Electron microscopy of trypsin-digested peripheral nerve myelin. Sciatic nerves from mice were removed and soaked in either PBS (phosphate buffered saline) or PBS plus I% trypsin (Sigma Type III) for various periods of time. Specimens were soaked at either room temperature or 37-degrees C at pH's ranging from 7.5 to 8.0. The epineural and perineural sheaths were split to allow the trypsin to penetrate the nerve. Tissue was prepared for electron microscopy by fixation in cacodylate buffered formaldehyde-glutaraldehyde solutions, post-fixed in OSO4 and embedded in Epon 812 or in glutaraldehyde-urea resin without osmication. After four h incubation at 37-degrees C or eight h at room temperature, the basement membranes of the Schwann cells became fragmented and detached and the myelin intraperiod band lost some density. After 18 h, myelin with swollen intraperiod bands displaying a loss of electron density and split main period bands was noted adjacent to normal myelin. Other areas had been transformed into vesicles indicating that the membranes of these vesicles appeared to have been derived from the detachment of both the intraperiod and main period bands within the myelin. Evidence is presented for the presence of trypsin digestable proteins in both the main period and intraperiod bands of peripheral nervouse system myelin.


Axon-glia relationships in crab nerves.

Axon-glia relationships in crab nerves. The nerves of the walking legs in the crab Lebidoclea grammania were studied by electron microscopy. Particular atthetion was directed to the structure of the connective tissue, its arrangement within the axon sheaths and its association with the glial cells. The connective tissue of the neural lamella of the giant axons and the fascicles is formed by collagen fibrils aand bands of mucopolysaccharides. Prolongations of the neural lamella divide the fascicles into bundles of contiguous axons, groups of loosely sheathed axons and nerve fibres wrapped by layers of glial cell processes alternating with layers of connective tissue. The glial cell processes close to the axons contained numerous microtubules whereas glycogen granules predominated in the more peripheral processes. These observations suggest that the connective tissue and glial cell processes forming the envelopes of the axons together participate in the maintenance of the microenvironment around axons.


Synaptic changes in frog brain after stimulation with potassium chloride. In vitro preparations of frog brains, stimulated by application of CKl were fixed by freeze substitution and examined electron microscopically. Control preparations were bathed in a calcium-free physiological solution with Mg added or in salt solution cooled to 5-10-degrees C. The isolated brain remains viable in the physiological solution as indicated by the direct cortical responses which can be led off from the forebrain. Control preparations were characterized by a row of vesicles situated close to the presynaptic membrane and by the absence of a well-developed postsynaptic web. In KCl stimulated preparations there were, in addition to synapses resembling those in the controls, synapses exhibiting fusion of synaptic vesicles with the membrane of the axonal ending, synapses in which the vesicles had retreated from the presynaptic membrane but were attached to it by a narrow stalk and synapses exhibiting a pronounced postsynaptic web. The synaptic gap was of a less uniform width than in the control preparations. The KCl stimulated preparations were furthermore characterized by a paucity of extracellular space and often showed invaginations formed by the presynaptic membrane and the plasma membranes of the postsynaptic or adjacent glial structure.


The node of Ranvier in experimental allergic neuritis: an electron microscope study. Pathological breakdown of the node of Ranvier in experimental allergic neuritis (EAN) in the rabbit was examined by electron microscopy. The study was concerned principally with the mechanism of disruption of paranodal myelin. Two types of change in myelin structure were observed, both apparently related to the presence of cytoplasmic processes of macrophages: (1) a vesicular disorganization of myelin lamellae and (2) a separation of myelin lamellae. Both methods of disorganization were used by macrophages as they apparently lifted off the myelin terminal loops of the paranode from the underlying axon and also penetrated between myelin loops and adjoining myelin lamellae. In some pathologically damaged nodes of Ranvier no macrophages were observed. The findings raise important immunological and electrophysiological questions concerning the involvement of the macrophage in the autoimmune response and the effect of the loss of paranodal myelin on nerve conduction.


Degeneration of sensory and motor axons in transplanted segments of a crustacean peripheral nerve. Segments of sensory and motor axons 0.3-0.5 mm in length were taken from crayfish peripheral limb nerves and transplanted into the abdominal cavity of the same animal. Transplanted sensory axons showed relatively few ultra-structural changes after one week, many had undergone complete lysis within two weeks, and almost all degenerated within three weeks. Transplanted motor axons appeared normal after one week, except for some hypertrophy of their surrounding glial sheaths. After two weeks, glial sheaths were grossly hypertrophied around motor axons; axonal mitochondria had increased in number and many had migrated from the periphery to the centre of the axon. The axonal membranes of all motor axons were still intact after three weeks, although most were no longer continuous after four weeks. By five weeks, all axonal material had completely disintegrated. These data suggest that axonal synthetic processes in crayfish sensory (and presumably motor) axons can maintain the axons relatively intact for 7-14 days and that transfer of substances form hypertrophied glial cells to motor axons may account for the longer survival times of transplanted motor axons.


Morphometric studies of dense-cored vesicles in type I cells of rat carotid body. Two subclasses of Type I cells of rat carotid body were recognized by analyzing the diameters of dense-cored vesicles. One group of cells contained vesicles with a mean diameter of about 52 nm; in the other group of cells the vesicles measured about 71 nm. The mean volume of the small vesicle cell (SVC) was roughly 3/4 that of the large vesicle cell (LVC). Furthermore there were significant differences between SVC and LVC in volume densities of vesicles extensions typical of the Type I cells were more common for LVC than for SVC. The majority of the nerve-endings observed terminated on LVC. The significance of these differences has yet to be determined.


Radiofrequency percutaneous Gasserian ganglion lesions. Results in 140 patients with trigeminal pain. Percutaneous radiofrequency ablation of the Gasserian ganglion or posterior root, or both, was performed in 140 patients. Of the 135 patients with trigeminal neuralgia, satisfactory analgesia was achieved in 121. Postoperative complications included unintentional first-division analgesia (10), transient sixth-nerve palsy (1), neuroparalytic keratitis (2), and anesthesia dolorosa (2). The phenomenon of facial blush may be helpful in avoiding unwanted first-division analgesia. In four of five patients with other forms of neuralgia, the procedure did not relieve pain; the fifth patient experienced significant relief from pain due to carcinoma of the mandible.


Long-term results of Gasserian ganglion electrocoagulation. This report is a follow-up study of 315 patients under 46 years old who suffered from trigeminal neuralgia and were treated by electrocoagulation of the Gasserian ganglion. The average foll-up period was 12.7 years, the maximum 33 years. Eighty percent had a return of pain, but 96.7% ultimately attained freedom from pain after repeat electrocoagulation.


Local spinal cord blood flow in experimental traumatic myelopathy. Focal blood flow was measured in the lateral funiculus and center of the spinal cord in the rhesus monkey both before and after a 600 gm-cm injury at T-10. Measurements made by the hydrogen clearance technique showed that blood flow in the lateral funiculus more than doubled within 4 hours after injury, returned to normal by 8 hours, and remained in the normal range for 24 hours. At no time was a hypoperfusion in the lateral funiculus present. Blood flow in the center of the spinal cord, at the level of the lesion, began to fall within 1 hour following injury and continued to fall for 4 hours. These data challenge the notion that spreading ischemia of the white matter is an important factor in the pathophysiology of experimental spinal cord injury.


Effect of delayed local cooling on experimental spinal cord injury. The authors report studies indicating that delayed local cooling is effective in minimizing the neurological deficits of experimental spinal cord injury in cats. Cortical evoked responses were useful in predicting the neurological outcome; untreated animals whose evoked response disappeared for 6 hours failed to recover whereas all treated animals in the same group recovered dramatically. Decompression by laminectomy alone proved ineffective. Possible explanations for the therapeutic effects of cooling and the significance of the delay are briefly discussed.


Vasogenic edema following acute and chronic spinal cord compression in the dog. The T-13 spinal cord segment of dogs was compressed both acutely and chronically by means of a balloon catheter. The vascular permeability to protein was assessed using Evans blue albumin (EBA), and the dorsal column evoked potential recorded to monitor conduction failure. With acute compression sufficient to cause conduction failure there was a marked leakage of EBA from the intermediate gray matter, which spread into the dorsolateral white matter. The degree of edema was similar whether the compression was maintained or released. Chronic compression maintained over 4 to 5 hours did not increase vascular permeability, but following release of compression leakage of EBA occurred in the same cord locations observed with leakage from acute compressions. This increased permeability following release of chronic compression may result from reactive hyperemia. Dorsal column conduction returned after the release of both acute and chronic compression. The extravasated EBA was present both in the extracellular space and within cells. The results and their clinical application are discussed.


Catecholamine levels in the injured spinal cord of monkeys. The authors report a study of catecholamine levels in the spinal cords of monkeys following a 300 gm-cm blow to the midthoracic spinal cord. There was a progressive decrease in norepinephrine (NE) activity as a first-order process with a half-life of 6.4 hours. The NE activity in injured tissue never exceeded control levels, which remained unchanged both above and below the injured segment. Dopamine activity remained unchanged in the injured tissue as well as in control segments above and below the area of trauma for the first hour.


Cervical spine injuries in infants. Problems in management. The authors point out the unique anatomical and therapeutic considerations involved in injuries of the cervical spine and cord in infants. The special problems encountered in the treatment of such patients are illustrated by three cases, a "Hangman's" fracture, a C6-7 fracture-dislocation, and an acute quadriparesis associated with dysgenesis of the posterior elements of C1-3.


Results of treatment of intracranial aneurysms by wrapping and coating. The authors report the results of treatment of 58 intracranial aneurysms by wrapping with muscle or muslin gauze, and/or coating with Selverstone plastic material. They conclude that reinforcement with muscle is of little value, but that muslin gauze and plastic produced satisfactory results.


Effect of respiratory movement on cerebrospinal fluid dynamics in hydrocephalic infants with shunts. The authors report a study of the effect of respiratory movement on intracranial, auricular, and intraperitoneal cerebrospinal fluid (CSF) pressure in hydrocephalic infants with shunts. Postoperative intraventricular pressures were also recorded for comparison. The intraventricular, right auricular, and intraperitoneal pressures rose during expiration and dropped during inspiration; the pressure changes were most marked while the infants were crying or straining. All pressures dropped simultaneously at the time of inspiration, but the auricular pressure was most significantly affected. It dropped to -100 to -200 mm H2O when the patients cried, while intraventricular and intraperitoneal pressures remained above O mm H2O. The postoperative intracranial pressures were in accord with these results; the pressures after ventriculoatrial shunt were significantly lower than those after ventriculoperitoneal shunt when the same pressure valves were used.


