of di- and trihydroxy conjugated salts produced no changes at concentrations of 5 to 20 mM. Fusidate (5 mM) produced similar changes to 5 mM DC. Compared with control values DC (1,2-5 and 5 mM) and fusidate (5 mM) produced highly significant (P less than 0-001) reductions in c/1h ratios. DC-induced damage was completely abolished by mixed micellar solutions, whereas pure micellar solutions provided no protection. These results indicate, (i) a molecular specificity for bile salt-induced mucosal damage, and (ii) that the effects of the unconjugated dihydroxy species on mucosal structure depends not only on their intraluminal concentrations, but also on the relative concentrations of conjugated bile salts and lipids present in the lumen.


Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion. Gentamicin sulphate was administered to male Wistar rats by intramuscular injection at varying dosage and for varying periods. At high dosage (50-100 mg/kg/day) gentamicin causes tubular necrosis. At dosages equivalent to that given to man (5 mg/kg/day) obvious degenerative changes are produced. Similar changes are seen in human tubular epithelium and urine deposits of patients treated with gentamicin. There is increased excretion of urinary enzymes proportional to the degree of tubular damage. The importance of these changes in man is stressed.


A population of Pasmodium colmbiense sp. n. in the iguanid lizard, Anolis Auratus. Plasmodium colombiense sp. n. is described from 274 naturally infected Anolis auratus from western Colombia. Host blood pictures, parasitemia, parasite structure, infection states, and host population dynamics are correlated. Local epidemics occur, but in contrast to temperate zone species there is little regional synchronization. Active infections occur year-around, being somewhat more common in dry seasons; however, chronic infections predominate. Mature schizonts have 3 to 14, usually 6, 8, or 10 merozoites, reduced to 4 to 6 in chronic infections. Gametocytes are round to oblong, measuring 6 by 5 mu, and the pigment in microgametocytes occurs in a single peripheral vacuole. Parasitemia averaged 2.5% and seldom surpassed 20 to 30%. Infections cause significant anemia, and parasites in active infections are most common in immature erythrocytes. Host response is similar to avian or primate infections, including erythropoiesis, phagocytosis, and interference with parasite growth.


The effects of selected gases on excystation of coccidian oocysts. The mechanism of CO2 action in changing coccidian oocyst wall permeability was indirectly studied by substituting NO, NO2, N2O, H2S, SO2, CH4, NH3, and 8M urea in place of CO2 in an established excystation procedure. Changes in oocyst wall permeability of Eimeria stiedai, E. bovis, and E. tenella were determined by incubation in test gases and cysteine HCl followed by attempted activation of sporozoites by trypsin and bile and staining of intraoocyst components with methylene blue. The gases CH4, NO2, and N2O were negative for all 3 tests, as were SO2, NH3, and 8M urea which, in addition, were toxic to the oocysts. Both H2S and NO were capable of mimicking the action of CO2 and are related chemically to the reducing agent, and thus tend to underscore its importance in excystation. It now appears that the role of CO2 is that of an allosteric effector enhancing the action of the reducing agent.


Effects of antiphagocytic agents on penetration of Eimeria magna sporozoites into cultured cells. Madin-Darby Bovine Kidney cells were treated with sodium flouride, iodoacetate, and 2-deosyglucose, reagents that block glycolysis, and thus reduce phagocytosis. Sporozoites readily entered cells whose ATP stores were largely depleted. They also entered cells treated with colchicine, colcemid, and vinblastine. These latter agents did not inhibit sporozite motility after 6 hr incubation. Cytochalasin B prevented penetration of cells by inhibiting the motility of sporozoites. This effect was reversible. Warm sporozoites entered cold cells 4 times more radily than cold sporozoites into warm cells. The above findings suggest that phagocytosis is not the mechanism for entry of E. magna sporozoites into cultured cells, but that sporozoite motility is of primary importance.


Eimeria juniataensis sp. n. (Protozoa: Eimeriidae) from the map turtle, Graptemys Geographica, in Pennsylvania. Eimeria juniataensis sp. n. is described from the map turtle, Graptemys geographica, in Pennsylvania. The spherical to subspherical oocysts of E. juniataensis are 11.5 to 18.5 mu by 11.5 to 16.5 mu (mean, 13.5 by 12.9mu). The broadly fusiform sporocysts are 7.5 to 10 mu by 4 to 6.5 mu (mean, 8.3 by 5.0mu) and a Stieda body is present. Oocyst and sporocyst residua are present. This is the first report of an eimerian species from Graptemys.


The fine structure of Schistosoma mansoni sperm (Trematoda: Digenea). The sperm of the blood fluke Schistosoma mansoni consist of a bulbous head 8 by 2 mum, with a rounded anterior tip and tapering posterior region, followed by a relatively short flagellum ca. 20 mum long. Electron microscopic observations revealed that these sperm are devoid of an acrosome, while a few undifferentiated mitochondria accumulate at the anterior part of the head. The nucleus appears dense, except for some electron-lucent patches. The flagellum starts at the basal body, posterior and slightly lateral to the nucleus, and the axial complex is of the 9 + 0 type. A layer of microtubules runs longitudinally, just beneath the plasmalemma, from the anterior part of the head to the initial part of the flagellum, where they overlap with the axial complex. It is suggested that this relatively rudimentary type of the S. mansoni sperm is probably related to the low activity required for fertilization.


