Comparison of Type A and nutrient standard menus for school lunch. II. Management aspects. An extensive study compared school lunches planned to meet a specific nutrient standard (NSM) with those planned according to the Type A pattern. Average daily participation, food and labor costs, accuracy of the menus, and differences in the four-week menus between the two methods are reported. Twenty-nine menu planners representing a variety of living environments quickly learned the NSM method and enthusiastically planned and served the Type A and NSM test menus to fifth and tenth grade students. Type A data were collected in the fall and NSM data in the spring of the 1972-73 academic year. Changing from Type A to NSM menu planning resulted in no significant change in lunch participation or food and labor costs. Work functions also did not vary significantly when the menu planning method was changed. Menu planners of varying education and experience successfully planned accurate NSM menus and endorsed the method as an exciting and viable alternative to the Type A pattern. Sixty per cent preferred NSM due to its nutrient assurance, flexibility, and potential for nutrition education.


Comparison of Type A and nutrient standard menus for school lunch. III. Nutritive content of menus and acceptability. The caclulated nutritional value of school lunches for fifth and tenth grade students planned according to the Type A pattern and a nutrient standard (NSM) WEre compared on the basis of meals as planned, served, and eaten. On an "as eaten" basis, menus planned by both methods were low in calories, iron, and thiamin. Although the differences were small, the NSM menus were consistently higher in nutrients, including calories, iron, and thiamin, and lower in percentage of calories coming from fat. The number of schools where the lunches, on the average, furnished less than 60 per cent of the standard for calories, iron, and thiamin was significantly less for NSM than for Type A. Animportant reason for the higher level of nutrients in NSM menus was that a higher ratio of food planned was actually served. In addition, in the case of iron, a higher nutrient: calorie ratio was observed. Food ratings, as determined in the classroom before the meal, correlated positively with food consumption as determined by plate waste analyses. Milk beverages had the highest ratings and consumption, followed by starches, baked goods, sandwiches, and entrées. Salads and vegetables were rated low and consumed least.


Entry-level clinical dietetic practice as viewed by clients and allied professionals. A pilot study. This study was carried out to ascertain whether nutritional care clients and the professionals who serve them hold similar views related to clinical activities performed by entry-level clinical dietitians. Questionnaires were sent to clinical dietitians, their clients, educators, and employers. Clients were asked to state how dietitians had helped them. Dietitians, educators, and employers were asked to rate client-identified activities and other selected activities of dietitians according to their importance to the delivery of nutritional care. Dietitians were also asked to rate these same activities according to the relative time spent in performing them. There was significant agreement among all participating groups on the relative importance attached to client-identified activities, and also among dietitians, educators, and employers as to the relative importance attached to all activities under investigation. The data also imply that the importance dietitians place on an activity will affect the time spent in that activity. It is hoped that this study can be replicated periodically, to provide a dynamic research base for the development of educational objectives based on changing performance requirements which reflect changing client needs.


Eating habits and opinions of teen-agers on nutrition and obesity. Opinions about good nutrition, causes of obesity and its prevention, as well as certain eating habits, were studied in 482 Israeli children (251 boys and 231 girls), thirteen to fourteen years old. Height, weight, and triceps skinfolds were measured. Mean relative weight and relative logarithmic skinfold thickness were close to standard, although 8 per cent of the boys and 9 per cent of the girls weighed more than 120 per cent of standard weight for their age and sex. Weight was closely associated with skinfold thickness. Over two-thirds of both boys and girls believed that daily consumption of milk, bread, fruits, eggs, cheese, meat, and tomatoes is desirable, and about two-thirds stated that overeating is a cause of obesity. More overweight than thin and normal-weight children indicated that, to prevent obesity, all kinds of food are permissible, but only in limited amounts. Most children believed in the fattening value of cakes, sweets, fried and fatty food, potatoes, bread, and nuts. The belief in the fattening value of potatoes, bread, and nuts was shared by a higher percentage of overweight than of under- and normal-weight children. Overweight children, particularly girls, reported eating less bread, cake, and cream, adding less sugar to beverages, and eating sweets and ice cream less frequently than thin and normal-weight children. A higher percentage of the obese group reported skipping one meal and eating no snack at school. Overweight teen-agers appear to be more conscious of their food intake than under- and normal-weight children.


Calcium and phosphorus in diet therapy of uremia. Significant advances have been made in understanding the pathogenesis of renal osteodystrophy. Several factors play a role in the development of uremic bone disease, such as secondary hyperparathyroidism, PTH resistance at the level of bone, abnormalities in vitamin D metabolism, and factors contributing to extraosseous calcification. Through a better understanding of the pathogenetic mechanisms, a more rational approach to the dietary management of patients with chronic renal failure has been possible. In view of present knowledge, the following preventive and therapeutic interventions can be recommended: provision of liberal calcium intake in the diet, appropriate restriction of phosphorus intake, provision of potent vitamin D analogs, and close attention to the calcium-phosphorus product. With careful attention to these recommendations, the bone lesions of secondary hyperparathyroidism and osteomalacia may be minimized and even prevented.


Composition of diets containing 25 and 35 per cent calories from fat. Analyzed vs. calculated values. In a dietary study conducted to evaluate the effects of low-fat, low-cholesterol diets on the reduction of blood lipids in man, meals were analyzed for proximate composition, ten vitamins, fourteen minerals and trace minerals, fatty acids, tocopherols, and cholesterol; Validity of the calculated nutrient composition of the diets was assessed by comparing calculated with determined values. Comparisons were also made of the determined values with 1974 Recommended Dietary Allowances. Analyzed values and those calculated from Agriculture Handbood No. 8 were exceptionally close, except for calcium; By analysis, on a per-kilogram basis, the 35-per-cent-fat-calorie diet more nearly met the Recommended Dietary Allowances for most of the nutrients than did the 25-per-cent-fat-calorie diet. However, on a per-1,000-kcal basis, there were few differences between nutrients in diets with the two levels of fat calories.


Comprehensive evaluation of fatty acids in foods. I. Dairy products. A thorough search of the post-1960 world's literature has produced a voluminous amount of information of the fatty acid content of milk fat. The composition and quantity of fat in cow's milk are affected by many variables, including breed, nutrition, stage of lactation, and season. Seasonal fluctuation in fatty acid content was considered in compiling data. Data were evaluated with reference to adequacy of esterification procedure and gas chromatographic analysis. Techniques for converting methyl ester data to a form suitable for food table use are illustrated. The detailed fatty acid profile of milk fat derived through the current study is presented. Reliable and up-to-date tables of fatty acids in dairy and selected non-milk fat products are provided for the use of dieticians, nutritionists, and workers in food technology and related fields.


Nutritional status of black preschool children in Mississippi. Assessment by food frequency scale. Food frequency data were studied in relation to the nutritional status of 372 black preschool children in three Mississippi counties. The following data were utilized: quantitative dietary intakes for four or seven days, from which intakes of eight nutrients and energy were calculated and frequency of consumption of all individual foods was obtained; and anthropometric (height) and biochemical (hemoglobin) meausres. Six Guttman scales of food consumption frequencies were constructed: in four scales, all foods consumed in four or seven days were assigned to one of nine food groups which formed scale steps; two scales represented foods from single food groups--breads and milk and milk products. The wide range of individual consumption frequencies required special handling of the data, using a method devised by TenHouten in his work on scale gradient analysis. Kendall's tau correlation coefficients were calculated for relationships between all scales and commonly used indicators of nutritional status, including calculated intakes of eight nutrients and energy, height percentiles, and hemoglobin values. Two total food consumption scales based on seven-day dietary intakes were valid indicators of nutritional status, i.e., the scales were significantly correlated with all three indicators of nutritional status. The milk scale was significantly correlated woth two total food consumption scales, height percentiles, and nine calculated intakes; this finding suggests that a milk scale warrants further investigation. This research focused on relationships between the food scales and nutritional status indicators as an initial step in a study of overall family development. According to the family development model, the food scales and scales dealing with other areas of home and family life are all measuring the capacity of the family to process information. The food scale alone, which has meaning for both the nutritionist and the sociologist, has implications for nutrition education in determining what to teach, selecting teachers, and evaluating change in food practices.


Primordial follicles with normal oocytes in the ovaries of postmenopausal women. In ultrastructural studies, the ovaries of postmenopausal women were compared with those of pre- and perimenopausal women. Primordial follicles containing apparently normal oocytes were found in all postmenopausal ovary samples. Differentiating follicles were often found in these samples, but they were in various states of atresia. The findings suggest that the menopause does not result exclusively from exhausation of the primordial follicles.


Medical planners and the geriatric imperative. The health needs of old people demand a change in the attitudes of physicians and social planners. There is a great gap between complicated models for health care and the delivery of that care to the ill elderly. Physicians should have better training in geriatrics in better and more coordinated facilities. Home health services are important. However, it is essential to avoid false starts and to adhere to sound principles. This is the job of the planners rather than the prophets; it is the geriatric imperative.


The longevity of gerontologists.

The longevity of gerontologists. The forces of mortality are the prime determinants of longevity. Longevity is a basic consideration of gerontology and includes the life expectancy of the species, the average expectancy of survival at birth, and the average of lifespan. In the history of the study of old age, for which the modern period began about 1930, there are no reports of the average lifespan for the students of aging. A survey revealed that the average lifespan of 28 special groups (15,000 individuals) was 68 years; this included an average of 68.01 years for 394 gerontologists during the same eras. These figures are comparable because the attainment of a particular status in a profession or vocation is evidence of survival to maturity. Comparison could not be made with data for the general population whose vital statistics begin at birth. The average duration of life for men whose work in part or in whole prior to the 20th century was in gerontology falls midway between the high level of 77 years for classical Greek authors and the low level of 51 years for revolutionary statesmen, and exactly between the levels of life duration for eunuchs and physical and medical scientists.