Incidence of postoperative deep vein thrombosis in neurosurgical patients. This preliminary report on the use of 123I-fibrinogen and Doppler ultrasound techniques for the diagnosis of postoperative deep vein thrombosis (DVT), shows that neurosurgical patients are at considerable risk. The DVT was often asymptomatic, bilateral, and extended into the more proximal veins.


Experience with videotape monitoring of microscopic neurosurgical procedures. This report describes technical details of a low-cost color videotape system for monitoring microneurosurgical procedures. The participation of audiovisual specialists was proven essential in insuring maximum effectiveness of these projects.


Spinal cord compression due to extramedullary hematopoiesis in homozygous thalassemia. Case report. The authors report a case of homozygous thalassemia in which a mass of hematopoietic tissue in the vertebral canal caused spastic paraparesis. Surgical removal of the tissue plus radiotherapy were successful. The pathological findings indicated direct extension of hematopoietic tissue from the adjacent bone marrow into the epidural space of the vertebral canal.


Posttraumatic bilateral middle cerebral artery occlusion. Case report. The authors report a case of bilateral posttraumatic middle cerebral artery occlusion. Previously reported unilateral cases are reviewed and possible pathophysiological mechanisms disscussed.


Pulmonary arteriovenous malformation: scintigraphic demonstration and analysis. Scintiphotographic demonstration of a pulmonary arteriovenous malformation in an 8-year-old child is presented. Using a data processor, the transit of radiopertechnetate through the lesion as well as various portions of the lung is shown. The "steal" of blood flow from the left lobe is documented.


Initial clinical experiences with a Fresnel zone-plate imager. First clinical studies with a Fresnel zone-plate radioisotope imager demonstrate high resolution, sharp tomography, and freedom from scatter. Improved radionuclide imaging is demonstrated, at least for small organs like the thyroid. Certain limitations are present that indicate a need for additional development before application to routine clinical practice.


Changes in 87mSr concentractions in skeletal metastases in patients responding to cyclical combination chemotherapy for advanced breast cancer. Serial 87mSr bone scintigrams were performed on a series of patients being treated by cyclical combination chemotherapy for metastatic breast cancer. All the patients investigated responeded to the chemotherapy, but initially the scintigrams showed an apparent deterioration, in that the tumor-to-normal isotope uptake ratios increased. Following this initial "flare" the scintigram appearance improved with a decrease in the tumor-to-normal uptake ratio. It is suggested that deterioration in the scintigram in the early stages of treatment should not be regarded as an indication that the patient is failing to respond.


Changes in liver scan following splenectomy. Changes in liver shape, position, and uptake of colloid have been noted by us in liver scans in patients following splenectomy. These changes have resulted in confusion in interpretation. Four cases are described to illustrate some of the possible misinterpretations. These include migration of the left lobe of the liver into the left upper quadrant mimicking residual or accessory spleen, mass lesion in the region of the porta hepatis, or recurrent foci of disease.


Phonton absorptiometry and skeletal mass in the treatment of osteoporosis. Thirty-six osteoporotic patients who underwent several therapeutic regimes were studied on two occasions by photon absorptiometry and total-body neutron activation analysis (TBNAA). These determinations were made at a mean interval of 8.9 plus or minus 0.8 months. The 8-cm radial site was chosen for the photon absorptiometry which was performed with the Norland-Instruments Densitometer. Mean initial bone mineral content (BMC) was 0.724 plus or minus 0.069 gm/cm and mean bone width was 1.235 plus or minus 0.072 cm. The mean percent change in BMC (%deltaBMC) was 1.02 plus or minus 4.2. The initial total-body calcium (TBCa) as determined by TBNAA was reduced when compared with values that would be expected from empirically derived formulas. The mean percent change in TB-Ca (%deltaTB-Ca) was -3.2 plus or minus 4.7. Most patients displayed a change in BMC and TB-Ca that was at least 2 s.d. greater than the precision of the methods used (%deltaTB-Ca greater than 2). No relationship was found between the deltaBMC and the deltaTB-Ca (r = 0.17). These findings suggest that changes in the radical BMC at the 8-cm site cannot be extrapolated to indicate changes in skeletal mass in response to treatment of osteoporosis. Whether photon absorptiometry at other sites or at multiple sites provides a closer relationship to changes in skeletal mass (TB-Ba) remains to be determined.


Scintigraphic imaging of a blind-ending ureteral duplication. The scintigraphic image is compared with the urographic appearance of blind-ending ureteral duplication.


Application of annihilation coincidence detection to transaxial reconstruction tomography. A study was carried out to investigate the use of annihilation coincidence detection (ACD) in emmision transaxial reconstruction tomography. The ACD was evaluated in terms of spatial resolution and sensitivity with depth, detection efficiency, effect of pulse-height analysis on resolution and efficiency, correction for attenuation, and cold spot contrast. A prototype positron emission transaxial tomograph (PETT) consisting of a hexagonal array of 24 Nal (Tl) detectors employing ACD was constructed. A fast Fourier transform algorithm was employed to generate the reconstructed image. Computer simulations and phantom and animal studies were carried out to demonstrate that this approach yields tomographic radionuclide images that have high resolution and contrast (hot and cold spot) and that are independent of activity above and below the plane examined. The ACD yields a quantitative nuclear medicine imaging device with high detection efficiency. Comparisons are presented between the ACD and the scintillation camera and scanner. Discussion of the possible applications of the PETT in nuclear medicine is included.


Radiochromatographic quality control: a simplified system. A simple means of graphically displaying the degree of radiocompound binding purity using a shielded G-M tube integrated with a rate metar and strip cahrt recorder is described. The instrument produces a permanent quality-control record  and eliminates time-consuming radio-chromatographic segment counting.


Component resolution indices for scintillation camera systems. From published overall resolution indices for three Anger camera systems, measured with three straight-bore collimators and 99mTc in air and with a water absorber present, the components due to inherent camera resolution, collimator geometry, and scatter are derived at various depths. Replacement of S-11 multiplier phototubes by bialkali phototubes improves calculated inherent Pho/Gamma III camera resolution by about 30% and by a further 33% upgrading to a high-performance model. At distances 2, 5, 8, and 10 cm from each collimator face with an intervening water absorber, mean scatter components of overall resolution indices are 6, 8, 9, and 10 mm, respectively. In typical clinical 99mm Tc imaging situations with a scattering medium present, the relative contributions of camera, collimator, and scatter to the total overall system resolution are presented.


Anaphylactoid reaction to human albumin microspheres. The first case of an anaphylactoid reaction to the intravenous administration of 99mTc-labeled human albumin microspheres is reported.


Technetium-99m-diphosphonate accumulation in amyloid. A well-documented case of multiple myeloma complicated by histologically demonstrable amyloidosis is presented. Technetium-99m-diphosphonate in the areas of amyloid deposition about the shoulders and hips is shown. This adds another dimension to the extraosseous sites without demonstrable calcification where accumulation of bone-seeking radiopharmaceutical can be observed. In patients where symmetrical uptake of such agents is noted in the periarticular soft tissue, particularly of the hips and shoulders, amyloidosis must become a diagnostic consideration. This is particularly true in patients presenting with undiagnosed arthralgia.


Radioactive embolization from upper-extremity thrombophlebitis. A lung scan in a patient with upper-extremity thrombophlebitis showed "hot spots" that apparently resulted from embolization of a propagative thrombus.


A potential new brain-scanning agent: 4-77Br-2,5-dimethoxyphenylisoproplamine (4-Br-DPIA). A centrally active drug containing bromine has been synthesized with 82Br and 77Br and appears to concentrate in normal human brain tissues, suggesting its potential use as a brain-scanning agent.


A 82Sr-82Rb isotope generator for use in nuclear medicine. An improved 82Sr-82Rb generator system, based on the complexing ion-exchange resin Chelex-100, has been developed. Columns of this material can be easily and rapidly milked, and the rubidium-strontium separation factor for a fresh generator under the experimental conditions studied was found to be greater than 10-7. Approximately 80% of the 82Rb present can be delivered in a 15-ml volume of aqueous 0.2 M NH4Cl solution. After more than 6 liters of eluant had passed through the generator, the rubidium-strontium separation factor was still observed to greater than 10-5 and no unusual strontium breakthrough behavior was seen in the system over nearly three 82Sr half-lives.


Foramen of Morgagni hernia diagnosed by liver scan. A case of foramen of Morgagni hernia (partial eventration of the right diaphragm) containing liver was diagnosed by hepatic scintiphotography. Diagnostic pneumoperitoneum has been recommended as the procedure of choice in the past. It is suggested that this be replaced by liver scaning. The similarity between eventration of the right diaphragm and foramen of Morgagni hernia is discussed.


Dynamic study of exocrine function of the pancreas in diabetes mellitus with scintigraphy using 75Se-selenomethionine. A dynamic study of scintigraphy of the pancreas using 75Se-selenomethionine in diabetic patients was performed. Patients were selected who complained of abdominal pain or diarrhea or both and whose pancreatic exocrine functions were thought to be disturbed. Selenium-75-selenomethionine (3 muCi/kg body weight) was injected intravenously and radioactivity (cpm) was recorded by a scinticamera for 10 min successively up to 120 min. After 20-30 min the increase of radioactivity in the selected area of the displayed pancreas usually reached a plateau. Pancreozymin (1 Harper unit/kg) and secretin (1 harper unit/kg) were administered intravenously and decrease of radioactivity in the same area was followed for 60 min to examine pancreatic exocrine function. After 75Se-selenomethionine injection, the angle of the initial increase of radioactivity, the height of the plateau, and the reactive decrease of radioactivity after pancreozymin and secretin were analyzed in each case. Radioactivity recorded on data tape was reproduced for each 10-min period on a cathode-ray tube display. Areas of interest were selected for dynamic analyses. To supplement the diagnosis by visual image of a scintigram of the pancreas, the scintigram was quantified in the present study and the dynamic curves of radioactivity in the selected area of the displayed pancreas were studied for a total of 3 hr. Application of the dynamic study of the pancreas scintigraphy and the additional data analyses seemed useful for the early detection of pancreatic exocrine dysfunction in diabetic patients in whom the ordinary laboratory pancreatic exocrine function tests gave uncertain results.


