Basic science in a predoctoral family practice curriculum. A course in applied basic science was designed with topic material organized according to anatomic body regions. Details of the diagnostic method were explained early in the course, and clinical procedures for data gathering and problem analyzing were followed while the significance of basic science knowledge in dealing with clinical situations was described. A collection of 35mm slides constituted the focal point of the course. The authors conducted the course together and an atmosphere of intellectual honesty was developed through open discussion between faculty and students. Student curiosity was respected and rewarded. Summaries of the discussions were prepared retrospectively by the faculty instructors for review gy the students. This experience proved that family physicians can demonstrate effectively the relevance of basic science to clinical medicine.


Documentation of resident exposure to disease entities. The medical privilege application forms of hospitals in 15 southern states were examined for the degree of privilege delineation required. Forty-nine percent of the responding hospitals require extensive delineation of privileges. Residents in the Anderson, South Carolina Family Practice Center have instituted a method of systematically recording exposure to disease entities encountered in the patient population not enrolled in the Family Practice Center. These records can be integrated with existing tabulation of enrolled patients. There are potential benefits for residents' future hospital privilege applications as well as for modification of the curriculum by faculty.


What do family physicians in a prepaid group do in their offices? Each family physician at the Permanente Group of San Diego was observed for one half-day. As with two earlier time studies, the time spent with each patient was tabulated to show the number of minutes used in each of the usual activity categories that are encompassed in a patient encounter. Previously, similar studies had been carried out with rural practitioners in Missouri (1965) and rural and urban physicians in New Zealand (1975). The Missouri physicians practicing in pre-Medicaid days spent less time doing administrative work than their counterparts in this study, but appreciably more time in treatment and preventive activities. The time utilization of the physicians in prepaid groups was remarkably similar to that of the physicians in the fee-for-service system in New Zealand.


Organizational complexity in family practice: a sociological model of a family practice group. The growth of a family practice goup is presented as a case study. Enlarging size and increasing functions require organizational change--from solo to collegial to bureaucratic to political systems. Organizational theory distinguishes between the characteristics and functions of individual, collegial, bureaucratic, and political organizations. Different styles and strategies are appropriate at different stages.


Elevated blood pressures in infants and children. Blood pressure should be routinely measured in all infants and children. Measurements should be performed with an appropriate size cuff and observed pressures compared to normal values for age. Elevated blood pressure is seen in one to ten percent of children, depending on the age group surveyed and the definition of hypertension selected. Thirty to fifty percent of children with elevated blood pressures are asymptomatic. The remainder have symptoms which are nonspecific, including headaches, visual disturbances, seizures, congestive heart failure, and facial palsy. Hypertension in children, unlike hypertension in the adult, usually has a definite cause which often responds to adequate medical and/or surgical treatment. For this reason, children with well-confirmed hypertension should be thoroughly evaluated. The most common causes of hypertension found in children are renal disease (pyelonephritis, vascular disease, structural malformations) and coarctation of the aorta. An approach to the child with transient or persistent hypertension is described. Diagnostic studies should be individualized and should follow clinical clues where possible. Medical management of the child with acute hypertension is discussed.


Arenavirus defective interfering particles mask the cell-killing potential of standard virus. Lymphocytic choriomeningitis virus (LCM) and Pichinde virus grew readily and produced cytopathology in MDCK and PK-15 cells. It is known that in these cell lines, the synthesis or function of defective interfering (DI) virus particles is restricted. Survival curves of single MDCK cells infected with low multiplicities of LCM showed one-particle-to-kill kinetics. At high multiplicities of infection, there was a maximum degree of cell-killing, or even a reduction in the amount of cell-killing, depending on how much DI virus was present in a particular standard virus stock. DI LCM virus could completely prevent standard virus from producing c.p.e. in MDCK monolayers with one-particle-to-protect kinetics. It could still prevent killing of the cells when added within a short time after infection with standard virus, but was able to interfere with synthesis of standard virus when added even later, On passage of LCM or Pichinde virus without dilution in MDCK cells, there was no homologous auto-interference. Furthermore, there was only slight interference with the synthesis of standard virus when these cells were pre-treated with DI virus.


Adaptation of an Aedes aegypti mosquito cell line to growth at 15 degrees C and its response to infection by Sindbis virus. Aedes aegypti mosquito cells, usually cultured at 28 to 30 degrees C, were adapted to grow at 15 degrees C. They were designated A. aegypti (c) cells, and had an estimated doubling time of 10 days. Sindbis virus (SV) replicated in these cells to peak titres of over 1.0 x 10(9) p.f.u./ml 8 to 10 days after inoculation. These, or about 10-fold lower titres, continued to be produced over a 130 day test period without causing visible cell damage. Continuous virus proliferation and the yield of uniformly large plaque forming progeny viruses are the two most important features which differentiate infection with this virus in A. aegypti (c) cells from that of A. aegypti cells grown at 28 degrees C (Peleg & Stollar, 1974). Absence of homologous interference vis-à-vis cell-virus coexistence suggests that homologous interference is not a prerequisite for maintaining cell-virus coexistence. Preinoculation of A. aegypti (c) cultures with a small plaque forming Sindbis virus (SV-S) leads, under certain conditions, to the establishment of homologous interference.


Defective particle assembly in wild type P2 bacteriophage and its correction by the lg mutation. The mutation lg of phage P2 has been located on the genetic map of P2 to the right of, and closely linked to, the del2 deletion, probably within tail gene F. The lg mutation causes larger burst sizes, compared with the wild type, especially at high incubation temperatures. The frequency of defective particles is lower in preparations of P2 lg than in those of wild type P2. It seems that the mutation lg improves the efficiency of particle assembly.


Isolation of a new avian paramyxovirus from budgerigar (Melopsittacus undulatus). In 1974 an epizootic occurred among budgerigar flocks in Kunitachi, Tokyo, and a causative agent which possessed haemagglutinating, neuraminidase, and haemolytic activities was isolated from the lung of a dead budgerigar. This agent was 100 to 300 nm in diamter and pleomorphic. The width of the ribonucleo-protein was estimated to be about 20 nm. These results indicated that the virus, designated Kunitachi virus, was a member of the paramyxovirus group. The virus contained in the amniotic fluid from infected embryonated hen's eggs, however, at times displayed no haemagglutinating activity with different erythrocytes and complete haemagglutination could only be detected in purified preparations. The Kunitachi viruses including three strains recently isolated from the same host were found to be serologically distinct from the known paramyxovirus strains and appeared to constitute a new subtype of avian paramyxovirus.


Cellular and humoral immunity in guinea pigs to two major polypeptides derived from hepatitis B surface antigen. Guinea pigs immunized with hepatitis B surface antigen (HBsAg), types adw, adr and ayw, and with two major polypeptides derived from HBsAg/adw developed cell-mediated immunity as determined by the macrophage migration inhibition assay. Peritoneal exudate cells from animals immunized with a 22000- or a 25000-mol. wt. polypeptide derived from HBsAg/adw showed significant migration inhibition after challenge with either polypeptide or with purified HBsAg. Significant inhibition of macrophage migration was not observed when polypeptide-sensitized cells were challenged with normal human serum or with normal human liver extract. Similarly, a cell-mediated immune response was not observed in peritoneal exudate cells from animals sensitized to normal human serum or normal human liver extract which were challenged with either of the polypeptides. The humoral immune response to either of the polypeptides, as measured by radioimmunoassay, was substantially lower than that observed in animals immunized with intact particles. This apparent difference between cellular and humoral responses suggests that the macrophage migration assay is a sensitive indicator of the immunogenicity of the smaller mol. wt. HBsAg-derived polypeptides in guinea pigs.


A quantitative confirmation of visual capture of curvature. An investigation was performed to quantify the experience of contour curvature formed under sensory discrepancy inspection conditions. N = 80 male and female undergraduates were used. Experimental Ss finger-tracked a horizontal straight edge while viewing limb movements through a curve inducing lens. Control Ss inspected the edge unimodally, either through vision (distorted) or proprioception. Rather than relying on verbal reports all Ss were required to match their impressions of contour shape with an adjustable metal curve. Findings indicated that (a) the mean impression of contour shape derived from discrepant visual and proprioceptive information was curved and did not differ from that derived from distorted visual information, (b) proprioceptive inspection alone resulted in accurate judgements of physical straightness, (c) response modality effects did not emerge, and (d) a manipulation designed to direct Ss attention to the left contour shape and during sensory discrepancy inspection did not affect mean curvature matches but created sizeable variability among matches. A sensory organization versus a selective processing interpretation of visual capture was discussed.


Further observations on the incremental stimulus intensity effect and habituation of the human electrodermal response. Two studies are reported which examined the relative effectiveness of an incremental series of stimulus intensities for reducing electrodermal responsiveness to a test stimulus. In the first study, employing five pairs of male undergraduates matched on electrodermal responsiveness, habituation to a 100 db (re 20muN/m2) noise burst was compared following two training procedures. In one, stimulation began at 64 db and increased by 4 db up to 96 db whenever two consecutive presentations of the stimulus failed to elicit a response. In the other, an equivalent number of presentations with a 100 db noise burst were provided. While habituation occurred during both training conditions, subsequent habituation to a 100 db test stimulus was more rapid following incremental training. In the second experiment, employing 40 female undergraduates, incremental and fixed conditions of training were compared for effectiveness using more moderate intensities of test stimulus: viz., 60 db and 80 db. A these levels, the fixed training series was superior to the incremental in reducing responsiveness. The data extend previous findings on the incremental stimulus intensity effect with the human electrodermal response but suggest limiting conditions for its demonstration.


Prismatically induced eye strain and autokinetic direction frequency. Autokinetic movement (AKM) as assessed by number of reported direction changes was evaluated for 25 college sophomores as a function of prism displacement strength. The results indicated that the strain on the eye muscles produced by prism displacement significantly affected frequency of direction change reports: the greater the displacement, the fewer the number of reported direction changes. These results were interpreted according to outflow theory in terms of the prism-imposed strain effectively increasing the level of noise in the outflow monitoring system, thereby making the detection of a cancelling response signal, the direction change, more difficult.


