Monitoring of lead in the environment.

Monitoring of lead in the environment. Children living near a lead works and children of employees at the works were selected in order to analyse the lead content of their blood as the biological counterpart of a monitoring exercise for lead in the environment. The overall mean for the 262 children in the survey was 0.91 mumol/l and results were within the normal reference range of 0.3 to 1.8 for all except two children. The results compared favourably with similar areas, and with a survey in the same area in 1972. The mean for the 71 children of employees at the lead works was 1.02 mumol/l, significantly higher than the mean for the other children in the survey (0.88 mumol/l). No appreciable differences were found in housing or wind direction. The means for all groups were unexceptional, but some of the differences were significant. Younger children had significantly higher blood lead levels than older children, and the group of 26 children with levels of 1.3 mumol/l or more was doubly weighted with the youngest age group. After careful investigation, no deviations from normal health were found in this group. The weighting of younger children also contributed to the significance of the higher mean found for children living in the central half of the area.


The association between blood pressure and serum cholesterol in healthy men: the Oslo study. The association between serum cholesterol and blood pressure (BP) has been studied in 16 525 men. The study reveals that these Oslo men in their forties present with a serum cholesterol value which is on average 0.71 mmol/l (27.4 mg/100 ml) higher at diastolic BP greater than 110 mmHg than at BP less than 70 mmHg. According to earlier studies in Oslo, this cholesterol difference alone imparts a 10-year myocardial infarction morbidity difference of 25--30%. These findings might be of practical importance for epidemiological studies and for preventive measures against the two factors. The influence of other variables on the association between blood pressure and cholesterol has been studied in a multivariate analysis. Of these variables, only body mass index and serum triglycerides significantly influence the relationship between blood pressure and cholesterol, whereas age, cigarette smoking, non-fasting blood sugar, season, socioeconomic status, and physical activity at work and leisure do not influence the correlation.


Interpregnancy interval. Association with birth weight, stillbirth, and neonatal death. Pairs of first and second births and pairs of second and third births to the same Norwegian mothers were studied to determine the association between interpregnancy interval and birth weight, stillbirth, and neonatal death. Use of the pair approach provides one birth which could possibly have been affected by the length of the interval and one birth which could not. The association of interval and birth weight for births which precede an interval is found to be equivalent to that for births which follow an interval. The data on stillbirth are compatible with higher rates at long intervals while the data on neonatal death are consistent with higher rates at short intervals. However, we conclude that manipulation of the interval between pregnancies is unlikely to have any marked, direct, beneficial effect on outcome of pregnancy.


An epidemiological study of blindness in an Indian rural community. A house-to-house survey of blindness in an Indian rural community covering a population of 20 134 in 12 villages revealed a prevalence rate of 35 blind and 144 partially blind persons per 10 000 population. Blindness was significantly associated with the age, sex, marital status, occupation, and socioeconomic status of the respondents. Caratact, glaucoma, smallpox and trachoma were the main causes of blindness. Preventive measures can reduce the toll of blindness in such a community.


Changes in local clinical practice following an experiment in medical care: evaluation of evaluation. The changes in clinical practice following a randomised controlled trial of early discharge for inguinal hernia and varicose veins are reviewed. A significant reduction in mean length of stay was recorded in the study area between 1970 (the year before the start of the study) and 1975 (two complete years after the study). This change was not found in two adjacent health districts.


Occupational mortality: work or way of life? For more than 100 years the Registrar General has reviewed mortality in depth in a series of supplements relating extra information provided by decennial censuses to deaths in a period before and after the census. The volume describing occupationl mortiality in 1970--72 was recently published (Registrar General, 1978). Here we consider in more detail one of the questions raised by occupational mortality studies: how much does mortality of an occupation group reflect work environment and how much way of life? We first describe the traditional method of distinguishing these direct and indirect influences (that is, the comparison of the mortality of men following an occupation with that of their wives) and then introduce an alternative which we call 'social class standardisation'.


A national study of asthma in childhood. A history of asthma was obtained in 3.5% of a representative national sample of children aged 11 years. A further 8.8% had a history of wheezy bronchitis. In the 12 months before the interview, 2% had experienced attacks of asthma and a further 2.9% attacks of wheezy bronchitis. Both conditions were significantly more common among boys than girls, and a history of asthma was reported more frequently among children from non-manual than from manual social classes. Children with frequent attacks of wheezing had lower mean relative weights. A history of eczema and hay fever was more frequently discovered in children with reported asthma than in those with wheezy bronchitis, whereas migraine or recurrent headaches, recurrent abdominal pain, and recurrent throat or ear infections were more commonly associated with wheezy bronchitis than with asthma. The modified Rutter home behaviour scale, which reflects the parental view of the child's behaviour, was significantly raised among children with a history of wheezing, but their school behaviour as judged by the Bristol social adjustment guide showed no such difference. In spite of increased absence from school because of illness, no differences were found in educational attainment between children with a history of asthma or wheezy bronchitis and those with neither condition.


Factors related to respiratory and cardiovascular symptoms in the United Kingdom. Factors related to eight respiratory and cardiovascular symptoms have been studied in a sample of 12 736 men and women aged 37 to 67 living in England, Scotland and Wales. The prevalence of each of these symptoms was independently associated with increasing age, with lower social class, with living in wales, and with exposure at work to fumes or to dust, especially in mines or quarries. Prevalence of some symptoms was also increased in those who were divorced, separated or widowed, who took less exercise or who were seriously over or under weight. Respiratory symptoms increased with the number of cigarettes smoked, with level of inhalation, and with the smoking of plain rather than filter cigarettes, though the last two associations were significant only for some symptoms. Smokers who had given up for five years or more had levels of symptoms similar to those who had never smoked, while pipe and cigar smokers had markedly fewer symptoms than cigarette smokers. The relationship between smoking and cardiovascular symptoms was not as clear as the relationship between smoking and respiratory symptoms.


Parental smoking related to adenoidectomy and tonsillectomy in children. Histories of adenoïdectomy and tonsillectomy were ascertained, as well as smoking habits of both parents, using questionnaires answered by 3920 schoolchildren aged 10 to 20. Adenoïdectomy and/or tonsillectomy, considered as an index of repeated upper respiratory tract disease in early childhood, was very significantly related to the amount of smoking by each parent. This relationship persisted when age, sex, day nursery attendance, sibship size, and history of appendicectomy were controlled.


Effects of stimulus frequency on two-tone suppression: a comparison of physiological and psychophysical results. The effects of stimulus frequency on two-tone suppression were investigated in single auditory-nerve fibers of anesthetized cats and compared with human psychophysical data. In the physiological experiment, both average discharge rate and phase-locked activity were measured in response to one- and two-tone stimuli. The first component f1 produced an increase in rate above spontaneous activity when presented alone. The second tone f2 was always well below the fiber's characteristic frequency and was held at a fixed sound pressure level appropriate to produce two-tone suppression. Responses were plotted as a function of stimulus level of the first tone both alone and in the presence of f2. For different values of f1 with f2 fixed, suppression was maximum with f1 near fiber CF. In the psychophysical experiment, similar stimulus parameters of f1 and f2 were used as the masker in a forward-masker paradigm. In this experiment the addition of the second masker tone at frequency f2 could produce less masking of the signal. When f1 was varied with f2 fixed, the relative decrease in masking, analogous to suppression, was greatest when f1 was equal to the signal frequency.


Acoustically dependent latency shifts of BSER (wave V) in man. The latencies of wave V in Brain Stem Evoked Responses (BSER) elicited by a set of acoustic transients were measured. The stimuli were produced by delivering pulses to two filters, arranged in series. The filters were set so that the maximum acoustic energy in the transients, i.e., filtered clicks, occurred at 0.5, 1, 2, 4, or 8 kHz. The filtered clicks were presented via earphones at a rate of 30/s at 20, 40, or 60 dB HL to ten subjects with normal hearing. The latencies of wave V varied systematically with center frequency of the filtered clicks when they were each at the same HL. Stimuli presented at 40 dB HL produced the greatest opportunity for relating stimulus frequency to latency. The latencies for a smaller set of responses to stimuli presented at 10/s were the same as those for the principal data taken at 30/s. The changes in latency of wave V due to frequency are similar to those observed by other investigators in whole-nerve responses recorded in man.


The influence of middle-ear muscle contraction on auditory threshold for selected pure tones. The influence of middle-ear muscle (MEM) contraction on auditory threshold has been measured for pure tones of 0.25, 0.5, and 1.5 kHz. The reflex-activating signal was a 3-kHz pure tone. Signal paradigms were chosen to reduce or eliminate the effects of binaural loudness summation, contralateral direct masking, and contralateral remote and backward masking effects, and to maximize the influence of MEM contraction. Results indicate that under no condition was behavioral threshold affected by the MEM contraction induced using a pure-tone stimulus of 3 kHz, 105 dB SPL.


Amplitude-modulated noise: the detection of modulation versus the detection of modulation rate. Modulation threshold, that is, the modulation depth required to discriminate a sample of amplitude-modulated (AM) noise from a sample of unmodulated noise, was measured as a function of modulation rate (16--320 Hz), modulator waveform (sine or square), and the bandwidth of the AM noise (0.5--8.0 kHz). Modulation threshold increases monotonically with modulation rate, sine-wave thresholds are greater than square-wave thresholds, and threshold rises as the bandwith of the AM stimulus decreases. These effects all support the use of some form of energy detection model to explain modulation threshold. The modulation thresholds were compared with pitch thresholds gathered under precisely the same conditions. Pitch threshold or, alternatively, rate threshold was taken to be the modulation depth required to decide which of two samples had the higher modulation; the rate difference was 20%--just over three semitones. In the region above about 70 Hz, rate threshold is essentially a constant multiple of modulation threshold, indicating that the primary constraint on rate threshold is the audibility of the modulation. Below 70 Hz, rate and modulation threshold diverge; it is argued that the limit on rate threshold in this region is probably the length of the correlation required to extract the periodicity.


