Realizing that you don't understand: elementary school children's awareness of inconsistencies.

2 factors were proposed to affect awareness of one's comprehension failure: the inferential processing requirements, and the kind of standards against which comprehension is evaluated. These studies investigated elementary school children's awareness of their own comprehension failure when presented with inconsistent information. Study 1 showed that children were more likely to notice explicit than implicit contradictions. However, even 12-year-olds judged as comprehensible a sizable proportion of essays with seemingly obvious inconsistencies. Yet, the children had good probed recall of the information, the logical capacity to draw the inferences, and were not generally reluctant to question the experimenter. In subsequent studies children were (a) asked to repeat sentences in order to guarantee that the 2 inconsistent propositions were concurrently activated in working memory, and (b) warned about the existence of a problem in order to promote more careful evaluation. Taken together, the results suggest that to notice inconsistencies children have to encode and store the information, draw the relevant inferences, retrieve and maintain the (inferred) propositions in working memory, and compare them. Third through sixth graders do not spontaneously carry out those processes that they are capable of carrying out.


Acceptance of lack of closure: is it an index of advanced reasoning?

Lunzer reported data suggestive of a stage of cognitive development manifest between 9 and 11 years of age characterized by the ability to avoid drawing premature inferences when faced with ambiguity (i.e., accept lack of closure [ALC]). The present study sought to test this hypothesis. Inference tasks emphasizing ALC, memory, and hypothetico-deductive reasoning were administered to 67 males and 74 females (5-12 years in age). Although use of ALC increased with age, considerable use was evidenced on a simple task among 7-8-year-olds. On tasks hypothesized to place increasing demands on working memory, longer tasks were found to be more difficult. Marked improvement due to memory aids suggested that task difficulty results from limitations in working memory as predicted by Pascual-Leone's theory. Tasks requiring hypothetico-deductive reasoning were found to be most difficult. Performance was related to subject's spontaneous use of ALC. Lack of appropriate strategies was hypothesized to prevent solution rather than lack of logical competence. In conclusion, the relationship of ALC to age appears to be mediated by memory development rather than logical development.


The developmental relation between cognitive stage and the comprehension of speaker uncertainty.

3 hypotheses were tested concerning the developmental relation between children's concepts of physical uncertainty and their comprehension of a speaker's uncertainty. 2 cognitive tasks of physical uncertainty were used to assign 56 subjects (aged 5-4 to 17-11) to 1 of 3 cognitive stages. 2 tests for comprehension of speaker uncertainty were administered to all participants. The results indicated that cognitive stage was related to (a) comprehension that a speaker could be uncertain, (b) comprehension that uncertainty could be expressed in different degrees or magnitudes, and (c) the internal consistency of judgments made about the relative degree of uncertainty conveyed by an utterance. These findings are interpreted as evidence for the position that development of cognitive stages is structurally related to comprehension of speech act uncertainty.


The effect of active versus passive exploration on memory for spatial location in children.

The effect of active exploration upon memory for spatial location of an event was assessed for children at 2 age levels. Each child took a walk through the same unfamiliar hallway in search of a hidden object which he was later asked to relocate. Half the children were accompanied by an adult holding their hand (passive condition), while the other half proceeded on their own with an adult following behind (active condition). An age x condition interaction revealed that active exploration significantly improved performance of the 3- and 4-year-old group while not affecting the performance of the 9- and 10-year-olds. The 3- and 4-year-olds in the active condition, however, were still significantly less accurate than the older children, despite their experience of self-directed exploration. The results are interpreted as supporting the hypothesis that self-directed activity serves to increase attention of preoperational children to relevant topological cues in the environment, whereas concrete operational children, due to their knowledge of projective and Euclidean space, demonstrate increased capacity to efficiently encode spatial information regardless of the mode of exploration.


Perceptual development and category generalization.

This work is concerned with developmental changes in the structure of classifications. The central claim is that young children's undifferentiated perceptions of complex stimuli are highly structured by wholistic similarity whereas older children's perceptions are structured by component dimensions. It is shown in 2 experiments that young children systematically and spontaneously generalize a category if it is well organized by overall similarity but not if it is organized by a criterial dimension. Older children, on the other hand, spontaneously apprehend and extend a category by its dimensional structure. The third experiment was designed to test the hypothesis that criterial property categories are preferred in classification tasks requiring the explicit discovery of a general rule. It was found that younger children's attention to the dimensional relations within a category increases under rule-discovery instructions, although they still have difficulty ignoring wholistic similarity relations. The trend from similarity to dimensional classification is discussed in the context of Piagetian classification tasks and family-resemblance accounts of natural categories.


Infant perception of the invariant shape of objects varying in slant.

In a previous study employing habituation-recovery techniques, partial confirmation for shape constancy in 12-week-old infants was found. The infants may have been responding to changes in slant or slant-related cues, leaving unresolved the question of whether shape perception should be considered proximal (retinal) or distal (objective). In the present experiment 12-week-old infants were desensitized to changes in slant prior to test. Following habituation to a shape exposed at varying slants, magnitude of recovery was overwhelmingly greater for a different shape than for the same shape, indicating that the constant real shape of the habituated figure had been perceived across rotational transformations.


The relationship of visual attention to children's comprehension of television.

The study experimentally tested the relationship between visual attention and comprehension of a TV program. 72 5-year-old children watched a 40-min version of the TV program "Sesame Street." Half the children viewed the program in the presence of a variety of toys and half viewed without toys. The children were then tested for their comprehension of the program. Although visual attention to the TV in the no-toys group was nearly twice that in the toys group, there was no difference between the groups in comprehension. There were, nevertheless, significant within-group correlations between visual attention and comprehension even for questions concerning only auditorily presented material. The results were interpreted as indicating that in a normal TV viewing setting, variations in the comprehensibility of the TV program may determine variations in children's attention to the TV.


On the development of the augmentation principle: a perceptual approach.

Previous research in the development of causal schemata has relied upon verbal descriptions of behavior to convey causally relevant information. In the present study, however, a perceptual analogue of Kelley's augmentation principle was created in animated films depicting the movements of 2 objects toward a goal--1 which overcame an obstacle (inhibitory cause present) and 1 which did not (inhibitory cause absent). Both forced-choice and scalar measures indicated that kindergarten, second, and fourth graders all perceived greater motivation (internal facilitative cause) in the inhibited than noninhibited object, but that age differences emerged in the ability to explain these responses. In a second experiment, the 2 target objects were inhibited by obstacles of different sizes. For this quantitative version of the principle, age differences emerged for all measures; fourth graders and most second graders responded in accord with augmentation-principle predictions. These results were compared with the earlier findings that kindergarten and fourth-grade children did not understand this principle. The contrasting methods of stimulus presentation were discussed and implications of this technique for attribution research were noted.


The effect of delayed feedback on infant learning reexamined.

The study reexamines the effect of delayed reinforcement upon contingency behavior in 6- to 8-month-old infants and attempts to account for the temporal discrepancy between span of integration and contingency memory. A modified delayed-reinforcement scheduling procedure enabled a previous methodological criticism to be discounted. The findings confirmed that whereas infants revealed reliable acquisition under immediate reinforcement, a 3-sec delay (whether reset or nonreset) precluded response acquisition, as did 6-sec and 10-sec delay of reinforcement. The findings are interpreted in terms of an informational-load hypothesis which relates short-term memory to the integration and/or segregation of multimodal input.


The relation of conceptual tempo to aggression and its control.

The relationship of conceptual tempo to fantasy and overt aggression and its control was examined in order to test the generalizability of this cognitive style to domains of social and personality functioning. Fifth-grade boys and girls were administered the Matching Familiar Figures Test and a projective measure of fantasy aggression and its control and were rated sociometrically by peers and teachers on physical, verbal, and indirect forms of overt aggression. While reflective and impulsive children did not differ in degree of fantasy aggression expressed, impulsive children, especially boys, were found to exercise less control over their aggressive thoughts than the other 3 conceptual tempo groups. Impulsive and slow-inaccurate children were also more overtly aggressive, especially in comparison with fast-accurates. In addition, fantasy aggression predicted overt aggression in impulsives but not in reflectives. This study presents new evidence that conceptual tempo relates to areas beyond problem solving involving the child's social-emotional makeup.


Preterm infant interaction with the caregiver in the first year of life and competence at age two.

Caregiver-infant interactions were studied for 50 preterm infants and their primary caregivers. Naturalistic observations in the home were made when the infants were 1, 3, and 8 months of age. The social transactions in the first year were related to competence at age 2, thereby extending a previous report showing a moderate association between caregiver-infant interaction and competence at 9 months. The frequency of early social transactions was predictive of the infant's competence at age 2 on the Gesell Developmental Schedules, a sensorimotor scale, a measure of receptive language, and the Bayley Mental Scale. Early social transactions were as predictive of 2-year competence as were caregiver-child transactions at age 2. The study suggests that social transactions as early as 1 month reflect some quality of the relationship between the caregiver and the infant that is important to the child's later mental performance.


Measurement of infant difficultness.

The Infant Characteristics Questionnaire (ICQ) was developed as a short, factor-analytic screening device for difficultness. Responses of 322 mothers of 4-6-month-old infants suggested that they regard the fussy, hard-to-soothe, labile infant as difficult. Mother report on the ICQ, particularly on the main fussy-difficult factor was found to have adequate reliability over time and convergence with the Carey Survey of Temperamental Characteristics, with father report on the ICQ, and, to a lower degree, with home data collected by independent observers. It was also found that mother characteristics may affect perceptions of infant difficultness: multiparous, extraverted mothers tended to rate their infants as easy.


Predicting IQ from mother-infant interactions.

Longitudinal observations of maternal and infant characteristics were used to investigate the consequences of early day-care intervention for infants at high risk for intellectual retardation due to sociocultural factors. High-risk infants and their mothers were compared on social and intellectual characteristics with a control group not enrolled in an intervention program and with a random sample of mother-child dyads from the general population. Results from group comparisons indicated that mothers of high-risk infants in a day-care intervention group interacted with their infants in ways quite similar to mother of high-risk infants who were not enrolled in the intervention program. Both high-risk groups differed from the general population of mothers on interaction and attitudinal measures. Changes across time on the measures taken were roughly parallel from all three groups. Multiple regression analyses using maternal variables and mother-infant interactional variables to predict 36-month Stanford-Binet scores for the high-risk samples indicated that children's intelligence was predictable from previous maternal behaviors and attitudes, particularly for the control group, and that early day-care intervention apparently had altered the predictiveness of some maternal factors.