The timing of reproductive cell development and movement in Schistosoma mansoni, S. japonicum, and S. haematobium, using techniques of autoradiography and transplantation. Tritiated thymidine was incorporated into gonial and vitelline cells of male and female Schistosoma mansoni, S. japonicum, and S. haematobium after 2 hr of incubation. Spermatogonial cells developed into labeled mature sperm after 6 days of transplantation in all species. Insemination of females was detected on the same day indicating copulation is frequent. Oogonia labeled in the initial incubation matured into primary oocytes after 7 days of transplantation for S. mansoni and S. haematobium and after 6 days in S. japonicum. Cytoplasmic thymidine label was observed after 2-hr incubations in the primary oocytes of all species. Initial label in the vitellaria was scattered and heavy. After 3 days of transplantation, label was considerably diluted and by day 6 was undetectable in vitelline glands. These times for development and movement of reproductive cells are considered to be standards against which the effects of stressful conditions on the reproductive system can be assessed.


Host-parasite relationships of Fasciola hepatica in the white mouse. VII. effects of anti-worm incubate sera on transferred worms and successful vaccination with a crude incubate antigen. Mouse antisera against the 16-day-old worm incubate and sera from 25-day infections in mice debilitated migrating flukes in recipient animals as measured by worm recovery and host mortality. Mouse antisomatic and 100-day infection sera produced no such effects. Host mortality was significantly lower after challenge in mice given one ip immunizing injection of the worm incubate; however, worm recovery was not significantly reduced. Injections at 2, 7, 12, and 24 hr with the worm incubate elaborated over a 24-hr period protected 75% of the mice from infection after challenge, and reduced the worm burden by 83.3%.


Acanthocephalus tahlequahensis sp. n. (Acanthocephala: Echinorhynchidae) from the the stippled darter, Etheostoma punctulatum (Agassiz), in northeastern Oklahoma. Acanthocephalus tahlequahensis sp. n. was recovered from the intestines of 4 species of freshwater fishes, Etheostoma punctulatum, E. spectabile, Nocomis asper, and Notropis pilsbryi, collected in northeastern Oklahoma. The new species is distinguished from all other species of Acanthocephalus, except A. japonicus (Fukui and Morisita 1936) Petrochenko 1956, and A. fluviatilus Paperna 1964, by having smaller proboscis hooks. The length of the proboscis hooks for males is 27 to 38 (33) mum and for females 35 to 46 (42) mum. A. tahlequahensis is smaller than either A. japonicus or A. fluviatilis, and has about half the number of longitudinal rows of proboscis hooks of A. japonicus and half the number of proboscis hooks in each longitudinal row of A. fluviatilus. In addition to having smaller hooks. A. tahlequahensis differs from other species of Acanthocephalus parasitizing North American fishes by its smaller, spindle-shaped trunk and more hooks in each longitudinal row.


Influence of potassium ion and osomtic pressure on development of Haemonchus contortus in vitro. Development of infective larvae of Haemonchus contortus to the fourth stage in vitro was impaired if the concentration of potassium ion in the medium was 0.26 mM or less. At or below 0.015 mM, development was almost completely stopped. High concentrations of potassium, in solutions with a ratio of sodium to potassium from 150 down to 1.3, were all equally favorable for development, but solutions composed only of salts of potassium were unfavorable. Development was impaired by osmotic pressures below 200 mosm/kg or above 350 mosm/kg and ecdysis was arrested by high but not by low osmotic pressures.


Effect of desiccation on the survival of infective Haemonchus contorus larvae under laboratory conditions. When stored in water at 4 and 20 C, respectively, 42 and 36% of free 3rd-stage, infective larvae of Haemonchus contortus were alive after 256 days. When stored at -95 C, 73% of the free, desiccated larvae died during the 1st half hour and 80% during the 1st half day; thereafter no more died for 255 days, the duration of the experiment. Desiccation protected the larvae against death on storage at temperature below freezing, but it was harmful at temperatures above freezing. H. contortus larvae do not withstand a single episode of desiccation as well as Trichostrongylus colubrformis larvae.


Probstamyria gombensis sp. n. (Nematoda: Atractidae) from the chimpanzee. The worm is distinguished by the presence of both unequal spicules and a gubernaculum in the male and also the elongated nipplelike tip of the right spicule. P. gombensis was found to be a common parasite within a troop of feral chimpanzees living in Gombe National Park, Tanzania.