Masking-level differences for repeated filtered transients. Masking-level differences (MLDs) for the repeated high-pass (2000-Hz) and low-pass (2000-Hz) 100-microseconds pulses were obtained as a function of the number of transient repetitions and the repetition rate. MLDs compared to the NoSo condition were obtained for the NoSpi and NoSd binaural configurations (Sd refers to the conditions in which there was a 1.1-ms interaural delay for the transient signals). MLDs of 11--14 dB were obtained for the low-pass transients independent of the number of transients, repetition rate, or type of binaural configuration. MLDs of 2--4 dB were obtained for the high-pass transients only if the transients were repeated 12 or more times. The results for the high-pass transients did not depend on the repetition rate or type of binaural configuration. The results suggest that high-frequency binaural auditory channels can process noisy low-frequency temporal envelopes, but not as well as low-frequency temporal and spectral information.


Intensity of guitar playing as a function of auditory feedback. Subjects played an electric guitar while auditory feedback was attenuated or amplified at seven sidetone levels varying 10-dB steps around a comfortable listening level. The sidetone signal was presented in quiet (experiment I) and several levels of white noise (experiment II). Subjects compensated for feedback changes, demonstrating a sidetone amplification as well as a Lombard effect. The similarity of these results to those found previously for speech suggests that guitar playing can be a useful analog for the function of auditory feedback in speech production. Unlike previous findings for speech, the sidetone-amplification effect was not potentiated by masking, consistent with a hypothesis that potentiation in speech is attributable to interference with bone conduction caused by the masking noise.


Aural harmonics: estimation consistency from tone-on-tone masking measurements. Amplitudes of inaudible "subjective" signals are inferred from tone-on-tone masking measurements. Several methodological issues are involved, e.g., the problems of how many and which measurements to include. To explore such sampling questions, sets of masked thresholds using a 250-Hz masker and a 500-Hz maskee are determined at various phase angles. These measurements are distributed into subsamples of (n=) 13, 9, 7, 5, or 4 each, and repeated estimates of the second aural harmonic inferred. For n greater than 4, these estimates averaged to within +/- 1 dB of one another,, although individual estimates vary considerably with the smaller n's (to 13 dB with n=4). Sets of five consecutive measurements also were analyzed when the masker : maskee phase angle was incremented in 90 degrees steps through two complete periods (of the maskee). Again, the reestimates for individuals can vary by at least 6 dB, but the averages over seven subjects remain within 2 dB of each other. Apparently, for n's of six or more, it matters little which masker: maskee phase angles are used to estimate the aural harmonic amplitudes.


Corticosteroid effect on immunoglobulins. The corticosteroid (prednisone) effect on serum immunoglobulins in 9 atopic asthmatic patients who required corticosteroids for the control of asthma was evaluated. Serum immunoglobulins were determined before corticosteroids were administered, an average of 15 days while on corticosteroids, and again an average of 22 days after corticosteroids were discontinued. While on corticosteroids (averaging 16.8 mg prednisone daily) for 15 days, mean serum IgG was significantly decreased (-22%, p less than or equal to 0.01), mean serum IgA tended to be decreased (-10%), and mean serum IgM was essentially unchanged. Serum IgE was initially significantly increased (p less than 0.01) when compared to levels of other serum immunoglobulins (IgG,A,M). An average of 22 days after corticosteroids were discontinued, mean serum IgG was still significantly decreased (p less than 0.05), and mean serum IgA again tended to be decreased. Serum IgM remained unchanged and mean serum IgE now was significantly decreased (p less than 0.01). Corticosteroids appear to have a significant effect on levels of some serum immunoglobulins.


IgE response in heterophil-positive infectious mononucleosis. Nineteen patients with heterophil-positive infectious mononucleosis were followed with serial blood sampling for an average of 14.6 mo. A preillness serum sample, obtained more than 2 mo before onset of illness, was available from 9 patients. A total of 141 samples were tested under identical conditions for total IgE levels by a paper-disc radioimmunoassay. Hematologic and serologic studies were also done. IgE changes showed a definite pattern, consisting of an elevation early in illness, rapidly followed by a significant drop reaching a nadir by the third month, then gradually returning to the preillness level (PIL) over a period of about a year. On the average, the peak was about 3 times the PIL, and the nadir about half the PIL. The IgE peak always coincided with the peak of atypical lymphocytes, and in no instance did it occur later than the peaks of other hematologic or serologic changes. No definite relationship was noted between IgE levels and the severity of illness. Heterophil-positive infectious mononucleosis is the first well-defined infectious disease found to be associated with such a pattern of IgE response.


Radiographic contrast media studies in high-risk patients. Patients with prior anaphylactoid reactions (AR) to radiographic contrast media (RCM) are at increased risk for another reaction upon repeat exposure to RCM. One hundred one patients, who had prior AR to RCM, who gave informed consent, and who had an essential need for a  repeat RCM study, were pretreated with prednisone, 50 mg orally every 6 hours for 3 doses ending one hour prior to RCM study, and diphenhydramine, 50 mg intramuscularly, one hour prior to RCM study. The repeat RCM study was then carried out using standard procedures with resuscitation equipment readily available. Ninety-six patients had no reaction. Five of the 101 (4.95%) developed AR. These AR consisted only of mild urticaria or pruritus. No significant or life-threatening reactions occurred. Pretreatment decreases the risk in this population of patients and is recommended as standard prophylaxis for patients requiring RCM who have had a previous AR.


Farmer's lung disease among farmers with precipitating antibodies to the thermophilic actinomycetes: a clinical and immunologic study. Farmers were evaluated for the presence of farmer's lung disease by serologic methods and by clinical histories. From a large farming population screened serologically, 40 of 92 farmers with precipitating antibodies to the thermophilic actinomycetes consented to be evaluated for clinical evidence of farmer's lung disease. Each subject completed a standardized questionnaire which was reviewd by a trained observer. On the basis of the questionnaire and an indepth clinical history, the subjects were grouped into those farmers who had a history of farmer's lung disease (38%), those with no history (50%), or a doubtful group (12%). When these groups were compared for radiologic changes, pulmonary function abnormalities, and immune function, no differences were discernible. None of the parameters tested were useful in predicting which farmer would develop clinical farmer's lung disease. The parameters tested did not provide reliable criteria for differentiating those patients who present without acute symptoms but relate a history of recurrent pulmonary illnesses associated with moldy forage.


Dietary status of lactating women. II. Relation of nutritional knowledge and attitudes to nutritional intake. Dietary practices of sixty-one nursing mothers who had been breast-feeding their infants an average of four months were examined in relation to their knowledge of nutrition and their attitudes about nutrition, taking vitamin supplements, meal preparation, and meal planning. The women were fairly knowledgeable about nutrition, and most exhibited an attitude that "nutrition is important". Nutritional knowledge, as measured by performance on a reliable test instrument, correlated well with the attitude that "nutrition is important" and with education. Nutritional knowledge also correlated well with four dietary factors used as dependent variables. Associations between nutrition-related attitudes and dietary factors were much less strong. Path analysis was used to test the knowledge-to-attitudes-to-behavior paradigm. Results, using multiple regression analysis, indicated that this model was not supported by the data. Rather, path analysis supported the model of attitudes-to-knowledge-to-behavior. This research suggests that nutrition education programs should adopt, as a primary goal, that of instilling positive attitudes about nutrition and demonstrating to learners that "nutrition is important". Once such attitudes have been formulated, ability to learn and comprehend nutritional facts and concepts will be facilitated, thus resulting in improved dietary intake of crucial nutrients.


A survey of undergraduate programs for the community practitioner. The purpose of the survey of college and university undergraduate programs in community nutrition, community dietetics, and public health nutrition was to characterize undergraduate programs which prepared entry-level practitioners in order to facilitate planning at the graduate level. The survey, which sampled known problems areas, revealed the diversity, confusion, and accomplishments of a field of study that is changing. The rapid growth and early stage of development of many of the undergraduate programs suggested that measures may be taken to promote excellence in both undergraduate and graduate education. Specific problems in the organization, administration, and curricula of the programs surveyed were identified. Recommendations were made to the Association of Faculties of Graduate Programs in Public Health Nutrition and the State and Territorial Public Health Nutrition Directors to promote surveillance of these programs, to encourage problem-solving communications, and to conduct educational research. The report and the recommendations have been referred to the newly formed ad hoc committee of the joint associations for further action.


Dietitians as behavior--change agents.

Dietitians as behavior--change agents. The traditional relationship between the client and the dietitian or nutritionist has been that of student and teacher. In the past, a patient has received excellent dietary counseling and advice from the dietitian, but has often ignored what he or she has taught. Until recently, the referring physician could only blame the patient, the dietitian, or both for this failure. Dietitians needed some new tools. The behavioral sciences have taken a new look at the problems of obesity, including a new assumption, viz.at some time, the obese have learned to eat in a way that results in excess caloric intake. Treatment now includes not only nutritional and caloric instruction, but also an attempt to change eating habits and behaviors. With these new tools, the dietitian-teacher becomes a dietitian-behavior-change agent; in addition to food content, the context of food becomes important in dietary counseling. Although dietitians are not usually trained in behavioral counseling, the weight loss in groups led by dietitans, after only minimal instruction, is comparable to that reported for groups led by psychiatry residents.


Changing dietitians' attitudes toward client counseling. Based on experiences with and observations of dietitians with responsibilities for client counseling, a course was designed to teach them the skills necessary to help clients manage their nutritional care at home, as well as to improve the dietitians' attitudes toward client education. A tool involving the development of Likert-type, summated scale was developed to measure dietians' attitudes. Statements were collected and subjected to item analysis. After such culling, statements discriminating between dietians with positive attitudes and those with less than positive attitudes were retained. During the first session of the class, the instrument was administered; the average mean value of the sample (N = 30) was 3.63. The post-instruction mean score was 4.14. After the course, dietitians demonstrated more positive attitudes toward clients, educational methods, and client counseling.


