Anorchia and persistent Müllerian duct: a variant of the embryonic testicular regression syndrome. A 20-yr-old phenotypical male with a 46, XY chromosome complement, a hernia uteri inguinale, and bilateral anorchia was studied. Eunochoidal body proportions, infantile type of male external genitalia with empty scrotum, underdeveloped sexual characteristics, and delayed bone age suggested the existence of inadequate testicular function. Extremely low levels of circulating testosterone and a lack of response to hCG stimulation was found. Persistently elevated blood levels of LH and FSH with an adequate pituitary response to an iv bolus of synthetic LRH was demonstrated, thus indicating inadequate endocrine gonadal function as well as functional integrity of the hypothalamic-pituitary unit. At the time of an inguinal hernioplasty, a small but well developed uterus was removed. No gonads were found within the true pelvis, inguinal canals, or along the anatomical pathways of testicular descent. A cord-like structure found in the left inguinal canal contained only fibrous tissue without gonadal elements. It is proposed that the occurrence of two altered events during embryogenesis, failure of Müllerian duct regression and late testicular regression, may explain the underlying defect in this unusual abnormality of sexual differentiation.


Variations in the structure of thyroglobulins from normal and goitrous human thyroids. Thyroglobulin samples were prepared individually be gel chromatography from the thyroids of five persons without thyroid disease and four with goiters. Gel electrophoresis at different pHs and gel concentrations showed a single major band corresponding to 19S thyroglobulin in rabbits, with occasional faint bands corresponding to 12S and 27S species. The thyroglobulins of the normals differed from each other in electrophoretic pattern on sodium dodecyl sulfate (SDS)-urea gels and in composition of iodine, monosaccharides, and amino acids. Nine amino acids showed significant variation among the five thyroglobulins at the P less than 0.01 level, and only two (lysine and alanine) did  not vary. The content of both sialic acid and fucose varied widely, but their sum was similar among the five samples. Thyroglobulin samples from the goiters differed from the normals and from each other in composition and in pattern on SDS-urea gels. The variability itself was more impressive than were differences in any particular component. Relative to the normals, these thyroglobulins showed increases in content of sialic acid (P less than 0.01) and lysine (P less than 0.10), and increases in the faster bands on gel electrophoresis in SDS-urea. Two goiters were from patients with the multiple hamartoma syndrome, and the only metabolic abnormality found was a low content of iodothyronine in thyroglobulin. The other two goiters also showed inadequate coupling of iodotyrosyls. In addition, one contained a soluble iodoprotein of very high molecular weight, which was immunologically identical to 19S thyroglobulin but differed in chemical composition. We conclude from the compositional data that there is not a single structure for "normal" thyroglobulin, but that multiple molecular configurations occur naturally and are compatible with adequate hormone synthesis. Extensive variations in thyroglobulin structure are frequently found with goiter, and we suggest that these may be involved in its pathogenesis.


Plasma prolactin-releasing factor-like activity in the amenorrhea-galactorrhea syndrome. An in vitro bioassay for plasma PRL-releasing factor-like activity has been developed. The method is a three-phase methanol extraction of plasma with extracts of 1.0 ml plasma adjusted to a final volume of 50 microliter. Single 50-microliter aliquots of extract were incubated in 1.0 ml Krebs-Ringer phosphate (KRP) buffer with one rat hemipituitary after a 1-h preincubation. Samples were obtained basally and 30 min after addition of the extract. During each set of incubations, a parallel series of hemipituitaries was incubated in KRP alone. The total nanograms of rat PRL released per mg pituitary tissue during the initial 30 min after preincubation was calculated for all studies. The mean quantity released in KRP alone was considered basal and was subtracted from values obtained during incubation with plasma extracts. The quantity remaining was considered PRL-releasing activity (PRA) of plasma, expressed as nanograms of rat PRL released per mg pituitary. The PRA in plasma from 13 patients with the amenorrhea-galactorrhea syndrome was 132 +/- 17 ng/mg pituitary (X +/- SE), which was significantly greater (P less than 0.001) than the PRA in plasma from eight matched controls [31 +/- 10 ng/mg pituitary (X +/- SE)]. The patients' individual PRL levels were elevated (range, 48-248 ng/ml), and when compared to the PRA in the samples, a highly significant (P less than 0.001) positive correlation evolved. These results indicate that a circulating PRL-releasing factor-like material present in normal plasma is higher in plasma from hyperprolactinemic patients in direct relationship to the PRL concentration. It is possible that this material is related to the pathogenesis of PRL-secreting pituitary disorders.


Effect of human chorionic gonadotropin on thyroid function in euthyroid men. The effect of large doses of commercial hCG on thyroid function was studied in eight men who received 100,000 or 150,000 IU hCG iv. These large doses of hCG produced definite thyroidal iodine release (TIR) responses in all eight men. The TIR after hCG administration was more delayed and of lesser magnitude than the TIR responses to TSH and TRH. There were no significant changes in serum T4, T3, or TSH for 48 h after hCG administration. No clinical side effects were noted in the subjects after iv administration of these large doses of hCG. The results of this study indicate that hCG is a weak thyroid stimulator in man.


Progesterone induced acute release of prolactin in estrogen primed ovariectomized women. Progesterone (10 mg) administered intramuscularly induces a concurrent release of prolactin as well as gonadotropin in estrogen-primed women. The time course of pituitary release of all three of these hormones appears to include a latent phase of 4 hrs and is maintained for at least 5 hrs. It is considered that this effect of progesterone may be mediated through a reduction of hypothalamic dopamine.


Luteinizing hormone and follicle-stimulating hormone secretory dynamics in Turner's syndrome. In eight teenage patients with Turner's syndrome, LH and FSH were measured at 20-min intervals for 24 h. The 24-h mean LH and FSH levels ranged from 20.2-70.5 mIU/ml and 60.4-229 mIU/ml, respectively. There was a significant positive correlation between the individual LH and FSH levels in the eight patients; the common correlation coefficient was 0.449 (P less than 0.001). The 24-h mean estradiol level was measurable in only two of the patients and the 24-h mean testosterone level for the eight patients was 0.10 ng/ml. The mean LH concentration during sleep was significantly higher (P less than .01) than during waking. The mean FSH concentration during sleep was also significantly higher (P less than 0.05) than during waking. The LH and FSH peak levels after LRH were significantly correlated with the 24-h mean LH (r = 0.918; P less than 0.01) and FSH concentrations (r = 0.754; P less than 0.05), respectively.


