Guidelines for deciding care of critically ill or dying patients. Medical technology is usually beneficial in the care of sick or injured persons, sometimes dramatically so. However, since it is often intrusive, occasionally cruel, sometimes of little or no value, and almost always expensive, its use must be assessed critically, particularly in ICUs. Guidelines for doing this are proposed. To ensure the most caring approach to patient care and family support, the values and autonomy of patients and their families, one by one, are emphasized in all decision making and the roles of nurses and social workers as well as those of physicians are considered central. If these guidelines are used, many, perhaps most, of the ethical and legal issues and the problems of human relationships in ICUs will be resolved.


Relevance of the gestational age distribution of meconium passage in utero. The incidence of meconium staining of the amniotic fluid among the admissions to a newborn special care unit was determined. Meconium staining of the amniotic fluid was present in 251 (7.5%) of 3,374 admissions. The majority of those with meconium staining (98.4%) was of 37 weeks gestation or greater and none was less than 34 weeks gestation. The possible relevance of this gestational age distribution is discussed.


Nasal septal trauma in children.

Nasal septal trauma in children. If the septal component of a nasal injury is adequately managed, usually the entire nasal injury will be well managed. Major or minor nasal trauma can cause cartilage fracture, deviation, dislocation, hematoma, or abscess formation, and the various associated sequelae, some of them life-threatening. A negative x-ray report should never be used as a substitute for a complete intranasal examination in any child with nasal trauma. Any nasal abnormality should be referred for immediate evaluation and treatment.


Posterior fossa hemorrhage in the term newborn: report of two cases. Two term newborn infants born by frank breech delivery had posterior fossa hemorrhage diagnosed by CT scan within the first 72 hours of life and underwent successful surgical drainage of hematoma. Previously reported cases with long-term postoperative survival have included 12 term newborns with good outcome in nine. Most remaining reported examples of posterior fossa hemorrhage in newborns have been from autopsy reports on premature infants. It is suggested that operative intervention is often indicated in cases of early neonatal posterior fossa hemorrhage and that additional data on long-term outcome of operative intervention as well as outcome in nonoperated cases are needed. One of the two cases reported here and one previously reported presented with onset of seizures as the initial clinical manifestation.


Inaccuracy of the Clinitemp skin thermometer. The Clinitemp Fever Detector (Clinitemp) is a newly marketed thermometer consisting of plasticencased thermophototropic esters of cholesterol that change color over a specific short-range of temperature. The manufacturer states that the instrument can identify fever by measuring skin temperature in children. On the basis of a patient's report of one inaccurate Clinitemp, we undertook to investigate the accuracy of this thermometer. One hundred fifty-two children presenting to the Children's Hospital Emergency Room had their temperature taken with two thermometers, an electronic thermometer that had been checked for accuracy with a National Bureau of Standards thermometer and the Clinitemp. Clinitemps, purchased over a two-month period from three pharmacies, were tested on different children. Thirteen of thirty children (43%) with fever (rectal temperature greater than or equal to 38.3 C (101 F) or oral temperature greater than or equal to (37.8 C) (100 F) identified by the electronic thermometer, were correctly classified as having fever using the Clinitemp. When fever was defined to include children with a rectal temperature greater than or equal to 38.0 C (100.5 F) or an oral temperature of greater than or equal to 37.4 C (99.5 F), the Clinitemp correctly identified 13 (32.5%) of 40 children with fever. There appears to be an appreciable risk that someone with a serious illness may delay seeking medical attention on the basis of a normal temperature as measured by the Clinitemp.


Recurrent abdominal pain in children: lactose and sucrose intolerance, a prospective study. Thirty-eight consecutive children with recurrent abdominal pain underwent lactose tolerance tests; 28 of these were also given sucrose tolerance tests. Abdominal pain and abnormal lactose tolerance tests were noted in 11 of 38, while none of the 28 had an abnormal sucrose tolerance test; however, 1 had abdominal pain. Elimination diet for 4 weeks produced significant or total pain relief in 10 of 11 (lactose free) and 0 of 1 children (sucrose free). Lactose intolerance seems to play a contributory role in recurrent abdominal pain in children, while sucrose intolerance does not.


Negative effects of oral fatty acid supplementation on sweat chloride in cystic fibrosis. Essential fatty acid supplementation with oral safflower oil (1 gm/kg/day) to 11 cystic fibrosis patients (aged 6 months to 14 years) for one year produced no significant change in sweat chloride concentration (mEq/liter) or sweat rate (gm/min/m2), Addition of vitamin E (10 mg/kg/day) to the safflower oil had no effect on sweat chloride concentration or rate compared to placebo. No clinical improvement could be detected compared to a control group. These results do not support previous reports of the effects of fatty acid supplementation on sweat electrolyte concentrations in cystic fibrosis.


Diagnosis of neonatal bacterial infection: hematologic and pathologic findings in fatal and nonfatal cases. Consecutive newborn autopsy cases were divided into infected and noninfected groups on the basis of pathologic findings and cultures, and were compared to a concomitant consecutive group of neonatal survivors with proven bacterial sepsis. Newborns dying with bacterial infection often demonstrated leukopenia, neutropenia, and thrombocytopenia, usually associated with normal bone marrow cell production. Those with nonfatal sepsis frequently had neutrophilia with an increase in absolute band counts. Of infected newborns 80% showed one or more hematologic abnormalities as did 43% of newborns dying without bacterial infection. Of newborns dying with bacterial infection 13% had no hematologic abnormality. Blood cultures were negative in 18% (seven) of the infants dying with bacterial infection. Abnormalities of the white blood cell, differential and platelet counts are not invariably specific for bacterial infection nor do normal values adequately exclude it. Blood cultures may be negative in newborns dying with significant foci of bacterial infection.


Bathtub drownings: report of seven cases. The domestic bathtub is an important site for infant drownings. A total population study of drowning and near-drowning accidents involving Honolulu infants has enabled the risks to be specified with greater detail. A series of seven consecutive bathtub immersion accidents is presented. The "at risk" profile comprises highly mobile families of lower socioeconomic status; usually younger siblings in larger families are involved and often the father had immediate care of the infant at the time of the accident. Another case of bathtub immersion as a form of nonaccidental injury is described. In five of the other six cases reported, the drowned child was left attended by an older sibling. Preventive strategies are discussed.


The "In-Training Examination" of the American Board of Pediatrics: does it test for "new" or "old" information? The American Board of Pediatrics In-Training Examination or "Pre-Test" is not in widespread use as a means of evaluating the cognitive knowledge and problem-solving skills of hourse officers. The examination is modeled after the certifying examination of the American Board of Pediatrics. The 1977 Pre-Test was analyzed in an attempt to determine whether awareness of recent medical knowledge was required to pass this examination. The 7th through 10th editions of the Nelson Textbook of Pediatrics were used as a reference source. These editions represent information that is from 5 to at least 20 years of age. Analysis of the 190 items revealed that the correct answer was known for 148 or 78% of the questions at least 20 years ago. These results suggest that the Pre-Test, and presumably the American Board of Pediatrics certifying exam, measures the candidates' knowledge of long-standing core information.


Aflatoxin B1; its role in the etiology of Reye's syndrome. Seven cases of Reye's syndrome in which aflatoxin B1 was isolated from the blood or liver or both are presented. In two cases aflatoxin B1 was found in the blood during the acute phase of the disease; a finding not previously reported. In six cases aflatoxin B1 was recovered from autopsy specimens of liver. A number of case reports linking aflatoxin B1 to Reye's syndrome have appeared in the literature but until now only one case had been reported from the United States. Aflatoxin B1 and its possible role in the etiology of Reye's syndrome is discussed. It is concluded that Reye's syndrome is the result of multiple interrelated factors.


Evidence for hypertyraminemia in Reye's syndrome. Utilizing a specific and sensitive radioimmunoassay, palsma and urine tyramine were measured in 14 consecutive patients with liver biopsy-proven Reye's syndrome. Plasma tyrosine was measured in 11 of these patients. The results revealed significant (P less than .003) elevation in plasma (3.4 +/- .52 ng/ml) (mean +/- SEM) and urine (1.00 +/- .26 mg/24 hr) tyramine as well as plasma tyrosine (204 +/- 52.5 mumole/liter) at the onset of the disease when compared to the levels of tyramine and tyrosine in a group of hospitalized patients without hepatic disorders. Furthermore, there was a positive correlation between plasma tyramine and days in coma (r = .86; P less than .001), and between plasma tyramine and tyrosine (r = 0.80; P less than .001). These data suggest that there is s substantial disturbance of tyrosine metabolism in Reye's syndrome and that the accumulation of this amino acid and its metabolite, tyramine, may contribute to the encephalopathy of this disease.


Correlations between appointment keeping and reorganization of hospital ambulatory pediatric services. Over a period of 13 months before and after a university-affiliated hospital's daytime ambulatory pediatric facility was upgraded from an episodic care clinic to a primary care unit, 260 subjects were interviewed in an attempt to predict compliance with return appointment scheduling. The parents of patients more than 10 years of age were the least compliant, but most of the differences in compliance appeared due to the subject's evaluation of the diagnostic ability, thoroughness, and sympathy of the physician at the initial visit. Although no changes were noted in the subjects' demographic characteristics or in their general opinions of ambulatory health care delivery or of attitudes desired of physicians, their evaluations of recent visits improved and the missed appointment rate declined by 46% in the course of the study. Moreover, the pediatric house officers, who evaluated the patients, demonstrated an increased ability to assess the characteristics the subjects found important in physicians. Improvements are still needed, especially in the amount of communication between house officers, patients, and parents, but heeding clients' opinions about the provision of primary health care may help to make missed appointment rates negligible.


Myiasis presenting as cellulitis of the cheek. A case of myiasis due to the northern cattle grub (Hypoderma bovis) in a 2 1/2-year-old girl presenting as cellulitis of the cheek and periorbital cellulitis is detailed in this report. A literature review of similar cases reported over the past five years is included.


Polyneuropathy in childhood.

Polyneuropathy in childhood. Polyneuropathy is an uncommon neurologic disorder that occurs in childhood. An evaluation of 61 patients over a period of seven years showed the Guillain-Barré syndrome and degenerative polyneuropathies to be the most common diagnoses. Other etiologies included metabolic, toxic, and neuropathies associated with systemic diseases. A group of idiopathic neuropathies was identified in which an unusual finding was a large subgroup of children with chronic or progressive central nervous system disease.