Nutritional knowledge, attitudes, and food patterns of women athletes. Nutritional knowledge, attitudes, and food patterns of women athletes at the University of Nebraska at Lincoln were studied. Mean test scores for nutritional knowledge were higher for questions relating to "nutrition for the athlete" than to "general nutrition." Attitudes toward nutrition were generally favorable, with a positive correlation between nutritional knowledge and attitudes. Athletes who had received some form of nutrition education had higher nutritional knowledge and attitude scores than those who had not. Respondents were especially concerned with diet as it relates to weight control; those with higher knowledge scores consistently followed food patterns for weight-control diets similar to those used in training and pre-event diets.


Physicians' opinions and counseling practices in maternal and infant nutrition. Opinions and practices regarding maternal and infant nutrition of general practitioners, pediatricians, and obstetricians in the province of British Columbia were surveyed by mail questionnaires. Scores were significantly higher for physicians who: (a) Were female; (b) consulted with a nutritionist-dietitian; (c) had additional training; (d) attended continuing education programs; and (e) had studied nutrition in their medical school curriculum. Pediatricians' and obstetricians' practice scores were significantly higher than those of general practitioners. However, there were no significant differences among the nutrition opinion scores for the three groups of physicians.


Nutrient levels of some foods of Eskimos from Artic Bay, N. W.T., Canada. Native food samples of caribou, seal, and arctic char were collected from resident Eskimos in Arctic Bay, N.W. T., and analyzed for nutrients. Caribou and seal meats were similar in protein and fat content in comparison with beef. Arctic char was above the average in protein and fat content for fish. Ascorbic acid was present in significant amounts only in baby seal liver. Thiamin, riboflavin, vitamin B12, folacin, and pantothenic acid content ranged from average to high for seal and carbiou meat, respectively, in comparison to published values for pork and beef. The vitamin B6 content of caribou meat was comparable to average values reported for pork and beef but was lower in seal meat. Baby seal liver contained similar levels of thiamin, riboflavin, vitamin B12, folacin, and pantothenic acid and less vitamin B6 than those reported for pork, beef, calf, and lamb liver. Arctic char was not appreciably different in these vitamins from other fish. The iron content of the Eskimo foods was higher than the meat group of the mixed Canadian diet. The macro mineral nutrients in these foods were comparable to those in beef and fish. The amino acid composition of caribou and seal meat was similar to beef, except that seal meat had a lower content of sulfur-containing amino acids and a much higher content of histidine. The sample of seal and arctic char were relatively high in concentrations of long-chain unsaturated fatty acids.


Baked products for the fat--controlled, low--cholesterol diet. Shortened cakes, sugar cookies, pastry, biscuits, muffins, and yeast bread were made with oil in place of hydrogenated shortening with little change in quality. Either 1 c. or 3/4 c. oil could be subsituted for hydrogenated shortening in shortened cakes, biscuits, muffins, and yeast bread. Sugar cookies were best when 1 c. oil replaced 1 c. hydrogenated shortening. Pastry was best when 3/4 c. oil was substituted for 1 c. shortening. The effect of method of mixing on product quality often was greater than the effect of the amount of oil.


Pathology of centenarians. II. Urogenital and digestive systems. The urogenital and digestive systems in 23 centenarians (7 males and 16 females) were examined pathologically. In the urogenital system, macroscopic scar formation, chronic pyelonephritis and arterio- and arteriolosclerosis of the kidney usually were pronounced. Six instances of prostatic glandular hyperplasia were demonstrated, and three of these were associated with well-differentiated adenocarcinoma. The testis, ovary and uterus usually showed a strong tendency toward atrophic changes. In the digestive system, senile atrophy of the liver and formation of colonic diverticula were noted. In this series of aged subjects, malignant lesions of the gastrointestinal tract were rare. It is also noteworthy that the unsuspected lesion of massive gastrointestinal hemorrhage associated with the various observed disorders might have been the cause of death in some of these centenarians.


Evaluation of goal attainment in geriatric settings. Determination of the impact of programs designed to enhance the functional independence of geriatric residents requires prior specification of goals in terms that clearly indicate the desired outcomes. The Geriatric Resident Goals Scale (GRGS) is a listing of specific goals developed to provide a systematic means of assessing resident status and program effectiveness. For male residents in a VA Nursing Home Care Unit, the obtained internal consistency reliability coefficient was .97 (N = 198), and the reliability coefficient reflecting a combination of test-retest and interrater consistency was .95 (N = 22). For a group of 178 residents, the GRGS was predictive of level of independence ratings (r = .82) and mental status (r = .71). The data showed the GRGS to be a highly reliable and valid means of assessing the functioning of geriatric residents, lending support to an assessment process based on a listing of specific goals. The GRGS can be viewed as a general procedure that is adaptable to a range of geriatic settings and programs.


The nursing home and training in geropsychiatry. Although the elderly have a higher incidence of mental illness than other groups, their need for psychiatric services is not being met adequately. This situation could be improved by providing psychiatrists with a broader education in aging and more extensive supervised experience in treating mentally ill old people at an early stage of their training. The Bronx-Lebanon Hospital established a program for this purpose in cooperation with the Daughters of Jacob Geriatric Center. Second-year residents in psychiatry are given regular assignments, under supervision, in this multiservice nursing home. They become knowledgeable about the aging process, gain a better understanding of the effect of physical, emotional and social factors on mental health in late life, and acquire a special competence and greater interest in treating the mentally ill aging. The success of the program suggests its value as a means of encouraging psychiatrists to take a more active and responsible role toward the aging.


Carcinoma of the liver: cytopathologic diagnosis. Primary cancer of the liver is a rare disease, especially in countries with temperate climates. It is reported to be found in only 0.3% of all autopsies in these countries. An exact diagnosis is not always easy, especially in the elderly. In three aged patients, cytologic examination of material obtained from the liver by aspiration after puncture with a thin needle, indicated the diagnosis. Cytologic examination of aspirated liver tissue, although it can never be a substitute for biopsy, may be very useful not only in diagnosis but in monitoring the treatment of obstructive jaundice in elderly patients.


An attributional approach to psychotherapy with the aged. The continued growth of the number of aged persons potentially requiring psychotherapeutic service should be met with a concomitant increase in relevant theory and research. An attribution theory approach to individual psychotherapy with the aged is suggested insofar as it: 1) is explicitly responsive to the possible negative consequences of the old person's diminished use of social consensus to validate the interpretation of behavioral events, 2) is relatively concrete in terms of implementation, and 3) may be used on a short-term basis.


Occult cardiac arrhythmias associated with falls and dizziness in the elderly: detection by Holter monitoring. Sixteen elderly patients with occult cardiac arrhythmias presented with signs of neurologic dysfunction that often had led to traumatic falls. Holter electrocardiographic monitoring was a valuable tool in defining the arrhythmia for which specific treatment was successful.


Falls in the institutionalized elderly.

Falls in the institutionalized elderly. The reports on 72 of 190 accidents occurring among 189 nursing home residents during a 3-month period were drawn at random and reviewed. The majority of the accidents were falls, either major or minor. Personal data on the residents included age, sex, mental status, number of diseases, and number of drugs administered. Data on environmental factors included the time of day and location of the accident, and the concomitant nursing staff patterns. Women of advanced age were more likely to be involved in a major fall, whereas younger men were more likely to be involved in a minor one. Alert, wheelchair-bound elderly patients were at the highest risk, whereas those who used assistive devices were at the lowest risk. Falls were directly related to the number of diseases present and the use of drugs. Most accidents occurred at the bedside during the evenings and nights, with the greatest frequency during the changes in nursing shifts or when the patient was either rising or retiring.


[Contraception and antenatal care (author's transl)]. Taking a representative sample selected from 11,220 deliveries the authors set out to study the interrelationship between contraception, antenatal care and socio-cultural factors. They show that there is a liaison between the first two variables even taking account of the socio-cultural factors which were found. This result leads to the conclusion that the spread of contraceptive information brings with it an improvement in the statistics for perinatal results.


[The histogenetic significance of dysplastic lesions of the cervix (author's transl)]. From the morphological studies that they have carried out the authors describe dysplasias of the cervix of the uterus as a collection of lesions developed from the vestigial cells which are situated at the endo-exocervical junction. The embryological origin of this junction is the sinus. These dysplasias consist of cells with basophil cytoplasm with edges that are not sharp. These form streams which run from the external os of the cervix towards the endocervix, where they replace and disturb the cylindrical epithelium wherever they meet it. These lesions may take on two forms: regular or irregular according to the degree of nucleo-cytoplasmic disharmony. The slow and insidious evolution of these lesions must be distinguished from dystrophic endocervical lesions which are caused by a disturbance in the nutrition of the tissues, which itself is of hormonal or inflammatory origin, and from exocervical lesions which, in common with all lesions of the malpighian mucosa, can undergo atypical scarring.


[Haemangiopericytomas of the uterus. 4 case histories (author's transl)]. The authors report four cases of uterine haemangiopericytoma. These vascular tumours develop at the expense of the pericytes of Zimmermann. They are very rare since only 64 cases have been reported. The haemangiopericytomas of the uterus are clear cut histologically and as far as their ultrastructure is concerned. They therefore can be clearly distinguished from other connective tissue tumours which develop in the uterus and especially in the stroma of the endometrium. They should be considered as slow growing sarcomata of the myometrium as a study of the embryogenesis of the genital tract shows. Their prognosis is guarded.


[Balanced translocations with abnormal phenotype (author's transl)]. Four cases of balanced translocations with phenotype abnormalities are reported. Three of them are reciprocal translocation, one is a Robertsonnian translocation. The consequences of the phenomene on genetic counselling and prenatal diagnosis are discussed.


[The relationship between palmitic acid and stearic acid on the pharyngeal secretions of the newborn (author's transl)]. The authors report on their study of the ratio of palmitic acid to stearic acid (P/S) in the pharyngeal secretions of the newborn before the sixth hour of life. Four groups of infants were studied: 78 infants used as controls who hac no respiratory distress, 36 with hyaline membrane disease, 16 with transitory respiratory distress and 5 with perinatal asphyxia. The aetiological diagnosis of the respiratory distress was based on clinical as well as radiological and biological criteria. The P/S ratio is always less than 3 with hyaline membrane disease and above 3 in asphyxias. In the control group and the group with transitory respiratory distress the ratio ranged between 1.3 and 14 which was evidence of false negative results, probably attributable to treatment with cortisone given to the mother in premature labour in a certain number of cases. Study of the P/S ratio in amniotic fluid and in the pharyngeal secretions of 27 children born by Caesarean operation embodies a contradiction in the results the newborns in whom the ratio in the amniotic fluid was greater than 3 never had respiratory distress although the ratio studied at the same time in the pharyngeal secretions was low and sometimes less than 3.


