Zinc content and the zinc-to-calorie ratio of weighed diets. The zinc content of weighed, self-selected diets of high school girls and college women varied widely. A majority of the diets contained less than the 15-mg. recommended allowance for zinc and a significant number provided less than two-thirds of the allowance. Approximately one-third of thirty diets planned and prepared for a metabolic study contained less than 10 mg. zinc. The zinc content of the metabolic diets appeared to reflect the kind of meat included. Zinc-to-calorie ratios of the self-selected diets were 8.6 and 8.8 mg. per 1,000 kcal for high school girls and college women, respectively. The metabolic diets provided a mean of 6.6 mg. zinc per 1,000 kcal. Consideration of the energy values and the zinc-to-calorie ratios of these diets suggests that energy restriction and choice of foods are important factors contributing to zinc intakes below the recommended amount.


Effect of aging on thyroid economy in man. The effects of aging on the thyroid are discussed under the headings of metabolic indices, thyroid function, hormone production, blood concentration, and thyroregulatory mechanisms. Possibly elderly men differ from elderly women with regard to thyroid economy, but the available data are too few and contradictory to permit drawing firm inferences about the effects of aging.


A psychogeriatric assessment program. IV. Interdisciplinary aspects. The interdisciplinary aspects of the psychogeriatric assessments described in three previous papers are discussed on the basis of factor-analysis findings and their significance in diagnosis, treatment, planning and theory. The difference between basic biopsychologic dysfunctions (including pathohistologic changes and various counter-regulations) and psychosocial dysfunctions (lifestyle) becomes clear statistically as well as clinically. This difference probably is fundamental, in the sense that intact biopsychologic functions are elementary tools for the psychosocial functions.


Observations on the natural history of atherogenesis. Longstanding scoliosis of the lumbar spine with convexity to the left leads to severe atherosclerosis in the adjacent segment of the abdominal aorta. By contrast, the lateral wall of the ascending aorta, which is free to pulsate, usually is not affected even in very old persons. This relative immunity, however, is not maintained in cases of syphilitic mesaortitis; damage to the elastic tissues of the media leads to atherosclerosis. Man is the only mammal known to be highly susceptible to severe atherosclerosis. The concept is advanced that the erect posture of man, which leads to the physiologic anterior curvature of the lumbar spine, predisposes to atheroma formation in the abdominal aorta, particularly in women. Evidence for the osteoporosis-atherosclerosis concept is presented. Sustained muscular activity starting early in life can delay osteoporosis and atherosclerosis. A possible mechanism for the onset and gradual progression of physiologic osteoporosis is suggested. The concept of atherogenesis advanced here is based on observations which suggest a correlation of aging processes in the mesenchymal tissues. These aging processes, in conjunction with mechanical factors partly caused by the erect posture, may account for the unique susceptibility of man to severe atherosclerosis.


Prediction of short-term outcome in newly admitted psychogeriatric patients. Thirty-six consecutive admissions to a geriatric service recently reorganized to function within a community psychiatric framework were evaluated by means of a series of behavioral and psychologic measures. Assessments upon admission and at three, five and eight weeks and five months afterward, revealed that the greatest therapeutic responses and the most discharges occurred within the first few weeks after admission. Patients remaining for longer periods tended to stabilize at a lower level of functioning or to deteriorate. A combination of two simple measures used in evaluation upon admission and relating to physical and mental functioning was found to predict the patient's status at five months (still in the hospital, dead, or discharged) with 75 percent accuracy. Use of the lambda statistic for judging the predictive power of measures is suggested.


Nocturnal neurosis of the elderly: failure of agencies to cope with the problem. About half of the elderly seen in medical consultations in several midtown Manhattan facilities have "nocturnal neurosis." This syndrome is characterized by a mixed neurosis with a pronounced nocturnal increase in the severity of symptoms, occurring in recently isolated persons. Apparently, failure of the neighborhood social network to function during the evening hours largely accounts for the problem. Few Centers provide nighttime activities. A proliferation of evening programs might significantly reduce the prevalence of nocturnal neurosis in the elderly.


Polymyalgia rheumatica.

Polymyalgia rheumatica. Polymyalgia rheumatica should be considered when a syndrome of constitutional symptoms, especially weight loss, low-grade fever, weakness, wasting proximal muscles, fatigue, malaise and depression, is seen in the elderly. Giant-cell arteritis plays a part later in the course. Thus the need for biopsy of a long segment of the temporal artery to help in determining diagnosis and therapy. An elevated erythrocyte sedimentation rate (ESR) is an important clue. The usual high value is about 80 mm/hour; if it is over 100 mm/hour, giant-cell arteritis should be suspected. Salicylates, indomethacin, phenylbutazone and hydroxychloroquine produce some clinical improvement but do not lower the high ESR; moreover, the patients are prone to experience relapses. Prednisone, however, not only produces clinical improvement but lowers the high ESR. Potassium p-aminobenzoate may be useful in maintaining the remission.


The medical director in an extended care facility. The growth of the aged population has increased the need for Extended Care Facilities. The role of the Medical Director in these institutions is extremely important in developing the needed programs and in formulating policies to insure that medical care is maintained at a high-quality level.


Errors and omissions in diagnostic records on admission of patients to a nursing home. The primary and secondary diagnoses for 100 geriatric patients consecutively admitted to a nursing home were reviewed for accuracy and omissions. Primary diagnoses were identified as the direct basis for nursing home admission. Other physical, biochemical or behavioral disorders requiring continued therapeutic care were identified as secondary diagnoses. A comparison was made of the diagnosis offered by the referring physician and the diagnosis as determined by the medical staff of the nursing home immediately after admission. In 64 percent, the secondary diagnoses were either lacking or inaccurate. The extraordinarily inadequate medical performance with respect to identifying the primary clinical and therapeutic problems of the chronically ill aged was remarkably consistent, regardless of the source of the patient's referral, whether from a general or psychiatric hospital, a private home, or another nursing home. The results of this study revealed a significant degree of unpreparedness and malaise in some members of the medical profession concerning the care of the chronically ill aged, particularly when such patients demonstrate behavioral disorders superimposed upon physical disease. Failure to identify the patient's needs through diagnosis must result in poor, inadequate or inappropriate treatment programs.


The problem of dizziness and syncope in old age: transient ischemic attacks versus hypersensitive carotid sinus reflex. In the elderly, a transient ischemic attack (TIA) and a hypersensitive carotid sinus reflex (HCSR) often co-exist and can pose a diagnostic challenge. Seven cases are presented. HCSR is a relative condition; besides increased irritability of the receptor or target organs, susceptibility of the nerve center to ischemia probably is induced by a slow heart rate or low blood pressure in any patient with pre-existing occlusive cerebrovascular disease. Dizziness and syncope of this type represent hemodynamic TIA in contrast to thromboembolic TIA. The carotid sinus massage test is recommended for differentiating the two types of TIA; the treatments differ. At present there is no uniform management that can be applied to either TIA or HCSR routinely. Therefore, treatment should be approached on an individual basis, keeping in mind the different pathophysiologic factors operating in the specific patient.


Physiologic responses of men 49 to 65 years of age to endurance training. A study was made of the effects of training for 30 minutes, three days a week for 20 weeks on certain physiologic measures of sedentary men between 49 and 65 years of age. Twenty-two subjects volunteered for the experimental group, and 8 others for the control group. Exercise sessions were conducted on a quarter-mile track and consisted of continuous bouts of walking and jogging. The average daily energy expenditures progressed from 228 to 365 kilocalories between weeks 4 and 20. For the same period, average exercise heart rates (HRs) progressed from 149 beats/minute (83 per cent maximum HR) to 155 beats/minute (91 per cent maximum HR). The experimental group showed significant increases in maximum oxygen intake (VO2 max) from 2.47 to 2.90 liters/minute (18 per cent) and in maximum pulmonary ventilation (VE max) from 105 to 121 liters/minute (BTPS), and decreases in resting HR, diastolic blood pressure, body weight, skinfold fat, and abdominal girth. Serum cholesterol and triglyceride levels and heart volume remained unchanged. The control subjects showed no significant changes. Regression analysis, with use of age as a covariate, showed a small but significant inverse relationship with changes in VO2 max. It was concluded that men of the 49-65 age group respond favorably to endurance exercise and show a magnitude of change similar to that found in previous investigations of similar design with younger subjects.


A morphometric study of the density of mitochondrial cristae in heart and liver of aging mice. Mitochondria in sections of left ventricular wall and liver from C57BL/6J mice, 9, 18, and 36 mo. old, were analyzed using stereological procedures. At 9 mo. of age mu2 cristae surface per mu3 cytoplasm(Sv-c/c was fivefold greater in heart compared with liver reflecting the larger values in the former for both mu2 cristae surface per mu3 mitochondrion (Sv-c/m) and mu3 mitochondria per mu3 cytoplasm (Vv-m):Sv-c/c = Sv-c/m. Vv-m. At 36 mo. in both tissues, Sv-c/c had decreased to 65% of the earlier value. This was due to a decrease in Vv-m alone in heart and both Vv-m and Sv-c/m in liver. In both tissues the number of mitochondria per mu3 cytoplasm (Nv-m) also decreased with age while mu3 organelle average volume (vm) remained constant, supporting previous observations: Vv-m = Nv-m-vm. These data support the views: different tissues in the same organism age independently; and mitochondrial inner and outer membranes have a semi-independent existence.


Age-related changes in hepatic fine structure: a quantitative analysis. Age-related changes in hepatic fine structure were quantitatively evaluated in virgin and retired breeder (RB) male rats by morphometric analysis. Centrolobular hepatocytes increase in size, at least up to 480 days of age, and this increase is reflected in larger volumes of nuclei, cytoplasm, organelles, and ground substance. The surface area of the smooth-surfaced endoplasmic reticulum (SER) continues to increase with age in both groups of animals, although there is a significantly greater amount of both SER and rough-surfaced endoplasmic reticulum in the livers of the virgin rats. In addition, aging is accompanied by a gradual increase in the relative volume of the lysosomes and a linear decrease in the surface area of the Golgi membranes. Evidence from this study suggests that specific alterations in hepatic fine structure occur as a function of age.