Scanning electron microscopy of the lip denticiles of Ascaris suum adults of known ages. Purebred Hampshire pigs, farrowed and maintained under conditions precluding extraneous helminth infection, were exposed to a single dose of 10,000 Ascaris suum infective eggs. The pigs were killed at intervals of 28, 41, 55, 86, 115, 145, 175, and 206 days after infection. At necropsy, no gross lesions were found in the lungs or livers of infected pigs. The worms were recovered from the small intestine, identified, counted, and fixed. The heads were excised, critical point dried, mounted en face, and examined by scanning electron microscopy. Worms 28 to 115 days old had unworn denticles that were triangular when viewed laterally but blunt when viewed tangentially. Wearing of the denticles was observed first with 145-day-old worms; wearing increased with age both in numbers of denticles affected and in degree of wear so that by 206 days after inoculation, almost all denticles in the center of the lip were worn. Worn denticles appear truncated when viewed from any angle. The denticles outside the central area were not affected by wear. The size of the denticles varies not only between specimens of the same age, but also on each specimen. However, average denticle size is directly related to the size and, accordingly, to the age of the worm. External to each denticle is a corresponding depression that we have called the denticular groove. One 28-day-old specimen had some extra denticles aligned irregularly along the lip; this irregularity gave the appearance of a double row. The denticles of the two subventral lips are similar to those of the dorsal and are equally affected by wear. There was no detectable difference in denticles of male and female worms. Since wear can now be specifically correlated with age, we conclude that the denticles are functional and become worn through use. Consequently, adult A. suum may be an even more injurious pathogen than heretofore supposed.


Didelphostrongylus hayesi gen. et sp. n. (Metastrogyloidea: Filaroididae) from the opossum, Didelphis marsupialis. Didelphostrongylus hayesi gen. et sp. n. from the opossum, Didelphis marsupialis, is distinguished from other genera of the Angoistrongylinae by the structure of the dorsal and lateral rays, complex gubernaculum, and ovoviviparity. Third-stage larvae developed in Mesodon perigraptus and Triodopsis albolabris. The prepatent period was 22 days in experimentally infected opossums.


Natural infection of Aedes trivittatus (COQ) with Dirofilaria immitis in central Iowa. Juveniles identified as Dirofilaria immitis were recovered from Aedes trivittatus and Anopheles punctipennis collected CO2-baited CDC light traps in Ames, Iowa, during 10 days in July and August 1975. Ae. trivittatus composed 58.7% of the mosquitoes collected, and D. immitis was recovered from 18 of 393 (4.6%) dissected and from 7 of 31 pools (911 mosquitoes; 0.77%). Approximately 1.0% of the Ae. trivittatus collected harbored infective-stage juveniles, and as many as 27 were recovered from a single mosquito. This is the first report of Ae. trivittatus supporting the development of D. immitis. An. punctipennis was the only other species infected, with 2 of 468 harboring first-stage juveniles. The data suggest that Ae. trivittatus probably is the principal vector of D. immitis in central Iowa.


Efficacy of p-Toluoyl chloride phenylhydrazone against gastrointestinal helminths in ovines. A new anthelmintic candidate, p-toluoyl chloride phenlylhydrazone, was administered to lambs in a paste formulation. The efficacy of this drug was determined at dose rates of 20, 30, 40, and 50 mg of active ingredient per kilogram of body weight. Helminths expelled by these dosages included Haemonchus contortus, Ostertagia circumcicta, Trichostrongylus colubriformis, T. axei, Nematodirus filicollis, Cooperia curticei, Strongyloides papillosus, Oesophagostomum columbianum, Bunostomum trigoncephalum, Chabertia ovina, Moniezia expansa, and M. benedeni.


Studies on resistance in snails. 4. Induction of ventricular capsules and changes in the amebocyte-producing organ during sensitization of Biomphalaria glabrata snails. Formation of an amebocyte aggregate in the ventricular cavity of Biomphalaria glabrata can be induced 30 hr or more after a single infection by irradiated or (less frequently) by normal Echinostoma lindoense miracidia. The resulting amebocyte mass frequently encapsulated and destroyed the developing E. lindoense sporocysts within the ventricle. The constituent amebocytes of the capsule correspond in vitro and by staining characteristics to circulating amebocytes of uninfected snails, but with additional inclusion bodies, increased mucopolysaccharide, acid phosphatases, and  lipid-positive staining reactions. Mitotic activity, rapid growth, and later regression of the amebocyte-producing organ (located between the posterior mantle epithelium and anterior pericardial endothelium) follow the growth and regression sequence of the ventricular capsule. Though peripheral foci of secondary amebocyte production have been found and were previously known, the amebocyte-producing organ appears to be the primary amebocyte source responsible for the snails' rapid intraventricular sporocyst encapsulation.


Studies on resistance in snails. 5. Tissue reactions to Echinostoma lincloense in naturally resistant Biomphalaria glabrata. Laboratory-raised juvenile albino Biomphalaria glabrata snails show a wide range of natural resistance to a single infection with 50 or 100 miracidia of Echinostoma lindoense. In the most resistant snails all sporocysts are destroyed in peripheral tissues soon after miracidial penetration. In less resistant snails some sporocysts reach the heart where they are encapsulated. In fully susceptible snails, all sporocysts rapidly migrate to the heart, where they mature and continue to develop. The greater part of our B. glabrata colony consists of snails in which sporocysts reaching the heart will survive, but in which a varying number of sporocysts will be destroyed in the tissues. These snails are usually considered susceptible, as they do become infected. Tissue reactions induced by sporocysts following a single infection in naturally resistant snails are similar to reactions in snails with an acquired resistance. In fully susceptible snails, the amebocyte-producing organ remains small and inactive. It is slightly to moderately stimulated in partially resistant snails in which destruction of sporocysts occurs in the tissues and surviving larvae are found in the ventricle. In snails in which amebocyte aggregates or capsules develop in the ventricle, the organ becomes markedly enlarged. Migration of sporocysts in the snail appears not to be continuous, as periodic rests seem to occur. Migration follows intrusion of the sporocyst through the tissues, induced by bodily distension and contraction, and then proceeds within the arteries against the blood flow, passing from one endothelial attachment site to another, possibly aided by negative pressure during ventricular diastole.


