Comparison of the effects of atenolol and propranolol in labile hypertension. The effects of a single daily dose of 100 mg. of atenolol and an equivalent dose of propranolol were compared during a crossover, 15 day blind trial in a group of young labile hypertensives. Arterial pressure, heart rate, systolic time intervals and the carotid pulse upstroke time, recorded by external non-invasive procedures, were measured before and 4 and 8 hours after the last dose of both drugs. Both beta blocking agents significantly reduced and stabilized the arterial BP and the heart rate to normal values. However, a tendency to return to abnormal values was observed 8 hours after propranolol administration. Both drugs provoked an increase in the pre-ejection period, but with propranolol this increase was related to a larger isovolumetric contraction time, pointing to a negative inotropic action. The carotid pulse upstroke time was increased to normal values with atenolol. Propranolol failed to alter this value. Atenolol in a single oral daily dose is recommended in the treatment of labile hypertension.


Stimulation of reparative processes in the damaged myocardium by the RNA preparations. RNA preparations were used as stimulants of reparative processes in rat myocardium damaged by diathermocoagulation. Administration of RNA accelerated the proteosynthesis in the zone of the lesion, as indicated by the intensity of incorporation of 14C-labelled amino-acids. Morphological examinations of the myocardium revealed increased synthetic activity in fibroblasts, proliferation of fibroblasts, and accelerated scar healing. The results prove the stimulating effect of RNA preparations on reparative processes in the damaged myocardium.


The effect of propranolol on myocardial oxidative processes. The effect of single i. v. dosis of propranolol, 1.5 mg/kg of body weight, on the oxidative processes in rabbit myocardium at the mitochondrial level was investigated. Analyses were carried out at minutes 0 and 15 after intravenous infusion of propranolol. Under the influence of propranolol the mitochondrial oxygen uptake was reduced. This finding reveals the metabolic background of the antianginal effect of propranolol. Simultaneously, however, the mitochondrial metabolic efficiency was negatively affected, as manifested by decreases in mitochondrial respiration control, oxidative phosphorylation, and phosphorylation rate. The described changes signalize a disturbance in myocardial energy production and represent a subcellular metabolic background of potential myocardial damage during administration of propranolol.


A time to live, a time to grieve: patterns and processes of mourning among the Yolngu of Australia. Anthropological studies of mortuary ceremonies have focused primarily on their social and structural correlates and functions. Little attention has been given to their role in facilitating the expression and resolution of grief by the bereaved. The elaborate and extended mortuary rites of the people of northeastern Arnhem Land, Australia (the "Murngin") have several characteristics which promote and structure the mourning process and facilitate the full reintegration of the bereaved into the social life of the community.


Espanto: a dialogue with the gods.

Espanto: a dialogue with the gods. Espanto or susto has been analysed from various points of view in the last fifteen years. From a survey covering 109 case analyses collected in Nicolas Ruiz (Chiapas, Mexico), we reached the conclusion that this folk illness cannot be conceived of as a syndrome in the medical sense. A semiological analysis showed that espanto can be better described as an indigenous theory whose function is to relate illness events to other levels of reality. According to indigenous belief, the Holy Earth and the chtonian spirits of the underworld play an important role in the origin of the illness. This origin is associated with an opening of the earth as is illustrated in the earthquakes or the volcanic eruptions forming the prototype of a fright experience leading to espanto; or, it is attributed to agents who inhabit locations where the earth presents a fissure (river, ravine, cave). It is through these holes that the Holy Earth exerts her power. Concomitantly, the body of the victim is believed to open itself to the influences of the bad winds of espanto. Trembling is another aspect of the phenomenon which is observed at numerous levels: first, during the fright experience; second, when the victim falls ill (chills jumping in bed); and third, when the curandera takes the pulse of the patient to see if the blood is afraid. These multiple analogies lead to the assumption that there is a meaning shared by these separate manifestations.


Demonic explanations of disease among Moroccan Jews in Israel. Demonic explanations of disease preserved among Moroccan Jews living in two Israeli moshavim are described and amalyzed. Applied most often to sira, a traditional ailment involving somatic and anxiety symptoms, these explanations are construed as a two-level ordered sequence of steps including elements from both ordinary reality and the demonic world. Traditional patients are usually more aware of the manifest chain of precipitating events centering around emotional consequences of a real trauma. Their rabbi-healers, however, are predisposed towards molding these events into a covert-demonic pattern, the core of which involves a human injuring a jinn and the latter's retaliation. In the explanatory scheme the real-traumatic and the demonic plots are intermingled and this fusion lends the etiological sequence a meaningful rationale as exemplified by two case illustrations. Nevertheless, our analysis renders the demonic substratum quite vulnerable, since the manifest-traumatic plot may be singled out as an autonomous explanation under the impact of the mainstream of modern Israeli society. Reasons for the hitherto tenacious preservation of the demonic component among traditional segments in Israel are presented by comparing the explanatory status of demons and psychoanalytic concepts. Certain vulnerabilities of the denomic explanation which throw doubt upon its long-term survival in modern context are discussed as well.


Definitions and diagnoses: cultural implications of psychiatric help-seeking and psychiatrists' definitions of the situation in psychiatric emergencies. This paper explores lay and psychiatric actors' definitions of mental illness by focusing on several aspects of emergency psychiatric diagnosis. First, it considers psychiatric diagnosis as a social and cultural process in which mental illnesses are defined with increasing specificity as individuals move from lay to psychiatric contexts. Second, the paper considers variation in psychiatric residents'  conceptions of mental illness, their role in emergency contexts, and lastly, their diagnostic styles. Diagnostic styles are shown to exist and to be grounded in residents' definitions of the situation. It is suggested that the variation in psychiatrists' definitions of the psychiatric situation, especially as regards etiology, plays a prominent, but as yet unnoted, role in producing variability in psychiatric diagnosis. It is also argued that actors' definitions are cultural, grounded in non-professional lay ideology, and are not products of secondary professional socialization.


Facial patterning and infant emotional expression: happiness, surprise, and fear. Although recent studies have convincingly demonstrated that emotional expressions can be judged reliably from actor-posed facial displays, there exists little evidence that facial expressions in lifelike settings are similar to actor-posed displays, are reliable across situations designed to elicit the same emotion, or provide sufficient information to mediate consistent emotion judgments by raters. The present study therefore investigated these issues as they related to the emotions of happiness, surprise, and fear. 27 infants between 10 and 12 months of age (when emotion masking is not likely to confound results) were tested in 2 situations designed to elicit hapiness (peek-a-boo game and a collapsing toy), 2 to elicit surprise (a toy-switch and a vanishing-object task), and 2 to elicit fear (the visual cliff and the approach of a stranger. Dependent variables included changes in 28 facial response components taken from previous work using actor poses, as well as judgments of the presence of 6 discrete emotions. In addition, instrumental behaviors were used to verify with other than facial expression responses whether the predicted emotion was elicited. In contrast to previous conclusions on the subject, we found that judges were able to make all facial expression judgments reliably, even in the absence of contextual information. Support was also obtained for at least some degree of specificity of facial component response patterns, especially for happiness and surprise. Emotion judgments by raters were found to be a function of the presence of discrete facial components predicted to be linked to those emotions. Finally, almost all situations elicited blends, rather than discrete emotions.


Reflection-impulsivity and the evaluation process. The relationship between reflection-impulsivity, hypothese generation and testing, and evaluation of the quality of one's own solutions was explored in the framework of Kagan's theory. The Matching Familiar Figures test (MFF) and a pattern-matching task were administered to 94 children from 8-0 to 11-11 years. Multiple regression analyses and analyses of variance showed that children who were inaccurate on the MFF were more likely to offer a solution on the pattern-matching task before they had sufficient information to guarantee a correct solution and to make errors despite sufficient information to have avoided those errors. Thus reflection-impulsivity as measured by the MFF were related to 2 other measures of the evaluation process on another visual match-to-sample task. Only 1 of 3 hypothesis-testing variables was significantly related to MFF performance, and that relationship was rather small.


Selective attention deficits in poor readers? Dichotic listening, speeded classification, and auditory and visual central and incidental learning tasks. Poor readers (PRs) and controls (i.e., normal readers) from the second, fourth, and sixth grades were compared on four tasks chosen to measure the development of selective attention. The PRs performed more poorly than controls on the central but not on the incidental portion of an auditory memory task. The differences on the central task were interpreted as a function of group differences in mnemonic skills rather than selective attention. There were no group differences on either central or incidental portions of a visual memory task. In a speeded classification task, PRs exhibited a slower rate of information processing, measured in bits of information transmitted per second, than controls, but this difference in rate was not affected by distraction. On a dichotic listening task, PRs performed more poorly than controls under a variety of conditions in which the presence of distraction, the rate of information presentation, and attended ear were manipulated; the pattern of differences obtained, however, was not readily interpretable as a function of greater distractibility on the part of PRs than controls. As a whole, the results did not support the hypothesis that PRs show deficits in selective attention relative to age-matched normal readers. In addition, correlations computed among indices of selectivity (residualized gain scores) derived from the four tasks were uniformly low, suggesting that the four tasks did not measure the same cognitive construct. The implications for the study of reading disabilities and for the construct of selective attention in developmental studies are discussed.


Developmental issues in cognitive mapping: the selection and utilization of environmental landmarks. 2 studies were conducted to investigate developmental differences in the ability to select and use environmental landmarks for cognitively organizing distance information from a walk. In experiment 1, second-grade, fifth-grade, and college subjects viewed a simulated walk and selected scenes that were high in potential landmark value. In experiment 2, children from the same grade levels first viewed the walk and then ranked distances among either the test scenes most frequently selected by their peers or those selected most frequently by adults. Results indicated that (a) adults and children may not spontaneously select the same features as real-world landmarks; (b) children are less capable than adults in judging the value of potential landmarks as distance cues; and (c) the ability to use environmental landmarks as cues for distance information developmentally precedes the ability to assess this potential information value.


