Effects of perinatal androstenedione on sexual differentiation in female rats. Androstenedione was administered prenatally, postnatally, postnatally, or both pre-and postnatally to female rats. The extent to which reproductive morphology, ovarian functioning, and adult sexual behavior were masculinized and defeminized depended on the dosage, timing, and duration of the hormone treatment. The combined pre-plus postnatal treatment resulted in the greatest degree of modification in that such females were anatomically masculinized and did not ovulate. When tested in adulthood, they showed a high potential for the male copulatory pattern and little lordotic behavior. It is concluded that androstenedione, while not as potent an androgen as testosterone propionate, nevertheless has the potential to participate in the process of sexual differentiation.


Effects of simultaneous oral-intragastric ingestion on meal patterns and satiety in humans. Simultaneous oral-intragastric ingestion of a liquid diet was compared with oral ingestion for 15-21 days in four males or normal weight, 18-21 years old. All the subjects are significantly more (M= 222 cm3 or kcal [930 kJ] per meal, p less than .025) during simultaneous compared with oral lunches and dinners. Subjects reduced the size and frequency of breakfasts and snacks, which were always ingested orally, however, and did not gain weight. In a second experiment, the same four subjects ate significantly more (M-177 cm3 more, p less than .001 at lunch when the rate of ingestion was 200 cm3/min compared with 100 cm3/min regardless of route (oral, intragastric or simultaneous). They also ate significantly more (M=135 cm3 more, p less than 0.25) during simultaneous meals compared with oral or intragastric meals ingested at the same rate. Thus, rate of ingestion and oral stimulation are important determinants of meal size in humans.


Rat hippocampus and memory for places of changing significance. Rats were tested once daily on a four-choice delayed match from sample task with a water reward. Each day the correct place changed, and a single exposure to it was provided on information trials. Lesions of the hippocampal formation that involved the fornix, or dorsal hippocampus bilaterally, produced a severe impairment in the performance of previously trained rats. By contrast, lesions of the ventral hippocampus did not preclude reacquisition of the place-memory task. Some otherwise impaired rats with fornical lesions were able to find the water when aided by nonplace cues that consistently signaled reward. Reducing the number of choices from four to two did not aid the impaired rats. Certain lesions of the hippocampal formation in the rat produce a deficit appropriately described as amnesia. The memory deficit is consistent with a role for the hippocampus in processing of place information and shows some parallels to the amnesia seen in persons with temporal lobe lesions.


Ontogeny of behavioral arousal: the role of environmental stimuli. During the course of ontogenesis the developing rat has been reported to pass through a transient period of intense behavioral arousal which peaks at 15 days of age, a phenomenon that has been interpreted to reflect a sequential caudal to rostral development of excitatory and inhibitory systems in the mammalian brain. In a series of four experiments it was shown (a) that this period of intense hyperactivity occurs only when the animal is tested alone in an unfamiliar environment, that the degree of arousal is proportional to the dissimilarity between the home cage and the test environment, and that isolation per se is insufficient to elicit the arousal response; (b) that environmental temperature has a minimal influence on the degree of behavioral arousal seen in either familiar of unfamiliar environments; (c) that unlearned responses to pheromonal or other naturally occurring nest odors do not suppress the high levels of locomotor activity evoked by unfamiliar environments in the 15-day old rat pup; and (d) that it is fear or distress evoked by the unfamiliar environment rather than curiosity that underlies this developmental phenomenon. It is concluded that the sequential increase and decrease in locomotor activity that occurs during ontogenesis cannot be used to support the principle of caudal to rostral development of excitatory and inhibitory centers in the central nervous system.


Auditory spatial responses of young guinea pigs (Cavia porcellus) during and after ear blocking. Newborn guinea pigs were tested to determine their ability to approach an auditory stimulus early in development. Observations of the behavior of 1-4-day-old animals in a circular eight-choice maze revealed a pronounced tendency to orient toward and approach a tape-recorded signal of guinea pig vocalizations. The occurrence of approach responses was reduced to chance in animals tested with one ear occluded by wax ear plugs which attenuated but did not totally eliminate sound. The effect of monaural ear blocks was more severe than binaural blocks, which reflects the importance of binaural cues in the maintenance of approach responses to sound. In a second study, the ability of older animals, 11-31 days of age, was examined. Directional approach responses to sound were also evident at this age, and ear plugs disrupted performance only under monaural conditions. Furthermore, in animals raised from birth with monaural ear blocks but tested without ear plugs, there was a subsequent disruption of performance for at least 21 days. These results indicate the importance of binaural cues in the development of early auditory spatial responses and suggest the need for appropriate binaural experience for subsequent localization of sounds.


Deficits in visual learning produced by posterior temporal lesions in cats. Eight cats with lesions in the posterior temporal (PT) cortex, seven cats with lesions in the basolateral amygdala (BLA), and eight intact controls were observed on eight tests of visual discrimination learning and of spontaneous responses to salient visual stimuli. The effects of the two lesions were somewhat dissociable. The PT lesions were accompanied by a severe deficit in pattern discrimination learning but no loss in visual tracking or orientation to the silhouette of a threatening cat. The BLA lesions produced a milder and less consistent loss in pattern discrimination but serious defects in tracking and reponse to the cat silhouette. Both operated groups performed well on the visual cliff. The deficit from PT lesions appeared independent of damage to the geniculocortical system. The parallel of symptoms from PT lesions in cats and inferotemporal lesions in monkeys is discussed.


Behavioral effects of neurotoxic lesions of the ascending monoamine pathways in the rat brain. Intracranial microinjections of 6-hydroxydopamine or 5,6-dihydroxytryptamine into six ascending monoamine pathways produced the expected patterns of depletion of telencephalic serotonin, dopamine, and norepinephrine. Serotonin level was specifically lowered after dorsal or median raphe lesions but not after mesolimbic or nigrostriatal system lesions which lowered both norepinephrine and dopamine. Lesions in the locus coeruleus or ventral nor-adrenergic bundle lowered only norepinephrine, and locus coeruleus lesions elevated serotonin level. Behavior was examined in an open field, one-way active avoidance, and two passive avoidance tasks, and measures were taken of water consumption and body weight. Dorsal raphe lesions had no effect on any of the measures; the other five lesion groups exhibited deficient acquisition of the one-way active avoidance task. In the appetitive passive avoidance task, only the substantia nigra lesion group exhibited a deficiency. In the step-through passive avoidance task, both the substantia nigra and the median raphe groups exhibited a deficit, with the median raphe group exhibiting hyperactivity in the start box during testing. Water consumption was decreased by lesions in the ventral noradrenergic bundle during the first postoperative week and was increased in the median raphe group by the fourth postoperative week. Lastly, lesions in the locus coeruleus dramatically decreased activity in the open field. The results are discussed in regard to the search for specificity of behavioral functions of the distinct ascending monoamine pathways.


Medial septal lesions: disruptions of microregulatory patterns and circadian rhythmicity in rats. The microregulatory patterns of food and water intake were examined in male and female rats bearing medical septal lesions and in sham-operated controls. Medial septal ablation, although not affecting the total amount of food or water ingested, resulted in a profound disruption of the pattern of intake. Circadian rhythmicity was disrupted for a period, returning to normal by 25 days postlesion. Permanent disruptions occurred in feeding patterns in the rats with septal lesions ingested more frequent but smaller meals. There was also a marked increase in food-intake-associated drinking and a decrease in non-food-intake-associated drinking. The results are interpreted to reflect two separate independent effects, a general circadian disruption and an alteration in requlatory behavior produced by a chronic depletion of body fluid.


Central catecholamine and peripheral noradrenaline depletion by 6-hydroxydopamine and active avoidance learning in rats. Three experiments are reported on the relation among catecholamine (CA) depletion, plasma corticosterone (11-OHCS) levels, and active aversive learning. A baseline study showed no significant relation beteen resting levels of 11-OHCS and central and/or peripheral CA depletion. On a two-way avoidance learning task, depletion of brain CAs produced a widespread learning deficit. When both central and peripheral CAs were depleted, only escape learning emerged. Similar effects occurred on a one-way task, but differences were not so marked. The findings are discussed in terms of a theory of CA-dependent cues.


Colostral constituents including immunoglobulins in the first three milkings postpartum. Colostral changes in immunoglobulin (IgG), dry matter, ash, total protein, and whey protein were studied over the first three milkings postpartum. Immunoglobulin IgG concentration in colostrum from Holstein cows beginning their first, second, or third lactation was similar. However, older animals had more IgG in colostrum. Its rate of disappearance from colostrum was greater in younger animals. Dry matter, ash, total protein, and whey protein concentrations decreased from the first to the third milking (24 h) postpartum. Protein was the most variable constituent between cows at the same postpartum time.


Sources of variation of semen output.

Sources of variation of semen output. Data from 5033 ejaculates during 1 yr from 55 mature Holstein bulls were analyzed to determine the effects of ejaculate number, days between ejaculates, month of the year, solunar periods, and sires on spermatozoal output and seminal characteristics. First ejaculates contained 49.7% more sperm and 40.8% more sperm per ml than second ejaculates. Increasing the interval between collections from 2 to 6+ days resulted in 45.9% more sperm per ejaculate, 31.0% more sperm per ml. and 14.0% greater volume. However, daily sperm output was highest when bulls were ejaculated most frequently. Lowest semen output was in February and March, associated with a decrease in sperm per ml. Highest semen output was in April and June, associated with the highest concentration of sperm per ml. Solunar periods had no effect on any measure of semen output. The concentration of sperm per ml varied more than the volume per ejaculate and had the largest influence on variation in total sperm harvested per ejaculate. Frequency of ejaculation was a major factor in total sperm harvested per bull per year.