Effects of stimulus size, intensity, color, and eye strain on autokinetic movement: an error signal and noise analysis. In two experiments, with a total of 116 male and female undergraduate S s, predictions were tested from the following hypothesized explanation of autokinetic movement (AKM): undetected eye drifts lead to movement of the AKM target across the retina; this movement or error signal leads to the initiation of a cancelling response, and the AKM is directly due to CNS monitoring of the efferent responses or signals sent to the eye muscles with subsequent detection of these signals against a background of efferent noise. The error signal variables studied were stimulus color (yellow or blue-green), stimulus intensity (dim or bright), and stimulus size (1.0 or .1 deg visual angle). Small, dim lights foveally viewed and yellow as opposed to blue-green lights led to significantly more error signals and hence more AKM as measured by mean number of perceived direction changes. Also, increasing retinal displacement by changing viewing angle (from zero to 60 deg) or increasing displacement by increasing diopter strength of prisms (from zero to 30) decreased AKM as measured by number of direction changes, and this effect is due at least in part to the increase in efferent noise caused by the increases in eye muscle tension involved. It was concluded that retinal displacement affects both error signal and noise variables in the AKM and, presumably, in the perception of real movement as well.


Extroversion and reminiscence following a frustrating paired-associate task. Two experiments were reported relating extroversion to reminiscence following a frustrating paired-associate (PA) task. In the first experiment a group of 30 male and female college students was randomly assigned to one of two tasks in which they learned a PA list of high or low stimulus similarity. All PA lists were mixed lists composed of half solvable and half unsolvable (randomized) stimulus-response items. Recall for solvable items was tested immediately, 15 min, and 30 min after criterion was reached. Results indicated a significant difference between high and low stimulus similarity with superior recall for low similarity. The predicted reminiscence effect for high stimulus similarity recall was present but not significant. Comparison of recall scores for extroverts and introverts indicated a significant difference in recall favoring the introverts. The second experiment made a similar test of recall for two groups of S s that had been established as extreme extroverts or introverts (N = 8 in each group). The superiority of recall for introverts was replicated, and a reminiscence effect was found for the extroverts. Results were discussed in relation to Eysenck's formulation and previous conflicting results.


The reinforcing effects of the recommendation in the threatening communication. An instrumental escape conditioning paradigm was used to test the drive reducing effects of the recommendation in a threatening communication. Analogies were drawn between threatening communications and conditioning. Instrumental response speed was a monotonic decreasing function of delay of reinforcement: 0, 2, 6 sec (p less than .001). Each of the three delay groups acquired the instrumental response (p less than .001). Speed = 1/latency, automatically measured to .01 sec by a Lafayette digital stop clock. The Ss were 54 undergraduate males. A procedure was introduced to allow the separation and analysis of the drive inducing and reinforcing components of a threatening communication. Significant differences were detected between the reinforcing effects of communications (p less than .008). The results were interpreted in terms of the fear reduction model of persuasive communication.


Methadone dose, plasma level, and cross-tolerance to heroin in man. The development of cross-tolerance between methadone and heroin was studied in postaddict volunteers who had been drug-free for at least 6 weeks. Two methadone dose schedules were used; each was employed in six subjects. One schedule brought the subjects to a dose of 40 mg, while the other brought them to 80 mg of methadone a day. Subjects received injections of heroin (0.214 mg/kg) and placebo at various times before and during methadone treatment. Pupillary and subjective effects of injections were measured. Plasma levels of methadone were determined concurrently. Subjects on both treatment schedules developed an incomplete cross-tolerance to this dose of heroin. As the dose and plasma level of methadone increased with time, the cross-tolerance to all heroin effects increased. Plasma levels did not affect the development of cross-tolerance independently of methadone dose. The most important contribution to the cross-tolerance to pupillary effects was made by the duration of methadone treatment. Furthermore, the cross-tolerance to the subjective effects of heroin developed earlier than that to the pupil effect.


The clinical utility of the hand-held tachistoscope. A hand-held tachistoscope for use at the bedside was constructed and used to examine 40 normal controls and 170 psychiatric and neurological patients. This instrument quickly provided an index (perception time) which distinguished between idiopathic psychiatric illness and delirium, and between cortical and subcortical neuropathology. Slow perception time was seen in patients with delirium or cortical neuropathology.


The Klüver-Bucy syndrome in man.

The Klüver-Bucy syndrome in man. It is apparent that the importance of the limbic system is essentially for survival. The inability to discriminate enemy from friend as well as loss of the proper affective response to what is dangerous or safe to the organism may be thought of as more central to survival than what is described as "other higher intellectual functions." The case described is a dramatic expression of such a transient limbic dementia originally described by Klüver and Bucy in their syndrome. Since Klüver and Bucy originally described their syndrome, the structural and functional understanding of the limbic system has been greatly increased. Although a rare occurrence in man, the Klüver-Bucy syndrome serves as a demonstration of an unusual brain syndrome whose theoretical and experimental basis has been greatly enlarged since first described.


Hyperactivity: diagnostic confusion.

Hyperactivity: diagnostic confusion. Histories of hyperactive symptoms were evaluated for two samples of young men and women under treatment for drug or psychiatric disorders. More than one in five had shown hyperactivity but almost all of these developed pictures of other psychiatric problems, frequently the antisocial personality, by late adolescence. This picture is felt to reflect inaccurate use of hyperactive labels in difficult-to-handle children. The potential consequences of these practices are discussed.


Effects of subliminal and supraliminal stress on symptoms of anxiety. Two experiments were carried out with volunteer subjects to test whether the subliminal viewing of emotive material induced anxiety and its associated bodily symptoms. In one experiment 24 subjects looked at anxiety-inducing words presented singly through a tachistoscope under supraliminal or subliminal conditions, and in the other study 50 subjects looked at a neutral and an emotive movie film under similar conditions. Subliminality was insured in the first experiment by reducing the duration of exposure and in the second by reducing the level of illumination. The results showed that ratings of anxiety were significantly increased under subliminal emotive conditions, and reduced following subliminal neutral exposure. Correlations between psychic and somatic symptoms of anxiety were significantly higher under supraliminal conditions compared with subliminal ones. The possible role of subliminal stimulation in investigating the psychic and somatic components of anxiety is discussed.


Size estimation in paranoid and nonparanoid schizophrenics. Fifteen paranoid and 15 nonparanoid schizophrenics and 15 normal controls were administered a size estimation task which featured two administrations of nonthematic standard stimuli. The standard stimuli were presented under three conditions of background stimuli: a) surrounded by four smaller stimuli of the same kind; b) surrounded by four larger stimuli of the same kind; c) presented without background stimuli. Standard stimuli were presented at exposure times of 33 and 4000 milliseconds. On the first administration, nonparanoid schizophrenics were found to overestimate size relative to paranoidschizophrenics with normal controls intermediate in performance between the paranoid schizophrenics and nonparanoid schizophrenics, particularly on longer stimulus exposure times. The groups did not differ on the second administration. This replication of the results of earlier investigations suggest that the repeated administration of size estimation procedures in which the effects of sequence and thematic content stimuli were inextricably confounded may have contributed to recent conflicting findings in the size estimation literature. Contrary to predictions generated by Cromwell's stimulus redundancy formation, the paranoid schizophrenics were not more affected by the size of the background stimuli than the nonparanoid schizophrenics.


Cardiac chamber imaging: a comparison of red blood cells labeled with Tc-99m in vitro and in vivo. A detailed comparison was performed between the quality of cardiac images obtained using red blood cells labeled in vitro and in vivo. Both methods gave cardiac images of high quality. The in vitro method resulted in subjectively superior images, better intravascular retention of injected radioactivity, and a higher left-ventricle-to-background count ratio (p less than 0.05). The differences in image quality and left-ventricular blood-pool activity were not great, however, and the slight advantage of the in vitro method was offset by a somewhat more complicated preparative procedure. We believe that both agents are suitable for radionuclide imaging of the cardiac chambers.


Normal adrenal asymmetry: explanation and interpretation. Although adrenal imaging with 19-iodocholesterol provided much useful diagnostic information, spatial resolution was less than ideal. With the greater target-to-background ratios afforded by NP-59, differences between the right and left adrenal glands--in terms of position, configuration, and depth-related activity--can now be defined. Analysis of the scintigrams of 21 individuals with no evidence of adrenal disease has allowed us to characterize the normal degree of adrenal asymmetry. Appreciation of this asymmetry is necessary if the potential for greater diagnostic accuracy afforded by NP-59 is to be realized.


Liver scintigraphic features associated with alcoholism. The relationships between scintigraphic features and clinical alcoholism were studied by review of 2,406 liver scintiphotos. Two distinct patterns were significantly associated with alcoholism: (a) heterogeneous distribution of radiocolloid in the liver, and (b) jointly increased uptake of tracer by the spleen and vertebral bone marrow. A total of 13 overall patterns were found to distinguish, with considerable reliability, alcoholics from all other patients. This finding reflects the frequency with which alcohol abuse is associated with hepatic dysfunction in hospital patients. These observations indicate an important role for the nuclear medicine physician in detection of alcoholism among patients referred for liver-spleen imaging, and they form a basis for comparison with the diagnostic efficacy of other methods of evaluating diffuse liver diseases.


Ventilation-perfusion lung imaging and selective pulmonary angiography in dogs with experimental pulmonary embolism. To determine the accuracy and limitations of Xe-133 ventilation and Tc-99m perfusion lung images (V-P images) in detecting pulmonary emboli (PE), these studies were performed in 23 dogs after experimental production of PE by a modified Wessler technique. Fourteen of the animals also underwent selective pulmonary angiography. Xenon-133 abnormalities were seen immediately after embolization in two of the 23 animals (8.7%). Perfusion images revealed the location of 83% of emboli that completely obstructed pulmonary vessels, but only 26% of those that partially obstructed flow. Defects were seen with 97% of emboli that completely occluded vessels larger than 2.0 mm in diameter, but in only 66% of those occluding smaller vessels. Oblique perfusion images provided the only evidence of the perfusion defect associated with five of 88 (5.7%) angiographically proven emboli. V-P imaging is a sensitive technique for detecting PE unless the emboli lodge in very small vessels or incompletely obstruct a vessel. Xenon-133 abnormalities occur infrequently following PE, and should not be a common cause for a false-negative V-P match in clinical practice.


Relative renal accumulation of Tc-99m penicillamine as an index of differential renal function: concise communication. The relative renal accumulation of technetium-99m penicillamine (TPEN) was evaluated as an index of differential renal function. Using a scintillation camera interfaced to a computer, renal uptake of TPEN was determined for each kidney by subtracting the renal activity at 10 min from that at 25 min. This percentage of TPEN activity in the left kidney was compared with the percentage of total creatinine clearance contributed by the left kidney in six patients with ureteral obstruction and nephrostomy drainage. The two measurements agreed extremely well, with a correlation coefficient of 0.98. The relative renal uptake of TPEN and similar cortex imaging agents such as Tc-99m dimercaptosuccinic acid can probably be used to assess differential renal function.


The increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter. Patients treated with 10 mCi of I-131 for toxic diffuse goiter in the period January 1974--June 1976 were evaluated for development of hypothyroidism. Fifty percent were hypothyroid within 3 mo and 69% within 1 yr of treatment. Our data suggest that there is a higher incidence of hypothyroidism after standard doses of I-131 in the 1970s as contrasted with treatment groups in the 1950s and 1960s. The pathophysiology of this increased incidence is not known with certainty; however, infrequent use of thionamide medication, together with recent increases in dietary iodine, may render the gland more radiosensitive.


Thallium-201 imaging in thyroid carcinoma--appearance of a lymph-node metastasis. Before surgery, thallium-201 chloride detected a supraclavicular metastasis from a mixed follicular and papillary adenocarcinoma of the thyroid.


Cerebral perfusion deficit masked by Paget's disease of skull. Prominent extracerebral perfusion on an emission angiogram of the head in a patient with Paget's disease of the skull masked an underlying intracerebral perfusion deficiency, due to occlusion of the left middle cerebral artery.


Imaging the adrenal glands with radiolabeled inhibitors of enzymes: concise communication. Although radioiodinated cholesterols furnished the first noninvasive imaging of the adrenal glands, it would be desirable to decrease the time for imaging and decrease the radiation dose. The relative tissue distributions of two radiolabeled enzyme inhibitors [3H] metyrapol and I-125-SKF-12185 were studied in dogs and man. Their percentage uptakes and target-to-nontarget ratios were similar. The adrenals of three dogs were imaged sharply at 2 hr after injection with 4--6 mCi of I-131-SKF-12185, confirmed by subsequent imaging with 1 mCi of I-131-6-beta-19-nor cholesterol at 5 days after injection. The use of 1 mCi of I-123-SKF will permit imaging of the adrenals in 1--2 hr and will decrease the radiation dose in the human to 0.76 rads to the adrenal, 0.18 rads to the ovaries and 1.7 rads to the liver.


The use of videotape for off-line viewing of computer-assisted radionuclide cardiology studies. Videotape offers an inexpensive method for off-line viewing of dynamic radionuclide cardiac studies. Two approaches to videotaping have been explored and demonstrated to be feasible. In the first, a video camera in conjunction with a cassette-type recorder is used to record from the computer display scope. Alternatively, for computer systems already linked to video display units, the video signal can be routed directly to the recorder. Acceptance and use of tracer cardiology studies will be enhanced by increased availability of the studies for clinical review. Videotape offers an inexpensive flexible means of achieving this.


Studies on ribosomal RNA synthesis in vivo in rat liver during short-term protein malnutrition. To better understand the increased incorporation of [14C] orotate into rRNA, as detailed study of liver rRNA synthesis was performed on young rats fed a 6% casein diet for 1 week. From 10 to 180 minutes after i.v. injection of [14C] orotate, nucleolar RNA specific activity of malnourished rats was 1.6 times higher than controls. Polyacrylamide gel electrophoresis revealed that 45S pre-rRNA from malnourished rats was synthesized more rapidly than controls. Specific activities of other nucleolar RNA species was increased but the time of appearance of labeled peaks did not change. The cellular cytoplasmic rRNA pool was reduced to 70% of controls, the time of appearance of labeled rRNA in the cytoplasm was the same, but cytoplasmic rRNA specific activity was 2.1 times greater than controls. Absorbance profiles and radioactivity patterns of nucleoplasmic RNA were similar in the two groups of rats. Nucleoplasmic radioactivity patterns were complex and heterodispersed, and the amount of radioactivity was greatest in RNA from malnourished rat liver. Our data indicate that short-term dietary protein restriction leads to cellular events which increase the synthesis of nuclear RNA. Nucleolar RNA is processed and transported to the cytoplasm in a manner similar to controls.


Dietary components and gastrointestinal growth in rats. Groups of young rats, weighing 50--80 g, were fed nutritionally adequate purified diets containing different types of protein, carbohydrate, lipid and fiber, or no fiber. Effect of diet on growth of the gastrointestinal tract was evaluated from differences in size of the organs and organ weight: body weight ratios at the end of a 5 week feeding period. The results suggested that type of dietary protein (casein or soy protein), or carbohydrate (dextrose, sucrose, hydrolyzed starch), or lipid (mixed animal + vegetable, corn oil or lard) did not seem to influence growth of the stomach, small intestine, cecum or colon. However, fiber (mixed vegetable, from oats or cellulose) in the diet appeared to have enhanced growth of the small intestine, and more markedly that of the colon (both its length and weight) but not that of the stomach or cecum. On the basis of crude fiber, growth enhancement appeared to be greater in response to the diet with mixed animal and vegetable components than to the semi-purified diets containing oats or cellulose.


The effects of prenatal protein restriction on the developing mouse cerebrum. Purified low protein maternal diets cause a reduction in total weight and protein content but not in DNA content (cell number) of the cerebrum of newborn mice. Female mice were fed diets in which 8%, 11%, 15%, or 27% (control) was casein as the sole source of protein for 1 or 2 months prior to mating and throughout gestation. A 15% casein diet fed for 1 month had no effect on brain weight, DNA content (cell number) or protein content in the cerebrums of newborn mice. Female mice fed an 8% or 11% protein diet for 1 or 2 months prior to conception and throughout gestation gave birth to young that had a decreased cerebral weight and protein content. However in neither case was the amount of cerebral DNA (cell number) of the newborn from females in the low protein group significantly different from that in the cerebrums of mice born to females on the normal protein diet.


Dietary protein intake and arginine requirements in the rat. Experiments were conducted with immature rats fed L-amino acid purified diets varying in total N and arginine. The experiments demonstrated that total N intake was the factor responsible for increased orotic acid excretion during arginine deficiency. Increased orotic acid excretion was accompanied by increased liver transaminase activities and increased liver concentrations of NH4-N and glutamine. Arginine requirements for growth and normal metabolite excretion increased as dietary N was increased. Accompanying elevated urinary citrate during N deprivation and arginine deficiency was a depression of liver isocitrate dehydrogenase activity. Citrate excretion was lower if arginine was fed as the HCl compared to the free base. During a partial or total arginine deficiency citrate excretion was elevated at varying dietary N concentrations. Urinary pH was not significantly changed by level of dietary N or arginine.


Age-related changes in ribosomal profiles and in vitro protein synthesis in skeletal muscle during fasting and subsequent refeeding of rats. Age-dependent changes in ribosomal profiles and in in vitro protein synthesis in skeletal muscle (gastrocnemius muscle) were studied in rats subjected to fasting and subsequent refeeding. Male rats of 4, 7, and 21 weeks of age were used. Incorporation of 14C-leucine into protein in vitro using skeletal muscle ribosomes from fed rats decreased with the age of the animals. Sucrose density gradient analyses of ribosomal profiles revealed that the changes in protein synthesis were accompanied by progressive declines in the concentrations of polyribosomes and total RNA in skeletal muscle. After fasting for 1 or 2 days, protein synthesis in muscle of young rats dropped markedly and this change could be attributed to the fall in the concentrations of polyribosomes. Also, the concentration and total RNA in the muscles of the young rats decreased. During refeeding of rats after fasting for 2 days, the incorporation of 14C-amino acids into protein recovered more efficiently using ribosomes of skeletal muscle of young animals compared with using those of older animals. This rapid increase in the protein synthesizing activity of skeletal muscle may be related to the efficient recovery of the ribosomes toward heavier aggregates. The results indicate that young animals adapt more efficiently to fasting and refeeding than do older animals.


The determination of thiamin pyrophosphate in blood and other tissues, and its correlation with erythrocyte transketolase activity. A sensitive method for the specific measurement of thiamin pyrophosphate (TPP) has been developed using the apoenzyme recombination concept. Yeast pyruvic decarboxylase apoenzyme can be reconstituted by the addition of TPP or samples containing TPP, yielding the holoenzyme with activity proportionate to the amount of TPP added. Using this technique, reaction mixtures containing 0.2 to 1.5 ng TPP can be assayed. Normal human erythrocyte TPP ranges from 50 to 150 ng per ml packed cells. When rats are fed a thiamin deficient diet, the erythrocyte TPP level falls more rapidly than the erythrocyte transketolase activity. After 8 days, the level of TPP in the erythrocytes of deficient animals was 10% of the level in pair-fed controls. At this time, however, there was no appreciable decrease in their respective transketolase activities. The level of TPP in the liver also is decreased drastically after 8 days. Therefore it appears that erytyrocyte and liver TPP stores have begun to be depleted and suggest that erythrocyte TPP levels are a more sensitive indicator of thiamin status.


Choline deficiency and the reversibility of renal lesions in rats. A transient choline deficiency was induced in young rats subsequently fed a nutritionally complete purified diet during recovery periods of 0 to 119 days. The purpose was to investigate the pathomorphology of the renal lesions and relate this to observed biochemical changes. Acute renal lesions consisting of tubular epithelial cell necrosis and tubulorrhexis were observed in rats immediately after the insult. Chronic renal lesions consisting of interstitial nephritis and scarring were observed 28 to 119 days after the insult; these lesions were qualitatively similar at all times but showed a healing trend as the recovery period lengthened. Kidney and liver weights, liver fat concentration, and serum urea nitrogen concentration were higher in treated rats than in control rats at 0 days (no recovery period allowed) but treatment effects at all other times were minor. Significant changes occurred in serum phenylalanine and tyrosine concentrations and in the phenylalanine to tyrosine ratios after recovery periods of 0, 42 and 84 days. It was concluded that the proximal convoluted tubule was most seriously affected and that the chronic lesions represent a potential threat to kidney function in a stress situation. Some implications for human nutrition are discussed.


Variable effects of iron status on the concentration of ferritin in rat plasma, liver, and spleen. The present studies were conducted to determine the relationships between iron status and ferritin levels in plasma, liver, and spleen of rats. Rats were fed either iron-adequate or iron-deficient purified diets, and measurements of hemoglobin and plasma and tissue ferritin levels were made at various times during iron depletion and iron repletion. Although mean plasma ferritin concentrations of iron-deficient rats were directionally less than those of iron-adequate rats, these differences were not statistically significant due to high variability among similarly treated animals. During iron repletion plasma ferritin concentrations again were so variable that no significant effect of iron repletion on plasma ferritin concentrations was observed. On the other hand, liver and spleen ferritin concentrations of similarly treated rats were much less variable. Ferritin liver and spleen stores decreased more rapidly than hemoglobin during iron deficiency and were restored more slowly than hemoglobin during iron repletion. There was no evidence of correlation between liver and plasma ferritin concentration. Because of the variable responses of plasma ferritin concentration to iron depletion and repletion and the lack of relationship between plasma and liver ferritin concentrations, it is concluded that plasma ferritin concentration is not a good indicator of iron status in rats.