Data storage and retrieval system for a nuclear medicine department. A mark sense IBM data card was designed specifically for the nuclear medicine department. The data card functions as a flow sheet with coded information added in sequence by secretary, technician, and physician. Statistical information, patient identification, quantitative results, physician interpretation, and discharge diagnosis can be easily coded and entered on the card by the appropriate individual. The completed card can be punched, filed, and retrieved by machine. Filing and retrieving can also be done by hand for flexibility. The stored data can easily by programmed and converted to computer handling and storage. The card is inexpensive to produce. Card design is extremely flexible for varying needs. If sorting and punching equipment is not available, this can be contracted for in the community as low cost.


Deadtime characteristics of Anger cameras. The deadtime characterisitcs of Anger cameras are analyzed from theoretical and experimental points of view. An investigation of two Searle Radiographics cameras revealed that they had both paralyzable and nonparalyzable components, the deadtimes of which varied with analyzer window width, the energy of the gamma rays counted, and the position of the "time constant selector" switch in the A-scope module of these cameras. A mathematical model for two-component systems is presented.


Breast scintigraphy with 99mTc-pertechnetate and 67Ga-citrate. Radionuclide breast scintigraphy was evaluated as a noninvasive tumor-localizing modality. Technetium-99m-pertechnetate (99mTcO4) demonstrated good correlation between malignancy and postive scintigraphy (88% accuracy in 16 cases of breast carcinoma). The high false-positive rate (29% of proven benign breast disease) limits the use of 99mTcO4 as an aid to differential diagnosis. Gallium-67-citrate (67Ga) is limited as a diagnostic adjunct (localizing in only five of ten breast malignancies). Refined techniques of positioning, shielding, gamma camera imaging, and computer assistance have helped in visualizing abnormal radionuclide accumulation.


Nomogram for estimating normal liver weights. A nomogram was constructed by which the normal weight of a patient's liver can be estimated from the patient's height and weight.


Autoradiography of live and dead mammalian cells with 99mTc-tetracycline. Considering the diagnostic significance of a few 99mTc-chelates in the diagnosis of myocardial infarct, we have recently developed a necrosis model in tissue culture obtained from mammalian cells, where the dead cells showed enhanced binding of 99mTc-tetracycline like the necrotic cells of infarcted myocardium. Technical details of the principles of labeling, fixing, washing and drying, dipping in emulsion, exposure, development and staining of mammalian cells have been described. Considering the short half-life of 99mTc-radioisotope, the recently available techniques have been modified to make autoradiography possible in a reasonably short period of time. Technetium-99m in different physical and chemical states is playing a very important role in a variety of diagnostic procedures. The autoradiography of 99mTc-labeled cells and tissue will shed further light on the mechanism of cellular uptake and subcellular distribution in normal and pathologic states. Presently no information is available regarding autoradiography with 99mTc-chelates of mammalian cells obtained from tissue culture.


Loculation as a contraindication intracavitary 32P-chromic phosphate therapy. Loculation of instilled 99mTc-sulfur colloid solution in the peritoneal cavity was observed in a patient being considered for intracavitary therapy with 32P-chromic phosphate. Since intracavitary instillation of a therapeutic dose of a radiopharmaceutical agent into a loculated space would risk therapeutic failure and tissue necrosis, prior instillation of a tracer nuclide is recommended to insure adequate dispersion before beginning such therapy.


Lung scan and wide mediastinum.

Lung scan and wide mediastinum. A patient with dissecting aneurysm of the ascending aorta and hemopericardium showed a widened mediastinum on posterior lung scan.


Visualization of pancreatic pseudocyst.

Visualization of pancreatic pseudocyst. In a 44-year-old woman, a pancreatic pseudocyst was demonstrated on delayed images obtained up to 8 days after the intravenous administration of 0.250 mCi 75Se-selenomethionine. The initial routine pancreas image study failed to visualize both the pancreas and the pancreatic pseudocyst. The diagnosis was confirmed at surgery and the fluid of the pancreatic pseudocyst contained 0.73% of the injected dose of the radioselenium.


Multiple pulmonary arteriovenous fistulas demonstrated by dynamic radionuclide pulmonary perfusion scanning. Dynamic radionuclide perfusion scintigraphy performed with 99mTc-labeled microspheres was instrumental in establishing the diagnosis of multiple, small-vessel, pulmonary arteriovenous fistulas in a 14-month-old patient with cyanosis. Computer analysis of the sequential distribution of tagged microspheres in the pulmonary parenchyma normally demonstrates a curve that rises rapidly to a plateau as the particles microembolize. In the case reported here, the pulmonary flow curve rose rapidly to a maximum and then fell within 2 sec to a plateau of less than 50% of the maximum count, indicating that a large proportion of the microsophers passed through the pulmonary circulation. Conventional pulmonary contrast angiography did not demonstrate any intracardiac shunting but did confirm the presence of multiple pulmonary arteriovenous fistulas.


Urea, citrate and orotate excretion in growing rats fed amino acid-deficient diets. Male, weanling rats were fed a control purified amino acid diet or the same diet with lysine, phenylalanine, tryptophan, valine, or arginine omitted singly, or both arginine and lysine omitted. Blood urea reached three to four times that of control levels with all deficient diets. Urea excretion increased almost linearly with time during the first 3 days of amino acid deficiency. Rates of urea excretion on day 3 in decreasing order for various deficiencies were as follows: lysine and arginine combined are more than lysine is more than tryptophan equals valine is more that phenylalanine equals arginine. Urinary citrate was 26 and 21.8 times that of control values without arginine and 11.4 and 6.2 times that of control values without lysine on days 2 and 3, respectively. By day 8 citrate excretion had returned to control levels without lysine but not without arginine. Citrate excretion was unchanged with other deficiencies. Orotic acid excretion increased markedly only without arginine and slightly without tryptopahn. A deficiency of arginine and lysine increased urea and citrate excretions to a greater extent than either deficiency alone. Two injections of arginine or homoarginine (0.50 mmole/injection) given at 12-hour intervals to rats fed no lysine and arginine for 3 days decreased citrate excretion immediatedly and on the following day. Urea excretion decreased with injected homoarginine, but not with arginine. Orotic acid excretion increased more than four times on the day of homoarginine injection compared with that of the preceding day. Arginine injection returned orotic acid excretion to nearly control levels within 24 hours. Urea degradation in the gastrointestinal tract was increased in animals fed amino acid-deficient diets.


Use of a whey protein concentrate as a supplement to maize, rice and potatoes: a chemical and biological evaluation using growing rats. Liquid whey has long been known to contain proteins of high nutritional value, but their use in human nutrition has been complicated by the high lactose and low protein contents of the whey. Modern technological processes of gel filtration and ultrafiltration have made possible the production of whey protein concentrates (WPC) low in lactose. In this investigation, the supplementary effect of WPC on maize and rice proteins was compared with the corresponding effect of dried skim milk (DSM). Protein quality was studied by chemical and biological methods on growing rats. Biological tests performed on both raw and boiled protein mixtures showed WPC to be superior to DSM in supplementing maize and rice proteins. The nutritive value of a potato-WPC mixture was also studied and compared with those of potato-lactalbumin and potato-egg mixtures, both of which are known to contain protein of very high quality for man. The comparison indicated that a potato-WPC mixture may also possess high protein quality.


Influence of dietary 1,3-butanediol on wieght gain, blood, and liver metabolites and lipogenesis in the pig and chick. The influence of dietary 1,3-butanediol (BD) on body weight gain, blood and liver metabolites, and on lipogenesis in pigs and chicks was studied. Body weight gain and energy intake of both pigs and chicks were depressed when the dietary energy derived from BD exceeded about 20 percent. Circulating beta-hydroxybutyrate and acetoacetate levels were markedly increased by dietary BD. Plasma triglyceride levels were increased in pigs and unchanged in chicks fed BD-containing diets. In vitro rates of fatty acid synthesis and the activities of fatty acid synthetase and malic enzyme in pig adipose tissue were not affected by the dietary BD. Neither addition of 18 percent dietary energy in the form of BD to the diet nor addition of BD to the incubation buffer affected glucose conversion to fatty acids by chick liver slices. Dietary BD did not affect long-chain acyl CoA levels in freeze-clamped chick liver but did increase the free CoA levels slightly. The hepatic lactate: pyruvate ratio was decreased when chicks were fed a BD-containing diet.


Circadian rhythms in mice fed a single daily meal at different stages of lighting regimen. Circadian rhythms in systemic and cellular variables were studied in three groups of mice on different schedules of daily food accessibility: (1) only during the first 4 hours of the 12-hour light span; (2) only during the first 4 hours of the 12-hour dark span; and (3) at all times. The amplitudes of circadian variation in rectal temperature, serum corticosterone, and liver glycogen were increased by "meal-feeding" in either early light or early darkness. The overall averages of corticosterone and glycogen were also increased by meal-feeding at either stage of the lighting regimen. The time of peak values in temperature, corticosterone, and glycogen were determined by the time of food presentation, regardless of its relation to the lighting regimen. On the other hand, the interval between food presentation and peak values in the corneal mitotic index was greater when feeding was restricted to early darkness. These differences among the three groups of animals resulted in different relations among varibles at any given interval after feeding onset. Such effects concerning total bodily function, energy storage, hormonal regulation, and basic cellular processes indicate the pertinence of meal timing to nutritional research and practice.