Bromocriptine: effect on serum prolactin and growth hormone in psychogeriatric hospital patients. Serum prolactin (PRL) and human growth hormone (HGH) were assessed before, and three hours after oral administration of 2.5 mg of bromocriptine in 39 hospitalized geriatric patients with organic brain syndrome. Serum PRL concentrations decreased significantly irrespective of initial values (also in the 7 geriatric control subjects), but HGH levels were low in all patients and did not change during the three hours after administration of bromocriptine. Closer scrutiny of the HGH responses to bromocriptine in 5 patients and 5 controls showed that the serum HGH response was more variable among the patients than among the controls. The findings are discussed in relation to neuroendocrine changes associated with aging, institutional living, and mental disease.


Brain function, intellectual impairment and education in the aged. In assessing behavioral problems of the elderly there is a need for procedures which reliably indicate the presence and extent of impaired brain function. In this study, the relation of two mental status measures [the Mental Status Questionnaire (MSQ) and the Face-Hand test] to intellectual performance and education was evaluated. The sample consisted of 153 consecutive inpatients and outpatients referred to a gerontology clinic. Intellectual performance was assessed with 8 tests of learning and memory, such as Paired Associates and Babcock Story Recall. The findings indicate that positive ratings for impaired brain function on either mental status test were related to lower intellectual performance at each of three levels of education - grade school, high school, and college. Subjects with more education and mental status scores indicating mild impairment performed better on intellectual tests than did less educated persons with no brain dysfunction, but they showed significant deficits compared to other subjects with similar education and intact brain function. Larger intellectual deficits were found when the patient made more test errors and when both tests gave positive ratings. These results confirm the importance of the MSQ and Face-Hand tests as screening devices for the intellectual deficits associated with impaired brain function in a clinically heterogeneous population.


Sliding inguinal hernia in patients over 70 years of age. In a 1973 study of 200 aged patients with groin hernias, a comparatively high incidence of the type known as sliding hernia was noted. The present study of 60 patients over age 70 seen at the Henry Ford Hospital between the years 1940 and 1972 was devoted specifically to the problem of sliding hernias. The threat of bowel strangulation is often advanced as a reason for the operative repair of such hernias, but this complication is rare. Bowel dysfunction, constipation and local discomfort are far more common, and gave rise to annoying symptoms in 75 percent of the patient studied. Barium enema x-ray examinations often revealed some degree of bowel obstruction. Most often the sigmoid colon the left side and the ileocecal segment on the right side constituted the sliding components of the hernia; the bladder was involved less often. Repair of 62 sliding hernias in 60 patients was performed successfully. There were no deaths, and only one recurrence of the hernia.


The social behavior of elderly aphasic versus nonaphasic long-term patients. A study was made of the social consequences of communicative disorders among 51 elderly hospitalized long-term patients. Independent variables used to account for variations in social behavior were: 1) the presence or absence of aphasia, an impairment resulting in varying degrees of loss of verbal recognition, comprehension and language production; 2) sex; and 3) the level of nursing-care needs as an indicator of overall physical independence. A rating scale for measuring "Social Involvement" was constructed. It involved four analytically-derived factors - Interpersonal Behavior, Familial and Social Contacts, Group Participation, and Extent of Social Contacts. Since a comparison of the 15 aphasic and 36 nonaphasic subjects on the basis of these four factors revealed no substantial main effect, it would seem that social isolation was not attributable to aphasia per se. Rather, a number of significant interactions indicated that differences in the levels of social involvement were attributable to the combined influences of sex, presence or absence of aphasia, and varying levels of physical independence. The relationship between social involvement and social isolation has implications for the overall management and rehibilitation of long-term patients.


Disengagement versus engagement - a need for greater expectations. An attempt is made to clarify some existing perspectives of successful aging. The environmental milieu of the aged is laden with potent and pervasive implications about successful adaptation. Considerable exploration is required to facilitate a realistic focus upon various theoretical contributions already presented. The influence of stresses and adaptive energy depletions preceding the senescent state is discussed in an effort to facilitate knowledgeable assimilation of the potential impact of the socioeconomic milieu upon the aged. It is the author's contention that the elderly person, upon retirement, presents an adaptive energy reserve highly personalized in its ability to accommodate to change, and especially dependent upon the nature, number and intensity of environmental stressors to adapt, successfully or unsuccessfully, to senescence. Various environmental stressors are identified (e.g., changes in social opportunities and expectations which create new needs and constrict the realm of emotional and vocational influence, thus reducing opportunities and diminishing self-esteem). Heavy emphasis is placed upon role theory, interaction ritual, and transactional analysis. These concepts are extended to the institutional setting - an environment which serves only to magnify mechanisms occurring throghout the social system while adding its own unique dimension to the stressors confronting the elderly.


Electron microscopic study of bone surface changes during aging. The loss of cellular control and biofeedback. An electron microscopic study was made to determine (1) the effects of aging on periosteal and endosteal bone surfaces and (2) whether the membrane-like arrangement of osteoblasts at bone surfaces was retained during aging. Short-lived BNL inbred Swiss albino mice 5 to 130 weeks of age were perfused with glutaraldehyde. Femoral samples were taken and fixed in cold glutaraldehyde, decalcified in EDTA, and postfixed in OsO4. Epon sections were cut and stained with uranyl acetate and lead citrate. In young mice, during bone formation a zone of osteoid was observed while the preosseous zone above consisted of young collagen fibers in formation. The osteoblasts formed a tight membrane-like structure at all bone surfaces. Where bone formation did not occur, single and multiple osmiophilic laminae were observed. With increasing age collagen formation became diminished as did the width of the preosseous and osteoid zones. Subsequently, the zones disappeared. Increased surface structural complexity was seen in some areas, while other areas revealed simplification with advancing age. This depended upon the net accretionary or resorptive activity at a given surface. The membrane-like arrangement of osteogenic cells was lost in 104-week-old animals, exposing bone surfaces to physio-chemical changes not under cellular control and biofeedback.


Body weight increment and length of life: the effect of genetic constitution and dietary protein. Groups of inbred A/J and C57BL/6J mice and hybrid F1 mice were fed low dietary protein (4% casein) or normal dietary protein (26% casein), with 50 mice in each of the six subgroups. For individual mice within subgroups, growth rate was negatively related to longevity; i.e., the slower the rate of growth the greater the life-span. Between subgroups, the longer the mean growth duration, the longer the mean lifespan. Positive relationships were obtained within subgroups for peak body weight and longevity. It is concluded that, for mice, slowing the rate of growth and increasing growth duration results in a significant increase in the life-span, and the life-span increment is not related to high peak body weight since high body weight, per se, was not correlated with life-span.


Serum testosterone and testicular response to HCG in young and aged male rats. Serum testosterone and testicular response to HCG was measured in young (3 - 6 mo) and aged (20 - 30 mo) male Long-Evans rats. Serum testosterone was measured by radioimmunoassays on serial blood samples taken before and after injections of HCG. Control group serum testosterone concentrations were lower in aged compared to young groups. Intravenous injection of 1, 5, and 20 IU of HCG increased serum testosterone in both age groups and testosterone remained elevated throughout the 150-min sampling interval. The increase in serum testosterone concentrations following acute HCG stimulation was greater in young than in aged rats. Serum testosterone concentrations and testicular response to intravenous HCG injections were increased to similar levels in young and aged male rats following 7 days of daily subcutaneous injections of 5 IU of HCG/100 gm bw. These data suggest that while testicular secretion and responsiveness is reduced with age, the aged male rat retains the capacity to secrete more testosterone than it normally maintains.


Effect of sodium fluoride, inorganic phosphate, and oxymetholone therapies in osteoporosis: a six-year progress report. Elderly osteoporotic males treated with sodium fluoride or inorganic phosphate for 4 years plus 2 years of follow-up observations exhibited a mean but not significant decrease in the rate of bone mass loss in comparison with those receiving oxymetholone or a placebo. No hip fractures occurred in the patients who received fluoride, while 11 hip fractures occurred in the patients in the phosphate, oxymetholone, and control groups. Because the densitometric trends and fracture incidence are impressive, the progress of all subjects will be followed for an additional 4 years.


Effect of aging on the peripheral blood lymphocyte count. Analysis of 1684 inpatient and 884 outpatient peripheral blood counts revealed the following: (1) The absolute lymphocyte count declines sharply from 5000/microletre to 2000/microletre in the first two decades, remains constant for three decades, then declines at an accelerated rate beginning in the 40s, to reach 1500/microletre at age 90. (2) The absolute granulocyte count does not show age-dependent variation, remaining essentially constant throughout life. (3) The values of absolute lymphocytes are indistinguishable for ambulatory or hospitalized subjects except for higher absolute lymphocyte counts in hospitalized children in the first decade. (4) The data support other evidence for declining cellular and humoral immunity in aging man.


Modifiability of fluid intelligence in aging: a short-term longitudinal training approach. The aim of this study was to examine to what degree fluid intelligence can be modified in aged subjects. The effectiveness of a cognitive training program designed to enhance one primary component of fluid intelligence, Figural Relations, was assessed by comparing the posttraining performances of 15 experimental and 15 control subjects (mean age: 69; age range 59-85) using a transfer paradigm and three posttraining assessments conducted approximately 1 week, 1 mo, and 6 mo following training. The post-training performance of the two groups was compared on three near (fluid intelligence) and one far (crystallized intelligence) transfer measures. A hierarchical pattern was predicted with the magnitude of training effects ordering themselves in descending order from near to far transfer measures. The training program was successful in enhancing performance on the fluid-nearest measure on all three posttests and for the next fluid-near measure on the first posttest. In addition, significant retest effects resulted which, however, were neither task-specific nor hierarchically ordered, but general and therefore indicative of ability-extraneous factors, such as test sophistication. The findings contribute to a position implying that intellectual performance in old age is more modifiable through short-term behavioral intervention than traditionally assumed.