Dietary protein, life-span, and biochemical variables in female mice. The 50% mortality of female C57BL/6J mice fed ad libitum a diet which contained 26% or 4% casein, was 23.5 and 28 mo., respectively. Diet did not markedly affect the age-associated changes in the collagen content of the extractability of collagen of skin. In general, the activities of enzymes based on DNA were low in the restricted animals.


Dietary protein life-span, and physiological variables in female mice. The 50% mortality of female C57BL/6J mice fed ad libitum a diet which contained 26% or 4% casein, was 23.5 and 28 mo., respectively. Significantly lower rectal temperatures and higher oxygen consumptions were observed in the animals offered the 4% compared to the 26% casein diet. Changes in body temperature and oxygen consumption could not account for the total increase in life-span brought about by feeding a low protein diet.


The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. Standard true 24-hour creatinine clearance determinations were performed on 884 subjects of the Baltimore Longitudinal Study. On the basis of clinical data, subjects were placed in categories indicating the presence of specific diseases or medications which might alter glomerular filtration rate. Subjects not included in these categories were considered normal (N=548). In the normals, cross-sectional analysis by 10-year age groups showed a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80. Three or more serial clearances were obtained at 12- to 18-mo. intervals on 293 normal subjects. These longitudinal data showed an acceleration of the rate of decline in creatinine clearance with advancing age. The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly. A nomogram constructed from these data provides normative age-corrected standards for creatinine clearance.


Matching of successive auditory stimuli as a function of age and ear of presentation. Subjects in three age groups matched pairs of tone stimuli as "Same" or "different." Combinations of stimuli were presented in succession to the Same ear or to different ears. Matching times increased with age but were not related to slowing of simple RT. Word stimuli were matched more rapidly than tone stimuli for all conditions, but RT scores suggested that subjects were matching in term of the physical properties of word and tone stimuli rather than verbal-nonverbal dimensions. "same" and "different" reaction times differed depending on ear of stimulus presentation. Sex differences were nonsignificant and no Sex by Age interaction was observed.


The ages of adulthood: a question of numbers. To examine the number of subjective age categories in the post-high school portion of the American lifecycle, adult respondents, selected on a probability basis in Lafayette-West Lafayette, Indiana, sorted cards describing people in terms of major life events and classified them according to age. A nonlinear decrease in the number of age distinctions occurred in the late portion of middle age (46-65 years). The decrease was explained in terms of the developmental cycle of domestic units and age homogeneity of the kinship network.


Age differences in central perceptual processing: a dichoptic backward masking investigation. Age differences in central perceptual processing were investigated using young (mean age 19.5 years) and old (mean age 64.2 years) subjects in a backward masking paradigm known to produce central interference. Subjects were presented with symmetrical, straight-lined letters as target stimuli (TS). The masking stimulus (MS) was a pattern of line segments of the same width as the strokes of the letters spaced evenly over the part of the visual field occupied by the letters. The TS was presented to the right eye and followed by the MS to the left eye. A robust masking effect was found for both young and old across conditions in which TS energy was much greater than MS energy. The asynchrony between TS and MS onset (SOA) was found to be the variable describing escape from masking for both age groups. However, the older group required 24% longer SOAs than the young to escape masking, suggesting a slowing with age in central perceptual processing.


Paired-associate learning in young and old adults as related to stimulus concreteness and presentation method. This study investigated the learning of young and old adults as related to two variables, stimulus concreteness (low vs. high) and presentation method (recall vs. multiple choice vs. associate matching). The main findings were: (a) the elderly did not perform as well as the young adults, (b) for both age groups performance was better for the pairs with concrete stimuli than for the pairs with abstract stimuli, and (c) for both age groups performance was best with the associative matching method and poorest with the recall method. The paired-associate performance of the elderly is characterized by deficiencies in both response learning and associative learning.


Attitudinal predictors of devaluation of old age in a multigenerational sample. Utilizing a semantic differential measurement technique and a sample of college students (N=123), middle-aged adults (N=90), and elderly adults (N=108), this study investigated devaluation of old age in comparison to age in general. Devaluation was predicted from attitudes toward: (1) cultural values and (2) negative concomitants of old age, as well as (3) demographic variables, and (4) self-reported intergenerational contact. All age groups devalued old age. Attitudes toward personal productivity, achievement, and independence contributed significantly to devaluation of old age. Negative attitude toward death was a significant predictor of devaluation of old age among the young and middle-aged sample. The most consistent predictor of devaluation was negative attitudes toward poor health.


Social class and association membership: an analysis of age-graded and non-age-graded voluntary participation. This paper examines the relationship between social class and both age-graded and non-age-graded voluntary association membership in a sample of 320 older people. Special attention is focused on one age-graded association with an examination of recruitment, participation, and attrition over a 6-year period. No significant social class differences were found in the tendency to hold at least one association membership, or in the tendency to be extensively involved in voluntary associations. Higher class individuals, however, were more likely to belong to age graded associations. There were no significant class differences between new members and those who failed to join as the result of an aggressive peer recruitment effort by members of one "senior center." Similarly, for those who joined there were no class differences in participation or attrition over a 6-year period.


Selected social and psychological differences between men and women in later life. Older men and women (3630) were examined for sex differences in selected social and psychological characteristics. Compared to older men, older women were found to be as work-oriented and more likely to take a long time adjusting to retirement. Older women were more likely to report "negative" psychological symptoms, while older men were more likely to see changes in social participation. Implications of the findings for current theories are discussed.


Employment, retirement, and morale among older women. This study constitutes an effort to apply to females the role-theoretical orientation to work and retirement in old age which has often been applied to men. Cross-sectional data from a national probability sample of 2,398 women age 65 and over are used to test the hypothesis that older working women have better morale than those who do not work. With the exception of women with annual incomes in excess of +5,000, the findings show small but statistically significant differences both between older working women (who had the best morale) and retirees, and between retirees and women classified as never having worked (who evidenced the lowest moral). Satistically significant differences remained between these groups after simultaneously isolating the effects of age, income, and health, lending tentative support to the hypothesis and suggesting that work may indeed have a salutary thought limited psychological influence among women in the post-65 years.


Two conceptual models of the senior center. Two models of the senior center are examined: (1) the social agency model, which views senior centers as programs designed to meet the needs of the elderly and postulates that the poor and the disengaged are the most likely candidates for participation in senior centers; (2) the voluntary organization model, which hypothesizes that the elderly who are more active in voluntary organizations and who manifest strong attachments to the community are also the ones who make use of senior centers. Personal interviews were conducted with a random sample (920 respondents) of 40 elderly men and women in each of 23 New York State communities. The findings support the voluntary organization model: (1) a high score on the Chapin Social Participation Scale is associated with membership in a senior center; (2) a high score on the Community Attachment Scale is associated with membership in a senior center; (3) there is no association between social class and participation in senior centers; and (4) senior center members do not differ from nonmembers in age identification or in a preference for organizations exclusively for the elderly.


Report from the National Institute on Aging. NIH support of cellular aging research: the human diploid "fibroblast" model. The National Institute on Child Health and Human Development, NIH, had earlier committed staff time and resources toward the encouragement of the use of the cultured human cell, particularly the cell line WI-38, as a model for cellular aging. Central to this activity was a contracted supply of cells, and the support of workshops and courses. Continued support of the use of cell and tissue culture in gerontology is anticipated by NIA.


Purification of the sixth and seventh component of human complement without loss of hemolytic activity. Procedures for the isolation of the human complement proteins C6 and C7 have been described. These procedures allow isolation of the two proteins without any loss of hemolytic activity. Apparent activity gains of 160% and 140% were observed for C6 and C7, respectively, when the activity of the isolated proteins was compared with their activity in serum. The recovery of C6 was 3.5 to 11% and that of C7 was 7 to 13% of the amount present in serum. C6 has a m.w.of 128,000 and an electrophoretic mobility at pH 8.6 of -2.6 times 10(-5) cm2 s-1 v-1. C7 has a m.w. of 121,000 and an identical electrophoretic mobility. With 3 times 10(7) assay cells, 63% hemolysis was achieved with 1 ng of C6 and 3.8 ng C7. On polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and after reduction with mercaptoethanol, C6 and C7 behaved as single polypeptide chain proteins.


K cell cytotoxicity against antibody-coated chicken erythrocytes in tumor-bearing mice: its development with progressively growing tumor and the effect of immunization against the tumor. Antibody-dependent (K cell) cytotoxic activity of spleen cells from mice bearing a chemically induced fibrosarcoma has been studied by using antibody-coated chicken erythrocytes as target cells. Spleen cells from tumor-bearing animals caused a significantly greater degree of target cells destruction than did those from control animals. The elevated cytotoxic activity in tumor-bearing animals increased with time after the tumor inoculation and correlated directly with the size of the tumor. The development of increased cytotoxic activity could be circumvented by surgical removal of the tumor. Mice that received x-irradiated tumor cells of x-irradiated tumor cells followed by a live challenge did not show a tumor growth and also failed to show increased K cell cytotoxic activity. It has been concluded that the increased K cell activity results directly from the active growth of tumor. The role of K cells in immunosurveillance has been discussed.


Characterization of the target cell receptor for IgE. II. Polyacrylamide gel analysis of the surface IgE receptor from normal rat mast cells and from rat basophilic leukemia cells. Purified rat peritoneal mast cells (RMC) and cultured rat basophilic leukemia (RBL) cells were surface labeled with 125I by using lactoperoxidase, incubated with unlabeled rat monoclonal IgE and subjected to solubilization by treatment with Nonidet P-40 (NP-40). With both cell types significant amounts of radioiodinated material could be specifically precipitated by a "sandwich" system consisting of rabbit anti-rat epsilon-chain and goat anti-rabbit Ig. The precipitates were dissociated with sodium dodecyl sulfate (SDS) and urea and subsequently analyzed by SDS-polyacrylamide gel electrophoresis. With RMC three radioactive bands were seen. One corresponded to IgE present on the RMC at the time of isolation. A small band migrating in the region of light chain was seen with both sepcific (anti-IgE) and control precipitates. It showed no demonstrable relationship to IgE. The major radioactive band corresponded to a m.w. of 62,000. This band was dependent upon the presence of IgE and was not found when non-IgE binding control cells were used. With RBL cells, only the IgE-dependent 62,000 dalton peak was present. Saturation of the IgE receptor sites of the RMC or RBL cells before lactoperoxidase labeling almost totally eliminated this radioactive band, indicating that cell-bound IgE rendered this membrane component inaccessible to the radiolabel. These results strongly suggest that this cellular component is identical, at least in part, with the target cell surface receptor for reaginic antibody. The data also further support the hypothesis that the neoplastic RBL cells have a normal surface receptor for IgE.