Correlates of the echocardiographic waves of the mitral valve in normal subjects of various ages. A cardiographic study was performed on 71 subjects including 14 children, 42 young and middle-aged adults, and 15 old persons without evidence of heart disease. The echocardiogram of the mitral valve was recorded in the A mode by an analog method and was compared with the electrocardiogram, phonocardiogram, apex cardiogram, and carotid and jugular tracings, simultaneously obtained. The intervals between the various waves recorded by these methods were measured and the results were compared with those reported in the literature. A comparison of the duration of the intervals in the various age groups showed statistically significant differences. In particular, the intervals between the second heart sound and the peak of the E-wave and the E-F intervals in the echogram were longer in adults than in children and also longer in old persons than in younger adults. This important age difference should always be taken into account before attributing any echocardiographic deviations to disease.


Some differences between elderly people who use community resources and those who do not. This study initially involved 120 subjects in four groups of 30 members each. It was designed to compare institutional aged persons (Jewish Home for the Aged, or JHAs) with ambulatory persons who used community resources (Jewish Community Center, JCCs). Controls were selected from a stratified sample in a community-wide study of the Detroit Jewish population; half of the control subjects lived alone (LAs) and half lived with their families (LWFs); none of them used community resources. All 120 subjects were at least 60 years old. The female:male ratio was 71:49. They were asked to fill in a 442-item questionnaire which yields data about personal and family background, current status, attitudes, interests and self-evaluation. The 30 JHAs were significantly older than the 30 JCCs, but otherwise there were few differeneces. Therefore the focus of the study was shifted to a comparison of the 30 JCCs, who used community facilities, with the 30 LAs and 30 LWFs, who did not. The JCCs were not well educated and were of low economic status. They obtained social gratification through group activities. They had many acquaintances but few close friends whose loss could be a threat. As a group, they seemed content. The LA and LWF groups were better educated, more successful financially, and more likely to derive personal satisfaction from their work. They formed closer family attachments and were more object-oriented, so they were more vulnerable to lossof home and family. Setting high value on individual capacities, they were more likely to be threatened by illness. Any attempt to extend a helping hand to elderly citizens who do not avail themselves of community resources will have to take into account the prevalence of these distinctly different life styles.


Mid-life temperature-transfer effects on life-span of annual fish. When annual fish are transferred from 20 C. to 15 C. at slightly less than the midpoint of lifespan of those kept throughout life at 20 C., the survival of the transferees exceeds theoretical expectations. They live longer than those maintained throughout life at 15 C., which had previously manifested the longest survival. These results indicate that the influence of temperature on life-span is not uniform throughout the life of a poikilothermic vertebrate. The phenomenon of partial temperature-independency had been previously demonstrated in invertebrates.


Incorporation of (14C) leucine into protein and tubulin by brain slices from young and old mice. Tubulin, the protein of neurotubules, aids in the movement of other proteins and organelles within axons and may be involved in the pathogenesis of senile dementia in man. This led us to investigate the effect of age on the synthesis of tubulin and of total brain protein of mice. Brain slices from 5-, 12-, 18-, and 25 mo.-old mice were incubated with [14C] leucine. The slices were then homogenized and tubulin was precipitated from the 100,000g supernate by vinblastine. Protein synthesis was measured by [14C] leucine incorporation into hot trichloroacetic acid-insoluble protein and tubulin was quantitated by [3H] colchicine binding. The 4 age groups did not differ significantly in the relative specific activities of their total protein or of their tubulin. The content of the colchicine-binding protein (tubulin) also was not affected by age. These findings suggest that, at least in mice, aging does not significantly affect the rate of synthesis of brain protein or tubulin.


Effect of age upon the thyroid gland and pituitary thyrotrophs of the rat. Male and female rats ranging in age from birth to 26 months, were used to study age changes in the rat thyroid and pituitary thyrotrophs. The thyroid follicular cells were cuboidal in shape until 10 mo. of age. Between 10-15 mo. the follicular cells became columnar in shape and contained intracellular colloid droplets. After 15 mo. the gland appeared mixed and consisted of both dilated follicles lined with flattened epithelium and hyperplastic follicles. The pituitary thyrotrophs were not demonstrable at birth but were visible at weaning. The size of the thyrotrophs correlated with the morphological status of the thyroid. Cytoplasmic vacuoles were first evident at 10 mo. and became more prominent as age progressed. The presence of large vacuolated thyrotrophs appeared to be related to the senile hyperplastic thyroid. No sex differences were noted.


An apparently paradoxical action of aging: decrease of acute hypoxic mortality in male aged rats. Mortality of SPF male rats due to hypoxic challenge is less in old than in young rats. This apparent antinomy may be related to a decrease in oxygen consumption because of the relation of volume-surface and, in very old rats (590-700 days old), to a selection process wherby only the hypoxiaresistant rats reach old age.


Gerontological data of C57BL/6J mice. I. Sex differences in survival curves. A group of 1,052 C57BL/6J mice (296 males and 756 females) was kept under well-defined, clean laboratory conditions from the age of 6 weeks until natural death. The survival curves of males and females (computer-produced 3, 4, and 5 parameter curves, Gompertz curve histogram) were established and shown to follow a logistic function. The average life-span amounted to 878 plus or minus 10 days for males and 794 plus or minus 6 days for females. These values distinctly exceed comparable values given in the literature. They are attributed to favorable conditions of animal care and to supposed alterations in genetic background. A genetic drift in sex-dependent mean survival time occurred in the genetically unstable C57BL/6J strain between 1966 and 1970. Before this drift, the males died sooner; after it, they lived longer.


Scale-checking styles on the semantic differential among older people. Two groups of older (60 plus) respondents, matched on age but differing in educational level, and a group of young university undergraduates were compared for scale-checking styles on the Semantic Differential. Subjects rated six concepts pertaining to stages of life on 27 pairs of bipolar adjectives. Although the three groups did not differ in frequency of endorsing extreme scale positions, the less well-educated older group showed a greater tendency to use fewer intermediate scale positions and more neutral midpoint positions than either the undergraduates or the group of retired professors emeriti. Data were interpreted as a propensity for older people to emphasize concrete, well-anchored scale positions in making ambiguous multiple-point scale discriminations, a tendency related to educational background but not to age per se.


Retrieval from semantic memory as a function of age. Twenty-four subjects, 12 of whom were in the age range 18-30 years and 12 of whom were between 55-65 years, performed two semantic memory tasks. One task involved the recall of an instance from a designated category starting with a specified letter, and the second task required subjects  to indicate whether a given work was or was not a member of a designated category (the recognition task). There was a differential effect of age on recall and recognition, the older subjects responding more slowly on the recognition task, but not on the recall task. The response times of the older subjects were less affected by the dominance of the to-be-retrieved information than were the younger subjects. These results suggested that subjects in the older age group may have retrieved information faster than the young subjects, but that they required longer to decide upon response.


Behavioral rigidity as a mechanism for facilitation of problem solving for aged rats. Mature-young 5-mo.-old and aged 25-mo.-old rats (N=28 of each age group) at the same level of motivation were given forced-correct-response training trials on a 14 unit T-maze by blocking off all wrong turns. During later test trials in the maze, when the 14 culs-de-sac were open, aged rats made significantly fewer errors than mature-young rats. The effect of distribution of test trials were relatively minor, but comparison of distributed practice groups with control groups not given forced-correct-response training also indicated a strong differential age effect of training procedure on the reduction of errors during test trials. The deleterious effect of age on learning and problem solving is not immutable.


Studies of mortality and morbidity data. II. Mortality from all causes in Ontario Counties during 1964-1968. Age-adjusted mortality rates, for all causes of death, are tabulated for all ages by sex for the 55 Ontario counties and districts. The rates are based on all deaths of Ontario residents during 1964-1968 and 1966 census populations. The consistent trends in rates, both for the two sexes and for various 10- and 20-year age groups, indicate that there is a region of about eight adjoining counties, across the center of the province, which has abnormally high mortality, and two regions to the east and west of York, each consisting of three adjoining counties which have abnormally low mortality. The relevance of these findings to aging studies is indicated, and possible further investigations of them are discussed.


Work and retirement: a test of attitudinal relationships. Recent studies report contradictory findings on the hypothesis of an inverse relationship between work satisfaction and retirement attitude. In an effort to clarify the situation, it has been suggested that only in instances where work acts as a key organizing factor in the workers' lives should the inverse relationship be observed. Data testing these hypotheses were analyzed from a study of employed males aged 50 years of age and older (N=1,922) residing in a midwestern state. Results of this study offer only marginal support for the hypothesis. A work  satisfaction-retirement attitude typology based on combinations of the two attitudinal areas is discussed.


The status and integration of the aged in Japanese society. Japan is an exception to the general rule that modernization causes a sharp decline in status and integration of the aged. Most of the Japanese elders continue to live with their children and perform important functions in the householf. The majority of men over 65 continue to be in the labor force. The elders are also well integrated into their communities through clubs and visits with neighbors. The high status of the elders is reflected in many private and public practices which give precedence to older persons. Thus, even in modern societies, a culture which promotes respect for the aged can maintain high levels of status and integration for its older citizens.


Common themes among morale and depression scales. This paper reports on the intra- and interbattery scaling of three morale and depression batteries comprised of self-reported items: PGC, G-H, and ZUNG. Responses to the three scales were sought from a sample of long-term residents of a state mental hospital. First, the batteries were factor analyzed separately to identify the intrabattery scales; then the resultant scales were compared using canonical correlation and super matrix factor analysis to identify the interbattery themes. These analyses resulted in the identification of a Clinical Depression domain across all three batteries and single independent themes in both the Zung and PGC batteries.