Orienting task effects on EDR and free recall in three age groups. The present investigation was designed to examine the effects of orienting task-controlled processing on electrodermal response and free recall at two delay intervals for 94 young, 49 young-old (age 55 to 70), and 61 old-old (age 71 to 85) individuals. Subjects were presented with a list of 25 words and performed one of the following tasks: semantic, nonsemantic, or passive listening, presented in an incidental memory paradigm, or intentional memorization. Recall was obtained 2 min or 48 hours after list presentation. At the 2-min delay, the pattern of recall across tasks for the young-old and old-old subjects was similar to that of college students. Overall, the old-old recalled fewer words than the young and young-old, while the young-old recalled as many words as the young. After 48 hours, the task-related recall pattern was observed only in the young group. The skin conductance data indicated that task effects were similar across the three age groups and that response magnitude was lower in the old-old than the two younger groups. No differences in skin conductance were found between the young and young-old. Age differences in memory processing suggest that difficulties in delayed retrieval of semantically encoded words may increase during late adult years. Differences in electrodermal responses in the old-old compared to the young and young-old suggest that the range of autonomic responsivitiy to task demands may become restricted in advanced age.


Evaluation of job applicants: the effects of age versus success. 177 participants evaluated female job applicants on the basis of a transcript of a job interview. One-half of the participants were told that the applicant was 63, one-half that the applicant was 24. Success or failure in obtaining the job was also manipulated. In addition, participants' scores on an attitude scale were compared to their assessment of the job applicants. There were no clear differences in evaluation of young and old applicants. Scores on the attitude scale were also unrelated to these evaluations. However, female participants rated the older applicants more positively than did males. In addition, knowledge of the outcome of the interview affected ratings. Regardless of age, people who were hired were rated more positively than those who were not. These results are disucssed in terms of implications for future studies of attitudes toward the elderly.


Retirement reorientation: senior adult education. Senior Adult Educational Programs are being implemented widely as an avenue to social reorientation and greater fulfillment after retirement. Although this investigation of one program reveals limited impact on the SMSA, the findings do indicate successful retirement adjustment for program participants. The average enrollee is white, middle-class, Protestant and female, and living in close proximity to the Community College campus where the program is based. The data indicate that participation in the Senior Adult Education Program eases the transition from the primary occupational role into the retirement role. Intergenerational social distance appears to be minimal between older and younger college students, thus facilitating the sharing of a common campus.


Liberalizing the social security retirement test; who would receive the increased pension benefits? The article examines the distributional impact of liberalizing the social security retirement test. The results of simulations that explore ten liberalization alternatives are presented. The distribution of pension benefit gains from liberalization of the test are determined for the aged who were affected by the test in 1972. The relative costs of various liberalization alternatives are compared with complete abolition of the test.


Survival after early and normal retirement. This paper describes an epidemiological study of the patterns and correlates of survival after early (age 62 to 64) and normal retirement (age 65) among 3,971 U.S. rubber tire workers. For the two companies, death rates were significantly elevated during the first, fourth, and fifth years after early retirement. Among normal retirees, elevations in death rates occurred during the third or fourth years after retirement in Company B and Company A, respectively. When the experiences of both companies were combined, no significant mortality excesses were observed. Comparisons of deaths (cases) within 5 years of retirement with survivors (controls) showed that pre-retirement health status was the only significant predictor of survival after early retirement. Among normal retirees, lower status workers were more likely to die within 3 years of retirement than higher status workers, who were more prominent among deaths 4 to 5 years after retirement. Risks of dying were greater among normal retirees with a history of repeated medical and nonmedical absences.


Organizational position and perceptions of problems in a nursing home. This paper examines perceptions of problems expressed by persons living and working in a 100-bed skilled nursing home. Data were obtained from administrative staff, professional and nonprofessional nursing staffs, therapy staff, auxiliary staff, and residents by means of interview, observation, and analyses of records. The relationship between perceptions of problems and location within the organization and the scope and content of roles played was studied. We sought to ascertain the extent to which members agree or disagree with one another as to what are problems, to locate areas of agreement and disagreement, and to relate the results to the broader issue of the quality of care provided elderly institutionalized persons. Position and associated roles of members were found to be related to perceptions of problems. Differential perceptions of the numbers of problems and their priority were observed. Some problems were mentioned more frequently than others. Perceptions of problems varied both within and between organizational units. A person's location within the nursing home was related to the identification of problems as important and the frequency with which different problems were mentioned.


Return migration of the elderly in the USA: 1955-1960 and 1965-1970. This paper reports on changes in the volume and rate of return migration among the population aged 65 and over in the USA for the periods 1955-1960 and 1965-1970. Based on the earlier findings of Long and Hansen and of Eldridge, it is not surprising to find that return migration is not primarily a movement of persons returning to their place of birth to retire. Only about 5% of all return migrants in the USA are of retirement age. Return migration is more important in the migration stream of the elderly than in the total migration stream, and the rate of return migration increased at a greater rate for older persons than it did for the population as a whole.


Alterations in intramembrane particle distribution during interaction of erythrocyte-bound ligands with immunoprotein receptors. Freeze fracture studies have been performed on rabbit pulmonary alveolar macrophages and a nonphagocytic murine lymphoblastoid cell line, PU-5 Fc+, incubated with sheep erythrocytes, sheep erythrocyte-IgG Forssman antibody complex, sheep erythrocyte-IgG Forssman antibody-C complexes and aggregated IgG. Alveolar macrophages show redistribution of intramembrane particles after interaction with (EIgG) and E(IgM)C. The murine lymphoblastoid cell line shows intramembrane particle redistribution consequential to binding of E(IgG) and aggregated IgG. The results demonstrate that after specific immunoprotein receptor-ligand interaction, there is extensive plasma membrane reorganization which results in a redistribution and loss of intramembrane particles. Changes are observed in the protoplasmic face of the plasma membrane after the binding of ligand to the outer membrane surface. The findings suggest that interaction of erthrocyte-bound ligands with specific lymphoid and macrophage plasma membrane receptors leads to a generalized redistribution of integral membrane components in the membrane.


Colonic basophil hypersensitivity.

Colonic basophil hypersensitivity. Contact hypersensitivity reactions were elicited by intraluminal application of DNCB to the colon of guinea pigs and were found sometimes to contain large infiltrates of basophils. These colonic basophil hypersensitivity reactions were accompanied by systemic sensitization and were not seen in nonspecific colonic inflammatory responses induced by croton oil. The heterogenous immune inflammatory responses induced in the colon by DNCB contact sensitivity may serve as a model for the study of inflammatory bowel disease.


Functional and biochemical properties of the early classical complement system of mice. Mouse serum and EDTA plasma were subjected to low ionicity precipitation, gel filtration, and ion exchange chromatography in an attempt to purify C1, C4, and C2 to functional and chemical homogeneity. In marked contrast to human and guinea pig components, those of the mouse could not be separated by these techniques. Except for partial separation of C1 from C4 and C2 on DE-52 cellulose columuns with EDTA in the eluting buffers, there was no separation of those three components on ion exchange chromatographic columns. Sephadex G-200 gel filtration columns, or with precipitation of euglobulins from serum or plasma. Generation of EAC142 by incubation of EA in whole serum followed first order kinetics when mouse serum was used and second (or greater) order kinetics when human or guinea pig sera were used. Generation of EAC142 by incubation of EA in whole mouse serum followed by incubation in EDTA containing buffers resulted in rapid loss of all three activities from the cell. These experiments indicated that there were significant differences between the early classical C system of mice and those of human and guinea pig. In addition, they indicated that under a variety of in vitro conditions, murine C1, C4, and C2 behaved biochemically and functionally as a unit. The reasons for the major differences in behavior of the murine C components with not become clear until methods to stabilize their function are found so that they can survive multiple purification steps.


Autochthonous, allogeneic, and exenogeneic cells as targets for vaccinia immune lymphocyte cytotoxicity. The cytotoxicity of vaccinia-immune rabbit spleen cells against autochthonous, allogeneic, and xenogeneic vaccinia-infected target cells was studied by using the 51Cr release assay. The results showed that whereas effector cells from rabbit spleen could not lyse the xenogeneic target cells, there was no consistent difference in lysis of autochthonous and allogeneic targets. Antibody-mediated cytotoxicity showed the resistance to cell-mediated lysis in this system not to be the result to reduced virus antigen on the cell surface. The data also showed the established cell line RK13 eas markedly more sensitive to immune spleen cell lysis than short-term rabbit skin fibroblast cultures. The data suggested that it is possible to develop standardized tests to evaluate cell-mediated immunity to virus infections in a noinbred population.


The selective binding of aggregated IgG to lipid A-rich bacterial lipopolysaccharides. To explore the mechanism by which certain bacterial lipopolysaccharides (LPS) enhance platelet stimulation by aggregated IgG, we studied potential interactions between the two ligands. Lipid A or the lipid A-rich LPS from Salmonella minnesota R595 (LPS R595) selectively increased the sedimentation of aggregated rather than monomer IgG in sucrose density gradients. Insolubilized IgG aggregates adsorbed LPS R595 from solution. These two experiments suggested binding of IgG aggregates to LPS R595 or lipid A and this was confirmed by isopycnic density gradient ultracentrifugation studies. The presence of R595 LPS shifted the equilibrium density profile of aggregated IgG from its usual equilibrium density at 1.30 g/ml to a new position superimposable with that of the LPS R595. The possibility that a selective binding of IgG aggregates to LPS may represent a fundamental mechanism of the action of LPS on cellular mediation systems is proposed.