Attachment, positive affect, and competence in the peer group: two studies in construct validation.

2 studies were undertaken to assess the positive affective correlates of secure attachment in infancy and to assess the relation between secure attachment in infancy and competence in the peer group at age 3 1/2 years. In study 1, smiling and smiling combined with vocalizing and/or showing toys distinguished securely from anxiously attached infants during free play at age 18 months. Rated quality of affective sharing distinguished securely from anxiously attached infants during free play at 18 months and 24 months. Thus, secure attachment involves more than the absence of negative or maladaptive behavior directed toward a caregiver. Study 2 assessed cross-age, cross-situational, and cross-behavioral consistency in quality of social adaptation. Quality of infant-mother attachment relationships at age 15 months was related to Q-sort assessments of personal and interpersonal competence in the preschool play-group at age 3 1/2 years. The results contribute to the validation of attachment as an important developmental construct. They also suggest that age appropriate assessment of developmental social competence constructs can be a useful alternative to the study of homotypic behavioral continuity.


Efforts to control by children and adults with the type A coronary-prone behavior pattern.

Glass and his colleagues have suggested that the type A coronary-prone behavior pattern, which is characterized by competitiveness, aggressiveness, and impatience, is a response style aimed at maintaining and asserting control over poentially uncontrollable events. The present investigation examined the initial reactions of type A and type B boys and men to uncontrollable events. Children and adults pressed a button to earn nickels on one of the following schedules of reinforcement: a variable ratio of 7 or a fixed ratio of 7. The variable ratio schedule was assumed to appear less controllable than the fixed ratio schedule. The task was either of high or low salience (prominence). Results replicated previous research that type A's initially respond to highly salient uncontrollable events with more vigorous efforts to assert control than type B's. More importantly, the findings provided the first evidence that (1) the initial response to loss of control of type A and type B boys parallels that of their adult counterparts; and (2) the boys' response to the salience of the task is similar to that of their adult counterparts. Implications of the children's responses to uncontrollable events for the maintenance of type A behavior into adulthood and for the etiology of heart disease are discussed.


Sex and age differences in young children's reactions to frustration: a further look at the Goldberg and Lewis subjects.

This study reports 1-year follow-up data on the children originally observed by Goldberg and Lewis in a barrier frustration situation. Changes in reactions to frustration over a 2-year time span were examined for age and sex differences. Regardless of sex, over the first 2 years of life, barrier frustration was responded to with a decrease in stress and an increase in problem-solving behavior. The data suggest that sex differences in success at coping with the frustration may change with age and may be dependent on what behaviors are considered to be more instrumental in solving the frustration. Sex differences related to behavior in the barrier frustration were highly age specific. As previously reported in Goldberg and Lewis, at 1 year of age boys cried less and made more active attempts to get around the barrier than girls. However, at 2 years of age, girls vocalized more for help from the mother and made more attempts at problem solving than boys.


Environmental influences on vocational interest development in adolescents from adoptive and biological families.

Family influences on vocational interest development were studied by hypothesizing that parents with similar interests are more likely to have adolescents who also develop those interests than are parents whose interests are very divergent. In order to unconfound genetic and environmental influences, the 844 parents and adolescent children in 114 biologically related and 101 adoptive families completed the Strong-Campbell Interest Inventory. Parent-child interest difference scores were regressed on parent-parent difference scores (PPDIF), a dummy variable for family type, and the interaction between family type and PPDIF. For all parent-child pairs except mother-son, greater PPDIF scores predicted greater parent-child difference scores (indicating influence of family environment), and there was no family type X PPDIF interaction (indicating that the environmental influence was operating in both biological and adoptive families). Evidence of genetic variance in interest sytyes was also confirmed.


Synchrony in mother-infant interactions.

A measure of mother-infant synchrony was developed and used to compare the interactions of mothers with preterm and mothers with full-term infants. Each mother-infant dyad was observed during a standard bottle-feeding session on 3 separate occasions: once prior to hospital discharge and 1 and 3 months after discharge. Synchrony, defined by the correlation between mother and infant behavioral rates during corresponding segments of the observation session, was found to (1) distinguish between preterm and full-term groups at 3 months and (2) successfully predict below-average Home Observation for Measurement of the Environment (HOME) scores at 9 months for dyads in which mother and infant behavioral rates were inversely related. Further analysis identified certain interaction characteristics related to synchromy.


A developmental study of automatic word processing in a picture classification task.

Second-grade children, third-grade children, and adults judged whether pictures were members of a positive or negative memory set while trying to ignore irrelevant words printed inside the pictures. There were 3 types of picture-word relation. In 1 condition, the words corresponded to the pictures. In a second condition, the pictures and words were incongruent, but the words corresponded to the correct response (e.g., with dog and horse the positive set pictures, a picture of a dog containing the word "horse"). In the third condition, the pictures and words were incongruent and corresponded to conflicting responses. For all 3 subject groups, the type of picture-word relation reliably affected response latencies, indicating that subjects automatically processed the irrelevant printed words.


Performance on a stage IV object-permanence task with standard and nonstandard covers.

Piaget's description of object concept development is based on success in performing a series of search tasks. However, failure to perform successfully may result from undeveloped aspects of the cognitive or motor system unrelated to a concept of objects. This study examined the role of perceptual-motor development in a typical Stage IV task by comparing performance given a standard cloth cover or a small card cover. Subjects were 10 infants 147--187 days old (median age = 160 days). A pass was defined as the retrieval of the toy within 30 sec on 2 out of 3 trials. The difference in performance between the 2 cover conditions was significant (p = .032). These results advise caution in interpreting Stage IV performance in terms of a developing object concept.


Adjustment of reaching to change in object position by young infants.

4-month-old infants manipulated and fixated an object less when it was presented in a new rather than a familiar place. Evidence was also found for persistence of manipulation and fixation at the empty place previously occupied by the object. At 5 months, changing the position of an object had no effect on the manipulation and fixation of the same infants, and there were no signs of persistence of manipulation and fixation at the object's original place. A comparison is made between these changes in reaching and changes in tracking behavior. 2 hypotheses are considered to account for these changes, 1 based on the development of an object concept and the other on improvement of motor skill.


Internal radiation therapy of hepatic cancer.

Established cancer in the liver can, in selected patients who have a good arterial circulation in these tumors, be effectively treated by intrahepatic artery radioactive yttrium-90 resin microspheres. Even in unselected patients treated in the last five years by the author, 17 of 25 patients treated have had good objective regression of cancers, improvement of symptoms and prolongation of life. Treatment is relatively simple and associated with few side effects. For adjuvant therapy of colon cancer having positive nodes (Dukes C), internal radiation therapy of the liver is best done with Phosphorus-32 Colloid passed through the circulation of the gut to be effectively and homogeneously trapped by the Kupffer cells of the liver. Four such patients have been subjected to a pilot study--three of the four are doing well without significant side effects and no evidence of liver cancer after two years. When the fourth died of brain metastases, he too had less liver cancer than would be expected.


Colorectal schistosomiasis: clinicopathologic study and management.

Forty patients with colorectal schistosomiasis who failed to respond to medical therapy were studied. They had dysentery with bloody mucus and anemia, polyps, pericolic masses, and schistosomal ulcers. Two patients had cecal masses which appeared to be intussusception and appendicitis. Three patients had chronic intestinal obstruction. Diverting transverse colostomy, followed by other surgical procedures, is the safest method of management.


Left-sided colonoscopy in the office: a practical procedure.

Routine left-sided colonoscopy, instead of sigmoidoscopy, is a practical office measure. However, details of preparation and positioning of the patient are critical. The procedure has high productivity worth the added cost and effort. Cancer prevention is enhanced. Barium-enema examinations were found to have limited accuracy in polyp discovery, to a degree not previously appreciated.


Ileorectal anastomosis for inflammatory bowel disease: 15-year follow-up.

A personal series (E.S.R.H.) of 37 patients with inflammatory bowel disease, treated by colectomy and ileorectal anastomosis 15 years or more ago, is reviewed. Twenty-one patients (57 per cent) continue to be in satisfactory condition. Patients subjected to the two-stage operation have a notably lower rate of conversion to ileostomy than those treated by one-stage colectomy. One patient developed a carcinoma of the rectal stump. This 15-year review leads support to the opinion that ileorectal anastomosis has an important place in the treatment of inflammatory bowel disease.


A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. VII. Anal fistula: a simplified classification.

The pathology of anal fistulas was studied in 300 patients and a simple classification is put forward. Two main types of fistula are recognized: intrasphincteric and extrasphincteric, according to the relation of the track to the external sphincter. All fistulas start as a central space infection which either remains confined to the intrasphincteric compartment or spreads extrasphincterically. Intrasphincteric fistulas include both central and intersphincteric fistulas. The latter fistula, as well as the extrasphincteric, are either low or high according to the relation of the track to the levator plate. The classification is simple and practical. It clearly demonstrates the precise anatomic position of fistulas as related to anal musculature so proper planning for the treatment can be safely achieved.


Method for determining individual contributions of voluntary and involuntary anal sphincters to resting tone.

With simultaneous recordings of the external anal sphincter EMG activity and the anal resting pressure, it is possible to estimate the isolated part played by the internal anal sphincter on the resting pressure by means of a correlation calculation with extrapolation to zero EMG amplitude. The value of the method was proven by comparative investigations in conscious and curarized patients under general anesthesia. In a group of 20 normal people we found that the part the internal sphincter has in the total resting pressure was 75 per cent. Because of the very low standard deviation of +/- 5.5 per cent the method is superior to others for comparing various anal disorders.


Recurrence of volvulus after sigmoidectomy.

Three patients had recurrences of left-sided colonic volvulus after allegedly total resections of redundant sigmoid loops. All three patients had chronic, acquired megacolon. Other instances of late recurrence of volvulus after sigmoidectomy are documented in the literature. Sigmoidectomy may be an inadequate operation for sigmoid volvulus in younger patients and/or in patients with severe chronic megacolon. The decision to perform an interval operation and the selection of the type of operation must take this into account.