[Endolymphatic myosis low grade sarcoma of the endometrical stroma. II. Clinical (author's transl)]. Various clinical parameters of myosis have been reviewed in the light of the literature. This is a rare tumour which manifests itself generally by metrorrhagia in the pre- or perimenopausal age groups. The first treatment which among other operative forms of treatment offers the best prognostic chances is total hysterectomy with bilateral salpingo-oophorectomy. Radiotherapy and endocrine therapy with progestogens have their place in cases of relapse of metastases. There are several anatomo-pathological and clinical features which point to the fact that stromal myosis is hormone-dependent.


[Perforation of the uterus after voluntary termination of pregnancy using the aspiration technique. Two serious cases (author's transl)]. The authors formulate some safety rules in view of two case histories of bowel complications following voluntary termination of pregnancy using suction techniques. Where it is not certain that a perforation has occurred laparoscopy is necessary. When perforation has been confirmed a laparotomy is undertaken in order to check the state of the bowel throughout its length, because when lesions of the digestive tract are treated rapidly the results are good whereas when they have to be treated for peritonitis the outlook is poor.


[Feto-maternal transfusion. A rare cause of acute fetal distress. A case history (author's transl)]. The authors report a case of feto-maternal transfusion which showed as acute fetal distress spotted by fetal cardiac rhythm monitoring. Following this observation the authors point out such occurrences are rare with a possibility of intra-uterine fetal death at 1/1000. They also point out the value of fetal cardiac monitoring and of systematic performance of amnioscopy at the start of labour and of carrying out the Kleihauer test in every case of neonatal anaemia as well as in every case of unexplained perinatal death.


[The treatment of benign pathological conditions of the breasts with progesterone and progestogens. The results according to the type of breast condition (260 case records) (author's transl)]. This work reports the clinical results which were obtained after treating 260 women who had pathological conditions of the breasts using a combination of a progestogen which was given by a generalised route (orally or by injection) and progesterone which was applied locally so that its effect would be percutaneous on the breasts. These results were evaluated according to the effectiveness of the treatment according to the different symptoms or groups of clinical symptoms and radiological findings which had been noted at the time of the first examination. A better therapeutic effect was found in cases of early lesions where oedema was the dominant factor (mastodynia) and glandular hyperplasia (diffuse polyadenomatosis). On the other hand, longstanding lesions (sclerocystic mastopathia) where sclerosis was marked showed a much more variable result of treatment with progestogens. Therefore its seems that benign conditions of the breasts should be treated early and particularly in the stage of mastodynia if development into irreversible sclerotic conditions is to be avoided. It also has to be carried on for a long time, especially if there are other risk factors for cancer which are associated with conditions in the breast. The prophylactic role of this treatment in regard to cancer of the breast is discussed.


[Disturbances in ovulation following on artificial insemination with donors (A.I.D.) (author's transl)]. The authors report on the results of statistical analysis of temperature curves in 139 patients before artificial insemination from donors (A.I.D.) and in the cycles in which they were inseminated. It appears that frequently the practice of A.I.D. causes ovulation to come early or late. Late ovulation seems to be the most frequent cause of failures which are then considered to be due to "psychogenic sterility".


[Prostaglandins E2 and F2alpha in induction of labour, induced abortion and molar abortion. (70 case histories) (author's transl)]. The authors report on their experience using prostaglandins E2 and F2alpha in obstetrics. 70 cases are involved: 30 inductions of labour, 33 abortions and 7 hydatidiform moles. The results as far as induction of labour is concerned are encouraging (76.6 p 100 success), but in the doses used no better than those achieved with synthetic posterior-pituitary oxytocins. On the other hand, as far as abortions are concerned, prostaglandins, whether given intravenously, intra-amniotically or extra-amniotically, are the method of choice because they are practically free of danger in the second trimester of pregnancy (93.9 p. 100 success). Side effects are common but are usually not severe and do not interfere with the treatment.


Digital sensibility following replantation. The amputated digit serves as an excellent model for the examination of digital nerve repair. When amputation is complete, there is no question of cross-over or anomalous innervation. The sensibility of 35 replanted digits in 29 patients was evaluated. Sensory return was related most closely to restored digital vascularity, as measured by Allen test, pulse volume flow, and Doppler. Level of amputation, mechanism of injury, and age of patient also affected ultimate sensation. All patients experienced cold intolerance and some were considerably disabled because of it. The severity of cold intolerance with pain and requiring prolonged rewarming was directly proportional to digital vascularity. When one digital artery thrombosed, ipsilateral digital sensation was not diminished as long as flow through the contralateral vessel was adequate. Two-point discrimation in our series was not as good as that reported for digital nerve repair in the nonamputated digit. Establishing and maintaining adequate digital flow at the time of replantation is essential to obtain good digital sensibility and to avoid symptoms of cold intolerance.


Anatomic dissections relating the posterior interosseous nerve to the carpus, and the etiology of dorsal wrist ganglion pain. Prompted by the finding of a neuroma, which clinically simulated a recurrent ganglion, we dissected the terminal branches of the posterior interosseous nerve. A constant relationship between these terminal branches and the scapholunate ligament was demonstrated. Since most, if not all, dorsal wrist ganglions arise from the scapholunate ligament, we suggest that the aching wrist pain associated with a dorsal wrist ganglion may be due to a compression neuropathy of the posterior interosseous nerve.


The mechanism of the intrinsic-minus finger: a biomechanical study. To demonstrate in the cadaver model that the sequence of extension of the flexed metacarpophalangeal and proximal interphalangeal joints of the intrinsic-minus finger can be explained on the basis of moment ratios about these joints, the engineering concept of free body analysis was applied. Intrinsic-minus fingers, i.e., fingers of a cadaver in which all forces exerted by the intrinsic muscles were removed, were observed to hyperextend maximally at the metacarpophalangeal joint before extension of the proximal interphalangeal joint began. Mathematical calculation of moments provides an explanation of this sequence. This study confirmed that, when an equilibrium of forces at the hyperextended metacarpophalangeal joint is reached, the proximal interphalangeal joint is incompletely extended. These forces include: (1) the proximal pull of the extensor tendon; (2) the distal loading of the extensor tendon by the flexor tendons; (3) the force preventing spanning of the laminae.


Temperature monitoring in digital replantation. Postoperative monitoring of replanted and revascularized digits with skin temperature probes was performed on the 20 patients admitted to the Duke University Medical Center Orthopaedic Replantation Service from April to July, 1977. Using multiple probes, temperatures were recorded for the replanted digit, a control digit on the same hand, and the dressing which represented the ambient temperature. In addition, the following simultaneous clinical inspections were performed on the digits: capillary refill, skin color, turgor, audibility of arterial Doppler tones, and amplitude of pulp pressure tracing. Temperatures of the replanted digits were in the range of 26.0 degrees to 35.0 degrees C. Control temperatures remained relatively stable, in the range of 33.0 degrees to 35.0 degrees C. From the authors' experience the patterns of temperature change which signaled changes in perfusion of the replanted digit and possible poor prognosis were (1) the temperature of the replanted digit dropping more than 2.5 degrees C while the control temperature stayed constant; (2) the temperature of the replanted digit dropping below 30.0 degrees C for longer than 1 hour; and (3) the control temperature dropping below 30.0 degrees C with no correctable cause found.


Two families with congenital nail anomalies: Nail formation in ectopic areas. Two families with congenital nail anomalies are reported. The nail covered not only the dorsal but also some of the palmar aspect of the distal phalanx. The ungual phalanges of the affected fingers were lacking in the crescent-shaped cap and had a blunt Y-shaped bony projection. The anomalies may have been transmitted by an autosomal recessive gene.


Nutrient pathways to flexor tendons of chickens using tritiated proline. The nutrient pathway to the flexor tendons within the digital flexor sheath of adult chickens was investigated using tritiated proline. There was no difference in the uptake of the radioactive tracer by free segment tendons (detached from blood vessels) and the intact tendon lying in synovium. The uptake of tracer by tendons isolated from the synovium (but with unaltered vascular attachments) was significantly less than by the intact tendons. Radioactive tracer not only diffused across the synovium into the tendon, but along the course of the tendon itself. There was no difference in the uptake of radioactive tracer by 2-week-old tendon grafts with and without adhesions.


Treatment of mallet finger due to intra-articular fracture of the distal phalanx. When a mallet finger deformity results from an intra-articular fracture of the distal phalanx comprising more than one third of the articular surface, an accurate reduction of this fracture is necessary to prevent secondary degenerative arthritis. A technique for open reduction is described in which the distal interphalangeal joint is exposed by dividing the extensor tendon and permitting a precise reduction of the fracutre fragment. Elective division of the extensor tendon had not compromised the results.


Flexor tenosynovectomy in the rheumatoid finger. The usual operation fo stenosing flexor tenosynovitis is resection of the proximal pulley. In the rheumatoid hand this operation may not be proper because motion still may be limited by the thickened synovium more distally, and also because there is a greater chance for the production of ulnar drift later on if the proximal pulley system is obliterated. The operation we recommend for the finger with rheumatoid tenosynovitis is a tenosynovectomy, but with maintainence of the pulley system and resection of one slip of the superficialis in order to decompress the digital theca. We have performed this operation on 54 fingers with satisfactory results.


Reconstruction of the unstable proximal interphalangeal joint: The double superficialis tenodesis. A technique is described for reconstructing the unstable proximal interphalangeal joint where there has been a break in continuity of both the volar plate and the collateral ligament. Both slips of the superficialis are used. They are divided proximally and tenodesed in appropriate positions on the proximal phalanx.