Defective tumoricidal capacity of macrophages from C3H/HeJ mice. Peritoneal macrophages from C3H/HeN mice treated i.p. with T cell mitogens or viable BCG organisms were cytotoxic to syngeneic tumor cells in vitro. Macrophages from endotoxin-unresponsive C3H/HeJ mice treated with BCG or T cell mitogens, however, were not tumoricidal. Furthermore, unlike cells from C3H/HeN mice, macrophages from C3H/HeJ mice could not be activated for tumor cytotoxicity after in vitro treatment with bacterial endotoxins or with lymphokine-rich supernatants. The subnormal induction of cytotoxic macrophages after in vitro or in vivo treatments in C3H/HeJ mice appears to be a highly selective defect. Macrophage responses (yield, phagocytosis, or peroxidase staining) in inflammatory exudates induced by BCG, T cell mitogens, or heterologous serum in C3H/HeJ or C3H/HeN mice were identical. C3H/HeJ macrophages also responded normally in vitor to chemotactic lymphokines. Thus, C3H/HeJ macrophages possess a profound and selective defect in tumoricidal capacity. This defect was not dependent upon exogenous endotoxins. Defective macrophage cytotoxic responses may reflect non-LPS related functions regulated by the LPS gene.


Lymphocyte cytotoxicity in x-irradiation-induced rat small bowel adenocarcinoma. III. Blocking by 3 M KCL extract. Hypertonic salt extracts (3 M KCl) of x-irradiation-induced Holtzman rat small bowel adenocarcinomas blocked the in vitro destruction of allogeneic cultured cells of this malignancy by sensitized lymphoid cells obtained from tumor-bearing animals. The protective effect were mediated by a blocking action at both the effector and the target cell level. The extracts were separated into 50% ammonium sulfate soluble and insoluble fractions with the soluble fraction being more effective in blocking the cytotoxic responses through interaction with the lymphoid cells whereas the insoluble one had a greater effect upon tumor target cells. Associated with both fractions was the oncofetal glycoprotein previously identified with the cellular membrane of this x-ray-induced malignancy. Immunoglobulins were identified with insoluble fraction; some were able to bind the oncofetal protein, thus clasifying it as a fetal antigen. The protective effects of the soluble fraction and this neoantigen were found to be citric acid labile, whereas the effects due to the insoluble fraction were unchanged.


Responses of human platelets to immunologic stimuli: independent roles for complement and IgG in zymosan activation. Analysis of the zymosan (Z)-induced human platelet response with washed platelets, fresh agammaglobulinemic plasma, and purified human IgG has identified a previously unrecognized role of IgG in this reaction, in addition to the previously reported requirements for C and fibrinogen. The rate-limiting step involves the assembly of C components on the Z particles and is independent of immunoglobulin. After the heat-labile components (supplied by agammaglobulinemic plasma) are Z bound, Z-specific IgG (apparently antibody) can bind to Z very rapidly, conferring on the previously inactive Z-complement-fibrinogen intermediate the capacity to induce platelet aggregation and serotonin release. The critical function of this Z-bound IgG appears to be in the interaction of the active Z complex with the platelet through Fc receptors, since soluble Fc fragments of each IgG subclass can totally block platelet activation. It is proposed that the human platelet requires a dual, or multi-site, stimulation to become activated during some forms of immunologic injury. These findings may provide some insight into clinical syndromes involving thrombocytopenia and intravascular coagulation during sepsis.


Antibody response and tumor growth in syngeneic mice immunized to partially purified B16 melanoma-associated antigens. Soluble murine melanoma-associated antigens (MAA), partially purified from the media of B16 melanoma cells in culture by ammonium sulfate precipitation and Sephadex G-200 chromatography, were tested for their effect on tumor growth. MAA were immunogenic in syngenic mice as evidenced by their ability to induce anti-melanoma antibodies and partial protective tumor immunity. The level of immunity was variable. It ranged from retardation of tumor development to almost complete suppression of tumor growth. The results were influenced by the nature of the control group, since immunization to either normal tissue antigens or complete Freund's adjuvant enhanced tumor growth. Overall, 46 of 91 MAA immunized mice, but none of 114 control mice, survived over 6 weeks (p less than 0.001). The protective immunity was specific since MAA immunized mice were not resistant to challenge with an unrelated syngeneic tumor (BW 10232 ADENOCARCINOMA). Partially purified normal tissue antigens were also immunogenic in syngeneic mice. They induced low levels of antibodies to, and enhanced the growth of, melanoma. These findings indicate that the culture media of melanoma cells contains tumor antigens that retain their biologic activity after partial purification, and that can induce specific, although only partial, protective immunity to melanoma.


A method for testing for synergy with any number of agents. The standard checkerboard titration for detecting synergy between antibiotics is practicable for combinations of two antibiotics, laborious for combinations of three, and not feasible for combinations of four or more. Nevertheless, methods for testing of combinations of several antibiotics are urgently needed because some combinations might be superior to those in use and enable the successful treatment of infections resistant to current therapy. A simple method for measurement of synergy (or antagonism) with combinations of any number of agents has been developed which requires less effort than the standard checkerboard titration of two agents. With this method, the concentrations of each of n agents producing some specified effect (such as minimal inhibitory concentration or minimal bactericidal concentration) are determined. A reference combination made up of 1/n of each of these concentrations is titrated to find a dilution that produces the specified effect. The degree of dilution required is equal to the sum of the fractional inhibitory concentrations (concentration of each agent in combination/concentration of each agent alone) as conventionally determined by checkerboard titrations; sums of less than 1, 1, and greater than 1 indicate synergy, additivity, and antagonism, respectively.


Experimental osteomyelitis. V. Therapeutic trials with oxacillin and sisomicin alone and in combination. Oxacillin was used alone and in combination with sisomicin in the treatment of experimental osteomyelitis due to Staphylococcus aureus in rabbits. Within diseased bone, levels of oxacillin and sisomicin remained higher than the minimal inhibitory concentration for 2 and 6 hr, respectively, after injection of 50 mg of oxacillin/kg and 10 mg of sisomicin/kg. Treatment with 50 mg of oxacillin/kg four times daily or 50 mg/kg every 4 hr around the clock for 28 days sterilized 30% of the rabbit bones. Sisomicin (10 mg/kg) injected twice daily for 28 days sterilized only 5% of the rabbit bones. In contrast, treatment with the combination of oxacillin and sisomicin for either 14 or 28 days was significantly more effective, sterilizing 78% and 85%, respectively, of the bones of treated animals. S. Aureus isolated from bones of animals treated with sisomicin alone contained aminoglycoside-resistant microcolonies. Resistant microcolonies were not recovered from animals treated with oxacillin or with the combination of oxacillin plus sisomicin. In vitro studies of bacterial killing by each antibiotic alone and in combination showed more bacterial killing with the combination than with either agent alone; in vitro the combination prevented emergence of resistant microcolonies. Combination antibiotic therapy appears to be more effective in treatment of experimental osteomyelitis due to S. aureus than therapy with a single agent.


Repeated gonorrhea: an analysis of importance and risk factors. This study was designed to assess the epidemiological importance of repeated infections due to Neisseria gonorrhoeae and to analyze variables potentially associated with repeated gonorrhea. The retrospective analysis was of 7,347 patients seen during one year, and the prospective study was of a stratified randomly selected sample of 429 patients. The 492 retrospectively identified repeaters constituted 0.06% of the county population and 6.7% of the clinic population. The 492 repeaters had 21.6% of the cases of gonorrhea reported from the county and 29.4% of the cases reported from the clinic. The repeaters tended to be younger than those without repeated infection (P less than 0.001), male (62%), black (81.7%), and residents of areas of lower socioeconomic status than those who were not repeaters (P less than 0.001). Most repeaters (73.5%) had not graduated from high school. Repeaters did not have significantly greater numbers of sex partners (P greater than 0.05) or greater exposure to prostitutes or clients than those who did not have repeated infections and less frequently had sexual contact while symptomatic. Intensive follow-up of the small number of high-risk repeaters and their contacts could result in a major reduction in the number of reported cases of gonorrhea.


Bacterial adherence to virus-infected cells: a cell culture model of bacterial superinfection. MDCK cells (a line of stable canine kidney cells) infected with influenza A/NWS/33 virus (a neurotropic variant of the Wilson Smith strain) were tested with 18 selected bacterial species to determine whether mammalian cells become susceptible to bacterial adherence as a result of virus infection. Cell monolayers were washed and examined microscopically for adherence. Bacteria of only two of 18 species were seen to adhere to the infected cells: a group B Streptococcus and Streptococcus sanguis. Control monolayers were negative for adherence. Pretreatment of virus-infected cultures with mouse ascitic fluid containing antibody to influenza A virus completely blocked adherence of the bacteria. Further testing with the strains representative of the five serotypes of group B Streptococcus disclosed that adherence occurred with types Ia, Ic, and II, but not with types Ib and III.


Cyclic thrombocytopenia induced by a Rickettsia-like agent in dogs. Hematologic manifestations and the ultrastructure of a platelet-specific microorganism isolated from a dog in Florida were studied. The agent was readily transmitted experimentally to adult dogs by intravenous inoculation with infected blood. Parasitemias and concomitant thrombocytopenias were cyclic in that both recurred within relatively constant periods of one to two weeks following experimental infections. Hemorrhage was not a manifestation of the disease even though thrombocytopenias were severe. Microorganisms were visualized by light and electron microscopy. They were observed only in platelets and were composed of single or multiple subunits (morula forms). The microorganisms were ultrastructurally very similar to those reported in Ehrlichia canis infections of dogs and Anaplasma marginale infections of cattle. Microorganisms were surrounded by single membranes which more or less conformed to the external surfaces of subunits that were surrounded by double membranes. From electron microscopic studies, it is suggested that these organisms be classified in the order Rickettsiales.


Outcome of chronic active hepatitis: influence of histocompatibility antigens and triggering factors. Twenty-five patients with chronic active hepatitis triggered by external factors (viruses or drugs) and 20 patients with cryptogenic chronic active hepatitis were studied for two to five years. The first group showed a significantly higher frequency of clinical and biochemical resolution at the end of the observation period than did the second group. The group with cryptogenic disease had a predominance of females carrying the histocompatibility antigen HLA-B8, whereas the group with virus- or drug-induced hepatitis did not differ from normal controls in regard to the distribution of HLA antigens. HLA-B8 and HLA-B12 were found in all but two patients in the group with cryptogenic hepatitis; this group of patients had elevated levels of gamma-globulin and autoantibodies in their sera more frequently than did the group with virus- or drug-induced disease. The results suggest that there are at least two types of chronic active hepatitis: one genetically determined, with signs of enhanced immunoreactivity and with a low degree of healing in five years; and another type triggered by external factors and without predisposing genetic factors. The data suggest that the clinical outcome is more favorable for patients with the second type of chronic active hepatitis.