Children's internal organization of locative categories. 4 locative categories were investigated to determine whether their examples were organized according to the prototype/nonprototype distinction. A ranking task was presented to 30 adult subjects to see whether they would judge those instances which had been designated as prototypes by the experimenter to be the best exemplars of each category. An elicited-drawing task was administered to see whether there was a preference for drawing adult-designated prototypical instances. A matching task was presented to determine whether fewer errors would occur in response to adult-designated prototypical instances. The latter 2 tasks were presented to 4-year-olds, 6-year-olds, and adults, with 17 subjects in each group. The results provide strong evidence of prototype/nonprototype organization in 3 of the locative categories and weak evidence in the fourth. Tentative conclusions regarding the development of such organization are drawn.


Children's memory for orientation in the absence of external cues. Some have interpreted children's reliance on external visual cues as evidence that they are unable to use internal cues for orientation. This hypothesis was examined in experiment 1, where 24 preschoolers were tested on left-right, vertical-horizontal, and mirror-image oblique discriminations under essentially context-free conditions. Subjects succeeded on all discrimination problems and performed equally well on vertical-horizontal and mirror-image oblique discriminations. Thus, preschoolers can use an internal frame of reference to code orientation. Experiment 2 contrasted children's performance under context-free conditions with their ability to discriminate orientation in the presence of external visual cues. Children who had discriminated left-right oblique and nonoblique mirror-image forms in experiment 1 failed to so discriminate in experiment 2. This result is discussed in terms of a breakdown in the ability to use internal cues when external visual cues are available.


The effects of introtacts on hypothesis testing in kindergarten and first-grade children. Kindergarten and first-grade children were trained against their initial dimensional preference in a 2-dimensional simultaneous discrimination learning task. One third of the children received pretraining in using a sequential hypothesis-testing strategy, one third received pretraining in which they experienced solutions to tasks of the same type, and one third received no pretraining. Half of the children received introtact probes prior to each trial in the criterion task. Introtact probes had no effect on the performance of kindergarten children but facilitated the performance of first-grade children who received pretraining. Performance was generally better in the pretraining conditions than in the control condition and was generally better for first graders than for kindergarten children. Indices of the use of the sequential hypothesis-testing strategy were obtained from the responses to introtact probes. 75% of the first graders who received pretraining in hypothesis testing showed high proficiency in using the strategy, whereas only 38% of the kindergarten children did so. A strong tendency to become fixated on the irrelevant dimension was evident at both age levels.


Cognitive scanning processes in children. Third- and fifth-grade children and adults were presented with 8-item letter sequences of varied approximations to English in a tachistoscopic single report, cue delay task. Age differences in report accuracy suggested that younger children, as compared with adults, may be at a double disadvantage in tasks requiring perceptual-memory processing: Their initial intake capacity and/or selective processing abilities may be more limited than those of adults; and the subsequent strategy employed by children to transfer iconic information into a more permanent memory store appears to be qualitatively, as well as quantitatively, different (less systematic, less orderly, and less efficient) than that used by adults. The suggestion that children's reading experience and ability (as assessed by a word recognition task) may be related to their systematic use of an orderly left-to-right iconic transfer strategy was also examined. In addition, the results suggested that the differential letter-pattern familiarity effect between children and adults may not be attributable to visual intake components but, rather, may be related to the relative rates with which familiar letter patterns are transferred out of iconic memory.


Bidimensional sorting in preschoolers with an instrumental learning task. 74 lower- and middle-class children aged 2 1/2, 3 1/2, and 4 1/2 years who were successful at unidimensional sorting of 2 objects by either color or form were given feedback for correct bidimensional sorting of 3 objects, 2 of which had been used in unidimensional testing. Four of the 10 2 1/2-year-olds and 58 of the 64 3 1/2- and 4 1/2-year-olds reached criterion on the bidimensional sorting task. Neither social class nor performance on a verbal comprehension test (the Peabody Picture Vocabulary Test) was significantly correlated with success on either unidimensional or bidimensional sorting, although social class and test scores were significantly correlated. The results indicate that Piagetian centration (i.e., the inability to transcend unidimensional attention) is a task- or situation-specific phenomenon, and biodimensional responding is the rule rather than the exception for 3 1/2- and 4 1/2-year-olds in an instrumental situation involving a limited number of stimuli.


Effects of maternal interference on the attachment and exploratory behavior of one-year-olds. Effects of maternal interference on social behavior toward mother and exploratory play were examined in a laboratory experimental paradigm. Subjects were 40 1-year-olds and their mothers. Mothers of the 20 interference-group infants were instructed periodically to physically interfere with their child's independent object play during the first half of the observation session. A postinterference free-play period immediately followed. The 20 control-group infants were permitted by mother to play freely throughout the session. Groups were matched for exposure to play materials. Despite its aversiveness, interference had no subsequent effect on infant social initiatives to mother, responsiveness to mother's social bids, or exploratory play.


Signal functions of infant facial expression and gaze direction during mother-infant face-to-face play. Recent studies of adult-infant interaction suggest that adults modify their behavior in order to change or maintain an infant's state of arousal. We pursued this question by asking whether mothers modify their actions in response to infant facial expression or gaze direction. Subjects were 7 mother-infant (4--8 month old) pairs in which mothers were instructed to bet their babies to smile. From these filmed interactions the infant's mouth, gaze, and head direction were coded, and the mother's movements were coded as single acts or bouts. Results of an exploratory analysis indicate that, when trying to get a baby to smile using tactile and kinesthetic stimulation, mothers tend to respond to negative changes of affect and attention by changing the content of their actions, taking a long pause, or decreasing the number of acts in a bout.


Recognition of facial expressions by seven-month-old infants. 3 experiments examined 7-month-old infants' ability to discriminate the facial expressions of happy vs. fear. Experiment 1 revealed that infants demonstrated discrimination of happy vs. fear expressions when posed by a single model but that this discrimination was affected by the order of stimulus presentation. In experiment 2 infants were shown 2 models posing the happing and fearful expressions and did not demonstrate generalization of the discrimination of happy versus fear across these models. The third and main experiment varied the test procedure. Here, infants demonstrated reliable generalized discrimination of the 2 expressions across different models. As in experiment 1, however, these results were constrained by the order in which the stimuli were presented. These consistent order effects were not due to the initial salience of the 2 expressions but, instead, appeared to reflect differential rates of habituation to happy vs. fear expressions.


Infant behavioral state and speech sound discrimination. In order to investigate the interaction between infant state and speech sound discrimination, records of state were obtained from infants participating in 3 speech sound discrimination experiments which employed the high amplitude sucking procedure. A total of 94 individual records were rated for state by 2 independent scorers. When treated as an independent variable, state interacted with responsivity to sound change as measured by sucking rate increases. Infants in the more alert states demonstrated significantly higher rates of sucking following sound change. Treating state as a dependent variable revealed that state was not significantly affected by a change in stimulus conditions.


Habituation of infants' cardiac response to speech stimuli. In an attempt to explore the relation between the amount of variability in a stimulus and rate of habituation to that stimulus, 4 groups of infants 4 1/2--5 1/2 months of age were presented with repeated speech stimuli which were synthesized exemplars of [baba], natural exemplars of [baba] or [kaba], or novel syllables of each trial. Infants' cardiac responses to the auditory stimuli were recorded, and the number of trials to a proportional criterion of habituation of the heart-rate decelerative response was determined. Infants were found to habituate most rapidly to the synthesized [baba] stimulus which remained constant across trials and least rapidly to the speech syllables which changed from trial to trial.


Infants' tactual discrimination of novel and familiar tactual stimuli. 40 10-month-old infants were given 2 min to explore tactually an object in a totally darkened room. Subsequently, during a 2-min test trial in the dark, half of the infants were given the same object and half were given a novel shape. Infants presented with the novel shape evidenced significantly longer durations of manipulation than infants presented with familiar forms. Infants are thus capable of tactually discriminating novel and familiar shapes in the absence of vision and demonstrate a preference for novelty within the tactual modality.


Effects of perceptual training on the salience of information in a recall problem. Kindergarten children were given a salience-assessment task to determine each child's salience hierarchy for the dimensions of form, color, and position. The children were then assigned to either a control condition or one of 3 conditions providing different types of perceptual training with the child's least salient dimension. In a subsequent location recall task, children in all 3 training groups made significantly fewer errors recalling values of their least salient dimension than children in the control group. The results indicated that perceptual exposure alone was sufficient to increase the perceptual salience of the least salient dimension and its subsequent conceptual evaluation.


The effects of stimulus and task on preschoolers' ability to identify visual sequences. The effects of task and stimuli on the ability of 3- to 5-year-old preschoolers to identify simultaneously presented visual sequences was further assessed. A same-different task was compared to a matching task and familiar pictorial stimuli were compared to unfamiliar letters. Materials consisted of 3 element strings with 1 element repeated; both the standard and alternative(s) remained in full view on each of 25 trials. Older children performed better than younger children. The same-different task was easier than the matching task; this effect was not maintained when the differential effects of chance in the 2 tasks were removed. This pictorial stimuli produced better performance than the letters and also interacted with the type of error made. Reversal errors occurred most often in all conditions, but other kinds of errors were more frequent in the letter than the picture condition. This was particularly true for the matching task. The use of reversal errors to the exclusion of all other error types was associated with high overall accuracy on visual sequence discriminations.


Rehabilitation of socially withdrawn preschool children through mixed-age and same-age socialization. 24 socially withdrawn preschool children were located through classroom observations and assigned to 3 conditions: (a) socialization with a younger child during 10 play sessions, (b) socialization with an age mate during a similar series of sessions, and (c) no treatment. The socialization sessions, particularly those with a younger partner, were found to increase the sociability of the withdrawn children in their classrooms. Significant increases occurred mainly in the rate with which positive social reinforcement was emitted. Generally, the results support a leadership deficit theory of social isolation. Possible mechanisms responsible for the observed changes are discussed.