A short survey on experimental studies with relevance to vascular use of metrizamide.

Metrizamide was originally developed for application in the subarachnoid space. Later the contrast medium was tested for angiographic possibilities in extensive animal experiments. The effects of metrizamide, as examined successively on the kidneys, liver, lungs and heart, were compared with those of ionizing contrast media. The effect of metrizamide on the kidneys and liver proved similar to those of the ionizing contrast media but the toxic action of metrizamide on the remaining organs was found to be smaller.


Risk-decreasing factors in the angiographic examination of intracranial haemorrhage.

The neuroradiological examination in patients with clinical symptoms of intracranial bleeding is indicated in a high percentage of cases, especially since large series of CT examinations have proven that in many cases the false clinical diagnosis of cerebrovascular accident is made with patients actually bleeding out of arterial lesions. In a large number of cases angiography will be necessary in addition to CT examination. Naturally the complications which may occur with these angiographic procedures should be avoided as much as possible. Measures to minimalize the haemodynamic effect of catheterization or puncture and the following contrast injection in the brachiocephalic vessels are discussed. The application of metrizamide as a contrast medium with these angiographic analyses is explained.


Patient reactions in angiography of the head and neck using an ionic and a non-ionic contrast medium.

In a group of 51 patients metrizamide was compared in a double-blind fashion to meglumine ioxithalamate, the contrast medium currently in use at our department, with regard to sensations of warmth or pain elicited by the intra-arterial contrast injection. In all arteries of the head and neck metrizamide injections produce less painful reactions than injections of meglumine ioxithalamate. This difference, however, is statistically significant only for the external carotid and for the vertebral arteries, as pain reactions are much less often elicited in other vessels. It is concluded that in neuroradiology the favourable properties of metrizamide with respect to pain responses can best be utilized in 'sensitive' vascular areas (superselective external carotid angiography, spinal angiography, vertebral angiography).


Angiography with metrizamide in neuroradiological examinations.

A summary is given of the results of vascular studies with metrizamide (Amipaque) in four territories: four-vessel studies in children under 1 year of age, vertebral angiography in adults at risk, spinal angiography and superselective studies in the external carotid territory. A comparison is made with the results obtained with meglumine iothalamate and meglumine ioxithalamate.


Peripheral angiography with metrizamide.

Metrizamide, tested in 41 patients, caused less discomfort than injection of Isopaque Cerebral, when injected into the abdominal artery. In view of the high price of metrizamide, it is indicated for what angiographic studies the Malmö General Hospital employs this contrast medium.


New low osmolality water-soluble contrast compounds in selective arteriography of the peripheral limbs. A comparative study.

Metrizamide (Amipaque) and ioxaglate (Hexabrix), both new low osmolality contrast agents, were evaluated in a comparative study of 50 patients with peripheral arterial diseases undergoing in total 118 angiograms. The degree of discomfort caused by the highly selective injection of these compounds and the normal available water-soluble media was estimated. Metrizamide resulted as the optimal contrast medium and Hexabrix is second best. Intra-arterial lidocaine reduced serious discomfort from 70 to 15% in conventional media. None of the evaluated contrast compounds was changing blood flow in this group of patients. But pharmacoangiography with high dosages of tolazoline could provide additional information on vascular pathophysiology.


The venous phase in hand angiography.

It has been found that the venous phase of hand angiography can be reliably visualized with metrizamide. There are indications that the venous phase can provide important information on the validity of fingers with arterial occlusion.


Amipaque in coronary angiography.

Comparative studies between Isopaque Coronar and Amipaque with equal concentration of iodine (370 mg I/ml), have been carried out in more than 130 patients. Hemodynamic and electrocardiographic registrations before, during and after selective coronary angiography showed that the diastolic blood pressure and heart rate decreased significantly less with Amipaque, while no significant differences were observed in various ECG parameters. Interestingly, it was observed that the left coronary artery contrast transit time was longer when using Amipaque. This phenomenon may reflect a difference between ionic and nonionic contrast media, but also a difference in viscosity. The quality of the angiograms was the same irrespectively of the contrast medium used.


Use of metrizamide in coronary arteriography.

In the investigation of the arteriae coronariae by means of angiography, a comparative study has been done of two contrast media in the same patients, by injecting these media in a randomized order. The contrast media are sodium methylglucamine diatrizoate (10:66) and metrizamide, both used in a concentration of 370 mg I/ml. The reaction of the heart was registered in different ways with which also the influence on the blood pressure was measured. The quality of the films was judged by persons who were not acquainted with the sequence of the injections.


A comparison of Isopaque Coronar 370 and Amipaque in angiocardiography in infants.

Experimental studies and some clinical investigations have indicated that Amipaque (metrizamide) is less cardiotoxic than other contrast media in common use for angiocardiography. It, therefore, seemed motivated to find out whether these findings are valid in the high-risk group of neonates and small infants subjected to angiocardiography.


Comparative study in angiocardiography in children, evaluating the side-effects of non-ionic and ionic contrast media.

The study concerns 127 consecutive patients, presenting congenital heart disease, with an age distribution from neonatal to 15 years (mean 5 years). With non-ionic Amipaque, 164 injections were performed, with ionic Isopaque Coronar 81. Isopaque Coronar caused in 51% of the cases a clear discomfort for the patient; with Amipaque the side-effects were reduced to 9% (p less than 0.001). The mean body temperature rise with Amipaque was only 0.09 degrees C, against 0.28 degrees C with Isopaque Coronar (p less than 0.001). The changes in the heart rate reached 8.35% with Amipaque and 15.2% with Isopaque Coronar (p less than 0.001). Amipaque caused a mean of 1.8 extrasystoles per injection; Isopaque Coronar 2.2 (p less than 0.05). The quality of the angiogram with Amipaque was quite better than with Isopaque Coronar (p less than 0.0025). The non-ionic Amipaque is a much safer and better tolerated compound that the ionic Isopaque Coronar for paediatric angiocardiography.


Side-effects at phlebography with ionized and non-ionized contrast medium.

In two studies 267 consecutive patients with suspected venous thrombosis were examined 125I-fibrinogen uptake test at phebography. In 161 patients meglumine metrizoate (Isopaque Cerebral) and in 106 patients metrizamide (Amipaque) was used as contrast medium. The quality of the examinations was equal in the two groups. During the examinations most of the patients examined with meglumine metrizoate had symptoms from the calf described as a cramp-like pain. Only few of the patients examined with metrizamide had such symptoms. In the two groups 47 patients examined with meglumine metrizoate and 41 examined with metrizamide had normal phlebography as well as initially normal 125I-fibrinogen uptake test. After phlebography, 29 of the patients in the first group had a significant rise in fibrinogen uptake while such a rise was not found in patients from the second group. Rephlebography showed fresh deep vein thrombosis in 7 out of 9 patients examined with meglumine metrizoate indicating that thrombosis could be provoked in as many as about half the patients with this high osmolar contrast medium. We have now used metrizamide in about 400 patients without any side-effects.


Thrombosis after phlebography?

In contrast to the report by Albrechtsson, we have never seen clinically manifest thrombosis in more than 20,000 phlebographies; only small, clinically insignificant thrombi in a very few cases. The reason is because we have used only 40 cm3 of a 45% contrast medium in connection with heparin precaution. However, there is the possibility that the deep venous valves are damaged. Therefore Amipaque is important for the phlebography. Our test, 20 cm3 45% conventional contrast medium injected directly into varicose veins, always gives a venous thrombosis of about 20 cm. The same amount of Amipaque has never shown a reaction.


Lumbar epidural double-catheter venography with metrizamide (Amipaque).

Epidural double-catheter venography may be considered as a most reliable method of demonstrating lumbar disc herniation. In our case material the diagnostic results proved to be more accurate than the results of lumbar myelography, especially when very lateral disc herniations are concerned. In the operated patients the diagnostic accuracy of the venograms was 94% versus a myelographic accuracy of 85%. Systematic use of two catheters and simultaneous contrast injection provides the possibility to obtain homogeneous filling and excellent opacification of the anterior epidural veins at any lumbar level. During the procedure a choice can be made out of over 20 catheter position combinations to obtain good quality venograms. In 40 patients metrizamide (Amipaque) is used as a contrast agent in an iodine concentration of 350--370 mg/ml. This concentration does improve the opacification of the epidural venous plexus, providing better diagnostic information. Metrizamide causes hardly any discomfort to the patient, even when 50--70 ml are injected within 5 sec.


Angiographic and microradiographic demonstration of the linear vascular pattern in renal neoplasms.

The linear striated vascular pattern in the kidney is discussed in the light of nine new examples. Based on the histomicroangiographic findings in 2 cases, the pathogenic mechanism underlying this phenomenon is discussed, and the pattern is considered a sure sign of venous tumor infiltration.


Angiographic appearance of benign retroperitoneal lymphoma.

The authors report on a quite unusual case of the very rare angiofollicular lymph node hyperplasia (Castleman's tumor). This one appeared as a large retroperitoneal mass. According to the anatomical structure, the X-ray showed it as being obviously malignant.


Arteriovenous malformation involving the galenic system. A chance finding in an elderly female.

An elderly female being treated for an unrelated medical condition was found to have an arteriovenous malformation involving the vein of Galen. The florid radiological features are described, including the computed tomogram (CT) appearances. The pathology and usual modes of clinical presentation are reviewed. This patient is the oldest yet described with an arteriovenous malformation involving the Galenic system. It is suggested that the condition is more common in adults than previously thought.


Embolization of the arteria iliaca interna as treatment of life-endangering haemorrhages caused by intrapelvic malignant tumours.

Embolization of the arteria iliaca interna was employed to treat the severe, life-endangering haemorrhage in 8 patients with inoperable bladder tumour, 3 patients with uterine cancer (2 carcinoma colli uteri stage IIIb, 1 carcinoma corporis uteri stage III), and 1 patient with richly vascularized sarcoma, infiltrating the walls of the rectum and the vagina. Percutaneous catheteral embolization of the arteries of the haemorrhagic pelvic tumours is considered an intervention with little risk and accompanied by moderate general stress. In the treatment of tumourous patients under appropriate technical conditions, it is a suitable procedure for the prevention of fatal haemorrhage.