Studies of gonadotropin-gonadal dynamics in patients with androgen insensitivity. Four patients with androgen insensitivity had plasma LH and FSH measured at 20-min intervals for 24 h and at 15- to 30-min intervals for 3 h after the injection of LRH. Twenty-four-hour mean testosterone (T), estradiol, and androstenedione (delta 4) levels were also measured. Patients with androgen insensitivity had significantly elevated LH levels (P less than 0.05) and an increase in the number of LH secretory episodes (P less than 0.001) compared to normal subjects. The amplitude of the LH secretory episodes, expressed as the absolute increment, was significantly higher than normal controls (P less than 0.005). The LH response to LRH (absolute increment) was twice that of normal, but was not significantly different from normal subjects. The 24-h mean FSH levels were normal in three of the patients and elevated in one. This patient had the mildest degree of androgen insensitivity on clinical exam and the greatest degree of testicular atrophy. The 24-h mean T, estradiol, and delta 4 levels were higher than normal, but only the delta 4 was significantly increased (P less than 0.05). To determine if the elevated LH levels were in response to a decrease in the free T level, we measured T-binding capacity (TBG), TBG was higher than normal controls but was not significantly different, suggesting that elevated LH levels were probably in response to a decrease in T action at the hypothalamic-pituitary level. This was further supported by the inability of prolonged dihydrotestosterone administration to affect LH secretion in one of the patients with the Reifenstein syndrome.


Serum prolactin response to thyrotropin-releasing hormone and metoclopramide in patients with prolactin-secreting tumors before and after transsphenoidal surgery. Seven female patients with amenorrhea, galactorrhea, and hyperprolactinemia were examined before and after selective transsphenoidal removal of a PRL-secreting microadenoma. Before adenomectomy, metoclopramide (MCP; 10 mg orally) and TRH (200 micrograms iv) did not increase PRL blood levels in any of the seven patients. On the contrary, after oral administration of 10 mg MCP, a positive response was noted in a group of eight lactating women 3 days postpartum. After surgery, serum PRL level returned to normal in all patients. A positive PRL response to MCP and TRH was found in six of the seven patients 1 month after surgery. One patient, who had the lowest PRL level, failed to show a PRL increase after both stimuli. These findings indicate that hypothalamic pituitary function can be restored to normal after transsphenoidal removal of PRL-secreting pituitary tumors.


Hormonal pattern of adolescent menstrual cycles. Serum FSH, LH, PRL, estradiol, pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, and androsterone were measured radioimmunologically in 20 normal girls aged 13-17 yr. Samples were taken every day or every second day during one menstrual cycle. The cycles recorded could be divided into three groups. The first and oldest group consisted of 10 girls with a mean gynecological age (years since menarche) of 2.9 yr. The luteal phase was at least 11 days and the progesterone concentration was at least 5 ng/ml. The testosterone rise (mean, 55%) on the day of LH surge correlated well with the simultaneous progesterone rise (mean, 270%) and the following luteal progesterone secretion. A negative correlation was seen between the FSH concentration on days 3-4 of the cycle and the length of the follicular phase. The second group consisted of 4 girls who had a mean gynecological age of 1.5 yr. The luteal phase was of 4- to 8-day duration and the progesterone secretion was lower than in group I. The follicular phase testosterone concentration was lower in group II as compared to group I. No "periovulatory" testosterone increases were seen, although every cycle displayed an LH and FSH peak. The third group consisted of 6 girls with a mean gynecological age of 1.1 yr. These cycles were anovulatory, as the serum progesterone concentration never exceeded 1.0 ng/ml. In two cycles, signs of follicular maturation were seen. In the four others, the androgen levels tended to be elevated. In two cases, the testosterone and androstenedione concentrations were 2-4 times elevated from the beginning of these two cycles. Thus, the hormonal pattern of adolescent menstrual cycles is far from uniform. It is very likely that in addition to gonadotropins, estradiol and progesterone, androgens may also have a role in the development and maintenance of normal menstrual function in the female.


Functional and structural relationships in steroidogenesis in vitro by human ovarian follicles during maturation and ovulation. To investigate steroidogenic function of human follicles in the light of their structures, eight antral follicles of different sizes were mechanically isolated from ovaries of patients laparotomized in the follicular phase of the menstrual cycle with or without pretreatment with human menopausal gonadotropin (hMG). A portion of each follicle was taken for histology and slices of each follicle were incubated with [1-14C]-acetate. Incorporation into progestins, androgens, and estrogens was assessed by the reverse dilution technique with recrystallization to constant specific activity. A predominant incorporation into 17 beta-estradiol was observed in two maturing follicles, whereas a marked increase in incorporation into 17 beta-estradiol with a concomitant decrease in incorporation into androstenedione was verified in two other mature follicles. Remarkable enhancement in relative incorporation into C21 steroids was commonly noted in four preovulatory follicles. However, with the progress of preovulatory stages toward ovulation, as judged from structural changes of the follicles, actual incorporation into C19 and C18 steroids showed a moderate increase, followed by a drastic decrease around the time of ovulation. hMG injection induced similar relationships between the steroidogenic pattern and the follicle structure of different stages, although overall incorporation was considerably increased. We conclude that marked qualitative and quantitative changes in the steroidogenic function and accompanying corresponding changes in structure occurred over the period of follicular maturation and ovulation.


Enzyme immunoassay of human chorionic gonadotropin employing beta-galactosidase as label. An enzyme-linked immunoassay was applied to the determination of hCG, a glycoprotein hormone usually assayed by RIA. For this purpose, an enzyme hormone conjugate was prepared by reacting hCG with beta-D-galactosidase (beta-Gal.) of E. coli in the presence of N-(m-maleimidobenzoyloxy) succinimide (MBS) as coupling reagent. The conjugate, after purification by affinity and gel chromatographies, was shown to exhibit sufficient enzyme activity and immunoactivity. The immunoassay of hCG was performed by the double antibody method and, using this assay, 0.4-250 mIU/ml hCG were detectable. This was about 10 times as sensitive as the RIA. Difficulty was experienced when this method was utilized for the determination of hCG in plasma samples from patients. Since the presence of the plasma may have affected this assay method, the following improvements were made: 1) the same volume of hormone-free plasma was added to the standard solutions of hCG, and 2) the volume of plasma sample was 10 microliter. The performance and validity of this assay were comparable to the RIA using [125I]hCG as tracer. The dose-response curves of both assay have the same slope and there was no significant difference between the values (correlation coefficient, Y = 0.96X + 1.53).