Continuity of individual adaptation from infancy to kindergarten: a predictive study of ego-resiliency and curiosity in preschoolers. In this longitudinal study, individual differences in security of attachment at 18 months and effective autonomous functioning at age 2 years were related to the dimensions of ego-control and ego-resiliency at age 4--5 years. The kindergarten or nursery school teachers of 26 children completed California Child Q-Sorts. The children were also given a short form of the Block's laboratory battery (Banta's curiosity box, level of aspiration, motor impulse control delay of gratification, the Shure and Spivack Preschool Interpersonal Problem-solving Test, and the Lowenfeld mosaics). Following the Blocks, composited ego-resiliency and ego-control scores were derived from each data set. Children earlier classified as securely attached were, as predicted, significantly higher on ego-resiliency on both laboratory and Q-sort composites. They were also higher than anxiously attached infants on 3 independent measures of curiosity. An independently composited index of competence from 2-year tool-using measures also correlated significantly with later resiliency, as did 2-year measures of mothers' support and quality of assistance. The data provide initial links between the infant's quality of attachment, the toddler's effectiveness in a problem-solving situation, and competence during the preschool years.


Individual differences in infant-mother attachment at twelve and eighteen months: stability and change in families under stress. 100 economically disadvantaged mothers and their infants were observed in the Ainsworth and Wittig "strange situation" at 12 and 18 months. Infants were classified as secure, anxiously attached/avoidant, or anxiously attached/resistant. In addition, mothers reported occurrence of stressful events related to the stability of the caretaking environment during the 12--18 month period by completing a 44-item checklist concerning work, finances, family, neighbors, health, etc. 62 infants were assigned to the same attachment classification at both 12 and 18 months (p less than .01). Despite this stability, significantly more infants changes classification than in a recent study of stable middle-class families. With the present sample, anxious attachment was associated with less stable caretaking environments than secure attachment; change from secure to anxious attachment was associated with higher stressful-event scores than stable secure attachment.


The naive theory of the infant and other maternal attitudes in two subgroups in Israel. 104 mothers of 1- and 3-year-old children were interviewed. Half of the mothers were of high and half of low SES. Low SES mothers believed that infants acquire basic cognitive skills, such as vision, hearing, and comprehending speech, at a later age than high SES mothers. Low SES mothers also believed that the introduction of cognitively stimulating activities during the first years, such as buying the first book or starting to feed the self, should occur later than did high SES mothers. No status group differences were observed in the favored timetable of physical caregiving, such as toilet training or weaning. Nor were there status group differences on the strictness/leniency dimension or in the unwillingness to put pressure on infants for accelerated development. The naive theory of the infant as a cognitive being and the timing of cognitively enriching activities were found to belong to a common cluster, separated out from the rest of the maternal attitudes, in an analysis of the intercorrelation matrixes obtained in the two samples.


[Late infections after artificial joint replacement with a septic course]. Acute staphylococcal sepsis is a rare complication following artificial joint replacement. Daignostic problems are due to the systemic toxic effects of staphylococci. Loosening of the prosthesis is generally observed later. For therapy of staphylococcal sepsis the prosthesis has to be changed early, using a tested antibotic mixed with the bone cement, Palacos. Prophylaxis is most important. It includes the elimination of infectious foci, the strong indication for all therapeutic measurements and the general use of the antibiotic, Gentamycin, with the bone cement, Palacos.


An analysis of spindle ultrastructure during prometaphase and metaphase of micronuclear division in Tetrahymena. Mitotic micronuclei were isolated from Tetrahymena thermophila in a medium containing hexylene glycol and their ultrastructure was analyzed using thin section techniques. The two stages selected for analysis were early prometaphase and metaphase. A comparison of data from these two stages revealed several differences in nuclear morphology. Metaphase nuclei were longer, they contained more microtubules, and the distribution of microtubules at metaphase was different from that at early prometaphase. Increases in microtubules, which are a unique class of microtubules that can be distinguished from other classes on the basis of their close association to the nuclear membrane. Growth of peripheral sheath microtubules is thought to be significant because it could be the mechanical basis of nuclear elongation. Crossbridges were observed throughout the spindle between all classes of microtubules, but the exact function of these elements remains to be determined.


A comparison of chromosomal and allozymal variation across a narrow hybrid zone in the grasshopper Caledia captiva. A hydrid zone between the Moreton and Torresian taxa of the grasshopper Caledia captiva in S.E. Queensland has been characterised in terms of allozyme and chromosome variation within the same individuals.--On chromosomal criteria (pericentric rearrangements), the zone is asymmetrical with evidence of high levels of introgression of Torresian chromosomes into the Moreton taxon. This is apparent from the analysis of two independent transects across the hydrid zone. Major changes in chromosomal frequency occur over distances of less than 0.5 km. and the level of introgression differs between the two transects, with much higher levels in the northern Moreton populations, characterised by an acrocentric X-chromosome, when compared with the southern metacentric-X Moreton populations. Chromosome analysis of samples taken from the same transect over two years has revealed no major changes in the structure of the zone. Moreover, a Moreton population located only 0.5 km. from the null point was found to be stable over 6 generations with evidence for a new balanced genome having originated following the differential incorportation of Torresian chromosomes.--Contrary to the chromosomal situation, the same hybrid zone was found to be symmetrical with respect to allozyme variation with evidence of movement of diagnostic alleles in both directions across the zone. The alleles are independent and not tightly linked to any of the pericentric rearrangements. Thus these 5 alleles are acting as markers of the background genome and reveal the relatively free movement of genes which are located outside the pericentric rearrangements.--It is proposed that the hybrid zone in Caledia captiva is unstable and is moving slowly in a westerly direction into the Torresian territory. This is due to the ability of the Moreton taxon to incorporate more readily into its genome those Torresian chromosomes or chromosome segments which increase the fitness of the Moreton taxon. On chromosomal criteria, the Torresian taxon does not share the same capacity.--It is suggested that, so long as the two taxa retain their ability to hybridise with subsequent asymmetrical introgression, the zone will continue to move westwards and eventually lead to the selective incorporation of the Torresian genome into the Moreton taxon. This will result in a polymorphic situation with clinal variation in chromosomal frequencies. The structure of the zone is dependent upon a fine balance between genomic reorganisation in recombinant genotypes and the relative dispersal capacities of the two hydridising taxa.


Gold nephropathy in rheumatoid arthritis and in juvenile chronic arthritis. During gold therapy a patient with rheumatoid arthritis developed nephrotic syndrome, and a patient with juvenile chronic arthritis proteinuria. Electron microscopic examination of bioptic specimens of the kidneys revealed in both instances membranous glomerulonephritis with typical epimembranous deposits and intracellular gold inclusions. Immunofluorescent examination performed only in the second patient revealed that the deposits in the wall of the glomerular capillaries contain IgG which suggests an immunocomplex mechanism of the development of the renal disease, induced very probably by chrysotherapy.


Clinical importance of antibodies against double-stranded ribonucleic acid in systemic lupus erythematosus and similar diseases of connective tissue. Prolonged repeated analyses of sera from 98 patients with systemic lupus erythematosus (SLE) and 76 patients with similar diffuse diseases of connective tissue by a radioisotope membrane binding method for the assessment of antibodies against double-stranded ribonucleic acid (anti-ds-RNA) revealed that these antibodies are most frequently encountered in patients with the evolutive form of SLE (53%), but also in approximately one fifth of patients with non- evolutive SLE and in patients with similar diffuse diseases of connective tissue. Anti-ds-RNA are not linked with stages of clinical activity; their occurrence is on the whole independent on the occurence of antibodies against ds-DNA and nuclear ribonucleoprotein. There is a very close association with the incidence of antibodies against denatured DNA and a substantially small association with antibodies against acid nuclear antigen (Sm). The occurrence of anti-ds-RNA is a favourable prognostic sign, as in the majority of patients who had such antibodies at any time in their serum, later the disease can be suppressed by treatment, while patients who never had anti-ds-RNA in serum remain for a long time in the active stage of the disease.


Epidemiology of tumours in the Oncological Research Programme of the Research Institute of Clinical and Experimental Oncology. The author submits the results of initial epidemiological investigations, conducted at the department for the epidemiology of tumours in the Research Institute of Clinical and Experimental Oncology, which have the character of statistical epidemiological surveys. He compares the incidence of tumours in the CSSR, CSR and South Moravian region. He draws special attention to the different incidence of tumours among women in the South Moravian region, as compared with the incidence in the CSR.


Classification of primary articular chondrocalcinosis. Based on long-term observations the authors submit a categorization of primary (hereditary and solitary) articular chondrocalcinosis into three different sub-populations. Attention is drawn to the fact that the extent of the qualitative disorder of the articular cartilage, obviously conditioned genetically, is linked with the age factor and determines the quantitative differences of pyrophosphate arthropathy in primary chondrocalcinosis. In young age, as a rule in the third decade, severe polyarticular condrocalcinosis (first sub-population) develops which causes relatively soon invalidity, in middle age (5th and 6th decade) milder condrocalcinosis develops (second sub-population) which combines with extraarticular, tendinous and tissue calcifacations, and finally in advanced age oligoarticular chondrocalcinosis develops (third sub-population) which is usually associated with ankylosing hyperostosis of the spine. Articular chondrocalcinosis (CCA) which we described by this term as a special metabolic arthropathy which occurs in families and solitary and which we defined as a special nosological unit (35, 36,) has become generally known and firmly established in rheumatology. As ensues from numerous publications, primary (idiopathic) CCA which comprises the hereditary and solitary (sporadic) form is characterized by pyrophosphate arthropathy which develops on articular cartilages not damaged by another process (13, 25, 26, 37); on the other hand as secondary CCA we consider pyrophosphate arthropathies which are associated with metabolic, endocrine or other diseases (9, 30). The common sign of both basic forms of CCA is the presence of microcrystals of calcium pyrophosphate dihydrate (CaPD) in articular cartilages, synovial fluid, or other articular structures (capsules, tendons, ligaments), characterized originally by McCarty et al. (11, 18) and later by other authors (2, 23, 27, 32). In addition to semantic (terminological) problems there were also questions of the classification of CCA because, based on an analysis of major groups of patients, it was revealed that there is a varied picture of chondrocalcinosis or pseudogout (18, 19) or deposition disease (17). of calcium pyrophosphate dihydrate crystals. In our paper we are presenting our view on the primary form of CCA and submitting the characteristics of classification which ensued from more than 20 years observation of our group of patients, in particular based on the evaluation of the beginning of the clinical and X-ray manifestations and the further development of the disease.