Glucogenic and ketogenic capacities of lard, safflower oil, and triumdecanoin in fasting rats. The glucogenic and ketogenic capicities of lard, safflower oil, and triundecanoin were compared. Rats were fed diets containing 30 percent of either lard (a ketogenic fat), triundercanoin (a glucogenic fat), or safflower oil (a fat high in linoleic acid). After 61 days, the rats were fasted for 72 hours. Plasma glucose and ketone body concentrations and carcass fatty acid loss were measured during fasting. The lard-fed animals, which lost mostly saturated even-chain length fatty acids during fasting, did not maintain their prefasting plasma glucose levels and became ketotic. The animals that had been fed triundecanoin (which mobilized considerable odd-chain fatty acid) maintained their prefasting plasma glucose levels and did not become ketotic. The animals fed safflower oil (which mobilized massive amounts of linoleic acid) showed even lower levels of plasma glucose and higher levels of ketone bodies than did the animals fed lard. This failure of safflower oil to avert fasting hypoglycemia suggests that linoleic acid is oxidized in a manner more like the saturated fatty acid of lard than like the glucogenic odd-chain fatty acid (undecanoic).


Lipogenesis and glyceride synthesis in the rat: response to diet and exercise. The responses of hepatic and adipose tissue malic enzyme (ME), citrate cleavage enzyme (CCE), glucose-6-phosphate dehydrogenase (G6PD), and glyceride synthetase (GS) to exercise training and exhaustive exercies and the potential of a high fat or high carbohydrate diet to modify these responses were studied in male Carworth rats. Characteristic elevation and depression of ME, CCE, and G6PD were decreased in skeletal muscle, liver, and adipose tissues of high carbohydrate-fed rats. A significant two-way diet-training interaction was indicated for hepatic ME and G6PD. This interaction resulted from an apparent training modulation of ME and C6PD responses to the high fat and high carbohydrate diets. Adipose tissue G6PD was significantly decreased by training. Exhaustive exercise performed immediately prior to sacrifice did not significantly alter ME or CCE activities in either liver or adipose tissues, but decreased adipose tissue G6PD in untrained rats. Exhaustion was also associated with decreased GS activity in muscle and liver. Physical training was associated with a significant increase in GS in muscle and adipose tissues. In contrast to glyceride synthesis, no increase in adipose tissue lipogenic potential was noted in response to training, indicating that the physically trianed rat may have an enhanced ability to store but not synthesize fatty acids.


Effect of dietary calcium deficiency during pregnancy on zinc mobilization in intact and parathyroidectomized rats. The effects of dietary deprivation of calcium on teratogenicity of zinc deficiency were studied in both intact and parathyroidectomized rats. Intact females fed a diet deficient in both zinc and calcium during pregnancy had larger litters, fewer resorptions, and fewer malformed fetuses than did those fed a diet deficient in zinc alone, In addition, ash, zinc, and calcium contents of maternal bone were reduced. However, alleviation of the teratogenic effects of zinc deficiency by a diet simultaneously lacking calcium did not occur in parathyroidectomized rats. Furthermore, ash, zinc, and calcium concentrations of maternal femur were not decreased in these animals, indicating that they were unable to mobilize skeletal calcium or zinc. Thus, intact parathyroid glands are essential for alleviation of the teratogenic effects of zinc deficiency by dietary calcium deficiency. These results provide further evidence to support the hypothesis that conditions bringing about resorption of bone increase the availability of skeletal zinc.


Effect of choline deficiency on utilization of labeled precursors of choline and turnover of choline in the liver of mature Japanese quail. Studies were conducted to determine the effect of choline deficiency on utilization of various labeled precursors of choline and rate of choline biosynthesis in mature Japanese quail. A deficiency of dietary choline did not change the in vivo incorporation of 14C-label from (1,2-14C) ETHANOLAMINE, N, N-dimethyl (1,2-14C) ethanolamine, and L-(methyl-14C) methionine into liver phosphatidylcholine (PC) or total phospholipids. Incorporation of radioactivity from (14C) serine into liver PC was increased, but the difference was not significant (PGREATER THAN3.35). In vitro studies confirmed these observations as there were no differences in liver microsomal methyltransferase activities, expressed as the incorporation of methyl-14C from labeled S-adenosylmethionine into microsomal PC from quail fed a purified diet with with or without choline. Rats appeared to incorporate an increased amount of 14C into PC when fed a diet devoid of choline, but the differences were not significant. There were differences in methyltransferase activities among species, and quail had the lowest activity. A slower turnover of choline was found in quail liver (t1/2=7.5 hours) as compared with that of hen liver (t1/2=2.0 hours). The methyltransferase responsible for the first methylation of phosphatidyl-ethanolamine from quail liver appears to differ from most other biosynthetic enzymes in that it occurs in liver and catalyzes the reaction at a slow rate but cannot adapt to exogenous choline supply to meet the requirements for normal bodily functions in quail.


Growth and ascorbic acid metabolism in rats and guinea pigs fed cereal diets. The nutritional values of the whole grain principal cereals, namely, wheat, rice, corn, and a millet bajra, were investigated by growth studies and studies on ascorbic acid metabolism in rats and guinea pigs. Growth was markedly retarded by feeding the rats unfortified whole grain cereals. Among the whole grain cereals, rice provided the lowest nutritional value, and the cooking of rice affected the nutritional value further. In weanling rats, ascorbic acid synthesis at the subcellular level was inhibited, and tissue storage of ascorbic acid was decreased in rats fed whole grain cereals. In guinea pigs fed whole grain cereals, the utilization of ascorbic acid was increased. Ascorbic acid supplementation at various levels indicated that the requirement for ascorbic acid increased five times in guinea pigs fed whole grain cereals. The increased intake of the vitamin was not needed when the whole grain cereals were enriched with 15% casein.


Nutrient interrelationship of ascorbic acid and iron in rats and guinea pigs fed cereal diets. Iron at a daily dose of 5 mg per animal was toxic to rats and guinea pigs fed unfortified whole wheat flour and whole rice flour diets. In rats, a species capable of synthesizing ascorbic acid, iron supplementation resulted only in decreased growth. In guinea pigs, iron administration resulted not only in decreased growth but also in high mortality. The apparent toxicity of iron was not observed when wheat flour was fortified with 15% casein. In guinea pigs, administration of ascorbic acid (k mg per 100 g body weight per day) along with iron not only counteracted the toxic effect of iron, but also led to a greater utilization of iron as revealed by increased hemoglobin and serum iron levels accompanied by decreased spleen iron content. Iron administration, however, resulted in decreased ascorbic acid synthesis (in rats only) and increased ascorbic acid utilization as revealed by lowered urinary, blood, and other tissue levels of the vitamin.


Cecal nitrogen metabolism and amino acid absorption in the rabbit. Nitrogen balance and weight changes were determined in two groups of rabbits fed diets containing all natural protein or part nonprotein nitrogen from urea. The rabbits were fed the experimental diets for a 10-week period starting at 7 weeks of age. No significant differences in weight gains or nitrogen retention were found between groups. Total nitrogen, ammonia, urea, and free amino acid levels were determined in the contents of several segments of the gastrointestinal tract of the rabbits fed both diets. Significantly less total nitrogen, ammonia, and free amino acids were found in the lower colon compared with the cecal contents of both groups. Subsequent studies with (C)alanine revealed considerable fermentation of alanine in both the cecum and upper colon contents, but there was little absorption into the blood. It was concluded that the disappearance of nitrogen that occurred between the cecum and colon was in the form of ammonia, and that the value of urea as a nitrogen source resulted primarily from tissue synthesis of dispensable amino acids and coprophagy.


Effect of force-feeding a valine-free diet on gastrointestinal function of rats. To study the effect of an essential amino acid deficiency on gastrointestinal functions, rats were force-fed a 10% amino acid diet devoid of valine for several days, and subsequently a complete amino acid diet. Force-feeding of the valine-free diet for a few days delayed the disappearance of dietary nitrogen from the gastrointestinal tract. ASINGLE FEEDING OF THE COMPLETE AMINO ACID DIET CONTAINING 14C-labeled amino acids or (14C)glucose to rats previously fed the valine-free diet did not improve disappearance of the nitrogen. The absorption of the dietary carbohydrate as well as dietary nitrogen was delayed after feeding the valine-free diet. In spite of the delayed disappearance of dietary 14C-labeled amino acids or (14C)glucose from the gastrointestinal tract, the incorporation of these dietary 14C-labeled amino acids into liver lipids was not different between rats fed the complete amino acid diet and those fed the valine-free diet. Under these experimental conditions, changes in disaccharidase activities in the intestinal mucosa were in parallel with changes in the disappearance of nutrients from the gastrointestinal tract.


Step size in the Munsell color-order system by pair comparisons near 5Y 7.5/1 and bisections near 10R 7/8. Pair comparisons were used to assess the perceptual uniformity of the Munsell value (V) and chroma (C) scales near 5Y 7.5/1 for both small (0.25-0.75) and larger (1-2) increments in V and C. We conclude that in this region perceptual linearity is retained down to steps of 0.25 V and C. Bisection experiments showed that around 10R 7/8 perceptual linearity in Munsell hue (H), V, and C was retained down to step sizes of 0.25 H, 0.10 V, and 0.25 C.


The first urinary tract infection in the female infant. Prevalence, recurrence, and prognosis: a 10-year study in private practice. Eight hundred healthy female infants presenting for routine care were systematically screened for bacteriuria from early infancy to 2 years of age. The initial urinary tract infection was established in 29 infants, 3.6% of the series, at a median age of 9 months. Continued systematic screening of 25 of these 29 infants with bacteriuria to 6 years of age revealed recurrent infection in nine of them and the development of pyelonephritis in three. Recurrent episodes of infection occurred at close intervals of 2 weeks to 4 months in these nine infants and were clustered within an 18-month period. There were no recurrences after 3 years of age. Characteristically, both the initial and recurrent infections were asymptomatic. Lower urinary tract signs of infection, however, were evident to the "instructed parent," i.e., one instructed in the use of the urinary diary, a written log of the parents' observations of the infant's voiding habits. Pyelonephritis developed early in the children with recurrent infections; it was clinically inapparent and developed in infants with (initially) normal urinary tracts.


Early predictors of incomplete recovery in children with Guillain-Barr'e polyneuritis. Case histories of 47 children with strict criteria for Landry-Guillain-Barré-Strohl polyneuritis admitted to a rehabilitation facility from late 1959 through 1972 were analyzed retrospectively. The children were followed to full recovery (good to normal strength in all muscle groups) or for three years without full recovery. The data were then compared statistically for possible predictive indicators of recovery or lack of recovery within three years. The most significant early predictor of incomplete recovery was the time interval between the greatest weakness and beginning improvement; a period longer than 18 days of plateau before gains are evident is indicative of incomplete recovery within limits of 99% confidence.