Hyperactivity and related behavioral characteristics in a sample of learning disabled children. 64 learning disabled and 12 minimal brain-damaged children were evaluated by their teachers on 11 categories of behavior. Analysis showed that behavioral characteristics associated with hyperactivity did not differentiate among subjects. Teachers rated poor motor coordination as the outstanding trait of this sample.


Reaction time and visual brightness: within-subject correlations. An experiment was conducted to compare visual reaction time and visual brightness within the same subjects. Simple reaction times and magnitude estimates of brightness were obtained in response to 1000-msec. flashes of 60.7, 67.5, 76.4, 85.1, and 93.4 dB re 10(-10)L white light. The relationship between reaction time and stimulus intensity was best described by a negative logarithmic function, while the relationship between magnitude estimates of brightness and stimulus intensity was best described by a power function. Linear correlations between reaction times and magnitude estimates indicated that visual reaction time and brightness are not proportional within all subjects. Previous reports of proportionality between these two measures were discussed as possibly being the result of inappropriate cross-experiment comparisons.


Influence of movement activities on shape recognition and retention. Three groups of 4-yr.-old children were asked to complete a form perception assessment instrument prior to, 1 hr. after, and 1 wk. following a treatment. Group 1 participated in a movement-based form perception program, while Group 2 was instructed using a traditional classroom method. A third group which acted as control participated in unrelated movement activities. A repeated-measures analysis of variance gave a main effect of tests and an interaction of groups X tests. Group 2 displayed significantly higher performance on the posttest than Group 1; however, after 7 wk. the performance of Group 2 had decreased to a level below that of Groups 1 and 3, which remained stable.


Facial expressive cues in person perception. The effect of facial expressions on estimates of the likelihood that a person will again commit an offense for which he has been arrested was studied. Such information did not affect estimates of 34 male and 36 female undergraduates as much as did the objective information provided about the offense. The results suggest directions for research on the role of facial expressions in interpersonal judgments.


Primary grade children's memory for parts of speech. Developmental differences in elementary school (kindergarten, first and second grade) children's free recall for parts of speech were investigated using sentences with normal and scrambled word order. The children were presented four sentences with normal syntax and four sentences with scrambled word order. There were significant effects of age, syntax, and rate of presentation; these replicated previous research. The unusual finding was that the kindergarten children, when presented with scrambled word strings, recalled more verbs than either the first or second grade children. It was hypothesized that this occurred because either the kindergarten children failed to detect the scrambled nature of syntaxless strings, or there is a change in the comprehension strategies which de-emphasizes the role of the verb.


WAIS test-retest reliability for a clinical out-patient sample. WAIS test-retest reliabilities were calculated for a clinical out-patient sample with testing intervals varying from 1 to 10 yr. There was no relationship between test-retest interval and the stability of test scores and the correlations between IQs were quite satisfactory (Full Scale IQ = .897, Verbal IQ = .906, Performance IQ = .876). Reliabilities remained high even when the sample was divided by diagnosis into organic, neurotic, personality disorder, and schizophrenic subgroups.


Reliability of the Finger Tapping Test and a note on sex differences. The reliability of the Finger Tapping Test was investigated in two studies. In the test-retest condition 30 male and 30 female college students were tested twice by the same examiner. In the inter-examiner condition 30 male and 30 female college students were tested once by each of two examiners. Reliability coefficients for the dominant and nondominant hands were high in both studies (about .8), as contrasted with that of the ratio score (about .5), casting doubt on the use of the ratio score to lateralize impairment. Significant sex differences (males about 3 taps faster) were found, calling into question the use of single test interpretation schemes. Slight inter-examiner differences in mean scores were also detected.


Duration of the motion aftereffect as a function of retinal locus and visual field. The duration of the aftereffect induced by viewing a rotating disc was recorded separately for the four hemiretinae of the left and right eyes using a new method of measurement. The results showed duration of aftereffect to differ between nasal and temporal hemiretinae of the right eye and between left and right cerebral hemispheres.


The Babcock Story Recall of behaviorally disordered children scoring high or low on extraversion. Short-term memory for a meaningful story was studied in 47 learning disordered boys and 34 girls aged 5 through 10 yr. 11 mo. High and low scores on Extraversion predicted differences in mean scores on verbatim Immediate and Delayed Recall of the Babcock Story.


Role of familiar size in spatial judgments under natural viewing conditions. The purpose of the present experiment was to examine the role of familiar size in judgments of size and egocentric distance under natural (non-reduced) viewing conditions. Independent groups (ns = 14) judged normal and large off-size chairs and control objects presented at a distance of 25.6 m. Subjects also judged the size of unfamiliar objects (adjacent stimuli) attached to the chairs and stakes. The results indicate that the effects of familiar size are specific to spatial judgments of the familiar object itself since judgments of the adjacent stimuli were unaffected by familiar size.


Temporal and intensitive factors in comparative judgments of tactile space. Temporal imbalances between the successive stimulation of pairs of loci on each forearm altered judgments of the equality of the spatial extents between sets of loci. The spatial judgments became increasingly inaccurate as the temporal imbalance was increased, i.e., the Tau effect. Changes in stimulus intensity also influenced the dependency of spatial judgments on temporal factors. The data suggest that concomitant variations of spatial, temporal, and intensitive components of a vibrotactile stimulus "package" can produce systematic perceptual effects of potential significance in the design of vibrotactile sensory substitution systems.


Residual sensory capacities of the deaf: a signal detection analysis of a visual discrimination task. This experiment compared the visual sensory sensitivity of deaf and hearing subjects in a signal detection paradigm. Subjects (ns = 6) were required to give forced-choice responses to a brightness discrimination task under three stimulus probability conditions (0.25, 0.50, and 0.75). A total of 1,800 trials were given to each subject and utilized to construct isosensitivity functions and d' and Beta, indices for sensory sensitivity and response bias, respectively. The results showed that no enhanced sensory sensitivity is present for these deaf children and questions the classical sensory compensation hypothesis. Furthermore, the deaf subjects responded in a relatively bias-free manner to variations in stimulus probability.


Influence of cognitive style on an incidental memory task. The present study investigated the interaction between cognitive style, imagery, and memory. The Tactual Performance Test Location Score from the Halstead-Reitan battery was used as a measure of incidental tactual memory and mental imagery. The Group Embedded Figures Test was used to assess cognitive style. Results for 38 Caucasian males of mean age 49.9 yr. suggest that cognitive style is related to an individual's ability to perform a non-verbal, non-visual memory task. Further, cognitive style may be an important mediating variable influencing intrapersonal behaviors such as non-verbal memory and mental imagery.


Some aspects of sleep disturbance in coronary patients. Of 42 coronary care patients studied during 10 hr. of polygraphically recorded sleep, 28 were in an open-ward coronary care unit and 14 were in a semi-private telemetry unit. The observed sleep disturbances were not a function of type of unit, length of hospitalization, sex, or medications. Sleep was significantly less fragmented in those patients judged less severe in pathology. These results indicate that alterations in normal sleep patterns occur routinely within coronary care environments, even in the absence of disturbing environmental stimuli and suggest that a closer analysis be made of sleep in these settings in light of the known relationships between sleep and cardiac function.


Hand movements and nondominant fluency in bilinguals. 16 subordinate bilingual subjects produced 5-min. monologues in their nondominant languages, i.e., English or Spanish. Hand-movement activity manifested during the videotape monologues was scored and related to measures of fluency in the nondominant language. The hand-movement behavior categorized as Groping Movement was significantly related to all of the nondominant-language fluency measures. These correlations support the assumption that Groping Movement may have a function in the process of verbal encoding. The results are discussed in terms of the possibility of monitoring central cognitive processes through the study of "visible" motor behavior.


Effects of left-right orientation and position reversals on spatial perspective taking in young children. 50 boys and 50 girls, from Grades K through 4, were presented with 180 degrees perspective-taking tasks that varied arrays in terms of the number of front-back and left-right orientation reversals and left-right position reversals. Results confirmed existing evidence that left-right orientation reversals are more difficult than front-back orientation reversals in arrays of one object. However, with arrays of two objects, left-right orientation reversals appear easier than front-back orientation reversals, apparently because of the relationship between the objects.


Effects of chromatic targets on a throwing task for subjects referred for learning disability. The purpose of the study was to determine the effects of chromatic and achromatic targets on performing a throwing task for subjects referred for learning disability. 20 boys referred to the Perceptual Motor Development Center practiced under achromatic or chromatic target conditions. After 5 practice bouts, each subject immediately performed on the opposite condition. When subjects were aware of chromatic and achromatic target alternatives, chromatic targets facilitated performance.


Factorial pattern description and comparison of functional abilities in neuropsychological assessment. A principal factor analysis of 36 neuropsychological test variables yielded eight readily definable factors. These factors represent the kinds of general functions evaluated in the assessment of organic brain damage. The functional categorical scheme produced by the factor analysis was compared with other empirical and theoretical schemes. Shortcomings of the traditional neuropsychological battery were discussed in terms of the factors.


Facial imagery and personality development. The empirical relationship between judgments obtained with a motorized facial-distortion mirror and relevant personality and rating measures was examined. Subjects were 88 school children. The findings indicated general trend differences between males and females in perceiving facial distortion shown in a mirror. Although not statistically significant, a relationship between teachers' ratings on hygiene, self-concept, sociability, and two scales of the High School Personality Questionnaire were noted.


Assessment of cognitive deficiency with the McCarthy Scales and Stanford-Binet: a correlational analysis. The present study tested matched samples of 15 retarded and 15 normal children on the Stanford-Binet Intelligence Scale and the McCarthy Scales of Children's Abilities. Pearson correlations between Stanford-Binet IQs and the six McCarthy Scale Indexes for retarded subjects were lower than coefficients obtained from the normal subjects and from previous research. While the General Cognitive Index may be interchangeable with IQ in the Normal range of intellectual functioning, this relationship was not found for the retarded subjects in the present study. The "venerable" Stanford-Binet retains its position as the most broadly applicable measure of intellectual functioning. Implications of the study as well as an outline for future research were included.


Correlational analysis of speakers' heights, weights, and temporal speech features. Correlation coefficients on height, weight, and temporal features were computed separately for 15 female and 15 male speakers. With only one exception, speakers' heights and weights were not significantly correlated with their temporal characteristics. Implications of these findings and suggestions for future research are discussed.