The feet in diabetes. Roentgenologic observation in 1501 cases.

The manifestations of diabetic osteoarthropathy are described. Computerized analysis of the films of the feet of 1501 diabetic patients showed one or more lesions in 55% of patients. Exostosis (36%), vascular calcifications (25%) and osteoporosis (12.2%) are by far the most frequent symptoms. Geodes (3.7%), destructive lesions (3.9%), sclerosis (4%) and articular lesions (5.1%) are second in frequency. Osteolytic lesions and reconstruction showed a high female predominance, whereas sclerosis is predominant in males (61.6--38.4%).


[Recanalization by catheter of the occluded artery after acute myocardial infarction (transluminal recanalization (author's transl)].

Using guide-wires and special catheters the occluded infarct-related coronary artery was recanalized in 10 patients with acute myocardial infarction 6.6 +/- 7.1 hours after the onset of symptoms. There were no complications. Immediately after recanalization there were 80-95% lesions at the site of the previous occlusion. Angiography, performed in 9 patients in the chronic stage of myocardial infarction, revealed patency of the recanalized vessel in all instances. There was a marked decrease in the narrowing at the time of the second angiogram in 6 patients. Changes in left ventricular function from the acute to the chronic stage were assessed in 8 patients: the ejection fraction increased in 6. The results of this pilot study indicate that transluminal recanalization of acutely occluded coronary arteries is possible without harmful side-effects. Early restoration of flow may salvage the jeopardized myocardium. Further application of this method of treatment in selected patients and efforts to improve the technique seem to be justified.


[Possibilities of treatment reduction in Hodgkin's disease (author's transl)].

Exploratory laparotomy with splenectomy was performed before or after multiple chemotherapy in 182 patients with clinically localised Hodgkin's disease in clinical stages IB, II3A, IIB, III A and III B. There was a 50% probability of clinically not diagnosed infradiaphragmatic involvement in patients with clinically localised stage IB, II B or II3A. Restaging was necessary in 20% of patients with clinical stage III, because infradiphragmatic involvement was histologically not demonstrable. Infradiaphragmatic involvement occurred in 12% of patients who had received six chemotherapy cycles according to the MOPP scheme, before exploratory splenectomy. When chemotherapy produced complete clinical remission, only 2.7% patients had any infradiaphragmatic involvements. Exploratory laparotomy with splenectomy is not required, therefore, in such patients.


[Tetanus antibody determinations in children (author's transl)].

Tetanus antibody determinations in 109 children aged 1 1/2 to 15 1/2 years showed that 98.2% had a sufficiently protective tetanus antitoxin titre. There were no significant differences between completely and incompletely first immunised children. Increased titres of up to 25 IU/ml serum were found shortly after multiple boostering. According to the observed titres boostering after trauma is at the earliest necessary after 5 years in complete or incomplete primary immunisation or after the last boostering. Passive immunisation is only indicated in the traumatised non-immunised and in patients with wounds of larger standing who have not been immunised for more than 5 years.


[Total and free testosterone in the male depending on body weight (author's transl)].

Total testosterone, the fraction of unbound testosterone and free testosterone were measured in 116 males of varying body weight in the range of 80 to 256% of the ideal weight. There are 3 groups for the establishment of normal ranges of testosterone. Testosterone and the fraction of unbound testosterone were fairly constant in group I (80--160% of the ideal weight). In group II (160--200% of ideal weight) there was a tendency towards lower values. The relatively wide normal range for testosterone was not reached in only 5 of these 20 patients. In contrast, in group III (more than 200% of ideal weight) clear-cut changes of total testosterone were demonstable reaching only 38% (P less than 0.001) of control values. Changes were also clear for unbound testosterone which increased from 2.24 to 3.9% (P less than 0.001). The concentration of free testosterone decreased to a lesser extent (P less than 0.01). Despite the low total testosterone hypogaonadism was not demonstable clinically in the extremely obsese patients. According to these results "normal values" for total testosterone, the fraction of unbound testosterone and free testosterone could be established depending on body weight.


[Massive obesity with disturbance of glucose tolerance (author's transl)].

A long-term study of 63 extremely obese persons with disturbed glucose tolerance showed a further deterioration of glucose tolerance over 10 years. In 9 out of 23 patients manifest diabetes mellitus developed despite partial weight reduction (greater than or equal to 10% of the initial weight excess). Out of 14 patients who did not lose weight during this time even 11 developed manifestations of diabetes. All patients who were in different weight groups at the 5- and 10-year follow-up showed a deterioration in glucose tolerance after 10 years. In the individual groups there were only minimal differences in other characteristics apart from the different weight behaviour.


[Interaction of quinidine and digoxin in humans (author's transl)].

After full digitalisation, 11 healthy subjects received 0.375 mg digoxin daily as maintenance dose. Under steady-state conditions and determination of serum concentration and renal clearance of digoxin, they were then given 500 or 1000 mg quinidine daily in addition to the digoxin. While serum concentration of digoxin rose significantly from 0.75 +/- 0.2 ng/ml after one week on 500 mg quinidine, and to 1.8 +/- 0.6 ng/ml after 1000 mg of quinidine, renal digoxin clearance fell from 186.2 +/- 67.4 to 125.4 +/- 61.8 ml/min after 500 mg of quinidine. Raising quinidine dosage to 1000 mg daily caused no further digoxin clearance reduction. During the total experimental period endogenous creatinine clearance remained unchanged. The results indicate that the rise in serum digoxin concentration on simultaneous quinidine administration is largely due to reduction in renal digoxin clearance. A clinical observation confirms the considerable practical importance of this interaction.


[Nosocomial infections (author's transl)].

Within 3 years 2546 nosocomial infections were registered among 18 897 hospitalised patients of a gynaecological-obstetric university hospital, Results were obtained in a prospective study on the use of nurses specially trained in hygiene. The incidence of nosocomial infections was 13.5% including predominantly asymptomatic bacteriurias and 3.9% without bacteriurias. It was higher after major surgical intervention and lowest in pregnant women, postnatal patients, vaginal deliveries and minor operations. Bacteriurias were the most common infection in all patient groups. They made up 71% of the total, followed by postoperative pelvic infections (7.3%), phlebitis at the site of infusion (6.5%) and abdominal wound infection (4.2%). During the control programme, introduction and reinforcement of various hygienic measures and continuous instruction and control of the wards and treatment rooms by the specially trained nurses the incidence of all nosocomial infections decreased by 48.1% and of urinary tract infections by 42.7%.


[Henoch-Schoenlein purpura (author's transl)].

Routine EEG investigations and observance of discrete neurological and psychological symptoms in 13 children in the acute phase of Henoch-Schoenlein purpura showed that involvement of the central nervous system in this disease is the rule rather than the exception. Capillary resistance was reduced in 51 out of 76 investigated children. On the other hand a reduction in factor XIII activity was much less commonly found (n =6). Immune complex determination in 28 children, together with antibody studies, showed that in 13 of them the Henoch-Schoenlein purpura was triggered off by an influenza-A-virus infection of the upper respiratory tract. Two thirds of the patients had markedly raised levels of total serum complement which fell weeks within several.


[Results of treating acute nonlymphoblastic leukaemia in adults (author's transl)].

Between July 1974 and December 1976 a total of 69 patients were treated for acute nonlymphoblastic leukaemia. The mean age was 42 years. Seven had been previously treated. Induction treatment with daunoblastin and cytarabine was given to 67 patients. It produced complete remission in 37 (55.2%) and partial remission in two. Twelve patients received a minimum of two courses of induction treatment without remission (definite treatment failures). Sixteen patients died during the first 30 days after onset of treatment. Treatment to maintain remission consisted of cytarabine and alternating 6-thioguanine, cyclophosphamide, lomustin and daunoblastin. Treatment could be continued as planned in only a quarter of the patients, because of serious side effects in the others. One year after conclusion of the study (31. 12.77) the median remission period was 42, median survival time for all patients 33 weeks (73.5 weeks for those responding and 8 weeks for those not responding to treatment). Age, fever, and chromosomal status of bone-marrow cells had an effect on prognosis.


[Differential diagnosis of hypercalcaemia by measurement of renal calcium excretion during parathormone administration (author's transl)].

Rapid differential diagnosis of hypercalcaemia due to primary hyperparathyroidism or malignancy with or without bone metastases may be life saving. A parathormone infusion test (6 USP units/kg body wt X 20 min) enables a differential diagnosis within three hours by means of measurement of renal calcium excretion. In normal persons calcium excretion decreased from 147 +/- 90 to 79 +/- 54 mumol/h (x +/- s, n = 10). In primary hyperparathyroidism with hypercalcaemia the high calcium excretion remained unchanged: 716 +/- 162 mumol/h before and 804 +/- 130 mumul/h 120 minutes after the PTH infusion (n = 12). In patients with hypercalcaemia caused by bronchial carcinoma with (n = 5) and without (n = 1) bone metastases calcium excretion decreased from 552 +/- 182 to 163 +/- 114 mumol/h. As a consequence of these data this test is advisable when the indication for operation in cases with hypercalcaemia has to be reached within a few hours.


[Frequency of peripheral arterial occlusive disease in patients with coronary heart disease with and without infarction (author's transl)].

In 107 consecutive patients the frequency of peripheral arterial occlusive disease in coronary heart disease was assessed by selective coronary angiography and sonographic Doppler pressure estimation. Among 75 patients with coronary heart disease 21 (28%) had arterial occlusive disease, among 32 patients without coronary heart disease only one (3%). There was no statistically significant correlation between the severity of both diseases. 40 out of 75 patients with coronary heart disease had suffered from cardiac infarction. Infarction frequency showed a highly significant correlation with increasing severity of the coronary heart disease, but none with increasing severity or frequency of arterial occlusive disease. When there was no arterial occlusive disease all degrees of severity of coronary heart disease were found. Analysing the literature it becomes evident that coronary heart disease is frequently an isolated or premature manifestation of arteriosclerosis.


[Thoracic actinomycosis with superior vena cava obstruction (author's transl)].