Prolonged negative feedback suppression after estradiol administration: proposed mechanism of eugonadal secondary amenorrhea. The finding of normal gonadotropin and estradiol levels in eugonadal women with secondary amenorrhea suggests a disordered feedback relationship of the hypothalamic-pituitary-ovarian axis. To identify possible defects in negative and positive feedback, we compared the effects of five daily injections of 17 beta-estradiol (E2) in 13 normal women and 11 eugonadal patients with absent cyclic menses. The suppression phase of negative feedback was normal, as LH and FSH were similarly lowered in both groups on day 3. Continued LH (P less than 0.01) and FSH (P less than 0.02) inhibition on day 10 of the protocol, 5 days after the last E2 injection, indicated a defect in the recovery phase of negative feedback in the 11 amenorrheic women. In the 4 patients studied gonadotropin suppression persisted for 3 weeks, E2 did not blunt pituitary responsiveness to GnRH in the amenorrheic women, suggesting a central nervous system site for prolonged gonadotropin inhibition. Nine normal but only 2 amenorrheic women X2 = 4.15; P less than 0.05) exhibited a positive feedback increase in LH on days 4-6. We propose that a defect in the recovery phase of negative feedback to E2 rather than absent positive feedback may be the dominant physiological abnormality which causes secondary amenorrhea by preventing early follicular phase gonadotropin increments and follicular maturation.


Effect of thyrotropin-releasing hormone and bromoergocriptine on growth hormone and prolactin secretion in perfused pituitary adenoma tissues of acromegaly. To determine the site of action of TRH and 2-brom-alpha-ergocriptine (CB154) on pituitary hormone release in acromegalic patients, the effect of these substances on GH and PRL secretion was examined in perfused pituitary adenoma tissues obtained at surgery from subjects with acromegaly. Relatively stable baseline secretion levels of GH and PRL were followed by an abrupt and marked discharge of the hormones after TRH infusion in all of the experiments. The pattern of GH response was essentially the same as that of PRL. Moreover, a dose-response relationship was obtained between the TRH concentrations infused and the magnitude of GH and PRL responses. The infusion of CB154, on the other hand, inhibited both GH and PRL secretion in three experiments performed on different adenoma tissues. This effect of CB154 was prompt and lasted for a long period even after the infusion was discontinued. When TRH was perfused concomitantly with CB154, the stimulatory effect of TRH on GH release was maintained, while TRH-induced PRL secretion was completely blocked. The results suggest that both TRH and CB154 possess a direct action on pituitary adenoma cells of acromegaly and that aberrant GH responses to TRH and dopaminergic agonists in acromegalic patients may be explained by the altered cellular membrane receptors of the adenoma of these subjects.


The relationship of changes in serum estradiol and progesterone during the menstrual cycle to the thyrotropin and prolactin responses to thyrotropin-releasing hormone. The responses of serum TSH and PRL to TRH (500 microgram) were studied in normal young women in the early follicular, periovulatory, and midluteal phases of the menstrual cycle in order to examine the relationship of these responses to the levels of estradiol relationship of these responses to the levels of estradiol (E2) and progesterone. Each woman was studied twice in each phase in order to assess intraindividual variability. There was no significant difference in either the TSH or PRL responses among the phases of the menstrual cycle nor was either response affected by the periovulatory rise in E2 or by the luteal rise in both E2 and progesterone. Thus, the interpretation of the TSH and PRL responses to TRH in normal women is not affected by the menstrual cycle although both responses are greater in women that in men. Both the peak TSH and peak PRL after TRH were highly correlated with the basal levels of TSH (r = 0.85; P less than 0.01) and PRL (r = 0.67; P less than 0.01), respectively, indicating that the TSH and PRL responses to TRH in women are directly proportionate to the basal levels of the respective hormones, as previously shown for the TSH response in men. The mean intraindividual variability (coefficient of variation) of the TSH response to TRH was 18%, but ranged as high as 56%, while that of the PRL response was 16% and ranged up to 31%; variability was not affected by the phase of the menstrual cycle. The normal range of the peak TSH after TRH in women is 7-33 microU/ml (mean +/- 2 SD); however, because of the variability, a normal woman may sometimes have a peak TSH after TRH as low as 4 microU/ml. Repeating the test will result in a normal value if the woman is truly normal. Similarly, the normal peak PRL after TRH in women is 22-111 ng/ml (mean +/- 2 SD); usually, however, the lower limit is 30 ng/ml with lower values due to intraindividual variation. The data suggest that the higher average level of E2 in women compared to women, but that the cyclic changes in serum E2 or progesterone in women have little or no additional effect.


Direct inhibition of Leydig cell function by estradiol. Suppression of plasma testosterone levels from a mean of 760 ng/dl to a mean of 295 ng/dl could be induced in normal young adult men 24 h after a single injection of 2 mg aqueous 17 beta-estradiol. Maximum suppression to 123 ng/dl was noted 36 h after estradiol administration. Neither LH nor FSH levels were similarly affected. After administration of 5000 IU hCG to a similar group of subjects, daily blood samples were obtained for testosterone and estrogen. Maximum testosterone levels of 2060 ng/dl (basal, 784 ng/dl) were seen 96 h after hCG administration. Maximum estrogen levels of 13 pg/ml (basal 73 pg/ml) were seen 36 h after hCG administration. The testosterone response to hCG could be attenuated by preceding hCG administration with an injection of 17 beta-estradiol. These results can be explained by the concept of enzyme inhibition; estrogen acts directly on the Leydig cell to effect changes in the activities of certain enzymes important for testosterone synthesis. Whether endogenous estrogen production by the Leydig cell may be important in this postulated short loop feedback is as yet unclear.