An exploration of perception of body boundary, personal space, and body size in elderly persons. A study of 108 elderly persons using the Body Distortion Questionnaire and the personal space simulation technique test did not support hypotheses that elderly persons with a large personal space will have a larger distortion of body boundary, a larger perception of large body size, a smaller perception of small body size, a larger distortion of body size, and a larger body distortion than elderly persons with a small personal space. The analyses with one-tail t tests showed elderly persons with a small personal space have a larger perception of large body size and a larger distortion of body size than elderly persons with a large personal space. When the extremes of personal space were used the results were the same. Males have a larger personal space and greater distortion of skin perceptions than females.


Age differences in movement time over distances proportional to size. Investigations of the differences in movement speed over the age span, childhood to early adulthood, have typically confounded age with size differences which bring about mechanical differences in the task. The present study investigated the effect on arm movement time of confounding age and limb length. Young adults and children 7 to 9 yr. of age were tested over a distance proportional to their arm length. Despite moving over a proportionally shorter distance, the children were significantly slower than the adults, suggesting that age differences in performance are not solely attributable to size differences among subjects.


Prediction of neurosurgical results by psychological evaluation. There has been an increasing interest in the role of personality factors in the outcome of medical treatment. The present study examined the role of personality measures in predicting the outcome of neurosurgery for patients with a well-documented disruption of one or more discs. Each of 15 male and 16 female patients whose average age was 40.8 yr. received the Minnesota Multiphasic Personality Inventory before surgery and received a follow-up at least one year after surgery or until a final, stable level of recovery was attained. A multiple correlation of .64 between the personality measures and treatment outcome suggested that even in cases with a well-documented need for surgery, psychological factors can play a major influence in the eventual outcome. Possible psychological interventions before surgery which might increase the likelihood of a good outcome are briefly outlined.


Decrements in olfactory sensitivity due to ozone exposure. Approximate olfactory thresholds were determined in an exploratory study in which subjects were exposed to ozone (O3). The odorants were butyl alcohol (BA) and acetic acid (AA). Preliminary data suggest (1) temporary increases in thresholds due to O3 exposure, (2) diminution of O3 effects with repeated exposures, and (3) greater and more reliable effects for BA than for AA.


Extent of psychological differentiation and creativity. Among the extensive array of studies relating Witkin's construct of psychological differentiation to many psychological functions and variables, none seem to have adequately tested its relationship to creativity, although these two variables have personality traits and development characteristics in common and require similar skills for effective performance. Eighty-five male high school students were separated according to Embedded Figures Test, and the extreme groups tested for creativity by eight factorially pure tests developed by Guilford, and by Schaefer and Anastasi's Biographical Inventory. Statistical procedures included analysis of covariance, analysis of variance, and a matrix of intercorrelations. With intelligence controlled, field-independent persons performed significantly better than field-dependent persons on measures of visualization, spontaneous flexibility, adaptive flexibility, and creativity in mathematics and science but not significantly better on the other six creativity tests.


Comparison of culturally deprived school achievers and underachievers on memory function and perception. To compare the memory function and perception of culturally deprived achievers with underachievers, 36 culturally deprived children were assigned to one of two groups according to their achievement level, in relation to their age and IQ. Underachievers were children achieving 6 mo. or more below expected level. Achievers were children achieving within at least 5 mo. of expected level. All subjects were between the ages of 8 and 12 yr. and were in Grades 4, 5, or 6. Four tests were administered, the Block Design and Digit Span subtests of the WISC, Memory-for-Designs, and the Minnesota Percepto-Diagnostic Test. The two groups did not differ on the first three tests, but the achievers performed significantly better on the last test than the underachievers. It was speculated that the differences were related to level of motor execution.


Comparison of accuracy in auditory and tactile recognition memory for environmental stimuli. Accuracy rates for auditory and tactile recognition of naturalistic stimuli over a 7-day period are compared. 40 subjects listened to 50, 107, or 194 naturalistic sounds and were tested immediately or after delays of 2 or 7 days. 30 other subjects handled but did not visually inspect 150 common objects and were tested over the same three delay intervals. Recognition accuracy for sounds was 87.5%, 82.5%, and 80.4% while common objects were recognized at 96.0%, 93.8%, and 88.5% rates of accuracy. Tactile recognition memory was superior to auditory recognition memory. The recognition accuracies of both modalities were affected by the delay interval. The number of items inspected had no effect on the recognition memory for sounds. Following a delay of 1 wk., the accuracy of recognition relative to the original level of function was 92% for both modalities.


Critical analysis of a study on field dependence in young children. Kojima's conclusion that our method of scoring performance in the rod-and-frame test did not produce satisfactory results in young children was invalid because our scoring method was used incorrectly, fallacious reasoning was used to reject our scoring method, subjects were classified wrongly, and the procedure used to test vertical perception in the children probably was unreliable.


Birth order and intelligence: an immunological interpretation. The literature indicates that the IQs and school performance of children tend to decline with increasing order of birth. A hypothesis is here presented that the effect of birth order upon intellectual performance may result from an increasing probability of maternal immune attack upon the fetal brain in utero with order of parity. In support of this hypothesis, evidence is adduced from the literature that the fetal brain is antigenic, that fetal antigens may reach the immune system of the mother, that the incidence of maternal sensitization to fetal antigens increases with parity, that antibodies may readily cross the placenta and reach the fetal brain, that antibodies can be highly teratogenic, and that certain antibodies may damage, in a lasting way, the structure, function, and learning capacity of brains in experimental animals and human infants.


[Intestinal polyposis (author's transl)]. Recto-colonic polyposis is typical of pre-malignant lesions. Recognition and the application of appropriate treatment offer true prophylaxis against recto-colonic carcinoma in sufferers. Careful study should be made of other family members, the only way in which latent forms may be discovered before the stage of malignant change.


[Panhypopituitarism and dwarfism in a man with a primary empty sella turcica (author's transl)]. Endocrine features associated with the primary empty sella turcica syndrom are rare; they are usually related to a pituitary microadenoma and more rarely to an idiopathic panhypop ituitarism. A pituitary dwarfism with an idiopathic panhypopituitarism of hypothalamic origin, associated with an "empty" sella turcica containing functional and stimulable pituitary tissue, is reported in a 27 year old male Moraccan.


[Percutaneous transhepatic drainage of the biliary tree (author's transl)]. For some mechanical jaundice surgery may be hazardous or even of no use. Percutaneous transhepatic drainage of the biliary tree is a new technique allowing a quick and durable resolution of the jaundice. It is a non drastic procedure which can be done under local anesthesia. Here is the report of the authors first case. They propose the likely indications of such a drainage.


[Glycosylated hemoglobin: résults of 550 cases (author's transl)]. A selective estimation of glycosylated hemoglobin, HbA1C, exclusive of other minor components, is propably one of the best available tests. Such an automated method is proposed, which was experimented in 550 cases. It demonstrates a quite narrow gaussian distribution in controls. In contrast, a large dispersion is observed among long term diabetics, most of them with ocular complications with only a minority of results in the normal range. This is still more evident in case of juvenile diabetes.


[Mortality due to carcinoma of the stomach between 1954 and 1974. Changes in France (author's transl)]. A study of changes in mortality due to carcinoma of the stomach in France between 1954 and 1974 was undertaken on the basis of probable levels standardised on the French population in 1968. There was a marked fall in this mortality for both sexes. In the male, the initial level in 1954 was 54.8/100 000 and the decrease was of the order of 1.35 deaths per 100 000 per year, i.e. an annual fall of -3.21%. This phenomenon was more marked during the second period (1965--1974): - 3.88%, than during the first period (1954--1963: - 2.38%. In the female, with an initial mortality rate of 31.25/100 000, the annual decrease was 31.25/100 000, i.e. an annual fall of - 3.49%. This fall was - 3.09% for the first ten year period and - 4.80% for the second period. Thus in France, in common with many other countries, there has been a marked decrease in mortality due to carcinoma of the stomach, for both sexes, and this phenomenon became progressively more notable during the period of the study.


[Combined revascularisation of the superficial and deep femoral arteries by vein graft (author's transl)]. When venous bypass is indicated in order to reconstruct the femoral bifurcation, or its branches, it is desirable to revascularise the superficial and deep femoral at the same time. There are three technical possibilities: bifurcated graft, scarf graft, bypass with interfemoral graft. If there is a lack of venous material, the bypass will be mixed: goretex-vein. There are numerous indications for these procedures: obliterative arterial disease with stenosis of the division of the common femoral, repeated of septic surgery of the femoral tripod, aneurysms of traumatic lesions involving the femoral bifurcation.


[The hepatitis B virus markers, in leprous patients (author's transl)]. The hepatitis B virus markers were studied on 553 leprous sera and 100 controls sera. HBs Ag detected by RIA were present on 25,4% of leprous and 12% of controls; the anti-HBs by RIA were revealed in 44,1% of patients out 38% of controls. The leprous was not carrying this markers were HBe Ag or anti-HBe or anti-HBc positive. By this vertical study it appears that 2,4% of the cases presented recent or acute hepatitis; 23% were chronic carriers; 41,7% had been in times past infected but were cured and the third remaining had been infected but coat markers were absent, it is more than likely that is an old infected group. The study revealed no significant difference in hepatitis chronic forms frequency between lepromatous and tuberculoïd patients.


[Gastric emptying of an ordinary meal in man. Study by a radio-isotopic method (author's transl)]. A radio-isotopic method was used to study the gastric emptying of an ordinary meal in 15 control subjects. The technique developed may be used for direct measurement of the early phase of gastric emptying and a simultaneous study of emptying of liquid and solid phases, respectively labelled with Tc99m and Cr51. Emptying of the liquid phase of the meal takes place in accordance with a mono-exponential curve in relation to time, the T 1/2 of which is 54 min +/- 6 (MSD). Emptying of the solid phase is significantly slower than that of the liquid phase. The reproductibility of the method was confirmed and the imprecision of each measurement does not exceed 5%.