Chronic mallet finger: The use of Fowler's central slip release. The use of Fowler's central slip release is reported in five patients considered to be failures of closed management in a personal series of 100 consecutive "mallet fingers" seen over a period of 3 years. Fracture-subluxation of the distal interphalangeal joint, avulsion fractures of the extensor tendon, and distal phalangeal epiphyseal injuries are excluded to regidly control the data interpretation. In all five the central slip release was employed as a salvage procedure-as Fowler recommended. In four cases the result was rated as excellent; the remaining case was rated as good, with minimum follow-up of 1 year.


Medical and surgical importance of the arterial blood supply of the thumb. The arterial supply of the thumb was studied in 50 cadaver hands. In 80% the princeps pollicis artery was the first palmar metacarpal artery, a major branch of the deep radial arch. In 50% of the specimens the princeps pollicis artery also supplied the proper radial digital artery to the index finger. Variations of the thumb arterial patterns were present in 25%. In 75% there was a single end-arterial blood supply to the thumb. The anatomic findings are correlated with problems of radial artery injections, thrombosis, and surgical injury to illustrate the clinical importance of the princeps pollicis artery.


Unstable fracture dislocations of the proximal interphalangeal joint of the fingers: a preliminary report of a new treatment technique. A linkage of Kirschner wires activated by a single rubber band creates a force couple across a fracture-dislocated proximal interphalangeal joint. The method dynamically achieves concentric joint reduction, which is maintained through a full active range-of-joint flexion and extension. Two case reports accompany a description of the technique.


Clinical and experimental studies on the effect of extensor carpi radialis longus transfer in the rheumatoid hand. Digital ulnar drift in the rheumatoid hand is a complex problem. The radial deformity of the wrist causes abnormal forces on the extrinsic flexor and extensor tendons which aggravate metacarpophalangeal ulnar drift. Analysis of the results of the transfer of the extensor carpi radialis longus to the extensor carpi ulnaris in 20 wrists showed that 13 of 20 had significant correction of the wrist deformity. The transferred tendon did not contract during active ulnar deviation. Laboratory studies of the transfer on cadaveric rheumatoid wrist models showed correction of the wrist deformity. The dorsal ulnar capsule was determined to be a stabilizer of wrist position, as evidenced by deformity after transection.


The effect of early experience on the exploratory behaviour, learning ability and on the synaptosomes of the mice brain. This study deals with the effects that are produced by an enriched early experience on the mitochondrial fraction on the mice brain. The total content of lipids and proteins in mitochondrial fraction, the morphology of the mitochondries and the density of synaptosomes were investigated. A significant difference in the total quantity of lipids of the mitochondrial fraction and the density of synaptosomes was observed between mice subjected to an enriched environment and others subjected to an impoverished environment. These mice, which were subjected to a psychological study before proceeding to the extraction of the mitochondrial fraction, displayed distinct characteristics. The enriched group displayed a greater exploratory behaviour and a greater capacity to learn than the mice raised in the impoverished environment.


Studies on the immune response to fixed antigens. III. Induction of helper function for antibody-dependent cellular cytotoxicity responses. Heavy trinitrophenylated sheep red cells (TNP128SRC) and glutaraldehyde-treated SRC (G-SRC) could not induce cellular cytotoxicity against 51Cr-SRC. In contrast, the native antigen SRC could stimulate a cytolytic response against the radiolabeled homologous target cell. However, fixed SRC could stimulate a priming function that accelerated and augmented the secondary cytotoxic response to SRC. Such fixed antigens could stimulate a delayed-type hypersensitivity (DTHS) response also. Thus, the immunologic memory to the chemically modified antigen, as well as the DTHS response, are completely dissociated from the primary cytotoxic responses. The primary and the secondary cytotoxic responses that were developed in the spleens of the injected mice were mediated by antibody-dependent cellular cytotoxicity (ADCC), since the active supernatant that was released from the spleen cells could lyse the target cells in the presence of normal splenocytes. The active supernatant was identified as antibody. We suggest that B effector cells cytolyzed the antibody-coated target cells. Normal cells from nude mice could mediate the cytolytic process as efficiently as spleen cells from other strains of mouse. The results are discussed in terms of selective stimulation of T cell subpopulations.


Participation of the humoral immune system in the myeloma-specific transplantation resistance. Studies are reported that examine the participation of humoral and cellular responses in the myeloma-specific transplantation resistance induced by preimmunization of BALB/c mice with purified myeloma protein M315. A plasmacytoma spleen colony-forming assay was used to provide a quantitative estimate of the tumor immunity in recipients of unfractionated spleen cells or serum from mice immunized four to seven times with M315. The primary findings were: 1) that the tumor immunity can be transferred by immune spleen cells provided that a boost of M315 is given to adoptive hosts, and 2) that passively transferred serum containing anti-M315 idiotype antibody (a-Id315) can also inhibit tumor growth. Adoptive transfer was successful in the presence of minute amounts of a-Id315, whereas passive transfer required relatively large amounts of activity. The passive transfer experiments involved an extended injection schedule and thus could not discriminate between direct effects of antibody or idiotype-specific humoral substances on tumor cells or inductive effects on the cellular immune system. Experiments examining the properties of the immune elements involved in the transplantation immunity demonstrated that, once established, they are resistant to acute radiation (to 800 R) and cortisone damage.


In vitro activation of suppressor cells from spleens of mice treated with radioactive strontium. Mice were treated with two 100-muCi injections of 89Sr to deplete marrow-dependent (M) cells. Mice so treated responded normally to immunization with sheep red blood cells (SRBC) in vivo; moreover, spleen cells from 89Sr-treated mice were able to respond to SRBC after infusion into irradiated recipient mice. However, spleen cells from mice treated with 89Sr did not respond to SRBC in vitro and mixtures of normal spleen cells with the latter were also not able to respond in vitro. The discrepancy between in vivo and in vitro responses was abolished by culturing spleen cells for 24 hr before testing their ability to respond to SRBC in the adoptive transfer in vivo. Pretreatment of spleen cells from 89Sr-treated mice with 1000 R of gamma-radiation lessened their suppressive activity. The suppressor cells were detected in spleens of athymic nude mice treated with 89Sr. The suppressive activity, after the 24-hr culture period, was not abolished by irradiation and was active in vivo as well as in vitro. Thus, depletion of M cells by 89Sr results in the appearance within the spleen of thymus-independent suppressor cells, which require a short period of in vitro cultivation before becoming functionally active.


Cell-mediated cytotoxicity against virus-infected target cells in humans. I. Characterization of the effector lymphocyte. In a 51Chromium release assay performed without immune sera, purified lymphocytes from randomly selected healthy donors killed significantly more allogeneic virus-infected than noninfected fibroblasts. An incubation period of 18 to 20 hr was optimal for determining cytotoxicity, but increased cytotoxic activity against infected cells was observed as early as 6 hr from the start of the test. No correlation could be found between donors' antibody titers to any virus tested and the cytotoxic efficiency of their effector cells: virus-infected cells were lysed by both seropositive and seronegative individuals. With several different cell fractionation techniques, the effector cell in this system could not be distinguished from the human natural killer cell, which is a lymphocyte with receptors for the Fc fragment of IgG but with no surface immunoglobulin. When lymphocytes were separated on the basis of ability to form rosettes with neuraminidase or AET (2-aminoethylisothiouronium bromide hydrobromide)-treated sheep erythrocytes, the majority of cytotoxic activity was consistently recovered in the nonrosetting fraction. A portion of it, however, was always present in the rosetting fraction and was, again, mediated by lymphocytes carrying receptors for the Fc fragment of IgG.


Serologic and immunochemical characterization of HLA-A9 xenoantisera. The specificity of A9 antiserum produced in rabbits immunized with high density lipoprotein-associated HLA-A9 from serum was investigated by using serologic and immunochemical approaches. After suitable absorption, the xenoantiserum No. 2958 is monospecific for A9 antigens in direct cytotoxic test. Data from lysostrip experiments and from blocking of cytotoxicity with Fab2 fragments indicate that the A9 xenoantiserum No. 2958 react with the same or closely associated antigenic structures recognized by A9 alloantisera. Immunoprecipitates obtained with the specific xenoantiserum No. 2958 and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis contained only proteins of the size of detergent-solubilized HLA and beta2-microglobulin (45,000 and 12,000 m.w.). Immunodepletion experiments indicated  that the precipitation was mediated by antibodies directed to the heavy chain, and not the light chain of the complex. These results indicate that monospecific HLA-A9 xenoantisera have the same discriminatory capacity of alloantisera and can be useful for the serologic and immunochemical characterization of HLA antigens.


Sulfated glycosaminoglycans of guinea pig basophilic leukocytes. Cytoplasmic granules of basophilic leukocytes stain metachromatically and have been thought to contain sulfated glycosaminoglycans, presumably heparin. To test this hypothesis, we identified the [35S]glycosaminoglycans synthesized by guinea pig blood basophils in culture and in vivo. Basophils isolated from guinea pig blood were cultured for 20 hr in F12 medium--10% guinea pig serum containing sodium [35S]sulfate. Alternatively, basophils were purified from animals receiving repeated i.v. injections of sodium [35S]sulfate. Glycoaminoglycans were isolated from these basophils after pronase digestion and identified by the use of selective glycosaminoglycan-degrading enzymes. Approximately 55% of the [35S]glycosaminoglycans was degraded by chondroitinase AC, indicating the presence of chondroitin sulfate; an additional 30 to 35% could be degraded by chondroitinase ABC, indicating that dermatan sulfate was also present. The 15% glycosaminoglycan remaining after chondroitinase ABC digestion was degraded by purified heparitinase (heparanase), which has no effect on authentic heparin but degrades heparan sulfate. Thus, the glycosaminoglycan content of guinea pig basophils is a mixture of chondroitin sulfate, dermatan sulfate, and smaller amounts of heparan sulfate. No heparin was detected.