In a 40-year-old farmer's wife presenting with fatigue, shortness of breath on exertion and occasional extrasystoles a space-occupying lesion of the mediastinum leading to obstruction of venous return in the superior vena cava was found. Prior to intended surgery the patient suddenly died following cerebral haemorrhage. Actinomycosis of the mediastinum leading to almost complete stenosis of the superior vena cava was found at necropsy.


[Ultrasonographic diagnosis in disturbances of early pregnancy (author's transl)].

Ultrasonography using high-magnification, modern ultrasonographs enables information on intactness of pregnancy in early disturbed pregnancy. The ultrasound findings can be correlated with the clinical diagnoses, such as incomplete abortion. A final diagnosis, such as missed abortion, can frequently only be made after exact ultrasonographic investigation. The failure rate depends on the equipment and the experience of the investigator. Exact knowledge of the gestational age clearly influences the accuracy of an ultrasonographic diagnosis in early pregnancy. A gestational age earlier than the calculated one may be mistaken for a pregnancy that is no longer intact.


[Goitres with "cold" nodules in an endemic goitre area (author's transl)].

Of 339 goitres with "cold" nodules 17.7% were histologically malignant. Related to all cold nodules which were examined, this suggest a "true" malignancy rate of nodules of about 0.4%. The risk of malignancy is highest in patients over 60 years of age. The malignancy rate was high, at 23%, in cold nodules of recurrent goitres. Fine-needle aspiration biopsy pre-operatively will correctly diagnose over 90% of malignant nodules.


[Treatment of diabetic patients with insulin resistance and allergy using des-phe-insulin (author's transl)].

Eleven patients were treated with pure porcine des-phe-insulin (Insulin 02S Hoechst). In seven patients insulin 02S was used because of high insulin requirements. Three cases were treated successfully, one case moderately successfully, there was no success in two cases and in one case the result remains to be seen. In more than half of the patients a considerable decrease of  insulin requirement could thus be achieved. Four patients received insulin 02S because of allergy. Success was evident in three cases and at least probable in the fourth case. Results up to now showing less immunogenicity and antigenicity of des-phe-insulin seem to be confirmed clinically.


[Correlation between genome mutations and the cell division types in immunological sensitization states].

The authors examined the frequency of cells with polyploidy-P, with amitot division-AD and with mitotic division-MD in 25 patients with schizophrenia and proven anticerebral autoimmune sensibilization by means of blast-transformation test-BS, in 20 partners of marriages with multiple spontaneous abortions and suspected isoimmunization-PCA as well as control group of 63 healthy adults and newborn infants. Simultaneous increase of the frequency of cells with polyploidy and amitotic division was established in patients with schizophrenia--1,16% of P and 0.40% AD in 4 women with spontaneous abortiosn -- 1.5% of P and 0.80% of AD compared with the control values of 0.54% of P and 0.17% of AD. The highest percentage P -- 1.12 and AD -- 2.1 was found in BS with chronic process, in whom the blast-transformation reaction to brain antigen --34% was mostly manifested. In the cultures of BS, treated with brain antigen, AD reached up to 1.38%. The increase of AD was accompanied with lowering of mitotic index: BS -- 1.2% of MD and 0.40 of AD; PSA -- 2,04% of MD and 0.50 of AD compared with the control values of 4% of MD and 0.17% of AD. The results showed that immunologic sensibilization was accompanied by an increase of genome mutations and amitotic division and with lowering of mitotic index; they revealed polyploidy and amitotic division as compensatory mechanisms of the organisms under certain conditions.


[Sulfhydryl and amino groups in the cell fractions of white rat tissues: ontogenetic characteristics].

The author investigated total protein, percentage of protein sulfhydril and amino-groups of those in the cytoplasm and total sulfhydril groups in mitochondria, lysosomes and cytoplasm in liver, kidney and spleen of rats. There was a tendency to an increase of total protein in single tissue components with the advancement of age. The amount of sulfhydril groups was altered with advancement of age as well. Their maximal value was in animals, aged 5 days. In all examined cell fractions there was a statisticaly significant lowering in the subsequent age group, which tendency continued till the end of the examined period (5, 10, 15, 20, 25, and 30 -- day rats). The changes, observed in amino-groups were statisticaly significant and reflected the specificity in the metabolism of the three examined organs in accordance with their functions. Statistificaly significant lowering of the present sulfhydril groups, determined by DYNB, and nonsignificant changes of amino-groups showed that proteins in the examined tissues exposed various amount of sulfhydril groups probably due to the various water content of the tissues at different age periods. Perhaps there could be an effect of other factors as well, having connection with oxidation and reduction of sulfhydril groups.


[Effect of bee venom and its low- and high-molecular fractions on embryogenesis in rats].

The authors injected 3 groups of pregnant rats with 1/5 of LD50 of whole bee venom and its low and high weight molecular fractions daily between the 6th and 14th day of gestation. The embryos of the treated animals, aged 20 days, showed a reduction of the weight and dimunution of the activity of lactate dehydrogenase and isocitrate dehydrogenase in their liver homogenate. There were autolisis and dead rats in the uterus of the treated animals (embryotoxic effect). There were no teratogenic alterations. The low weight molecular fraction of the bee venom revealed more manifested embryotoxic effect.


[Comparison of 2-aminopyridine, 3-aminopyridine and 4-aminopyridine hydrochlorides and iodomethylates by the degree of decrease in curare toxicity].

The authors carried out studies on rats with apnoea, indiced by (+)-tubucurarine and found protective action, due to galantamine, neostigmine, hydrochlorides and jodometilates of 2-aminopyridine, 3-aminopyridine and 4-aminopyridine. Jodmethylates had protective action in larger doses in comparison with the respective hydrochlorides of nonsubstituted pyridilamines. The authors proposed a method for determination and comparison of the effect of compounds, eliminating the action of antidepolarizating myorelaxants, on tubocurarine toxicity.


[Mechanisms of hexobarbital anesthesia potentiation by hydrocortisone].

The authors carried out studies on white rats of Wistar strain and investigated some of the mechanisms, metabolic and central, by means of which hydrocortisone affected hexobartital sleep. They established that hydrocortisone in dose of 25 and 50 mg, administered singly, together with hexobarbital or after a 30-minute interval, potentiated hexobarbital sleep significantly. The concentrations of hexobarbital in blood serum and in brain on the 30th minute after its administration were higher in the experimental animals, treated with hexobarbital in comparison with the controls of both sexes. The experiments with determination of the activity of liver microsomal hexobarbital enzymic system showed convincingly a considerable inhibition of enzymic activity (with 53%) of hydrocortisone after 20 minutes after its application in vivo. Subthreshold sreep dose of hexobarbital, determined by the method of Lewy, was lowered than that of the experimental group and higher in the control rats. Hexobarbital concentrations in blood serum and in brain at the moment of waking were lower in experimental animals, treated with hydrocortisone, and higher in the control animals. The obtained results gave foundations to the authors to assume that metabolic and central nervous mechanisms participated in potentiation of hexobarbital sleep.


[Ultrastructural manifestations of the secretory function of the chondrocytes in elastic cartilage].

The authors examined ultrastructural manifestations of the secretory function of chondrocyetes in the auricular tendon of rats. They found that chondrocyetes were active secretorily in the prenatal and early postnatal ontogenesis; in later age such activity possessed mainly those chondrocytes located subperichondricaly. The existance of direct communications of cysternas of the granulated endoplasmic reticulum with extracellular area was interpreted as a possibility for direct release of the secretory products. Small coated vesicules with dense content were followed-up from the Goldi's organs till their openings on the cellular surface. Two types of vacuoles were differentiated-some with optically dense content, localized in the Goldi's organs, and others-optically empty, which were encountered in their boundaries as well. A concept was given that the first type originates from the granulated endoplasmic reticulum and transported protein product, but the second type-from the Goldgi's complex and transported probably polysaccharides.


[Dynamics of the restorative processes in the liver in chronic poisoning with zolon].

The authors examined the dynamics of the repairing processes in liver of rats after 2 and 4-month intoxication, caused by the phosphor-organic preparation ZOLON. They found that the changes in liver were reversible at this length of intoxication. Glycogen and RNA storage recovered almost to their initial values. Kupffer's cells were hyperplastic and the number of two-nuclear liver cells was increased diffusely in the lobule. The changes in the vascular walls of the periportal areas persisted. The degree of the repairing processes in liver depended on the dose used and the duration of the action. The obtained data could be taken into consideration in preparing hygienic and prophylactic measures for the individuals working with this preparation.


[Appropriate and inappropriate use of foreign words in the language of Bulgarian experimental medical disciplines].

The authors make an attempt to indicate inappropriate usage of some frequently used words and expressions in the medical literature, adopted in the Bulgarian language most frequently from the English language. They stress to keep close to the classical languages-Greek and Latin, which are at the base of the medical terminology. The authors present examples of words from contemporary languages, which are universally accepted and in which the semantic purity of the native language could lead to pedantry and vagueness. They point out that the concepts with smaller volume could be expressed by the most suitable words from the Bulgarian language, for example the names of methods or concepts, describing private regularities.


[Irrigation of the internal organs and the effect of the protein hydrolysate, Hydroport, in deep burns in rats].

The authors caused buring of III to IV degree, 10--15% in rats of the Wistar strain. The animals were divided into 4 groups: 1) healthy; 2) burned-nontreated; 3) burned-treated with saline; and 4) burned-treated with hydrolysate. Saline and hydrolysate were administered immediately after thermic trauma, and vascularization was examined by means of radioisotopic methods (86Rb) six hours after burning. Increased blood flow in the internal organs was found 6 hours after inducing the thermic trauma, excluding the pancreas. Saline revealed a certain tendency to normalization of the circulation, but this effect was insignificant and could not be referred to all organs. The protein hydrolysate most sensitively and significantly corrected deviations as in almost all organs they reached practically the norm.


Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion.