Hapten concentrations in the circulation of animals actively immunized with hapten-protein conjugates. Animals immunized with hapten-protein conjugates subsequently circulate high concentrations of hapten bound by antibody. The levels of hapten detected are capable of significantly reducing antibody titer in the sera immunized animals. In the case of steroid-protein conjugates, the main source of increased plasma steroid concentration is the immunizing conjugate, although a contribution from increased host secretion may also occur. The results for rabbits immunized with digoxin-BSA indicate that the appearance of circulating digoxin followed the appearance of circulating antibody to digoxin. Appearance of digoxin in circulation appears to coincide with the operation of the immune response and may be related to macrophage activity. Similar conclusions are drawn from results obtained for circulating morphine in the serum of a sheep immunized with morphine-BSA. Injected hapten-protein antigens are probably processed by macrophage to produce low molecular weight haptenic fragments which are maintained in circulation for prolonged periods in the form of antibody-hapten complexes.


The class-specific immunoglobulin composition of fluids obtained from various levels of the canine respiratory tract. Sensitive and specific radioimmunoassays capable of accurately measuring the three major classes of canine immunoglobulins in the 50 to 200 ng/ml range were developed. The concentrations of IgG, IgA, and IgM in samples of fluid obtained from various levels of the canine respiratory tract (stimulated saliva, tracheal washes, and bronchopulmonary lavage supernatants) and in serum were determined by using the radioimmunoassays. The composition of the immunoglobulin classes, expressed as per cent of the total immunoglobulin content of each sample, differed markedly among the respiratory tract-derived fluids and between respiratory fluids and serum. Pilocarpine-stimulated saliva contained predominantly IgA while bronchial washes contained predominantly IgG. The contents of IgA and IgG in tracheal washes were intermediate between those of stimulated saliva and bronchial washes. There appeared to be a progressive decrease in the content of IgA (83% to 19%) and a progressive increase in the content of the IgG (6.3% to 75%) as sampling proceeded from the upper to the lower respiratory tract. The mean IgG/IgA ratios were as follows: stimulated saliva, 0.1; tracheal washes, 2.1; bronchial washes, 4.1; and serum, 23.2. All respiratory tract-derived fluids contained small amounts of IgM. Local and systemic immunization with sheep erythrocytes failed to alter the per cent composition of immunoglobulins in bronchial washes during the primary immune response. The results demonstrate major differences in the composition of immunoglobulins derived from the upper as opposed to the lower respiratory tract. The findings suggest that functional differences may exist in the immunologic apparatus associated with various levels of the respiratory tract.


The distribution of terminal deoxynucleotidyl transferase (TdT) among subsets of thymocytes in the rat. Terminal deoxynucleotidyl transferase (TdT), a unique DNA-polymerizing enzyme,has been shown to be present in a moderately dense subpopulation of rat thymocytes separated on discontinuous Ficoll density gradients. This subpopulation has been characterized by using antigenic and functional markers to identify directly and quantify cortical and medullary thymocytes. The TdT-positive thymocytes are depleted by cortisone administration, lack responsiveness to phytohemagglutinin, concanavalin-A, and histocompatibility alloantigens, bear surface antigens characteristic of cortical thymocytes (bone marrow lymphocyte antigen) and lack surface antigens characteristic of medullary thymocytes (rat-masked thymocyte antigen and histocompatibility antigens). The results indicate that TdT is present exclusively (or in markedly higher concentrations) in a subset of cells which comprised about 65% of cortical thymocytes. Two other major subsets of cortical thymocytes were identified which appeared to be TdT-negative. A minor subset of very low density cortical thymocytes was also defined. These observations have provided insight into the possible pathways of thymocyte ontogeny.


Pathogenetic mechanisms in immune polioencephalomyelitis: induction of disease in immunosuppressed mice. Immune polioencephalomyelitis (IPE) was induced by the i.p. injection of x-irradiated (10, 000 R) syngeneic line Ib malignant lymphocytes into C58 mice that were 7 or more months old and in young mice immunosuppressed by x-ray or drugs. The occurrence of IPE in young immunosuppressed C58 mice was systematically analyzed. When mice less than 2 weeks old were x-irradiated with 600 R, IPE could not be induced. The incidence in 1-month-old mice was approximately 50% and increased progressively with the age except for a drop in incidence at 3 months. An analysis of the dose effects of x-irradiation on the occurrence of IPE in mice of different ages revealed a marked increase in the incidence in 3- and 5-month-old mice beginning at dose levels of 450 R and 300 R, respectively. Considered together, these data indicated that two subpopulations of immunocytes differing in x-ray sensitivity interacted to protect mice from IPE. It appears that under natural conditions an x-ray sensitive cell population, possibly having suppressor function, decreased with age and made mice susceptible ot induction of IPE. Five-month-old mice were immunosuppressed with an LD10 of cyclophosphamide, prednisolone, or methotrexate to determine whether mice immunosuppressed with drugs also were susceptible to the induction of IPE. The incidence was 89%, 13%, and 5%, respectively. The mouse strain specificity of IPE induction also was studied. In 6- to 8-month-old mice suppressed with 600 R, IPE could not be induced in non-H-2k strains: BALB, C57BL/6, NZB. Of the H-2K strains tested (CBA/J, C3H/He, AKR/J, C58), the disease could be induced only in the C58 and AKR/J strains. Histopathologic studies showed that CNS lesions in immunosuppressed C58 and AKR/J mice did not differ significantly from those in old C58 mice with IPE. Taken together, the results of these studies indicate that IPE can be used as a model for analyzing age-dependent diseases of suspected immunopathologic etiology.


Activation of C1r by proteolytic cleavage. C1r was unable to cleave and activate proenzyme C1s unless first incubated at 37 degrees C in the absence of calcium before the addition of C1s. The acquisition of ability to activate C1s was associated with, and paralleled by, cleavage of each of the two noncovalently bonded 95,000 dalton chains of the molecule into disulfide linked subunits of 60,000 and 35,000 daltons, respectively. Thus, C1r is converted from an inactive form into an enzyme, C1r, able to cleave and activate C1s by proteolytic cleavage in marked analogy to the activation of several other complement enzymes. Trypsin was also found to cleave C1r but at a different site, and its action did not lead to C1r activation. C1r activation was inhibited by calcium, polyanethol sulfonate, C1 inactivator, and DFP but not by a battery of other protease inhibitors. C1 inactivator inhibited C1r by forming a complex with C1r via sites located on the light chain of the molecule. In other studies, cleavage of C1r was not accelerated by the addition of C1r ot C1s. C1r and C1r were found to have the same m.w., sedimentation coefficient, and diffusion coefficients. They differed, however, in charge with C1r migrating as a Beta-globulin and C1r as a gammaglobulin on electrophoresis in agarose. The amino acid composition of C1r and of each of the two polypeptide chains of Clr was determined. Both chains contained carbohydrate. Proteolytic cleavage of the C1r molecule was found to occur on addition of aggregated IgG to a mixture of C1q, C1r, and C1s in the presence of calcium. Neither C1q, C1s nor aggregated IgG alone, not C1r nor C1s induced C1r cleavage. Liquoid, an inhibitor of C1 activation, inhibited C1r cleavage. Thus, proteolytic cleavage of C1r appears to be a biologically meaningful event occurring during the activation of C1.


A rapid technique for the isolation of human IgD myeloma proteins employing ultragel AcA34. A relatively rapid technique for the isolation of human IgD myeloma proteins from whole sera is described. It is based on the use of the newly available Ultragel AcA34 gel filtration medium which yields a very substantially purified IgD fraction from whole serum. The absence of IgG from this fraction allows further purification on DEAE cellulose under conditions where the IgD protein is not absorbed but other protein contaminants are retained. The overall yield of IgD protein is estimated at greater than 90% and the technique is particularly applicable to the isolation of IgD from small serum volumes.


A solid-state competitive binding radioimmunoassay for measurement of antigens solubilized from membranes. A sensitive, solid-state, competitive radio immunological method for quantitation of antigens solubilized from membranes is described. This method is based on the measurement of the displacing activity of unknown samples of antigens on 125I-labelled antibodies bound to antigen-coated polyvinyl microtitre wells.


A rapid, sensitive and specific radioimmunoassay for human chorionic gonadotrophin. A specific, quantitative assay for human chorionic gonadotrophin (hCG) in plasma has been developed using an hCG-beta antiserum and an assay procedure lasting four hours. It employs a double antibody method and in a procedure prior to assay the two antibodies are pre-incubated in bulk and then stored in ampoules in lyophilised form ready for use. The assay procedure is a dis-equilibrium (sequential saturation) system in which the sample or unlabelled antigen is first incubated with the pre-incubated antisera followed by the addition of the labelled antigen and a further incubation. The antigen-antibody complex is separated from free antigen by vacuum filtration on glass fibre discs. The assay sensitivity is 100-200 picograms hCG/ml (0.68 mIU/ml) and is uninfluenced by normal concentrations of luteinising hormone in the sample.


Liquid scintillation counting for measurement of tritiated uptake in lymphocyte transformation in vitro: a new direct-suspension procedure. Liquid scintillation counting of trichloracetic acid extracts of [3H] TdR-labelled lymphocytes has been studied by a direct suspension method without previous solubilization. In this new method, mixing of the labelled powder in water suspension with Scintillator Emulsifying Mixture (SEM) results in a firm gel whose mechanical properties provide an heterogeneous sample ready for counting. Counting efficiency and stability of such samples are related to the amount of labelled cells. Comparative studies with standard hyamine procedure have shown that this simple and rapid method gives reliable results.