Effects of age, diet and lactation on lipogenesis in rat adipose, liver and mammary tissues. Four diets varying in safflower oil content from zero to 20% were used in a study of interactions among diet and physiological state. Increasing fat in the diet did not alter food intakes but decreased digestibility coefficients. Increasing safflower oil intake did not alter milk fat content in lactating rats but increased relative amounts of unsaturated fatty acids in milk fat. In liver and perirenal adipose tissues from young male and non-lactating female rats, low fat diets increased rates of lipogenesis from glucose in vitro and specific activities of enzymes whose functions are closely associated with lipogenesis. This adaptive hyperlipogenic response was not evident or was less prominent in aged or lactating rats. In the case of lactating rats it appears that lactation produces a marked reduction in adipose lipogenesis when low fat diets are fed. Reduced glyceride glycerol synthesis in lactating as compared to non-lactating rat adipose coupled with reduced fatty acid synthesis and in increased lipolysis indicated a shift in adipose function in the direction of increased fat mobilization as would be supportive of lactation. Only minor diet effects upon mammary enzyme patterns and rates of in vitro lipogenesis were observed.


Nitrogen dioxide-induced pulmonary disease: five new cases and a review of the leterature. Twenty-three patients exposed to nitrogen dioxide in agriculture or industry were referred to the University of Wisconsin Medical Center. Eighteen experienced a transient upper respiratory tract syndrome; five developed pulmonary edema or bronchiolitis obliterans. This latter group responded to steroid therapy but all demonstrated evidence of persistent pulmonary dysfunction on follow-up studies. Combining our findings with those in the literature we concluded: (1) exposure to NO2 is more common than generally appreciated; (2) case fatality is high--29% for silo-filler's disease; (3) steroids are effective therapy and should be continued for at least eight weeks; (4) although the majority recover without significant sequelae, some individuals may develop persistent functional abnormalities; (5) there is no evidence that long-term exposure to low concentrations of NO2 leads to chronic airway obstruction; and, (6) NO2-induced pulmonary disease could be elminated with appropriate preventive measures.


Stress levels of ambulance paramedics and fire fighters. Responses to Rahe and job stress questionnaires and urinary concentrations of cortisols and catecholamines served to indicate work related stress in 56 fire fighters and 67 paramedics. Although the average Rahe test scores, indicative of stress arising from life events, were comparable, those of the job stress test were statistically significantly higher for the paramedics. The paramedics felt their jobs more exhausting, less satisfying and requiring too much responsibility. For the paramedics, statistically significant higher levels of epinephrine and elevated levels of norepinephrine were found for the work as compared to the off day. For fire fighters, higher levels of cortisol and norepinephrine evident on the off day rather than the work day apparently reflect the relatively light work load experienced during the span of urine collections.


Meat worker's asthma.

Meat worker's asthma. A meat cutter who experienced wheezing when working in the area where price labels were heated, was challenged with the inhalation of the emission of heated price labels and nebulized phthalic anhydride. Only exposure to the emissions from the heated price labels evoked a response. The spectrum of emissions from heated price labels, analyzed by gas chromatography and mass spectrometry, was found to include phthalic anhydride, 2,5-di-tert-amyl quinone and dicyclohexylphthalate.


Industrial Grenz ray overexposure: report of a case. A case of accidental industrial exposure to a single large dose of ultrasoft (Grenz) x-rays is reported. Certain inferences can be made by estimating average skin target dosage, average kilovoltage, milliamperage and duration of exposure. From these data the quality and skin depth dosage of the ray can be tentatively estimated. Comparison of these figures with known biological phenomena such as immediate x-ray burn reaction, late cutaneous sequelae and temporary epilation permits a reasonable estimate of probable skin surface dosage and prognosis.


Byssinosis and chronic respiratory disease in U.S. cotton gins. A pilot study of cotton gin workers was undertaken in the ginning industry so as to determine if a definitive study could be undertaken and to make some first order estimates of byssinosis and chronic respiratory disease and to compare the findings to those reported in the African and European gins. Baseline medical data were collected on 203 gin workers and 260 controls, consisting of a medical symptom questionnaire, a chest x-ray and the forced expiratory spirogram pulmonary test. Results revealed a prevalence of functional reactors equal to that found in the textile industry and other gin studies (44%) as determined by spirometric testing, without any association to smoking history. The major reaction group within the ginning population was those working in the baling press area. These same workers demonstrated evidence of chronic depressions in their spirometry data. No excess of chronic respiratory disease as determined by the questionnaire was detected within the gin worker population.


Monomethylformamide levels in human urine after repetitive exposure to dimethylformamide vapor. Eight healthy male subjects were exposed to DMF vapor at a concentration of 8.79 +/- 0.33 ppm for six hours daily for five consecutive days. All urine voided by the subjects was collected from the beginning of the first exposure to 24 hours past the end of the last exposure and each sample was analyzed for monomethylformamide (MMF). MMF was rapidly eliminated from the body with urine values peaking within a few hours following the end of each exposure period. Very little was found in the 24-hour postexposure sample and none was found in a 48-hour postexposure sample. There was no increased excretion of MMF in the urine following repetitive exposure. The mean for the seven-hour (end of exposure) sample was 4.74 microgram/ml or 736.8 microgram. Lower and upper one-sided 95% tolerance limits for 95% of the population were 1.2 microgram/ml (367 microgram) and 13.9 microgram/ml (1625 microgram). The coefficient of variation (CV) for microgram MMF/ml was approximately 25 times more variable than the CV for total microgram.


Occupational asthma due to tetrachlorophthalic anhydride. The plastics industry utilizes a number of organic chemicals which have the potential of producing pulmonary reactions, particularly in susceptible individuals. Five workers are reported who were involved in the production of epoxy resins and developed recurrent respiratory symptoms and physiologic abnormalities following exposure to tetrachlorophthalic anhydride (TCPA). Inhalation challenge with TCPA reproduced their symptoms and demonstrated both an immediate and late (4-6 hours) physiologic response. Although the clinical picture strongly suggested a hypersensitivity reaction, immunologic studies failed to demonstrate precipitating or specific IgE antibody. Avoidance of exposure resulted in resolution of symptoms; however, three of the five individuals had residual functional impairment.


Physiological effects of rotational work shifting: a review. The high cost of capital equipment, demands of the world markets, and continuity requirements of many technological processes have forced industry to operate three-shift, 24-hour days. Workers on fixed schedules experience no particular problems from shift work, but those who are shifted periodically can undergo physiological and emotional disturbances. These disturbances occur because most human systems function according to circadian rhythms that can be easily disoriented. The primary cause is the periodic shifting of the light-dark, wake-sleep cycles. Extensive literature exists on the cause and symptoms of disturbances in the human physiological rhythms. The information contained in this literature can be applied to protecting the health and well-being of the worker.


Changing habits--an experience in industry. A company-sponsored No Smoking Clinic was attended by 118 persons. The sessions consisted of a total of eight hours divided over five consecutive work days. A 12 month follow-up showed a "quit rate" of 25%. This experience in behavior modification is consistent with the goals of preventive medicine and can be adapted to an industrial setting. Approaches of this type should offer us a challenge in the future.


Population biology and behavior of larval Eustrongylides tubifex (Nematoda: Dioctophymatida) in poikilothermous hosts. A total of 178 channel catfish (Ictalurus punctatus), 162 freshwater drum (Aplodinotus grunniens), 60 smallmouth bass (Micropterus dolomieui) and 2,488 yellow perch (Perca flavescens) were examined for larval Eustrongylides tubifex (Nitzsch 1819) Jägerskiold 1909 during 1973 and 1974. Older, large fish exhibited higher prevalence, larger mean numbers of larvae in infected fish, larger mean numbers of larvae in all fish examined, and wider range of intensity of infection. Infections were most extensive in yellow perch. The majority of larvae were removed from mesenteric cysts. Under experimental conditions, larvae migrated from cysts through the body wall when environmental temperatures reached or exceeded 40 C. Fourth-stage larvae removed from yellow perch successfully reinfected a variety of poikilothermous experimental hosts. Both young-of-the-year and I+ age/size class yellow perch exhibited increasing monthly larval worm burdens during portions of the sampling period. Older (II+) age/size class yellow perch did not exhibit significantly increasing worm burdens. No significant differences were noted in numbers of male and female larvae or in worm burdens in male and female yellow perch.


Cuticular morphology of five species of Dirofilaria: a scanning electron microscope study. Cuticular markings of five species of Dirofilaria were examined by SEM. Variations in the patterns on the en face view were observed among the species. Transverse striations were observed on the cuticles of all five species, but longitudinal ridges were lacking on Dirofilaria immitis, the type species of the subgenus Dirofilaria. They were present on the other four species, Dirofilaria repens, Dirofilaria tenuis, Dirofilaria corynodes, and Dirofilaria magnilarvatum, members of the subgenus Nochtiella. Longitudinal ridges and other cuticular structures and patterns were seen to vary among the species and with the portion and aspect of the worm examined. It is suggested that SEM would be a good tool for a detailed study of specific cuticular morphology of all species of Dirofilaria, thus contributing toward their differentiation and recognition.


Increased susceptibility to infection with Brugia pahangi in aged female jirds (Meriones unguiculatus). Female Mongolian jirds, Meriones unguiculatus, from 5 age groups of 2, 12, 16, 21, and 28 months, were infected with Brugia pahangi. Infections were followed for 125 days by weekly bleedings beginning 55 days postinoculation. Jirds were then killed and adult parasites recovered. Results showed a significant shortening of the prepatent period in the 12-, 21-, and 28-month-old groups. The proportion of gravid female worms did not vary significantly among the 5 groups. Similarly, the ratio of females to male worms showed little variation from group to group. Microfilaremia data for the 5 infection groups show an age-associated increase in numbers of circulating microfilariae. Some individuals in the 28-month group demonstrated 1,500 to 3,000 microfilariae per 0.25 ml peripheral blood, a level that was not approached by young females.