A precise quantitation of gene number by saturation hybridization using cloned DNA. This paper describes a precise method of gene titration as applied to the alpha- and beta-globin genes in the mouse. The three salient features of the method are: (i) the use of saturation hybridization in probe cDNA excess, (ii) the use of highly purified cDNA probes prepared by preparative hybridization with cloned globin sequences (Longacre and Mach (1978) J. Biol. Chem. 253, 7500) and (iii) the use of cloned globin sequences to calibrate the system internally. The results indicate that there are two genes for alpha-globin and two genes for beta-globin in the BALB/c mouse. The significance of these results are discussed in relation to other data regarding adult and embryonic globin genes.


Rapid synthesis of oligodeoxyribonucleotides. III. Effect of added carboxylate ion on the efficiency of internucleotide bond formation. Solid-phase synthesis of the dodecanucleotide, d(pT-A-A-C-T-G-C-T-C-A-C-T). In solid-phase oligodeoxyribonucleotide synthesis the addition of benzoic acid to internucleotide phosphodiester bond-forming reactions lowers coupling yields by far greater amount than anticipated on a simple nucleotide-carboxylate molar ratio. High coupling yields were consistently obtained in synthesis of the dodecanucleotide, d(pT-A-A-C-T-G-C-T-C-A-C-T), using rigorously purified nucleotide starting materials.


Influence of nucleotide sequence adjacent to duplex DNA termini on 3' terminal labeling by terminal transferase. We have analyzed the effect of base-pairing at the exposed ends of Hinc II fragments of SV40 DNA on the efficiency of ribonucleotide incorporation catalyzed by terminal transferase. Wide variations in the labeling efficiency of individual DNA fragments have been observed. To elucidate the nature of this variation at the molecular level, we have correlated this effect with nucleotide sequence adjacent to the cleavage site. We found that a G:C base pair right at the exposed end drastically reduces the incorporation of ribonucleotides. Furthermore, the higher the number of G:C base pairs adjacent to the exposed end, the greater the reduction in labeling efficiency. From these results, we conclude that the labeling efficiency is determined by the degree of 'terminal breathing' of the DNA molecule at the exposed end of the duplex.


The respective roles of the protein kinase and pppA2' p5' A2' p5 A-activated endonuclease in the inhibition of protein synthesis by double stranded RNA in rabbit reticulocyte lysates. Double-stranded RNA (dsRNA) inhibits protein synthesis in rabbit reticulocyte lysates by activating the synthesis of the endonuclease effector pppA2' p5' A2' p5' A(2-5A) and a protein kinase which phosphorylates the protein synthesis initiation factor eIF-2. Under certain assay conditions, high concentrations of dsRNA are without inhibitory effect in many lysates (high dsRNA "reversible" lysates). In these lysates natural dsRNA at low concentrations stimulated protein kinase activity to a greater extent than did the synthetic dsRNA poly rI.rC. Synthesis of 2--5A was greater when poly rI.rC was used. However, a number of factors, including the salt concentration and messenger RNA used, combine to determine the overall effect of dsRNA on protein synthesis under any given set of experimental conditions.


Synthesis of human insulin gene. Part I. Development of reversed-phase chromatography in the modified triester method. Its application in the rapid and efficient synthesis of eight deoxyribooligonucleotides fragments constituting human insulin A DNA. Preparative reversed-phase thin layer chromatography on silanized silica-gel (RP-2 and RP-18) has been developed to purify triester deoxyribooligonucleotides prepared by the modified triester method. The effectiveness of this technique has been demonstrated in the rapid synthesis of eight pure deoxyribooligonucleotides constituting the sequence of human insulin A DNA. The sequence of each of the deoxyribooligonucleotides was confirmed by the two-dimensional mobility-shift method of finger-printing.


Cromatin and core particles formed from the inner histones and synthetic polydeoxyribonucleotides of defined sequence. Chicken erythrocyte inner histones (H2A, H2B, H3 and H4) were associated with the two complementary homopolymeric polydeoxyribonucleotides and the two alternating copolymeric polydeoxyribonucleotides. No evidence for formation of chromatin-like structures was obtained for the complexes with poly(dG) . poly(dC) or poly(dA) . poly(dT). Both poly (dGdC) . poly(dGdC) and poly(dAdT) . poly(dAdT) could be folded by histones to yield material digested by DNAase I to multiples of about 10 and by staphylococcal nuclease to 146 bp core particles. Due to the lack of sequence heterogeniety in the complex of histones with poly(dAdT) . poly(dAdT), core particles with remarkable fine structural detail are obtained. The internal organization of DNA in the AT-containing and GC-containing core particles appears not to be identical.


DNA replication in Physarum polycephalum: electron microscopic and autoradiographic analysis of replicating DNA from defined stages of the S-period. Electron microscopic and autoradiographic analysis of replicating DNA from Physarum showed that replication occurs at a rate of 0.4 micron/min/per replicon and that replicons of size 10--15 mu occur in temporal clusters with an average of about 4 replicons per cluster. These results are compared with previous hydrodynamic measurements and with those obtained in other organisms.


Unique sequence arrangement of ribosomal genes in the palindromic rDNA molecule of Physarum polycephalum. R-loop and restriction mapping procedures reveal the organization of coding regions at each end of the giant rDNA palindrome of Physarum polycephalum. A 19S coding region of 2.10 +/- 0.21 kb is located at each end of a very long central spacer (35.64 +/- 2.08 kb). An internal spacer of 1.66 +/- 0.12 kb lies distal to the 19S gene. The 5.8S rRNA coding region is located in this spacer. The 26S gene lies distal to the internal spacer. The 26S gene is unusual among those of eukaryotes in that it consists of 3 coding regions (alpha, beta and gamma) interrupted by 2 intervening sequences. The 26S alpha (most central) coding segment of 2.41 +/- 0.33 kb is separated from the 26S beta segment by an intervening sequence of 0.68 +/- 0.13 kb. The 26S beta segment (0.70 +/- 0.11 kb) is separated from the most distal 26S gamma segment (0.59 +/- 0.14 kb) by an intervening sequence of 1.21 +/- 0.14 kb. The 2 intervening sequences are present in at least 88% of ribsomal genes from active plasmodia, indicating that genes containing these sequences are transcribed. The rDNA termini contain a heterogeneous region which varies in length by +/- 300 base pairs.


Core nucleosomes by digestion of reconstructed histone-DNA complexes. Reconstructed complexes of the inner histones (H2A, H2B, H3, H4) and a variety of DNAs were digested with micrococcal nuclease to yield very homogeneous  populations of core nucleosomes (nu 1). Nucleosomes containing Micrococcus luteus DNA (72% G+C); chicken DNA (43% G+C), Clostridium perfringens DNA (29% G+C); or poly(A-dT.poly(dA-dT) have been examined by circular dichroism, thermaldetenaturation, electron microscopy, and DNAse I digestion. Circular dichroism spectra of all particles show a typically suppressed ellipticity at 260--280 nm and a prominent alpha-helix signal at 222 nm. All particles show biphasic melting except nu 1 (dA-dT), which show three prominent melting transitions at ionic strength less than or equal to 1 mM. DNAse I digestion of nu 1 (dA-dT) produces a ladder of DNA fragments fiffering in lengthy by one base residue. nu 1 (dA-dT) contain 146 base pairs of DNA and exhibit an average DNA helix pitch of 10.4-10.5 bases per turn. There appear to be two regions of different DNA pitch wihtin nu 1 (dA-dT). It is suggested that the two regions of DNA pitch might correspond to the two regions of the melting profiles.


Conformation of DNA in chromatin protein-DNA complexes studied by infrared spectroscopy. The following observations concerning the DNA secondary structures in various nucleohistone complexes were made by infrared spectroscopy: 1/ in chromatin, chromatin extracted by 0.6 M NaCl, nucleosomes, and histone-DNA reconstituted complexes, the DNA remains in a B type conformation at low relative hygrometry; 2/ in chromatin extracted by tRNA and in non histone protein-DNA reconstituted complexes, the DNA can adopt an A type conformation. Infrared linear dichroism data show that in NHP-DNA complexes the low relative hygrometry conformation of DNA may be modified and that the infrared parameter -1090 is close to that measured for RNA's or DNA-RNA hybrids. It is concluded that the histones block the DNA in a B form and that some of the NHP could be involved in the control of the secondary structure of DNA in chromatin.


Operators and promoters in the OR region of phage 434. The OR operator region of phage 434 contains three 14 bp blocks with sequence ACAAGA-A--TTGT which are presumed to be the 434 repressor recognition sites. Operator constitutive mutations are located in two of these blocks, while a mutation affecting repressor levels in the lysogenic state is located in the third. Two transcripts obtained in vitro, one leftwards and one rightwards, are tentatively identified as the Prm and PR transcription starts. the arrangement of the 434 operator region appears to be very similar to that of the OR of phage lambda.


Salt-dependent interconversion of inner histone oligomers. The inner histone complex, extracted from chicken erythrocyte chromatin in 2 M NaCL AT pH 7.4, has been characterized by sedimentation equilibrium and sedimentation velocity. High speed sedimentation equilibrium studies indicate that in 2 M NaCl the inner histones are a weakly associating system with contributions from species ranging in molecular weight from dimer to octamer. The appearance of a single boundary (3.8S at 2 M NaCl) in sedimentation velocity studies conducted over a wide range of protein concentrations and ionic conditions indicates that the various histone oligomers present are in rapid equilibrium with one another. At higher salts the equilibrium is shifted to favor higher molecular weight species; in 4 M NaCl essentially all of the histone is octameric at protein concentrations above 0.2 mg/ml. The facile interconversion of histone oligomers suggests that small alterations in histone-histone interactions may be responsible for changes in nucleosome conformations during various biological processes.


The effect of aphidicolin on DNA synthesis in isolated HeLa cell nuclei. The effect of the inhibitor aphidicolin on DNA synthesis in isolated nuclei from HeLa cells and on the activities of partially purified DNA polymerases has been tested. Aphidicolin inhibited DNA synthesis and DNA polymerase alpha very efficiently whereas DNA polymerases beta and gamma were insensitive to the drug. The results indicate that DNA polymerase alpha is the polymerase active during elongation as well as in the gapfilling process of discontinuous DNA synthesis.


31P NMR studies of the solution structure and dynamics of nucleosomes and DNA. 31P NMR studies of 140 base pair DNA fragments in nucleosomes and free in solution show no detectable change in the internucleotide 31P chemical shift or linewidth when DNA is packaged into nucleosomes. Measurements of 31P spin-lattice relaxation times T1 and 31P-[H] nuclear Overhauser enhancements revealed internal motion with a correlation time of about 4 x 10(-10) sec in double helical DNA, both free in solution and bound to nucleosomal core proteins. This result implies greater dynamic mobility in double helical DNA than has previously been supposed.