Some epidemiological outlooks on cancer mortality in Czechoslovakia. Study of the total mortality evolution of the population in Czechoslovakia indicated the steadily increasing and recently 20% participation of the malignant neoplasms and their leading, second position among main causes of deaths. The crude cancer mortality rates of all sites showed in the period 1946--1975 substantial increase more expressed in males, while the pattern of age-adjusted mortality rates of men were lower and in the women remained quite stable during the whole evaluated period. Cancer mortality in this period was characterized also with increasing overmortality of men. Analysis of age-specific death rates revealed not only higher mortality of males but also the shifting of the peaks to older age groups in both sexes. The malignant neoplasms of lung, stomach, prostate and rectum in men and the tumors of breast, stomach, colon, rectum and of genital organs in women were the most important individual sites. Finally, the actual cancer mortality rates of all sites in Czechoslovakia were compared with those of some European countries.


Value of the abdominal plain film after angiocardiography in congenital heart disease. The urinary tract visualized on plain abdominal film 10 min after angiocardiography revealed 49 abnormalities of the urinary tract in 680 patients with congenital heart disease (7.2%). The diagnostic value is high, as among the 49 abnormalities 40.9% had no urinary symptoms. 5 abnormalities of the urinary tract required rapid surgical treatment.


Isolated developmental anomaly of the vena cava inferior and vena azygos imitating a mediastinal tumor. A developmental anomaly of the vena cava inferior in its suprarenal portion with an azygos continuation which imitated a mediastinal tumor is described. The importance of phlebographic investigations in unexplained shadows in the mediastinum is stressed.


True and false avascular areas in carotid angiography. The cause of avascular areas in carotid angiograms is discussed in an effort to facilitate their correct interpretation. True avascular areas are due to extracerebral haematomas. False avascular areas are due to anatomical or technical factors, which can, to some extent, be eliminated.


Computer-assisted myelography in degenerative abnormalities of the cervical vertebral column. In 19 patients with symptoms suggestive of a cervicobrachial syndrome due to degernative lesions of the cervical spine, a CT scan was made after intrathecal administration of metrizamide. The images thus obtained supply adequate information on the extent of bone apposition, if any, on the degree of displacement and compression of the spinal cord, and on the condition of the intervertebral foramina. A CT scan is indicated in the case of discrepancy between myelographic findings and clinical diagnosis. In the case of recurrent postoperative symptoms, too, CT scans have proved to supply valuable information.


Arthritis of the sacro-iliac joints in patients with psoriasis. In a series of 58 patients with psoriasis and skin involvement in the absence of any symptoms of an associated joint or bone disease, 49 individuals had definite signs of an arthritis of the sacro-iliac joints, while only slight changes were present in the others. The authors reached the conclusions that arthritis of the sacro-iliac joints occurs in all patients with psoriasis, without any exceptions; and thus not only in those who have simultaneous symptoms of bone or joint disease, which are well known in psoriasis, but equally in those in whom the clinical symptoms are missing.


Multidirectional CT of the posterior fossa. Computer tomography of the head using the standard views parallel to the orbitomeatal line, does not demonstrate the anatomy of the posterior fossa to the best advantage, because the slices pass obliquely through the brain stem and cerebellum. The cranial and caudal borders of the posterior fossa (tentorium and foramen magnum) are also cut obliquely. A series of slices lying in optimal anatomical planes are suggested. The results are discussed.


Response to chemotherapy of breast carcinoma bone metastases: assessment by bone scan. 3 patients suffering from bone metastases of breast carcinoma were followed by utilizing bone scan during treatment with combination chemotherapy. The advantages of bone scan for the assessment of the response to chemotherapy are discussed.


Xeroradiographic study of haemophilic arthropathy. The results of a xeroradiographic study of 50 patients with haemophilia in various stages of severity are reported. In comparison with traditional radiographic examination, the xeroradiographic method seems preferable especially in the early stages of disease, when alterations are limited to the soft tissues and the skeletal structures are intact. The main indications and methods of further research are discussed in this preliminary report.


Importance of computer-assisted myelography in diseases affecting the vertebral column. Of a series of 20 patients in whom CT scans revealed lesions of the vertebral column, 6 cases are discussed which confirm the efficacy of this method of investigation. Good information is obtained in particular on pathological processes in which optimally exact localization is required preoperatively and in tumor relapses. CT scanning is also indicated when myelography proves to be impossible, e.g., due to adhesions. Computer-assisted myelography, however, does not yet seem suitable to be used as a routine procedure.


Thoracopagus conjoined twins: radiological evaluation of one case. Radiological study of conjoined thoracopagus twins. The digestive and biliary tracts, the urinary and cardiovascular systems have been examined. The problems and difficulties encountered in the various procedures and in the interpretation of their results are described.


Inflammatory pseudotumors of the stomach. 3 patients are presented in whom radiologic examination revealed large filling defects in the stomach. The mass-like lesions were proved to be caused by nonspecific, nongranulomatous circumscribed inflammation of the gastric wall. This condition is radiologically often indistinguishable from gastric carcinoma or lymphoma and in many reported cases was diagnosed only after surgery. The mucosa may be hypertrophic, atrophic or normal in the region of the thickened wall. The thickening is produced by the inflammatory infiltration and edema of the gastric wall. In most cases the cause of this localized inflammation remains unknown.


Common bile duct visualization with a nonvisualized gallbladder in oral cholecystography: radiological and surgical study. A series of 203 cholecystectomied patients in which the gallbladder was not visualized in oral cholecystography is analysed. In 72 cases the common bile duct was seen. In 4 cases it was dilated. At operation, cholecystolithiasis was found in 189 cases, a calculus in the common bile duct in 3 cases, and a neoplasm in 3 cases. In 6 cases there was inflammation but no calculi. Administration of 2 g of sodium iopanoate on 2 successive days before the examination seems to result in frequent visualization of the common bile duct. It also seems to be an accurate method in biliary tract disease when the gallbladder was not adequately visualized.


Gray scale ultrasound signs of gallbladder stones: clinical and experimental study. 200 patients with radiologically detected gallbladder stones were examined with gray scale ultrasound. Nine different ultrasound signs caused by the stones were found. A physical and chemical analysis of the gallstones of 33 patients from different image groups was performed. Viscosity of the bile and the thickness of the gallbladder wall were measured. Phantom experiments were performed and four different ultrasound signs were found but there was no significant correlation between these and the physicochemical properties of the gallstones.


Television tomometry in intravenous cholangiography. Out of 93 infusion cholangiographies carried out with a remote control stand, television tomometry could be applied to the tomographic cut localization in 79 cases. The accuracy of the method was considered very good in 86% and--including the former--sufficient in 95% of the cases. With certain exceptions the method was considered suitable in the routine intravenous cholangiography. The importance of training for successful operation is emphasized.


Comparison of ultrasound and roentgen examination of biliary tract. The relative merits of gray-scale ultrasound and roentgen examinations of biliary tract diseases have been compared. Sonography was able to give a definite diagnosis in 74 of 95 roentgenologically unclear cases, and roentgen examination gave a diagnosis in 70 out of 105 cases unclear at sonography.


Accuracy of computed tomography in the screening of obstructive jaundice. Percutaneous transhepatic cholangiography (PTC) has come back into greater use thanks to Chiba's needle. PTC, however, is useful only in obstructive jaundice (OJ). Since in OJ the dilatation of the intrahepatic biliary tract (IHBTD) is constant, the authors discussed CTs reliability in evaluating IHBTD in a series of 33 patients with OJ studied with PTC. The threshold of CT diagnosis of IHBTD was found to be equal to a doubled caliber of the normal biliary tract. This value is reached by 85% of the patients 2 weeks after the onset of OJ and in 98% between 2 and 3 weeks. CT is therefore usable as a screening method of PTC, as long as it is not performed before 2 weeks after the onset of OJ. After 2 weeks, if CT does not reveal IHBTD, it is possible to exclude OJ.


Gastrointestinal manifestations of chronic lymphatic leukemia. In chronic lymphatic leukemia there are also leukemic changes in the gastrointestinal tract; these can be detected roentgenologically and endoscopically.


Intrathoracic stomach: CT evaluation of two cases. 2 cases of intrathoracic stomach, 1 of them associated with hernia of the splenic flexure of the colon and a right-situated thoracic descending aorta, are evaluated by computed tomography.


The posterior tracheal band in the lateral chest radiograph. The appearance and variations of the posterior tracheal band (PTB) was studied from 406 upright chest radiographs, taken from 293 individuals of varying age. PTB is visualized in about 80% of individuals well enough to be diagnostically useful. Its average width is 3 mm, and patient positioning can cause variations not exceeding 2 mm. Progressive widening by 2 mm or more, blurring of previously sharp margins or an overall width exceeding 5 mm should be considered suggestive of mediastinal or related abnormality.


Stenosis of the popliteal vein caused by an osteochondroma of the distal femur: a case report. This report describes a 14-year-old girl presenting with unilateral distal leg edema which developed on the basis of popliteal vein compression by a large osteochondroma of the distal femur. Excision of the osteochondroma relieved the venous obstruction, and the leg returned to normal. Lesions of tibial arteries and veins caused by osteochondromas of the distal femur are discussed.