Dirofilaria immitis: experimental infections in the ferret (Mustela putorius furo). The ferret, Mustela putorius furo, was found to be susceptible to Dirofilaria immitis infection when exposed to low (14) or high (280-420) numbers of infective larvae harvested from Aedes aegypti. Eight ferrets (half of them cortisonized) were inoculated subcutaneously with 14 larvae each. All of them were subsequently found to harbor D. immitis in the heart, and all but one of them had worms of both sexes. Six of these ferrets were examined for microfilaremia at 31 to 35 weeks after inoculation; 3 were positive (one observed only at postmortem examination) and there was evidence that fertilization of female worms had occurred in one other. Females up to 25.5 cm and males up to 16.0 cm were recovered. There was no evidence that the cortisonization of some ferrets had affected the infections. Both male and female ferrets became infected. Four cortisonized ferrets were inoculated with 280 or 420 larvae of D. immitis (divided equally between subcutaneous and intraperitoneal routes). All of them died 16 to 18 weeks after inoculation, yielding 102 to 125 immature D. immitis. In these lethal infections, worms were recovered from the heart and adjoining vessels, and also from vascular and extravascular sites throughout the body.


Dirofilaria cancrivori sp. n. (Nematoda: Filarioidea from the crabdog, Procyon cancrivorus, in Guyana. Dirofilaria cancrivori sp. n. is described from subcutaneous tissues of the crabdog, Procyon cancrivorus, in Guyana, South America. The filarid is morphologically distinct from Dirofilaria tenuis, parasite of a related host, the raccoon, in the southern United States, and all other species of Dirofilaria. The parasite can be distinguished from other dirofilarias based on a combination of morphological features including its size, number, and arrangement of caudal papillae on the male tail, size and shape of the spicules, the presence of longitudinal ridges and transverse striations on the cuticle, and the microfilaria.


Ultrastructural characterization of the cuticle of Onchocerca volvulus microfilaria. Previous ultrastructural studies on various microfilariae have suggested the presence of a trilaminar membrane at the parasite cuticle. In the present report, the formation of the cuticle of Onchocerca volvulus microfilariae was studied at different developmental stages by transmission electron microscopy of samples obtained from subcutaneous nodules of untreated patients. The cuticle is formed by the layering of surface coat fibrillar components of the hypodermal cells. No plasma membrane is found at the cuticle of the microfilaria. The use of freeze-fracture replication confirmed the absence of a classic plasma membrane at the parasite cuticle. Our results suggest that immunogenic determinants of the microfilaria cellular elements are hidden from the exterior by the acellular cuticle. This may explain the lack of cellular reaction usually found around living O. volvulus microfilariae in the dermis of onchocerciasis patients.


The life cycle of the tick Hyalomma marginatum rufipes Koch (Acarina: Ixodidae) under laboratory conditions. The life cycle of Hyalomma marginatum rufipes Koch was studied under laboratory conditions at 26 +/- 1 C. The preoviposition period was 7.1 +/- 0.23 days. The mean (+/- SE) number of eggs was 6,867 +/- 2,609 (max. 13,180, min. 3,184). The greatest egg production was recorded on day 3 (avg 1,170 egg/female). The incubation period was 29.3 +/- 2.96 days. The feeding time of larvae and nymphs of this 2-host tick was 22.8 +/- 0.13 days. Nymphs producing males weighed less (23.1 +/- 0.748 mg) than those producing females (26.8 +/- 1.19 mg); the combined larval-nymphal feeding time of the former was shorter (21.9 +/- 0.1 days) than that of the latter (22.9 +/- 1.12 days). The premolting period of nymphs to adults of both sexes was similar.


Phalacropsylla oregonensis sp. n., with a key to the species of Phalacropsylla Rothschild 1915 (Siphonaptera: Hystrichopsyllidae). A new species of flea belonging to the genus  Phalacropsylla is described. The known distribution and host associations of the 5 recognized species are briefly discussed, and a key to these taxa is included.


Glochidiosis of salmonid fishes. II. Comparison of tissue response of coho and chinook salmon to experimental infection with Margaritifera margaritifera (L.) (Pelecypoda: Margaritanidae). Coho salmon (Oncorhynchus kisutch) are more resistant to experimental infection with the glochidia of the freshwater mussel (Margaritifera margaritifera) than are chinook salmon (Oncorhynchus tshawytscha). Histological sections made at intervals during the infection showed that coho salmon sloughed the parasites from their gills by 4.5 days postinfection, but the parasites remained encysted in the gills of chinook salmon for 12 weeks, when metamorphosis to juvenile mussels was complete. Coho salmon sloughed the parasites by a well-developed hyperplasia. No such pronounced hyperplastic reaction was seen in the gills of chinook salmon.


Effect of coccidiosis on blood coagulation in broilers. Severe infection with Eimeria acervulina, Eimeria maxima, Eimeria necatrix, and Eimeria tenella increased the prothrombin times in broilers compared with the times in uninfected birds. Recalcification time was not affected. The increase in prothrombin time was related to the severity of infection (as measured by lesion score), and was significant (P less than or equal to 0.05) only in the most severely infected birds. The increase was of short duration, lasting only 1 or 2 days, and first appeared on day 5 or 6 postinoculation. Restricting the feed intake of uninoculated birds to the amount of feed consumed by infected birds showed that the reduction in feed intake with coccidiosis was not responsible for the increase in prothrombin time.


The endogenous stages of Eimeria utahensis (Protozoa: Eimeriidae) in the kangaroo rat, Dipodomys ordii. The endogenous life cycle of Eimeria utahensis is described from experimentally infected kangaroo rats, Dipodomys ordii. The endogenous asexual cycle consisted of 4 generations of meronts. First-generation meronts were concentrated in the anterior third of the small intestine. The succeeding generations of meronts and the sexual stages were concentrated in the middle third of the small intestine. First-generation meronts had a mean diameter of 9.7 micrometer and contained 12 to 16 merozoites. Second-generation meronts had a mean diameter of 8.0 micrometer and contained 12 to 16 merozoites and a residual body. Third-generation meronts had a mean diameter of 12.4 micrometer and contained 4 to 8 merozoites. Fourth-generation meronts had a mean diameter of 8.6 micrometer and contained 16 to 24 merozoites. Young gamonts were located in epithelial cells of the crypts of the small intestine. Shortly after the parasites entered the epithelial cells, the infected cells became displaced into the lamina propria, and most of the mature gamonts were in this location. The nuclei of host cells containing young sexual stages became greatly elongated and flattened. A few young gamonts were seen in cells in which the host cell nuclei were dividing. During development, nuclei of microgamonts became arranged on the periphery of numerous compartments. Only one type of wall-forming body could be distinguished in the macrogamonts.


Allencotyla pricei sp. n. (Microcotyloidea: Heteraxinidae) from the gills of the pile surfperch, Damalichthys vacca (Girard), in southern California. Allencotyla pricei sp. n. (Monogenea: Heteraxinidae) from the gills of pile surfperch, Damalichthys vacca (Girard), from Redondo Beach, California is described. This species is distinguished primarily by the prebifurcal position of the genital atrium and vagina, and by possessing an elongate esophagus. The systematic arrangement of microcotyloid forms characterized by an asymmetric haptor is discussed.


Parasitism in some east Atlantic bathypelagic fishes with a description of Lecithophyllum irelandeum sp. n. (Trematoda). Eighty-four bathypelagic fishes collected at depths from 975 to 1,555 m in the eastern Atlantic Ocean were examined for animal parasites. Ninety-five percent (including all the Gonostomatidae) were free from parasites. A digenetic trematode, Lecithophyllum irelandeum sp. n. from the stomach of one specimen of the family. Melamphaidae, is described. One copepod was found in the kidney of Bathylagus euryops, and another copepod infected the liver of a melamphaid. This paucity of parasites is of a different pattern from that found in mesopelagic waters. Some environmental factors that may be involved in the causes of this differences are mentioned.


Scanning electron microscope observations on miracidium, cercaria, and cercarial papillar patterns of Schistosoma japonicum. The surfaces of Schistosoma japonicum miracidia and cercariae were examined with the scanning electron microscope, and argentophilic papillae of S. japonicum cercariae, presumed to be sensory, with both the scanning electron microscope and the light microscope. Miracidia are covered with cilia, and the apical papilla is covered with cytoplasmic folds that form an anastomosing network. There is an excretory pore on the posterior one-third of the body. The tegument of S. japonicum cercariae is covered with spines that point in a posterior direction. The tail has a more irregular surface than the body, with fewer spines. The openings of the penetration gland ducts on a disclike area with netlike ridges at the anterior tip of the head organ are linearly arranged in 2 lateral crescents each containing 7 separate apertures. The basic number of the body papillae of S. japonicum (excluding those at the anterior end) is 56: 18 ventral, 4 acetabular, 18 dorsal, and 16 lateral (8 on each side). The number of papillae at the anterior tip is 14 (7 on each side). There are 9 papillae on the ventral side of the tail, and 10 on the dorsal and lateral sides.


Survival of protoscolices of Echinococcus granulosus at constant temperatures. A study was conducted to determine the effects of storage at constant temperatures upon the survival of protoscolices of Echinococcus granulosus from hydatid cysts removed from infected sheep. Parallel tests were conducted on intact cysts from both lung and liver, and on protoscolices stored within 1-ml samples of hydatid fluid. The longest survival times of any of the samples tested at each temperature were: -20 C, 1 hr; -10 C, 4 hr; 1 C, 16 days; 10 C, 16 days; 20 C, 8 days; 30 C, 4 days; 40 C, 2 days, and 50 C, 2 hr. In general, protoscolices survived considerably better when stored within intact cysts than when in 1 ml of hydatid fluid. At temperature ranges where putrefaction occurred, protoscolices in cysts from lung survived longer than those from liver. The ability of these protoscolices to survive extended periods of time after an infected sheep has died or been killed suggests that stringent preventive and control measures should be established in areas where hydatid disease is endemic. Animal pits at community dumping grounds where sheep carcasses might be discarded should be enclosed or covered, and all stray and roving dogs in those regions should be rigidly controlled.