The biological activity of a series of natural catechol estrogens was examined under conditions of continuous administration. 2-Hydroxyestradiol (2OH-E2), 2-methoxyestradiol (2MeOE2), 4-hydroxyestrone (4OH-E1), 4-methoxyestradiol (4MeOE2), 2-hydroxyestrone (2OH-E1), and 4-methoxyestrone (4MeOE1) were delivered at the rate of 1 microgram/h from osmotic pumps implanted in ovariectomized rats. Uterine growth and plasma LH concentrations were measured 24, 48, and 72 h after implantation. Little or no uterotropic activity was exhibited by the 2-hydroxylated metabolites 2OH-E1 and 2MeOE2 at any interval, while 2OH-E2 exhibited anomalous uterotropic activity, which terminated at 48 h. The 4-hydroxylated compounds 4MeOE2, 4OH-E1, and 4MeOE1 all produced substantial and progressive uterine growth. Tonic LH secretion was suppressed by 2OH-E2, 4OH-E1, and 4MeOE1 in proportion to their uterotropic activity. 2OH-E1 was the only substance which increased plasma LH concentrations. The nuclear receptor occupancy by 2OH-E2 was substantially shorter than that of E2. Binding studies of the test and other related estrogens to the uterine cytosol estradiol receptor showed that their relative binding affinities in many instances did not correlate with their biological activities.


The insulin receptor of embryonic chicken cartilage.

Highly purified plasma membranes have been obtained from embryonic chicken cartilage by physical means rather than enzymatic digestion. Rapid and reversible binding of [125I]iodoinsulin to these membranes is demonstrated. Similar to the insulin-binding properties of rat liver and adipocytes and human mononuclear cells, optimal specific binding of insulin to chondrocyte plasma membranes has a sharp pH optimum at 8.0, and maximal binding occurs at 2--4 C. Analysis of equilibrium binding reveals a curvilinear Scatchard plot, whose high affinity segment generates a maximum affinity of 1.0 X 10(9) M-1, and a receptor concentration of 0.4 pmol/mg membrane protein. This affinity constant is similar to those generated for insulin binding to membranes prepared from embryonic chicken liver (2.5 X 10(9) M-1), rat liver (1.4 X 10(9) M-1), and mouse liver (0.6 X 10(9) M-1), whereas the receptor concentration is less than that of embryonic chicken liver membranes (1.1 pmol/mg), which in turn was less than those of rat liver membranes (2.8 pmol/mg) and mouse liver membranes (3.5 pmol/mg). Kinetic studies show augmentation of insulin-receptor dissociation by excess insulin when initial receptor occupancy, is low, suggesting that negative cooperativity is present. There is little or no interaction of other hormones with the chondrocyte insulin receptor, with the exception of proinsulin and the insulin-like growth factors. Porcine proinsulin, bovine proinsulin, somatomedin C, and nonsuppressible insulin-like protein prevent [125I]iodoinsulin binding to chondrocyte plasma membranes with dose-response curves which are parallel to that of unlabeled porcine insulin itself, but with molar potencies relative to porcine insulin of 15%, 9%, 2.5%, and 1.4%, respectively. Porcine insulin and proinsulin both prevent binding of [125I]iodosomatomedin C to chondrocyte plasma membranes but with molar potencies less than 1% that of unlabeled somatomedin C. These observations are consistent with the presence of a specific independent insulin receptor in embryonic chicken cartilage which is similar in its characteristics to the insulin receptor in previously described tissues. Insulin has a weak interaction with the chondrocyte receptor for somatomedin C. Interaction with the somatomedin receptor may be the mechanism by which insulin exerts anabolic effects on cartilage when used in pharmacological amounts.


Phylogenetic and anatomical distribution of somatostatin in vertebrates.

Immunoreactive GH release-inhibiting factor [somatostatin (SRIF)] was detected in hypothalamus, extrahypothalamic brain, pancreas, and stomach extracts of the rat, pigeon, tortoise, frog, teleost (cichlid), and elasmobranch (dogfish) and in the whole brain of the cyclostome (hagfish). The SRIF concentration was higher in the pancreas and gastrointestinal tract than in the hypothalamus and extrahypothalamic brain in most species. Extracts of the various tissues from the different species assayed in serial dilutions gave displacement curves parallel to those of synthetic mammalian SRIF. Cation exchange chromatography of hypothalamic extracts from the various species revealed two major immunoreactive peaks, one of which correpsonds to synthetic SRIF in elution volume, the other being less basic. Affinity chromatography-purified immunoreactive SRIF from frog brain, pancreas, and stomach extracts coeluted with synthetic SRIF in high pressure liquid chromatography. The results indicate that immunoreactive SRIF in various tissues and in different vertebrates is indistinguishable and suggest that there has been no change in the molecule during at least 400 million yr of evolution.


A new perspective on the mechanism of corpus luteum regression.

Wide angle x-ray diffraction has been used to examine the phase behavior of microsomal membranes from regressing corpora lutea of prepubertal pseudopregnant rats. During periods of optimal progesterone secretion, all of the membrane lipid was in the liquid-crystalline phase at physiological temperature and, therefore, was fluid. However, mixtures of liquid-crystalline and gel phase lipid were observed under identical conditions in microsomal membrane preparations from animals undergoing spontaneous or prostaglandin F2 alpha-induced regression. This was accompanied by a parallel rise in the lipid phase transition temperature. In addition, the proportion of lipid in the gel phase increased with time after prostaglandin F2 alpha treatment. These results indicate that the mechanism of corpus luteum regression may involve phase changes in the phospholipid bilayer of cellular membranes. The resulting presence of gel phase lipid in the membrane matrices could contribute to the loss of tissue function.


Effects of estradiol and the antiestrogen tamoxifen on steroid hormone receptor concentration and nuclear ribonucleic acid polymerase activities in rat uteri.

The antiestrogen tamoxifen has been used successfully in the treatment of breast cancer. In an attempt to elucidate its mode of action, its effects on steroid hormone receptor concentration and RNA polymerase activities in the uteri of ovariectomized rats have been compared with those of estradiol. A single dose of estradiol and tamoxifen, separately or in combination, produced slight increases in uterine wet weight 12 h after injection. Whereas both estradiol and tamoxifen could promote translocation of the estrogen receptor, only estradiol caused cytoplasmic replenishment of the receptor. Both compounds, separately and in combination, stimulated the production of cytoplasmic progesterone receptor 12 h after treatment. Estradiol produced and maintained significant elevations in RNA polymerase I activity, whereas the effects on this enzyme brought about by taxoxifen were less and transitory. However, estrogen and antiestrogen caused equal increases in RNA polymerase II activity, but, again, the effects of taxoxifen were shortlived when compared to those brought about by estradiol. Stimulation of RNA polymerase II activity was due to the availability of increased numbers of apparent initiation sites. These results point to a basic inefficacy in the antiestrogen-receptor complex; although it is able to promote early tissue responses characteristic of an estrogen, these cannot be sufficiently maintained.


Characterization of different forms of the androgen receptor.

Three forms of the androgen receptor have been characterized at high ionic strength in partially purified cytosol and nuclear fractions of rat ventral prostate, epididymis, testis, and seminal vesicle by ion exchange chromatography on phosphocellulose, gel filtration in Sephadex G-200, and sedimentation in sucrose gradients. The three forms have the following properties, respectively: elution from phosphocellulose at 0.15--0.20, 0.3--0.5, and 0.20--0.32 M KCl; gel filtration radii of 53, 36, and 22 A; sedimentation coefficients of 5.0S, 3.6S, and 3.0S; frictional ratios of 1.65, 1.4, and 1.0; and molecular weights of 115,000, 55,000, and 29,000. In testis and epididymis cytosol, the 53 A, 5S form was more abundant than the 36 A, 3.6S form. In ventral prostate, the 36 A, 3.6S receptor was the predominant form. Variable amounts of all three forms were observed in seminal vesicles. Conversion from 36 A, 3.6S to 22 A, 3.0S was induced by heating ventral prostate cytosol and could be blocked by serine protease inhibitors. The 22 A, 3.0S receptor fragment from heated prostate cytosol was similar in size and symmetry to receptor extracted in 0.5 M KCl from prostate nuclei labeled in vivo. Extracts of epididymis and seminal vesicle nuclei contained both 36 and 22 A forms.


Estrogen-binding proteins in the oviduct of the turtle, Chrysemys picta: evidence for a receptor species.

Estradiol-binding proteins in the reproductive tract of the turtle, Chrysemys picta, were characterized. Cytosol was prepared from the oviducts of mature female turtles, and estradiol binding was measured using charcoal adsorption and glycerol density gradient centrifugation. A sex steroid-binding protein (SBP) similar to that found in turtle plasma was demonstrated in oviduct cytosol. The characteristics of this SBP-like binding were as follows: Ka = 10(8) M-1; capacity, 10(-12) mol/mg protein; and sedimentation coefficient, 6--7S in low salt gradients. The SBP-like protein binds testosterone and progesterone as well as 17 beta-estradiol but does not bind diethylstilbestrol. No receptor-like binding activity could be demonstrated using these techniques. Explant culture and DNA cellulose affinity chromatography were used to remove the SBP-like material before assay of [3H]estradiol binding. Using these techniques, a high affinity (Ka = 10(9) M-1), low capacity (n = 10(-14) mol/mg cytosol protein) estradiol receptor was demonstrated. The putative turtle receptor exhibits steroid specificity and sedimentation profiles (6S and 8S in low salt, 4S and 5S in high salt) comparable to those of estrogen receptors in mammalian species. These results suggest a certain degree of physiochemical similarity between putative estrogen receptors in mammalian and turtle reproductive tracts.


Enhancement of immunoreactive somatostatin release into hypophysial portal blood by electrical stimulation of the preoptic area in the rat.

Electrical stimulation of the preoptic area resulted in a significant increase in the secretion rate of immunoreactive somatostatin (IRS) and its concentration in the hypophysial portal blood of urethane-anesthetized rats. In contrast, stimulation of the ventromedial nucleus did not cause any changes in portal immunoreactive somatostatin. The flow rate of portal blood also increased significantly by electrical stimuli to the preoptic area but not to the ventromedial hypothalamus. These findings support the view that the preoptic area plays an inhibitory role in the regulation of GH secretion by increasing the release of somatostatin into hypophysial portal vessels in the rat.


Properties of somatostatin-like immunoreactive polypeptides in the canine extrahypothalamic brain and stomach.