Mood as an indicant of happiness: ags, sex,social class, and situational differences. Does mood vary as a function of age, sec, or situation? In four investigations, 6,452 persons aged 4 to 99 were interrupted at leisure, at home, at school, and at work and asked to assess their mood as being happy, neutral, or unhappy. Moods of happiness and neutrality were each reported about 45% and unhappiness about 10% of the time. Females more frequently reported moods of happiness or unhappiness than males, while mood did not vary as a function of age. Persons at leisure reported more affectively pleasant moods than those at work, at home, or at school. Persons of higher socioeconomic status reported more happy moods than those of lower status. In another study, a class of 255 students was administered various personality scales and then interrupted 21 times over the course of the quarter and their mood indexed. Tested religiosity negatively correlated with frequency of pleasant moods, the Barron Ego-Strength Scale was uncorrelated with frequency of kind of mood, and the Eysenck Neuroticism Scale correlated with frequency of unpleasant moods.


Anticipatory grief and aged widows and widowers. The purpose of this investigation was to explore the preventive value of anticipatory grief on the medical adjustment of the aged bereaved. Data were collected for 81 surviving widows and widowers 6 mo. after their loss. Sixteen of the bereaved had spouses who died of a chronic illness. These two groups were compared on three criteria of medical adjustment: physician office visits, feeling ill without contacting a physician, and use of psychotropic medications. The data indicated that the aged bereaved of a lengthy chronic fatal illness did worse than the bereaved of a shorter chronic illness death. By sex, no significant differences were found between widows and widowers of a short-term illness death. However, differences were noted for the chronic illness category, and within this category for length of chronicity. In both cases widowers showed more medical problems than widows.


Society of the alone: Freedom, Privacy and Utilitarianism as dominant norms in the SRO. The social world of the aged SRO tenant is described and analyzed. Charteristic features include an impoverishment of social roles and relationships which result in a "world of strangers". Dominant norms of SRO life which preclude the establishment of intimacy are examined; these include prescriptive norms of privacy, freedom, and utilitarianism


Splenic regulation of the clinical appearance of small tumors. The Cloudman (S91) melanoma elicits an immune response in syngeneic DBA/2 mice which prolongs the time before the tumor becomes detectable but does not signigicantly alter the growth rate subsequent to its appearance. The spleen can either enhance the immune response and prolong the lag phase when stimulated with high doses of tumor cells or suppress it and shorten the duration at lower doses. This bidirectional effect of the spleen is similar to previously reported activity of regulatory T cells which reside in the spleen. This observation is discussed in contrast to the role of the spleen in animals bearing tumors which elicit concomitant immunity.


Regulation of the release of colony-stimulating activity from mitogen-stimulated lymphocytes. Lymphocytes stimulated by Concanavalin A (Con A) as well as other mitogens release colony stimulating activity (CSA) which stimulated granulocyte and mononuclear cell formation from hematopoietic progenitor cells in vitro. Removal of Con A from lymphocyte cultures by the competitive inhibitor, alpha methyl mannoside, resulted in the cessation of CSA release regardless of the time the inhibitor was added to the culture. However, removal of Con A after 6 hr of incubation had no effect on cellular DNA synthesis and lymphocyte transformation. In addition, vinblastine and cytosine arabinoside completely inhibited DNA synthesis but had no effect on CSA release. CSA release is dependent on an active energy process since it was completely and reversibly inhibited by the inhibitors of protein synthesis puromycin and cycloheximide. These results suggest that CSA release from stimulated lymphocytes requires continuous binding of mitogen and active protein synthesis but is not dependent on DNA synthesis and cell proliferation.


Properties of conjugated protein immunogens which selectively stimulate delayed-type hypersensitivity. If bovine serum albumin (BSA) is covalently conjugated with dodecanoic acid, its ability to stimulate delayed-type hypersensitivity (DTH) is enhanced whereas its ability to stimulate antibody production is suppressed. Conjugates of BSA prepared with negatively charged succinyl groups and positively charged amidine groups were unable to stimulate any detectable DTH to BSA even though their ability to bind anti-BSA antibody in a radioimmunoassay was similar to that of dodecanoyl-BSA which stimulated strong, sustained DTH. By analyzing a series of conjugates of BSA with fatty acids of varying chain length, we found that enhancement of the ability of a preparation to stimulate DTH to BSA could be separated from the suppression of its ability to stimulate antibody formation. The ability of a preparation to stimulate DTH correlated with the covalent conjugation of a large number of hydrophobic groups whereas the suppression of the ability to stimulate antibody formation correlated with covering of antibody-combining sites as measured in a radioimmunoassay.


Evidence for macrophage C3d-receptor active in phagocytosis. Evidence is presented that guinea pig peritoneal macrophages possess membrane receptors able to recognize the C3b inactivator-cleaved third component of complement. This conclusion is based on the finding that rosette formation and phagocytosis by macrophages of EA-IgM-C1423 were equal regardless of whether EA-IgM-C1423 had been pretreated with C3b inactivator or not.


Studies on the contact sensitization of man with simple chemicals. III. Quantitative relationships between specific lymphocyte transformation, skin sensitivity, and lymphokine activity in response to dinitrochlorobenzene. Dinitrochlorobenzene (DNCB) coupled to peripheral blood erythrocytes or leukocytes forms a particulate complex, DNCB-antigen. The addition of DNCB-antigen induced blastogenesis and DNA synthesis in leukocyte cultures from DNCB-sensitized human subjects and not in leukocyte cultures from nonsensitized controls. In general, sensitized subjects who displayed a higher degree of cutaneous reactivity to DNCB, as manifested by duration and intensity of dermatitis, also showed a greater blastogenic response to DNCB-antigen in vitro. This quantitative correlation, however, was not invariant. Certain soluble factor(s), or lymphokines are released following the addition of DNCB-antigen to leukocyte cultures prepared from some sensitive subjects who were rechallenged one or more times with DNCB. These lymphokines induce blastogenesis in secondary target leukocyte populations from nonsensitized subjects. Extended studies are presented which slow little or no lymphokine activity in peripheral blood leukocyte cultures during a primary immune response, despite high degrees of blastogenic activity in response to DNCB-antigen. Significant lymphokine activity was observed only following additional rechallenge with DNCB. Blastogenesis and skin reactivity specific for DNCB have been shown to develop at about the same time during a primary immune response. This, along with the quantitative correlation shown in this communication, suggests that both processes probably reflect thymic-dependent cellular immunity. The appearance of lymphokine activity following rechallenge with DNCB suggests that DNCB-induced lymphokines may represent an amplifying mechanism of the cellular immune response that involves recruitment of previously uncommitted lymphocytes.


Assay of therapeutic doses of methotrexate in body fluids of patients with psoriasis. A microbiologic technique for the assay of methotrexate (MTX) in urine, serum, erythrocytes, feces, and skin is described. The accuracy of the method equals that of routine microbiologic assays of folic acid. Important differences in serum MTX levels in psoriatic patients during the 24 hours after standardized intravenous and intramuscular administration were demonstrated. Repeated intravenous doses tended to be cleared from the blood univormly. After oral doses many patients achieved peak serum levels within 2 hr. with fall of level by 4 hr. Others achieved lower levels and responded less well clinically. Persistence of high serum levels at 24 and 48 hr did not confer obvious clinical benefit or necessarily give rise to by renal function when the creatinine clearance was greater than 50 ml/min. However, impaired renal function was clearly correlated with slow clearance. Routine measurement of MTX blood levels is of value in patients with suspected malabsorption or partial renal failure.


Organ culture of human skin in chemically defined medium. Explants of adult human skin were grown in vitro in a chemically defined medium without serum. Under these conditions the epidermis was well maintained for up to 7 days, during which time new stratum corneum formation was observed. Most often the stratum corneum was orthokeratotic and associated with a prominent granular layer. Parakeratotic regions were also evident and these were not associated with a granular layer. During the first 5 days in culture there was a signficant increase in DNA synthesis (as measured radioautographically) and mitosis.


A comparison of His bundle electrograms recorded from the aortic root and from a plaque sutured near the His bundle. For careful analysis of His bundle electrograms in the dog it is useful to have a stable rather than moving recording site. In this study we have compared the characteristics of His bundle electrograms recorded by two methods in each of ten anesthetized dogs. Records obtained with a Hoffman-type plaque electrode sutured in the vicinity of the His bundlewere not significantly different from ones obtained with a recording catheter wedged in the aortic root. In addition to measurements made during the resting state, comparisons also included those during selectively  produced acute but transietn complete A-V block, sinus bradycardia, A-V junctional tachycardia, A-V junctional bradycardia, and various degrees of incomplete A-V block. A stable and accurate His bundle electrogram can be obtained from the aortic root and has the experimental advantage of not having to open the right atrium or place sutures near the A-V node of His bundle.


In vivo evidence for the functional heterogeneity of transferrin-bound iron. I. Studies in normal rats. Functional heterogeneity of iron atoms bound to transferrin as postulated by Fletcher and Huehns was demonstrated by in vivo studies in rats. Serum transferrin was selectively double-labeled by adding 59Fe to 90 per cent saturation of iron binding capacity, incubation with rat reticulocytes to reduce the saturation to 50 per cent or less, and then adding back 55Fe. Rats were killed at various times after intravenous injection of this double-labeled transferrin, and the ratios of 55Fe to 59Fe were measured in plasma, circulating erythrocytes, bone marrow and spleen heme, whole liver and isolated hepatic Kupffer and parenchymal cells, and in small intestinal segments. Selective uptake of erythroblast-oriented 55Fe was observed in red cells and heme from marrow and spleen; storage-oriented 59Fe was selectively removed by liver cells and small intestine. Greater polarization was achieved by using Fe3+-nitrilotriacetic acid instead of ferrous ammonium sulfate and by injecting transferrin selectively double-labeled at less than 50 per cent saturation. These studies confirm the hypothesis of Fletcher and Huehns that the iron atoms of transferrin are functionally different and support the concept that transferrin plays a selective role in the distribution of iron to tissues in the rat.