Influence of collimator design on the shape of isodose curves in high energy electron beams. Families of isodose curves for electron beams of 20 and 34 MeV were obtained for two different kinds of collimator designs. The lucite localizer of the original collimator of the betatron was replaced by a modified metal device. Electron isodose distributions were obtained for circular, and rectangular field sizes employing film dosimetry. The results show that an improvement was achieved in the symmetry of the beam and in the reduction of the penumbral region when the original lucite localizers were replaced by brass defining plates at the patient's skin. The new proposed electron-localizers are described in this study and their influence on depth dose distributions is discussed.


Blood glucose profiles in insulin-dependent Zambian diabetics. Six male stable insulin dependent diabetics were admitted to the University Teaching Hospital (U.T.H.) to define the insulin regiment that best controls their fasting and 2 hr postprandial blood glucose. Lente and Soluble insulin regiments were evaluated. For this study, blood glucose was estimated in six control subjects and in the six diabetic patients before breakfast lunch and supper and two hours after each of these meals. Each diabetic was allowed three days to stabilise on his usual insulin regimen and for the next three days blood glucose was estimated at the times indicated. Then for the next three days the patient was given the other insulin regimen and then for the last three days and while still on this second regimen blood glucose was estimated at the time indicated. Lente insulin was given as a twice daily dose before breakfast and supper while soluble insulin was administered either as a twice daily dose before breakfast and supper or as a thrice daily dose before breakfast, lunch and supper. The overall control of blood glucose before and two hrs meals was better with soluble insulin regiment than with the Lente insulin regimen.


Recessively inherited, late onset spondylar dysplasia and peripheral corneal opacity with anomalies in urinary mucopolysaccharides: a possible error of chondroitin-6-sulfate synthesis. Two male and two female sibs with an unusual form of spondyloepiphyseal dysplasia were reported. The main clinical features were low stature, moderate shortness of trunk and neck, abnormal span: height ratio, low-normal UBS: LBS ratio, and peripheral corneal punctate opacities only seen by the slitlamp. Normal mental status was present. Typical metachromatic granules were not seen either in bone-marrow cells or in peripheral blood cells. The X-ray picture showed spondylar and pelvic dysplasia. Qualitative rather than quantitative anomalies were shown in the urinary mucopolysaccharides, mostly involving chondroitin-6-sulfate. The genetic data are consistent with autosomal recessive inheritance.


Prenatal diagnosis of Wolman disease.

Prenatal diagnosis of Wolman disease. Two pregnancies at risk for Wolman disease were monitored by assay and electrophoresis of acid lipase in cultured amniotic-fluid cells. Cells from patient 1 had 5% of control levels of acid lipase, using 14C-triolein as substrate; however, when artificial substrates (esters of 4-methylumbelliferone and p-nitrophenol) were used to measure acid lipase, these cells had 30% of control levels. Electrophoresis of cell extracts revealed the absence of the A form of acid lipase, consistent with the diagnosis of Wolman disease. Analysis of fetal tissues following prostaglandin termination of this pregnancy confirmed the diagnosis. Assay of fetal-skin fibroblasts with 14C-triolein, as well as with artificial substrates, showed marked deficiency of acid lipase activity. Electrophoresis of fetal-tissue extracts also demonstrated the absence of the A form of acid lipase. Amniotic-fluid cells from patient 2 showed normal levels of acid lipase with all substrates tested; the electrophoretic pattern of acid lipase was normal. The results suggest that the prenatal diagnosis of Wolman disease be made using the radioassay of acid lipase and/or electrophoresis.


Effect of prostaglandin synthetase inhibitors on pressor response to angiotensin II in human pregnancy. Pregnant women destined to develop pregnancy-induced hypertension (PIH) lose refractoriness to the pressor effects of infused angiotensin II (A-II) several weeks before the onset of hypertension. This loss of refractoriness to A-II is unrelated to plasma renin activity or circulating levels of A-II. In animal studies it has been shown that the prostaglandins are important mediators of vascular reactivity. Specifically, the uterine blood flow appears to vary directly with prostaglandin E concentrations in uterine venous effluent. The present study was designed to evaluate the effects of prostaglandin synthetase inhibitors on the pressor effects of A-II in human pregnancy. The "effective A-II pressor dose" (nanograms of A-II X kg-1 X min-1 necessary to cause a 20 mm Hg rise in diastolic pressure) was determined in 14 pregnant women before and after treatment with either 25 mg indomethacin or 600 mg aspirin given twice, 6 h apart. The effective pressor dose required before treatment [22.7 +/- 3.4 ng X kg-1 X min-1 (mean +/- SE)] was significantly greater than that after treatment [8.7 +/- 1.2 ng X kg-1 X min-1 (P less than 0.001)]. The refractoriness to A-II observed in normal human pregnancy may be mediated in part by the action of prostaglandins or related substances produced in the arteriole.


Dynamic evaluation of prolactin secretion during the early hours of life in human newborns. PRL secretion was evaluated in 30 human newborns during the early hours of life. Both levodopa and pyridoxine administration failed to suppress PRL release in all subjects. Synthetic TRH elicited a constant, prompt increase in PRL levels. No significant changes were observed after somatostatin injections. These results demonstrate normal pituitary PRL reserve in newborns. The failure to respond to levodopa and pyridoxine administration might reflect partial immaturity of the pituitary dopaminergic receptors.


Detection of ovulation by a radioreceptor assay for human luteinizing hormone. A specific, sensitive, and rapid radioreceptor assay (RRA), employing membranes from bovine testes as receptor and [125I]hLH as radioligand, has been developed for measurement of human LH in serum. This RRA was used to determine the time of ovulation in seven women. For comparison, four hourly values around midcycle were measured by RIA. The sensitivity of the RRA was 0.78 ng/ml serum and could be increased by prolonged incubation. The coefficient of within and between assay variation at the 50% inhibition level was 7% and 13%, respectively. The mean index of discrimination (RRA/RIA) was 1.02, expressed by the slope of the regression curve. The coefficient of correlation was 0.97. In all women, the LH surge was detected by RRA, and the subsequent ovulation was verified within 30 h by endoscopic examination of the ovaries, as well as serum progesterone concentrations of more than 5 ng/ml on the fifth day after ovulation. As shown, prospective ovulation timing can be done by this simple and accurate method. The RRA can be useful in infertility therapy such as artificial insemination.