DNA sequence selection by tightly-bound nonhistone chromosomal proteins. Extraction of chicken reticulocyte chromatin with 2.0 M NaCl removed 96% of chromosomal protein and yields two DNA components after dialysis and high-speed centrifugation. The bulk of chromosomal DNA (ca. 99%) is rendered free of protein, and is thus soluble in 10 mM Tris-HCl, pH 8.0. The other component (ca. 1%) displays a high protein/DNA ratio, and is insoluble in 10mM Tris-HCl, pH 8.0. These DNAs can be separated on the basis of their solubilities. Analysis of the reassociation kinetics with total chicken DNA of these DNAs reveals marked differences. Whereas total DNA and the soluble component (DNA-S) have rapidly reassociating components, the insoluble component (DNA-P) is devoid of these components, and is therefore composed completely of unique sequence DNA. Cot 1/2 values indicate that DNA-S is substantially depleted of some DNA-P sequences. We conclude that this segregation, as determined by tightly-bound nonhistone chromosomal proteins, selects a subset of total genomic DNA sequences, and suggests sequence-specific interaction between the tightly-bound nonhistones and DNA.


Differences in the circular dichroism spectra of of eu- and heterochromatin fractions from rat liver. Significant differences are observed between the CD spectra of eu- and heterochromatin prepared by fractionating mechanically sheared rat liver chromatin on linear sucrose density gradients. Heterochromatin has a broad positive CD at 270--280 nm, a cross-over point at 256 nmn, and a negative shoulder at 248 nm. Euchromatin displays a shift in the positive peak to 267 nm and the cross-over point to 254 nm, as well as an intensification of the 267 nm peak. The negative shoulder at 248 nm is absent in euchromatin. These spectral differences between eu- and heterochromatin are present in both low and high ionic strength media. Mechanical shearing does not induce CD alteration and anomalous light scattering is absent in our system. The greater RNA content of euchromatin compared to heterochromatin cannot account for the spectral differences. These results suggest that the DNA conformation of euchromatin is distinct from that of heterochromatin and they may provide clues to the reasons for the greater transcription of euchromatin.


Conformational changes induced in DNA by in vitro reaction with N-hydroxy-N-2-aminofluorene. The conformation of DNA modified in vitro by the covalent binding of N-OH-AF was investigated by ultraviolet absorbance, circular dichroism and by radioimmunoassay using specific antibodies against Guo-AAF and nDNA-AAF. The results obtained by both physico-chemical and immunological methods are in agreement with a model involving destabilized regions in the double helical DNA around the carcinogen molecule in which, however, the -AF residues are stacked to the adjacent nucleotides. The RIA results show that the -AF residues are less accessible to antibodies in native than in denatured DNA-AF and thus suggest -AF residues partially buried in the interior of the DNA helix. The present model is compared to the one existing for DNA modified by reaction with N-AcO-AAF (DNA-AAF) (1,2).


Fluoride ion catalyzed alkylation of purines, pyrimidines, nucleosides and nucleotides using alky halides. Alkyl halides react rapidly with purines and pyrimidines in the presence of fluoride ion. Alkylation of thymidine leads to novel dimeric nucleoside derivatives bridged through N3. Alkylation of thymidine mono and dinucleotides leads to alkylation at the base (N3) as well as diester and triester formation at the phosphate.


Neutron scattering on nuclei.

Neutron scattering on nuclei. Very small angle neutron scattering studies have been made on intact nuclei under a variety of solution conditions. Scattering maxima are observed at 30 to 40 nm and at 18 nm in most environments. Although the spacing, intensity and presence of the maximum near 40 nm varies considerably with environment the 18 nm is rather constant. The 30 to 40 nm maximum appears to be best interpreted by the presence of 35 to 50 nm diameter fibers in nuclei. An important result is that no scattering maximum was observed near 11 nm, suggesting that a tightly super coiled nucleofilament with such a pitch is not present.


Nucleosome cores reconstituted from poly (dA-dT) and the octamer of histones. In this paper we describe a detailed investigation of the reconstitution of nucleosome cores from poly (dA-dT) and the octamer of histones. We also attempted the reconstitution from the copolymers poly dA.poly dT, poly dG.poly dC and poly (dG-dC). The repeat of the reconstituted chromatin fibre is discussed. The micrococcal nuclease released poly (dA-dT) core particle is found to contain a considerably narrower DNA size distribution that of the native random DNA nucleosome core (12). In addition we have succeeded in obtaining small crystals of the poly (dA-dT) nucleosome core. The DNAase I digestion pattern of the poly (dA-dT) containing nucleosome core is presented. The periodicity of DNAase I cutting sites is found to be about 10.5 bases and is similar to that of the native nucleosome core (12, 13).


The effects of salt concentration and H-1 depletion on the digestion of calf thymus chromatin by micrococcal nuclease. We have removed histone H1 specifically from calf thymus nuclei by low pH treatment, and studied the digestion of such nuclei in comparison with undepleted nuclei. By a number of criteria the nuclei do not appear damaged. The DNA repeat-length in nuclear chromatin is found to be the same (192 +/- 4 bp) in the presence or absence of H1. These experiments demonstrate that the core histone complex of H2A, H2B, H3, and H4 can itself protect DNA sequences as long as 168 bp from nuclease. Our interpretation is that this represents an important structural element in chromatin, carrying two full turns of superhelical DNA. Depending on conditions of digestion this 168 bp fragment may be metastable and is normally rapidly converted by exonucleolytic trimming to the well-known "core-particle" containing 145 bp. Larger stable DNA fragments observed indigestion of H-1 depleted nuclei appear to arise from oligomers assembled from 168 bp cores in close contact exhibiting trimming of 0-20 bp at the ends. Electrophorograms of undepleted nuclear digests reveal oligomer bands in several size classes, each corresponding to one or more combinations of 168 bp particles, H1-protected spacers of about 20 bp length, and particles with ends trimmed to varying degrees.


Antibiotic induced electrophoretic mobility shifts of DNA restriction fragments. Several antibiotics, netropsin, distamycin A, actinomycin D, Hoechst 33258 and olivomycin, which demonstrate base specificity in their DNA binding properties have been found to alter the electrophoretic mobility of DNA restriction fragments in native polyacrylamide gels. The antibiotics mostly reduced the migration of larger DNA fragments, but netropsin and Hoechst 33258 were observed to increase the migration rate of several DNA fragments of intermediate size. DNA fragments of similar molecular weight which comigrate as a single gel band can at times be separated as the result of differential mobility shifts promoted by antibiotic DNA complex formations.


The effect of antibiotics on the T4 polynucleotide ligase catalyzed template dependent polymerization of oligodeoxythymidylates. The poly(dA) dependent T4 polynucleotide ligase catalyzed polymerization of oligodeoxythymidylates is dependent upon duplex stability. The antibiotics ethidium bromide, netropsin and Hoechst 33258 stabilize the duplex poly(dA) . P(dT)n (n = 6-10) to thermal denaturation. Ethidium bromide to DNA ratio of 1.25 and netropsin or Hoechst 33258 to DNA ratio of 0.1 the Tm of d(pT) 10 . poly (dA) was increased by 10 degrees and 25 degrees C respectively. The T4 polynucleotide ligase activity was not inhibited under these conditions and temperature optimum of joining of d(pT) 10 . poly(dA) was increased 5 degrees to 10 degrees by the binding of the antibiotics. Duplexes containing shorter oligodeoxythymidylates required lower concentrations of the antibiotics netropsin or Hoechst 33258 to show no inhibition of T4 polynucleotide ligase. The temperature optima of joining the duplexes d(pT)6 . POLY(DA) and d(pT) 8 . poly(dA) were increased by 5 degrees C upon binding of the antibiotics. Polyacrylamide gel analysis of the T4 polynucleotide ligase catalyzed joining of the oligodeoxythymidylates showed that the presence of antibiotics affected the product distribution of the polymerized oligomers.


Properties of in vitro transcription by isolated Xenopus oocyte nucleoli. Some properties of in vitro transcription by isolated Xenopus oocyte nucleoli were described. When incubated with labeled RNA precursors, Xenopus oocyte nucleoli exhibited prolonged incorporation of radioactivity into RNA. The synthetic activity was exclusively due to type I RNA polymerase as revealed by its insensitivity to low and high doses of alpha-amanitin. The size of the in vitro transcript was mostly larger than 28S at 10 minute incubation and became smaller as incubation proceeded. When [gamma-32P]ATP was included in the reaction mixture, 32P radioactivity was incorporated into RNA suggesting the possible initiation of transcription in this system. However, analysis of the terminal nucleotide of the transcript revealed that the incorporation of radioactivity from [gamma-32P]ATP was not due to the initiation of transcription but due to polynucleotide kinase activity in the nucleolar preparation. These results demonstrate that the incorporation of radioactivity from [gamma-32P] labeled nucleoside triphosphates cannot necessarily be regarded as an index of the initiation of transcription.


The expression of a plant genome in hnRNA and mRNA. Representation of genomic kinetic sequence classes and sequence complexities were investigated in nuclear and polysomal RNA of the higher plant Petroselinum sativum (parsley). Two different methods indicated that most if not all polysomal poly(A) -RNA is transcribed from unique sequences. As measured by saturation hybridization in root callus and young leaves 8.7% and 6.2%, respectively, of unique DNA were transcribed in mRNA corresponding to 13.700 and 10.000 average sized genes. Unique nuclear DNA hybridized with an excess of polysomal poly(A)mRNA to the same extent as with total polysomal RNA. 3H-cDNA - poly(A)mRNA hybridization kinetics revealed the presence of two abundance classes with 9.200 and about 30 different mRNAs in leaves and two abundance classes with 10.500 and 960 different mRNAs in callus cells. The existence of plant poly(A)hnRNA was proven both by its fast kinetics of appearance, its length distribution larger than mRNA, and its sequence complexity a few times that of polysomal RNA.