Premature craniosynostosis-a complication of thyroid replacement therapy. Three hypothyroid children with premature craniosynostosis are presented, who have been treated intensively with 1-thyroxine from early infancy. It is postulated that the craniosynostosis is the result of iatrogenic hyperthyroidism during a critical period of skull growth. Various regimens of treatment for hypothyroidism are discussed with recommendations for avoiding this potentially hazardous complication of therapy.


Calcification of intervertebral discs in childhood. Over 75 cases of intervertebral disc calcification in childhood have been reported, but the illness is seldom considered in the differential diagnosis of back pain inchildren. This paper reports two children who required surgery for intervertebral disc calcification. The histologic changes, which have not been described previously, include an amorphous calcification within the nucleus pulposus without any inflammatory reaction. The etiology of disc calcification remains unknown, but it can be differentiated both clinically and pathologically from other causes of calcified intervertebral discs and from spondylarthritis.


Cerebro-hepato-renal syndrome of Zellweger. A report of eight cases with comments upon the incidence, the liver lesion, and a fault in pipecolic acid metabolism. Studies of eight patients with this syndrome confirm the characteristic pattern of abnormalities and the autosomal recessive mode of inheritance. The incidence is estimated to be approximately 1 in 100,000 live births. The liver lesion proved to be variable, with features of progressive parenchymal damage rather than a developmental defect of small bile ducts as previously suggested. Elevated levels of pipecolic acid were found in blood and urine and may be related to the basic defect.


Fetal phallic growth and penile standards for newborn male infants. No appreciable difference in size of the fetal clitoris versus the fetal penis was noted until 14 weeks' gestation, which is after the period of masculine differentiation of the external genitals. However, significant differences in the rate of penile and clitoral growth were evident in second trimester fetuses. The majority of the prenatal growth of the penis occurs after 14 weeks gestation at an almost linear rate. The penile stretched length of the full-term infant was 3.5 cm plus or minus 0.7 cm and the diameter was 1.1 cm plus or minus 0.2 cm.


Parathyroid function in infants of diabetic mothers. Serum parathyroid hormone and total and ionized Ca, Mg, and P levels were determined serially from birth to 96 hr of age in 28 infants of diabetic mothers (IDM, 15 Class A, 13 Class B, C, D) and their respective mothers at the time of delivery. In spite of marked decreases in concentrations of serum total and ionized Ca from birth to 24 to 48 hr, there was an insignificant increase in serum PTH values over this period in infants of insulin-dependent mothers. Infants of Class A diabetic mothers had an equivocal PTH response. Nineteen term control infants were similarly examined and had a significant increase in serum PTH postnatally. Relatively higher values of serum ionized Ca at birth in IDM were followed by greater decreases in ionized Ca from birth to 24-48 hr of age, and by decreased neonatal parathyroid function. The data support functional hypoparathyroidism as a basis for the hypocalcemia and hyperphosphatemia of IDM. It is speculated that increased concentrations of serum ionized Ca in utero and suppression of activity in the fetal parathyroid glands may be a cause for the functional hypoparathyroidism.


Fontanel size and epiphyseal ossification in neonatal twins discordant by weight. Size of the anterior fontanel and ossification of the epiphyseal centers at the knee were measured in 13 "discordant" twin pairs. There was a highly significant (p smaller than 0.01) negative correlation between fontanel size and epiphyseal ossification. Severe intrauterine growth retardation (demonstrated by the lighter twin) may result in retardation of membranous as well as enchondral ossification.


Increase in bilirubin-binding affinity of serum with age of infant. The bilirubin-binding affinity of infant serum, as determined by Sephadex gel filtration, began to increase during the first week of life and continued to increase gradually until the age of 5 months, when it reached that of adult serum. This increase might be due to a transition from a fetal to an adult type of serum albumin and/or to a decrease in the concentration in serum of the substances thought to compete with bilirubin for binding to albumin.


Correction of the malabsorption of the preterm infant with a medium-chain triglyceride formula. After receiving milk-based formula for one week, 16 preterm infants, weighing 1,300 to 1,800 gm, were fed two isocaloric formulas containing either medium-chain or long-chain triglycerides for 15 days; the alternate formula was given for a second period of identical duration. While receiving MCT, the infants had greater (P smaller than 0.01) percent fat absorption (83.4 leads to 97.1%) and weight gain (7.5 leads to 11.5 gm/kg/100 calories). Because metabolic acidosis occurred with the LCT formula, the chloride content was adjusted to that of the MCT were confirmed and, in addition, there was a higher (P smaller than .01) percent retention of nitrogen (67.3 leads to 82.1).


Congenital malformations associated with the administration of oral anticoagulants during pregnancy. Three small infants whose mothers had received oral anticoagulant therapy during the first trimester of pregnancy are described. These infants all had hypoplasia of the nasal bones, and two had stippling of epiphyses and bones and deformities of the bones of the hand. One child is mentally retarded. It is suggested that these abnormalities may be related to maternal oral anticoagulant therapy during the first trimester.


Treatment of trichuriasis with a new drug, mebendazole. Effectiveness of mebendazole, a new anthelminthic drug recommended for treatment of Trichuris trichiura infection, was evaluated in 50 children attending a pediatric outpatient clinic in New York City. Mebendazole, 100 mg. administered orally twice daily for three days resulted in an apparent cure of 48 children. Posttreatment stools of the remaining two children had a substantial reduction in the number of eggs. A second course of treatment, identical to the first, led to the elimination of eggs in the stool specimens of these two children. Mebendazole appears to be an effective drug against Trichuris trichiura.


An analysis of the function of color in the Rorschach. Slide reproductions of a standard and an achromatic series of Rorschach plates were rated by 120 Ss on 12 bipolar adjective pairs. Four adjective pairs from each of the three major factors of meaning were used. Mean factor scores were computed for each factor, and a comparison among cards was made. The chromatic cards were rated, in general, as more positive and more active but less potent than their achromatic representations. There was a significant inverse relationship between the evaluative factor and the potency factor. No sex differences were found in the connotation of the cards. The results of this study are consistent with prior studies.


Free association and repression-sensitization. It was predicted that Subjects' scores on Byrne's Repression-Sensitization (R-S) Scale would be related to free associative style. When administered the R-S Scale, Subjects at the high and low extremes then took part in a free association task. Repressers manifested a prevalence of "avoidant" and sensitizers a prevalence of "approach" associations. However, this was true only of male Subjects.


A multiple-choice version of the sentence completion method. A sentence completion (SC) measure of children's autonomy was adapted to a multiple choice (MC) form. Criteria were proposed which MC should meet in order to be reasonably equivalent to SC. MC should not be obvious to the child; thus, the means and variances of the two tests should be similar, and MC should not show a congregation around the "good" answers, nor should it correlate positively with a measure of social desirability. Both tests should correlate significantly with one another. Any factor structure present in SC, which suggests a differentiation within the concept of autonomy should be duplicated in MC. Most of these criteria were met, and it was concluded that a multiple choice form corresponding to a sentence completion measure, testing clearly defined personality areas, could be a resonable alternative for many purposes.


Behavioral correlates of WAIS profile patterns: an exploratory study. To assess the feasibility of both an empirical derivation of WAIS subtest patterns and an actuarial assignment of behavioral descriptions to these patterns, 11 potential patterns were delineated. Three of these were studied in depth, and one of these was the focus of this report. The derivation and cross validation groups of this one pattern displayed highly similar WAIS scores on all 11 subtests, but differences between the groups in age, marital status, and some output descriptors were noted. These results were explained in terms of age acting as a moderator variable. In general, the results suggest that patterns of WAIS subtest scores can be identified and that these can be reliably associated with specific behavioral descriptors.


Sculpture preferences and personality traits. Factor analyzed the preference ratings of 70 male and 70 female undergraduates for 36 slides of sculpture. A principal factors solution with orthogonal rotations yielded 6 factors: ambiguous abstraction vs. controlled human realism, mildly distorted representation, emotional detachment, traditional portraiture vs. surrealism, highly distorted representation, and geometric abstraction. Some of these factors were similar to the Apollonian, the Dionysian, and the Pythagorean dimensions previously postualted by Nietzsche and Knapp. Preference scores for each factor were computed and correlated with scores on the 16 PF and with selected educational and physical variables. A few small, significant (p less than .05) correlations were found, supporting the hypothesis that artistic style preferences resemble the personality traits of the spectator.


Stereotyped sex role behavior and sex guilt. A study of self-reported sex guilt and sex behavior in college students closely replicated previous findings. In addition, it was found that high guilt subjects were more likely to act in conformity with social expectations regarding sexual behavior. That is, high guilt males were more likely to be assertive in their sexual behaviors than low guilt males, and high guilt females were more likely to engage in passive sexual behaviors than low guilt females. Assertion was defined as acting upon another, and passivity was defined as being acted upon.


Detection of a nonlinguistic stimulus is poorest at the end of a clause. Subjects detected a brief near-threshold tone while encoding two-clause sentences for later report. The objective tone locations were at the end of the first clause, at the beginning of the second clause, or in the clause boundary. The effects of intensity variations of the speech signal were assessed by having subjects detect the tones in the same speech stimuli played backward. Tones at the end of a clause are relatively harder to detect than in other positions, comparing forward and backward speech. This supports the view that listeners are preoccupied with internal processes at the end of a clause.


Scaling of apparent accentedness by magnitude estimation and sensory modality matching. In each of three experiments, 24 students judged the accentedness present in the speech of eight Spanish-English bilinguals. Ss gave magnitude estimations and also squeezed a hand dynamometer to indicate the amount of accentedness in the reading of an English passage by each of the speakers. There was significant agreement among Ss regarding the speech samples with each scaling method, and interscale agreement was good. Power functions fitted to the data had exponents falling in the range expected from earlier psychophysical studies. Scale values correlated significantly with the frequency of accented pronunciations by the speakers as judged by two independent judges. The use of these scaling methods for future research on linguistic features of accent and on the relation between accent and language attitudes is discussed.