Intestinal helminths of some Nile fishes near Cairo, Egypt with redescriptions of Camallanus kirandensis Baylis 1928 (Nematoda) and Bothriocephalus aegyptiacus Rysavý and Moravec 1975 (Cestoda). Of 10 species of Nile fishes collected during the summer of 1975 at Giza near Cairo, Egypt, 7 harbored 7 helminth species. Recovered material includes 3 species of nematodes: Camallanus kirandensis Baylis 1928 (new host and geographical record), Cucullanus barbi Baylis 1923, and Rhabdochona congolensis Campana-Rouget 1961 (new host record); three species of cestodes: Khawia sp. (new in Africa), Polyonchobothrium clarias (Woodland 1925) Meggitt 1930, and Bothriocephalus aegyptiacus Rysavý and Moravec 1975; and one acanthocephalan species, Acanthosentis tilapiae Baylis 1947 (new geographical record). Morphologic observations of each species are reported. C. kirandensis and B. aegyptiacus are redescribed.


Is psychodiagnostic assessment humanistic? The views of psychologists associated with the humanistic orientation in regard to psychodiagnostic assessment was examined. For the most part these theorists describe assessment as nonhumanistic. Their concerns about assessment were divided into five categories: that assessment is reductionistic; it is artificial; it does not pay attention to the examiner-patient relatinship; it judges people; it is overly intellectual. These concerns were elaborated and then responded to from a pro-assessment stance. Although these criticisms could be valid, their validity was said to reflect poor diagnostic practice rather than an inherent weakness in the assessment enterprise. As long as the examiner attempts actively to engage the patient in the assessment process and is aware of the interpersonal context of the test responses and behavior, then psychodiagnostic assessment is consistent with a humanistic orientation.


Six-month prognostic norms derived from studies of the Rorschach Prognostic Rating Scale. The Rorschach Prognostic Rating Scale (RPRS) was introduced in 1951 by Klopfer. Kirkner, Wisham, and Baker. The predictions of Klopfer et al. are compared to the outcomes in four studies of the RPRS. The originalinterpretation is shown to predict higher percentages of success than revealed by the empirical studies. A second interpretation of the scale is proposed on the basis of the experimental data. This interpretation relates RPRS scores to the chance for substantial improvement within 30 weeks of once weekly therapy by client-centered, rational-emotive, desensitization, aversion, or traditional methods. For any given RPRS score, the chance for substantial improvement is approximately the same for every type of therapy, and increases as the RPRS score increases. The second interpretation is proposed in both tubular and algebraic forms as a stimulus to further research and clinical applications.


The Rorschach response process.

The Rorschach response process. Five groups of subjects, consisting of 20 schizophrenics, 20 depressives, 20 nonpatient adolescents, and 40 nonpatient adults split at the median on the MMPI K Scale, were instructed to give as many responses as possible to each Rorschach card within a 60-second time limit per card. The average number of answers given by each group was dramatically greater than the mean number obtained under standard test conditions, with approximately two-thirds of all answers occurring during the first 30 seconds of card exposure. Evaluation of form quality shows no deterioration of goodness of it with the increase in R, that is, all groups, except the schizophrenics, consistently gave good form quality answers. After testing was completed, subjects in the four adult groups were asked to select their two "best" answers to each card. The high K nonpatients and depressive tended to select the greatest number of Popular answers while the schizophrenics selected the fewest Populars and picked a significant number of poor form answers. In a related study, 20 therapists recruited two each of their own patients for testing. Each therapist tested one of his own patients while the second patient was tested by another therapist. Results show that therapists and to obtain longer and more "revealing" protocols from their own patients. The findings of these studies are discussed in the context of stimulus assimilation, ranking of interpretations, and the issue of social desirability.


Reality testing and Rorschach perceptual regression in female patients. In an effort to study the relationship between severity of psychological disturbances and developmental level scoring of the Rorschach, 43 female psychiatric inpatients were divided into two groups based on whether or not they were displaying behavioral evidence of poor reality testing. As expected, the poor reality testers group produced a significantly greater percentage of responses at the lowest developments level (amorphous responses). The more intact group produced a greater percentage of vague responses, as would be anticipated in patients fending off further regression or emerging from a regressive state. Findings add to the information available on the developmental system's utility within clinical settings and its applicability to female patients.


The power motive, n power, and fear of weakness. Among 85 male undergraduates, high need for power as measured by the 1968 Winter scoring system is shown to relate to high drinking frequency (p less than .01), high alcohol consumption (p less than .05), and taking the first drink at age 16 or less (p less than .05); to the Disinhibition ("Swinger") factor on Zuckerman's Sensation Seeking Scale (p less than .05) to poor academic performance (p less than .05); and to generate a regression equation with the California Psychological Inventory that suggests qualities of personal disorderliness and intellectual aggression. These findings, considered in terms of power motive theory, are seen as replicating earlier evidence that high n Power is maladaptie, voyeuristic and power avoidant.


The interpretative validity of the FAM: long-term psychotherapists' ratings of psychiatric inpatients. Newmark, Conger, and Faschingbauer (1976) found a significant difference between mean ratings of MMPI and FAM (Faschingbauer's Abbreviated MMPI) based interpretations. Since this may have been specific to lack of rater experience, the present study attempted a replication using long-term psychotherapists as raters. The only significant difference was for 20 male psychiatric inpatients. Females (n = 16) and the pooled sample showed no significant differences between ratings regardless of the source test. When the present results are compared to those of Newmark, Conger and Faschinbauer (1976) and earlier work by Fashcinbauer (1973), it appears that the FAM yields interpretation as accurate as one would expect given its psychometric dissimilarity from the MMPI.


Item subtletly and faking on the MMPI: a paradoxical relationship. The X-zero distinction has been used as the operational definition of MMPI item subtlety in previous research. A consistent finding has been that the X items, which are obvious in terms of pathological content, can be faked whereas the more subtle zero items cannot be faked. The present study examined the relationship between instructional sets and endorsement patterns, using a more refined, comprehensive measure of item subtlety. Sixty (30 male, 30 female) subjects completed two MMPI protocols, one under a standard instructional set and the other under either a fake-good or fake-bad response set. Order of administration and sex were counterbalanced. In general, the findings for the sublte-obvious dimension paralleled the previous findings with the X-zero distinction. Endorsement of obvious items was a direct function of instructional set, whereas endorsement of sublte items was inversely related to instructional set. Because subtle items did not appear to measure the constructs for which they had been originally intended, other uses for subtle items were discussed.


The laugh of Satan: a study of a familial murderer. A teenage murderer who killed his mother, his tiny half-brother, and his step-father was studied through the imagery he associated to three different editions of inkblots. These sets included the Rorschach, Behn-Rorschach, and Ka-Ro plates. The data were used to theorize about clues, dynamics, and diagnosis in this extreme case of adolescent violence. Family background and developmental history are included. The author takes the position that a conventional analysis of these data alone is not sufficient to fully understand familial murderers. Several of C.G. Jung's concepts, notably his view about the power of shadow-projections to influence conscious percepts and his philosophy about evil as a collective phenomenon, were used to speculate about ways we might extend our understanding of this subject's extreme form of violence. Defining the archetype as an energy-complex, the discussion theorized about possible ways different forms of paranoid ideation may arise.


Hypotensive phospholipids. Some stable analogues of Darmstoff. 2-Pentadecyl-4-hydroxymethyl-1,3-dioxolane monosodium phosphate (1) has been shown to exhibit bradycardia and hypotension in rats. It is, however, unstable in aqueous solution. In this study, the stable analogues of 1, 2-pentadecyl-5-hydroxymethyltetrahydrofuran monosodium phosphate (7), and 1-hydroxymethyl-3-pentadecylcyclopentane monosodium phosphate (17) were prepared. These substances exhibited cardiovascular effects similar both qualitively and quantitatively to those elicited by 1 and were stable in solution for about 24 and at least 72 h, respectively.


Acetylenics. 2. Synthesis and pharmacology of certain N,N-diakyl-3-phenylpropyn-2-amines. Some analogues with tryptamine-like behavioral effects in mice. A number of N,N-dialkyl-3-phenylpropyn-2-amines 7 have been prepared and tested for their biological action. Certain analogues show tryptamine-like behavior effects in mice. The tryptamine-like activity of these compounds appears to be controlled by their lipophilicity. These compounds show only weak inhibition of rat liver monoamine oxidase. Although these compounds exhibit tryptamine-like action, experiments seem to indicate that there is no interaction with the tryptamine receptors.


Analgesic and tranquilizing activity of 5,8-disubstituted 2-aminomethyl-3,4-dihydronaphthalenes. Interesting analgesic activity approaching that of meperidine and codeine was observed in standard animal models for 8-chloro-3,4-dihydro-5-methoxy-2-pyrrolidinomethylnaphthalene (compound 7). This compound was orally effective and its analgesic activity was not reversed by the opiate antagonist, naloxone. A limited number of other 2-aminomethyl analogues displayed activity in neuroleptic screens.


Diazepines. 5. Synthesis and biological action of 6-phenyl-4H-pyrrolo[1,2-a][1,4]benzodiazepines. A series of 6-phenyl-4H-pyrrolo[1,2-a][1,4]benzodiazepines (2) has been prepared with 2-phthalimidomethylfurans (12) and 1-phthalimidoalkane-2,5-diones (15) or 2,5-dimethoxy-2-phthalimidomethyltetrahydrofurans (16) as the key intermediates and subsequently evaluated for CNS activity. The structure-activity data generated indicate that, in general, introduction of the methyl and/or ethyl group(s) in the pyrrole ring and a chlorine atom at the ortho position of the 6-phenyl group increases the activity and that substitution of the above chlorine atom for a fluorine atom decreases the activity. 8-Chloro-6-(2-chlorophenyl)-1,3-dimethyl-4H-pyrrolo[,2-a][1,4]benzodiazepine (2p), the most potent among the compounds synthesized, was equipotent in taming and sedative activities to diazepam. The acute LD50 of 2p in mice was larger than 3000 mg/kg po.


Synthesis and antitumor activity of halogen-substituted 4-(3,3-dimethyl-1-triazeno)quinolines. Halogenated 4-(3,3-dimethyl-1-triazeno)quinolines were synthesized as potential antitumor agents on the basis of the biochemical pharmacological properties of existing triazenes, their structural-activity relationships, and the high melanin binding of chloroquine and iodoquine in vivo and in vitro. They were synthesized by diazotization of appropriate halogen-substituted 4-aminoquinolines in fluoboric acid at -5 degrees C followed by coupling with dimethylamine. Among these new compounds, 8-chloro-4-(3,3-dimethyl-1-triazeno)quinoline produces significant antitumor activity against both P-388 and L1210 murine leukemias. Although only marginally active or inactive against P-388, the other chloro, bromo, or iodo analogues show activity against L1210 comparable to that of dacarbazine (DIC). However, none of these compounds is active against B-16 melanoma. Compared with DIC these new agents demonstrate a higher in vitro affinity for melanin; however, this affinity is apparently not correlated with their antitumor activity.