Immunoadsorbents: non-specific binding of proteins to albumin-sepharose. Human serum albumin-Sepharose was prepared by coupling human serum albumin to cyanogen bromide activated Sepharose 4B. This immunoadsorbent showed considerable non-specific protein adsorption. The adsorbed proteins were mainly immunoglobulins which could not be separated from required antibody. It is suggested that basic groups formed in the preparation of the albumin-Sepharose are responsible for this non-specific protein adsorption. Non-specific protein adsorption could be completely eliminated by neutralizing the basic groups of the albumin-Sepharose with the anionic dye blue dextran. The resultant blue dextran-albumin-Sepharose allowed purification of anti-albumin-antibody with high yield. It is shown that the isolated antibody is pure and retains its native properties.


Ultrastructure of the human dermal microcirculation: the horizontal plexus of the papillary dermis. Electron microscopy was used to define the ultrastructure of the various segments of the human cutaneous microcirculation in normal forearem skin. The organization of the vessels in the horizontal plexus of the papillary dermis was reconstructed from 1-mum plasticembedded sections. Ultrathin sections were taken at 10- to 20-mum intervals over a distance of 450 mum. Arterioles were followed through the capillary bed to their venous connections. Terminal arterioles, arterial and venous capillaries, and postcapillary venules were identified on the basis of size, cellular composition of their walls, and their relationship to the other segments of the microvascular bed. The arterial segments were characterized by a homogeneous basement membrane and the venous segments by a multilaminated basement membrane. The elastic lamina in the arterioles was a discontinuous layer which gradually disappeared from the arteriolar wall to form an external sheath just before the arteriole connected with the arterial capillary segment. The vascular walls varied from 1 to 5 mum in all of the segments of the microvascular bed. Criteria are proposed for identifying the various segments of the microcirculation so that their roles in dermatoses and vascular malformations can be evaluated.


Oxytalan, elaunin, and elastic fibers in the human skin. The elastic system of normal human skin was studied by light and electron microscopy. By light microscopy three different types of fibers were observed: oxytalan, elaunin, and elastic. The most superficial ones (oxytalan fibers) are very thin and directed perpendicularly to the dermoepidermal junction. They start from a plexus with the tinctorial characteristics of elaunin fibers which is connected with the thicker elastic fibers of the reticular dermis. At the electron microscopic level the oxytalan fibers are formed by bundles of tubular microfibrils 10 to 12 nm in diameter. In the deepest layers of the dermis an amorphous material is seen in the core of these bundles. In the elaunin fibers the amorphous material is sparse, while in the elastic fibers it is abundant and compact.


Prostaglandins and chemotaxis: enhancement of polymorphonuclear leukocyte chemotaxis by prostaglandin F2alpha. Prostaglandins E1, E2, F1alpha, and F2alpha did not demonstrate direct in vitro chemotactic properties either to rabbit peritoneal polymorphonuclear leukocytes or to rabbit or human polymorphonuclear leukocytes isolated from blood. Prostaglandin F2alpha, however, enhanced the chemotactic responsiveness of human polymorphonuclear leukocytes to the chemotactic agent casein.


The influence of corticosteroids and topical indomethacin on sunburn erythema. The extent to which topical and intradermal corticosteroids and topical indomethacin suppress sunburn erythema was investigated in human volunteers. Both agents retarded the onset and decreased the magnitude of delayed erythema. Suppression by corticosteroids was not demonstrable with ultraviolet doses larger than 2 MEDs (minimal erythema dose). Below 2 MEDs, topical betamethasone valerate produced a dose-related suppression of erythema. Indomethacin was more effective and produced a measurable dose-dependent suppression against 3 and 6 MEDs. Despite significant inhibition of erythema, sunburn damage to epidermal cells was not altered by these drugs.


Glutathione-S-epoxide transferase in mouse skin and human foreskin. Glutathione-S-epoxide transferase activity in skin was determined in six mouse strains as well as in human foreskin (from 2- to 4-day-old neonates) using two substrates, styrene oxide and 3-methylcholanthrene-11,12-oxide. Of the strains used in this study, the highest enzyme activity was noted in the skin of the Balb/c mouse. The enzyme was not inducible in skin by prior administration of 3-methylcholanthrene to the mice. Human foreskin activity was lower than that present in the adult mouse skin and ranged from 1.93 to 5.28 with styrene oxide (at 22 degrees C) and 0.17 to 0.46 nmoles/mg protein/5 min with 3-methylcholanthrene-11,12-oxide (at 37 degrees C) as substrates.


A rat skin acid esteroprotease hydrolyzing benzoylarginine ethylester: purification and properties. A benzoylarginine ethylester hydrolyzing enzyme from rat skin has been purified 54-fold by chromatography on arginine methylester-CH-Sepharose and Sephadex G-200 prior to isoelectrofocusing. The molecular weight of the enzyme is approximately 125,000. The enzyme hydrolyzes bensoylarginine ethylester, acetyltyrosine ethylester, benzoylarginine methylester, benzoyllysine methylester, and benzoylalanine methylester. Casein is slightly hydrolyzed at an optimum pH of 6.5. The enzyme is inhibited by diisopropylfluorophosphate, and p-chloromercuribenzoic acid. KC1 enhances the extraction of the enzyme, increased its activity, and is essential for its stability.


Growth requirements and lipid metabolism of Pityrosporum orbiculare. The yeast, Pityrosporum orbiculare, isolated from lesions from lesions of tinea versicolor, grows in vitro only if fatty acids from the C12 to C24 series are added to the culture medium. Except for elaidinic and nervonic acids, all saturated and unsaturated fatty acids tested support growth. P. orbiculare can synthesize various lipid fractions containing both saturated and unsaturated fatty acids from a single fatty acid. Glucose and asparagine stimulate growth but exogenous vitamins do not.


Mouse model for protoporphyria. III. Experimental production of chronic erythropoietic protoporphyria-like skin lesions. Albino mice were made protoporphyric with griseofulvin according to an established procedure. Photosensitivity flares were elicited once a week throughout a 10-month period, using black light as a source for 410 nm radiation and the flares were monitored by the intravenous injection of vascular tracers and by light and electron microscopy. Each irradiation led to a selective destruction of the endothelial cells of superficial capillaries which was followed by massive vascular leakage. The basal lamina remained largely intact, providing the scaffold for regenerating endothelial cells which deposited new basal lamina material at their periphery. Subsequent exposures to 410 nm radiation reproduced the endothelial damage and subsequent basal lamina formation; multiple irradiations thus resulted in excessive, concentric, tubelike basal lamina deposits around dermal vessels which light microscopically appeared as PAS-positive hyaline material and clinically gave the skin a thickened, waxy appearance. This model thus reproduced the skin of erythropoietic protoporphyria clinically, microscopically, and at the ultrastructural level.


Comparison of sulfobromophthalein (BSP) and sulfobromophthalein glutathione (BSP-GSH) disposition under conditions of altered liver function and in the isolated perfused rat liver. Disposition of sulfobromophthalein (BSP) and sulfobromophthalein glutathione (BSP-GSH) was compared in control, phenobarbital, or alpha-naphthylisothiocyanate-(ANIT)-treated rats, and in the isolated perfused rat liver preparation. After dye administration, BSP-GSH was found to have a more rapid early plasma disappearance rate, a more rapid appearance in the liver, and a greater rate of biliary excretion both in vivo and in the isolated perfused liver, than that of BSP. In considering these observations, it is concluded that hepatic uptake as well as biliary excretion of BSP-GSH is faster than that of BSP. Comparing BSP and phenobarbital, augmentation or reduction in plasma dye concentration, mean plasma half-life (2 to 30 minutes), hepatic dye content, and bile dye concentration, were of the same order of magnitude for both dyes. However, with dye infusion of 3.6 mumoles per kilogram per minute, phenobarbital significantly enhanced the rate of biliary excretion of BSP but not BSP-GSH and ANIT treatment had a greater inhibitory effect on biliary excretion of BSP-GSH than BSP.


On the site of decreased fluid reabsorption after release of ureteral obstruction in the rat. Fluid reabsorption in surface nephrons was studied by micropuncture 3 hours after release of complete left ureteral ligation (LUL) or after unilateral release of bilateral ureteral ligation (BUL). In 11 rats with LUL, glomerular filtration rate (GFR) averaged 0.23 +/- 0.04 ml. per minute in the experimental vs. 1.25 +/- 0.11 ml. per minute in the control kidney. GFR averaged 0.18 +/- 0.02 ml. per minute in BUL. Single nephron glomerular filtration rate (SNGFR) was decreased in the experimental kidney of LUL or BUL when determined at proximal or distal sites as compared to the SNGFR determined in shams or the left kidney following right ureteral ligation (RUL). Fractional water excretion was increased after release of obstruction. LUL 2.72 +/- 0.66 per cent; BUL 12.3 +/- 2.82 per cent when compared to sham-operated rats (0.48 +/- 0.07 per cent) or to the untouched kidneys of the RUL group (0.60 +/- 0.09 per cent). Despite increased water and sodium excretion after release of unilateral ureteral ligation and BUL there were marked differences in tubular fluid reabsorption between these two groups. Following release of LUL there was increased fractional water reabsorption along the accessible length of surface nephrons of the experimental kidney. At 55 per cent of proximal tubular length TF/Pin averaged 4.02 +/- 0.02 in LUL vs. 2.18 +/- 0.06 in shams. The mean TF/Pin at 90 per cent of distal tubular length was 31.0 +/- 1.37 in LUL vs. 10.6 +/- 0.08 in sham-operated rats. In contrast, water reabsorption after BUL was slightly but significantly suppressed proximally (TF/Pin 1.95 +/- 0.02) and markedly depressed distally (TF/Pin 3.35 +/- 0.29). These results suggest that the change in fluid reabsorption observed after relief of LUL is located at a site beyond the accessible length of surface nephrons, most likely in the collecting duct. However, the data could also be explained by alterations in fluid reabsorption in deep nephrons. The changes in fluid reabsorption seen following release of BUL reflect the additive effects of release of obstruction and a marked reduction in functioning nephron mass.