Physicochemical separation of two distinct Fc receptors on murine macrophage-like cell lines. By using radiolabeled myeloma proteins specific for each of two distinct Fc receptor activities on macrophage-like murine cell lines ("aggregated IgG FcR" activity and "monomer IgG2a FcR" activity), we have been able to detect solubilized FcR of both types in detergent lysates of these cells. The two solubilized Fc receptors can be distinguished and physically separated from one another by means of affinity chromatography and by sucrose gradient centrifugation. They also differ in their sensitivity to phospholipase C. The detergent solubilized monomer IgG2a FcR can be removed from solution with a Sepharose IgG2a column, has an S value of 4 to 5 and is resistant to phospholipase C. The solubilized aggregated IgG FcR does not bind to insolubilized IgG2a, has an S value of greater than 19, and is sensitive to phospholipase C treatment. We conclude from these studies that two different cell membrane macromolecules are responsible for the Fc receptor activities observed in macrophage-like cell lines.


Spontaneous cytotoxicity of cultured human cell lines mediated by normal peripheral blood lymphocytes. III. Kinetic parameters. The mechanism of spontaneous cell-mediated cytotoxicity (SCMC) of cultured cell lines has been investigated and compared with antibody-dependent cell-mediated cytotoxicity (ADCMC) by detailed kinetic analysis. The mechanism of SCMC resembles that of an enzyme, as does ADCMC where effector cells are analogous to an enzyme and the 51Cr-labeled target cells are analogous to the substrate. Temporal kinetic studies revealed an induction period of about 1 hr before significant 51Cr release for SCMC, but not for ADCMC. This induction period is not due to differences in effector-target affinity between SCMC and ADCMC. On the basis of kinetic analysis it was shown that SCMC approaches simple Michaelis-Menten enzyme kinetics, allowing determination of a Michaelis constant, Km, and maximal velocity, Vmax, for the interaction between a given effector and target cell. The Km values thus determined were found to be identical for the lysis of several target cell lines of varying SCMC susceptibility to effector cells from a given donor, whereas Vmax values for lysis of different target cells varied considerably. However, effector cells isolated from the peripheral blood of different donors exhibited different Km values for the target cells tested. Moreover, the Km value obtained for ADCMC effected by a given donor's lymphocytes was found equal to the Km value obtained for SCMC by that donor.


Phagocytic properties of isolated human eosinophils. Viable eosinophils from normal human peripheral blood were separated by sedimentation through a nutrient-enriched linear gradient of sodium hypaque. Ingestion experiments with these cells showed that eosinophils would phagocytose latex beads coated with a mixture of allergen and corresponding allergic human serum. The stimulatory activity of the allergic serum correlated with the IgG fraction and not with those properties associated with IgE. Eosinophils isolated from allergic donors were found to be inferior in their phagocytic ability when compared with eosinophils from normal cell donors.


Fc receptors induced by herpes simplex virus. I. Biologic and biochemical properties. Radioiodinated normal rabbit IgG was used to detect Fc receptors on the surface of HeLa S3-2 cells infected with herpes simplex virus (HSV). Unlike the Fc receptors present on most leukocytes, these virus-induced Fc receptors were found to be sensitivite to trypsin at concentrations of enzyme as low as 0.1 mg/ml. Treatment of infected cells with neuraminidase enhanced the binding of IgG. Yet the HSV-induced Fc receptor(s) is probably a glycoprotein because its synthesis was inhibited by 2-deoxy-D-glucose at concentrations inhibiting glycoproteins but not total proteins. Binding of radioiodinated IgG to Fc receptors on infected HeLa S3-2 cells was unaffected by F(ab')2 fragments prepared from antisera against uninfected HeLa S3-2 cells or against human beta2-microglobulin. By contrast, anti-HSV F(ab')2 or Fab' fragments decreased binding of radioiodinated IgG to HSV-infected cells by 85%, and binding of radioiodinated Fc was also inhibited by anti-HSV Fab'.


Light transmission analysis of lymphocyte activation by mitogens: a new technique. In vitro lymphocyte transformation was evaluated by laser light transmission cytometry. Criteria are given for optimal application of this system to assessment of total cells and proportion of lymphoblasts in cultures. The light transmission studies revealed that cell numbers in mitogen stimulated cultures increase steadily, reaching a plateau. The percentage of lymphoblasts reached a peak after 4 days culture. The kinetics of [3H]-thymidine incorporation are similar. The increase in total cell number concomitant with decrease in [3H]thymidine incorporation at the fifth and sixth days indicates discordance between the cell proliferation and utilization of exogenous thymidine. The kinetics of total cell numbers and percentage of lymphoblasts suggest that in vitro reversion of lymphoblasts to small lymphocytes occurred. In addition to examining directly the cellular events during blastogenesis with ease, the current method appeared to be more reproducible than the [3H]thymidine incorporation assay.


Human antibodies to immunoglobulin A (IgA). A radioimmunological method for differentiation between anti-IgA antibodies and IgA in the serum of IgA deficient individuals. In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/ml) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 microgram IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA deficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearance of anaphylactic reactions after transfusion of IgA.


Nephelometric method for determination of rheumatoid factor. We have developed a nephelometric technique for determining titers of rheumatoid factor. Serum dilutions are added to a mixture of commercially available latex particles of small size (0.098 micrometer) and human gamma-globulin. Rheumatoid sera induce a substantial increase in the light scattering properties of the mixture, and the highest dilution significantly increasing the light scattering is considered as the titer for that serum. This technique is simple to use, provides objective results, and can be automated for analysis of large numbers of samples.


Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and ficoll-hypaque. When mononuclear leukocytes are isolated directly from whole human blood using Ficoll-Hypaque or Plasmagel, cytophilic immunoglobulin is detected on cell surfaces. Upon incubation at 37 degrees C, this cell-associated immunoglobulin is shed slowly into the medium. However, when cells are prewashed in phosphate-buffered saline prior to isolation, they appear to be free of cytophilic immunoglobulin. Compared to prewashed cells, populations retaining cytophilic immunoglobulin on their surfaces demonstrate a decreased binding of soluble immune complexes and radiolabelled trimeric rabbit IgG. The data suggest that Ficoll-Hypaque and Plasmagel cause serum IgG to bind with abnormally high affinity to human mononuclear leukocytes, probably via Fc receptors. This artifact of preparation can lead to erroneous estimates of the numbers of cells bearing Fc receptors or intrinsic membrane immunoglobulin within a given population of cells and to an inaccurate assessment of the average number of Fc receptors per cell.


A set of analytical electrophoresis experiments to predict the results of affinity chromatographic separations: fractionation of allergens from cow's hair and dander. Analytical affinity electrophoresis experiments are described as analogues of column and batch affinity experiments. The are based on crossed immunoelectrophoresis with included affinity, here concanavalian A (con A) and con A-Sepharose. Reactions with serum proteins and allergens from cow's hair and dander are described, and a purification scheme for the latter is described.


A highly sensitive and reproducible microcytotoxicity assay for demonstrating cytotoxic antibodies to cell surface antigens. An assay is described, in which target cells are suspended in diluted rabbit serum (as a source of complement) and pipetted into the wells of Falcon No. 3034 Microtest plates, to which diluted antiserum (or control serum) has been added. After 18--24 h of incubation, the plates are stained with crystal violet and counted using an electronic Quantimet image analyzer. This technique could reproducibly detect complement-dependent cytotoxic antibodies to target cell H-2 antigens and to MuLV gp70 on cell lines which expressed this antigen, at serum dilutions up to 1:160,000. The cytotoxic antibodies could be removed by absorption of sera with cells carrying the respective antigens.


Recovery of lymphocytes from clotted blood for HLA typing. A method to recover lymphoid cells from clotted blood for the microcytotoxicity test used in HLA typing is described. The procedure consists of disruption of the clotted blood followed by Ficoll-Hypaque gradient purification of the mononuclear cells. The results of HLA typing of lymphocytes from unclotted and clotted blood were identical.


Receptor modulation and mast cell secretion. Co-workers and I examined the early events in the interaction of rat peritoneal mast cells with a number of noncytotoxic mast cell stimuli. These studies demonstrated that an interaction limited to the cytoplasmic membrane is sufficient to induce a secretory mast cell response. Additional experiments suggested that a continued interaction between the stimulus and the membrane receptor is required for maintenance of the secretory response. We have provided evidence to support the concept that different mast cell activators interact with different receptors on the cell membrane and initiate distinct biochemical pathways leading to secretion. Finally, we have shown that pretreatment of mast cells with concentrations of a stimulus that, by themselves, are incapable of initiating a secretory response can profoundly affect the ability of mast cells to respond fully to a subsequent challenge with an optional concentration of stimulus.


Purification and some characteristics of the human epidermal SH-protease inhibitor. An inhibitor of papain and other SH-proteases was purified 520-fold from human epidermis extracts by acetone fractionation, heat treatment, papain-Sepharose affinity chromatography, and Sephadex G-50 chromatography. The purified inhibitor had a molecular weight of 12,600 and contained no hexose, as tested by the anthrone reaction. The inhibitor survived in a boiling water bath, in 5% trichloroacetic acid, 20 mM Na3PO4 (pH 12.1) and 4 M NH4OH (pH 11.9). By isoelectric focusing 2 major activity peaks with pI's of 4.6 and 4.8, and a minor peak with a pI of 4.9 was fractioned, and 3 corresponding protein bands were seen after analytical isoelectric focusing. Immunization of rabbits with the purified inhibitor yielded a highly specific anti-inhibitor serum. The purified inhibitor inhibited papain, ficin, human cathepsins B and C, and slightly inhibited bromelain. No inhibition of serine proteases (bovine trypsin and chymotrypsin A, porcine elastase) or an acid protease (human cathepsin D) was observed. Evidence was obtained that the inhibitor formed a complex with both dithiothreitol-activated papain and enzymatically inactive mercuripapain.