Effect of chronic administration of estrogen, androgen, or both on serum levels of gonadotropins in adult men. Ethinyl estradiol (50 micrograms/day) or fluoxymesterone (10 or 20 mg/day), chosen because each is orally active and because fluoxymesterone is probably not converted to an estrogen, were given alone and in combination to adult men over several weeks. Measurements were made of serum FSH, LH, testosterone, and estradiol. The estrogen given alone suppressed serum FSH while the androgen given alone did not; however, the androgen may have enhanced the suppressive effect of the estrogen on the serum FSH. Neither steroid alone changed the serum LH but both together suppressed it. The estrogen alone decreased the serum testosterone, an effect probably mediated by the concomitant fall in serum FSH and a resulting decrease in sensitivity to the constant level of LH; a direct effect of estrogen on the testis seems less likely. The doses of estrogen and androgen used probably had a biologic effect equal to or somewhat above that of endogenously produced estrogen and androgen and thus reflected the maximum physiological effects of the endogenous steroids. Thus, in the chronic physiological control of FSH and LH in adult men, these data indicate that (1) testosterone alone, as an androgen, has little effect on FSH or LH, (2) estradiol (or total estrogen) has a greater suppressive effect on FSH than on LH and by its effect on FSH may indirectly regulate the secretion of testosterone, and (3) testosterone and estradiol together may be involved in the regulation of both FSH and LH.


Gynecomastia as a familial incomplete male pseudohermaphroditism type 1: a limited androgen resistance syndrome. Four postpubertal 46 XY male patients with an inherited form of bilateral gynecomastia were studied to delineate the nature of the disease. Normal serum FSH and moderately elevated serum LH with concomitantly increased circulating levels of testosterone (T) and estradiol (E2) were found persistently in all cases in blood samples drawn at frequent intervals. LRH pituitary stimulation resulted in an exaggerated LH response and a normal FSH response. Chronic administration of T-cyclopentylate failed to decrease serum LH levels. The peripheral conversion rate of androstenedione to estrone was within normal limits. All patients had low ejaculate volumes with relatively normal spermatozoa counts. Testicular biopsies revealed normal Leydig cells and complete spermatogenesis. Urological examination disclosed that the prostate gland was extremely small. The breast tissue demonstrated the presence of tubular structures as well as the specific binding of [3H]T and [3H]dihydrotestosterone (DHT), which was inhibited by nonlabeled T, DHT, E2, and progesterone, but not by cortisol. The pedigree suggested a recessive X-linked inherited trait. A patient with a nonfamilial form of gynecomastia served as a control in all studies. These data were interpreted as demonstrating that this inherited type of gynecomastia represents the mildest expression of the androgen resistance syndromes and, therefore, belongs to the type 1 form of familial incomplete male pseudohermaphroditism.


Radiographic features of fucosidosis.

Radiographic features of fucosidosis. Fucosidosis is an uncommonly recognized lysosomal storage disease which presents with psychomotor deterioration and progressing in some cases to death. The roentgenographic findings in five boys from three families are described. Skeletal abnormalities of a dysostosis multiplex nature are present and though not diagnostic should direct the clinician to perform appropriate biochemical and tissue assay studies to establish the diagnosis.


[Comparison of the transplacental effect of luminal and epileptic seizures in pregnant rabbits on the development of the fetal nervous system]. The aim of the study was to compare the effect of phenobarbital given to pregnant rabbits and of epileptic seizures on the course of pregnancy, the physical state, and central nervous system development of newborns. Phenobarbital was given orally during whole pregnancy or for the last ten days in amounts 18,5 mg/kg/body weight = 0,1 DL 50. Seizures of "grand mal" type were evoked with electrostimulator every day since the tenth day of pregnancy. Phenobarbital penetrates via placenta, reaches the organs of all fetuses, and seizures provoke hypoxaemia of fetuses. Phenobarbital administered during whole pregnancy exerts an teratogenous effect. Both injurious factors applied after teratogenous period cause a retardation of general development of fetuses. After phenobarbital administration slight brain lesions are visible in the light, electron microscopical and histochemical examination. More evident was the retardation of the development of the central nervous system after both of the examined injurious factors. In the brain stem and in the cortex the neurons are less mature and the synaptic junctions in the cortex are less numerous. In our experimental models phenobarbital seems to evoke more noxious effect than seizures in mothers.


On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. The role of ascending noradrenergic (NA) and dopaminergic (DA) systems in intravenous self-administration of cocaine in rats was investigated by examining the effects of 6-hydroxydopamine-induced lesions of these systems on responding for the drug on a FR-1 schedule of reinforcement. Lesions of the dorsal and ventral NA bundles that reduced hippocampal-cortical NA by 96% and hypothalamic NA by 72% failed to have any effects on responding for cocaine. Lesions of the nucleus accumbens that reduced the DA content of this nucleus by 90% resulted in a significant and long-lasting (15 days) reduction in self-administration of cocaine. Apomorphine self-administration was not affected in the same animals. Identical lesions of the n accumbens had only transient (2-3 days) effects on food-reinforced operant responding, suggesting that the prolonged disruption of cocaine self-administration was not the result of motor deficits. The results are discussed with reference to the possibility that DA terminals in the n accumbens may mediate some of the positive reinforcing properties of cocaine.


Alpha-L-fucosidase in cultured bone marrow fibroblasts from fucosidosis patients. Bone marrow fibroblasts were cultured from two patients with fucosidosis type 2, six control subjects, and three patients with other lysosomal disorders. Optimal conditions for measuring alpha-L-fucosidase activity in lysates of these cells with the fluorogenic substrate 4-methylumbelliferyl-alpha-L-fucoside were established. The pH profile of normal bone marrow fibroblasts showed three peaks and a shoulder of enzymatic activity, with maximum activity at pH 4.75. In cells derived from fucosidosis patients two peaks of apparent alpha-L-fucosidase activity were obtained; the pH optimum was 4.5. alpha-L-Fucosidase activity (mean +/- SD) in the fucosidosis and control bone marrow fibroblasts was 2.5 and 312.4 +/- 10.9 nmoles 4-methylumbelliferone per milligram protein per hour, respectively. A reduction in the apparent specific enzymatic activity in the fucosidosis cells was observed by using increasing concentrations of cellular protein in the assay system. Mixing experiments between normal and fucosidosis cells gave the expected activities. These findings indicate that cultured bone marrow fibroblasts can be used for the diagnosis and study of fucosidosis.