The effect of dietary sodium chloride on blood pressure, body fluids, electrolytes, renal function, and serum lipids of normotensive man. Eight normotensive white middle-aged men were given low, moderate, and high salt diets with constant potassium intakes each for periods of at least 4 weeks. There was a tendency for body weight, serum sodium, exchangeable sodium, and inulin space to increase. Indirect blood pressure measurements revealed no change in blood pressure, either supine or upright measurements, during the 3 study intervals. Inulin clearance (and presumably glomerular filtration rate) rose with increase in dietary salt. Urinary potassium excretion rose progressively as salt intake increased. Total body potassium tended to decrease with increase in dietary salt. There was no changes in the excretion of calcium, magnesium, phosphorus, nor were there changes in the blood level of potassium. There was no change in total body water. The serum cholesterol and triglyceride levels were not appreciably affected by the different dietary sodium intakes. Plasma renin activity and urinary aldosterone excretion rose progressively with the two levels of sodium restriction. These studies indicate that normal man is able to compensate for large differences in sodium intake with minor metabolic changes. These changes do not necessarily lead to hypertension over a one-month period. Nevertheless, many hemodynamic and hormonal compensatory mechanisms come into play. It is evident that hypertension might result should the sodium load not be excreted, the circulating volume become too great for the excretory capacity, or if neural or endocrine adjustments be inadequate.


Age as a determinant of renal sodium conservation in normal man. Age modifies a number of factors which determine renal sodium handling including the rate of glomerular filtration, renal hemodynamics, and the responsiveness of the renin-angiotensin-aldosterone system. This study was carried out, therefore, to examine the effects of age on the capacity of the normal human kidney to respond to restriction of sodium intake. Renal conservation of sodium and response to dietary sodium restriction was assessed in 89 healthy subjects who were free of cardiovascular, renal, or adrenal disease. The daily reduction in urine sodium which followed restriction of intake to 10 mEq. of sodium and 100 mEq. of potassium per day conformed well to an exponential function, defined by an unweighted least-squares fit. The half-time for the reduction in renal sodium excretion in subjects under 30 years was -17.6 +/- 0.7 hours, significantly faster than for subjects aged 30 to 59, who had a relatively constant half-time (23.4 +/- 1.1 hours). In subjects over 60 years of age the half-time was prolonged to 30.9 +/- 2.8 hours, significantly greater than that of the younger age group. These observations indicate that age significantly influences the kidney's capacity to conserve sodium. Age-related change must be considered in the assessment of this function in human disease.


Detrimental effects of ultrafiltration on diffusion in coils. Previous studies in dialysis coils have suggested decreases in diffusive transport with ultrafiltration. The present studies were designed to test whether increasing blood channel width, alterations in concentration gradients, or molecular sieving at high ultrafiltration rates might explain the phenomenon. Increases in blood channel width and molecular sieving can account only in part for the decreases in diffusion observed. The results suggest that ultrafiltration causes alterations in transmembrane concentration gradients from blood to bath presumably associated with solute accumulation on the bath side of the membrane or may alter bath flow kinetics. Increases in total dialysance with ultrafiltration would be even greater if decreases in diffusive transport could be prevented.


Solution properties of sulfobromophthalein sodium (BSP) compounds alone and in association with sodium taurocholate (TC). A series of in vitro studies have been performed utilizing the techniques of ultracentrifugation, freezing point depression, vapor pressure osmometry, and spectrophotometry, to study the colloid-chemical characteristics of various sulfobromophthalein sodium (BSP) compounds in aqueous solution and to evaluate the possibility of a direct physicochemical interaction between BSP and taurocholate (TC). The results of these studies indicate that: (1) BSP compounds self-associate in aqueous solution to form polymolecular aggregates. These aggregates are larger with conjugated BSP, where the aggregation number appears to increase with the concentration of BSP, compared with the more polar glutathione conjugate of BSP; (2) There is a marked physicochemical interaction between unconjugated BSP and TC and a much smaller effect between the bile salt and conjugated BSP. This interaction was minor between BSP and glycodeoxycholate or taurodehydrocholate but was reproduced fully by glycocholate. Such an interaction between BSP and TC may have physiologic importance and may help to explain the previously noted facilitated excretion of BSP observed after infusion of TC in experimental animals.


Extracorporeal treatment with cyanate in sickle cell disease: preliminary observations in four patients. The effects of extracorporeal carbamylation were determined in four patients with sickle cell anemia. Treatments were carried out in clusters every 4 to 6 weeks over a 6-month period. Mean carbamylation achieved in vivo was 1.3 moles cyanate per mole of hemoglobin. The mean in vitro P50 during treatment was 22.1 mm. Hg as compared to the pretreatment value of 30 mm. Hg. Hemoglobin concentration was increased over the 6 months by 24 per cent. The treatment resulted in the stimulation of erythropoiesis. Treated cells had a prolonged survival of about 40 days, but bilirubin did not fall. Blood volume and heart size remained unchanged. Carbamylation did not appear to alter the degree of sickling at any given O2 saturation. Painful attacks continued through the treatment period with a frequency of 84 per cent and a severity-frequency index of 77 per cent of that in the control period. There was no evidence of cyanate toxicity associated with extracorporeal therapy.


Eosinophil kinetics in the hypereosinophilic syndrome. The kinetics of 51-chromium-labeled eosinophils were studied in 6 patients with the idiopathic hypereosinophilic syndrome. The kinetics of these cells were compared with 51-chromium-labeled neutrophils of 9 normal subjects. The patient studies consistently showed that autologous labeled eosinophils transiently left the circulating cell pool in the first 3 hours after infusion, re-entered the circulating pool, and then disappeared from the circulation with a mean blood half-life of 44 +/- 2.0 hours. In contrast, the neutrophils of normal subjects left the circulation progressively with an estimated blood half-life of 12.4 +/- 2.0 hours. These data suggest that the leukocytosis of the hypereosinophilic syndrome may be due to the presence in the blood of an increased number of cells with a relatively long blood half-life.


Delivery of di-2-ethylhexyl phthalate to patients during hemodialysis. It has been determined that the plasticizer di-2-ethylhexylphthalate (DEHP) can be leached from plastic bags used to store blood. During hemodialysis patient's blood is in contact with various plastic tubings; thus, studies were undertaken to determine how much, if any, DEHP was delivered into patients undergoing hemodialysis. Serial arterial and venous blood samples were drawn into glass syringes; serum was separated in acid-washed glass test tubes and stored at -80 degrees C. until analyzed for DEHP by gas-liquid chromatography. DEHP was delivered to each of nine patients studied. The amount delivered increased with the length of dialysis, up to 150 mg. during a 5-hour hemodialysis. The metabolic fate and toxicity, if any, of infused DEHP remains to be determined.


Direct measurement of the platelet:collagen interaction by affinity chromatography on collagen/Sepharose. A method for studying the platelet:collagen interaction is described that permits simultaneous measurement of platelet adhesion to collagen and the collagen-initiated release reaction. Plasma-free platelets are passed through short columns composed of polymeric collagen covalently linked to agarose (Sepharose 2B). EDTA (0.3 mM) is used to prevent platelet aggregation. 14C-Serotonin is used to measure the extent of the release reaction. Measurement of adhesion is based upon 51Cr. In the experiments that are described, the extents of both adhesion and serotonin release were a function of the total collagen content of the column and of the number of platelets applied. Up to 100 per cent of the applied platelets adhered to the columns. As much as 70 per cent of the platelet serotonin was released. Intracellular 51Cr, lactate dehydrogenase, and pyruvate kinase, on the other hand, were not lost from the platelets. Plasma-free platelets were prepared by two different techniques: gel filtration and differential centrifugation. Both preparations gave the same results. The influence of the column temperature was also examined. At temperatures below 37 degrees C., there was a sharp drop in serotonin release, but only a slight decline in platelet adhesion to collagen. Our results suggest that the collagen/Sepharose assay system should provide a usable and greatly needed technique for studying the molecular basis for the platelet:collagen interaction for assessing platelet function in abnormal states and for investigating the mechanism of action of potential inhibitors.


The measurement of circulating red cell volume using nonradioactive cesium and fluorescent excitation analysis. Nonradioactive cesium, as an analogue of potassium, has been used to label autologous red blood cells for determination of the red cell volume in man. The initial and the equilibration concentrations of cesium are assayed by fluorescent excitation analysis (FEA), using a 600 mCi 241Americium source and a Si(Li) detector with a 1024-channel analyzer. Comparative studies with 51Chromium in 13 rabbits showed good correlation, but the intracellular cesium concentration achieved by simple incubation with 2.6 per cent cesium chloride solution was too low to be of practical value in humans. Incubation of the human red blood cells with 50 mug per milliliter of Nystatin in 2.6 per cent cesium chloride opened reversible "pores" in the red cell membrane which permitted high intracellular cesium labeling without demonstrable red cell damage. The cesium red cell volumes in 11 random human subjects differed from the 51Chromium red cell volumes by only 0.2 +/- 4.5 per cent and 2.5 +/- 7.6 per cent at blood sampling times of 10 minutes and 40 minutes, respectively. Blood cesium levels fell with a clearance half-time of 31.5 hours in 4 rabbits, and 2.4 days in 1 normal human. Fluorescent excitation analysis of cesium-labeled autologous red blood cells permits accurate determination of the red cell volume in man without associated patient radiation, thus making the procedure much more acceptable for children, pregnant women, normal volunteers, and for repeated studies in the same individual.


The value of impedance testing in diagnosis of middle ear effusion. An attempt is made to evaluate the role of impedance testing and pure tone audiometry in the diagnosis of middle ear effusions in children, by comparing the clinical predictions and the audiological predictions with the myringotomy findings. A number of cases are found to have unexpectedly dry middle ears, thus leading to a lower correlation rate for impedance testing in prediction of effusions, than in other published series. The possible explanations for this discrepancy are discussed.