Scintigraphic detection of gastric calcification in dialysis patients. The value of 99mTc HEDP bone scintigraphy as a means of detecting metastatic gastric calcification was studied in 45 chronic dialysis patients and in 55 former dialysis patients. For this group, all bone scans were obtained within 2 months after successful transplantation; radiotracer uptake by the stomach was not observed. In 15 of the first 35 chronic dialysis patients studied, gastric uptake was demonstrated without radioactive accumulation in the thyroid region. In all the dialysis patients, however, background activity had been normalized before scintigraphy by means of hemodialysis using recirculating dialysate. Without the latter, radioactive accumulation in the stomach was no longer noted. Thus, gastric uptake was presumably due to the formation of in vivo free pertechnetate, as a result of the dialysis method used, and in vitro experiments supported this hypothesis. These findings show that free pertechnetate can cause visualization of the stomach in the absence of thyroid imaging. The results of this study further indicate that bone scintigraphy is not a sensitive method for detecting metastatic gastric calcification in uremia.


Technetium-99m trapping index as a test of thyroid function. Thyroid examinations were performed in parallel in over 300 patients using 131I and 99mTc pertechnetate. The aim of the study was to evaluate the use of the 99mTc pertechnetate neck/thigh ratio as an index of thyroid function. Results presented indicate that the 99mTc trapping index can be reliably used as a simple and accurate index of thyroid function.


Androgens and brain differentiation. Effects of testosterone on protein synthesis in neonatal rat hypothalamic and cerebral slices. Protein synthetic activity of anterior hypothalamic and neocortical brain slices from androgenized neonatal female rats was studied in vitro in an attempt to clarify the mechanism of action of testosterone on the developing hypothalamus. The short-term effects of testosterone propionate injections of the animals on the protein synthetic activity of the slices were assayed by means of incorporation of 14C-leucine into acid-insoluble protein. Although a high dose (1 mg/animal) of testosterone propionate stimulated increased incorporation in neocortical and anterior hypothalamic slices, a lower dose and other approaches failed to demonstrate a stimulation regionally specific to the anterior hypothalamus. It is concluded that if testosterone has specific stimulatory effects on protein synthesis in the anterior hypothalamus of neonatally androgenized rats, these are not readily demonstrable by methods used with other steroid target tissues.


Effect of thyroid deficiency on the growth of the hippocampus in the rat. A combined biochemical and morphological study. The growth of the hippocampus was studied in normal and hypothyroid rats using both biochemical and morphological techniques, and the results were compared with observations on the whole forebrain or on the cerebral cortex. The longitudinal growth, area and the volume of the hippocampus was severely reduced in thyroid deficiency. In the cerebral cortex the longitudinal growth and some of the parameters of transverse development were significantly decreased at the rostral but not at the caudal level. On rehabilitation from day 35 to 160 the longitudinal growth remained decreased in both the brain parts while the transverse growth was restored to normal in the cerebral cortex but not in the hippocampus. In the normal hippocampus about 60% of the cells were formed during the first 3 postnatal weeks. This developmental increase was significantly depressed in hypothyroid rats; the final deficit in cell number was about 13%. The rate of cell acquisition was calculated from the slopes of the logistic curves fitted to the data of DNA content. At the age of maximal cell acquisition (at day 2-3) the daily deposition was 0.44x106 cells in controls and 0.34x106 cells in the hypothyroid rats. In controls the concentration of DNA decreased in the hippocampus during maturation. Thyroid deficiency did not influence this developmental trend. In contrast, a severe reduction was observed in the cellular composition of RNA and protein.


Development and aging of cholinergic synapses. I. Endogenous levels of acetylcholine and choline in developing autonomic ganglia and iris of the chick. Acetylcholine (ACh) and choline (Ch) levels were measured by means of a sensitive micromethod in developing irises, ciliary and sympathetic ganglia of the chick, starting at 5--7 days of incubation (DI) up to 1 year of age. The neurotransmitter is present in all three organs at relatively low levels (1--10 pmol) from 5 DI (iris) or 7 DI (ciliary and sympathetic ganglion). This is followed by a rapid and sustained 9-fold increase in all three tissues up to 14 DI. Thus, it appears that low levels of ACh may be sufficient for neurotransmission to occur in the primitive ciliary ganglion and iris. After hatching, total ACh levels continue to increase up to 1 year of age in the iris and ciliary ganglion and up to 3 months in the sympathetic ganglion. The increase may depend on either an increased functional demand for the neurotransmitter or an increased number of preganglionic terminals. In general Ch levels parallel closely the levels of ACh in each organ throughout development. It is concluded that ACh and Ch are present since the earliest detectable stages of development in the ganglia and iris, and their first increase seems to be correlated to the phase of innervation of the organs. The subsequent increase probably correlates to synaptogenesis. The close relationship between Ch and ACh levels indicates a regulatory role of Ch for ACh synthesis during neuronal development.


Effects of age on the metabolism of thyroid hormones by rat brain tissue in vitro. Using a newly-devised chromatographic method for the separation of the acetic and propionic analogues of triiodothyronine (T3) and thyroxine (T4), we studied the metabolism of radioactively labeled T3 and T4 in rat brain homogenates to determine whether the rates of metabolism and the types of products formed are influenced by the age of the animal. The separation of metabolites is achieved on silica gel H in a solvent system consisting of methylacetate-2.5% ammonia (W/V) (95:5 V/V). Results clearly demonstrate that the metabolism of both T3 and T4 is age-dependent. Metabolism of T3 occurred at a significant rate during the early postnatal period (11 and 23 days), declined sharply between 23 and 40 days and was almost completely absent in the adult brain (100 days). Free iodide was the only product that could be identified in extracts of the reaction mixture. Neither the acetic nor propionic acid analogues of T3 were present in significant amounts. In the case of T4, iodide was the major metabolite formed. In addition, a significant amount of triiodothyroacetic acid was present in extracts of homogenates from the 11- and 23-day-old rats but not in those from older animals. Although initially, the rate of T4 metabolism was greater in the younger animals, over a 6-hour period, the amount metabolized was approximately the same at all ages studied. We conclude that these age-dependent changes in the metabolism of T3 and T4 may influence T3 receptor interactions in brain tissue and thereby regulate hormonal activity at the cellular level during the critical period of brain development.


A procedure for purifying neuron-like cells in cultures from central nervous tissue with a defined medium. A serum-free medium (N1) containing the supplements insulin, transferrin, progesterone, putrescine and selenium was used to culture cells from a variety of embryonic chick central nervous system tissues, namely, optic lobe, neural retina, spinal cord and telencephalon. The N1 medium supported the survival of fiber-bearing cells (features typical of cultured neurons) as well as or better than horse serum, while permitting no, or almost no flat cells. Survival and growth of chick flat cells required fetal calf, but not horse serum. Cultivation of newborn mouse telencephalon under these conditions yielded similar results, except that either fetal calf or horse serum supported flat cells.


A stereological analysis of the neuronal and synaptic content of the frontal and cerebellar cortex of weanling rats undernourished from birth. The frontal cortex and granular layer of the cerebellum have been examined in 30-day-old rats undernourished from birth. Quantitative stereological procedures at the light microscopical level have been used to estimate the volume proportion and numerical densities of neuronal nuclei. Similar methods at the electron microscopical level were employed to calculate the numerical densities of synapses. Hence, synapse-to-neuron ratios have been calculated in these brain regions. In the frontal cortex, the undernourished group of rats showed a 37% deficit (P less than 0.05) in the synapse-to-neuron ratio. This was due to a combination of an increase in the numberical density of neurons and a decrease in the numerical density of synapses, although, individually, neither of these reached statistical significance at the 5% level. In the granular layer of the cerebellum there was a 31% (P less than 0.01) deficit in the synapse-to-neuron ratio. This was a function of the reduced numerical density of synapses, with no difference in the numerical density of granule cells between groups. For the frontal cortex, the volume proportion of neuronal nuclei was significantly greater in the undernourished group of rats. There were no significant differences between control and undernourished rats in the volume of the 'forebrain' occupied by cortex. The mean diameters of neuronal nuclei and synaptic discs did not differ in any given region between treatment groups. These observations are discussed in context with the previously published results on synapses and neurons in undernourished animals.


Fetal mediators of the relationships between increased pregnancy and labour blood pressure and newborn irritability. A prospective study of primiparous English women and their newborns failed to replicate previous findings that greater irritability was related to higher maternal blood pressure during pregnancy and labour. This apparent lack of replication prompted a search for fetal variables capable of mediating the blood pressure--irritability relationships. Relative fetal growth retardation was found in newborns of women whose peak antenatal blood pressure occurred from 20 to 32 wk gestation. Prenatal growth retardation and exposure to either oxytocin-stimulated labour or higher maternal blood pressure during spontaneous labour were associated with lower intrapartum fetal heart rate. Lower heart rate, in turn, was associated with greater crying and more frequent changes of state during behavioural assessments on the first and fifth days. It is suggested that intrapartum hypoxia is an immediate antecedent of newborn irritability. The blood pressure--irritability relationships may therefore reflect the influence of growth retardation, attributable to increased pregnancy blood pressure, and higher labour blood pressure, respectively, on the ability of the fetus to withstand hypoxia and the degree of hypoxia encountered during labour.


Preterm birth, growth retardation and acidemia in relation to neurological abnormality of the newborn. The Groningen Perinatal Project is a follow-up study relating pre- and perinatal conditions to early and late neurological sequelae. A description is given of the first cohort of 1507 children, examined neurologically during the neonatal period, and of their mothers and their pregnancies. In this preliminary analysis three 'final pathways' are considered, i.e. intrauterine growth retardation, preterm birth and acidemia (pH in umbilical vein below 7.20). Significant relationships were found between the 'final pathways' and the neurological findings. Since, however, these relationships account for only a small part of the variance of the latter, it is concluded that the (cumulative) effect of other antenatal variables must be taken into account as well. Results of analyses to this effect will be reported in forthcoming publications.