Studies on resistance in snails. 6. Escape of Echinostoma lindoense sporocysts from encapsulation in the snail heart and subsequent loss of the host's ability to resist infection by the same parasite. Formation of amebocyte aggregates in the ventricular cavity of Biomphalaria glabrata, induced by developing sporocysts of Echinostoma lindoense, does not always result in destruction of the parasites, as the sporocysts occasionally escape encapsulation in the heart. When this occurs, a remarkable loss of protective capacity follows and the host snails become highly susceptible to reinfection with the same species--even more so than in control susceptible snails exposed for the first time. Although the amebocyte-producing organ is considerably enlarged after a first infection and shows numerous mitoses, the amebocytes produced by snails harboring an "escaped" infection in the heart appear unable to attack the parasites of the first or of the second exposure. Instead, the amebocytes produced accumulate in the loose connective tissues between the liver lobuli, where early developmental stages of the parasites do not occur. These amebocytes apparently have lost their ability to recognize the parasites as foreign.


Resistance to Boophilus microplus (Canestrini) in genetically different types of calves in early life. Tick resistance and blood composition were studied in British (1/2 Shorthorn x 1/2 Hereford) and zebu (1/2 Brahman x 1/2 British) calves from birth to 33 days of age in a tropical grazing area in which B. microplus is endemic. Calves of the 2 breeds were either naturally infested or were, in addition, artificially infested with 5,000 larvae at 2 and 9 days of age. Total numbers of mature female ticks carried from either type of infestation were significantly lower (P less than 0.01) on zebu than on British calves. In the artificially infested calves of both breeds, the total number of ticks maturing between 20 to 26 days of age was significantly higher (P less than 0.01) than the number maturing between 27 to 33 days of age emphasizing that a major component of resistance is acquired. However, in the naturally infested calves, breed differences in the numbers of ticks maturing during these 2 periods suggested the presence of genetic differences in innate resistance. Within breeds, total tick numbers carried during the study were negatively correlated with calf weight gain and with the concentrations of serum albumin, total protein, and cholesterol.


A new observation on spermateleosis in ticks. The first phase of spermiogenesis in argasid and ixodid ticks is described. The inner core of the spermatid passes through the outer sheath so that speriogenesis is permitted to follow its course. The outer sheath is not ruptured in the process, but a well-defined operculum opens to let the inner core through. The opening of the operculum is a clear-cut indication of the beginning of spermiogenesis. In the examined species speriogenesis begins in Argasidae when the male transfers the spermatophore to the female genital opening, whereas in Ixodidae it starts only after the endospermatophore has reached the female genital tract.


The development of anorectal continence and its significance in the diagnosiso of Hirschsprung's disease. The development of the anorectal continence reaction was studied in a series of 138 electromanometric recordings performed in 62 newborn and six premature infants. Forty-five babies were observed in a longitudinal study. In 11% an internal sphincter relaxation was observed at the time of birth. The same reflex was present in about 50% after the third day and in all infants after the 12th day of life. The development of a rectal continence reaction depends on an intact internal sphincter relaxation. The puborectalis muscle, is fully functional at birth. On the basis of these findings electromanometric recordings can be used to exclude aganglionic megacolon as early as the first day of life. An absent internal sphincter relaxation reflex, is diagnostic only after the 12th day of life.


Manometric assessment of continence after surgery for imperforate anus. Of 49 children with imperforate anus, 23 underwent an abdominoperineal procedure for a high and seven for a low maliformation, 17 had a perineoplasty for a low and two for a high malformation. In each subject, rectal and anal sphincteric resting pressures were studied at least 1 yr after surgery. Of 30 subjects who had undergone an abdominoperineal procedure, eight were continent in contrast to 15 out of 19 patients who had had a perineoplasty (p less than 0.001). In patients who had undergone an abdominoperineal procedure, the rectal motility was of the colonic type, with waves of higher amplitude and lower frequency (p less than 0.01) than in the normal rectum in 23 cases and in most of these, peristalsis was recorded down to the anal margin. Incontinence was most frequently associated with abnormally short anal resistance, low anal pressure, reduced sensibility, weak voluntary contraction and absence of rectoanal inhibitory reflex. In the group of patients who underwent perineoplasty, continence was associated with normal mechanical parameters and normal physiologic behavior of the anal sphincter.