Semantic organization in deaf and hearing subjects. Hierarchial cluster analysis of data from the sorting of noun words was used to compare semantic structures in 63 profoundly deaf and 63 hearing adolescents. In the first study, performance differed only for a set of words referring to sounds, where deaf persons have no experience, and not for a set of common noun words and pictures. In the second study, differences between matched sets of high- and low-imaginary words were comparable for 63 deaf and 63 hearing subjects. It is concluded that deaf subjects manifested abstract hierarchical relations and were not dependent on "visual mediators" or hindered by the absence of "acoustic mediators".


The influence of listener perception of the speaker on recognition memory. Results are reported for an experiment which examined the influence of listener perception of speaker intention on sentence recognition. Given the same passage and recognition sentences, subjects displayed different false recognition patterns of test items depending on which of two speakers with opposing viewpoints the passage was attributed to. It is argued that the reconstructive process of memory is based on information from the context (e.g., the speaker's perceived intentions) as well as on the actual words used. Retention of different aspects of a message is seen to rely on information from different sources. Specifically, the results of the study indicate that retention of meaning involving the speaker's predictions, opinions, etc., is influenced by the listener's perception of the speaker.


Mothers' speech to children of four different ages. This study reports analyses, in terms of five different measures, of the speech on two standard tasks of 32 middle-class mothers to their children aged 1 1/2, 2 1/2, 4, and 6 years. Sex and birth order of child were not found to be related to mothers' speech. On four of the measures, both task and age of child had strongly significant effects. In general, with increasing age of child, mothers spoke more, in longer and grammatically more complex utterances, with greater diversity of vocabulary. The differences in speech addressed to 1 1/2-year-olds and that addressed to 2 1/2-year-olds were particularly marked.


Vaginally administered prostaglandin E2 as a first and second trimester abortifacient. One hundred women seeking interruption of pregnancy between 7-20 weeks were given prostaglandin E2 as a 20 mg vaginal suppository every four hours. Abortion was achieved within an arbitrary time limit of 36 hours in 97 patients and was complete in 76. Mean abortion intervals according to gestational length and parity ranged between 7.67 and 14.93 hours. Augmentive intravenous oxytocin, usually for placental expulsion, was given to 31 patients. Side-effects such as vomiting, diarrhea, and drug fever were encountered in the majority of patients but no sepsis was noted and no patient was transfused. The results are discussed with particular reference to other prostaglandin and hypertonic saline regimens for pregnancy interruption.


Intra-amniotic prostaglandin F 2alpha as a midtrimester abortifacient: effect of oxytocin and laminaria. An abortion interval time of 15.9 hours was achieved in a group of women treated in midtrimester with intra-amniotic prostaglandin F2alpha and intravenous oxytocin. Routine addition of intracervical laminaria to this regimen was not helpful. The most useful prostaglandin protocol seems to be 30 mg as an initial dose followed by a booster at six hours.


In vitro interaction of prostaglandin F2alpha and oxytocin in placental vessels. The interaction of prostaglandin F2alpha and synthetic oxytocin on placental vessels was studied in vitro. Resistance was measured near the placental margin after spontaneous term delivery. In seven experiments reactions to norepinephrine and oxytocin were PGF2alpha. PGF2alpha produced significantly increased vasoconstriction after a single administration of oxytocin. In eight experiments the perfusion medium contained oxytocin. There was no change after a single dose of PGF2alpha. The reaction after norepinephrine remained the same in both groups of experiments. There is thus an "enhancement effect" of PGF2alpha upon the reaction of placental vessels to oxytocin in vitro.


Fallopian tube occlusion in rabbits with silicone rubber. A new system for transcervically blocking the Fallopian tubes with cured-in-place silicone rubber has great potential for fertility control. Good retention, antifertility efficacy, and retrievability were observed in rabbits, and no adverse tissue reactions were seen in oviducts containing silicone elastomer. Continuing studies with rabbits and rhesus monkeys attempt to determine long term efficacy and histologic changes.


Rapid transport of alien eggs transplanted 66 hours post coitum in the oviduct of the rabbit. Alien (fixed and stained) rabbit ova were transferred into the oviduct of recipient rabbits 24, 48, 60, and 66 hours post-coitum and were observed at 48, 72, 72, and 72 hours post-coitum respectively, using a clearing technique. In all cases the transport of alien eggs was accelerated, so they caught up with native eggs. Alien eggs, transferred to the ampulla 66 hours post-coitum were transported to the uterus within six hours.


Gestational diabetes: diagnosis and management. Pregnancy is a diabetogenic condition and approximately one per cent of suspected patients will develop an abnormal glucose tolerance test during pregnancy. Generally, the gestational diabetic tends to be heavier, older, and multiparous. The diagnosis can be made from the patient's family history, previous obstetrical history, or from clinical tests such as urine glucose, fasting blood sugar, and glucose tolerance tests. The management of the patient includes patient evaluation, diet, evaluation of the fetus, and selecting the time of terminating the pregnancy. With correct care and treatment, the patient can deliver a normal and healthy infant.


Rubella susceptibility in Navajo women.

Rubella susceptibility in Navajo women. Rubella susceptibility among Navajo women equals that in other parts of the country. Even though crowded conditions exist in the homes, communicable disease is more prevalent than in other areas, and many children attend boarding schools. The present immunization policy is discussed and an alternative plan of immunization is presented as recently recommended by the Navajo Area Indian Health service committee on rubella.


Colposcopy: a prerequisite for cone biopsy. Colposcopy should be an integral part of the diagnostic investigation of all patients with cervical neoplasia demonstrated by Pap smear. If a cone biopsy is necessary, the surgery can be directed. This will improve diagnostic accuracy as well as reduce morbidity, expense and disability.


The academic role of the vice president for health sciences: can a walrus become a unicorn? The post of vice president for the health sciences was first developed in an attempt to interpret, modulate, and buffer the growing power of the medical school in the university and the different values that have existed there. The job has been greatly transformed over the past 10 years as a consequence of a variety of factors. Now a genuine creative effort applied to the design of the administration of health sciences centers and how they fit into universities is needed. The present modes of organization are not equal to the challenges that must be faced. New designs must be created which will recognize the special place of the health sciences in today's world and yet keep its function within the university frame.


Factors influencing medical school faculty disposition toward collective bargaining. Faculty attitudes toward collective bargaining at a prestigious public medical school indicate considerable ambivalence toward unionization. As might be expected, salary dissatisfaction is the greatest cause of faculty discontent; however, it is not the most important factor in favoring collective strength. The irony is that the faculty members most in favor of collective bargaining are least dissatisfied with their salary levels. Conversely, the highest earning faculty members are least in favor of unionization but most dissatisfied with their salary scale. The study reported here shows that faculties perceive the protection or enhancement of collegiality as the single most important factor influencing their attitudes toward unionization. This perception suggests that faculties see collective bargaining as a means of strengthening their position relative to greater inclusion in the decision-making processes of the medical school.


Performance of medical students admitted via regular and admission-variance routes. Twenty-three medical students from socioeconomically disadvantaged backgrounds and drawn chiefly from Chicano and black racial minority groups were granted admission variances to the University of California, San Diego, School of Medicine in 1970 and 1971. This group was compared with 21 regularly admitted junior and senoir medical students with respect to: specific admissions criteria (Medical College Admission Test scores, grade-point average, and college rating score); scores, on Part I of the examinations of the National Board of Medical Examiners (NBME); and performance in at least two of the medicine, surgery, and pediatrics clerkships. The two populations differed markedly on admission. The usual screen would have precluded admission of all but one of the students granted variances. At the end of the second year, average NBME Part I scores again identified two distinct populations, but the average scores of both groups were clearly above the minimum passing level. The groups still differ on analysis of their aggregate performances on the clinical services, but the difference following completion of two of three major clinical clerkships has become the distinction between a "slightly above average" level of performance for the regularly admitted students and an "average" level for students admitted on variances.


Area Health Education Centers: what are they and where are they going? Area Health Education Centers (AHECs) were one of the recommendations arising from the 1970 report of the Carnegie Commission on Higher Education, Higher Education and the Nation's Health: Policies for Medical and Dental Education. Subsequently, three separate federal programs were implemented. Since issuance of the commission's report, major changes have occurred in the health field. Many of the assumptions and predictions prevailing at the time of the report are now being questioned, leading to a need to reassess the policies underlying the AHEC concept. Enough time has elapsed that the AHEC programs can be evaluated in terms of the policies leading to their original recommendation, but they are still embryonic and diverse enough that they have not themselves become fixed policy. It is crucial at this stage of their development that the programs be assessed not only in relationship to each other but also in the context of the other programs and policies which together with AHECs presently comprise our unplanned national health strategy.


Uses and abuses of tenure.

Uses and abuses of tenure. The purposes of tenure are clear. The principle of tenure in an academic institution is widely accepted. Abuses and legal restrictions make it difficult to administer tenure so that it is equitable to both the institution and the scholar. Some problems could be alleviated by creating clear standards and practices for hiring, promotion, and dismissal; others could be lessened through more attention to definition and procedure. In some instances a change in the structure of the process itself may be necessary. A system combining tenure with periodic evaluation would be a viable alternative.


Goals of medical student psychiatric education. In this article the authors present a comprehensive statement of the goals of medical student psychiatric education. The focus is on content rather than on the process of teaching or of curriculum design. Many of the areas of learning are likely either to be taught by nonpsychiatric instructors or to be not specifically programmable into a curriculum. The approach of focusing on the desired competence in terms of knowledge, skills, and attitudes can result in these goals and their subsequent modifications serving as a benchmark for assessment of the adequacy of a particular program.


Comparison of the diagnostic methods of family physicians and internists. Two groups of physicians (nine family physicians and nine consulting internists) were presented with three clinical problems by a programmed "patient". Analysis of the recorded interviews showed that family physicians asked fewer history questions, requested fewer items of data about physical examination, and ordered fewer laboratory investigations. In two out of the three cases family physicians asked a higher proportion of questions about mental status and life situation. In an analysis of the "commonness" of questions asked by internists and family physicians, it was found that internists were more consistent among themselves in the questions asked. There were no significant differences in the final diagnosis reached by these two groups.