Patterns of breath intervals during non-nutritive sucking in full-term and 'at risk' preterm infants with normal neurological examinations. The interaction between respiration and non-nutritive sucking rhythms was investigated in 12 sleeping, normal full-term, newborn infants and in 14 preterm infants were were examined repeatedly at 34, 40 and 46 wk of conceptional age. Full-term infants showed a shortening of breath intervals in the middle of sucking bursts and a lengthening of the breath interval spanning the end of sucking bursts. The differences were more marked in females than males. A rhythm interaction between sucking and respiration was also observed in preterm infants as young as 34 wk of conceptional age. Clinical neurological examinations did not discriminate between preterm infants above and below a median score for optimal obstetric conditions, but the interaction between breathing and sucking rhythms made such discrimination, most clearly in females. Preterm infants with lower optimal obstetric scores showed less change of breath durations during sucking than preterms with higher scores. It was concluded that interaction of concurrent motor rhythms may be a sensitive index of central nervous system integrity in newborn infants, even when there are no clinical neurological signs of nervous system dysfunction.


Maternal attitudes to their obstetric care. Advocates of 'natural childbirth' are many and vocal, but there appears also to be a group of women who are in favour of more active obstetric management. Preference for a subsequent confinement seems to be influenced by previous experience.


The water content of the human umbilical cord. 105 umbilical cords from 53 term and 52 preterm newborn infants were freeze-dried after removal of the blood vessels, to determine the water content. The mean umbilical cord water content (i.e. mean of water content of fetal and placental ends of the cord), was 88.9% (SD 2.73) for term cords and 91.9% (SD 1.99) for preterm cords. The mean water content fell with increasing gestation. The fetal end of the cord had a significantly higher water content than the placental end. Similarly, the volume of a 4-cm length segment of cord was significantly greater at the fetal than placental end. There was no correlation between cord water content or volume and several other variables including birthweight, size for gestational age and placental weight. These observations suggest a metabolically active role for the umbilical cord.


Deciduous teeth contain histories of developmental disturbances. The crowns of the deciduous teeth are permanent structures which form by incremental growth during the second half of pregnancy and first year of life. These structures become available between the ages of 6 and 12 years with normal exfoliation and can then be studied histologically to demonstrate evidence of metabolic disturbances occurring during tooth development. As the chronology of disturbances can be assessed with reasonable accuracy, such studies provide a potentially valuable research tool.


Sucking patterns of human babies on the breast. Twenty-seven 5--8-day-old babies were filmed during normal breast feeding (one feed each). Sucking patterns were determined from the film from a total sample of 17,676 sucks. Intersuck interals fell on two distributions: one of intervals between sucks during bursts of sucking (1.3 sec and less), and the other of rests between bursts of sucking (1.3 to greater than 12 sec). As the milk flow dropped towards the end of the feed on each breast, the sucking rate within bursts increased (P less than 0.05), but there were more (P less than 0.001) and longer (P less than 0.001) rests between bursts of sucking. This study provides normative data on a normal population for use in studies of breast feeding.


Separation and reunion behaviors as criteria of attachment to mothers and fathers. Twenty infants were observed 4 times between 7 and 13 months of age in a short-term longitudinal study. Responses to separations from and reunions with mothers and fathers are reported. None of the measures showed a preference for either parent at any age. Other studies confirm that even young infants are attached to both parents. It is argued that greater attention must be paid to the family's role in social and personality development.


Structural changes in parathyroid glands exposed to vitamin D metabolites in vitro. Isolated parathyroid glands from normal adult Mongolian gerbils were incubated for 10 minutes to 16 1/2 hours at high, medium or low concentrations of Ca2+, with or without added 1,25-dihydroxycholecalciferol (1.25-DHCC) or 25-hydroxycholecalciferol (25-HCC), after which they were studied electron microscopically. 1,25-DHCC appeared to potentiate the inhibitory action of high calcium on parathyroid activity, whereas 25-HCC had no structurally detectable effect.


[T4 metabolism in age matched heavy and light rats with good and bad feed efficiency following high- or low-in-fat diet]. Rats, fed two diets (high or low in fat content), were at the and of the feeding-period separated in light and in heavy animal groups. The leaner rats from the diet group high in fat content show opposite to the heavier animals of this diet group significantly increased T4 distribution spaces, significantly shortened T4 half life time and lower feed efficiency. T4 serum values, absolute T4 degradation per day and body mass and free thyroxine index in these leaner rats also increased significantly. However comparing heavy rats feed a diet low and light rats fed a diet high in rat content the latter  show also a decreased feed efficiency, but no differences in T4 serum concentration or T3 binding capacity of serum proteins, free thyroxine index and T4 degradation. The results in T4 metabolism are discussed in relation to feed efficiency of the investigated animal groups.


[The diabetic polyneuropathy. I. Relation between impaired function in peripheral nerves and clinical findings]. 789 patients with diabetes mellitus were studied by clinical and electroneurographical investigation. Motor and sensory conduction velocities of the median nerve and motor conduction velocity of the tibial nerve were determined. 86.1% of the patients suffered from juvenile diabetes, and 13.9% from maturity onset diabetes. Average duration of the disease was 9.5 years, average age of the patients was 26.7 years. Clinical signs of polyneuropathy were found in 19.1%. In 40.9% of the patients at least one of 3 conduction velocities was found to be delayed. Patients with clinical signs of polyneuropathy exhibited delayed nerve conduction velocities and delayed distal latencies. Diagnosis of polyneuropathy almost with certainty is possible by determining the three nerve conduction velocities and the three corresponding distal latencies. 22% of patients without clinical signs of polyneuropathy exhibited electroneurographical signs of impaired peripheral nerve function. Heredity, body weight, lipid metabolism, actual metabolic balance, and treatment were found to be without any significant influence on nerve conduction velocity.


[The diabetic polyneuropathy. II. Polyneuropathy, angiopathy and nerve conduction velocity]. 789 patients with diabetes mellitus were studied by clinical and electroneurographical examination. Motor conduction velocity of the median and the tibial nerve and sensory conduction of the median nerve were determined. 81.1% of the patients we suffering from diabetes which began in childhood or adolescence, 13.9% were suffering from maturity onset diabetes. Average duration of the disease was 9.5 years, average age was 26.7 years. Clinical signs of polyneuropathy were found in 19.1%. Typical findings were pain and paraesthesia, lack or abolition of triceps surae reflexes, impaired pallaesthesia on lower extremities. 48.3% of 151 patients with clinical signs of polyneuropathy were suffering from combined angiopathy, 32.5% from microangiopathy, 7.9% from macroangiopathy. Severity of complicating retinopathy and macroangio,athy were found to be correlated with polyneuropathy. 58.2% of 323 diabetics with at least one delayed nerve conduction velocity exhibited signs of angiopathy. In nearly 30% of children and adolescents after comparatively short duration of the disease at least one conduction velocity was delayed. In diabetic children and adolescents metabolic disturbances are assumed to cause peripheral nerve dysfunction.


Regeneration of the neurosecretory tract in hypophysectomized catfish Ompok bimaculatus (Bloch)--an in situ study. Regeneration and reorganization of the proximal cut end of the pituitary stalk is demonstrated in Ompok bimaculatus with the aid of in situ staining technique. The lesioned end exhibited an increase of axonal density and some axons became prominent by their uncontrolled growth. In few instances the cut ends were reorganized into a neurohypophysis-like organ.


Thymidine kinase activity in murine lymphoid organs following glucocorticoid and heparin administration. Thymidine kinase (TK) activity was studied in thymus and spleen of mice after glucocorticoid and heparin administration. Glucocorticoids (cortisone and hydrocortisone) injected intraperitoneally caused a prolonged 80--90% decrease in TK activity of both lymphoid organs. Heparin per se administered in depot-form subcutaneously did not alter the enzyme activity in the lymphoid organs significantly. By contrast, heparin injected 6 hours before glucocorticoid treatment inhibited the decreasing effect of cortisone but not that of hydrocortisone on TK activity in the thymus and fully inhibited the effect of both hormones on the enzyme activity of spleen. In addition the combined use of heparin and cortisone increased the splenic TK activity above the control value on the 2nd day after treatment. The possible mode of action of heparin is discussed.


Total and free cortisol plasma levels in pre- and postnatal life. Total and free cortisol and cortisol binding globulin (CBG) levels were measured in plasma of 7 fetuses during 22 to 34 weeks of pregnancy and 80 infants aged 1 day to 30 months. In comparison with normal adults, total cortisol levels were significantly diminished (p less than 0.001) both in fetuses and newborn infants aged 2 to 8 days. However, low total cortisol levels were accompanied by extremely low CBG concentrations especially in prenatal but also in early postnatal life. Consequently, free cortisol levels during pre- and postnatal life were not significantly different from those of normal adults except the values immediately after birth, which were evidently elevated. With advanced age of the infants CBG values increased and reached the mean values of adults at 46 to 80 days of age. However, in infants aged 8 to 30 months CBG values were even significantly higher (p less than 0.01) than those of adults.


The regional distribution of adenylate cyclase in individual nuclei of rat hypothalamus. The regional distribution of adenylate cyclase (AC) activity in separated individual hypothalamic nuclei was studied. The highest activity was found in the paraventricular nucleus and the lowest activity in the median eminence. In several other hypothalamic nuclei, there was also found higher activity of AC than in the total hypothalamus. These data show that in the individual hypothalamic nuclei there exist considerable differences in the activity of adenylate cyclase that may indicate their different function in regulation of neuroendocrine phenomena.


Blood serum triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) concentrations in healthy children at the age of 1 and 2 years. The physiological mean concentrations of T3, T4 an TSH in 150 healthy children aged from 1 month to 2 years of life decreased gradually with age. The statistically significant difference was observed only in T3 levels between the first and second year of life. The remaining parameters did not show statistically significant differences.


[Triglycerides, fatty acids and cortisol in simple obesity in children]. In 50 children with obesitas simplex, 6-14 years of age, the triglycerides (TG), free fatty acids (FFA) and cortisol (F) levels in venous blood serum were estimated. In agreement with the development stages, studied patients were divided into the group of younger children in prematurity stage and the group of older children approaching the maturity. Obtained mean values of TG, FFA and F concentrations were analysed in the particular groups of obese children and compared with the healthy children of the same age. Mean concentrations of TG, FFA and cortisol in obese children were within the normal values and statistically did not differ from those of control healthy children. Also there was no difference in parameters studied if compared the younger and older groups of obese children. There was no interrelationship between the high birth weight and the degree of overweight as well as between the duration of obesity and the blood serum TG levels. In the course of obesitas simplex in children no detectable disturbances in the levels of TG, FFA and cortisol were found. It may depends on the more efficient adaptational mechanism connected with metabolism which are acting in the course of overfeed in the period of growth and development.