Analysis of the gross anatomical variations found in four cases of trisomy 13. The variations and defects observed during detailed gross anatomical dissections of four cases of trisomy 13 are described. Emphasis is on the muscular system where previously undocumented variations, absences, and supernumerary elements were observed. A muscle phenotype which includes absence of palmaris longus, palmaris brevis, plantaris, and peroneus tertius, the presence of pectorodorsalis muscles and muscles from the central tendon of the diaphragm to the pericardium near the pulmonary veins, and variations in the extensor indicis, extensor carpi radialis longus and brevis, biceps, and suprahyoid muscles is discussed. The brain defects which include absent olfactory bulbs and tracts and hypoplastic commissures are compared to those defects seen in cases of alobar holoprosencephaly wherein severe defects of the ethmoid bone are concomitants. Previously well-documented defects of the viscera are included.


Endocrine regulation of reproductive development and function in the male. Sexual development is an ordered process that begins at the moment of fertilization and terminates with the production and transfer of viable gametes. The formation of the male gonad depends upon genes located on both sex chromosomes and autosomes. Differentiation and growth of the male reproductive system is directed by the fetal testis through the production of a putative peptide which causes the regression of the Mullerian ducts and the secretion of testosterone which virilizes the Wolffian duct and thereby directs the differentiation of the internal accessory structures of reproduction. A third hormone, dihydrotestosterone, is synthesized intracellularly from testosterone within the urogenital sinus and tubercle. The action of this hormone controls the formation of the prostate and the external genitalia characteristic of the male phenotype. The postnatal growth of the testis and accessory sex tissues follows a characteristic curvilinear pattern with the most prominent increments coincident with the onset in testosterone production. Spermatogonial differentiation may proceed in the absence of hypophyseal or gonadal hormones but the respective maturation divisions of primary and secondary spermatocytes and the completion of spermiogenesis are clearly dependent upon testicular steroids produced under the influence of LH. Germ cells differentiate in a unique environment created, in part, by the blood testis barrier which arises as a result of tight-junctional complexes formed between adjacent Sertoli cells. Sertoli cells actively secrete fluids and export an androgen binding protein under the influence of androgens and FSH. Maintenance of spermatogenesis depends on high intratubular concentrations of testosterone, provided in part by the steroidogenic actions of LH on the Leydig cell and, in part, by the production of androgen binding protein by the Sertoli cell. Thus, both gonadotropins act in concert to maintain germ cell production. Selective removal of either LH or FSH curtails sperm production but testosterone supplementation, in adequate amounts, allows spermatogenesis to proceed in the absence of the pituitary gland.


Controlled evaluation of a hospital-originated community transitional system. The effect of a treatment program (E) providing inpatient care, a day hospital, community housing, and sheltered work are compared with a program (C) emphasizing rapid discharge. A group of 94 male general psychiatric patients were randomized to the two units. Outcome data collected at 18 months from admission revealed small but significant differences between the total samples in employment, maintenance of treatment contact, use of medication, and social adjustment. More C than E patients were in the hospital after the 14th month. Program effects varied considerably with patient type. Patients with less social disability had somewhat better employment outcomes with the E program, but no differences in use of services. Patients with a better prognosis by measure of psychopathology (Minnesota Multiphasic Personality Inventory cluster and diagnosis of schizophrenia) spent less inpatient time in the E program, but were not helped to better employment outcomes. Patients with greater social handicap were not differentially affected. More E patients than C with a poorer prognosis stayed in outpatient treatment and used antipsychotic medications. Patients in the E group with better previous employment and more social isolation used the E day hospital and community housing more heavily than other E subgroups.


[The meningoencephalitis syndrome in brain tumor]. In an evaluation of the medical records of 765 patients with brain tumours treated since 1951 in our clinic we selected those cases where there was a pleocytosis in the cerebrospinal fluid of more than 15/3 cells. We were interested to know whether a connection which would help diagnosis could be made between the occurrence and the degree of pleocytosis, the biological valence and the localisation of the tumour. In 181 cases (24%) there were more than 15/3 cells. Therefore, no conclusions about biological valence and tumour localisation could be drawn from the aspect of the cell picture which we observed and from the degree of pleocytosis. Basically, the occurrence of pleocytoses was more frequent in the case of malignant tumours and those tumours associated with the fluid canal system (plexus papillomata, ependymomata, craniopharyngeomata). Problems of unspecific meningeal irritative syndromes are being discussed in connection with brain tumours. These are being clarified on the basis of selected cases.


[Acute psychoses of advanced age].

[Acute psychoses of advanced age]. The group of acute psychoses in later life comprises: 1. acute psychotic pictures at the commencement or during the course of organic breakdown; 2. strictly speaking exogenous (symptomatic) psychoses 3. acute psychotic conditions during the processes in particular of endogenous psychoses; and 4. psychoreactive and situationally conditioned psychoses. In all these nosologically heterogeneous forms certain characteristics regarding their appearance and course can be perceived which are related to age a rudimentary type of syndromic pictures, their particular "senile" colouration, a preponderance of short and recurrent psychotic periods, a not infrequent change to dementia, and the occurrence of illnesses typical of old people (amnestic states of disorientation, complete optical illusions, etc.). The outlook for acute psychoses in later life is gloomy (almost 50% fatality); the recognition of basic illnesses causes particular difficulties. Some special clinical forms are being more intensively analysed.


[Catamnestic studies of 107 patients receiving inpatient treatment 1966-1969 because of attempted suicide]. An act of suicide is understood as a sort of decompensation inside a schizophrenia, a cyclic psychosis as described by Leonhard, or a reactive depression, but is in particular the expression of a depressive reaction and the end result of a depressive neurotic development. 107 patients (55 men and 52 women) were under constant treatment because of suicide attempts: 37 cases of depressive neurosis, 23 cases of depressive reaction, 7 cases of reactive depression, 10 cases of hysterical reaction, 8 alcoholics, and 22 endogenous psychotics. In 1974 there were still 50 patients under examination. 22 patients were no longer alive, 15 of which had committed suicide. Check-ups showed that the depressive neurotics and reactive depressives had an emotive personality stress, whilst the cases of depressive reaction appeared mostly beyond help.