The low-molecular-weight SH-protease inhibitor in rat skin is epidermal. The epidermis and dermis of rat skin were separated and the presence of the high-molecular-weight SH-protease inhibitor I1 and the low-molecular-weight inhibitor I2 in both was studied. Gel filtrations of the extracts revealed that 97% of the epidermal inhibitor activity was due to I2 and 89% of the dermal activity to I1. The presence of I2 mainly in the epidermis extract was confirmed by immunodiffusion of specific rabbit anti-I2 serum against purified I2, epidermis and dermis extracts, and rat serum. Most of the immunoreactive protein was seen in the epidermis extract, traces in the dermis extract and none in the rat serum. I2 was localized in rat skin by indirect immunofluorescence using rabbit anti-I2 serum and fluorescein isothiocyanate conjugate of goat anti-rabbit immunoglobulins. Intense fluorescence, much brighter than in the controls treated with rabbit non-immune serum, was seen in the epidermis, being most pronounced in the cytoplasms of cells in the granular layer. The weak fluorescence of the hair follicles, sebaceous glands, connective tissue cells and fibres was unspecific and was also seen in the controls. In view of its epidermal location, the name epidermal SH-protease inhibitor is suggested for I2.


Induction of delayed-type hypersensitivity to staphylococcal antigens in guinea pigs. Delayed-type hypersensitivity against staphylococcal antigens was induced in guinea pigs using Freund's incomplete as well as Freund's complete adjuvant. In animals sensitized with Freund's complete adjuvant the induction time and the duration of delayed-type hypersensitivity were longer and the skin reactions were stronger compared to animals sensitized with Freund's incomplete adjuvant. The difference between animals sensitized with Freund's incomplete or complete adjuvant may reflect the difference between tuberculin- and Jones-Mote type hypersensitivity.


8-Methoxypsoralen (8-MOP) in human skin: penetration kinetics. Penetration kinetics of 8-methoxypsoralen (8-MOP) into human skin have been investigated under in vitro conditions. The dependence of the resulting tissue concentration on time of penetration, drug concentration in the applied preparation and vehicle composition has been studied. Tissue concentration of the drug was found to increase with time of penetration; however, in both horny layer and epidermis, this increase was followed by a significant decrease in concentration, (after 100 to 300 min), although a large amount of unpenetrated drug was present on the horny layer surface at all times. In contrast to this, 8-MOP accumulated in the lower corium and subcutis and reached concentrations higher then those found in the upper corium and epidermis. This accumulation of the drug is a consequence of the in vitro conditions and its amount is proportional to that amount that under in vivo conditions would have been taken up by the capillary system. Penetration was dependent on vehicle characteristics and was found to increase with increasing polarity of the vehicle. The penetration was found to be directly proportional to the applied concentration; however, the percentage of the drug that actually penetrated was inversely proportional to the applied concentration.


The influence of water content, chemical treatment and temperature on the rheological properties of stratum corneum. The elastic modulus is determined as a function of water content for untreated stratum corneum, and stratum corneum treated with urea and LiBr. The modulus is also determined for stratum corneum at temperatures from 2 degrees C to 45 degrees C and on samples with the water solubles extracted. The modulus is independent of temperature, but may be modified by binding of small molecules to the protein in stratum corneum. The modulus is found to be a function of water content, not water activity.


Heat loss in anhidrotic ectodermal dysplasia. The dynamics of heat loss by 2 patients with classic anhidrotic ectodermal dysplasia were studied. Both were active in high school athletics and avoided heat injuries by various forms of behavior modification. Elevated core and skin temperature measurements were found at rest in comfortable environments. In a warm environment 35-45% of the heat generated was lost by radiation, 44-52% by conduction and convection, and only 4-6% by evaporation. Heat loss in control subjects was 9% by radiation, 17% by conduction/convection, and 67% by evaporation. The dry routes of heat dissipation used by the anhidrotic patients were inadequate to prevent a rise in core temperature.


Fibrous protein of human epidermis.

Fibrous protein of human epidermis. The fibrous proteins of the malpighian layer of human epidermis (prekeratin) have been isolated with citrate buffer, pH 2.65, and shown to consist of 7 polypeptide chains varying in molecular weight from 45,000 daltons to 67,000. Some variation in the number and amount of the components was observed in prekeratin prepared from the epidermis of different individuals. The fibrous proteins of the stratum corneum were isolated with Tris buffer, pH 9.0, containing 6 M urea and 0.1 M mercapto-ethanol and were found to have a pattern similar to prekeratin but not identical to it. However, fibrous protein isolated from the superficial layers of the stratum showed a considerably different pattern indicating that there was post-translational modification of the protein in the late stages of keratinization. These data show that human keratin has the same heterogeneity which was observed previously in cow epidermis. This was further confirmed by studying the polypeptide chain content of prekeratin from a large number of lesions showing benign epidermal hyperplasia, where considerable variation in composition was observed.


Individual differences in the bacterial flora of the skin of the forehead: Peptococcus saccharolyticus. Peptococcus saccharolyticus was a numerically important constituent of the bacterial flora of the forehead of 20% of 40 subjects. 16 of these subjects were studied over periods of 12 to 54 mo. It was consistently absent from 12 subjects, was present on every test of 3 subjects, and constituted 96 to 100% of the total flora on 1 subject tested 8 times in a 16-month period. On the forehead of one subject, Peptococcus saccharolyticus was recovered in only 1 of 5 tests.


Isolation and growth of adult human epidermal keratinocytes in cell culture. Human epidermal keratinocytes may be isolated in high yield from 0.1 mm keratotome sections of adult skin by short-term trypsin release. When plated on a collagen-coated plastic surface or on a collagen gel, keratinocytes attach with high efficiencies (greater than 70%) and form confluent, stratified cultures. Cell populations of predominantly basal cells produce proliferative primary cell cultures while populations of basal cells and malpighian cells result in nonproliferative primary cultures. Both nonproliferative and proliferative primary cultures may be subcultured on collagen gels following dispersion by trypsin and EDTA. Methotrexate strongly inhibits proliferative keratinocytes at low concentrations (0.1 microgram/ml) but has no cytotoxic effect on non-proliferative cells. L-serine and dexamethasone increase the multiplication rate of both primary and subcultured human keratinocytes.


Dopamine: a novel antitumor agent active against B-16 melanoma in vivo. L-dopa methyl ester has been shown to be an effective antitumor agent against the B-16 melanoma in vivo. We have now examined the analog, dopamine, a major catabolite of L-dopa. Dopamine administration at a daily dose of 600 mg/kg resulted in a 48% (p less than .001) increase in survival of treated mice as compared to non-treated controls. In vitro, an effect similar to that observed with L-dopa methyl ester was noted, specifically, a rapid and profound inhibition of thymidine incorporation with little effect on uridine or leucine incorporation. We have postulated that the inhibition of a DNA polymerase might be the site of action of these novel antitumor agents.


Necrotizing myocarditis in mice infected with Western equine encephalitis virus: Clinical, electrocardiographic, and histopathologic correlations. Western equine encephalitis (WEE) virus was found in myocardial tissue of adult mice during the first five days after inoculation of the virus, with a peak titer (5.0 log plaque-forming units/g) at 24 hr. Light microscopy revealed a multifocal necrotizing myocarditis with a prominent inflammatory response and hyaline and granular degeneration of myofibers. Electron microscopy showed cytoplasmic viral nucleoids and budding and free mature WEE viral particles. Serial electrocardiograms showed the development of disturbances of rate and rhythm, defects in conduction, marked elevation in the ST segment, and low voltage. Myocarditis has not been previously recognized as a complication of alphavirus infection in humans. and we found no evidence for myocardial damage in 11 persons with acute WEE virus infections studied electrocardiographically in 1975. Demonstration of myocarditis in the WEE virus-infected mouse, however, suggests the need to monitor human patients for possible cardiac involvement during future epidemics of WEE virus infection.


Mechanisms of infertility in genital tract infections due to Chlamydia psittaci transmitted through contaminated semen. Ten heifers inseminated with semen artificially contaminated with Chlamydia psittaci were not pregnant 40 days later, whereas five of 10 control heifers inseminated with the same semen mixed with control diluent became pregnant. Normal embryos were recovered two and one-half or three days after insemination of another group of animals with semen containing C. psittaci, a finding indicating that fertilization failure was not responsible for the infertility. Uterine biopsy samples taken from two heifers in this group contained scattered Chlamydia-infected cells that were detected by immunofluorescence in the subepithelial tissues of the uterine horns. This finding suggests that the infertility may result from an alteration in the uterine environment caused by multiplication of C. psittaci.


Isolation and characterization of protease-deficient mutants of vibrio cholerae. Mutants of Vibrio cholerae that were deficient in protease production were isolated by picking clones form gelatin or casein plates which showed reduced zones of proteolysis. All mutants showed reduced ability to degrade complex proteins (casein and gelatin), and those tested were deficient in ability to degrade chicken egg ovomucin. Some of the mutants demonstrated a decrease in neuraminidase activity. Almost all mutants showed a dramatic loss of virulence in the infant mouse, although toxin was still produced. A partial revertant, to protease-proficient, demonstrated a simultaneous increase in neuraminidase activity and also an increase in mouse virulence. The strains described had a variety of phenotypes.


Prediction of the concentration of penicillins in ascitic fluid from serum kinetics and protein binding of the antibiotics in serum and ascitic fluid of dogs. Ascites was induced in dogs by partial ligation of the inferior vena cava. Concentrations of ampicillin, penicillin G, oxacillin, cloxacillin, dicloxacillin, nafcillin, and methicillin in ascitic fluid and serum were each determined in three animals. All antibiotics were administered intramuscularly in a dose of 15 mg/kg (dry weight) for both single-dose and multiple-dose (eight doses at 4-hr intervals) studies. Binding of antibiotics to serum and ascitic fluid proteins was measured by ultracentrifugation. After single doses the highly protein-bound drugs (oxacillin, cloxacillin, dicloxacillin, and nafcillin) had lower percentages of penetration (ratio of peak in ascitic fluid to that in serum, multipled by 100) than did methicillin, ampicillin, and penicillin G, which have a lower degree of protein binding. The effect was partially overcome by repetitive doses, but five to six doses were usually required to reach equilibrium. In addition to protein binding, serum kinetics (particularly the log mean total concentration of drug in serum after multiple doses) were important determinants of antibiotic concentrations in ascitic fluid. The total antibiotic concentration in ascitic fluid at equilibrium can be accurately calculated from the log mean serum concnetration and the percentages of protein binding in serum and ascitic fluid.