[Blood serum cortisol level in children with palatine and pharyngeal tonsil hypertrophy]. Because the etiopathogenesis of the Waldeyer's ring hypertrophy is not fully recognized, evaluation of adrenal cortex function in this disorders was made. Serum cortisol level was determined by sulfuric acid fluorescence under resting conditions and 3 hours after ACTH injection. Investigations were performed on 20 children, aged 5-9 years, in all of them a marked hypertrophy of palatine and pharyngeal tonsils was found. These children were divided into two groups, the first one included 11 children with frequent angina and the second group consisted of 9 children with serious difficulties in breathing, but without angina. In these groups serum cortisol levels were estimated before and 3-4 months post tonsilectomy or adenotomy. 11 healthy children of the similar age were included into a control group. It was found that in the first group (hypertrophy and frequent angina) initial resting and ACTH stimulated cortisol levels were statistically significantly higher than in the control group. In the same group 3-4 months post surgery serum cortisol levels were lower and similar to those found in control group. On the contrary, in children of the second group (hypertrophy without angina) the resting and ACTH stimulated serum cortisol levels were lower than in control group and these levels did not change 3-4 months after surgery.


[Birth weight and motor development of infants with Turner's syndrome]. There were analysed 61 cases of Turner's syndrome, in this group--48 cases with 45,X karyotype. Author confirmed, that mean birth weight of these children was lower (2920 g), than in healthy girls (3400 g), especially in cases with 45,X karyotype (2894 g). The 1st birth order in 45,X cases decreased birth weight of these children (mean 2693 g). The most retardation of motor development--3 months--in locomotion was observed. Between two genotype groups 45,X (mean 2894 g) and 45,X/46,XX (mean 3015 g) the difference was statistically significant.


[Evaluation of human strain during interrupted exposure to vibration (author's transl)]. The psychophysical reactions to stochastic vibrations transmitted in vertical direction to sitting man are investigated in simulated experiments under laboratory conditions. In the framework of an appropriate concept of assessment, indicators related to bottleneck situations in functional systems of the organism for activity and strain measurements allow the evaluation of the recreation efficiency of interruptions in exposure time. The special meaning of the distribution and thus the frequency rate of the interruptions can be illustrated particularly by the variance in time of the strain processes of selected muscles. Between the degree of muscle fatigue and the period of uninterrupted exposure time (expressed in "exposition-interruption-distribution") a significant correlation results so that numerous interruptions of vibration exposure should be considered as a profitable guideline for work design with respect to ergonomics.


Quantitative study of free amino acids in human eccrine sweat excreted from the forearms of healthy trained and untrained men during exercise. The free amino acids in eccrine sweat collected from the forearms of 20 healthy trained and 20 healthy untrained men during controlled exercise were determined quantitatively using ion exchange column chromatography. Sweat was deproteinized by adding an equal volume of 5% sulphosalicylic acid. The amino acid concentrations showed a constant qualitative pattern in sweat and large individual differences. Essential amino acids, such as isoleucine, leucine, lysine, methionine, phenylalanine, and valine were excreted in relatively small amounts. As compared to the trained men, untrained men showed statistically significantly higher concentrations in sweat for the following amino acids: Alanine, arginine, glycine, histidine, isoleucine, leucine, lysine, ornithine, phenylalanine, serine, taurine, threonine, tyrosine, and valine. No significant differences were found for citrulline, cystine, ethanolamine, and methionine. The comparison of the amino acid excretions in sweat obtained under controlled exercise and in urine showed that the amounts of amino acids excreted in sweat under controlled exercise were comparable to the losses of amino acids in urine.


Renal blood volume regulation in trained and untrained subjects during immersion. To study the cause of the increased blood volume of endurance-trained athletes we assessed the renal blood volume regulating mechanisms in eight untrained (UT) and eight endurance-trained (TR) male subjects during a 4 h head-out immersion. In TR plasma volume remained constant whereas it decreased in UT by 2.4 ml/kg (p less than 0.025). Immersion diuresis of TR was only half as high as in UT (peak values: 3.22 ml/min in UT, 1.60 ml/min in TR). Free water clearance remained approximately constant in UT but temporarily decreased in TR (p less than 0.001). This points to poor or even absent inhibition of antidiuretic hormone secretion in the latter group. Osmolar clearance increased less in TR than in UT (p less than 0.02) which was partly due to a delayed increase of glomerular filtration rate. Plasma osmolality, creatinine, and protein concentrations as well as hematocrit values were reduced during immersion to a similar extent in both groups. The results indicate a reduced renal response of endurance-trained subjects to congestion of the low-pressure system resulting in an increase in blood volume.


Kinetics of S-adenosyl-L-methionine in isolated perfused rat liver and its effects on microsomal enzyme activity. S-Adenosyl-L-methionine (SAMe) levels in liver tissue were reduced by 35% after isolation and washing of the organ. The apparent half-life of SAMe (1,75-25 microM) during liver perfusion was between 120 and 460 min; however the uptake of the labelled methyl group by hepatic tissue of fed rats was low (6%). This value increased to 12% in organs isolated from 24-hour fasted animals. Addition of SAMe to the perfusion medium increased tissue levels of ATP. Except for N-demethylation of aminopyrine and cytochrome c reductase, liver microsomal activity was not affected by treatment with SAMe either in vivo or/and in perfused liver.


Disposition and metabolism of [14C]loperamide in rats. Following oral administration of [14C]loperamide hydrochloride in 1 mg/kg to rats, plasma levels of radioactivity reached maximum at 4 hrs and decreased with a half-life of 4.1 hrs. Radioactivity in 96-hr feces accounted for 95% of the dose, with 30% associated with unchanged drug, while that in urine only 3.5%. Radioactivity in 48-hr bile accounted for 42% of the dose associated entirely with metabolites. 3% of the dose was found at the level of the enterohepatic cycles. These findings show that about 70% of the dose with absorbed by intestine, the target tissue of the drug, a portion (30%) of which was excreted back into intestinal cavity after demethylation, while the remaining 40% transferred to liver by which it was extracted mostly, metabolized extensively and excreted largely into bile, as supported by in vitro demethylating activity in gut segments but none in gut contents, and by in situ marked hepatic extraction of the drug. Main metabolic pathways involved are described.


The metabolism and excretion of 7-mono-0-(beta-hydroxyethyl) rutoside in the dog. Following i.v. administration of mono-HR to the beagle, plasma levels of both mono-HR and its glucuronide conjugates fell rapidly, neither being detectable 8 h after injection. Following oral administration of 14C-mono-HR, mono-HR-glucuronide was detected in plasma, confirming the absorption of mono-HR, and low levels of 14C were detectable up to 72 h after dosage. Following either oral or i.v. administration of mono-HR, the major route of excretion was fecal elimination of the compound as its aglycone form. Urinary excretion was slight being less than 15% following i.v. dosage and 4% following oral administration. Metabolism of mono-HR was confined to glucuronidation and hydrolytic cleavage of the glycoside side chain. Ring fission products of mono-HR were not detected.


The intestinal absorption and excretion of 14C drotaverin in rats. The absorption and biliary excretion of drotaverin/a papaverine analogue/were studied in rats. In vivo loop technique was used. The absorption of the compounds from the jejunum was found to be rapid and the activity injected into the duodenal sac to disappear only when the common bile duct was ligated. An appreciable activity was detected in the bile collected by cannulation following both i.v. (67%) or per os (31%) administration. Considerable activity was excreted with the bile even 24 hours after drug administration. A partial entero-hepatic cycle for the drotaverin metabolites is suggested.


Metabolic pathway of the diethylamide of trans-3-methyl-4-phenyl-3-butenoic acid, an hypolipemic agent, in the rabbit. The metabolism of the hypolipemic agent 3-methyl-4-phenyl-3-butenoic acid diethylamide (I) after oral administration to rabbits has been qualitatively investigated. Four main metabolites were identified in the urine of animals deriving from three different metabolic processes: aromatic hydroxylation, lactonization and N-dealkylation. All metabolites occured in free forms, were pharmacologically inactive and the unchanged starting drug was never recovered. The metabolic pathway of compound I was also compared with that of the parent non-substituted amide, 3-methyl-4-phenyl-3-butenamide (II). The fate of the two structurally related drugs was similar, except for hydroxylation of the carbon in the alpha position to the amidic group, occuring in compound II but not in compound I.


Pharmacokinetics of 2-phenyl-1,3-indandione in the rat after i.v. and oral administration. The pharmacokinetics of the anticoagulant drug, 2-phenyl-1,3-indandione, after i.v and oral administration in the rat might be best described as a non-linear open two-compartment model with elimination fromthe peripheral compartment. The volume of the central compartment comprises the extracellular fluid.


Evidence for adrenalin secretion regardless of high extraglandular levels. Chronic adrenalin administration (4 mg/18 hrs) by means of a subcutaneous depot capsule leads to hypoglycaemia and adrenalin depletion of the suprarenal gland within 18 hrs. Stimultaneous application of glucose prevents hypoglycemia as well as adrenalin depletion. By injection of 3H-labelled tyrosine 10, 20 or 30 min before killing and subsequent detection of the quantity of labelled tyrosine and adrenalin in the sera by mixing them with a standard solution containing considerable amounts of unlabelled tyrosine and adrenalin, and by passing them through a Sephadex G-10 column and finally detecting the radioactivity of the fractions in a liquid scintillation-counter, we could prove that during the stage of hypoglycaemia an enhanced adrenalin synthesis and secretion did take place regardless of a high extraglandular level. In animals treated with adrenalin and glucose, NaCl solution or alpha-methyl-tyrosine methylester-HCl no increased resp. no turnover at all could be seen. Therefore, we conclude that there is not only a lack of a direct negative feedback system between adrenalin synthesis, secretion and extraglandular level but also that the enhanced synthesis of adrenalin that can take place in spite of a high serum level can initiate a fatel circulus vitiosus.