[Psychiatric first aid by telephone--"the telephone of trust"]. From the experiences of the telephone system for psychiatric advice "Telephone of Trust" installed in CSSR in 1964, and a closer observation of the telephone point which has been operating in Brno since 1965 (with over 48 calls to its name already) recommendations are being made regarding the eventual installation and operation of these telephone points, the usefulness of which, in the sense of advice in cases of "problems in life", has already been demonstrated, for primary and secondary prevention of psychic disorders, crisis intervention and psycho-hygiene.


[Motiveless extreme psychosocial forensic actions]. Theory, diagnosis and terminology of traditional psychology apply to the subject which had previously been dealt with exclusively, most of all to psychoses in which the habitual and constitutional aspects have always been in the foreground. For questions on acute psychiatry, here set down in the form of examples, the paper deals with the experience of these restrictions, the structural motivation of the process and the interpersonal situation. This is equally valid for healthy people, neurotics and psychotics.


[Acute disease conditions and emergency situations in psychiatry]. Beyond a fundamental observation of the characteristics of acute illnesses and emergencies in psychiatry (symptomatology, progression and personality as a pathogenic factor), pathogenic conditions (somatic causes, personality, environment) are described together with typical syndromes and therapeutic principles.


[Intensive neuroleptic treatment in schizophrenias]. A report is made on the first results of the treatment with Droperidol of subacute illnesses of the schizophrenic type. Droperidol is a quick-working, very potent neuroleptic which leads to rapid comfort in cases of psychomotor conditions of agitation. The idea is discussed that Droperidol tends to accumulate and, beyond mere sedation, produces an excessive anti-psychotic effect which provides a favourable medium for the further introduction of other neuroleptics.


[Pathophysiology of delirium].

[Pathophysiology of delirium]. Based on a series of known facts on clinical findings and changes in the metabolism of chronic alcoholics and delirious people the possible pathomechanism of cerebral imbalances is presented according to a synopsis. The clinical symptomatology, in particular vegetative symptoms and the coordination of reflexes - to which more attention should be paid than has been up to now - make delirium appear a diencephalic illness, the sympathicotonic and ergotropic development of which together with a preponderance of noradrenergic-adrenergic mechanisms, remains unexplained to this day.


[The danger of developing drug dependence in adolescents]. The authors, by reference to a number of patients taking higher-than-prescribed doses of tranquilizers, sedatives, and hypnotics, thus becoming addicted to using them as drugs, describe some of the motivations of juveniles to take drugs. Problems associated with habituation to the use of drugs are discussed from sociological, medical, and psychological points of view. Also, attention is drawn to the fact that disturbed secondary structures in both family and personal life as well as certain primary premorbid psychopathological structures may, in principle, lead to drug addiction. The need for early recognition and prophylaxis is pointed out.


[Complications and emergency conditions in acute inflammatory brain and spinal cord diseases]. A therapy comprising large doses of combined antibiotics and sulphonamides is the best way to prevent complications. Allowances are made for side-effects. OTC or similar widespectrum antibiotics, if there are no penicillin G or new better agents available, are to be used in conjunction with hydantoins because of the increase in excitability and the convulsivant effect, and cerebral decompensation as a result of the edematous effect should be prevented through early osmoregulation. In emergencies concerning central respiratory and circulatory disorders the best choice is artificial respiration with infusion therapy and osmoregulation. Success is gained by the use of discernment, both great and small amounts of effort, but most of all by the exercise of patience.


[Acute disease pictures of cerebrovascular origin in childhood]. To summarize it can be said that an analysis of 1080 cerebral angiographies of children and juveniles up to 16 years of age and an examination of clinical results obtained for a stock of unsifted pediatric and neurosurgical patients allowed as many as 145 cases of vascular processes to be detected in children and juveniles. This number appears to be relatively large even if we consider that we are concerned here with a selected patient stock of a supraregional specialized clinic. If we also consider that the number of angiographies presently performed in cases of vascular disease processes is still comparatively small and that patients have to wait indiscussibly long times before being finally angiographed, then it is obvious that many a vascular disease process still goes undetected or is either misinterpreted or made clear at too late a time. It is here that much remains to be done in order to provide the necessary material basis, for what we still lack is the necessary number of costly diagnostic facilities with highly qualified diagnosticians as well as the necessary follow-up facilities such as, for example, neurosurgical, vasculosurgical, and intensive care units. We therefore welcome recent improvements in this direction, especially since the realization of a large-scale project would make possible an optimum diagnosis and treatment of vascular disease processes in both children and juveniles.


[Diagnosis of increases in acute intracranial pressure in infancy and early childhood]. The results reported in this paper were obtained from 276 cases (babies and infants) with increases in intracranial pressure. In 88 cases the cause of disease was not clear, while 35 patients showed symptoms of an acute increase in intracranial pressure so that diagnosis was an urgent necessity. With subdural hygromata, clinical results obtained for acute rises of pressure usually differ greatly from those obtained for chronic increases of pressure. The diaphany of skull is usually negative. Fundal hemorrhages were observed in acute cases only. Critical cerebral pressures were most frequently observed in the case of tumors. The diagnosis is rather difficult. In the case of functional immaturity of the brain localized neurological symptoms are not usually observed. The cerebral pressure is generally counterbalanced for a long time so that an acute cerebral symptomatology is not produced until tumoral complications, shifts in cerebrospinal fluid passages, intracranial mass shifts, or tumoral hemorrhages occur. Unlike all other groups of diseases, symptoms of rises of intracranial pressure were very marked. Malformations of the posterior cranical fossa included acute occlusions in the case of Dandy-Walker syndromes and arachnoidal cysts. In the case of severe cerebral malformations, acute increases in intracranial pressure are sometimes erroneously concluded from an abnormal increase of the size of head accompanied by a complete lack of reactions on the part of children affected with them. Children with hydrocephalus caused by a disturbance of the circulation of liquor are now treated with pressure-controlled liquor drainage systems. Critical cerebral pressures may occur if the drainage system suddenly fails to operate properly.


[Post-traumatic intracranial pressure crisis in childhood]. The author in his present paper discusses traumatic cerebral pressure crises with particular reference to the aggregate of symptoms involved, the therapy to be employed, and the results of treatment obtained. So far as measurements of the pressure of liquor are concerned, single measurements were found to yield reliable values in rare cases only. On the other hand, the value of the pressure of liquor, when used in combination with the arterial systemic pressure, permits to roughly determine the cerebral perfusion pressure and build a suitable therapy thereon. Hyperventilation therapy, the use of which is strongly recommended here, has proved a very important addition to cerebral pressure treatment.