Infantile hypertrophic pyloric stenosis related to ingestion of erythromycine estolate: A report of five cases. During a 1-yr period an increased incidence of hypertrophic PS was noted in a closed referral population. These patients demonstrated a temporal relationship between the ingestion of EE and the development of PS. A sequence of events from pylorospasm to pyloric tumors was suggested from the data.


Congenital pyloric atresia: Report of a familial occurrence. Fifty-nine cases of congenital pyloric atresia have been previously reported. A familial occurrence has been described in thirteen infants in six families. This report adds two cases.


Malignant hyperpyrexia during anesthesia in childhood. Malignant hyperpyrexia is a highly lethal complication of general anesthesia. It occurs with sufficient frequency, particularly in children and young adults, to justify use of continuous temperature monitoring during adminnstration of general anesthesia. Fever may be a late manifestation of the malignant hyperpyrexia syndrome, and it is important to be aware of the early signs. Prompt recognition and aggressive management should lower the high mortality known to occur with this complication. Family members should be screened for CPK elevations to determine possible susceptibility to malignant hyperpyrexia. Two case reports illustrate these points of diagnosis and management.


Intestinal obstruction in Nigerian children. A 10-yr review of acute intestinal obstruction in 280 Nigerian children reveals that the condition is the major cause of surgical emergencies in Nigerian children, as in children of other developing countries. These are significant differences of pediatric intestinal obstruction in developing countries, as compared with the pattern in other parts of the world. Intussuscaption was the leading cause followed by incarcerated or strangulated hernia. Lateness in presentation was common, with a resulting high morbidity and prolonged hospital stay. The overall mortality was 16%, but mortality of 33% was recorded in the neonatal group.


The simultaneous occurrence of paraduodenal and paracecal herniae presenting with volvulus of the intervening bowel. A very rare coincidence of paraduodenal and paracecal hernia with volvulus of the intervening small intestine is reported. The unusual anatomical set up predising to volvulus of a large loop of small bowel has been described. Restoration of normal anatomy was made possible by the application of principles of treatment of internal herniae.


Leading points in childhood intussusception. Children whose intussusception is caused by a specific pathologic lesion are harder to diagnose and have a higher morbidity than those with the idiopathic variety. We have collected and analyzed 31 such cases found in a series of over 500 intussusceptions. The average age of these children was greater than is usually found in most cases, and the duration of the signs and symptoms was also longer than is usually seen. Almost 50% presented with a picture of advanced small bowel obstruction. Fewer barium enemas were done (50%) and none was successful in reducing the intussusception. There was a higher number of ileo-ideal intussusceptions in this group. The commonest leading points were Meckel's diverticula, polyps, and duplications. All patients with leading points required operation; three-fourths had a bowel resection performed. This study of 569 cases suggests that older children with intussusception and children with recurrent intussusception do not necessarily have leading points causing their intussusceptions.


Occult appendiceal abscess complicating cystic fibrosis. Three case histories illustrate the diagnostic dilemma encountered whenever a patient with CF who is receiving antibiotics is evaluated for abdominal pain. Although acute appendicitis with perforation and abscess formation is not a common complication of CF, it occurs more frequently than is generally appreciated. The large number of abdominal situations in CF which can cause pain confused with but not typical of acute appendicitis. The true underlying condition is further masked by the concurrent use of antibiotics for pulmonary infection. A higher index of suspicion is needed to rule out acute appendicitis in a patient with cystic fibrosis and abdominal pain. A greater awaremess of the possibility of occult appendiceal abscess may help to avoid this complication.


Aganglionosis of the entire bowel.

Aganglionosis of the entire bowel. Three cases of aganglionosis of the entire bowel are presented. Eight other cases from English literature are reviewed. Two histologic types are noted. The incidence of Hirschsprung's disease in sibling is four out of 11.


Toxic amoebic colitis and amoebic colon perforation in children: An improved prognosis. Fourteen children were treated for complications of severe colonic amebiasis. Seven had colon perforation; seven had toxic amoebic colitis. Those with perforation underwent colon resection limited to the perforation and adjacent abnormal colon. Those having toxic amoebic colitis without perforation were managed by temporary ileostomy. Vigorous general supportive treatment for endotoxic shopck and amebiasis was given pre and postoperatively. Careful barium enema examinations proved safe and effective in diagnosis and follow-up. Ten patients survived (72%), five from each group.


Colon interposition for the replacement of the esophagus in children. Thirty-two new cases of colon interposition for esophageal reconstruction are presented. Only one late death occurred in this series, which was unrelated to the colon interposition. Fifteen severe complication were observed in five patients with preexisting esophageal atresia and previously complicated courses following disastrous primary esophageal repairs. The most common complication was pneumonia which occurred 13 times. Five late strictures responded well to dilatation or revision. Long-term weight gain was compared between a group of colon transplant patients and a group of patients with repaired esophageal atresia. Although the esophageal atresia group followed the 25th percentile and the colon interposition group followed the 3rd percentile on the growth curve, no significant difference existed in weight gain over 12 yr.


Late repair of bronchial rupture in a child by bronchial replantation. A 3-yr-old boy suffered blunt trauma to the anterior chest. Immediate treatment resulted in resolution of acute respiratory distress. Subsequent events led to the recognition of previous bronchial rupture six months later. Primary bronchial repair was not feasible and bronchial replantation onto the trachea was employed. An excellent early result was achieved.