Circadian rhythm of hepatocellular structures in rats dosed phenobarbital. The circadian rhythm of liver weight and hepatic structures was studied in rats given a maximum tolerated dose of 70 or 80 mg/kg/day Phenobarbital during 7 days and killed at four different hours of the following day. The drug-induced increase in liver weight in % of body weight of rats was about 1% in the morning and in the afternoon in comparison with controls. At 6.00--7.00 during the glycogen maximum, the fine structure of hepatocytes was normal except enlargement and glycogen depletion of cells in the near neighbourhood of central veins. From 9.00--10.00 the mitotic activity was markidly increased and parallel to the progressive disappearance of glycogen the smooth endoplasmic reticulum (SER) became prominent. Hypertrophy of SER was fully developed at 15.00--16.00 and 17.00--18.00.


Bladder calculi in rats treated with nitrosomethylurea and fed artificial sweeteners. Female Wistar rats treated once with nitrosomethylurea (NMU) by urinary bladder instillation were given saccharin, cyclamate or calcium carbonate in the diet for life. X-ray examinations were performed every three weeks to detect early formations of urinary bladder calculi, while an intravenous pyelogram and cystography served as a method for detection of neoplastic alterations. No statistical correlation could be established between the occurrence of urinary bladder stones and neoplasma in the various groups.


Hydroelectrolytic movements in rat jejunum during the alterations of the mucosa induced by a single injection of 5-fluorouracil. Transmucosal movements of water and electrolytes were measured in male Wistar rats, using the intestinal perfusion technique after a single intramuscular injection of 40 mg/kg BW of 5-fluorouracil. These movements were studied, daily during 6 days after the injection, in relation to the histological study of mucosa. The results (1) may explain the diarrhoea observed in patients treated with this antimitotic agent; (2) suggest the existence of a secretion in crypts, followed by an incomplete reabsorption by villi; the secretion of crypts or the villus reabsorption are alternatively the driving factor depending on the reciprocal size of villi and crypts.


Ano-rectal profile in adult megacolon.

Ano-rectal profile in adult megacolon. A number of parameters of ano-rectal function were measured in 10 patients with adult megacolon and the values compared to those in an age- and sex-matched group of normal volunteers. The absence of inhibition of force in the anal canal on rectal distention in patients with adult Hirschsprung's disease was the most constant finding although a group of patients were shown to have high resting and canal pressures resulting in megacolon. No constant sensory or myoelectrical abnormality was apparent within the anal canal. However, an unusual electrical rhythm was noted from the rectum in 1 patient with adult Hirschsprung's disease.


Uptake and metabolism of long chain fatty acids in isolated chicken intestinal epithelial cells. The uptake and metabolism of long chain fatty acids in isolated mucosal cells from chicken small intestine are studied. The viability of the isolated enterocytes is proven by linear oxygen consumption, CO2 and lactate formation form glucose and the active transport of glucose. The transport of palmitic and oleic acid is mediated by passive diffusion. This is demonstrated by the following results: (1) no saturation kinetics in the concentration range of 0.1--10.0 mM; (2) no competitive inhibition of the uptake by structurally related compounds; (3) no influence of 2,4-DNP and cyanide of the uptake; (4) the uptake is independent of sodium ions. Uptake rates of palmitic and oleic acid from suspensions are significantly higher than from the corresponding fatty acid-bovine serum albumin complexes. In both cases the uptake of palmitic acid proceeds faster than the uptake of oleic acid. Palmitic acid is oxidized to CO2 and incorporated into glycerides by enterocytes. Glucose serves as a glyceride-glycerol precursor. Its addition decreases the oxidation of the fatty acids and enhances glyceride synthesis markedly. Free glycerol is phosphorylated by enterocytes and can also serve as a glyceride-glycerol precursor.


Sampling error and observer variation in the interpretation of esophageal biopsies. Esophageal autopsy specimens from 11 subjects were used to determine observer variation and sampling error in assessing alterations attributed to gastroesophageal reflux. Inter- and intraobserver variation exceeded 20% even when the diagnosis was limited to a normal and abnormal reading. Marked differences in basal cell thickness but not in papillary height occurred when specimens were obtained from different levels of the lower esophagus. The differences were less marked in specimens obtained from the same level. Based on these data the reliability of basal cell thickness and papillary height as an index of gastroesophageal reflux appears limited.


In vivo and in vitro relationship between lipoprotein-X and bile salts in cholestasis. Bile salts have been shown to act on lipoprotein-X (LP-X) in vitro to induce a false-negative electrophoretic test. The aim of the present study was to investigate the relationship between serum LP-X and serum bile acids in patients with cholestasis. The in vitro concentration of bile salts required to induce a negative or reduced concentration of LP-X was also studied. There was no relationship, either positive or negative, between serum LP-X and bile acids in 34 patients with cholestasis. Serum was incubated with various saline solutions of taurocholic, lithocholic, deoxycholic and glycocholic acids. The concentration of LP-X decreased only after the final concentrations of bile salts were over 2,000 mumole/1. This is more than five times the concentration of serum bile salts usually found in patients with cholestasis. It is concluded that the negative LP-X test in some patients with cholestases must be explained by some other mechanisms than bile salts.


Relation between liver function and hepatocyte ultrastructure in a case of paracetamol intoxication. In a case of reversible paracetamol intoxication ultrastructural changes were correlated to changes in tests of microsomal and cytosolic liver function: the prothrombin index (PP) and the galactose elimination capacity (GEC), respectively. The decrease in the PP was at maximum after 2 days and in the GEC after 5 days, when the PP was normalized. Liver biopsies were taken after 1 and 5 days. Electron microscopy of the early biopsy revealed midzonal increased vacuolization of the endoplasmic reticulum (ER), detachment of ribosomes, and centrilobular mitochondrial injury. The late biopsy exhibited midzonal organelle-depleted areas with pale glycogen rosettes, perinuclear proliferating granulated ER, and centrilobular frank necrosis. These observations are in accordance with the concept that paracetamol-induced hepatocellular injury is due to damage to the membranes of the ER and indicate that the chronological dissociation of the liver function tests reflects the time sequence of the structural changes.


Coagulation abnormalities in diabetic coma before and 24 hours after treatment. A coagulation screen consisting of measurement of the prothrombin time, thrombin time, kaolin caphalin clotting time, platelet count, plasma fibrinogen level, fibrin degradation products and ethanol gelation test was performed on 24 patients with impairment of consciousness due to acute diabetic metabolic decompensation at the start of treatment and 24 hours later. 22 out of 24 patients showed at least one coagulation abnormality on admission of which the commonest were a prolonged prothrombin time, shortened kaolin cephalin clotting.time and raised plasma fibrinogen level. After 24 hours of treatment these values were more normal but 20 out of 22 patients still displayed some abnormality. 15 patients had two or more coagulation abnormalities on admission including 3 patients with haematological abnormalities suggestive of disseminated intravascular coagulation. This group was older and had higher blood ureas than those with fewer abnormalities, but plasma glucose, sodium, potassium and bicarbonate levels were similar in both groups of patients. All 5 patients with hyperosmolar non-ketotic coma and all 3 patients who died without recovering consciousness had two or more coagulation abnormalities on admission.


Antitumor effect of pyridine N-oxides having 1-(2-chloroethyl)-1-nitrosoureidoalkyl and 1-methyl-1-nitrosoureidoalkyl groups. Pyridine N-oxides having 1-(2-chloroethyl)-1-nitrosoureidoalkyl or 1-methyl-1-nitrosoureidoalkyl groups were evaluated for their antitumor activity against AH13 hepatoma and L1210 leukemia. Among them, 1-(2-chloroethyl)-1-nitroso-3-(2-pyridylmethyl)urea N-oxide (1), its tosylate (2), 1-(2-chloroethyl)-1-nitroso-3-(2-pyridylethyl)urea N-oxide (4), and 1-(2-chloroethyl)-1-nitroso-3-(3-pyridylmethyl)urea N-oxide (6) were highly active against both tumors in ip-ip system. These compounds were also active in ip-iv and ip-po systems of L1210. On the other hand, pyridine N-oxides having 1-methyl-1-nitrosoureidoalkyl group were all inactive against AH13 and weakly active against L1210. Effect on blood cells in Donryu rats bearing EDEN-5 erythroblastic leukemia cells was tested with these 1-(2-chloroethyl)-1-nitrosoureidoalkylureas. These compounds caused leucopenia and compound (4) was only slightly effective against EDEN-5.


Relationship of carcinogenicity, mutagenicity, and K-region reactivity in benz[c]acridines. Benz[c]acridine and its 10 methyl-substituted derivatives were examined for chemical reactivity with osmium tetroxide and mutagenic activity on Salmonella typhimurium, and the results were contrasted with the electronic charge in the K region and the carcinogenic activity of benz[c]acridines. The addition of osmium tetroxide took place at the K region of benz[c]acridines. A linear relationship was established between the charge in the K region and the rate constant of the second-order reaction between osmium tetroxide and benz[c]acridines except the 5,7-dimethyl derivative whose substituent in the 5-position sterically hindered the reaction. Benz[c]acridines showed mutagenic activity in the presence of S-9 Mix, but not in the absence of S-9 Mix. There was a corresponding relationship among the K-region reactivity, mutagenic activity, and carcinogenic activity in benz[c]acridines. The only exception for this was the 7,11-dimethyl derivative in which the 11-methyl group had a steric effect on the ring-nitrogen atom. It was suggested that a common mechanism with regard to the reactivity of the K region is working in both carcinogenesis and mutagenesis. It was concluded that benz[c]acridines are activated, before they display a carcinogenic or mutagenic activity, to a proximate form such as 5,6-epoxides, through a metabolic process in which the nucleophilic property of the K region to react with electrophilic reagents plays an important role.