Adenocarcinoma of the para-nasal sinuses. 1. Adenocarcinoma in this series is commoner than squamous cell carcinoma. 2. Adenocarcinoma is a disease mainly affecting the ethmoid sinuses whereas squamous cell carcinoma is a disease mainly affecting the maxillary sinuses. 3. Patients with adenocarcinoma survive longer than those with squamous cell carcinoma. 4. Death from adenocarcinoma usually results from intra-cranial infiltration and therefore widespread resection with the assistance of a neuro-surgeon may be needed.


Haemangioma of the nasal bones.

Haemangioma of the nasal bones. A case of haemangioma of the nasal bones is recorded. A search of the world literature has revealed 17 previously reported cases. The clinical and radiological features are reviewed and the aetiology and differential diagnosis discussed. Primary surgery is the treatment of choice and the prognosis is excellent.


Effects of haloperidol on schedule-induced polydipsia. In dose-related amounts, the drug haloperidol attenuated schedule-induced drinking by rats prefed with 0.01-mg drug added to 0, 25, 50, 75 or all of 100 Noyes 45-mg pellets. Drug pellets also induced less drinking than did regular Noyes pellets by rats that obtained these pellets at 1-min intervals by bar pressing. Haloperidol also reduced bar pressing and, temporarily, rate of reinforcement. The results appeared not to be due to a general sedative effect of haloperidol but to its selective power to reduce angiotensin-induced drinking. Thus, schedule-induced drinking, which is abnormal in not causing satiation, is controllable by a drug that interferes with the renin-angiotensin hormone system thought to regulate normal drinking.


Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells. The process of erythroid differentiation in mouse Friend leukemia virus transformed cells (T3-C1-2) was examined by following changes in several enzyme activities of the heme biosynthetic pathway and in heme concentration while the cells were undergoing erythroid differentiation after treatment with dimethylsulfoxide. Untreated cells on the one hand, have a limited capacity for spontaneous differentiation. On the other hand, dimethylsulfoxide(DMSO)-treated cells showed an increase in the activities of delta-aminolevulinic acid (ALA) synthetase, ALA dehydratase, uroporphyrinogen-I synthetase, ferrochelatase, and heme concentration by days 1, 1.5, 2, and 4, respectively. The increase of the heme pathway enzymes and heme concentration followed the order of these enzymes or products as they are arranged in the heme biosynthetic pathway. These changes induced by DMSO were effectively inhibited by treatment with actinomycin D, suggesting that continued RNA synthesis is required for the differentiation process. 5-bromo-2'-deoxyuridine (BrdU) (10(-5) M) inhibited the DMSO-induced changes of the heme pathway enzymes. BrdU was most effective when it was present during the first 2 days of cell culture. It gradually lost its inhibitory effect when added after the 3rd day or later. The BrdU-mediated inhibition was completely overcome by the addition of thymidine (7 x 10(-5) M), but not by uridine (7 x 10(-5) M). All these data suggest that a sequential induction of the heme pathway enzyme takes place during erythroid differentiation of Friend leukemia cells, and that the sequential induction of the enzymes may be due to a sequential activation of genes coding for these enzyme activities.


Subversion of host defense mechanisms by murine tumors. I. A circulating factor that suppresses macrophage-mediated resistance to infection. The subcutaneous injection of cells of any one of five unselected murine tumors resulted very rapidly in the liberation into the circulation of a small molecular weight factor that severely impaired the capacity of the host to resist experimental infection with Listeria monocytogenes and Yersinia enterocolitica. It was found that the factor appeared in blood within 8 h of injecting tumor cells subcutaneously. That it possessed potent physiological activity was evidenced by the demonstration that an infusion of as little as 0.015 ml of tumor-bearer serum strikingly suppressed the capacity of normal recipients to resist bacterial infection. It was reasoned on the basis of the knowledge that the only cells in mice with the capacity to destroy Listeria are macrophages, that suppression of antibacterial resistance was caused by the ability of the tumor-suppressor factor to interfere, either directly or indirectly, with the antibacterial functions of these mononuclear phagocytic cells. The results are consistent with the hypothesis that at least some malignant neoplastic cells are naturally selected to avoid destruction by native and acquired antitumor mechanisms of mononuclear phagocytes.


Subversion of host defense mechanisms by murine tumors. II. Counter-influence of concomitant antitumor immunity. Subcutaneous injection of murine tumor cells first resulted in a state of severely suppressed macrophage-mediated antibacterial resistance and then in a contrasting state of greatly enhanced antibacterial resistance. Whereas, the state of suppressed antibacterial resistance corresponded to a state of suppressed resistance to a tumor cell challenge, the generation of enhanced antibacterial resistance corresponded to the acquisition of concomitant antitumor immunity. It was suggested on the basis of this evidence that changes in the level of macrophage-mediated antibacterial resistance that occur during growth of the primary tumor reflected changes in the level of the host's resistance to the tumor itself. It was further suggested that the coincidental suppression of antibacterial and antitumor resistance that occurs during the initial stages of growth of the primary tumor represents the operation of a mechanism that enables the tumor to avoid destruction by macrophages. The results support the view that macrophages play an important role in native and acquired resistance to malignant tumors.


Studies on the mechanism of solubilization of immune precipitates by serum. Antigen (Ag)-antibody (Ab) aggregates prepared with several different antigens are solubilized by fresh serum at 37 degrees C (complex-release activity of serum or CRA). The rate of solubilization varies in different systems and is strongly influenced by the affinity of Ab for the Ag in the immune precipitate. With a given Ag-Ab precipitate, the maximum amount of complex that can be solubilized by individual sera is independent of the initial concentration of complexes and cannot be increased by prolonged incubation. CRA occurs in the absence of C2 and C4, but not in the absence of C3 and factor B of the properdin pathway. Addition of C2 to C2-deficient serum or C4 to C4-deficient serum enhances CRA. Solubilization does not involve extensive degradation of the complexed antibody, as might be detected by acrylamide gel electrophoresis of released antibody after reduction and alkylation to separate H and L chains. Immune precipitates can also be solubilized by incubation with monovalent fragments (Fab or Fab') of antibodies against determinants of the Ab molecules in the immune precipitate. In contrast, F(ab')2 fragments decrease the solubility of the immune precipitates. In view of these findings, we propose that CRA is mediated by the binding of functionally monovalent C fragments (C3 and C4) onto Ab molecules in the precipitates.


Lymphocyte activation by monovalent fragments of antibodies reactive with cell surface carbohydrates. Antibodies reactive with cell surface carbohydrates were isolated from normal chicken serum and were found to be mitogenic for mouse splenic lymphocytes as assayed by both blast transformation and [3H]thymidine incorporation. The Fab' fragments of these carbohydrate-binding immunoglobulins were just as mitogenic as the divalent native antibody. Moreover, succinylated Fab' fragments, which probably would not form self-associating aggregates, showed similar mitogenic properties. All of these results indicate that, at least for saccharide-specific ligands, multipoint attachment and receptor cross-linkage on the cell to which the ligand is attached may not be a stringent requirement for activation.


Determinants of the enhancement of flavored-water intake by prior exposure. The intake of a 2.0% sodium saccharin solution in rats was observed to increase as a function of both the number (Experiment 1) and the duration (Experiment 3) of prior periods of access to the saccharin flavor, but did not increase when subjects were maintained on a fluid deprivation procedure in the absence of saccharin exposure (Experiment 2). The enhancement of intake was further influenced by the schedule of saccharin preexposures in the absence of variations in the amount of solution tasted (Experiment 4). The effect was not a function of the opportunity for subjects to determine their own pattern of contact with the saccharin flavor, the opportunity for association of the flavor with hunger and thirst reduction, or the amount of saccharin swallowed during preexposure (Experiment 5). These results suggest that mere exposure to a flavored solution is sufficient to increase subsequent intakes. The phenomenon is discussed in terms of the attenuation of neophobia elicited by the novelty of flavored solutions.


Modification of the rat's acoustic startle response by antecedent visual stimulation. Male hooded and albino rats were exposed to a light flash followed at various temporal intervals by a startle-eliciting 117 db. (re 20 muN/m2) burst of white noise. The visual stimulus engendered startle response inhibition (maximally when the lead time was 64-250 msec) as well as startle response latency reduction (maximally when the lead time was 2-8 msec). The temporal functions for the effects of visual stimuli paralleled those previously reported for startle modification by acoustic events. Further study revealed that, given optimal lead times, inhibition is produced reliably by weaker visual stimuli (3 X 10-6 cd-sec/cm2) than latency reduction (3 X 10-4 cd-sec/cm2). This differential sensitivity to visual stimuli is also analogous to previously reported findings for events in the acoustic environment. It reveals that the neural mechanisms that mediate latency reduction and inhibition can be engaged by either acoustic or visual stimulation.


Stimulus generalization: some predictions from a model of Pavlovian conditioning. Three experiments examined predictions generated by incorporating a common-elements account of stimulus generalization within the Rescorla-Wagner model of conditioning. All experiments employed rats in a conditioned suppression situation. Experiments 1 and 2 found that conditioning of a similar stimulus augmented the excitation controlled by a near-asymptotic target stimulus more than did further conditioning of the target itself. Prior discrimination training between the target and the similar stimulus enlarged this effect, compared with prior discrimination between the target and another dissimilar stimulus. Nonreinforced exposure of the similar stimulus prior to its reinforcement also increased the effect. Experiment 3 examined a related prediction for inhibition. After discrimination training, extinction of the previously reinforced stimulus revealed more inhibition to the previously nonreinforced stimulus when those two stimuli were more similar. These outcomes are consistent with deductions from the present model and encourage further testing of its expansion to the case of stimulus generalization.