The development of cognitive knowledge in clinical clerkships. As part of an attempt to match the seminar program in pediatrics to the increased level of sophistication that students during the latter half of their core clerkship year would possess compared with students who enter pediatrics early in the year, the faculty of the Department of Pediatrics at The University of Texas Medical Branch in Galveston developed a typical final examination (a 100-item, multiple-choice test) and administered it as a pretest to each section of the junior class as it entered pediatrics. Analysis of the data indicated the following. A substantial portion of the cognitive information required for success in the clinical years was acquired prior to entry to the clerkship; scores of students entering their last clerkship were almost the same in the pretest in pediatrics as were those of students who took the pretest 10 monts earlier; posttest scores were substantially higher than pretest scores for all groups of students. The paper includes some discussion of the reasons for the findings and a description of the steps being taken to remedy deficiencies in the educational and evaluation program revealed by the study.


A new type of facility in medical education: the Clinical Learning Center. The two independent forces leading to the development of a new type of facility for medical education were the desire to utilize modern educational concepts (some of which are difficult to employ in traditional hospital settings) and the need to expand students' contact with clinical patients. This special facility, known as the Clinical Learning Center, resembles the ultimate setting of medical practice, that is, the physician's office, and it depends upon volunteer patients who come there primarily to contribute to the educational program while deriving no medical care. Students and instructors have appreciated the opportunity for feedback; the quiet educational environment; the graduated learning experiences; and the use of various resources, especially videotape recording and playback of the clinical encounter. The recruitment of volunteer patients has been highly successful, and the center is proving to be a valuable adjunct to the learning of clinical skills.


Nonmalignancy of hybrids derived from two mouse malignant cells. II. Analysis of malignancy of LM (TK-) Cl 1D parental cells. The possibility that Cl 1D cell line, an L-cell line derivative, was a mixture of malignant and nonmalignant cells was investigated because previous experiments showed that some hybrids derived from Cl 1D and tumor cell lines grew in vivo, whereas others apparently did not have that capacity. More highly malignant Cl 1D cells were not selected by animal passage of tumors obtained from inoculation of cultures. The tumor-producing capacity of this line (10%) was greatly increased (81%) in X-irradiated hosts. These observations suggested that the low capacity of Cl 1D cells to grow in vivo did not result from varying degrees of malignancy but mainly from interference of immunogenetic factors between cells and their inbred hosts of origin. Numerous hybrids between tumor and host cells were in all tumors examined.


Separation of cells exhibiting acid phosphatase activity from disaggregated hamster prostate cells in an isokinetic gradient of Ficoll in tissue culture medium. Cells exhibiting histochemically demonstrable acid phosphatase were separated from suspensions of hamster prostate cells with velocity and isopyknic sedimentation. Unseparated suspensions of hamster prostate cells contained 57.2 plus or minus 11.3% cells with histochemically apparent acid phosphatase. After the cells were separated by velocity sedimentation in a previously described isokinetic gradient, the purest fractions from the gradient contained 97.2 plus or minus 0.8% cells with histochemically evident acid phosphatase. More than 99% of these separated cells excluded trypan blue. These cells were thought to be the acinar cells of the prostate. Isopyknic sedimentation was not as effective as velocity sedimentation for the purification of these cells.


Correlation between balance of specific chromosomes and expression of malignancy in hamster cells. Four 1-theta-D-arabinofuranosylcytosine (ara-C)-and one dimethylnitrosamine-transformed Syrian hamster cell lines were established. All produced tumors when inoculated into newborn hamsters. Specific chromosome changes were found in these lines consistent with changes observed recently by other investigators. Clones that had either high or low malignant potential were derived from two fibrosarcomas produced by one of the ara-C-transformed cell lines. The expression of malignancy in these clones was associated with an excess of 57 chromosomes over 73 chromosomes.


Experimental tumor induction in a circumscribed region of the hamster trachea: correlation of histology and exfoliative cytology. A method for the induction of carcinomas in a circumscribed region of the hamster trachea is reported. By means of a special catheter, a solution of N-nitroso-N-methylurea was applied twice a week to about a 6-mm length of the trachea 10- to 16-mm distal from teh vocal cords. Slight alteration of this catheter allowed sampling of cytologic specimens directly from the surface of the carcinogen0exposed epithelium. This procedure permitted the simple and accurate correlation of sequential histologic and cytologic changes observed during tumor development in the hamsters. Noninvasive dysplastic and metaplastic lesions were seen in animals killed after 5 and 10 weeks of carcinogen application. These epithelial changes could be readily correlated with abnormal exfoliated cells abundantly present in cytologic specimens from these animals. Exposure to carcinogen for 15 weeks induced a 100% tumor incidence exclusively at the application site. More than 75% of the malignancies appeared within 15-20 weeks after the start of carcinogen administration. Most tumors were epidermoid carcinomas but some anaplastic large-cell carcinomas were also observed. Cytologic specimens of tumor-bearing animals had many cells conclusive of malignancy. The new experimental system lends itself to study of the effect of topically applied anticarcinogenic or cocarcinogenic agents on different carcinogen-induced epithelial lesions whose regression or progression can be followed by exfoliative cytology.


Foreign-body tumorigenesis: number, distribution, and cell density of preneoplastic clones. Double 15 times 22-mm plastic films (two films on top of each other) were implanted subcutaneously in CBA/H-T6 mice. After 7.5, 8.5, and 9.5 months the films were removed. Each interior film (next to the abdominal wall), covered by a cell monolayer on one side only, was cut in four 7 times 10-mm segments. Wiping to 5 times 7, 4 times 4, 3 times 3, or 2 times 2 mm reduced the cell areas on three of them. They were then transferred to (CBA/H times CBA/Br)F1 or (CBA/H-Ty times CBA/Br)F1 recipient mice. Tumors arising from transferred film segments were analyzed as to chromosome number and morphology, sarcoma type, degree of anaplasticity, and posttransfer latency. We used these criteria to determine whether tumors originated from the same or different clones. From this information it was estimated that preneoplastic clones were present in limited numbers and that they were either widely disseminated or spatially restricted on the implant surfaces. The extent of clone dissemination appeared to be related to preneoplastic progression.


Polyinosinic-polycytidylic acid: inhibition of cell proliferation in carcinogen-treated epidermis and in carcinogen-induced skin tumors in mice. After administration of the synthetic double-stranded RNA polyinosinic with polycytidylic acid (poly l with poly C) to hairless mice, cell proliferation kinetics were studied in normal epidermis, in epidermis initiated with 3-methylcholanthrene (MCA), in hyperplastic epidermis treated topically with MCA for 15 weeks, and in MCA-induced skin tumors. Poly l with poly C did not influence the mitotic rate or the transit of cells from the G1 phase to the S phase in normal mouse epidermis. Pretreatment of poly l with poly C inhibited cell proliferation in mouse epidermis initiated with MCA for at least 24 hours. In mouse epidermis made hyperplastic by repeated applications of MCA. Poly L with poly C inhibited G1 cells from starting DNA synthesis. Skin tumor DNA synthesis was also altered after poly l with poly C administration. After a short period of enhanced 3-methylthymidine incorporation, tumor DNA synthesis decreased to less than half the control value. The results indicated thatthe antitumorigenic effect of poly l with poly C could be related to its influence on cell proliferation.


A simple cell-suspension method for transplantation of V2 carcinoma. A simple and rapid method for the preparation of an essentially monodispersed cell suspension from the rabbit V2 carcinoma, suitable for either large or small amounts of tumor tissue, did not require specialized equipment and yielded relatively large numbers of viable cells. Cell suspensions prepared by this method could be used to approximate a dose-response curve relating the percentage of tumor takes to the number of cells inoculated and could allow quantitative correlations not possible when macroscopic tumor fragments are used for implantation. The method, or slight modifications of it, should prove suitable for most tissues with a significant connective tissue component.


Hyperplasia of rat mammary gland in vitro. Rat mammary gland explants placed in organ culture underwent intraductal hyperplasia in the presence of insulin. The hyperplasia reached its maximum at about 2 weeks of culture and exhibited several morphologic variations. By ultrastructural criteria, it was shown that the proliferating cell was derived from the epithelial rather than the myoepithelial component of the ductal lining cells. Testosterone, added at the beginning of the experiment, partially inhibited the hyperplastic process.


Some aspects of host response to levamisole after chemotherapy in a murine leukemia. Levamisole (LMS), when used with an effective remission-inducing drug in leukemic mice, resulted in a high percentage of long-term survivors. Histologic examination of spleens from treated leukemic mice showed that LMS caused an earlier return of lymphoid cells in the splenic lymphoid follicles and lymphoid elements in the red pulp.


Alkaline phosphatase activity in hyperplastic and neoplastic urinary bladder epithelium of mice fed 2-acetylaminofluorene. Studies were made on the urinary bladder of 66 BALB/c mice of both sexes; 21 were fed a normal diet and 45, a diet containing 100-500 parts per million (ppm) of 2-acetylaminofluorene (2-AAF). Bladder epithelial hyperplasia was noted in 22 of 24 mice given 2-AAF for 7 months and in 20 of 21 given 2-AAF for 19 months. Transitional cell carcinomas were in 12 of 21 mice given 2-AAF for 19 months and in all except the 9 females given the low dose (100 ppm). Special stains revealed marked alkaline phosphatase activity in the bladder epithelium of untreated controls and slightly to moderately reduced activity in the hyperplastic epithelium, particularly the lower layers, of mice given 2-AAF for 7 months. Activity was markedly reduced and confined largely to the upper layers in mice treated for 19 months. The transitional cell carcinomas showed no activity except focally in a few tumor masses in 11 of 12 mice with tumors. Alkaline phosphatase activity was usually slightly to moderately increased in the sub-epithelial stroma after 7 months' treatment with 2-AAF and markedly increased after 19 months. Loss of alkaline phosphatase activity in the bladder epithelium may be a preneoplastic change.


Inhibition of migration of murine spleen cells by Rauscher leukemia virus-infected syngeneic cells. The in vitro migration of spleen cells from BALB/c mice infected with Rauscher leukemia virus (RLV) was markedly inhibited 10 days after RLV inoculation. Mixtures of infected and uninfected spleen cells used in the ratio of 1:4 in an effector-cell/indicator-cell system showed that viable RLV-infected spleen cells could inhibit the migration of uninfected spleen cells in a manner indistinguishable from that mediated by sensitized spleen cell reacting to specific antigen.