Adriamycin analogues. 2. Synthesis of 13-deoxyanthracyclines. The syntheses of several 13-deoxyanthracyclines are described. Koenigs-Knorr condensation of epsilon-rhodomycinone (12) with the protected daunosaminyl chloride 15 afforded 14 after deprotection. Efforts to decarbomethoxylate 12, as well as attempts to selectively deoxygenate the 13 position of daunomycinone and adriamycinone, were unsuccessful as approaches to 13-deoxyanthracyclines. However, reaction of the readily available tosylhydrazones 4 and 5, of daunorubicin and adriamycin with NaCNBH3 in acidic MeOH, afforded the 13-deoxy analogues 6 and 7 in satisfactory yield. These compounds retained antitumor activity, being comparable to the parent compounds in both efficacy and potency in the P-388 mouse leukemia screen. The epsilon-rhodomycinone glycoside 14 was less active than 6 and 7.


Metabolism of cis-delta4-15(S)-15-methylprostaglandin F1alpha methyl ester in the rat. The metabolic transformation and excretion of tritium-labeled cis-delta4-15(S)-15-methylprostaglandin F1alpha methyl ester (1) have been investigated in rats after chronic and single dose oral administration. Three metabolites have been identified from a partially purified urinary extract. They were the cis-delta4-15-methylprostaglandin F1alpha (2), 15-methyl-2,3-dinorprostaglandin F1alpha (3), and 15-methyl-2,3,4,5-tetranorprostaglandin F1alpha (4). The excretion of the drug-related species was significantly slower than that of the natural prostaglandin F2alpha. The slow excretion rate and the presence of unchanged cis-delta4-15-methylprostaglandin F1alpha in urine suggested that the metabolically protected prostaglandin could persist in the body and, therefore, exhibit longer duration of action.


Antineoplastic agents. Structure-activity relationship study of bis(substituted aminoalkylamino)anthraquinones. A structure-activity relationship study was conducted on a number of bis(substituted aminoalkylamino)anthraquinones. These compounds were prepared by the condensation of substituted or unsubstituted leucoquinizarin with appropriate amines, followed by air oxidation. Both the position and the nature of the center nitrogen atom of the side chain are vital to the antineoplastic activity. The possible mode of action of these aminoquinones was discussed. 1,4-Dihydroxy-5,8-bis[[2-(hydroxyethyl)amino]ethyl]amino-9,10-anthracenedione (DHAQ) was found to possess potent inhibitory activity against both the P-388 leukemia system (T/C of 299 at 0.5 mg/kg with 4/6 cures) and the B-16 melanoma system (T/C of 503 at 1 mg/kg with 7/10 cures).


Syntheses and biological activities of basically substituted isoalloxazines. A number of flavins possessing a 2-[bis(2-hydroxyethyl)aminolethyl side chain in place of the usual D-ribityl side chain at position 10 have been synthesized and evaluated for riboflavin antagnostic activity in the rat. Two flavins of those synthesized are potent antagonists of the vitamin.


A ureido group containing analogue of oxytocin comprising eight amino acid residues. A new analogue of oxytocin was constructed from L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparaginyl-L-lysyl-L-prolyl-L-leucyglycinamide. Reaction of this 8-peptide amide with di-p-nitrophenyl carbonate yielded a cyclic compound, in which the -CH2SSCH2-bridging portion of oxytocin formed by the oxidative linking of the two cysteine side chains was replaced by the -CH2CH2CH2CH2-group of lysine, while the epsilon-NH2 group of the same residue took the place of the alpha-CH of cysteine-1. The N-terminal amino group of oxytocin, which is not necessary for its hormonal activities, was omitted. The new analogue, referred to as [1,6-Nepsilon-carbonyl-L-lysine]oxytocin, possessed a rat uterotonic activity in vitro of 3.9 +/- 0.3 units/mg, less than 0.5 unit/mg of rat antidiuretic activity, and caused a marked tachyphylaxis in the rat pressor assay. Moreover, the analogue was a strong competitive inhibitor, with a pA2 value of 7.27 +/- 0.13 of the oxytocin induced vasodepressor response in chickens.


Piperidylalkylindoles. 1. Hypotensive activity of 3-[2-(phenoxypiperidyl)ethyl]indoles. A series of 3-[2-(phenoxypiperidyl)-ethyl]indoles was synthesized and evaluated for hypotensive activity in the spontaneous hypertensive rat. Maximum hypotensive activity appeared when the phenoxy substituent was para substituted and occupied the 4 position of the piperidine ring.


[1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),4-valine,-8-D-arginine]vasopressin, a potent and selective inhibitor of the vasopressor response to arginine-vasopressin. As part of a program in which we are attempting the design and synthesis of an antagonist of the antidiuretic response to arginine-vasopressin (AVP) [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),4-valine,8-D-arginine]vasopressin [d(CH2)5VDAVP] was synthesized and assayed for antidiuretic, vasopressor, and oxytocic activities. The required protected intermediate was synthesized by a combination of solid-phase synthesis and an [8 + 1] coupling in solution. d(CH2)5VDAVP has an antidiuretic potency of 0.10 +/- 0.02 unit/mg, less than 1/10000 that of its parent [deamino,4-valine,8-D-arginine]vasopressin (dVDAVP). d(CH2)5VDAVP is a specific antagonist of the vasopressor responses to AVP. It has an antivasopressor pA2 value of 7.68 +/- 0.05 when tested against AVP. It is also an antagonist of the in vitro oxytocic response to oxytocin (pA2 value = 6.62 +/- 0.07). With its negligible antidiuretic activity, absence of oxytocic activity, and its potent and specific ability to antagonize the vasopressor effects of AVP, d(CH2)5VDAVP is one of the most potent and selective vasopressor antagonists reported to date. It should thus be a useful tool with which to probe the possible role(s) that AVP may play in cardiovascular regulation under normal and pathological conditions.


Statistical aspects of extrapolation of dichotomous dose-response data. A mathematical model based on the hypothesis that carcinogenesis is a multistage process was proposed for the statistical problem of extrapolating the results of bioassay experiments performed at high dose levels of the carcinogenic risk at lower dose levels. This general multistage model had extrapolation characteristic similar to those of the more specific models that are commonly used; a graphic technique based on statistical likelihood procedures provided a measure of the uncertainty in this extrapolation problem. The examples used were 1) exposure to DES and mammary carcinoma and 2) exposure to DMN and liver carcinoma.


Enhancement of growth of allogeneic mouse tumor by the IgG1 fraction of alloantibody preparations. Because staphylococcal protein A binds all the known subclasses of mouse IgG except IgG1, ethanol-fixed staphylococci were used as an adsorbent to prepare IgG1 fractions of anti-BALB/c alloantibody-containing globulins and normal globulins of the same strains. The loss of more than 99% of the IgG2 as a result of this adsorption was demonstrated by immunodiffusion. The IgG1 fractions of C3H and CBA anti-BALB/c globulins were tested for their effect on growth of the BALB/c plasmacytomas MOPC-315 and MOPC-460 in C3H and CBA mice by incubation with the tumor cells before transplantation and by injection periodically thereafter into the hosts. With alloantibody-containing globulins that showed slight enhancement of growth of these tumors, or none, the IgG1 preparations caused considerable enhancement of tumor growth. Control preparations of normal C3H or CBA globulins, or IgG1 fractions similarly prepared from the normal globulins, showed no enhancing effect on the growth of these tumors.


Isolation from a murine fibrosarcoma of cell lines with enhanced plating efficiency in vitro. The technique for the isolation of mutants was applied to establish highly clonogenic cells from a fibrosarcoma (FSA) that had an extremely poor growth capacity in vitro (10(-6)--10(-7) of surviving fraction of cells). After consecutive clonings, the surviving fraction of cells increased to 1--5 X 10(-1), whereas that of the ordinarily maintained culture remained at a low level. Selected clones were analyzed in vitro and/or in vivo. The results indicated that the FSA was composed of heterogeneous cells or cells having a potential variability in cloning ability in vitro, metastatic ability in vivo [lung colony-forming efficiency (LCFE)], and DNA content. The relatively high DNA content of one of the clones, FSA 1233, continued after growth in vivo or in vitro, indicating its hereditary nature. FSA 1233 was also demonstrated to have a lower LCFE when the cell suspension was made from a tumor rather than from a culture in vitro. The difference of surviving fractions between the cells in the two conditions was not enough to explain the difference in LCFE's between them. These cells could grow under either in vitro or in vivo conditions and could be made readily into single-cell suspensions. The cells are, therefore, available as a system for analysis of the response of cells in vitro after in vivo treatment with various agents.


Carcinogenic effect of subcutaneously administered N-nitroso-2,6-dimethylmorpholine in Syrian golden hamsters. N-Nitroso-2,6-dimethylmorpholine (DMNM) was examined in Syrian golden hamsters in a comparative study of N-N-dipropylnitrosamine (DPN) metabolites. DMNM was administered sc, and the results were compared with those of a previous study in which the compound was given intragastrically. DMNM was more toxic when administered sc, and the respiratory tract was the main target organ (with a 100% tumor incidence). With an sc administration, neoplasms occurred earlier in the hamsters than with an intragastric administration, and fewer tumors of the pancreas and biliary tract were found. However, neoplasms of the upper digestive tract and vagina were seen only with sc treatment. These studies indicated the importance of the treatment route but did not substantiate the role of common metabolites, such as DMNM, formed by beta-oxidation from DPN, with regard to induction of a given tumor type.


Tumors induced in mice by N-methyl-N-formylhydrazine of the false morel Gyromitra esculenta. Continuous administration of 0.0078% N-methyl-N-formylhydrazine (MFH) in drinking water to 6-week-old outbred Swiss mice for life produced tumors of the liver, lung, gallbladder, and bile duct. The incidences of tumors in these four tissues were 33, 50, 9, and 7%, whereas in the untreated controls they were 1, 18, 0, and 0%, respectively. The higher dose (0.0156% MFH) given under identical conditions had no tumorigenic effect, since it proved too toxic for the animals. Histopathologically, the lesions were classified as benign hepatomas, liver cell carcinomas, adenomas and adenocarcinomas of the lungs, adenomas of the gallbladder, cholangiomas, and cholangiocarcinomas. Since the edible false morel Gyromitra esculenta contains a high amount of MFH, the human population should be dissuaded from consumption of this dangerous mushroom.