In vivo evidence for the functional heterogeneity of transferrin-bound iron. II. Studies in pregnant rats. Iron atoms from the two iron-binding sites of transferrin in the maternal plasma were selectively transferred to fetal tissues across the placenta of the pregnant rat. Rat serum transferrin was selectively double-labeled with 55Fe bound to the A-site and 59Fe bound to the B-site and injected intravenously into pregnant rats at 11 to 20 days gestation. Ratios of 55Fe to 59Fe were measured in various maternal and fetal tissues sampled from 30 to 120 minutes after injection. In the maternal tissues preponderance of A-site 55Fe was observed in circulating red blood cells and in heme extracted from bone marrow and spleen; B-site 59Fe predominated in the liver parenchymal cells and proximal small intestine. As predicted by the Fletcher-Huehns hypothesis, placental transfer of radioiron resulted in a selective concentration of A-site 55Fe in all the fetal tissues including the fetal placenta, yolk sac, whole fetus, and in the separately analyzed liver heme and ferritin and in fetal blood. When the placenta was bypassed by direct injection of the selectively double-labeled transferrin into the umbilical vein, a reversal of the 55Fe/59Fe ratios of heme extracted from the fetal liver was observed. These studies confirm the concept of functional heterogeneity of iron atoms bound to transferrin and indicate that the placenta of rats between the eleventh and twentieth day of pregnancy selectively removes erythroblast-oriented iron from transferrin and diverts it to fetal tissues.


One-stage assay of heparin.

One-stage assay of heparin. A simple and rapid one-stage plasma heparin assay based on the heparin-dependent neutralization of activated factor X (Xa) is described. Factor Xa is prepared in a concentration adjusted to produce a clotting time of 18 to 20 seconds when heparin-free plasma is tested in the system. The assay incubation mixture contains "standard human plasma", the heparinized test plasma, cephalin, and factor Xa. Clotting times are measured automatically after incugation and calcium addition. A linear relationship was found between the log of the clotting time and the heparin concentration for the standard curve from which the heparin level is determined. The lower limit of sensitivity is about 0.05 unit heparin per milliliter. Dilution of test plasma is required to bring the heparin level to between 0.05 and 0.2 unit per milliliter. The standard curve is reproducible with a coefficient of variation of 2 to 4 per cent. Ten different, nonheparinized samples had clotting times of 18.9 plus or minus 1.0 (plus or minus 2 S.D.) seconds. Theoretically calculated and experimentally determined heparin levels after pulse injection of heparin agreed well in 5 volunteer subjects with r values between 0.93 and 0.99. This assay is not affected by normal variation in the plasma levels of fibrinogen, prothrombin, and factor V or by the plasma defects induced by coumadin.


Coil planet centrifugation and its application to the observation of altered membrane properties of erythrocytes in hepatobiliary disorders. A coil planet centrifuge (CPC) is an apparatus aiming to obtain a centrifugal force exerting on particles suspended in a fluid in a coiled polyethylene tube (coil) which makes self-rotation around its axis and revolution around the principal axis simultaneously. If a linear osmotic gradient is prepared in the coil and a small amount of blood is applied to it and subjected to centrifugation, one is able to observe the membrane properties of erythrocytes in terms of the shift of hemolysis band appearing in the coil with high accuracy and precision. Coil planet centrifugation was applied to the observation of altered membrane properties of erythrocytes in hepatobiliary diseases. Remarkable shifts of end-point of the hemolysis band going in parallel with the severity of damage were visualized. Study as to its cause revealed that increased free cholesterol content of erythrocyte membrane which was the result of plasma cholesterol Esterstürz due to inhibition of lecithin-cholesterol acyltransferase by stagnant bile acids was responsible for this phenomenon. Elevation of serum bile acid concentration and increased serum leucine-aminopeptidase were closely correlated to the shift of hemolysis end-point toward the low osmolal side. CPC may be useful for detection and chasing the clinical course of patients with hepatobiliary disorders.


Structural analysis of compartmental models for the hepatic kinetics of drugs. The structure of some compartmental models for the analysis of the hepatobiliary kinetics of bromosulphalein (BSP) was studied in order to evaluate their adequacy in the estimation of the processes involved in the hepatic metabolism of drugs, namely uptake, conugation, and biliary excretion. Biological measurements were obtained from 4 cholecystectomized patients with a biliary T-tube. Blood and bile specimens were taken at various intervals after the administration of a single intravenous dose of BSP and analyzed for both direct BSP quantitation and chromatographic separation and estimation of BSP metabolic fractions. The structural analysis was carried out by using a mathematical model that described the kinetics of BSP. By means of computer simulations different measurement situations were analyzed, showing for each experimental condition the available information and the degree of accuracy of each estimated parameter. The obtained results show that the use of compartmental models can provide a useful theoretical framework by which the experimental data can be interpreted for the evaluation of the hepatobiliary metabolism and for a discriminant analysis between different physiopathological conditions.


Conditioned suppression of behavior maintained by intracranial stimulation as a function of stimulation intensity. Conditioned suppression was demonstrated in two experiments with rats lever pressing on a fixed-ration 1 schedule for lateral hypothalamic intracranaial stimulation (ICS)'n Experiment I, conditioned suppression of responding for low-intensity ICS was obtained with a moderate intensity of foot shock, In Experiment II, low and high intensities of ICS were alternated within the same session and the same animal The suppression that was exhibited with low intensity ICS was minimal or absent with high-intensity stimulation, despite the pairing of foot shock with each warning stimulus. Conditioned suppression was a function of ICS intensity, and was independent of response rates. The inverse relationship between ICS intensity and degree os suppression is consistent with a motivational analysis of conditioned suppression. Previous reports of resistance to suppression of behaviors maintained by ICS may now be attributed to the use of high-intensity stimulation.


A photoluminescence technique for detection of gunshot residue. Rapid, convenient detection of gunshot residue on the hands of a suspect, following a shooting, can be accomplished by the photoluminescence determination of the presence of lead (Pb) and antimony (Sb), which originate in the cartiridge primer. Following the firing of a gun, the backs of both hands are washed in a stream of distilled water. Each hand washing is filtered, and the residue collected on a membrane filter is dissolved in hydrochloric acid. Lead(II)and Sb(III) form chloride ion complexes with the acid, which luminesce strongly upon selective ultraviolet excitation at low temperature. Upon excitation, the Pb and Sb complexes emit light with maxima at wavelengths characteristic for the two metallic elements. By the use of this procedure, it is possible to detect as little as 1.0 ng of Pb and 10 ng of Sb. The total time for sample collection and analysis is less than 30 min.


Ballistic studies and lethal potential of tear gas pen guns firing fixed metallic ammunition. Illegal older model and foreign-made tear gas pen guns as well as illicitly manufactured pen guns were used to fire revolver or pistol cartridges of calibers .22, .25, .32, .38, .44 Special, and .44 magnum, as well as rifle cartridges of caliber .270. Velocity, range of accuracy, impact kinetic energy, and gelatin block penetrability of bullets fired from the various cartridges are presented. The characteristics of recovered bullets, cartridge casings, and firing pin impressions are described, and the hazards of these weapons to users and potential victims are discussed.


The interpretation of impact fractures in glassy polymers. While this study was not exhaustive of the area of impact fractures in glassy polymers, it does demonstrate that there are some significant differences between fractures in polymers and those encountered with glass. Those differences can be summarized as follows: (1) the occurrence of pronounced, highly curved hackle marks, which could in many instances be mistaken for conchoidal marks;(2)the appearance of the beveled edges bordering the cratering on the side opposite origin of force; and (3) a more apparent tendency toward an inverse relationship of muzzle velocity and energy to radial fracture length and degree of curving along crater boundaries. The physical laws applicable to the fracture of glass are identical to those extant in the fracture of glassy polymers; no new forces are at play. All of the differences are capable of being explained in terms of the differences in flexibility and flow between glass and polymers, and the resulting differences in tension development and fracture propagation.


Automotive body primers: Their application in vehicle identification. An approach to vehicle identification based on the varied primer color combinations used by the automobile manufacturers is outlined. A description is given of the primer color combinations found on a number of domestic and foreign cars. The expediency of this system of vehicle identification by successive elimation is discussed.


Multiple animal bite wounds: A case report. A case of multiple animal bite wounds is presented along with the techniques used to apprehend the culprits. The victim was a 13 month-old black female who had in excess of 80 puncture wounds. Initially the wounds were thought to be caused by a mechanical instrument but, after an autopsy, were determined to be caused by a large animal. Two German shepherd dogs were apprehended and impressions of their teeth compared favorably with the wounds from both the casts made from the body and the body itself. The etiology of the wounds was further substantiated by microscopic examination of one of the wound sites. The identification of bite wounds and the techniques used to confirm the identity of the culprit are discussed.


Tool marks in bones and cartilage.

Tool marks in bones and cartilage. The identification of the implement used is an important factor in the explantion of the causes of violent deaths. Hitherto existing knowledge has been almost exclusively confined to the damages to skull bones. This paper draws attention to tool marks in the area of pierced rib cartilage and considers the possibilities of their analysis. The evaluation of saw marks is further discussed on the basis of sawing experiments. Also, there are features and peculiarities which can help to solve the problems posed by criminal dismemberment.


Fatal anaphylaxis after intravenous iron dextran. This report records the first reported case of a fatal anaphylactic reaction to an intravenous infusion of iron dextran. An elderly woman was given an infusion of iron dextran in 5% dextrose. Shortly after the infusion started, she developed laryngeal stridor, shock, respiratory arrest, and died despite attempts at resuscitation. Necropsy findings are described and are consistent with death due to anaphylaxis. With the increased parenteral use of dextran and iron dextran complexes it is important for the clinician to be aware of the hazards of anaphylactic reactions. Since the reactions generally occur shortly after the administration has begun, a physician should be in attendance during the infusion of the first 25 cm3 (5 to 10 min). He should be able to promptly recognize and treat the asphyxia and hypotension should it occur. It is also important for the pathologist to be aware of the occurrence of anaphylaxis after the use of these drugs. However, the cause of death should not be based solely on the presence of classic clinical features of fatal anaphylaxis. Specific features of anaphylaxis should be searched for at autopsy and other causes of sudden death must be ruled out.