[Point of micropreparative high pressure liquid chromatography and thin-layer chromatography for the identification of indole compounds in human plasma (author's transl)]. Results are presented on the analysis of indolic metabolites of tryptophan in human plasma, using high-pressure liquid chromatography and thin-layer chromatography. Dichloromethane/ethanol extracts of denaturated plasma were analysed. Thin-layer chromatography proved to be more advantageous for the analysis of this class compounds because it is possible to use a specific staining reagent (4-dimethylaminobenzaldehyde). The advantage of high-pressure liquid chromatography lies in the rapid isolation and purification of unknown compounds for identification in an off-line method. This application is demonstrated with the isolation of N-acetyltryptophan from human plasma. Preliminary results are presented on the plasma concentration of indole-3-lactic acid, indole-3-acetic acid and N-acetyltryptophan in healthy persons, phenylketonurics, and uremic patients.


[Gas chromatographic determination of formic acid in urine as carbon monoxide (author's transl)]. A gas chromatographic method for determining formic acid in human urine is described. The analytical reliability of this method fullfills the criteria of statistical quality control. The rate of recovery is 101.2 to 105.7% the variability coefficients lie between 2.9 and 7.2%. The selectivity of this method is demonstrated by analysing a group of components normally occuring in urine which did not interfere with the determination of formic acid. The detection limit of about 4.3 mumol/1 formic acid in urine permits the determination of the concentration of formic acid in the urine of normal persons. The concentrations of formic acid in the urine of a group of normal persons lies between 0 and 2.79 mmol/1. The average concentration was 0.39 +/- 0.60 mmol/1.


The problem of peak identification in crossed immunoelectrophoresis: a modification of the technique of Platt et al. After a brief review of the known techniques for the identification of crossed immunoelectrophoresis peaks, the authors claim that the technique of Platt et al (1973), Clin. Chim. Acta 46, 419-429) is the most effective. This consists of blocking a protein in the first run, thereby causing the disappearance of the corresponding peak in the second dimension. The advantages of this technique with respect to the others are discussed.


[Comparative methods for the determination of the activity of serumcholinesterases (acylcholin-acyl-hydrolase E.C. 3.1.1.8) and their diagnostical value (author's transl)]. The activities of serum cholinesterases were determined in parallel with acetyl-, butyryl- and propionyl-thiocholiniodide in healthy persons and patients with acute and chronic hepatitis, cirrhosis of the liver, fatty liver, cholestasis, intoxication and malignant tumors. The following normal values were obtained: See Article. The correlations between the various methods, especially between butyryl- and propionylthiocholiniodide are statistically significant. Compared to healthy persons, the activity of serum-cholinesterases, determined with the three substrates, decreased significantly in patients with acute and chronic hepatitis, cirrhosis of the liver, intoxication and malignant tumors. A change of specificity of serum-cholinesterases towards acetyl-, butyryl- and propionylthiocholiniodide in normal persons and patients with endogenous or exogenous coma of the liver was not observed. In all cases a parallel decrease of activity in sera was determined.


Visual recognition memory for large and small binary pictures. Recognition memory for pictures was tested using matrices of 0s and 1s as stimuli in two experiments. In the first experiment dimensionality of matrices was varied (5 X 5 and 10 X 10 matrices). The results showed better recognition memory for 10 X 10 matrices. The second experiment investigated the importance of certain areas, such as center or surround, using 10 X 10 matrices only. The results suggested that neither center nor surround is given unusual weight.


Memory for descriptive and spatial information in complex pictures. Memory for several kinds of information in complex pictures was studied. Stimuli were line drawings of either real-world scenes or unorganized collections of objects. Memory was tested by recognition and reconstruction tests, given immediately and/or after a week. Organization of the pictures had little effect on memory for size, orientation, or physical appearance of objects in the pictures. There was only a small loss of these types of descriptive information over a week's time. Organization of the pictures had a major effect on memory for location of objects in the pictures. Memory for location on the horizontal dimension declined markedly for both types of pictures over a week. Performance remained high on the vertical dimension for organized pictures, and systematic distortion occurred on this dimension for unorganized pictures. Reconstruction data were compared with the performance of subjects who had not seen the pictures before. It was concluded that real-world schemata do not affect encoding of some types of descriptive information, but play an important role in both encoding and memory for spatial information.


Encoding-imagery specificity in alcohol state-dependent learning. A free-recall procedure demonstrated state-dependent learning using alcohol. Tests of long-term memory showed that both high- and low-imagery words were less likely to be recalled if stored while intoxicated rather than under sober conditions. However, information encoded and stored while intoxicated was more effectively retrieved when later tests of recall were performed while intoxicated, as compared to recall accomplished in the sober state. This dissociative recall effect was far more robust with low-imagery than with high-imagery words.


A data bank for patient care, curriculum, and research in family practice: 526,196 patient problems. The health care problems that 88,000 patients presented to 118 family physicians over two years were evaluated. As a result, 526,196 health care problems were noted. Ninety percent of all problems were contained within 169 descriptive problems using the RCGP coding system for primary care. Knowledge of the profile of patient problems as they present to the family physician will alow for the development of a logical curriculum for the family practice resident and of patient care systems in family medicine. An appropriate methodology for the development of curriculum is discussed.


Fever in childhood.

Fever in childhood. A clinical approach to the diagnosis of fever in childhood is presented. Fever can be caused by a viral or bacterial infection, drug reaction, collagen disease, neoplasm, central nervous disorder, blood diseases, or physiological changes. Short-term fever is usually a viral infection but may be a bacterial infection. Careful history and physical examination play the major role in making the diagnosis, followed by appropriate studies: throat culture , urinalysis, blood counts, x-rays, blood cultures, and specific tests. The latter are indicated for the diagnosis of prolonged fevers, which also are usually caused by common disorders. A high sedimentation rate is more likely to be associated with a serious disorder and warrants immediate investigation. Treatment is symptomatic; one should reserve specific treatment and/or antibiotics for specific illness.


Tympanometry in middle ear disease.

Tympanometry in middle ear disease. Tympanometry is an objective procedure which can aid in the identification of middle ear disease and eustachian tube dysfunction. This paper reviews its rationale, operation, and applications. The test procedure is simple and can be performed by trained personnel. The test is valid and reliable and can be used with children without discomfort. The results of tympanometry are quantifiable, recordable, and easy to interpret. The routine use of tympanometry in the family physician's office would offer a valuable tool in the identification and management of middle ear problems.


Evaluation of the Abuscreen for methadone. The increased use and abuse of methadone in recent years has posed a problem of both its identification and quantitation in body tissues. Recent development of a radioimmunoassay for methadone appears to have solved the problem. In our hands the assay was extremely sensitive and specific. It also appears to be an excellent tool when quantitative estimates are to be obtained. Although it initially appears to be relatively expensive, the time saved in doing a complete tissue distribution equalizes the cost. It is hoped that other radioimmunoassays currently under development will prove as satisfactory.


Correlation of lead and cadmium in human urine. A statistical evaluation of the relationship between elevated concentrations of lead and cadmium in human urine is presented. The importance of the 24-hour continuously collected urine sample is confirmed.


Studies on fluorescamine: Part I--Applications of fluorescamine in forensic toxicological analysis. This paper describes some applications of the fluorescamine spot test to forensic toxicological analysis. The fluorescamine test only reacts with primary amines; thus, this test makes a clear-cut distinction between amphetamine and methamphetamine. Previous common spot tests used reacted the same with these two amines. Fluorescamine is 100 times more sensitive in detecting amphetamine extracted from urine on thin-layer chromatograms than ninhydrin. Thus, it is a more sensitive method of detecting amphetamine abuse in urinalysis screening programs.


A rapid microtechnique for the detection of trace metals from gunshot residues. The most important facts and advantages of this method are as follows. 1. A simple separation and identification scheme for metals considered characteristic of gunshot residues was developed. 2. The apparatus used is inexpensive, simple, extremely versatile, and has moderate sensitivity. 3. Blanks of background ions present do not interfere with the test, but warrant consideration. 4. Few reagents are needed, and the results are preservable.


Time of firing of shot shells.

Time of firing of shot shells. The possibility of ascertaining approximate time of firing by utilizing the phenomenon of rate of escape of gaseous products of combustion has been investigated with special reference to 12-bore, 2 1/2-in. (6.35-mm), fired cartridges made by the Indian Ordnance Factory. The relative rate of escape of gases has been determined indirectly by ascertaining the time needed to develop color in reagents by escaping gases by diazotization and coupling reaction. It has been observed that although the time to develop color tends to increase with the time lapse after firing, the observations are not interpretable for all possible time intervals due to overlapping and insignificant increase in certain intervals. A choice of suitable time intervals may be found to be useful in ascertaining the approximate time of firing, which may be determined experimentally in each case. Normal variation due to atmospheric conditions has been found not to have significant influence under certain limits. The method suggested has been found to be comparatively more useful than the already existing methods.


Toxicological findings in victims of traumatic deaths. The toxicological findings from 6037 analyses of viscera obtained from victims of traumatic death are used to correlate the relative incidence of carbon monoxide, ethyl alcohol, narcotics, hypnotics, analgesics, and tranquilizers-antidepressants in deaths occurring under the following circumstances: fire related, asphyxia by hanging, by use of plastic bags, from physical obstruction of trachae, and by drowning; traumatic injury from impact of moving train, fall from height, and occupational accident; traumatic injury to pedestrian, driver, and passenger from vehicular accidents; and from violent death by shooting, stabbing, strangulation, and beating. The influence of alcohol, narcotic drugs, and tranquilizers on carbon monoxide can be seen in some of these traumatic deaths. Ethanol alone and in combination with other drugs was present in 42.3% and 19.5% of driver and pedestrian victims, respectively, of vehicular accidents in the year 1974. Comparative analysis is presented for the toxicological data obtained on victims of homicide (shooting, stabbing, strangulation, and beating) in New York City and similar data reported for victims of homicide in Detroit. In New York City 45.9% of such victims died while under the influence of alcohol or narcotic drugs, or both, with methadone predominating in the latter category. Tissue concentrations of drugs found in victims of traumatic death are presented. Diphenylhydantoin, diazepam, meperidine, and slow-acting barbiturates were found in normal therapeutic levels. Higher concentrations of amitriptyline, chlorpromazine, propoxyphene, short-acting barbiturates, and methadone were observed. The concentration of methadone in blood and brain (0.13 +/- 0.14 mg/100 ml) and in liver (0.53 +/- 0.42 mg/100 ml) in cases of traumatic death are not different from those observed in deaths classified as due to methadone overdose.