Transplantation of adenocarcinomas of the colon in mice. 1, 2-Dimethylhydrazine treatment induced multiple colon tumors in 100% of NMRI mice. Many of these tumors were transplanted and yielded five serially transplantable tumor lines. These subcutaneously transplanted neoplasms were all adenocarcinomas varying in degree of differentiation and mucin production. No evidence of dedifferentiation or change in growth rate has been seen in up to six transplant generations. These tumor lines appeared to provide relatively stable, well-differentiated models for colorectal cancer.


Chromatin proteins from human lymphocytes: a gel electrophoretic comparison between normal, mitogen-stimulated, cell-line, and chronic lymphocytic leukemia lymphocytes. Cell-line lymphocytes contained considerably more nonhistone chromatin protein than normal lymphocytes. The overall electrophoretic pattern of the nonhistone chromatin proteins from nonreplicating cell types with predominantly condensed chromatin (normal lymphocytes and chronic lymphocytic leukemia lymphocytes) was similar, as it was between replicating cell types with predominantly decondensed chromatin (mitogen-stimulated normal lymphocytes and cell-line lymphocytes), although all four cell types differed qualitatively. A "heavy" chromatin fraction from cell-line lymphocytes could be distinguished from a "light" fraction and had a pattern similar to that from cells of the condensed chromatin type. Normal lymphocytes contained two acid-soluble chromatin polypeptieds not found in cell-line lymphocytes.


Alterations in glycosyltransferase activity in human colon cancer. Glycosyltransferase enzymes were measured in homogenates of normal and neoplastic colon epithelium. The levels for exogenous galactosyltransferase and fucosyltransferase and endogenous N-acetylglucosaminyl-transferase were higher in the normal tissue. The levels for exogenous and endogenous sialyltransferase and endogenous galactosyltransferase and fucosyltransferase were comparable in the homogenates of normal and cancer cells. Incorporation of fucose and galactose into purified carcinoembryonic antigen (CEA), used as an exogenous acceptor by colon glycosyltransferases, was demonstrated by immunoprecipitation with rabbit antiserum to human CEA. The normal fucosyltransferase and galactosyltransferase showed higher activity with CEA than did the tumor enzymes.


A new apparatus for BCG scarification.

A new apparatus for BCG scarification. A procedure for administering BCG by scarification that allows for speed of application and standardization of technique was discribed.


Agglutination of 2,4-dinitrophenyl-tagged normal human leukocytes by concanavalin A: possible relationship to their ability to evoke production of leukemia-associated antibodies. Normal peripheral blood leukocytes were tagged with 2, 4-dinitrofluorobenzene at a ratio of 10-11 molecules/cell. One-tenth ml of various concentrations of concanavalin A (Con A) was added to 0.2 ml of either tagged or untagged cells (5 times 10-6/ml) and incubated for 20 minutes at ambient temperature, after which agglutination was scored visually. A readily discernible quantitative difference in the agglutinability of 2, 4-dinitrophenyl (DNP)-tagged versus untagged cells was seen at all concentrations of Con A in the range of 12.5 800 mug/ml. The reaction was maximal at 24 degrees C, somewhat diminished at 37 degrees C, and minimal at 4 degrees C. The agglutination of DNP-tagged leukocytes by 50 mug Con A/ml was completely blocked with 0.1 M methyl-alpha-D-glucopyranoside (alpha-MG), but as low a concentration as 0.001 M alpha-MG inhibited agglutination of untagged cells. The ability of Con A to agglutinate DNP-tagged normal leukocutes may be attributed to a lowering of the zeta potential, a topographic rearrangement of receptor sites, or the formation of new antigenic determinants similar to those found on malignant cells. The last alternative would be consistent with the observation that DNP-tagged normal leukocytes could evoke the production of antibodies that reacted with leukemic granulocytes.


Lung cancer mortality in World War I veterans with mustard-gas injury: 1919-1965. A study of the mortality experience of three samples of World War I veterans totaling 7,151 U.S. white males was extended from 1956 through 1965 to learn whether a single exposure to mustard gas with respiratory injury was associated with increased risk of lung cancer in later life. Rosters of men born between 1889 and 1893 [2,718 exposed to mustard gas, 1,855 hospitalized with pneumonia in 1918, and 2,578 with wounds of the extremities (controls)] were traced via the Veterans Administration's death records. The 4,136 deaths reported were 95% of that expected. The conclusions of the original study were not altered by the additional 10 years of follow-up. Observed deaths from lung cancer numbered 69, or 2.5% for the mustard-gas group as compared to 33, or 1.8%, for the pneumonia group and 50, or 1.9%, for the controls. The risk of death from lung cancer among men gassed relative to that for the controls was estimated as 1.3, with 95% confidence limits of 0.9-1.9. These figures failed to make a strong case for a carcinogenic effect, apparently because a suffcient dose of mustard gas was not received,


Diagnosis and prognosis in colon cancer based on a profile in immune reactivity. An immunologic profile consisting of measurements of circulating carcinoembryonic antigen (CEA), tumor antigen-induced inhibition of monomuclear cell migration (IMM) and skin reactivity to purified protein derivative, streptokinase-streptodornase, and mumps was assessed as a diagnostic and prognostic tool in 16 patients with colon cancer. Preoperatively, 10 of 14 patients tested had elevated CEA, 12 of 12 showed tumor antigen-induced IMM, and 10 of 11 failed to react to 2 or more recall antigens. Potential surgical cure (7 patients) was accompanied by normal CEA in 4, absent tumor antigen-induced IMM in all 7, and increased skin-test reactivity in 6. Disseminated cancer (9 patients) was associated with elevated CEA in all 9, with absent IMM in all 7 and with suppressed skin-test reactivity in 6 of 9.


Multiple primary neoplasms in blacks compared to whites. IV. Further cancers in patients with cancer of the digestive organs. Second primary cancers found among whites and blacks with initial cancer of the digestive organs were reported based on data from the Charity Hospital Tumor Registry. Observed second primary cancers were compared to expected numbers to obtain a direct estimate of risk. Both white and black men had about a twofold risk of developing a second cancer. For white men, the excess was limited to a subsequent skin cancer, but this finding was probably an artifact of reporting and lacked biologic significance. Among women, both white and black, large excesses of invasive cancer of the cervix and ovary were found after an initial cancer of the large intestine and anorectum was discovered. No excess of breast cancer was found.


Human antisera detecting leukemia-associated antigens on autochthonous tumor cells. Leukemia patients in remission were immunized with RAJI lymphoid tissue culture cell lines. Four of 7 patients developed antibody to the immunizing cell as well as to allogeneic leukemia cells. Sera from 3 patients were tested against autochthonous tumor cells either frozen or obtained at the time of disease relapse. Patient's sera were cytotoxic to their own leukemia cells; however, this cytotoxicity was lost at the time of relapse.


Regression of feline sarcoma virus-induced sarcomas in dogs. I. Morphologic investigations. In a study of morphologic changes in the development and regression of feline sarcoma virus (FeSV)-induced tumors in dogs, 27 weaned and newborn beagle and mongrel puppies were inoculated with FeSV in doses from 1.0 to 3.0 gEq; 2 beagle and 2 mongrel puppies were used as uninoculated contact controls. All animals were examined daily, and crude tumor volume was calculated from length, width, and depth measurements of the neoplasms. Biopsies were done at various stages of tumor development and regression. When tumors were no longer palpable, all puppies were necropsied. Two of 8 (25%) weaned beagle puppies, 10 of 12 (83%) newborn beagles, and 1 of 7 (14%) newborn mongrels developed tumors, all histologically confirmed fibrosarcomas. No metastatic tumor foci were detected. The tumor life-span was divided into approximately equal periods of growth and regression. The initial regression period was characterized by focal necrosis and accompanying neutrophil infiltration. The later stages of regression were characterized by lymphocytic or mixed mononuclear infiltrates. Thus the regression histopathology was not uniform and suggested that different immunologic mediation systems effect regression. Nonneoplastic morphologic changes consisted largely of lymphoid depletion and necrosis in lymph nodes and thymus after inoculation.


Host responses with solid tumors. I. Monocytic effector cells within rat sarcomas. Morphologic studies of two unrelated progressively growing sarcomas in rats revealed the presence of a large proportion of host cells distinct from tumor cells. Enzymatically or mechanically dispersed tumor suspensions were fractionated by the velocity sedimentation method, which resulted in a separation of host and tumor cells. The host cells had the typical morphology of macrophages and also were adherent to a plastic surface after a short incubation period. The proportion of host cells was greater in a young (10 or 12 days) than in an older tumor (35 days). These macrophage-like host cells isolated from sarcomas 12 and 35 days after implantation inhibited the colony formation of tumor cells in vitro in the nonspecific manner ascribed to activated marcrophages. In addition to these effector cells, the host fraction contained macrophage precursors able to proliferate in vitro but apparently inhibited by the presence of tumor cells. The results indicated that these macrophage-like effector cells may be the predominant host reaction within some rat sarcomas, and also that thymus- and bone marrow-derived lymphocytes act only indirectly if they are involved.


N-nitrosomethylurea as mammary gland carcinogen in rats. N-nitrosomethylurea (NMU) given intravenously to rats at age 50 days induced mammary carcinomas in 89% of BUF/N, 73% of Sprague-Dawley, and 89% of F344 females. Latent periods were, respectively, 77, 86, and 94 days. Mortality was negligible. Biologic properties of NMU-induced tumors were tested in the BUF/N inbred strain. Before treatment, it reduced the number of tumors per rat but not the incidence; and after the tumor was established, castration arrested tumor growth or caused a temporary regression of the tumor. Metastases to bone marrow and spleen were constant, but they were rare to the liver and lungs. After the primary tumor was removed, metastases continued to grow but at a slower rate than the growth of the primary tumor. Almost all tumors were transplantable intraperitoneally and/or subcutaneously in the inguinal area of intact as well as ovariectomized and adrenalectomized rats. Transplanted tumors were able to metastasize as were primary tumors. Doubling times of NMU-induced primary and transplanted carcinomas were similar to 7 days. Cachexia ensued at the 5th week from the onset of the first tumor. When the tumor was larger than 15 g, hypercalcemia was usually observed. The treatment described appears to be the simplest method for inducing in rats a most nearly complete model for human mammary carcinomas.