Dissecting aneurysm of coronary artery associated with drug abuse and pulmonary lesions. A dissecting aneurysm of the coronary artery (DACA) associated with cystic medial necrosis was discovered during the necropsy of a 32-year-0ld black man with evidence of intravenous drug abuse. Microscopic examination of the lungs revealed striking angiomatoid conversion of pulmonary arterioles. The cause of death and the possible relationship between the pulmonary vascular lesions and the DACA are discussed.


The screening of blood by gas chromatography for basic and neutra drugs. A GC procedure is described for the screening of biological fluids for the presence of basic and neutral drugs. Extracts are chromatographed simultaneously on a two-column system designed so that a wide range of drugs can be detected. A majority of the drugs is readily detectable in blood in concentrations of 0.1 mg per 100 ml. The procedure is illustrated with examples of casework as well as examples of "spiked" blood samples.


Shock therapy and psychiatric malpractice: the legal accommodation to a controversial treatment. Shock therapy has developed over the years into an accepted form.of psychiatric treatment for relieving the symptoms of certain mental illnesses. The development of shock therapy did and still does take place in a legal environment which leaves the reasonable psychiatrist free to experiment. The discovery of muscle-relaxing drugs and their introduction into the treatment procedure were undoubtedly encouraged by the possibility of malpractice suits arising from bone fracture caused by rapidly contracting muscles. Today the incidence of malpractie suits involving shock therapy has been reduced, and a reasonable psychiatrist exercising care remains free to treat without concern over the possibility of a successful malpractice action.


Characterization of different plaque-forming and defective temperate phages in Agrobacterium. Four Agrobacterium tumefaciens temperate phages (PB2A, PB6(omega), PV-1(LV-1) and PS8), were shown to have the same genome size. Moreover hybridization experiments by the heteroduplex method and electron microscopy showed a 100% homology between these four phage genomes. Indications for lysogeny were found by direct means for the Agrobacterum timefaciens strain 396, Agrobacterium radiobacter strain 8149 and Agrobacterium species 0362 and by the electron  microscope negative staining technique for the A.tumefaciens strains b6-806,b6-6,b6s3,b2as,cv-1,4452,11156,11158,396, and 925; for A.radiobacter strains tr-1 and 8149, the latter being bi-lysogenic, and for the A. species 0362. These isolated phage particles, most of which appear to be defective, could be grouped into different classes. No particles could be detected in the lysates of A. tumefaciens RV3, A. radiobacter strains 4718 and S1005, and A. species 0363. Further characterization by genome size was carried out for the defective temperate phages PB6-806, P4452,P8149 and P0362. No evidence for homology between PB6-806 and PB6 omega could be found. The defective phages PB6-806 and P4452 showed the same morphology but a different genome size, whereas the two phages P0362 and P8149 had a very different morphology and genome size.


Miniphage-a class of satellite phage to M13. Satellite or defective bacteriophage particles can appear in extensively recycled stocks of coliphage M13. These particles, herein known as miniphage, replicate using the wild type bacteriophage as a helper. Their physical properties (u.v. spectra, sedimentation of DNA and bacterophage, electrophoretic moblitiy) are described and a method for the isolation of specific satellite bacteriophage is presented.


Tubular particles in a case of recurrent lymphocytic meningitis followed by amyotrophic lateral sclerosis. A patient suffered recurrent episodes of aseptic lymphocytic meningitis for many years and then developed amyotrophic lateral sclerosis (ALS). Immune-complexes were deposited in the renal glomerular basement membrane and mesangia. The necropsy study revealed both lymphocytic meningitis and ALS. Study of the motor neurons with the electron microscope revealed proliferation of endoplasmic reticulum, small cytoplasmolytic areas and focal neurofibrillar accumulations in axons. Interwoven, serpentine 10-15 nm. tubules first appeared with ER proliferation and, presumably at a later stage, were sometimes present in large masses. These tubules might be virus material but virus cultures, including tissue culture, and animal inoculations have thus far been negative.


The effect of neonatal thymectomy on Tamiami virus-induced central nervous system disease. Tamiami virus, a member of the arenavirus group, produces an acute CNS disease in suckling mice manifested primarily by cerebellar ataxia, paralysis, convulsions, and death. Animals that survive are left with an asymptomatic cerebellar heterotopia. Neonatal thymectomy prevents both acute CNS disease and the resultant cerebellar heterotopia despite equivalent titers of virus and concentrations of viral antigen in the brains of both thymectomized and nonthymectomized infected mice. Inflammatory CNS disease and cerebellar germinal cell necrosis do not develop in thymectomized mice examined more than three months after infection. Viremia and complement-fixing antibody occur in both groups of mice with slightly higher antibody titers in nonthymectomized mice. Tamiami virus-induced cerebellar heterotopia appears to be immunologically-mediated, but the immunopathologic cerebellar lesion differs from the frank necrosis of the brain produced by both Tacaribe and LCM virus in newborn mice.


Cysteine-S-sulfate: brain damaging metabolite in sulfite oxidase deficiency. Cysteine-S-sulfate is an abnormal metabolite discovered in the urine and blood of a patient with cysteine oxidase deficiency, a rare disorder of sulfur amino acid metabolism associated with brain damage and mental retardation. The molecular structure of cysteine-S-sulfate closely resembles that of glutamate and related acidic amino acids which have both neuroexcitatory and neurotoxic properties (excitotoxic amino acids). Here we demonstrate that cysteine-S-sulfate induces the glutamate type of neuropathology in the rat central nervous system when administered subcutaneously to infants or intracerebrally to adults. It is postulated that cysteine-S-sulfate may be the neurotoxic agent responsible for brain damage in sulfite oxidase deficiency. The possibility that other excitotoxic amino acids could play occult roles in other unexplained neuropathologic conditions is discussed.


A presynaptic complex in the giant synapse of the squid. A presynaptic complex consisting of thin lamellae associated with vesicles was found frequently in presynaptic terminals of the squid giant synapse. The lamellae, made of osmiophilic material, had an average length and width of about 10 mum and a thickness of 30 nm; they were of rectangular shape. While most frequent in the axoplasm of the most distal, and largest, terminal of the presynaptic giant axon, the lamellae were found also in smaller terminal branches of this fibre; They have not been observed in the proximal parts of the presynaptic or postsynaptic giant axons. Vesicles the size of synaptic vesicles surrounded the sides of the lamellae. The presynaptic complex resembles the synaptic ribbons in sensory cells.


Zonulae occludentes of the myelin lamellae in the nerve fibre layer of the retina and in the optic nerve of the rabbit: a demonstration by the freeze-fracture method. Ridges and grooves composing extensive zonulae occludentes are revealed by the freeze-fracture method on split myelin lamellae in the nerve fibre layer of the retina and in the optic nerve of the rabbit. The junctions are located immediately internal to the outer loop of the myelin sheath and in corresponding areas of deeper myelin layers. They follow a straight or gently undulating course along the axis of the fibres. Only at the paranodal region of nodes of Ranvier do they deviate and assume a transverse course, The strands of these zonulae occludentes probably represent the radial thickenings of the intraperiod line described in thin sections.


Ultrastructure of motor end-plates during pharmacologically-induced degeneration and subsequent regeneration of skeletal muscle. A local anesthetic, methyl-bupivacaine was injected into the planta of adult mice, and the ultrastruct of motor end-plates was studied during the degenerative and regenerative cycle induced in lumbrical muscles. Muscle degeneration took place during the first day after drug administration. The postsynaptic part of the neuromuscular junction completely degenerated as did the whole injured muscle fibre. Nerve terminals, however, remained unaffected. By the second day after muscle injury, axon terminals were enclosed within Schwann cell cytoplasm and thus became separated from the residual sarcolemmal tube. One to three days later, when myotubes were formed by fusion of the surviving myoblasts, the layer of Schwann cell cytoplasm on nerve terminals was discontinuous. Subsequently nerve terminals approached the regenerating muscle cell and the subneural apparatus began to differentiate. Slight depressions and furrows appeared on the myotube surface below the nerve ending and the myotube membrane, covered with basement membrane, became undercoated by dense material in this region. Where the distance between nerve ending and myotube was reduced to that found in the normal neuromuscular junction, i.e. to about 500 A, junctional folds were formed. Fourteen days after drug administration, newly formed end-plates were indistinguishable from those in normal control lumbrical muscles.


Degeneration and regeneration of adrenergic nerves in mesenteric blood vessels, iris and atrium of the rat after 6-hydroxydopamine injection. Degeneration of adrenergic axons after 6-hydroxydopamine (6-OH-DA), 2 times 68 mg kg-1 i.v. within 6h, and the subsequent regeneration process over the following 205 days were studied in rat mesenteric vessels, wight atria and irides, using the histochemical fluorescence method of Falck and Hillarp. The objective of the study was to determine why noradrenaline is less depleted and recovers much more rapidly in the mesentery than in other tissues after 6-OH-DA (Finch et al., 1973). The mesentery was further studied by electron microscopy and noradrenaline content analyses, until day 29 after 6-OH-DA treatment. Virtually all adrenergic terminal axons in these tissues were destroyed one day after 6-OH-DA. The large nonterminal axon bundles which occur along the mesenteric vessels and rarely in the heart survived and revealed an intensified catecholamine fluorescence; correspondingly, the mesenteric noradrenaline content was only reduced to 29% of control values. In contrast, such large nonterminal axon bundles were not observed in control iris preparations, and no adrenergic fibres survived in the irides, as suggested by fluorescence microscopy. Regenerating axons were observed in all organs after 3-8 days. The number of nerve terminals along the circumference of the external elastic lamina, as observed in ultrathin cross sections of mesenteric vessels, appeared virtually normal 4 weeks after treatment. Meanwhile, the noradrenaline content of the mesentery returned to approximately 85% of control values. As suggested by fluorescence microscopy, complete adrenergic regeneration occurred in mesenteric vessels between days 46 and 105, while regeneration in atrium and iris was incomplete even at day 205; The density of adrenergic axons in the iris, morphometrically determined, was only 76% and 88% of controls on days 160 and 205, respectively. The survival of the many large nonterminal axon bundles in the mesentery with increased NA content explains the relatively small NA depletion of the mesentery; The rapid recovery of the mesenteric NA content is due to faster regeneration of adrenergic terminal axons in the mesentery as compared with iris and atrium. This is tentatively explained in terms of sprouting from the large axon bundles surviving close to the destroyed terminal axons of the mesenteric vessels, whereas in the other tissues no (iris) or only a few (atrium) large nonterminal axon bundles occur and persist to act as a source of quickly regenerated terminal axons.