Discrimination of hepatobiliary diseases by the evaluation of bromsulfophthalein blood kinetics. Blood BSP kinetics was studied by compartmental analysis in 10 normal subjects, 11 cirrhotic patients, and nine patients suffering from obstructive jaundice. Plasma levels of both free and conjugated BSP were determined at different times after intravenous injection of a standard dose (5 mg/kg body weight) of the dye. A six-compartment model was found suitable for the correct evaluation of hepatobiliary function, but simpler models cannot be used in this respect. Some of the parameters of the model can be adequately evaluated in the studied measurement situation and are used to carry out a diagnostic discrimination; they are lambda21 (transfer constant from blood to liver cells), alpha1 (expression of both conjugating and excretory activity), and beta (related to the blood level of conjugated BSP). It is shown that the values of these parameters allow a fairly good separation among the three groups of subjects under study.


Behçet's disease: possible role of secretory component deficiency, synovial inclusions, and fibrinolytic abnormality in the various manifestations of the disease. Detailed study of four patients with BD, four controls with recurrent aphthous stomatitis, and 12 healthy controls has demonstrated markedly decreased levels of salivary SC in both its free and bound forms, and normal total protein concentration in BD salivas. In two BD patients, SC deficiency was also found in jejunal fluids. Depressed in vitro response of blood T cells to mitogens was also noted in BD. Levels of IgA in serum were normal, as well as total numbers of T cells and IgA-carrying B cells in blood. A fluid phase abnormality of the fibrinolytic system as tested by the clot lysis assay was demonstrated in the blood from BD patients. Studies of BD SF and synovial membrane by light and electron microscopy showed inclusions composed of degenerated neutrophils inside monocytes. Abnormalities of host defense mechanisms at the mucous membrane level due to SC deficiency, together with a systemic T cell functional defect and fibrinolytic abnormality, could be important mechanisms in the pathogenesis of recurrent mucosal ulcers and thrombosis in BD.


Quantitative binding of penicillin G to tissue homogenates as determined with the preparative ultracentrifuge. The preparative ultracentrifuge was used to determine quantitative binding of penicillin G to rabbit serum and homogenates of muscle, liver, kidney, bone, lung, spleen, brain, skin, heart, and pancreas. At 10 U/ml rabbit serum bound 46.7% of penicillin G, and all tissues bound 9.0% or less. The ultracentrifuge method was reliable and reproducible and eliminated problems encountered in other methods used to study antibiotic-tissue binding. The results demonstrate only minor extravascular binding of penicillin G and allow prediction of total achievable tissue levels from knowledge of the concentration of unbound drug in the serum at equilibrium and the fraction of drug bound to each tissue. The small amount of extravascular penicillin G- tissue binding found would be expected to lower predicted serum levels by only 3.1%.


Normalization of plasma glucose of unstable diabetes: studies under ambulatory, fed conditions with pumped intravenous insulin. A program using continuously pumped IVI was devised to restore glycemia of unstable diabetes under ambulatory, fed conditions to that of nondiabetic subjects. Five patients with unstable diabetes were studied. The daily regimen consisted of four meals of equal carbohydrate, fat, and protein content taken at 8 A.M., 2 P.M., 8 P.M., and 2 A.M. and 1 hr of standardized exercise in the second postprandial hour (except after the 2 A.M. meal). Confirmation of physiologic replacement of insulin by the IVI program was possible because four patients had low insulin-binding antibodies and minimal distortion of serum IRI. Best glucose control was achieved by increasing the basal flow rate (mean, 0.15 mU/kg/min) 10-fold from 15 to 60 min after daytime meals and from 15 to 105 min after the 2 A.M. meal and doubling the basal rate overnight. Contrasted to the results with SCI, the IVI program significantly improved the mean blood glucose and mean amplitude of glycemic excursions. The IVI program restored the time to glucose peak and postprandial baseline glucose recovery to normal; the amplitude of glucose increase to peak remained somewhat greater than normal.


Determinants of baroreflex sensitivity in man. To determine the relationship of BRS to age, ACI, TPRI, and MBP, 61 male subjects, 19 to 65 years of age, whose MBP ranged from 77 to 134 mm Hg, were investigated. Partial correlative analysis was used to hold individual variables constant so that the effect of each on a given BRS relationship could be observed. An independent and significant relationship was observed between BRS and age; BRS and ACI correlated significantly through the influence of age, TPRI, and MBP; BRS and TPRI did not correlate; a significant BRS-MBP relationship existed through the influence of ACI. It was concluded that TPRI was not directly related to BRS and that the relationship of MBP to BRS was dependent on the influence of ACI whereas age was independently related to BRS.


Renal sodium retention and ascites formation in dogs with experimental cirrhosis but without portal hypertension or increased splanchnic vascular capacity. Renal handling of sodium was studied in five dogs where an end-to-side portacaval fistula was constructed prior to the induction of cirrhosis with DMN. Such a model permits the effects of cirrhosis to be studied separately from the consequences of portal hypertension. Three control animals without cirrhosis maintained normal liver and kidney function and remained in sodium balance for as long as 8 weeks following surgery. In the five cirrhotic dogs, urinary sodium retention preceded ascites formation and was independent of hyperaldosteronism, hypoalbuminemia, hepatic ischemia, or decreased renal perfusion. Portal venous pressure remained normal in all cirrhotic dogs, and the splanchnic area remained free of venous collaterals. Plasma volume expansion also preceded ascites formation, and this variable increased by 8.4% (p less than 0.05) following 6 days of sodium retention. These temporal relationships between sodium retention, expanded plasma volume, and ascites formation are similar to those observed in ordinary cirrhotic dogs previously studied in this laboratory. Total plasma volume increased by 13.2% (p less than 0.05) when measured during the ascitic phase of cirrhosis. However, when the splanchnic and nonsplanchnic ("effective") components of plasma volume were measured by an exclusion technique, the ratio of these components to total plasma volume was not different from that observed in normal dogs. Thus no preferential consignment of retained salt and water had occurred. We conclude that urinary sodium retention in cirrhotic dogs occurs independently of portal hypertension or augmented splanchnic vascular capacity and is associated with expansion of the effective plasma volume, even though ascites is present.


Dentigerous cysts of the maxilla.

Dentigerous cysts of the maxilla. Four cases of dentigerous cysts of the maxilla are recorded representing the three known types, namely: central, and multiple. The etiological theories are reviewed and treatment described.


Partial upper airway obstruction and sleep apnoea. An unusual case is described in which partial upper airway obstruction led to a sequence of events characterized by sleep disturbance, enuresis, somnolence and cardio-respiratory collapse. The upper airway obstruction was not immediately apparent as the cause of subsequent clinical events. Attention is drawn to the general medical problems which may be produced by upper airway obstruction, with particular reference to those accompanying obesity and abnormal stature.


Internal nasal implant to correct nasal valve obstruction. A simple method of correcting nasal valve obstruction is described. The procedure both widens and strengthens the nasal wall at this area. A flat piece of septal cartilage is placed so that it straddles the dorsal margin of the septum internal to the upper lateral cartilages which are not divided but remain in continuity across dorsum.


Hamartomas of the nose.

Hamartomas of the nose. Three cases of hamartomas of the nose, very rare conditions in otolaryngology are reported. According to the Willis (1953) classification two of these cases, belonged to the angiomatous, and the third one to the lipomatous, group of hamartomas.


Laryngeal involvement in multiple myeloma. A case of multiple myeloma who developed laryngeal involvement is described. The literature is reviewed to emphasize the variety of this condition. The possibility of a solitary lesion being part of a systemic condition is considered.


The use of intravenous lignocaine in the diagnosis and treatment of tinnitus. The effect of intravenous lignocaine upon the symptom of tinnitus has been assessed in seventy-eight patients and the results correlated with associated hearing loss. Lignocaine appears to be highly effective in suppressing tinnitus in patients with presumed damage or degeneration of the Organ of Corti and is less effective in other groups. It is postulated that tinnitus in patients with Organ of Corti damage is the result of abnormal hyperactivity in the auditory pathway following deafferentation.


Tinnitus: a theoretical view and a therapeutic study using amylobarbitone. A hypothetical discussion of the mechanisms producing tinnitus has been described along with an outline of previous treatments given. A small group of 40 patients with troublesome tinnitus were studied, 20 of whom were treated with amylobarbitone, and the results have been presented. An attempt is made to compare the subjective assessment made by patients of their symptom with an audiometric assessment of the same symptom both before and after the study.


The influence of nitrous oxide anaesthetic on middle-ear fluid. Nitrous oxide anaesthesia invades the middle-ear cavity, resulting in a positive pressure within this cavity. It has been suggested that the pressure may be sufficient to force open the Eustachian tube and evacuate fluid from the middle ear. This study examined the possible influence of nitrous oxide on middle-ear fluid. Pre- and intra-operative tympanograms were obtained on 39 children scheduled for myringotomy surgery. Fluid was found in 83.1% of the operated ears while the absence of fluid was noted in 16.9%. It is possible that the nitrous oxide anaesthetic did cause an evacuation of fluid from this latter group of ears prior to actual surgery.


Arterio-venous fistula of the ear.

Arterio-venous fistula of the ear. A case of congenital arterio-venous fistula involving the external ear in a 33-year-old female patient is described in this paper. She presented to the hospital with severe haemorrhage from the swelling over the ear necessitating immediate admission into hospital and transfusion of whole blood. The treatment of the case is described in detail. She is alive and well 3 years after her definitive treatment.