Heteroduplexes of phiX174 and G4 DNAs: orientation to genetic map and comparison with predictions from nucleotide sequences. Heteroduplexes between the viral DNA of phiX174 and DNA from the replicative form (RF) of phage G4 were examined by electron microscopy. The single Eco RI site of G4-RF was utilized as a physical marker by preparing the heteroduplexes from the denatured, linear DNA obtained by restricting G4-RF with Eco RI endonuclease. Restriction fragments of phiX were used in a separate series of heteroduplexes to align the heteroduplex map and the G4 Eco RI site with the similar genetic maps of the two phages. The positions of the branch migrating junctions of recombinant phiX-G4 figure-8s, previously located only with respect to the G4-Eco RI site, have now been located with high proability within the gene A region of the two genomes. The degree of mismatch between the known nucleotide sequences of phi X and G4 accounts for positions of all of the regions of single-strandedness in the observed heteroduplexes, but unexplained discrepancies were also found.


Photochemical cross-linking of secondary structure in HeLa cell heterogeneous nuclear RNA in situ 1. The psoralen derivative 4'-hydroxymethyl-4, 5', 8-trimethylpsoralen (hydroxymethyltrioxsalen) has been used in experiments with isolated HeLa cell nuclei to photochemically cross-link double helical regions in heterogeneous nuclear RNA in situ. Although there are other self-complementary sequences in hnRNA that can form base-paired structures upon phenol deproteinization of annealing, the present in situ cross-linking results demonstrate that some double-stranded regions are an authentic component of native hnRNA structure. Moreover, these special regions of secondary structure are apparently highly accessible to chemical probes within the intact cell nucleus, despite the fact that hnRNA possesses a ribonucleoprotein organization.


Studies on the structure of isolated chromatin in three different solvents. Properties of calf thymus chromatin, prepared by mild procedures, have been studied in various solvents. In 0.2 mM EDTA s-values ranged from 20 to 30 S and intrinsic viscosities from 5 to 24 dl/g. Dialysis against 0.15 M NaCl or 0.2 mM MgCl2 changed these values to 80 to 100 S and 0.2 to 5 dl/g, respectively, indicating an essentially more compact structure. In 0.2 mM EDTA X-ray scattering yielded a cross section diameter of 9 nm, which is associated with the tertiary structure of chromatin fiber (M/L = 21200 Dalton/nm). By dialysis against 0.15 M NaCl or 0.2 mM MgCl2 part of the material spontaneously formed quarterny structures (cross section diameters 25-29 nm). The rest of the material with cross section diameters less than 9 nm is supposed to be more strongly sheared tertiary structure which seems to be unable to form quarterny structure due to artificial conformational changes.


The use of ultraviolet light in the fractionation of chromatin containing unsubstituted and bromodeoxyuridine-substituted DNA. Two procedures are described for the fractionation of chromatin containing unsubstituted (LL) DNA and DNA unifilarly substituted with bromodeoxyuridine (HL). The two procedures rely upon the sensitivity of bromodeoxyuridine-containing DNA to UV light to induce either strand breakage or protein crosslinking. When a mixture of LL and HL chromatin is irradiated with UV light, the HL DNA fragments into molecules of smaller molecular weight than the LL DNA and crosslinks more chromosomal protein than the LL DNA. LL and HL chromatin can be fractionated on the basis of size by centrifuging through a neutral sucrose gradient. The HL DNA-protein adducts that are generated by the UV light have a unique buoyant density and may be isolated by isopycnic centrifugation in CS2SO4. The ability to fractionate LL and HL chromatin permits certain studies on the structure of replicating chromatin.


The pros and cons of estrogen therapy.

The pros and cons of estrogen therapy. Hormone deficiency is the most obvious indication for its use, but estrogen therapy is sometimes beneficial in other conditions. Since rather serious complications are now being associated with such therapy, however, a decision to use estrogen calls for caution in determining the dose and the duration of administration.


Acute abdominal pain in childhood. Finding the cause. The child with acute abdominal pain poses a problem of differential diagnosis. Selection of diagnostic studies and initial management depends on the unique characteristics of history or physical examination that narrow the range of possible underlying causes.


Varicose veins. Their symptoms, complications, and management. Varicose veins are a common problem that still presents a major challenge to the physician and the patient. Complete surgical removal of the malfunctioning veins has proved to be the most effective management for significant varicosities, although several nonsurgical methods are available for mild cases or those not suitable for surgery.


Pseudoleukemia: when "leukemia" is not leukemia. Several case reports6-8 in the literature have pointed out that a clinical and morphologic picture resembling that of acute leukemia may be secondary to infection or use of toxic drugs or alcohol. In these cases, the leukemic picture spontaneously returns to normal when the precipitating factor is no longer present. This condition has been termed pseudoleukemia. Unless the history of a precipitating factor is clear, the patient may be wrongly treated for leukemia. In the case reported here, initial findings suggested acute promyelocytic leukemia and chemotherapy was planned, but further investigation indicated that the condition was essentially reactive and related to a presumed viral infection. Even though pseudoleukemia is sometimes described as a leukemoid reaction, we believe that the term "pseudoleukemia" should be reserved for more specific differentiation.


Verifying the validity of outcome.

Verifying the validity of outcome. The first article in this series, published in May (page 241), dealt with selection bias and described how to tell if it had crept into  a clinical study. This article focuses on the next step in critically evaluating a study: How to assess validity of outcome. Examples illustrate the consequences of failure to fulfill each of the four criteria of valid measurement of outcome.


Genetic causes and workup of male and female infertility. 2. Abnormalities presenting between birth and adult life. At birth some 6/1,000 persons have chromosome abnormalities; in about 60% of cases these abnormalities cause death or infertility, and in one third fertility is reduced. Some 1.7% of persons (3.4% of couples) with recurrent spontaneous abortion, infertility, or both have a chromosome abnormality. Chromosome abnormalities are far more common in men than in women with infertility; 15% to 20% of men with azoospermia have the Klinefelter syndrome. Meiotic defects explain 20% of male infertility in patients with apparently normal somatic chromosomes. Congenital malformations of the genitalia are more common in males than in females; about 0.82% of liveborn males have hypospadias. Almost one sixth of women with primary amenorrhea have some form of müllerian atresia, usually with associated renal anomalies.


Disorders of defecation in children: evaluation and management. In a series of 123 children with disorders of defecation, constipation was the main problem in 89 and fecal incontinence in 34. All but three of the latter also had constipation. The principal physical findings were abdominal protuberance with palpable stool in the bowel and the presence of a fecal mass in the rectal ampulla. Laboratory and radiologic findings were nonspecific except in two of the three patients found to have congenital megacolon (Hirschsprung's disease). Rectal suction biopsy, performed in 69 patients, was diagnostic in all three with Hirschsprung's disease. Anorectal manometry, done in 11 patients, was of limited value. In general, treatment consists of patience and understanding on the part of physician and family, a regimen of orally administered (noncathartic) laxatives with dose gradually reduced over weeks to months, frequent telephone communication between physician and parents, and occasional office visits. Patients with nonretentive fecal incontinence require an intensive psychologic approach. A patient, empathetic, and available physician is one of the most important ingredients in the treatment regimen.


Primary care of the injured hand, part 1. Because the hand is the most frequently injured part of the body, primary recognition of injured structures, careful assessment of damage, and appropriate treatment or referral by the primary care physician are critical. Most fingertip injuries heal with conservative care. Ideally, the healed wound should be covered with well-padded skin, be free of scar tissue, and not adhere to underlying bone. Crushing fingertip injuries associated with underlying fractures are often overlooked initially, with resultant infection, nonunion, and nail deformity. In the evaluation of flexor tendon injuries, recognition of the location of severed tendon is critical. Improved surgical techniques, when performed by an experienced hand surgeon, have yielded gratifying results, especially in the primary repair of tendon severance in the distal portion of the digit and palm. Mallet deformities at the distal interphalangeal joint are treated with extension splinting for minimum of six weeks without immobilization of the proximal interphalangeal joint. Open reduction is often required when an associated fracture involves more than 30% of the articular surface.


Primary care of the injured hand, part 2. Nerve injuries in the forearm and hand are common, especially with concomitant tendon lacerations. The optimal time for repair of a clean sharp laceration is within the first 24 to 48 hours using magnification to achieve precise surgical reapproximation. Transfer to a facility equipped to perform replantation is indicated for multiple digit amputations, any thumb amputation, transmetacarpal amputation, wrist and arm amputation, and major amputations in children. Acute paronychial infections are treated with warm soaks, antibiotics, elevation, and immobilization. Surgical drainage is often indicated for a felon and should be done through a high midaxial incision. fractures of the hand are extremely common and require accurate diagnosis and precise anatomic reduction. Ensheathment syndromes--carpal tunnel syndrome, trigger finger, de Quervain's disease--are the most common nontraumatic disorders of the hand. If recognized and treated early they may resolve without need for surgery.


Psychogenic fever: entity or nonentity?

Psychogenic fever: entity or nonentity? A review of the literature suggests that body temperature may rise when a person is under emotional stress. The term "psychogenic fever" has been applied to this phenomenon. A study of temperature and pulse rate of psychiatric patients diagnosed predominantly as neurotic in a university teaching hospital was undertaken. Changes in pulse rate indicated that the period before ward rounds was more stressful than other times of the day. However, psychogenic fever in these patients was not found. One case of factitious fever was uncovered during the study.


Autoimmune hemolytic anemia. 1. Warm antibody type. Diagnosis of the idiopathic warm antibody type of autoimmune hemolytic anemia requires evidence for hemolysis and autoimmunity against RBC's ie, a positive direct antihuman globulin test. In addition, underlying disease states and drug therapy must be excluded as causative factors. Therapeutic measures are aimed at suppression of autoantibody production and include steroids (usually prednisone in tapering dosage), splenectomy, and less commonly, immunosuppressive agents.


Contributory cause: unnecessary and insufficient. Contributory cause is a clinically useful concept of causation. It requires demonstration that (1) the presumed cause precedes the effect and (2) altering the cause alters the effect. It does not require that all those who possess the contributory cause experience the effect. It does not require that all those who are free of the contributory cause be free of the effect. In other words, a clinical cause may be neither necessary or sufficient but it must be contributory.