Polypeptides with somatostatin-like immunoreactivity (SLI) and approximate molecular weights of 12,000, 3,000, and 1,600 were isolated from acid extracts of the canine extrahypothalamic brain and stomach by affinity chromatography, ion exchange, gel filtration, and isoelectric focusing. The 12,000-dalton SLI was acidic, whereas the 3,000- and 1,600-dalton forms were basic molecules. All SLI fractions diluted proportionally in a RIA employing an antibody directed toward the central region of somatostatin. Like synthetic somatostatin, the 1,600-dalton SLI inhibited pentagastrin-stimulated gastric acid secretion in rats. Neither of the two larger forms of SLI were dissociated by 6 M guanidinium HCl. However, treatment with dithiothreitol, which reduces disulfide bonds, resulted in the conversion of a large portion of the 12,000-dalton SLI to the 1,600-dalton form. These data are compatible with a model of a 12,000-dalton SLI consisting of somatostatin bound to an acidic polypeptide by a peptide bond and a disulfide bond. Variations in the relative rates of hydrolysis of the peptide bonds and reduction of the disulfide bonds in different tissues may result in three forms of the 12,000-dalton polypeptide in which both bonds are intact or one of the two bonds is cleaved.


Protein carboxyl-methylation in rat testes: a study of inherited and X-ray-induced seminiferous tubule failure.

Protein carboxyl-methylase (PCM), the enzyme that transfers methyl groups from S-adenosyl-methionine to free carboxyl groups on proteins, is highly localized in testes. The cellular distribution of PCM and its substrates, the methyl acceptor proteins, was investigated. Separation of testicular cells on an albumin gravity gradient revealed the preferential localization of both enzyme and substrates in spermatids. In young rats, PCM activity increases with age coincidently with germ cell maturation. Rats which are heterozygous for the Hre gene (Hre/+) are infertile as a result of germ cell depletion. In these animals, testicular PCM specific activity and total activity were, respectively, 4--6 and 40--50 times lower than in normal testes. Enzyme activity in testes from animals with x-ray-induced germ cell depletion was also very low. These observations suggest that PCM is located in germ cells.


Central nervous system insulin receptors in normal and diabetic rats.

The presence of specific insulin receptors in homogenates of various parts of the rat brain was demonstrated. Hypothalamic preparations exhibited the greatest insulin binding. Scatchard plots of the binding data were typically curvilinear. Insulin binding to the brain homogenates was influenced by pH, incubation time, temperature, and ionic milieu. The specificity of insulin binding to the brain homogenates was demonstrated by partial displacement of labeled insulin by insulin analogs according to their biological activities and by inhibition of insulin binding by serum containing an antibody to insulin receptors. Insulin binding to brain homogenates from streptozotocin-induced diabetic rats was similar to that from control animals and failed to indicate up-regulation of these receptors.


The influence of calcium on the basal and acetylcholine-stimulated secretion of pancreatic polypeptide.

The influence of calcium on basal and acetylcholine-stimulated pancreatic polypeptide (PP) secretion was investigated in an isolated pancreatico-duodenal preparation and compared to the secretion of glucagon and insulin. The stimulatory effect of 5 mmol/liter calcium on PP release was of the same magnitude as that obtained by 5 mmol/liter arginine or 10 nmol/liter isoproterenol but only one fifth of the PP response to acetycholine (1 mumol/liter). All stimuli were equipotent with respect to insulin and glucagon release. The acetylcholine (1 mumol/liter)-stimulated PP release was almost identical at calcium concentrations of 1.3 and 6.3 mmol/liter, whereas glucagon release was calcium dependent, with higher responses at high (6.3 mmol/liter) than at normal (1.3 mmol/liter) calcium concentrations. In a calcium-depleted medium, acetylcholine induced a prompt, short-lived, but repeatable PP response, whereas no increase in glucagon or insulin was found. Further, when calcium influx into cells was blocked by excess magnesium (5.0 mmol/liter), the basal and acetylcholine (1 mumol/liter)-stimulated PP secretion was only inhibited by 12% (P = NS) and 42% (2P less than 0.05), respectively, whereas glucagon release was inhibited 56% (2P less than 0.001) and 76% (2P less than 0.01), respectively. It is concluded that the secretion of PP is influenced by calcium ions; however, the PP release is much less dependent on extracellular calcium ions than are insulin and glucagon secretions.


Prolonged stimulation of adenylate cyclase activity and testosterone production by cholera enterotoxin with suppression of gonadotropin release in rats.

Endocrine effects of cholera enterotoxin (CET) on male gonads were investigated in normal and hypophysectomized rats. After intratesticular injection of 5 micrograms of CET in the bilateral testes of normal rats, serum testosterone concentration remarkably increased after 24 hr, remained significantly elevated for at least 3 days and returned to the control level in 7 days. Serum LH level decreased in the undetectable range after 1--3 days; serum FSH level also significantly decreased after 3 days. Both gonadotropin levels increased 28 days after the injection, when the CET-injected testis decreased in weight and was accompanied by marked loss of germinal cells. When 5 micrograms of CET was injected intratesticularly in the bilateral testes of hypophysectomized rats, adenylate cyclase activity of a CET-injected testis was remarkably stimulated after 6 hr, remained four times elevated for at least 3 days and returned to the control level in 7 days. In relatively good accordance with the increase in adenylate cyclase activity, testosterone content remarkably enhanced in the CET-injected testis. These in vivo data indicate that the intratesticular injection of CET prolongedly stimulates the adenylate cyclase activity of testicular cells including Leydig cells and increases testosterone production, and suggest that the prolonged enzyme stimulation results in the sustained elevation of serum testosterone concentration for at least 3 days, causing the stimulation of the negative feedback mechanism of hypophysealtesticular axis to decrease serum LH levels in the undetectable range.


Studies on the translocation inhibitor of 3H-dexamethasone-receptor complex.

Recent reports on the binding of glucocorticoid-receptor complexes to rat liver nuclei suggested the presence of components which inhibited the binding. The inhibitory component(s) of the receptor translocation was observed not only in the cytosol of the liver but also in cytosols of the kidney, the spleen and the thymus. The cytoplasmic levels of the inhibitor in these tissues were not modified by the administration of Dexamthasone (DEX). The liver inhibitor was macromolecular and clearly separated from the DEX-receptor complex on DEAE-cellulose chromatography. The mechanism of the inhibition seemed to be an interaction between the inhibitor and the steroid-receptor complex. In addition, the inhibition seemed to be less specific for the bindings of different steroid-receptor complexes to nuclei. The bindings of hepatic 3H-DEX-receptor complex by nuclei derived from livers of adrenalectomized and DEX-treated rats, in the presence or absence of the translocation inhibitor, were similar.


Effect of prostaglandin E1 on renin and aldosterone in hypertensive patients.

The effect of prostaglandin E1 (PGE1) on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was studied in the hypertensive subjects treated with or without 75 mg indomethacin or 60 mg propranolol for a week. Subsequent to the treatment with indomethacin for a week, PRA and PAC levels were decreased as compared to the control, without changes in the blood pressure and heart rate. During the infusion of PGE1, the blood pressure was decreased and the pulse rate was increased. PRA and PAC levels were also elevated. These changes of parameters were not different between the control and the indomethacin-treated subjects. PRA and PAC were suppressed after the treatment with propranolol. With the infusion of PGE1, the level of PRA was not significantly elevated, while, PAC was significantly increased by the infusion of 100 ng/Kg/min of PGE1. During the infusion of PGE1, the blood pressure was decreased while the pulse rate was increased in the subjects treated with propranolol. However, the elevation of the pulse rate was less remarkable than the control. These data indicate that PGE1 have important roles in the regulation of the release of renin and aldosterone. These findings also suggest that PGE1 may act to stimulate the secretion of aldosterone in man.


Hyperglycemic factor in submandibular glands and its etiological relations to diabetes mellitus in mice.

Bilateral ligation of both the submandibular and parotid ducts of adult normal and mutant hyperinsulinemic diabetic mice resulted in a significant hypoglycemic effect. Therefore, we postulated that duct ligation may result in the removal of hyperglycemic factor (Hoshino et al., 1976) rather than a change in insulin sensitivity. Indeed, no change in specific binding of 125I-insulin was observed in membrane fractions from several tissues obtained from mice of either sex or strains before and after duct ligation. After slices of the submandibular gland were incubated for 4 hr in Eagle's medium, an aliquot of the culture medium was injected i.p. into normal adult mice. A signigicant hyperglycemic effect was observed in 30 min in the injected animals. Eluates obtained by gel filtration of the crude extract of the submandibular gland were injected into normal adult mice, and hyperglycemia ensued. Thus, it is postulated that ligation of salivary ducts results in glandular atrophy and disappearance of the hyperglycemic factor which in turn leads to hypoglycemia and amelioration of diabetes mellitus, particularly of hyperinsulinemic type.


Nuclear progesterone receptor in the hen pituitary and hypothalamus.

The existence of specific progesterone-binding sites with a high affinity and a limited capacity was demonstrated by [3H]progesterone exchange in the nuclear fractions of the pituitary and hypothalamus as well as in those of the oviduct magnum in the hen.


Presence of triiodothyronine, no detectable thyroxine and reverse triiodothyronine in human milk.

Thyroxine (T4), triiodothyronine (T3) and reverse triodothyronine (rT3) concentrations in human milk were measured by radioimmunoassay in 114 samples obtained from 1 week to 8 months postpartum. Several assay systems applied for the determination of serum thyroid hormone concentration were proved to be unsuitable for human milk, and the method of separating free and antibody-bound hormone by polyethylene glycol was also inappropriate for milk specimens, which tended to give a falsely high value. The binding of finity  of T4 to milk was lower than that to serum protein, on which 8-anilino-1-naphthalene sulfonic acid showed no remarkable effect. In spite of the high sensitivity of 100 pg/tub in T4 assay system, no immunoassayable T4 was detected in all samples with or without ethanol extraction and trypsin hydrolysates of milk. In contrast, T3 was present in a measurable amount in most of the samples, the mean +/- SD value of which was 10 +/- 9 ng/100 ml, and those in colostrum were significantly higher than those in matured milk (P less than 0.01), whereas rT3 was not detectable in 76 samples tested. These results indicate that permeability of thyroid hormones through the mammary gland is different between T4 and T3 as well as in placental transport, and human milk can not be a source of thyroxine supply for the breast-fed infant.


Quantitative protein changes in the hypothalamic neurons of pubertal male rats, castrated neonatally.