Precocious 'feminization' of rat liver enzymes in the presence of ectopic pituitary tissue. The presence of ectopic pituitary tissue (derived from an adult rat) in prepubertal male and female rats caused the immature, masculine-type hepatic steroid metabolism to develop into female-type metabolism. It is concluded that the hypothalamus-pituitary system controls the ontogenesis of sex-dependent steroid metabolism in rat liver.


Internal quality control of radioimmunoassays. A modified cumulative sum technique has been applied to radioimmunoassay quality control data. The method is approximately 50% more efficient in detecting systematic changes in the mean and variance of quality control values for plasma samples than more widely used conventional methods. The salient features of the technique have been restricted to changes in the mean quality control value of a plasma pool, but potential applications to changes in variance and as a diagnostic aid to problems in radioimmunoassay have been evaluated. The method is independent of computing facilities and statistical expertise since all computations have been presented in the form of a nomogram and thus can be used by technicians at the bench.


Neurophysin(s) of the golden hamster (Mesocricetus auratus) and the effects of saline imbibition. The neural lobe of the golden hamster contains one major and two minor proteins. The major protein was identified as a neurophysin in view of its electrophoretic properties, its high cysteine content and its depletion from the neural lobe upon saline imbibition. The depletion of neurophysin and vasopressin from the neural lobe and the alterations of several indices of dehydration in the blood of the hamster were less than those found in the rat upon saline imbibition, suggesting that the hamster has a greater ability to adapt to conditions in which water is scarce.


Effects of anti-oestrogen treatment of neonatal male rats on lordosis behaviour and mounting behaviour in the adult. Male rats were treated daily with 100 microgram of the anti-oestrogen ethamoxytriphetol (MER-25) or oil during the first 10 days of life and tested for lordosis behaviour and mounting behaviour as intact adults, after castration and after castration and oestradiol benzoate or testosterone propionate treatment. The MER-25-treated rats showed higher levels of lordosis behaviour than oil-treated rats in all four treatment groups. Under each of these endocrine conditions, except after castration alone, the MER-25-treated rats showed a reduced capacity to ejaculate. Treatment of the neonatal rat with MER-25 reduced body weight in adulthood but did not change the weight of the accessory sexual glands, the testes, the number of cornified papillae on the glans penis or plasma testosterone concentrations during development. The response of the accessory sexual glands and cornified papillae on the glans penis to treatment with oestradiol benzoate or testosterone propionate after castration in adulthood was unaffected by treatment with MER-25. It is suggested that formation of oestrogen in the neonatal male rat brain from testosterone in the circulation inhibits the capacity to show lordosis behaviour and facilitates the capacity to ejaculate in response to ejaculate in response to gonadal hormone treatment in adulthood.


Radioimmunoassay of oxytocin.

Radioimmunoassay of oxytocin. The evaluation of a radioimmunoassay of oxytocin is described. The method involved careful collection and transportation of blood at 4 degrees C, acidification of the plasma, extraction with Fuller's earth and radioimmunoassay using antisera raised in rabbits immunized against oxytocin conjugated to bovine serum albumin and 125I-labelled oxytocin. The antisera showed insignificant cross-reaction with a variety of small peptides including vasopressin and vasotocin. The limit of detection of the assay was 2.5 pg with intra-assay and interassay coefficients of variation of 7-15% and 12-18% respectively. Seventy-seven per cent (88 out of 116) of the pregnant women tested had detectable maternal plasma oxytocin. Serial samples of maternal plasma showed a significant increase in oxytocin from the first to the second stage of labour and a significant decrease in the third stage. Oxytocin concentrations in the umbilical arterial plasma were significantly higher in patients in labour. The significance of these findings is discussed.


Effects of inhibition of adrenal steroidogenesis on compensation of fluid loss and on survivial after limb ischaemia in the rat. In rats injected with a specific inhibitor of adrenal steroidogenesis, 4alpha,5-epoxy-17beta-hydroxy-3-oxo-5alpha-androstane-2alpha-carbonitrile (WIN 24 540), the increase in the concentration of corticosterone in the plasma caused by bilateral hind-limb ischaemia was greatly reduced. The lethality of this injury was increased. Fluid loss into the hind limbs was unaltered but the compensatory movement of fluid into the plasma was imparied. The hyperglycaemia that occurred after the injury was markedly reduced by WIN 24 540, but this was probably unrelated to the poorer compensation of fluid loss as there was no corresponding fall in plasma osmolality. The effects of injecting WIN 24 540 could be completely reversed by the simultaneous injection of corticosterone, so as to restore the rise in its concentration in the plasma. We conclude that the adrenal cortex plays an active part in the early circulatory and metabolic responses to injury, in contrast to its reportedly permissive role in the later catabolic phase.


Perinatal changes in plasma and adrenal corticosterone and aldosterone concentrations in the mouse. The concentrations of corticosterone and aldosterone in the plasma and adrenal glands of foetal, newborn and mother mice were estimated during the last 4 days of pregnancy and throughout the perinatal period. The level of corticosterone in the maternal and foetal plasma fell from day 17 of gestation until birth, and then remained stable. Whereas the corticosterone content of the maternal adrenal glands did not change significantly, that of the foetal adrenal glands reached a peak on day 19 of gestation. At every stage of gestation, the level of corticosterone in the maternal plasma was higher than that in the foetus. Changes in the concentration of aldosterone in the foetal plasma and adrenal glands were similar and characterized by peak values at birth. In the mother during the last 4 days of pregnancy, the level of aldosterone in the plasma was higher than in non-pregnant mice, but lower than that in the foetus.


Neurohypophysial hormonal control of kidney function in the Furopean eel (Anguilla anguilla L.) adapted to sea-water or fresh water. Low doses of arginine-vasotocin (AVT), isotocin and oxytocin (1 pg-1 ng/kg body weight) were antidiuretic in eels adapted to fresh water but not in those adapted to sea-water. High doses (more than 10 ng/kg) were always diuretic. No effects on tubular water reabsorption were observed and the glomerular filtration rate (GFR) was proportional to the maximum reabsorptive rate for glucose (Tm(glucose)) in eels adapted to sea-water. Increases in urinary flow appeared therefore to result from glomerular recruitment. Infusion of AVT or isotocin at low rates reduced the GFR and urinary flow of freshwater eels to the levels found in seawater eels. Vasopressin (lysine or arginine) had no direct effect on kidney function in freshwater eels but blocked both the diuretic and antidiuretic actions of the other hormones. When infused into seawater eels it was diuretic. This effect could have been due to blockade of the actions of endogenous AVT and/or isotocin.


Migratory behavior of lymphocytes with specific reactivity to alloantigens. II. Selective recruitment to lymphoid cell allografts and their draining lymph nodes. A dual-antigen, dual-isotope assay has been used to monitor the migratory behavior of selectively labeled antiallogeneic lymphocytes in mice challenged subcutaneously in all four foot pads with semiallogeneic spleen cells. 3H-labeled anti-C3H and 14C-labeled anti-C57BL lymphocytes of DBA/2J origin were pooled and adoptively transferred to multiple groups of previously challenged DBA/2J recipients. In some of the studies, separate groups of recipients were challenged with either CDF or BDF spleen cells in all four paws, whereas in others CDF spleen cells were used to challenge the right paws of each mouse in the group and BDF spleen cells to challenge the left paws of each mouse in the group. At intervals varying from 24 to 96 h after challenge, a subgroup of four mice from each appropriate group was sacrificed and the relative numbers of anti-C3H and anti-C57BL lymphocytes present in the challenged paws, draining lymph nodes, and other tissues of each mouse were inferred from the mean 3H/14C ratios of the respective tissues of that subgroup. The results of these studies firmly establish that specific antiallogeneic lymphocytes are selectively recruited to the paws and draining lymph nodes of mice challenged subcutaneously in the foot pads with semiallogeneic spleen cells and are deleted from their circulating blood and nondraining lymph nodes. A mechanism for antigen-induced selective recruitment and its possible functional significance in tumor immunology are discussed.


Complement-mediated killing of schistosomula of Schistosoma mansoni by rat eosinophils in vitro. Eosinophils from the peritoneal cavity of normal rats, in the presence of fresh normal rat serum (NRS), adhered to schistosomula of Schistosoma mansoni in vitro and killed the majority of parasites within 18 h. The reaction differed from the previously described antibody-mediated eosinophil adherence to schistosomula which occurs in heat-inactivated immune rat serum (IRS) and where adherence is mediated through Fc receptors. Adherence of eosinophils in fresh NRS was shown to be due to the activation of complement at the schistosomular surface by the alternative pathway, and it was effected through C3 receptors. The ability of eosinophils to kill in Fc-mediated adherence. This enhancement of killer activity may be due to the generation by complement activation of eosinophil chemotactic factors which increase the concentration of cells at the target surface. It is suggested that eosinophil adherence mediated through complement activation could be the principla mechanism of destroying schistosomula in the host.