Myasthenia gravis: pathogenesis, diagnosis, and therapy. Myasthenia gravis most commonly affects the ocular muscles. Abnormal fatigability of the involved muscle groups is the most remarkable feature of the physical examination. Recent studies have demonstrated that a thymus-derived antibody plays a role in the pathogenesis of myasthenia gravis, which is now thought to be an autoimmune disorder. Its association with other autoimmune disorders has been recognized for some time. A high index of suspicion is the most essential element in diagnosis. Rapid and reproducible response to administration of anticholinesterase leaves little doubt of the diagnosis, but characteristic EMG findings in myasthenic muscle evoked by repetitive stimulation of peripheral motor nerve are definitive. Anticholinesterase drugs are the mainstay of therapy. Thymectomy is indicated in patients with thymoma and in some young persons with serious disease. Patients who respond poorly to anticholinesterase therapy or surgery are candidates for steroid therapy.


Cluster headache: relation to and comparison with migraine. Numerous factors, such as location of pain, sex, frequency and pattern of occurrence, and symptoms, distinguish cluster headache from migraine. Cluster headache is characterized by severe unilateral periorbital pain. Attacks lasting from several minutes to several hours occur many times a day over a period of weeks to months. Opinions differ as to whether cluster headache is a variant of migraine or a completely different disorder. For relatively mild attacks, abortive treatment with ergotamine tartrate is usually successful. Cases which do not respond to abortive measures require prophylaxis.


[Indications and value of chest radiography in patients with respiratory insufficiency (author's transl)]. Chest X-rays of patients with respiratory insufficiency provide different information depending on the stage of the disease. The indications for chest radiography should, therefore, be determined by whether the examination is intended to establish the diagnosis and causes of the respiratory disease, to arrive at the differential diagnosis or test the efficacy of treatment.


[Interpretation of chest roentgenograms of intensive care patients. A comparison of pathoanatomical and roentgenographic findings (author's transl)]. Chest roentgenograms made within 24 hours of death were compared to the autopsy findings. Out of 150 unselected autopsy records of the years 1973/74 and 1976/77 50 and 91 cases respectively were suitable for evaluation. Since 1973/74 the radiographic technique has been considerably changed by the introduction of powerful condenser discharge equipment and the use of highly intensifying screens. Daily discussions with the physicians in charge of the intensive care unit and routine comparison of the pathological and radiological findings were also introduced. The success of these measures is reflected in the greater diagnostic accuracy in respect of the case material for the 1976/77 period. Comparison of the findings in cases of pulmonary embolism exposed the limitation of diagnostic radiology.


[Classification of x-ray findings and correlated oxygen tensions in "shock lung" (author's transl)]. The classification of the radiological features of the "shock lung" into stages represents a description of the characteristic radiological changes as they develop in the course of the lesion. As these changes do not succeed each other step by step but are superimposed their attribution to a particular stage therefore describes only the dominant substrate. Since the radiological changes and the corresponding oxygen tensions generally show satisfactory correlation a lack of correspondence during treatment may be an early sign of secondary disturbances or complications.


[The chest roentgenogram during artificial respiration (author's transl)]. Chest roentgenography of artificially ventilated persons not only reveals morphological changes in the lungs but may also provide information regarding their pathogenesis and prognosis. To safeguard against misinterpretation of the findings they should be supplemented by blood gas analyses and function tests (e.g. effective compliance of the respiratory system). The chest roentgenogram also apprises of the development, and consequently of the need for treatment, of such complications as interstital emphysema, pneumothorax, pneumomediastinum, pneumoperitoneum and subcutaneous emphysema.


[Chest radiography for the detection of accidents during intensive care procedures (author's transl)]. One of the indications for chest radiography in intensive care units is the diagnosis for mishaps or sequelae arising, e.g., from failure to insert a central venous catheter, wrong position of the catheter, a too deeply inserted tracheal tube, a wrongly sited gastric catheter; also to find the causes of, e.g., lack of stimulation by a pacemaker or ineffective thorax drainage. Success in this type of diagnostic radiography presupposes a competent technique, radiopaque catheter material and a thorough acquaintance on the part of the radiologist with the procedures employed in intensive care. Abb. 7 a.


[Misinterpretation of chest roentgenogram in intensive care patients (author's transl)]. Misinterpretation of chest roentgenograms in intensive care patients can be largely obviated by a skilled technique and a thorough knowledge on the part of the radiologist of the structural changes in the lungs and their differential diagnostic significance. Correct interpretation is facilitated by relating the observed changes to the pathophysiological clinical findings.


[Radiological changes of the lungs induced by inhalation of irritating gases (author's transl)]. The radiological changes and clinical symptoms induced by in 109 persons by inhalation of irritant gases are described. Seven persons developed pulmonary oedema, abnormal radiological manifestations were observed in 19 while 81 persons there were no detectable radiological changes. Toxic pulmonary oedema is frequently detected earlier by roentgenologic means than clinically. The length of the radiological latent period depends not only on the concentration of the irritant but also on the type of the gaseous substance. The first roentgenologic signs of toxic pulmonary oedema are broadening and blurring of the outline of the hilar vessels. The pulmonary changes are characterized initially by disseminated small to medium sized shadows in the central portion and base of the lungs; later they tend to spread and merge.


[Pneumoperitoneum induced by artificial respiration and its diagnosis by peritonel lavage (author's transl)]. Ventilation with increased end-exspiratory pressure may, especially in cases of blunt chest trauma, result in pneumoperitoneum although there are no intestinal injuries. The case histories of four persons who developed this complication are reviewed. Differentiation between such a complication and a condition requiring laparotomy is often difficult because other injuries, particularly a cerebrocranial trauma, may obscure the clinical symptoms. Diagnostic peritoneal lavage may help towards differentiating between a ventilation-induced pneumoperitoneum and an "acute abdomen" caused by perforation or rupture of an intra-abdominal hallow organ.


[A new apparatus for the continuous measurement of the concentration of anaesthetic vapours (author's transl)]. A new apparatus is described for the continuous on-line estimation of the concentration of anaesthetic vapours. The results obtained with the apparatus for halothane were compared with those registered by a mass spectrometer; there was excellent agreement (r = 0.999). The equipment is very manageable and has already proved its value is anaesthetic practice.


[X-ray equipment for standardized diagnostic radiology in intensive care units (author's transl)]. The increasing demands made by intensive care medicine on chest and abdominal radiography and on angiography have created the need for new X-ray equipment that combines short exposure with high tension. Battery-operated medium-frequency generators have an adequate output to satisfy these demands. For visualizing peripheral vessels in intensive care patients xeroradiographic arteriography has proved its value.


The effects and interactions of scopolamine, physostigmine and methamphetamine on human memory. Seventy college age subjects learned and recalled a series of word lists prior to being injected with methamphetamine (0.2 mg/kg or 0.3 mg/kg), scopolamine (8 microgram/kg), or a placebo. Following the injection subjects were tested for their free recall and recognition of the words and they completed a short-term digit recall task. Subjects who had previously received scopolamine were next injected with either methamphetamine (0.2 mg/kg or 0.3 mg/kg), physostigmine (32 microgram/kg), or placebo, while other subjects received a placebo injection. The above memory procedure was then repeated with a second series of word lists. In addition, subjective feelings were measured with a questionnaire. Scopolamine and methamphetamine did not affect recall of information learned prior to injection. Scopolamine did, however, impair performance in both the digit recall task and in the second series of memory tests. Physostigmine and methamphetamine alleviated most of the memory deficits and sedation produced by scopolamine. Methamphetamine alone produced subjective arousal and a small improvement in recall of words learned after injection and a large increase in incorrect responding.


Increasing the rate of ethanol consumption in food- and water-satiated rats. The effects of food satiation, ethanol concentration, and the schedule of ethanol availability on the rate of ethanol consumption were investigated in rats. In Experiment 1 separate groups were exposed to 6.2 or 12.5% w/v ethanol and unlimited access to food. The food and ethanol were available concurrently for one to three hours daily. After approximately 15 sessions unlimited food was available whenever ethanol was not available. The rate of ethanol consumption was positively related to ethanol concentration and negatively related to duration of ethanol availability. In Experiment 2 similar procedures were followed, except rats had unlimited access to food throughout the experiment. The results were similar to Experiment 1. In Experiment 3 separate groups were exposed to 6.2 and 12.5% w/v ethanol for one hour every other day; unlimited food was available throughout the experiment. The results were similar to the one-hour availability groups in Experiments 1 and 2. In all experiments ethanol consumption rates increased to levels above baseline and above the usual ethanol metabolic rate found in rats. The results demonstrated new combinations of ethanol availability and non-availability durations that were sufficient to significantly increase the rate of ethanol consumption.


Effects of diazepam and ethanol alone and in combination on conditioned suppression of key-pecking in the pigeon. Pigeons were intermittently given grain reinforcement for key pecks. Occasional 30-sec keylight changes (warning stimulus) were followed by a brief electric shock, which suppressed responding during the warning stimuli. This suppression was reduced by diazepam and ethanol, yet combinations of the two drugs did not reduce suppression (antagonistic effect). Each drug reduced responding in the absence of the warning stimulus, and combinations of the drug produced still greater reductions in this safe-period responding (synergistic effect).


Interaction of food deprivation with different measures of amphetamine effects. The effects of d-amphetamine (0.0, 0.5, 1.0 mg/kg) on feeding, activity, and food-dish contact time of male Holtzman rats were investigated under 4 different levels of food deprivation (0, 12, 24, 36 hr). Differences in the amount of food deprivation significantly influenced the drug's effect on feeding and food-dish contact time, but not on activity. Also, differences in the amount of food deprivation significantly influenced the interrelationship (correlation) of amphetamine's effects on activity and food-dish contact time and on food-dish contact time and feeding, but not so much the interrelationship of the drug's effects on feeding and activity. These findings suggest that the amount of food deprivation differentially influences different general measures fo amphetamine effects as well as differentially affecting the interrelationship of amphetamine effects. The importance of the correlation data to the potential incompatibility of the drug's effects as well as to an interpretation of food-dish contact time is briefly considered.


Prenatal effects of alcohol on adult learning in rats. In an initial study, the rate of blood alcohol disappearance was not significantly different in pregnant compared to nonpregnant rats, but blood alcohol levels were significantly different depending on dose. In a second study, pregnant rats received daily administrations (p.o.) of ethanol (30% w/v) in single doses throughout gestation. Pair-fed vehicle-treated, and nondrug-treated rats fed ad lib served as controls. All pups were removed from their biological mothers at birth and were raised by nondrug-treated surrogate mothers. At five months of age, both male and female offspring prenatally exposed to ethanol weighed less than controls and female offspring performed significantly worse than the offspring of vehicle-injected pair-fed control mothers, on a two-way shock-avoidance task. There were no significant group differences, however, for either sex in water-escape maze learning.