Saturable first-pass metabolism of sulfisoxazole N1-acetyl in rats. Saturable metabolism of sulfisoxazole N1-acetyl in the rat during the initial pass of the drug from the intestinal lumen through the liver following oral administration of the drug (saturable first-pass metabolism) was investigated. The fraction of the total amount of drug recovered from the urine as the N4-conjugate fraction was apparent following the intravenous administration of sulfisoxazole acetyl or the oral administration of sulfisoxazole at the same dose levels.


Mechanism of action of BCG vaccine on neoplastic proliferation and host immune responses. BCG (Bacillus Calmette-Guerin) vaccine, Tice strain, caused a threefold increase in spleen weight of normal animals and a fourfold increase in spleen weight of sarcoma-bearing mice. In the latter group, the BCG vaccine caused infiltration of the sarcoma cells into the peritoneum and tumor metastasis in the spleen. Spleen lymphocytes from mice immunized with neuraminidase-treated sarcoma or from mice that had overcome an inoculum (100 cells) and a challenge (10(4) cells) of sarcoma P-1798 were cytotoxic against 51 Cr- or 14C-2-thymidine-labeled sarcoma cells. The serum of these mice enhanced the cytotoxic activity and inhibited the migration of the syngeneic lymphocytes. These serums also inhibited the migration of peritoneal macrophages from guinea pigs immunized with the sarcoma cells. BCG vaccine enhanced the development and growth of sarcoma P-1798; i.e., 50-100 viable sarcoma cells produced solid tumors in 8% of the untreated animals but in 100% of the BCG-treated animals. The serum of BCG-treated sarcoma-bearing animals inhibited the spleen lymphocyte-mediated cytotoxic action. The spleen lymphocytes from the BCG-treated sarcoma-bearing animals had no effect against 51Cr- or 14C-2-thymidine-labelled sarcoma cells. The data indicate that the serum from BCG-treated sarcoma-bearing animals blocks the spleen lymphocyte-mediated cytotoxic activities directed against proliferation and growth of the sarcoma.


Effect of alpha tocopherol (vitamin E) deficiency on intestinal transport of passively absorbed drugs. Alpha tocopherol (vitamin E) deficiency has been shown to cause changes in membrane structure. The present study relates alpha tocopherol deficiency with increased rates of transport and absorption of passively absorbed drugs. The pharmacokinetics of barbital in alpha tocopherol-deficient and control rats was studied. The barbital absorption rate constant in deficient animals increased compared to control values. This findings indicates that alpha tocopherol deficiency affects the intestinal membrane structure. This finding was confirmed by studying the intestinal transport of phenolsulfonphthalein, barbital, and salicylate using the everted gut technique. Phenolsulfonphthalein was transported more rapidly through the alpha tocopherol-deficient gut, but this difference was not significant after 30 min, probably due to membrane decomposition. Barbital, which is more lipid soluble and less dependent on changes in pore volume and size, was transported more rapidly through the deficient gut during the entire experiment. The transport rate of salicylate was not altered by the deficiency state. This result was expected since the drug is normally rapidly transported; therefore, comparatively small changes in permeability such as those induced by alpha tocopherol deficiency would be masked. After the oral administration of phenolsulfonphthalein to intact animals, a significantly higher amount of drug was recovered in the urine of the deficient group.


Automated in vitro dissolution rate analysis of potassium in plastic matrix slow release tablets. A fully automated system for dissolution rate analysis of potassium in slow release tablets is described. Aliquots are removed after 1, 2, and 4 hr from six samples, and potassium is analyzed in a flame photometer at 768 nm. A complete study of six samples takes 5.5 hr. The system may be run overnight. During the time intervals between the removal of aliquots, the system can be used for the determination of the total assay of tablets.


Structure and toxicity of alkaloids and amino acids of Sophora secundiflora. Seeds from Sophora secundiflora were extracted into three major fractions: lipids, alkaloids, and amino acids. Most of the lipid material was composed of steroid esters. These esters were hydrolyzed, and the fatty acid compositions were determined. The major alkaloid component was cytisine, with N-methylcytisine, anagyrine, and the fatty acid compositions were determined. The major alkaloid component was cytisine, with N-methylcytisine, anagyrine, and termopsine in lower concentration. The major free ninhydrin-positive compound was gamma-glutamyltyrosine. In addition to several common amino acids, pipecolic acid and 4-hydroxypipecolic acid were identified. Both the amino acid fraction and the alkaloid fractions caused minor pharmacological disorder when injected into rats. However, when both fractions were simultaneously administered, they were lethal.