Chemiluminescence of phagocytic cells caused by N-formylmethionyl peptides. N-formylmethionyl (F-Met) peptides, when added alone to macrophages or polymorphonuclear leukocytes (PMN), were found to induce a chemiluminescent response of shorter duration than that produced by the commonly employed particulate stimulant, zymosan. The cellular nature of F-Met peptide-induced chemiluminescence was indicated by its dependence on cell concentration, and by its inhibition by cell disruption, heat inactivation, or previous maximal stimulation by the peptides. Comparison of PMN and macrophages from different species showed that the maximal chemiluminescent response seen in the dose-response curve of F-Met- Phe was different in different cell types. Chemiluminescence reached highest values in human PMN, it was intermediate in guinea pig macrophages and PMN, and in rabbit PMN; but it was nonexistent in rabbit alveolar macrophages and very low in rabbit peritoneal macrophages. A definite relationship was observed between peptide structure and chemiluminescent activity. Met-Phe, F- Met and Phe were inactive even at millimolar concentrations, while F-Met-Phe caused chemiluminescence at micromolar concentrations. Four active peptides were tested in guinea pig, rabbit, and human PMN, and in guinea pig alveolar and peritoneal macrophages. The relative activity of these peptides was the same in all cells studied, e.g. F-Met-Leu-Phe >> F-Met-Phe > F-Met-Val > F- Met-Ala. The values of ED50 for each peptide were also comparable to previously reported ED50 values of these peptides in inducing lysosomal enzyme release. These results were seen both in the presence and absence ofthe chemiluminescent oxidant indicator, luminol. Low concentrations of superoxide dismutase (10 mug/ml) completely inhibited chemiluminescence caused by the F-Met peptides, suggesting the involvement of 0(2)(-) or O(2)(-)-derived compounds in this response. Sodium azide, an inhibitor of peroxidase reactions, had either no effect or a slight inhibitory effect on chemiluminescence. However, when the extracellular release of lysosomal enzymes was induced by cytochalasin B, an azide- inhibitable enhancement of chemiluminescence was seen in PMN, but not in macrophages. This effect appears to be correlated with the presence of granule-associated myeloperoxidase. Although azide-inhibitable peroxidases could be a potential source of light, they did not appear to be a significant contributor in these experiments. Based on these results and on those of previous investigators, we postulate that the F-Met-peptides stimulate 0(2)(-) production in addition to stimulating lysosomal enzyme release and chemotaxis. The similar structure- activity relationship which appears to exist for these processes may indicate that they are all initiated by a single receptor mechanism. Since F-Met peptides are formed in bacteria it is likely that their actions represent an important physiologic response.


Enhancement of platelet response to immune complexes and IgG aggregates by lipid A-rich bacterial lipopolysaccharides. The effect of the common lipid moiety of bacterial LPS on secretion from washed human platelets has been studied. The lipid A-rich LPS of S. minnesota R595 and a lipid A preparation both potentiated platelet serotonin secretion in response to IgG aggregates or immune complexes up to 50-fold but had little effect in the absence of IgG. Lipid A has been shown to bind immune aggregates, raising the possibility that its mechanism of action involved effective enlargement or insolubilization of the aggregates. IgG aggregates of dimer to tetramer size were shown to be platelet simuli, equivalent on a weight basis to larger soluble aggregates. The effect of both sizes of aggregates on platelets were equally enhanced by the LPS, indicating that increased size of aggregates alone could not account for the effect of LPS. Similarly, because lipid A-rich LPS enhanced platelet response to already insoluble immune complexes, its mechanism of action cannot simply be insolubilization of immune aggregates. These LPS did not enhance platelet stimulation by antiplatelet antibody, monosodium urate crystals, or thrombin and only slightly enhanced stimulation by insoluble human skin collagen. This indicates some stimulus specificity in the ability of LPS to increase platelet secretion. The enhancement of cell response to immune complexes by the common lipid region of LPS may represent a mechanism for the diverse effects of LPS in vivo and in vitro.


Hemagglutinin-specific complement-dependent cytolytic antibody response to influenza infection. The host defense response to influenza infection is complex. Specific humoral antibodies develop to the strain-specific surface antigens, the hemagglutinin and the neuraminidase, and to the internal antigens (matrix and nucleoprotein) which are common to all influenza A viruses (1). Antibodies to the hemagglutinin, which is the major surface antigen, neutralize viral infectivity (2). In addition to antibodies which have been detected against virion antigens, a cytotoxic T-cell response with specificity against the viral hemagglutinin on influenza-infected target cells (3-5) has been recently described. A more cross-reactive cytotoxic T-cell response has also been observed when a nonpermissively infected target cell is used in cytotoxicity assays (6,7). The present report describes the development during influenza infection and after vaccination of a cytolytic humoral antibody response which is directed against the hemagglutinin on infected target cells. This antibody-mediated lysis of infected cells in complement dependent, as has been reported with other virus infections (8-11).


Size scaling in visual pattern recognition. Human visual recognition on the basis of shape but regardless of size was investigated by reaction time methods. For successive matching of random figures, reaction time increased linearly with the linear size ratio of stimulus pairs. For single-character classification, reaction time increased with divergence between cued size format and stimulus format such that for character nonrepetitions, the increment in latency was approximately proportional to the logarithm of the linear size ratio of the two formats. However, when reactions to character repetitions were faster than those to nonrepetitions, the repetition reaction time function was similar to that for successive matching of random figures. The results suggested two processes of size scaling: mental-image transformation and perceptual-scale transformation. Image transformation accounted for matching performance based on visual short-term memory, whereas scale transformation accounted for size invariance in recognition based on comparison against visual representations in long-term memory.


Perceptual processes that may create stick figures and balance. A series of experiments looked at the pattern of dot placements created when people individually placed a single dot inside empty outline figures. The superimposed results were found to compare better with the predictions of Blum's grassfire model than with a size-constancy process. The pattern of superimposed dots conformed to the stick figure of the outlined contours. A perceptual model based on spatial harmonic analysis of complex visual scenes is offered as an explanation for the pattern of results.


An investigation of the cues responsible for figure impossibility. Two different perceptual confrontations produced by two different cues (sides that seem to twist and apparent levels of depth), which were thought to influence the perception of the degree of possibility of impossible torus figures, were examined in two experiments. In Experiment 1 it was found that net change in depth experienced with one scan around the figure was inversely related to magnitude estimates of possibility, whereas the number of apparently twisted sides was not. These results were verified in Experiment 2, a replication of Experiment 1 using stereograms of the figures, in which an interpretation of multiple levels of depth was more difficult.


Visual laterality patterns for pure- versus mixed-list presentation. In Experiment 1, an overall left visual field advantage for nonverbal form recognition was found in a pure list of forms, but an overall right visual field form recognition advantage was found when the form trials were randomly intermixed with word recognition trials. Form complexity also influenced the form recognition laterality pattern, but the complexity effects were independent of (i.e., additive with) those produced by randomly mixing forms with words. Experiment 2 found that the mixed-list laterality pattern was unchanged by a pretrial cue indicating whether a word or form would follow. Experiments 3 and 4 demonstrated that holding two nouns in memory on each trial in a pure list of forms has much the same effect on laterality pattern as mixing forms with words but that the combined effect of these two variables is no larger than the effect of either variable alone. The entire pattern of results suggests that (a) laterality patterns are caused by the interaction of several factors, (b) the effects of random mixing and concurrent verbal memory are both caused by selective left-hemisphere activation, and (c) the form-complexity effects are caused by some other mechanism--perhaps subtle difference in stimulus codability.


Binocular processing of brightness information: a vector-sum model. The relation between monocular and binocular brightness was examined. Clear evidence was found that the interaction between visual channels in binocular processing of brightness information implicates both an apparent averaging of monocular brightness when they are grossly different and a partial summation when they approach equality. A vector-sum model is shown to predict these properties. A nonmetric method was used to fit such a model to data from three experiments in each of which 15 subjects estimated brightness of binocularly fused targets. Magnitude estimation was used in two experiments, and cateogry ratings were obtained in the third experiment. When it was assumed only that subjects' responses were monotone with perceived brightness, estimates of the model's parameters from the data of the three experiments were almost identical, indicating that results from magnitude estimati;n and category rating can converge once nonlinear response functions are eliminated.


Invariance of odor strength with sniff vigor: an olfactory analogue to size constancy. Previous evidence has shown that detection threshold in humans and olfactory neural discharge rate in animal preparations both depend on flow rate of odorous vapor. But no data have been reported that show the effects of flow rate in humans on perceived odor strength at suprathreshold intensities. Subjects learned to inspire at two flow rates, one twice as great as the other, by adjusting (on a cathode ray tube) the transduced trace of a sniff-produced pressure change to match either of two target contours. They then made magnitude estimations of odor strength, while producing either weak or strong sniffs, for odorants presented over a wide range of concentrations via a specially designed sniff-bottle system. The odorant, diluted in diethyl phthalate, was n-butanol in two experiments and n-amyl acetate in two others. Subject-controlled flow rate had no effect on odor strength for either odorant. There was an apparent contradiction between these data and those on neural discharge rate that may, however, be resolved by adopting an odor constancy model: When sniff intensity varies during the olfactory exploration of an odor source, information about the rate at which odorant molecules are established at the receptor site is combined with information about sniff vigor so that the resulting percept is of invariant odor strength.


Critical-band effects in two-channel auditory signal detection. Two-channel auditory signal detection was investigated with 50-msec sinusoidal signals masked by binaurally uncorrelated noise. In the two-channel tasks, the signals in each earphone channel were presented with an independent probability during the single observation interval and the observers were required to detect the inputs in a single earphone (selective-attention condition) or in both earphones (divided-attention condition). When the signals in each earphone were within the same critical band (the assumed singled processing unit in frequency domain), there was a decrement in detection performance in both the selective- and divided-attention (i.e. dichotic) conditions compared with the monaural condition. However, when signals were separated in frequency by several critical bands, a decrement in dichotic performance, as compared with monaural performance, occurred only in the divided-attention condition. These findings are discussed in terms of their implications regarding models of multichannel signal processing and the definition of input channels in terms of earphones.


Levels of processing in speech perception. Four experiments are reported investigating previous findings that speech perception interferes with concurrent verbal memory but difficult nonverbal perceptual tasks do not, to any great degree. The forgetting produced by processing noisy speech could not be attributed to task difficulty, since equally difficult nonspeech tasks did not produce forgetting, and the extent of forgetting produced by speech could be manipulated independently of task difficulty. The forgetting could not be attributed to similarity between memory material and speech stimuli, since clear speech, analyzed in a simple and probably acoustically mediated discrimination task, produced little forgetting. The forgetting could not be attributed to a combination of similarity and difficutly since a very easy speech task involving clear speech produced as much forgetting as noisy speech tasks, as long as overt reproduction of the stimuli was required. By assuming that noisy speech and overtly reproduced speech are processed at a phonetic level but that clear, repetitive speech can be processed at a purely acoustic level, the forgetting produced by speech perception could be entirely attributed to the level at which the speech was processed. In a final experiment, results were obtained which suggest that if prior set induces processing of noisy and clear speech at comparable levels, the difference between the effects of noisy speech processing and clear speech processing on concurrent memory is completely eliminated.