Focal suppression and induction of hyperplasia by the bladder carcinogens butyl(4-hydroxybutyl)nitrosamine and buty(3-carboxypropyl)nitrosamine in organ-cultured rat bladder epithelium. The effects of the bladder carcinogens butyl(4-hydroxybutyl)nitrosamine (BBN) and butyl(3-carboxypropyl)-nitrosamine (BCPN) on proliferating transitional rat epithelium in organ culture were studied. At low to intermediate concentration ranges (0.5--2.9 mM), both compounds appeared to stimulate hyperplasia in some regions of epithelia. The major effect of both carcinogens, however, was to suppress hyperplasia in other regions of epithelia and, at higher concentrations (5--6 mM), to cause necrosis. For comparable concentrations, BBN was more effective in suppressing proliferation and causing necrosis than was BCPN.


Specificity of the deletion of chromosome No. 15 in mouse plasmacytoma: brief communication. Q-banding studies in two independent hyperdiploid mouse plasmacytomas, 63-1 and the NP-38-ABCD subline of MSPC-1, revealed that deletion of a No. 15 chromosome was common. The deletion of No. 15 appeared to result from a translocation between No. 12 and 15 in the NP-38-ABCD, as in most plasmacytomas. In 63-1, however, No. 10 was probably a recipient chromosome of the missing segment from the deleted No. 15, and both chromosomes No. 12 remained intact. These karyotypic features suggest that the deleted No. 15 is a tumor-specific marker chromosome in mouse plasmacytoma and that an abnormality of No. 12 is not essential for development of the tumor. The constitution of chromosomes in the two plasmacytomas remained remarkably stable in their homogeneous modal population.


Antiproliferative activity of highly purified mouse interferon: brief communication. The antiproliferative effect of mouse L-cell interferon, purified by bovine serum albumin--agarose chromatography (which yields a sp act of 3 X 10(8) international reference U/ml protein), and its two subcomponents, obtained by CH-Sepharose 4B chromatography, has been studied in Balb/3T3 fibroblast cultues. Four to 10 international reference U of interferon/ml resulted in a 50% inhibition of DNA synthesis and cell growth, as determined by the incorporation of [3H]thymidine and cell counts, respectively. Hence the degree of inhibition produced by the purified interferon preparations was comparable to that produced by the original crude interferon (sp act, 1.5 X 10(6) international reference U/mg protein). Our results, obtained with L-cell mouse interferon purified by two novel affinity ligands, provided further evidence linking the antiviral and antiproliferative activities of this molecule.


Subpopulations of cytogenetically abnormal cells in fibroblast cultures derived from workers exposed to mineral oil. Fibroblast cultures were grown from skin biopsy specimens from individuals with a high risk of cancer due to occupational exposure to mineral oil. A high frequency of chromosomally abnormal fibroblast subpopulations was found in cultures derived from tissue that had been exposed to the carcinogen, but these aberrant clonal populations were also present in control lines from the same individuals. Abnormal clones formed a greater proportion of the total cell population in the lines derived from the oil-exposed tissue compared with the control lines after a comparable time in culture. This difference in clone size may be a consequence of the in vivo exposure to mineral oil or other environmental agents.


Androgenesis as a cause of hydatidiform mole. Q-band chromosome studies were done in 3 molar conceptuses and their parents, with special attention to six pairs of chromosomes (No. 3, 13--15, 21, and 22) in which polymorphic variants occur frequently. Those six pairs of chromosomes were uniformly homomorphic in moles, whereas at least one of them was heteromorphic in both paternal and maternal cells. Closer analyses provided evidence strongly suggesting that the moles inherited two morphologically identical haploid sets from the father and none from the mother. Thus androgenesis seemed causally related to pathogenesis of complete hydatidiform moles.


Bone cancer among female radium dial workers. Latency periods and incidence rates by time after exposure: brief communication. Bone cancer in 1,250 women exposed to radium while working in the luminous watch-dial industry between 1913 and 1929 were analyzed for times of appearance ("latency periods") and incidence rates over time after first exposure. The lowest radium intake dose associated with bone cancer, among 751 women whose intake doses had been determined, was 202.5 muCi. Mean and median bone cancer latency periods tended to decline, but average survival among women without bone cancer also decreased with increasing intake level. Bone cancer incidence rates over time were compared in 2 intake-dose groups (200--749 and greater than or equal to 759 muCi) by means of an actuarial method that takes competing risks into account. Incidence rates were consistently higher in the higher intake-dose group versus the lower dose group at each 5-year period after first exposure. The variability in the odds ratios across the time periods was not statistically significant, and the actuarial method provided little evidence for an effect of intake dose on the pattern of incidence rate over time. With the use of similar methods, no significant variability was evident in the relative odds of bone cancer over time after exposure between one group of women first exposed to radium at less than 18 years of age and another group exposed when 18 or more years old.


Early clinical study of an intermittent schedule for maytansine (NSC-153858): brief communication. Maytansine, an ansa macrolide, was evaluated in an early clinical trial in 40 adult patients with various solid tumors. Severe nausea and vomiting, sometimes associated with watery diarrhea and abdominal cramps, and liver function abnormalities, mainly elevation of serum glutamic--oxaloacetic transaminase levels, together constituted what we considered dose-limiting toxicity. Mild hematologic toxicity (mainly thrombocytopenia), neurotoxicity, and possibly cardiac toxicity were also noted. No antitumor effect was seen. An iv dose of 0.750 mg/m2 on days 1, 3, and 5 (total dose, 2.25 mg/m2) repeated every 4 weeks is recommended for Phase II trials.


Fluorescent probe study of DNA conformation in briefly heated human squamous cells: brief communication. To determine whether temperature levels commonly encountered in hot beverages denatured the DNA of intact human squamous cells, a fluorescent probe and model system with trypsin-treated desquamated buccal cells were employed. The probe statistically distinguished between single- and double-stranded DNA in a population of suspended cells by the differential bond strengths of DNA-acriflavine complexes over a 4--25 degrees C temperature gradient. The fluorescence of complexed dye was quenched and that of freed dye was restored, which simplified analysis. After cell pellets were admixed with small volumes of suspension medium preheated to 70 or 80 degrees C for 6 seconds, quickly cooled, and stained with acriflavine under conditions favoring the intercalative mode of binding, a temperature-dependent increase occurred in the fraction of complexed dye that was released over the 4--25 degrees C test range. This increase suggested that brief heating partially denatured the DNA of human buccal squamous cells.


Pulmonary fiber embolism and granuloma.

Pulmonary fiber embolism and granuloma. Three infants had pulmonary fiber embolism and granuloma following cardiac catheterization. These complications were traced to the use of nondisposable woven synthetic fiber catheters. The fibrous linings of the catheter may fray and break, and the debris may become disseminated during angiography to the lungs to form emboli and intravascular and extravascular granulomas.


A legacy of Osler. Teaching clinical ethics at the bedside. The teaching of clinical medicine at the bedside is an enduring legacy of the Oslerian revolution in American education. The advantages of teaching clinical ethics at the bedside including dealing with actual cases to maximize personal accountability, reinforcing the relationship between technical competence and ethical decisions, involving the entire health care team, and possibly decreasing the resistance of the medical profession to formal medical ethics. The proposal to teach clinical ethics at the bedside is intended to indicate a primary role for ethicists and clinicians at different stages in the medical curriculum. During the preclinical years of medical school, ethicist-philosophers, assisted by clinicians, should assume primary responsibility for teaching medical ethics. During the clinical years, physicians, assisted by clinically informed ethicist-philosophers, should accept the primary obligation to teach clinical ethics at the bedside.


Severity of underlying disease as a predictor of nosocomial infection. Utility in the control of nosocomial infection. In a prospective study, we determined that severity of underlying disease at time of admission indicates medical patients at unusual risk of nosocomial infection. The nosocomial infection rate was 23.6% in patients with fatal underlying disease, 9.6% in those with ultimately fatal disease, and 2.1% in those with nonfatal disease. After an awareness program that promoted the use of established methods for prevention of nosocomial infections was established, there was a decline of overall incidence of endemic nosocomial infections from 9.2% to 4.8% (P less than .001) within an eight-month period. With subsequent discontinuation of the program, the infection rate rose to 8.1%. Reinstitution of the program resulted in a decline to 5.2% (P = .05).


Acute hemorrhagic cystitis. Industrial exposure to the pesticide chlordimeform. An outbreak of hematuria occurred from May 20 to May 23, 1975, among employees of a chemical packaging plant. Nine of 22 workers who packaged the insecticide chlordimeform in a separate shed became severely ill with abdominal pain, dysuria, urgency to void, or hematuria. None of 18 persons who worked in other areas of the plant were affected. Four additional workers who had packaged the chemical during the previous year had a history of similar symptoms. Bladder biopsy specimens from three affected persons showed severe hemorrhagic cystitis; chlordimeform and 2-methyl-4-chloroaniline, a metabolite of chlordimeform, were present in urine specimens collected three days after exposure. The illness lasted from one week to two months; the workers recovered completely. Chlordimeform that was injected subcutaneously into three cats produced similar, though less severe, changes in the bladders of two animals.


Endobronchial Hodgkin's disease.

Endobronchial Hodgkin's disease. Endobronchial involvement with Hodgkin's disease has been reported infrequently. A 26-year-old woman with previously diagnosed nodular sclerosing Hodgkin's disease had substernal chest pain and a right middle lobe infiltrate. Fiberoptic bronchoscopy showed nodular endobronchial lesions located at the carina, the right mainstem bronchus, and the right middle lobe orifice. A biopsy specimen of one of these lesions showed Hodgkin's disease. The patient was then treated with sequential systemic chemotherapy. Repeated bronchoscopy showed complete resolution of the endobronchial lesions, and the patient has remained in complete remission for 24 months.


Carcinoembryonic antigen test for recurrent colorectal carcinoma. Inadequacy for early detection. Serum carcinoembryonic antigen (CEA) tests were performed on 36 patients with histologically proved locally recurrent or residual malignant disease after resection of colorectal carcinoma but with no clinical evidence of distant metastasis. Only nine patients (25%) had abnormal CEA levels of greater than 5 ng/ml despite the fact that most patients had had symptoms of recurrence for several months. Among the nine of our patients, none had CEA values greater than 5 ng/ml, and only three had levels greater than 2.5 ng/ml (3.4, 3.8, and 4.7 ng/ml). The CEA assay is not a sensitive test for early detection of recurrence of colorectal carcinoma.