Canine mycoplasmas: pathogenicity of mycoplasmas associated with distemper pneumonia. Mycoplasmas of the following species were isolated from the lungs of dog with distemper: Mycoplasma cynos, Mycoplasma bovigenitalium, Mycoplasma canis, Mycoplasma spumans, and Mycoplasma gateae. One-week-old dogs were inoculated endobronchially with cloned cultures of each species. M. cynos induced a focal pneumonia that were characterized histologically by severe inflammation of bronchi and adjacent respiratory tract tissue. The inflammatory response was initially neutrophilic and later was histiocytic with interstitial lymphoid hyperplasia. M. cynos was recovered from the lungs of inoculated dogs until three weeks after inoculation. A mild inflammatory response was observed in lung tissue of the dog inoculated with M. bovigenitalium, whereas M. canis, M. spumans, and, M. gateae did not induce any visible lesions.


Infantile papular acrodermatitis (Gianotti's disease) and intrafamilial occurence of acute hepatitis B with jaundice: age dependency of clinical manifestations of hepatitis B virus infection. Infantile papular acrodermatitis (IPA, Gianotti's disease) is a clinical manifestation of hepatitis B virus (HBV) infection in childhood. An epidemic of of IPA occurred in Matsuyama, Japan, where 153 patients in a pediatric clinic had IPA between October 1974 and March 1977. In this period 12 mothers and two fathers of patients contracted acute hepatitis B with overt jaundice three to 14 months after their offspring had IPA. Analysis of the subtype of hepatitis B surface antigen (HBsAg) in the infants and their jaundiced mothers and/or fathers disclosed that HBV was transmitted from the infants. All of the index cases were one year old or younger, although the age of patients with IPA ranged from three months to 10 years. In approximately 40% of patients with IPA who were one year old or younger, HBs antigenemia persisted for one year. These facts suggested that the contraction of IPA in children, especially those one year old or younger, was an important route toward establishment of the carrier state of HBV which maintains the reservoir of this virus in the community.


Measurement of IgM and IgG antibodies to Yersinia by solid-phase radioimmunoassay. Solid-phase radioimmunoassays for IgM and IgG antibodies to Yersinia enterocolitica serotype 3. Y. enterocolitica serotype 9, and Yersinia pseudotuberculosis IA are described. Bacteria were adsorbed onto polystyrene balls, and serum antibodies bound to the antigen-coated balls were quantitated by their capacity to bind 125I-labeled antibodies to human immunoglobulins.


Incomplete inactivation of hepatitis B virus after heat treatment at 60 C for 10 hours. A 10(-3) dilution of pooled serum (positive for hepatitis B e antigen and DNA polymerase activity) containing hepatitis B virus (HBV) in a titer 10(5) times the chimpanzee-infectious dose, was heated under water maintained at 60 C for 10 hr. There was a twofold decrease in the titer of hepatitis B surface antigen (HBsAg) as measured by reverse passive hemagglutination after the heat treatment. The heated, diluted serum was still infectious and caused HBV infections in both seronegative chimpanzees given 1-ml iv inoculations of the diluted serum. However, the infectivity of the virus was decreased approximately 10(4)-fold by heat treatment as judged from the prolonged incubation period before appearance of HBsAg in blood. This figure was based on the inverse linear relation between the dose of HBV and the incubation period. The incomplete inactivation of HBV by heat treatment at 60 C for 10 hr should be emphasized because it is widely accepted that heat treatment destroys HBV.


Comparison of the in vitro antifungal activities of miconazole and a new imidazole, R41,400. R41,400 is a recently synthesized, water-soluble imidazole. Its antifungal properties were compared in vitro with those of miconazole using an agar dilution procedure and 175 isolates of human fungal pathogens. The filamentous forms of Histoplasma capsulatum and Blastomyces dermatitidis were inhibited by less than or equal to 2 microgram of either drug/ml; Coccidioides immitis was inhibited by less than or equal to 0.5 microgram of R41,400/ml. Among the yeasts tested, Cryptococcus neoformans and Candida parapsilosis were the most susceptibel to the two drugs, whereas Candida albicans and Candida tropicalis were the least susceptible; 0.5 microgram of either drug/ml was inhibitory for 90%-100% of tested isolates of C. neoformans but for only less than or equal to 20% of isolates of C. albicans, C. tropicalis, and Torulopsis glabrata. Both drugs were inhibitory for most isolates of Trichophyton and Microsporum species at concentrations of less than or equal to 4 microgram/ml; Epidermophyton floccosum was uniquely susceptible to both drugs.


Relationship of subtypes of hepatitis B surface antigen with e antigen and its corresponding antibody. A total of 3,212 samples of blood from asymptomatic volunteer donors positive for hepatitis B surface antigen (HBsAg) by radioimmunoassay and 860 samples negative for HBsAg were tested for the presence of hepatitis e antigen (HBeAg) and its corresponding antibody (anti-HBe) using a rheophoresis technique. Neither HBeAg nor anti-HBe was detected in any sample negative for HBsAg. Of the HBsAg-positive samples, 237 (7.4%) contained HBeAg and 749 (23.3%) had anti-HBe. HBeAg was significantly (P less than or equal to 0.0005) more likely to be in samples with high titers of HBsAg. Anti-HBe had an equal chance of occurring in samples with low or high titers of HBsAg. Both HBeAg and anti-HBe were found in samples with HBsAg subtypes ad or ay. However, a significant association (P less than or equal to 0.0005) between HBsAg/ay and HBeAg as well as an association between anti-HBe and HBsAg/ad was found.


Mechanism of iron chelation in the hypertransfused rat: definition of two alternative pathways of iron mobilization. The mechanism of action of two recently identified iron-chelating drugs, RA and CHA, was compared with that of two well-known chelating agents, DF and DTPA, in hypertransfused rats labeled with selective parenchymal and RE cell radioiron probes. The existence of two alternative pathways for the in vivo chelation of iron has been indicated by the present findings. The first of these pathways involves the extracellular chelation of RE cell iron and its subsequent excretion in the urine. The second pathway is concerned with the intracellular binding of hepatic parenchymal cell iron and its subsequent excretion in the bile. Iron chelation by DTPA is restricted to the first pathway, whereas iron chelation by CHA is confined to the second pathway. DF and RA have a dual effect and are able to enhance the urinary excretion of RE cell iron as well as the biliary excretion of hepatic parenchymal iron. Hypertransfused rats are a simple and useful experimental model for the study of iron mobilization by chelating agents of potential clinical usefulness. However, further studies are required to show whether the pathways of iron chelation identified in rats may represent the mechanism of iron chelation in patients with transfusional iron overload.


C-1 inactivator and cold-promoted activation of factor VII. When exposed to  temperatures between -5 degree and +5 degree C, plasma from pregnant women and from certain blood donors show shortening of the Thrombotest clotting time, kallikrein formation, and activation of blood-clotting factor VII. This phenomenon has been called cold-promoted activation of factor VII (CPA). In this study, it was found that CPA-positive plasma or serum samples which had been exposed to low temepratures showed spontaneous disappearance of C-1-inactivator activity in parallel to the shortening of the Thrombotest clotting time. C-1-inactivator antigen was not affected by storage at 4 degree C. In these CPA-possitive samples the loss of C-1-inactivator activity is caused partially by the formation of kallikrein at this temperature because when kallikrelin was added to C-1 inactivator, the latter was inactive when tested in the esterolytic assay. The formation of Hageman factor fragments may add to further loss. Purified C-1 inactivator effectively inhibited the CPA phenomenon, whereas alpha2-macroglobulin did so only weakly. This finding indicates that during exposure of CPA-positive plasma samples to low temperatures, Hageman factor fragments, which are inhibited only by C-1 inactivator, induce the activation of the kallikrein system and blood clotting factor VII. The reported lowered activity of C-1 inactivator in pregnancy is probably an artifact caused by generation of CPA during storage, since in fresh samples the levels were compeletely normal. Similarly, various subjects classified as belonging to the variant type of HANE (low C-1-inactivator activity with a normal antigen content) were found to have normal C-1-inactivator activity when determinations were made on fresh instead of frozen samples. It is recommended that plasma or serum samples should not be exposed to temperatures between -5degree and +5degree C prior to the determination of C-1-inactivator activity. Moreover, during purification procedures of kallikrein-binding antiproteases such as C-1 inactivator and also alpha2-macroglobulin, the occurrence of CPA should be avoided by the use of CPA-negative plasma as starting material.


Precise anticoagulation for routine hemodialysis. A pharmacokinetic model for minimal dose heparinization for chornic hemodialysis patients was recently described by Gotch and Keen. The model requires the determination of two parameters: dose sensitivity (computed for a given heparin dose from increase in WBPTT above a baseline value) and the heparin elimination constant. This study describes the extension of this model to the more precise control of anticoagulation during routine dialysis. S and K were measured in 30 stable chronic dialysis patients and were found to differ markedly (0.015 less than or equal to S 0.08 sec/unit; 0.04 less than or equal to K less than or equal to 1.7 hr-1). The mean S value was 0.041 +/- 0.002 sec/unit (N = 30) and the mean K value was 0.90 +/- 0.06 hr-1 (N = 30). In addition, the mean t 1/2 of heparin obtained in the group of 30 patients from individual rate constants was 0.86 +/- 0.06 hr, in excellent agreement with values obtained in normal subjects given similar doses of the drug. Variations in sensitivity during dialysis were minimal, but variations in elimination rate of up to 50% were encountered during modeling. However, the large variations in K did  not affect the applicability of the model of control clotting times during dialysis when infusion requirements were based on mean values of S and K taken over four to five dialyses. In an initial group of five patients, whose heparin requirements were reduced by an average of 38% +/- 20 (range  13% to 65%), there was no significant change in the degree of dialyzer clotting in comparing premodeling and postmodeling heparin therapy. In most of the remaining patients (N = 22) the pattern was similar: a reduction in total heparin administration without increased dialyzer clotting. In three patients (10%) over-all heparin dose had to be moderately increased (3% to 13%). Heparin modeling has been successfully applied to routine anticoahe technique cannot be extended to other clinical procedures involving either intermittent or continuous infusion of heparin. To assist in the application of heparin modeling, nomograms have been developed.