Morphological changes associated with stretch in a mechano-receptor. The S neurons of decapod crustacean coxal receptors respond to a constant stimulus with a steady-state response lasting for at least 20 min. This property makes it possible to fix neurons in the stretched or relaxed condition by rotating and pinning the coxa up or down respectively. In specimens perfused with 5 mM lanthanum chloride before fixation, it was found that the extracellular space around the nerve terminals, particularly the naked tubular endings, is open to ions. The cross-sections of the tubular processes (dendritic fingers) are about 25% smaller in stretched specimens, and the secondary dendritic branches connecting the fingers with the remainder of the dendrite appear shorter and thicker. The presence of mitochondria at the periphery of the main part of the dendrite and in the secondary branches, but not in the fingers, is interpreted as evidence for an electrical model similar to that proposed for vertebrate photoreceptors. The observed morphological effects of stretch are discussed in terms of this model.


Injection of cymopapain into intervertebral discs. Preliminary report on 72 patients with symptoms of disc disease. The author presents an evaluation of 72 patients given intradiscal chymopapain as the treatment for symptoms related to ruptured intervertebral disc. The rationale, criteria for patient selection, risks, and results are described. The author believes thatt this early follow-up suggests tha chymopapain may have a place in the treatment of symptomatic disc protrusions and extrusions.


Comparison of intervertebral disc disease treatment by chymopapain injection and open surgery. Chymopapain chemonucleolysis was performed on 100 patients with primary lumbar intervertebral disc disease. The results were compared with those of 174 patients who underwent laminotomy, foraminotomy, and discectomy. Primary lumbar intervertebral disc disease was arbitrarily divided into degenerative, complex, previous surgical, and simple disc syndromes. No difference was seen between chemonucleolysis and surgery in the first three divisions; between 55 percent and 60 per cent of patients responded successfully to treatment. In the simple disc division 89 per cent of the surgical and 60 per cent of the chemonucleolysis patients had successful results.


Transverse axial tomography of the spine. Part 1: axial anatomy of the normal lumbar spine. The authors describe the technique of transverse axial tomography of the spine and give a detailed description of the axial anatomy of the normal lumbar spine from L-4 to the sacrum. They demonstrate a specific repetitive pattern of intraosseous and articular segments, and stress the importance of the articular processes in shaping the vertebral canal and the intervertebral foramina. The authors believe axial tomography to be a simple, noninvasive radiological technique that allows cross-sectional visualization of the vertebral canal and articular processes in the living patient.


Experimental cerebral vasospasm. Part 2: effects of vasoactive drugs and sympathectomy on early and late spasm. The authors report the effects of vasoactive drugs and sympathectomy on experimental spasm using vertebral angiography. Papaverine and isoxsuprine injections into the vertebral artery released both early and late spasm. The antiserotonin agent, methysergide, adn the alpha adrenergic blocking agent, phentolamine, released early but not late spasm. In sympathathectomized dogs, early spasm was milder than in untreated dogs; however, late spasm was the same as in untreated dogs. The authors discuss an etiological difference between early and late spasm.


Bifrontal decompressive craniectomy in the management of head trauma. Retrospective analysis of 13 patients who had bifrontal decompressive craniectomy for the management of posttraumatic cerebral edema shows a significant decrease in expected mortality, but severe morbidity in the survivors. Only one patient returned to the pretrauma level of neurological function. No correlation could be found between the quality of survival and the neurological or operative findings. The need for more accurate prognostic criteria in the evaluation of severely head-injured patients is discussed.


Management of carotid-ophthalmic aneurysms. The authors present 26 cases of carotid-ophthalmic aneurysms that were surgically treated. Contrary to the opinion that these aneurysms, which often are of giant size, must be treated conservatively or by common carotid ligation, the authors favor radical surgery, believing that carotid ligation does not provide assurance against the risk of rebleeding, and frequently is associated with failure to restore useful vision. Often these aneurysms have a neck more suitable for ligation than shown by angiography, since a giant aneurysm may overlap the carotid artery in the angiogram. Preoperative criteria and some details of radical treatment are discussed.


Surgical embolization of cerebral arteriovenous malformations through internal carotid and vertebral arteries. Long-term results. The authors describe the clinical results of surgical embolization in 55 patients with large cerebral arteriovenous malformations. Follow-up intervals ranged from 2 months to 14 years, averaging 4 1/2 years. The authors believe the procedure is safe in properly selected patients and is useful as a preliminary to direct surgical excision. It relieves associated headaches, and usually reverses or stabilizes a progressive neurological deficit. The potential for seizures probably is not altered. The incidence of hemorrhage following embolization is low for patients with no previous history of hemorrhage; however, the procedure does not reduce the likelihood of recurrence in patients with a prior history of hemorrhage.


Psychological improvement following arteriovenous malformation excision. Case report. A patient with a right frontal lobe arteriovenous malformation demonstrated progressive intellectual deterioration on neuropsychological tests. Following complete excision of the arteriovenous malformation, the patient's visuomotor function and visual recall were greatly improved, probably the result of elimination of arteriovenous shunts that were taking blood away from functional tissue.


Angiographic demonstration of congenital absence of both internal carotid arteries. Case report. The authors present angiographic demonstration of bilateral, congenital, total absence of the internal carotid arteries in a patient with subarachnoid hemorrhage. Angiography demonstrated complete absence of both internal carotid arteries. The intracranial blood supply had been provided by communication between a hypertrophied basilar artery and the circle of Willis through the posterior communicating arteries. An aneurysm, believed to be the site of the subarachnoid hemorrhage, arose from the basilar artery. Absence of the carotid canals substantiated the congenital nature of the anomaly. The related embryology is reviewed.


Experience of tumors in a British plant handling 3 3' dichlorobenzidine. Dichlorobenzidine has been handled at a plant in Britain over the past thirty years. No case of cancer of the bladder has been found in the exposed population. The population of two hundred and 25 is not large enough to prove DCB will not cause tumors, but a negative incidence, taken with American experience and European figures, (unpublished) suggest that the measures advocated by Scott and Williams and at present adopted provide a satisfactory code of practice.


Development of physical profiles for specific jobs. Inherent risk of injury associated with heavy physical work tasks frequently obviates direct job analysis -- content validity -- for predictive or diagnostic purposes. A common alternative is an appraisal of the physical attributes manifest by the job requirements and the selection of tests of related physical factors. 241 job applicants were given a test battery composed of 40-items at the University of California Medical Center, Sacramento, California. A factor analysis reduced the initial 40-item test battery to an unweighted 6-item field test battery FTB. Standards scales were established for the FTB and applied to evaluate without prejudice a second group of 300 applicants. Since the present criterion for adequate job performance is simply the successful completion of climbing school, means for each test item of the FTB were evaluated for their predictive value. The mean scores for the step test and balance were found to be significantly different, smaller than .05 between the successful and unsuccessful applicants, whether male or female. Percent fat differed significantly only in the males and two strength tests and reaction times were not significant. Additional studies were conducted on two groups of young adults with known fitness levels to better characterize the strength factors which are considered essential to acceptable pole climb performance. Significant differences were found for both static and dynamic strengths, p equals smaller than .05. In summary, a FTB of simple, objective, job related test items can be identified and validated for predictive and diagnostic purposes. Probabilities for success can be established through a preliminary self-screening test program and administered by the employment office. The test items which comprise the FTB can be figuratively presented as a profile analysis and incorporated in the employee's medical file for longitudinalappraisal. If meaningful standards can be established for use in preemployment or job transfer screening, substantial financial benefits can accrue to the company in terms of reduced administrative and training costs and a reduction in "sick leave" and liability resulting from industrial accidents.


Long-term mortality experience of steelworkers. VIII. Mortality patterns of open hearth steelworkers (a preliminary report). The findings in this report of a deficit in mortality from cardiovascular diseases and an excess in diseases of the digestive system among open hearth workers indicate the need for further study of men working in hot environments. In future reports we hope to refine the comparisons by obtaining data which will enable classification of workers more precisely by intensity and duration of exposure within the open hearth. Of particular importance in future work are the evaluation of possible relationships between the actual levels of heat exposure and subsequent morbidity and mortality, as well as possible interactions between heat stress and physical exertion in terms of the incidence of heart disease and other select diseases.


An investigation of the chemical contact lens problem. An evaluation of the "chemical trapping premise" was made to determine if, in fact, chemicals do accumulate behind a contact lens if a wearer encounters chemical splash. Photographs were taken to document the effect of chemical splashes. A photograph of a normal eye, Fig 7, taken prior to the insertion of a contact lens is included for purposes of comparison. Under the conditions investigated, it was demonstrated that, for liquid irritant exposures, eyes are afforded more protection when wearing contact lenses than when not. Test results suggest the contact lens acts as a barrier to the irritant on the cornea. The investigators postulate that lid spasm occurs, causing the lens to tighten against the cornea, thereby effectively sealing off the area under the lens. Since the "barrier" effect appears to be a function of time, more testing of this variable is warranted. Moreover, further investigation is indicated using a broader spectrum of irritants and an extended environmental exposure to dust and vapors.