The effect of neonatal castration of male rats on the sexual differentiation of the hypothalamus at puberty was studied. Male rats were castrated on days 1, 5 and 7 after birth. Their brains were processed for study on days 83-85. The neurons and cell nuclei of the preoptic area, mediobasal and ventromedial nuclei were assessed for changes in cell and nuclear sizes and dry weight (calculated using interferometric methods). Neonatal castration resulted in size as well as dry weight increase in the neurons of the anterior and mediobasal hypothalamus. The dry weight increased by 34% (P less than 0.001) in the medial preoptic area, by 25% (P less than 0.001) in the arcuate neurons and by 22% (P less than 0.001) in the ventromedial nucleus. The cell nuclei exhibited perceptible weight increase too--in the medial preoptic area 68% (P less than 0.001); 55% in the arcuate neurons (P less than 0.001), and 39% in the ventromedial region. The weight and size increases in neonatally castrated males were equal to those of females of the same age. In rats castrated on day 7, the cell sizes and dry weights of the ventromedial nucleus increased but the cell nuclei exhibited only little change. It is assumed that the changes in the dry weight may be the result of increased synthetic processes in these groups of neurons which are connected with the tonic and cyclic release of gonadotropins. These changes also point to the hypothalamic differentiation shifting to the female type in the absence of the inducing effect of androgens.


Effect of maternal thyroparathyroidectomy before gestation on fetal development in rats.

Female rats were thyroparathyroidectomized (TPTX) at 24 (immature), 40 (pubertal) and 75 (matured) days of age, at least 21 days before mating. Thyroxine (2.5 microgram/kg) or parathyroid hormone (150 USP units/kg x 2) was replaced in two TPTX groups. Thyroxine deficient groups of all ages had reduced body weight, litter size and serum thyroxine and calcium level. Fetal weights at 20 days of gestation in all thyroxine deficient groups were significantly reduced but placental weight was generally increased. Maternal serum thyroxine and fetal weight was positively related when all groups were taken together, but maternal serum calcium and fetal weight was not related. There were no significant differences in gross, visceral or skeletal anomalies in the fetuses in any group.


Effect of deuterium oxide on the pituitary gonadotrophs of the brown spiny mouse. Mus platythrix Bennett.

Adult individuals of M. platythrix were maintained on 30 per cent D2O by volume in drinking water at varying periods of time. Qualitative and quantitative changes in pituitary FSH and LH cells were observed. The former revealed hyperplasia and hypertrophy by 10 days attaining their peak of activity and hyalinization by 20 days. In contrast response in the LH cells was rather slow. They showed a significant increase in number after 30 days and hyalinization by 50 days. FSH cells revealed decline in activity by 50 days whereas LH cells attained their peak numerically by 40 days and underwent no change thereafter. These observations suggest that in the adult male D2O reveals: 1. hyperactive influence on the gonadotrophs, and 2. differential in FSH and LH secreting cells.


Inhibition of testicular androgenesis by urinary antigonadotropins and melatonin in rats.

Comparative in vitro and in vivo studies of the effects of urinary gonadotropin-inhibiting substances and melatonin on the androgenesis in rat testicular homogenates were performed. When the urinary extract containing the inhibiting substances or melatonin was added directly to the incubation medium, and was also injected into rats 24 and 48 hrs prior to sacrifice, either one was effective in suppressing the conversion of pregnenolone to testosterone and/or androstenedione in testicular tissues. The urinary extract exerted the inhibitory effect on the conversion of cholesterol to pregnenolone in vitro and in vivo, whereas melatonin did not have this effect in vitro and in vivo. These findings suggest that the antigonadotropic substances are different from melatonin in their action on androgenesis in the rat testes.


Urinary testosterone and epitestosterone excretions in women with idiopathic hirsutism.

Urinary testosterone and epitestosterone were determined in 90 normal healthy women and in 90 women with idiopathic hirsutism, both groups aged between 16 and 46 years. Testosterone and epitestosterone excretion values were above the normal range in 27 of the 90 hirsute women (30%), and these 27 women had much more prominent hair growth than the others. When these results were statistically analysed according to the age groups or for all ages as a whole, they were found to be highly significant (P less than 0.0005). Therefore, it is concluded that the estimation of urinary testosterone and epitestosterone could be meaningfully applied to study the androgen status of hirsute women.


Effect of dexamethasone on plasma concentrations of LH, FSH and testosterone in women with hirsutism.

Thirty sexually mature women with hirsutism were treated with 3 x 1.5 mg dexamethasone per day over a period of three days. Before and after treatment, plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone were determined. While an effect of dexamethasone on LH plasma levels could not be established statistically, FSH and testosterone plasma concentrations decreased significantly in comparison to their initial values (p less than 0.01). Special attention is directed to the different effects of dexamethasone on LH and FSH plasma concentrations.


Pilocarpine and atropine effects on the mitotic activity of the adrenal cortex.

Because of the postulated presence of direct nervous cholinergic connections between the adrenal cortex and the hypothalamic centers, effects of pilocarpine and atropine on the adrenal cortex mitotic activity were examined. The obtained results show that pilocarpine stimulates and atropine inhibits the proliferation of cells in zona glomerulosa and zona fasciculata of the adrenal cortex. It seems that the stimulating effect of pilocarpine may be related to the muscarinic receptor activation on the level of the cholinergic nervous terminals in the adrenal cortex.


Increase by somatostatin of the arginine induced rise in blood glucose in untreated insulin requiring diabetics.

We have demonstrated previously that cyclic somatostatin (GH-RIH) exerts a diabetogenic action in healthy subjects. To further examine the impact of this phenomenon studies of blood glucose (BG), immunoreactive insulin (IRI), glucagon (IRG) and growth hormone (GH) were performed in insulin requiring diabetics (n = 6) receiving i.v. arginine (0.5 g/kg) both in the absence and presence of i.v. GH-RIH (500 microgram/h). The infusion of GH-RIH-resulted in a persistent diminution in plasma IRI, IRG and GH. BG fell during i.v. GH-RIH during the initial 30 min and was below control values up to 45 min after initiation of i.v. arginine, but subsequently exceeded control levels (p less than 0.05 - less than 0.025). The excess rise in BG occurred in spite of suppression by somatostatin of the ariginine induced release of IRG, IRI and GH. A fall in BG was seen following cessation of i.v. GH-RIH and during a rebound of insulin release with glucagon levels remaining in the basal range. These findings indicate a diabetogenic action of somatostatin also in insulin requiring diabetics as long as some residual capacity for insulin release is retained.


The effect of hyperosmotic mannitol and glucose on heart function.

In the dog heart-lung preparation the effects of glucose and mannitol induced hyperosmolality were examined on left ventricular water content, ventricular compliance, cardiac performance, and coronary blood flow. Glucose-induced increase of serum osmolality by more than 20% resulted in a decrease of myocardial water content and an increase of left ventricular diastolic stiffness if insulin was absent, but the changes did not develop if it was present. Insulin failed to prevent the alterations if hyperosmolality was induced with the nonmetabolizable sugar, mannitol. Coronary blood flow increased in each type of experiments. It is concluded that diagnostic and clinical treatment with hyperosmotic solutions of nonmetabolizable agents can account for disturbed left ventricular compliance and decreased cardiac performance, as it may occur in hyperosmolar diabetic coma.


Presence of sex steroid receptors in normal breast of human females.

Receptors for estradiol, progesterone and dihydrotestosterone have been demonstrated in normal growing breasts of young females below 25 years.


Inhibition of thyroid monoamineoxidase by thyroxine and some specific inhibitors.

Rat thyroid monoamine oxidase (MAO) was inhibited by the non-hydrazine derivatives paragyline and tranylcypromine to a higher degree than the hydrazine derivative iproniazide. MAO was also inhibited by monoiodotyrosine and thyroxine. These results indicate that MAO may be an important enzyme in the metabolism of biogenic amines, iodotyrosines and tyronines in the thyroid gland.


The triiodothyronine antagonistic effect of gamma-L-glutamyl-taurine (litoralon).

A recently recognized bioactive substance of the parathyroid glands, gamma-L-glutamyl-taurine antagonises the metamorphosis enhancing effect of triiodothyronine. Shortening of the body-length of tadpoles is significantly delayed by the substance. The experimental results imply that it fulfills the role of a balance hormone.


Observations on the electroencephalogram and photosensitivity of South African Black albinos.

An EEG survey of 70 normal South African black albinos was carried out to determine whether the lack of pigment in the retinae and eyelids would have any effect on the photoconvulsive response during intermittent photic stimulation. Only 2 out of the 70 (2.85%) showed photosensitivity on intermittent photic stimulation. The results do not confirm the "pigmentary protection theory." Other intrinsic inhibitory factors must be responsible for the level of the photoconvulsive threshold.


Antipyretic effect and plasma concentrations of rectal acetaminophen and diazepam in children.

Plasma levels of acetaminophen (paracetamol) and diazepam were measured in 9 children by gas chromatography after administering these drugs simultaneously in separate suppositories. The antipyretic effects of oral and rectal acetaminophen-diazepam combinations were also studied and compared with that of oral or rectal acetaminophen alone. Diazepam at a dose of 0.2 mg/kg did not increase the antipyretic action of acetaminophen. Acetaminophen and diazepam seemed to be well absorbed from the rectal suppositories, the maximal plasma concentration of diazepam after a rectal dose of 0.5 mg/kg just reaching the assumed anticonvulsant level in about 2 hr. In light of this study, an acetaminophen-diazepam combination in separate suppositories may be suitable for the prevention of recurrent febrile convulsions in susceptible children, but its practical value and efficacy require evaluation in clinical experiments.


Tears as the best practical indicator of the unbound fraction of an anticonvulsant drug.

Phenobarbital and carbamazepine concentrations were determined by the EMIT technique in tears, saliva, cerebrospinal fluid (CSF), and plasma of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios for the two agents. The phenobarbital CSF/serum ratio was in good agreement with data in the literature, and the higher ratio found for carbamazepine may be caused by an EMIT assay cross-reaction for the free fraction of carbamazepine-10,11-epoxide. In our hands, tears seem to represent the best practical indicator of the unbound fraction of an anticonvulsant drug, and the noninvasiveness of the method makes it specifically useful in pediatric neurology.