Additivity in adaptation to optical tilt. Tests of proprioceptive adaptation (head-hand), visual adaptation (eye-head), and both components (eye-hand) were made during 15-min exposure to 20 degrees tilt in two experiments. In both experiments, subjects alternated exposures in which they explored hallways (hall) or viewed their active hand (hand), but in Experiment 2 subjects received two exposures to each condition, while in Experiment 1 only one exposure was given. Hall exposure produced greater visual change, and hand exposure produced greater proprioceptive change; but in both conditions, when order of conditions was controlled, the sum of performance on visual and proprioceptive tests was not statistically different from performance on the common test. In Experiment 2, adaptive components appeared to be inversely related, both within and between exposure conditions, thus providing some evidence of a reciprocal relationship, but a reliable negative correlation between components was not found. Finally, adaptation increased over alternation-repetition of exposure tasks in the second experiment, even though adaptation appeared limited within any given exposure. Results are interpreted in terms of the linear model, and the possible role of attentional factors in processing sensory inconsistencies is discussed.


A two-factor theory of stimulus-repetition effects. It is a well-documented finding that children respond more slowly to a stimulus that has been presented repeatedly just before test than to a novel stimulus. The effect, for which a two-factor theory has recently been proposed, did not occur in the only previous study of adults using a comparable procedure. Experiment 1 demonstrated the effect with adults. The previous negative finding may have been the result of too few repetitions of the stimulus. Experiment 2 provided additional support for the two-factor theory. The theory suggests that the effect is the net result of partially counteracting changes in two attentional processes. One process, the alertness elicited by a stimulus, is held to decrease as a result of repeated presentation of the stimulus, while the second process, encoding, is facilitated. The hypothesis tested in Experiment 2 was that the alertness decrement dissipates over a brief passage of time, while the facilitation of encoding does not. Subjects exposed to a repeatedly presented color were tested either immediately thereafter or after a 15-min or 30-min interval. As predicted, the observed effect shifted from one of flower response to one of faster response to the repeated stimulus as the delay interval increased.


Functional representations common to visual perception and imagination. Subjects determined whether probe dots appearing in component squares of a 5 X 5 grid fell on a figure that, depending on the condition, was (a) visually presented as a pattern of darkened squares, (b) only remembered from a preceding presentation of such a pattern, or (c) imaginally generated from a verbal code. The speed and accuracy of the responses to the probes as well as the functional dependencies of the reaction times on structural variables were essentially the same whether the figural pattern was imagined, remembered, or actually seen. Reaction times averaged between 400 and 500 msec and were consistently faster (a) for on-figure than for off-figure responses, (b) for simpler figures that had fewer squares, (c) for off-figure probes that were more distant from the figure, and (d) for on-figure probes that consisted either of more dots on the figure or of a dot at the intersection of a horizontal and a vertical bar. The reults were consistent with a model in which a subject's perceptual or imaginal representations of these forms contain barlike units that respond independently to the probes.


Normalization of irrelevant dimensions in stimulus comparisons. When subjects compared two multidimensional stimuli with respect to a single (relevant) dimension in a same-different task, variation in the irrelevant dimension systematically affected reaction times. For same trials, reaction times increased monotonically with the amount of disparity between the stimuli on the irrelevant dimension. The dimensions were heights and widths of ellipses or hues and tints of color patches. The results were interpreted in terms of a normalization process that internally transforms the irrelevant dimensions of the two stimuli until they are equal. The amount of normalization, and hence same reaction time, increased with increasing disparity on the irrelevant dimension. These results suggest that in order to decide that two objects are equivalent in some criterial respect, it is often necessary to normalize irrelevant disparities.


Visual images preserve metric spatial information: evidence from studies of image scanning. Four experiments demonstrated that more time is required to scan further distances across visual images, even when the same amount of  material falls between the initial focus point and the target. Not only did times systematically increase with distance but subjectively larger images required more time to scan than did subjectively smaller ones. Finally, when subjects were not asked to base all judgments on examination of their images, the distance between an initial focus point and a target did not affect reaction times.


Comparisons of mental clocks.

Comparisons of mental clocks. Subjects in three experiments were presented with pairs of clock times and were required to choose the one in which the hour and minute hand formed the smaller angle. In Experiments 1 and 2, the times were presented digitally, necessitating a transformation into symbolic representations from which the angular size difference could be inferred. The results revealed orderly symbolic distance effects so that comparison reaction time increased as the angular size difference decreased. Moreover, subjects generally reported using imagery to make the judgment, and subjects scoring high on test of imagery ability were faster than those scoring low on such tests. Experiment 3 added a direct perceptual condition in which subjects compared angles between pairs of hands on two drawn (analog) clocks, as well as a mixed condition involving one digital and one analog clock time. The results showed comparable distance effects for all conditions. In addition, reaction time increased from the perceptual, to the mixed, to the pure-digital condition. These results are consistent with predictions from an image-based dual-coding theory.


Interitem structure and the facilitation of simultaneous comparison. The effects of bilateral display symmetry on simultaneous comparison were examined. Experiment 1 demonstrated that symmetric letter pairs are classified as same more rapidly and accurately than asymmetric letter pairs. Experiments 2 and 3 disentangled the contributions of single-letter and whole-display symmetries (these being confounded in normal letter pairs) and showed that the primary determinant of response facilitation is the presence and registration of interitem relational structure. The last three experiments suggested that this facilitation does not arise from the detection and diagnostic utilization of symmetry. It is concluded that bilateral display symmetry facilitates the normal operations of form comparison. The early operations of field segmentation are discussed as the probable locus for this facilitation effect.


Role of visual familiarity in the word-superiority effects obtained with the simultaneous-matching task. Three experiments assessed the effect of visual familiarity of words on same-different reaction times (RTs) in a simultaneous-matching task. Visual familiarity was disrupted by using upper- and lowercase letters within sequences. The results for same judgments in Experiments 1 and 2 indicated that visual familiarity was responsible for most of the large word-superiority effect obtained. The third experiment investigated the extent to which the effects obtained with word-frequency and orthographic-regularity manipulations were due to visual familiarity. For same RTs the results indicated both types of familiarity effects were dependent on visual familiarity. With pure-case stimuli, high-frequency words were processed faster than low-frequency words. Low-frequency words and orthographically regular nonwords produced similar reaction times, and both were processed faster than unpronounceable nonwords. These effects were not evident with mixed-case stimuli. All three studies showed visual familiarity to be responsible for differences in slope over sequence length between words and nonwords. Results with different judgments were dissimilar enough from the pattern of results for same judgments to present problems of interpretation, and it was suggested that additional or alternative processes were involved. The implications of these data for models of word processing were discussed.


Acute otitis media in children: diagnostic and therapeutic dilemmas. Otitis media is still a condition with a level of diagnostic confidence lower than physicians fresh from hospital training are accustomed to. Even with improved diagnostic criteria, there will still be other influences which will affect the physician's prescribing habits, especially in the treatment of early signs of otitis media. This study shows that the determinants of prescribing behavior by ambulatory care physicians are more complex than traditional teaching of students implies. The appropriate use of antibiotics is discussed, and the importance of limiting additional medication is stressed. It is the author's contention that the outcome of care is frequently being measured without attempting to examine closely the dilemmas facing ambulatory care physicians in their day-to-day decisions. Otitis media has been used as the model in this report, but the complexities of clinical judgment are equally applicable to other common infections presenting to the primary care physician.


Pit viper snakebite in the United States. Pit viper snakebite is a relatively uncommon medical emergency which must be adequately diagnosed and treated to minimize local tissue destruction and systemic complications and to prevent death. Severity is highly variable and may range from minimal local pain and swelling to marked pain, edema, tissue necrosis, hemorrhage, shock, and death within one hour. By far, the most common complication is local tissue destruction often resulting in loss of function. Pit viper venom is extremely complex, containing factors which directly destroy muscle, blood vessels, and renal tissues. Other components anticoagulate blood and cause hypotension, local edema, and pain. Neurotoxicity is unusual, but respiratory paralysis may follow Mojave rattlesnake bites. Proper first aid consists of a proximal mildly constricting tourniquet, superficial incision at fang marks, and constant suction. Medical management consists of early intravenous antivenin in adequate dosage, after hypersensitivity testing. Other measures are largely supportive. The early use of corticosteroids is controversial. Cryotherapy is to be avoided. Fasciotomy may be necessary when edema is severe and impairs arterial perfusion. Promising developments include immunization trials against pit viper venom as well as studies on the antivenom activity of rattlesnake plasma.


The management of patients with cerebrospinal fluid shunts. This article outlines the principles of management of the patient with a cerebrospinal fluid shunt, emphasizing the clinical and laboratory methods of determining shunt malfunction or infection. Appropriate therapies for each complication are described.


The application of behavior modification to behavior management: guidelines for the family physician. Treatment in ambulatory care settings depends on the patient's behavior to implement the regimen prescribed by the family physician. Behavior modification offers a means for developing behavioral programs that will improve the physician's ability to effectively influence the patient's behavior. This article outlines some of the principles of behavior modification as they can be applied in office settings to diverse behavioral problems. Some specific suggestions are made for identifying behaviors, setting goals, delineating the steps to reach these goals, monitoring progress, and developing treatment contracts that will aid the physician in the management of the behavioral aspects of treatment.


Family therapy techniques for the family physician. Since 1960, family therapy has emerged from the general field of psychotherapy as a discipline in itself. An extensive literature has been developed, much of it based on general systems theory. Family physicians have routinely recognized problem families within their practice. Skills and techniques are suggested in this article for introducing changes within a family system.