Dissolution rates of high energy sulfathiazole--povidone coprecipitates II: characterization of form of drug controlling its dissolution rate via solubility studies. Solubility studies were made to characterize the form of sulfathiazole controlling the rate of dissolution exhibited in previously reported dissolution rate studies of sulfathiazole coprecipitated with povidone. The aqueous solubility of the high energy form of sulfathiazole obtained using sulfathiazole--povidone coprecipitates was determined in the presence of polymer in solution. Its aqueous solubility in the absence of polymer was determined by extrapolation. The solubility value was much greater than either the supercooled melt or the crystalline forms of sulfathiazole. Stabilization of these sulfathiazole solutions supersaturated with respect to the more stable crystalline form was achieved by the addition of sufficient polymer to the solution to prevent nucleation of the crystalline form. The concentration of polymer required to prevent nucleation of the crystalline forms was much higher than the previously reported concentrations required to inhibit crystal growth of sulfathiazole. The ratio of the solubility value obtained for the coprecipitated sulfathiazole as compared with its crystalline form I was in agreement with the ratio of their dissolution rates obtained the plateau regions of the dissolution rate experiments reported previously. The extrapolated aqueous solubility values in the absence of povidone were obtained as a function of temperature and were utilized to obtain thermodynamic parameters. The difference in the heat of solution of the two forms of sulfathiazole from the slope of the van't Hoff plots of the extrapolated solubility values was 1618 cal/mole, in excellent agreement with the literature value. The free energy, enthalpy, and entropy at 27 degrees for the coprecipitated drug relative to its crystalline form I were 1125 cal/mole, 8439 cal/mole, and 24 eu, respectively, indicating the high degree of molecular randomness and lack of structure in these high energy systems. These results provide strong evidence for the presence of an amorphous state of sulfathiazole as the controlling phase of both the solubility and dissolution rate experiments involving the high energy form of sulfathiazole obtained by coprecipitation with povidone.


Catharanthus alkaloids XXXII: isolation of alkaloids from Catharanthus trichophyllus roots and structure elucidation of cathaphylline. Further examination of the cytotoxic alkaloid fractions of Catharanthus trichophyllus roots afforded nine alkaloids. Two of these alkaloids, lochnericine and horhammericine, are responsible for part of the cytotoxic activity. The structure elucidation of cathaphylline, a new beta-anilino acrylate derivative, is described.


GLC determination of griseofulvin in human plasma. A specific and quantitative GLC method for the determination of griseofulvin in human plasma is described. The method involves extraction with ether, evaporation, addition of the internal standard dissolved in benzene, and GLC analysis using an electron-capture detector. The sensitivity of the method is 0.05 mug/ml of plasma. The results obtained with this specific GLC method were compared with the results obtained with the more frequently used spectroflurometric method by analyzing duplicate plasma samples obtained from 12 subjects following a single dose of griseofulvin. It was deduced that the 30% higher plasma levels obtained spectrofluormetrically were due to the coextraction and presence of the metabolite 6-demethylgriseofulvin in the assay solutions.


Granule consolidation during compaction. The deformation of small cylindrical aggregates of dibasic calcium phosphate was measured during compaction. An analogy between these aggregates and cylindrical granules was proposed. No change in the original shape of the aggregates occurred; the cylindrical shape was maintained even at high compaction pressures. Relaxation of the aggregates occurred at pressures higher than 420 MNm-2 (60.9 x 10(3) lb in.-2) when removed from the compacts, but no relaxation took place at pressures below this value. In addition, the aggregates relaxed by an increase in thickness only; there was no corresponding change in diameter. Up to a pressure of 200 MNm-2 (29.0 x 10(3) lb in.-2), an increase in aggregate diameter occurred, which was accompanied by a reduction in thickness. This change produced only a small reduction in volume, which was attributable to interparticulate slippage resulting in a closer packed arrangement. At a pressure of 200 MNm-2, the aggregate diameter no longer increased because solid bridges were formed between the particles and the die wall, preventing further spreading. From 200 to 420 MNm-2, failure of the material occurred by plastic deformation, which produced only a decrease in aggregate thickness. From 420 to 800 MNm-2 (116.0 x 10(3) lb in.-2), a structure was formed that could support the applied load without further reduction of thickness, and this structure was shown to behave elastically.


Effect of cycloamyloses on apparent dissociation constants of carboxylic acids and phenols: equilibrium analytical selectivity induced by complex formation. Apparent dissociation constants of organic acids were determined by potentiometric titration in the presence of cyclohexaamylose or cycloheptaamylose. The quantity deltapKa' = pKa' (cycloamylose)-pKa (water) was positive or zero for all carboxylic acids studied and negative or zero for all phenols. The term delta pKa' can be related to the cycloamylose concentration, K11alpha, and K11b, where K11a and K11b are 1:1 stability constants for complexes of the acid and the anion, respectively. From the dependen1a and K11b can be obtained. If deltapKa' not equal to 0, then K11a not equal to K11b; for carboxylic acids, K11a greater than or equal to K11b; for phenols, K11b greater than or equal to K11a. Because of variable pKa' shifts, it is possible to carry out differentiating titrations of some acid mixtures in cycloamylose solutions, whereas the same acids cannot be differentiated in water. If an acid is weakened by cycloamylose, its conjugate base is strengthened, and some carboxylate salts can be readily titrated in the presence of a cycloamylose.