Hypertension in Oregon pesticide-formulating workers. In a statewide survey of hypertension prevalence among pesticideformulating workers and controls in Oregon, we found no difference in mean systolic and diastolic blood pressure values but a modest excess of hypertension prevalence among chlorophenoxy herbicide workers which was largely explained by a greater constitutional predisposition to hypertension as estimated by positive family histories. Neither our study nor other published to date are adequate to allay the suspicion that chronic pesticide exposure may increase the risk of hypertension manifestation.


Photopic spectral sensitivity of the peripheral retina. Photopic spectral sensitivity was determined in the mid- and far-peripheral retina by two methods. The first consisted of measuring increment thresholds on a background similar in spectral composition to CIE Source A. The resulting spectral-sensitivity functions displayed maxima at about 440 nm, in agreement with previous work. The second method consisted of measuring dark-adaptation curves following termination of the background. From these curves, spectral-sensitivity functions were derived for various times in the dark. The results showed that the 440 nm maximum quickly diminished. When photopic thresholds were estimated from the cone plateau of the dark-adaptation curves, the spectral-sensitivity functions peaked at about 550 nm and had much the same shape from the parafovea to the far periphery. We suggest that previous findings of maximum photopic sensitivity in the short-wave region of the spectrum resulted from chromatic adaptation induced by backgrounds (such as Source A) that were weighted towards middle and long waves.


Visibility of low-spatial-frequency sine-wave targets: Dependence on number of cycles. The number of cycles in a low-frequency sinusoidal display is a crucial variable in determining the visibility of the display. In particular, the threshold contrast is essentially independent of spatial frequency for these displays. We have extended the above experiments, using more cycles and a variety of targets and observer tasks. The results confirm previous findings; they also show that the type of target or task has little influence. For low-frequency sinusoids that contain up to about 3 cycles, the threshold contrast is determined by the number of cycles. For high-number-of-cycles targets with spatial frequencies above 6-10 cycles per degree, visibility is predominantly dependent on the spatial frequency. The results suggest that the low-frequency decrease in reported MTF's is due to the decrease of the number of cycles used in determining them.


Follow-up studies of long term survivors after hepatic portoenterostomy for "noncorrectible" biliary atresia. Fourteen patients with "noncorrectable" biliary atresia are living without jaundice for more than 2 yr after hepatic portoenterostomy or its modification. Retardation of physical growth was observed in one of them, and mental retardation in another, both of which seemed irrelevant to biliary atresia. Serial tests for liver function after operation revealed early recovery of serum bilirubin, transminase, and turbidity, and delayed improvement of alkaline phosphatase. Postoperative needle biopsy of the liver disclosed that changes in hepatic parenchyma and ductular proliferation were rapidly improved after successful operation. Improvement of fibrosis of the liver was delayed, and it was not satisfactory in patients whose preoperative changes in the liver were severe or in whom ascending cholangitis had been a frequent complication. Histologic features of hepatic cirrhosis were observed in the liver in three cases, in two of which there had been frequent episodes of cholangitis. Only one of these showed clinical signs of portal hypertension. Functional and morphologic cure can be achieved in "noncorrectable" biliary atresia by hepatic portoenterostomy or its modifications, although varying degree of hepatic fibrosis may remain according to severity of preoperative changes of the liver and postoperative complication of ascending cholangitis.


Sacrococcygeal teratoma: a 33-year experience. During the years 1941 through 1973, 48 patients, 16 males and 32 females, with sacrococcygeal teratoma were seen at the Childrens Hospital of Los Angeles. Forty-four patients have been followed, three are lost to follow-up, and one patient died 2 wk after excision of teratoma. Of the 44 patients with follow-up, 26 had teratoma with mature tissues only, all these patients are living. Six patients had tumor containing mature and embryonic tissues. Of these, five are living and one died with metastases of malignant teratoma 1 yr after excision of the primary tumor. Of the remaining 12 patients, 11 have died during the first 4 yr of life due to malignant teratoma and only one is living without recurrence 15 yr after excision of teratoma containing frankly neoplastic tissues. Recurrence  and/or metastasis of malignant sacrococcygeal teratoma was lethal in all instances.


Perforation of Meckel's diverticulum in infancy. Nine infants underwent operations for perforation of a Meckel's diverticulum over a 21-yr period. All of the infants were acutely ill when initially seen by the surgical service. Lethargy, irritability, anorexia, fever, abdominal tenderness, and passage of blood in the stools were common clinical manifestations. The preoperative diagnosis of perforated Meckel's diverticulum was not made in any of the cases. Skilled preoperative and postoperative management is important for the survival of these infants. There was no mortality and minimal morbidity. In retrospect, the peptic etiology of perforation in this age group is a key to early recognition. The past history of most of the patients includes previous episodes of blood in the stools and episodic abdominal complaints.


Major hepatic resections in children.

Major hepatic resections in children. Twenty-three major hepatic resections in children are presented. An unusually low number of associated injuries is noted in the trauma group. There was one operative death and complications were limited to five patients. Biliary decompression was not employed. Complications did not include respiratory, renal, or hepatic failure. Gastrointestinal bleeding was not seen. Although debridement seems adequate for subsegmental injuries, anatomic lobectomy must be considered for more severe injuries involving multiple segments of a single lobe.


Nasotracheal intubation in diphtheria.

Nasotracheal intubation in diphtheria. Nasotracheal intubation can be used effectively for the relief of upper airway obstruction in diphtheria. It has many advantages over tracheostomy; it avoids an operation and it eases anxiety of the parents. Of 57 patients so treated, 50 recovered without injury to the larynx in any patient.


Bacteroides: a cause of residual abscess? Bacteroides fragilis as a cause of residual abscess has not been previously demonstrated. This clinical and bacteriologic study of 54 consecutive cases of appendectomy in children suggests that if B. fragilis is found in the peritoneal fluid at the time of operation there is a strong possibility of residual abscess development. Special collection and culture methods are necessary to obtain positive cultures of this strictly anaerobic organism.


The relationship of intestinal adhesions to infrared heating lamp exposure. The incidence of postoperative intestinal adhesions and microscopic intestinal injury resulting from the use of overhead infrared heating lamps was studied in 45 rabbits. Exposure of intestine to infrared light for 2 hr or longer at a distance of 1-1/2 ft produced adhesions in 87% of the rabbits, whereas exposure to heat under the same conditions but at a distance of 3 ft resulted in adhesions in 37% of rabbits. The incidence and severity of adhesions correlated directly with the period of intestinal exposure to infrared heat. No histologic evidence of intestinal injury was apparent in intestine exposed to infrared heat under the conditions of this study.


Agenesis of the dorsal mesentery without jejunoilial atresia ("apple peel small bowel"). Agenesis of the dorsal mesentery with apple peel or Christmas tree deformity but without small-bowel atresia can occur beyond the neonatal period. The recognition of this entity is imperative as it is also associated with a marginal artery which may be the only blood supply to the majority of small bowel. Preservation of this vessel is necessary to avoid catastrophic bowel death.


Moral judgment in sociopathic and normal children. Mental age- and IQ-matched normal and sociopathic children were administered Kohlberg's moral development interview and the Wechsler Intelligence Scale for Children. The results revealed that level of moral reasoning was higher for normal than for sociopathic children at both mental age levels. Within each group, high-mental-age children tended to have higher moral judgment scores than low-mental-age children, suggesting the presence of a general cognitive factor underlying moral development. The poorer performance of the sociopathic children was interpreted as supporting the formulation that sociopathy is related to an arrest in moral development. Discussion focused on the relative lack of opportunities for role-taking and identification in the families of sociopathic children.


Endorsement of formal leaders: an integrative model. This experiment develops an integrative, path-analytic model for the endorsement accorded formal leaders. The model contains four independent variables reflecting aspects of group structure (i.e., group success-failure, the payoff distribution, the degree of support by others members for the leader, and the vulnerability of the leader). Also included are two intervening variables reflecting perceptual processes (attributed competence and attributed fairness), and one dependent variable endorsement). The results indicate that endorsement is greater when the group's success is high, when the payoff distribution is flat rather than hierarchial, and when the leader is not vulnerable to removal from office. Other support had no significant impact on endorsement. Analyses further demonstrate that the effect of success-failure on endorsement is mediated by attributed competence, while the effect of the payoff distributed is mediated by attributed fairness. These results suggest that moral and task evaluations are distinct bases of endorsement.


Physical attractiveness, social relations, and personality style. The relationship between physical attractiveness, social contact with members of the same and opposite sex, and personality factors was determined. Sixty male and 60 female university freshmen who were rejected, accepted, or unknown to their same-sex peers served as subjects. A reliable rating of physical attractiveness by independent judges showed that rejected subjects were most attractive, accepted subjects were next most attractive and unknown subjects were least attractive. There was a positive relationship between physical attractiveness and dating for females, but not for males. A factor analysis of subjects' personality inventory scores and subsequent analyses of variance of personality factors by sociometric groups showed that rejected subjects of both sexes were independent, achieving, and ambitious; accepted subjects were affiliative and affectionate; and isolated subjects were emotionally constricted, defensive, and withdrawn.


Comparison of social judgments of creativity and intelligence. Social judgment of creativity and intelligence was investigated by having subjects give trait ratings for stimulus profiles of actual art students based on abilities information alone, based on personality information alone, based on biographical information alone, and finally, based on the total set of all three types of cue information. Regression equations differed depending upon whether intelligence or creativity judgments were being predicted. For all types of information, there was a significant amount of variation unique to creativity judgments which could not be accounted for by intelligence judgments, and vice versa. However, the proposition of variation unique to each type of trait judgment was smallest when subjects had only abilities information available and was approximately four times larger when judgments were based on the total set of three types of cue information. Implications of this finding for the study of creativity are discussed.


Do people have inflated views of their own ability. An experiment tested a need-for-self-esteem notion that people inflate self-appraisals of ability, deny criticism, and overrespond to praise. Actors and bystanders rated actors' performances on a nonobjective task after hearing the performance praised or criticized or before hearing it evaluated. No evidence of self-enhancement was found; to the contrary, actors compared to bystanders rated themselves harshly, lowered their ratings after criticism equally, and showed relief after praise. A second experiment compared actor and bystander ratings of actors who expected evaluation of their performances or who expected no evaluation. Results suggested self-derogation by actors as a defense against possible loss of self-esteem.