Biochemical effects of cycloheximide in developing chick brain. The timecourses of inhibition of protein synthesis in forebrain roof 15 min to 24 hr after either intracerebral or peripheral injection of 40 microgram of cycloheximide (CXM), show maximum inhibition (68--85%) 1 hr after injection in 12 hr, 2-day- and 16-day-old chicks. In 2-day-old chicks, the level of free lysine was elevated by around 250% 1 hr after intracerebral injection of CXM. The total radioactivity in the forebrain roof/mg protein following peripheral injection of labelled lysine increased by around 80% compared to saline controls. Following unilateral injection of 20 microgram in 25 microliter CXM into a forebrain hemisphere, the inhibition of protein synthesis spread to the opposite forebrain hemisphere and both optic lobes within 5 min. Smaller volumes did not seem to give a clear unilateral inhibition capable of explaining the unilateral behavioural differences which have been reported. Central injection of CXM in 2- and 16-day-old chicks, resulted in an inhibition of liver protein synthesis of 55% and 40%, respectively. There were also gross signs of pathological effects in the liver and gall bladder. The implications of these effects of CXM are discussed in terms of the use of the drug in behavioural experiments.


Aversive properties of cycloheximide versus memory inhibition in chickens' formation of visually cued food aversions. No memory inhibition for a conditioned aversion in chickens, produced by pairing a novel colored food and lithium chloride (LiCl), was found when cycloheximide (CXM) was injected intracerebrally (IC) two or six hr before feeding. Good conditioned aversions were found when CXM alone was injected IC following consumption of the novel food. No aversions were found when CXM alone was injected IC two hr before feeding. Possible reasons for apparent memory inhibition using CXM in some appetitive paradigms are discussed.


Response perseveration in rats exposed to alcohol prenatally. Pregnant female rats consumed liquid diets containing either 35, 17, or 0% of the total calories as ethanol. Offspring of these females were tested for spontaneous alternation at 21 days of age and for reversal learning in a T-maze shock-escape paradigm at 20--21 days of age. In the spontaneous alternation test, rats exposed to alcohol prenatally took more trials than controls to enter the goal compartment opposite to that initially entered. In the T-maze escape study, alcohol-exposed offspring made more mistakes prior to criteron and more mistakes per trial than controls when the previously incorrect goal was made safe during reversal learning. In both studies linear dose-response functions were found. Furthermore, there was a significant tendency for the within-group variabitliy to increase as the level of prenatal exposure increased, perhaps indicating that the incidence as well as the severity of behavioral dysfunction was dose dependent. The results are interpreted in terms of a delay in the development of a central inhibitory system.


The effects of acetylmethadol on motor activity and schedule-controlled responding. The effects of levo-alpha-acetylmethadol (LAAM) on locomotor activity and operant behavior were examined in rats. LAAM increased locomotor activity when given intraperitoneally (IP) at doses of 1 mg/kg and 3 mg/kg, but 10 mg/kg produced a slight decrease in motor activity over the 10-hour period. The largest increases and decreases in locomotor activity occurred 6--8 hours after administration of the drug. Other rats were trained to lever press for food pellets under a fixed-interval 90-second, fixed-ratio 10-response multiple schedule. LAAM only decreased rates of responding under the multiple schedule. Marked decreases in rates of responding under both components of the schedule occurred with LAAM was administered IP either 3 or 6 hours before the session at doses of 3 mg/kg and 10 mg/kg. The rate- decreasing effects of LAAM became greater the longer the interval between administration of the drug and initiation of the session.


Generalization of norcocaine to the discriminative stimulus properties of cocaine. In rats trained to discriminate 10 mg/kg cocaine from 1 mg/kg saline, norcocaine, the N-demethylated metabolite, at doses of 2.5 mg/kg, 5 mg/kg and 10 mg/kg, produced a dose response curve similar to that of cocaine and generalized to cocaine at the two higher doses. As with cocaine, the discriminative stimulus produced by the norcocaine was partially attenuated by the dopaminergic antagonist pimozide and the amine depletor reserpine. Benzoylecgonine, benzoylnorecgonine and ecgonine methyl ester in doses of 10 mg/kg and 20 mg/kg did not generalize to cocaine.


Effect of addition of ethanol and NaCl on saccharin + glucose polydipsia. Rats received an ad lib choice of food, water, and a solution containing saccharin, glucose, and NaCl solutes either as single stimuli or in combinations. Ethanol was gradually added to these vehicles or water from 0.5--15% w/v. Ethanol intakes of all groups with vehicles containing glucose were higher than intakes of the water vehicle group. Ethanol intakes of the 0.125% saccharin + 3.0% glucose + 1.0% NaCl + ethanol group were highest, peaking at greater than 9.0 g/kg/day, and this group displayed the highest blood ethanol levels. However, there was no evidence of withdrawal syndrome, nor of increased intake of unflavored ethanol by groups previously receiving flavored ethanol. It is suggested that ethanol eliminative capacity limits free-choice ethanol intake when maximized by the addition of sapid congeners.


The effect of sulfinpyrazone on morphological changes in the coronary vasculature induced by prolonged unpredictable stress in the rat. It was confirmed that prolonged unpredictable stress in the rat induces morphological change in the coronary microcirculation. These changes include dilation in venules, deposits staining positive with PAS in the venules due to platelet aggregation and a breakdown of the endothelial lining in arterioles. Sulfinpyrazone is reported to prevent platelet agglutination, and shows effectiveness in the clinic in preventing re-infarction following infarction. Accordingly rats were exposed to the stress regimen for 50 days, and groups were treated with sulfinpyrazone, either prophylactically (receive drug for 50 days) or therapeutically (receive drug Day 30 to Day 50). The morphology of the hearts of treated animals were compared with those of placebo treated controls. It was demonstrated that therapeutic sulfinpyrazone did not prevent (p less than 0.01), but reduced the incidence of morphological change in the coronary microcirculation. Prophylactic sulfinpyrazone had a distinct protective effect (p less than 0.001). It was demonstrated that the plasma corticosterone levels in both drug groups did not fall to the level found in control groups. The results are discussed in terms of a glucocorticoid-sulfinpyrazone interaction preventing prostaglandin release which will prevent platelet aggregation. It is possible that the interaction relates to maintaining the integrity of the microcirculatory endothelial cells, thus preventing the local release of inflammatory substances.


Mescaline increases startle responding equally in normal and raphe-lesioned rats. To test the possible involvement of serotonin-containing cells of the midbrain in mediating the effects of mescaline on startle responding, electrolytic lesions were made in either the dorsal or median raphe nucleus in rats. Decreases in either striatal or hippocampal tryptophan hydroxylase activity confirmed the effectiveness of the lesions. One week later, startle was measured in response to 30 air-puff stimuli for each rat. Median, but not dorsal, raphe lesions increased startle magnitudes throughout the test session. The following day each group was divided into matched halves and were given 60 trials, 30 minutes after intraperitoneal injection of either saline or 10 mg/kg mescaline. Despite the large differences in baseline startle among the groups, mescaline produced comparable 25% increases in startle magnitudes in both sham- and raphe-lesioned animals. This result fails to support the hypothesis that increased startle responding produced by mescaline is mediated by the midbrain raphe nuclei.


Effects of methylphenidate on schedule dependent and schedule induced behavior. The effects of methylphenidate, 1.5, 3.0, 6.0 and 12.0 mg/kg, on lever pressing, schedule induced licking, and drinking were studied. The generator schedule was a fixed interval 1 min food reinforcement schedule. The effects were assessed when animals were reduced to 80% body weight by partial food deprivation and when allowed to recover body weight under conditions of ad lib eating. Results indicate that under body weight conditions methylphenidate significantly decreases schedule induced licking and drinking but does not affect lever pressing.


Relationship between facial flushing and blood acetaldehyde levels after alcohol intake. Normal subjects were divided into two groups, i.e., those showing, and those not showing, facial flushing after consuming a small amount of alcohol. In the flushing group, increases of pulse rate, facial skin temperature and carotid arterial pressure and blood flow rate, as well as changes of digital plethysmogram and electrocardiogram, were found together with a conspicuous rise in blood acetaldehyde levels after the drinking. However, significant changes of the signs as mentioned above and elevation of blood acetaldehyde did not occur in the non-flushing group. The maximum blood alcohol levels and the rate of alcohol elimination showed not difference between these two groups. Furthermore, urinary excretions of epinephrine and norepinephrine increased in the flushing cases after the drinking.


Effect on core temperature of restraint after peripherally and centrally injected morphine in the Sprague-Dawley rat. The changes in core temperature (Tc) evoked by morphine in the Sprague-Dawley rate were altered by restraining the rat. The Tc of the free-moving rat rose after the IP (5, 15, 30, 60 mg/kg) or intracerebral injections (10, 20, 50 micrograms) of morphine. In the restrained rate, however, identical doses of morphine evoked either a hyperthermia of lesser magnitude than in the free-moving rat or a drop in Tc. These findings reemphasize the importance of restraint in determinating the action of morphine on Tc and extend the finding to the Sprague-Dawley rat.


6-Hydroxydopamine reduces preference for conspecific but not other familiar odors in rat pups. Rat pups injected subcutaneously with 6-hydroxydopamine (6-OHDA) showed reduced preference for a familiar combination of conspecific and botanical odors when subsequently tested in a two-choice situation. However, drug treatment did not influence preference for the simple botanical odor. 6-OHDA also reduced norepinephrine (NE) concentrations in the forebrain and the olfactory bulbs. The data implicate NE in the ontogeny of the acquired responses to conspecific odors.


Effects of alcohol and caffeine on wheel running activity in the Mongolian gerbil. This study investigated the effects of various doses of alcohol (0.8, 1.6, 2.4 g/kg) and caffeine (5, 10, 15, 20 mg/kg) on wheel running activity in 180 male and female adult Mongolian gerbils. Animals were tested for two 10-min trials 48 hours apart. Thirty min prior to Trial 2, injections were administered intraperitoneally. The results indicate that low doses of both alcohol and caffeine increase and higher doses of alcohol decrease wheel running activity in gerbils of both sexes. These results agree with other findings on activity in other animals, and serve as a baseline for future drug research in the gerbil.