GLC determination of plasma concentrations of phenprocoumon. A GLC method for the quantitative estimation of phenprocoumon from plasma is described. Plasma containing phenprocoumon, to which a known amount of phenytoin is added as the internal standard, is acidified and extracted with ethylene dichloride. The drug and the internal standard are then back-extracted into alkali, which is acidified and reextracted with ethylene dichloride. The organic extract is evaporated, and the evaporated residue is mixed with 50 mul of trimethylanilinium hydroxide in methanol. Aliquots (1-2 mul) are injected into a gas chromatography equipped with a flame-ionization detector in which the injection port is held at 325 degrees. The methyl derivatives of phenprocoumon and the internal standard give sharp, well-separated, symmetrical peaks. The method is of sufficient sensitivity to determine 0.125 mug/ml of the drug in plasma with a coefficient of variation of 7%.


Analysis of tetracycline in pharmaceutical preparations by improved high-performance liquid chromatographic method. The analysis of tetracycline in pharmaceutical preparations by an improved high-performance liquid chromatographic (HPLC) method is described. The improved method uses a 30-cm long stainless steel column packed with octadecylsilane bonded on 10-mum silica gel, with a linear gradient from 10 to 60% acetonitrile in pH 2.5, 0.02 M phosphate buffer in 11 min at a flow rate of 1.0 ml/min (68 atm). The resolution functions obtained between 4-epitetracycline and tetracycline and between 4-epianhydrotetracycline and anhydrotetracycline were improved 150 and 250%, respectively. The analysis of a tetracycline sample takes approximately 16 min; the original method required more tan 25 min. The relative standard deviation for the analysis of tetracycline powder was 0.66%, and the recovery of 4-epianhydrotetracycline added in tetracycline was linear over the 0.3-100% range. Recovery of tetracycline from products was better than 99.6% at label concentration. The drug content of products as calculated from the HPLC data agreed well with those of the microbiological assay methods.


Synthesis of substituted thiobenzoxazoles/benzothiazoles: inhibition of cellular respiratory and monoamine oxidase activities and anticonvulsant property. Several 2-(substituted alkoxy/hydrazinocarbonyl acetanilidothio)benzoxazoles/benzothiazoles were synthesized and characterized by their sharp melting points, elemental analyses, and IR spectra. All thiobenzoxazoles/benzothiazoles possessed low anticonvulsant activity, which was reflected by the 10-40% protection afforded by these compounds against pentylenetetrazol-induced convulsions. All thiobenzoxazoles/benzothiazoles inhibited selectively the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, DL-isocitrate, and alpha-ketoglutarate by rat brain homogenates. NAD-independent oxidation of succinate remained unaltered. All 2-(substituted hydrazinocarbonyl acetanilidothio)benzoxazoles/benzothiazoles inhibited monoamine oxidase activity of rat brain homogenates. Greater monoamine oxidase inhibition was observed with thiobenzothiazoles than with the corresponding thiobenzoxazoles/benzothiazoles was found to be unrelated with their ability to inhibit cellular respiratory and monoamine oxidase activities of rat brain homogenates.


Synthesis of N,N'-bis(3-substituted benzylideneaminopropyl)-piperazines and their anti-inflammatory, antiproteolytic, and anticonvulsant properties. Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to 67%. The antiproteolytic activity of these piperazines was reflected by their ability to inhibit in vitro hydrolysis of bovine serum albumin and casein by trypsin. The inhibition of trypsin-induced hydrolysis was concentration dependent and competitive in nature.


NMR study of amphetamines using europium shift reagents. Amphetamine and certain of its methoxylated derivatives show a high degree of interaction with NMR shift reagents of the type tris (1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione)europium(III). The shifts are not accompanied by appreciable line broadening, and both the aliphatic and aromatic protons can be resolved. The strong interaction between amine and shift reagent diminishes rapidly as the amine function is alkylated. For derivatives containing ortho-methoxyl groups, a weaker interaction with this functionality also becomes evident as the amine is alkylated. The stereospecificity of the shifting process was investigated by employing tris[3-(trifluoroacetyl)-d-camphorato]europium(III), a chiral shift reagent, with stereochemically pure enantiomers and known enantiomeric mixtures. Although certain (R)-enantiomers showed greater downfield C-methyl groups shifts, these shift differences from the corresponding (S)-enantiomers were small and not well resolved.


Intestinal secretion of erythromycin base. Erythromycin fluxes into rabbit midjejunal segments were studied. When erythromycin was infused into the jugular vein of anesthetized rabbits, the antibiotic was secreted into the segments at a rate of 0.0136 +/- 0.0023 mg/min. Preloading of the segments with five and 20 times the plasma concentration did not diminish this secretion. Protein binding of the antibiotic within the lumen could not explain this secretion, since both ultrafiltration and chromatography of luminal solutions indicated that the biological activity was free erythromycin. Moreover, the transmural potential across the intestinal mucosa is likely to be theprincipal driving force, since greater than 80 mv would be required to sustain the observed secretion against an imposed 20-fold concentration difference between blood and lumen. The best explanation for the intestinal secretion of erythromycin appears to be an active transport pathway capable of concentrating erythromycin in the lumen. It is not clear what endogenous substances are transported by this pathway.