Effects of altered responsibility, congnitive set, and modeling on physical aggression and deindividuation. This laboratory investigation using 64 college students as subjects assessed the role of three disinhibiting variables in producing both physical aggression and an internal state of deindividuation. Altered responsibility, congnitive set, and modeling were manipulated in a factorial design, and all three variables significantly increased physical aggression. No interaction produced significant results. The increase due to altered responsibility and varying cognitions supports Zimbardo's theory of deindividuation which relates certain input variables to wild, impulsive behavior. Questionnaire data indicated that the increase in aggression was not accompanied by internal mediational factors such as reduced self-awareness. It appears that disinhibiting forces may produce increases in antisocial behavior without necessarily producing a deindividuated internal state.


Leader effectiveness and leadership conferral as determinants of helping in a medical emergency. This study investigated the contribution of an individual's qualification for discussion group leadership (LGD) and the method of leadership conferral, election versus appointment, upon his group's response to a medical emergency. Five-person, face-to-face groups with high LGD leaders responded more frequently and more rapidly to a confederate member's diabetic reaction than did groups with low LGD leaders. Low LGD leaders were frequently overthrown, while groups with high LGD leaders experienced continuity of leadership. Conferral process had no discernible effect on helping or overthrows. It was concluded that a victim is the more fortunate if his group's leader is assertive.


The antiarrhythmic and antifibrillatory actions of bretylium and its o-iodobenzyl trimethylammonium analog, UM-360. The antiarrhythmic, adrenergic-stimulating and blocking properties of bretylium and a structural analog UM-360, o-iodobenzyl trimethylammonium chloride, were studied in the anesthetized dog. Bretylium produced an initial sympathomimetic effect with a subsequent blockade of cardiac responses to sympathetic nerve stimulation. Bretylium was observed to produce an antifibrillatory effect when the vulnerability to fibrillation was measured as the current required to evoke ventricular fibrillation (ventricular fibrillation threshold) or the spontaneous development of ventricular fibrillation in response to a one-stage occlusion of the left anterior descending coronary artery for 20 minutes followed by release. In animals intoxicated with ouabain, however, bretylium was not effective in reversing the ventricular tachycardia. UM-360, in contrast to bretylium, did not produce adrenergic stimulation or blockade of sympathetic neuronal activity. UM-360, however, produced a marked antifibrillatory effect by increasing the electrical threshold to ventricular fibrillation and reducing the incidence of ventricular fibrillation in response to coronary artery occlusion. The results of this study suggest that the quaternary ammonium structure, as possessed by bretylium and UM-360, may be of significance with respect to the antiarrhythmic and antifibrillatory effects of these agents.


The correlation between spontaneous contractions and postjunctional supersensitivity of the smooth muscle of the rat vas deferens. Chronic postganglionic denervation of the rate vas deferens produces an increase in the sensitivity of the in vitro smooth muscle to norepinephrine, methoxamine, acetylcholine, potassium and electrical stimulation. The maximal contractile response to norepinephrine and acetylcholine is increased but the maximal response to potassium or electrical stimulation is not affected. In addition, the vas deferens becomes spontaneously active after denervation. The spontaneous contractions are not prevented by tetrodotoxin, phentolamine or atropine. The appearance and magnitude of the spontaneous contractions are temporally correlated with the development of postjunctional supersensitivity. At a given time after denervation there is a significant correlation between the magnitude of the spontaneous contractions and the sensitivity to norepinephrine, i.e., the sensitivity to norepinephrine being greatest in those tissues with the largest spontaneous contractions. There is an inverse relationship between the magnitude of the spontaneous contractions and the endogenous norepinephrine concentration. Pretreatment of rats with reserpine (1. 0 mg/kg/day for 5-7 days) results in supersensitivity of the vas deferens ,o norepinephrine and acetylcholine. Those tissues obtained from reserpine-pretreated rats which are supersensitive are also spontaneously active. It is concluded that the -ppearance of spontaneous contractions in the rat vas deferens is an index of postjunctional supersensitivity.


Inhibition of brain catecholamine synthesis and release of prolactin and luteinizing hormone in the ovariectomized rat. The effects of alpha-methyl-p-tyrosine (alpha-MT) on brain catecholamine synthesis and plasma prolactin and luteinizing hormone levels were determined in ovariectomized rats to ascertain whether the release of either hormone from the anterior pituitary is dependent on the release of newly synthesized dopamine and norepinephrine. Doses of alpha-MT ranging from 3.15 to 25 mg/kg were administered via a carotid cannula to unrestrained ovariectomized rats. Within 10 minutes, alpha-MT caused a significant dose-related increase in plasma concentrations of prolactin which became maximal 20 to 25 minutes after the injection. Plasma levels of luteinizing hormone were not affected. Alpha-MT caused a dose-related decrease in the accumulation of 3-H-norepinephrine and 3-H-dopamine in the brain after the administration of 3-H-tyrosine. The time course of the inhibition of catecholamine synthesis closely paralleled the increase in plasma prolactin concentration. Alpha-MT had no effect on endogenous catecholamines. The results suggest that catecholamine-containing neurons exert a tonic inhibitory influence on the release of prolactin in ovariectomized rats.


A sensitive method for the comparative bioassay of nonsteroidal anti-inflammatory compounds in adjuvant-induced primary inflammation in the rat. A method for the comparative bioassay of nonsteroidal anti-inflammatory agents is presented which exploits the early inflammation induced by injection of adjuvant into the plantar surface of a hind paw of the rat. The inflammation reaches a peak on the 4th postinjection day. Daily treatment with nonsteroidal anti-inflammatory agents reduces paw volumes and the associated impairment of body growth with optimal improvement on the 4th postinjection day. In this model, phenylbutazone has shown significant activity at doses as low at 1.33 mg/kg/day. Statistically valid comparative assays conducted at dose levels equivalent to or below those used in human therapy yield potency ratios with relatively narrow confidence limits. Potencies relative to phenylbutazone for inhibiting primary adjuvant-induced inflammation are: aminopyrine, 0.066 (0.36-0.11)95%; aspirin, 0.087 (0.039-0.19)95%; mefenamic acid, 0.98 (0.64-1.6)95%; flufenamic acid, 13 (7.4-26)95%; meclofenamic acid, 23(16-33)95%; and indomethacin, 53 (35-82) 95%. Ancillary and sometimes quantitative information is also provided by the improvement in well being of the animals as reflected in body weight changes with treatment.


Comparative activities, tolerances and safety of nonsteroidal anti-inflammatory agents in rats. Relative anti-inflammatory potencies of aspirin, phenylbutazone, indomethacin, three fenamates and several other nonsteroidal anti-inflammatory agents were obtained in several laboratory models of acute and chronic inflammation. Relative toxicities and ulcerogenicities were determined in rats of the same source, strain and sex. The acute ulcerogenic assay measures the minimal irritation potential of these agents and leads to a sensitive index of the safety of such compounds when compared with their therapeutic potencies. By these criteria, meclofenamic acid is a highly potent, acceptably safe and exceptionally well tolerated anti-inflammatory-antipyretic agent in rats when compared with other such drugs.


Thiol adducts of ethacrynic acid: a correlation of the rate of liberation of ethacrynic acid with the onset and magnitude of the diuretic response. It is thought that a derivative of ethacrynic acid (EA) must possess an intact alpha, beta-unsaturated ketone group in order to be capable of eliciting a diuretic response. The 2,3-dimercapto-1-propanol and the cysteine adducts of ethacrynic acid lack such a functional group and still have diuretic activity, especially the cysteine adduct. An in vitro study showed that various thiol adducts of EA liberate EA and the accompanying thiol at a rate that is primarily dependent on the nature of the functional groups present in the thiol portion of the adduct. When the thiol adducts of EA were injected into dogs, the cysteine and mercaptoethylamine hydrochloride adducts which rapidly release EA under specific in vitro conditions were as effective as EA in producing a diuretic response. The onset of action was also similar to that of EA. The thiosalicylic acid adduct of EA releases the accompanying thiol at an intermediate rate in vitro and was less effective than EA in a small dose (3.3 mumol/kg) and the peak response to it was slower to develop. Other adducts that release EA and the accompanying thiol slowly in vitro either produce a very weak response which takes considerable time to develop or are completely devoid of diuretic activity. Thus, the onset and magnitude of the diuretic response produced by various thiol adducts of EA (with the possible exception of the cysteine adduct) are governed primarily by the rate of in vivo release of EA.


Plasma testosterone levels in heroin addiction and during methadone maintenance. Heroin use was consistently associated with low plasma testosterone levels in narcotic addicts. Heroin addicts maintained on high dosage methadone (80-150 mg/day) also had depressed testosterone levels. Patients on low dosage methadone maintenance (10-60 mg/day) had testosterone levels which were not significant;y different from normal adult male controls. An inverse relationship between methadone dosage and plasma testosterone occurred during methadone detoxification. These findings indicate that heroin and methadone alter male androgen levels with possible derivative effects upon sexual and aggressive behaviors.


Pentaerythritol tetranitrate and metabolites in rat plasma. Intact pentaerythritol (PE) tetranitrate and all seven of its metabolites were present in blood withdrawn from the hearts of rats dosed by gavage with 14-C-PE tetranitrate (10 mg/kg). The plasma half-life (T 1/2) of PE tetranitrate was 2 hours which is far longer than the rat T 1/2 values of all other organic nitrates in clinical use. PE trinitrate, the obligatory metabolite of PE tetranitrate now in clinical trial, establishes much higher plasma levels and has a longer T 1/2 (3 hours) than its parent drug. PE trinitrate glucuronide acts as a reservoir for its aglycone and remains in blood for 48 hours after PE tetranitrate administration.