Age of attainment of mineralization stages of the permanent dentition. The ages at which the maxillary and mandibular teeth of 121 boys and 111 girls reached 14 mineralization stages were determined from serial cephalograms at the Burlington Growth Centre. The present data are more comprehensive than any previously available and can be applied to chronological age determinations in juveniles of indefinite age, and of specimens in anthropological and forensic investigations. The sexes differed in the age at which they attained the stages of mineralization, with the canines demonstrating the greatest difference. In each sex, the ages at identical stages were similar for the corresponding teeth in the maxilla and mandible. Variability in age was greater among the males, especially for the first premolars, and increased with age, except for the third molars. Variability in age of third molar mineralization was greater in females and diminished among both sexes at late stages of root formation.


Some aspects of normal behavior: their use in understanding problems encountered by document examiners. The premise that progress in document examination will depend on employing techniques useful in the more formal branches of science is not exactly logical. The correlation between the work of the document examiner and the behavioral sciences has been discussed by presenting some random thoughts which have occurred to the author over a period of years. The suggestion is made, by illustration and implication, that the unfortunate connotation of the word "behavior" with the word "graphology" has tended to direct the attention of document examiners away from a study of the behavioral sciences, a branch of science from which much can be learned. The fact that the subjective concepts of probability formed by the mature document examiner will approach mathematical expectation has been noted.


IBM correcting selectric typewriter: an analysis of the use of the correctable film ribbon in altering typewritten documents. From the point of view of a document examiner, the advent of the Correcting Selectric typewriter has not changed any of the procedures ordinarily used in the examination of altered typewritten material. The same precautions should be observed in conducting examinations of such material as would be observed in making examinations for any other type of possible alteration on negotiable instruments. The security question raised with the Correcting Selectric is no different than the questions raised when an eraser was put on a pencil or a chemical bleach was found to remove ink on paper. The Correcting Selectric might even be compared to the introduction of ball-point pens on the market in the late 1940s. At that time, financial publications were suggesting that ball-point pens should not be used on any negotiable or valuable document as the ink was considered to be too readily transferable, and it was thought that they left little in the way of individual writing characteristics. However, it was not long before financial institutions were supplying such pens on their counters. Because of the complexities involved in using the Correcting Selectric to alter a document, it is felt that such problems will prove to be less prevalent than those involving other means of alterations.


Loose associations and disordered speech patterns in chronic schizophrenia. The present research involves the development and utilization of a method to evaluate the free speech of chronic schizophrenic patients to measure aspects of thought disorder. Using this technique, two samples (one chronically hospitalized, the other nonhospitalized) of 15 chronic schizophrenic subjects each studied and compared. Severe types of looseness of association were not a prominent finding in the patients studied. On several of the other categories of speech patterns in investigated, multiyear hospitalized chronic schizophrenics were found to have significantly higher scores than a sample of chronic schizophrenics living in the community. This included a measure of paucity of speech, of perseveration, of repetition, and a measure of overally deviant verbalizations. The chronic schizophrenic patients generally showed high degrees of perseveration and paucity of speech, variables which may be related to impoverished thinking. The significance of these results is analyzed and discussed, with several aspects of the data suggesting that the differences may be due to severity of illness. The phenomenological scoring system developed and utilized is found to be reliable and seems to represent a useful tool for the study of many aspects of the schizophrenic patient.


The effect of a change of director in a psychiatric inpatient unit. Suicide, aggressive acting out, and increased numbers of AWOL patients are distinct possibilities if internal structures of psychiatric impatient units are altered-especially in units that offer intensive therapeutic experience on a short term basis to severely ill patients. One such time is when the directorship changes in this kind of unit. A sucessful unit is frequently thought to be the result of the charismatic leadership of its chief. With his departure, the unit loses its elan and becomes an uninspired pedestrian operation. Hence, such a unit loses personnel and even its program when the chief changes. In this paper, the authors give data to support the hypothesis that a unit with a specific philosophical treatment orientation will continue to function at a relatively high level of effectiveness and efficiency regardless of the difference between chiefs.


Suicide following psychiatric hospitalization. The hypothesis was tested that following psychiatric hospitalization, those subjects who subsequently completed suicide would be distinguished from those who did not by the interaction of two circumstances: a state of defenselessness at the time of hospitalization, and experience of adverse life events following release from hospital. Subjects were 40 male VA psychiatric inpatients: 20 who completed suicide following release, and 20 controls matched on age, race, and time at risk in the community. Defenselessness (the incapacity to defend against distressful negative self-feelings) was defined in terms of scores derived from the extended Brief Psychiatric Rating Scale administered shortly after the patient's hospitalization. Adverse life events were eight events characterized simultaneously as undesirable, unlikely to have been initiated by the subject, and having a score of 30 or above on the Social Readjustment Rating Scale. In confirmation of the hypothesis, it was found that completed suicide subjects were significantly and appreciably more likely both to have had high defenselessness scores at the time of hospitalization and to have experienced adverse life events during the posthospitalization period, whereas neither circumstance in the absence of the other was predictive. The findings support the position that suicide is a response to experiences with self-threatening implications, in the face of personal incapacity to defend against, adapt to, or cope with such experiences.


A 2-year follow-up of 72 hyperactive boys. Classroom behavior and peer acceptance. A 2-year, prospective follow-up of 72 hyperactive boys (94 per cent of the initial sample) examined classroom and home behavior, academic achievement, peer status, and depressive symptomatology for patients and a matched control group. Sixty-five per cent of the sample was still on medication at follow-up. The patient group continued to manifest behavioral and academic difficulty. Off-drug classroom behavior showed considerable stability from baseline to 2-year follow-up which did not appear to be significantly influenced by change of school or interim stimulant drug treatment. Academic difficulties, low peer status, and depressive symptoms exceeded that of the control group. Low peer status at 2 years were predicted for the patient group by baseline (but not current) classroom hyperactivity. The continued difficulties for this middle-class sample, in spite of faithful stimulant drug intake, ancillary educational and psychiatric support, are disappointing. However, as no untreated comparison group was available, the relative benefit of continued drug treatment could not be directly examined. Some indirect evidence, however, indicates that although drugs may continue to have a suppressant effect on impulsive and hyperactive behavior, peer status and academic achievement may not be improved. An "optimally medicated" group (86 per cent of responders from an initially randomly assigned group) had almost identical academic achievement and social acceptance as did a group of dropouts from drug treatment, or the sample as a whole.


Father-son incest: a case report.

Father-son incest: a case report. A case of father-son incest is presented. There were three sexual involvements over a period of 6 weeks that ranged in activity from genital fondling to anal penetration. The father was the initiator of the activity and was drunk during each of the episodes. The son passively submitted while the mother denied the activity when told about it after the first episode. The marital situation had deteriorated over the years to an almost complete breakdown of communication. The father had been struggling with latent homosexuality for a long time, and the alcohol triggered the incidents. There was no evidence of any special relationship between father and son, except for the acting-out behavior and the challenging of parental authority by this particular son. Short term, behavior-oriented marital sessions helped to improve the situation at home.


Recent life events and acute schizophrenic psychosis: a controlled study. In this case control study, first admission schizophrenic patients were found to report more recent life events overall and more events categorized as undesirable, familial, relocation, and legal than controls. Interpretation of the observations should be ventured cautiously given the small difference between schizophrenics and controls, the small number of subjects, the retrospective strategy, and the failure of events "independent of one's control" or events characterized as "threatening" to confirm the positive relationship of recent life events to the occurrence of illness. The present work is part of considerable recent research documenting a relationship between the amount and/or significance of recent life events and the occurrence of psychological symptomatology and major psychiatric syndromes. The overall difference between schizophrenics and normals in reporting events appears to be smaller in magnitude than the difference found between depressives and normals. Further, the significance of events for schizophrenics and for depressives is different. The number, type, severity, and pattern of recent life events reported by schizophrenics suggest a precipitating role of events rather than a formative one. These results are consistent with one other controlled study on schizophrenia and recent life experience.


Coping with interpersonal conflicts through life events and hospitalization. Previous studies have helped to explicate the coping process prior to hospitalization by investigating the frequency and pattern of life events during this period. The present study extends the empirical applicability of the model to the period following hospitalization. Predictive validity for the model is provided by an investigation of posthospital community adjustment and rehospitalization. It was found that the resolutions of interpersonal conflicts during the period of hospitalization enhanced the ability to predict these outcome measures substantially when the conflict resolutions were added as predictors to patients' demographic and background characteristics, their hospital behavior, and their therapists' evaluations. Two case histories are presented to illustrate the applicability of the model for furthering the understanding of individual patient's lives.


Centrol and peripheral correlates of anxiety: a comparative study. Physiological measurements and mood ratings were recorded in 32 normal subjects at rest and under differing stressful conditions designed to induce anxiety. The physiological measurements were recorded simultaneously using a polygraph and on-line computer analysis; these comprised the peripheral measurements of pulse rate, skin conductance, spontaneous fluctuations in skin conductance, respiratory rate, and finger tremor, and the central measurements of resting electroencephalogram and averaged evoked potentials to an auditory stimulus. Mood rating were recorded using analogue rating scales, the 16 scores obtained being reduced to three mood factors. Correlations were calculated between the mood factors and each of the physiological measurements. The highest correlations were between the anxiety factor and the central measurements, particularly the proportion of electroencephalographic activity between 7.5 and 13.0 Hz, and the latencies of the secondary components of the evoked response. The peripheral measurements correlated rather less well with mood, but skin conductance and fluctuations in skin conductance, pulse rate, and tremor near the peak frequency of 9 Hz all correlated significantly with anxiety. Only two correlations were greater than 0.4, illustrating that no measure was a specific index of anxiety. Refinement of central rather than peripheral measurements is likely to lead to closer correlations with anxiety and other mood states.