[Prognosis of childhood brain injuries in relation to acute post-traumatic syndrome]. Long-time follow-up examinations of 196 children, who had been suffering from severe and moderately severe cerebral traumata, gave abundant proof of the view that neurological disorders occurring at the age of childhood are characterized by a positive development of the disease, a view that is held by all authors. Cerebral ailments characterized by attacks usually manifest themselves within one year after the accident. The younger the children at the time of accident, the higher the number of posttraumatic diseases characterized by attacks. Children with convulsive phenomena in the acute posttraumatic phase usually show a greater tendency toward later diseases characterized by attacks. Every fourth child with initial convulsions and every seventh child without such an early symptomatology suffered from attacks in the further course of disease. Four out of 32 children were, in spite of careful treatment, not free from attacks after 10 years from the accident. The younger a child is at the time of accident the more unfavorable is the prognosis as regards personality development, intelligence, and scholastic records. Also, there is a clear dependence upon the severity of the cerebral trauma. Most pronounced permanent handicaps were observed in young children with severe cerebral traumata. A posttraumatic ailment characterized by attacks tends to worsen any prognosis.


[Early therapy of an apallic syndrome in childhood]. The various phenomenal forms of apallic syndromes are described from an etiological point of view, and it is shown that remission may be expected only in cases of apallic syndromes occurring as a result of acute traumatic, inflammatory, and metabolic and toxic processes. It is only in such cases that the use of all available means of reanimation treatment is fully justifiable. The most important aspects of maintaining vital functions especially in the initial stage as well as in the transitional phase of the apallic syndrome are described by the authors who also emphasize the necessity for continuous integrative cooperation between anesthetists and specialists in pediatric neuropsychiatry.


[Encephalic syndrome following trauma of the cervical vertebrae in childhood]. The author, by explaining and taking the "encephalic syndrome", which was first described in 1949 by Bärtschi and Rochaix, as a base, gives a detailed description of a corresponding syndrome for the age of childhood. After discussing the clinical symptomatology, course of disease, etiology, and pathogenesis, he describes the method of differential diagnosis that allows a clear distinction to be made between the encephalic syndrome and commotio cerebri and commotio spinalis. From a stock of 50 patients with vertebragenic headache it was possible to isolate 5 cases with encephalic syndromes due to cervical vertebral column traumata. The actual number of such cases would doubtless be much higher if it would be possible for pediatric neurologists to examine all cases of craniocerebral traumata in children. The clinical characteristic - according to anamnestic, actual clinical, and catamnestic findings - was a chronical and progressive symptomatology of headache after the disappearance of symptoms of commotion with resistance to therapy with conservative agents since this is a vertebragenic type of headache ("cervical migraine") caused by either a blockade of the upper cephalic joints or insufficiency of ligaments. The necessity of establishing a specific diagnosis arises from the fact that this allows the ailment to be treated by methods of manual and physical therapy, relieving both mother and child from the diagnosis of damage to the brain, which is highly disadvantageous to them from a social prognosis point of view.


[Problematic psychological status of epileptic children]. Among 1000 patients receiving medical treatment at the Budapest Center of Medical Care for Epileptic Children it was possible to repeatedly observe seizure-independent psychic conditions of a critical character. Those conditions which were most frequently observed were classified into six groups, namely Restlessness or pseudodementia caused by frequent seizures. Excessive doses or intolerance of drugs. Exaggerated alarm on the part of the parents. Neglect on the part of the parents. Reactive conditions in those cases where an unsuitable occupation was chosen. In the majority of cases, failures due to the contradiction between the subject's intellectual abilities and the expectations of the persons around him. Particular emphasis is placed on the importance of well-timed prophylactic and therapeutic measures.


[Convulsion in the child as emergency condition in a university polyclinic]. A total of 38 children suffering from convulsions were referred to our specialty clinic within a period of six months. However, what was necessary in this connection was that the attack of spasm should not have occurred more than 12 hours before admission to our clinic. The case histories are reported. Our diagnostic and therapeutic concepts are described.


[Acute myopathic syndrome].

[Acute myopathic syndrome]. Acute myopathic syndromes are very rarely encountered in the static neurological list of illnesses. Most of them have to do with crises, functional myopathia, for example myasthenia, paroxysmal paralyses, etc. The possibilities of therapy are outlined. A certain centralization of myological diagnoses, therapy and rehabilitation seems appropriate.


[Extreme psychogenic shock states in childhood]. An attempt is made in this paper to describe a syndrome consequent upon extreme psychogenic shock situations, which has been observed in a number of children. This syndrome is characterized by panic, flight, and anxiety during the actual event, which are followed by a relatively prolonged period of exclusion from consciousness of painful memories. Besides, there may be observed neurotic symptoms manifesting themselves in a decrease in proficiency level, refusal to establish contacts with other people, and mental digestion of the events. Assimilation of the events by intensive psychotherapy seems to be possible within about six months. Also discussed in this paper is the problem of actual neurosis and the origin of preconscious repression.


[Suicide attempts in children. Follow-up in picture figures]. This is a report on 15 children who, after having committed acts of taking their own lives voluntarily and intentionally, were admitted, between 1971 and 1974, to the Pediatric Clinic of Neuropsychiatry, Brandenburg District Mental Hospital. The number of boys (10) was greater than the number of girls (5). Fourteen children were at the age of puberty (i.e., between 12 and 15), while only one child was under 10. A brief description is given of the various causes of suicidal acts committed by children. The children's personalities are also described. All of the patients, right from the start of impatient treatment, were included in a program of drawing and painting in addition to the medical and psychotherapeutic treatment given to them. For this creative activity, a studio was made available where the children, in the presence of the therapeutist, could make drawings or pictures with paints. The explanations given by the patients of their respective drawings or pictures were carefully recorded by the therapeutist. The pictures made by two patients, who had made several attempts upon their own lives, are presented along with the explanations given by them. One of the boys is a child who had been in an educational establishment for many years, while the other boy came from an orderly family. Regarding the therapeutical drawing and painting program it can be said that this nonverbal form of expression results in the children becoming physically and psychically relaxed, making them willing to freely explain the contents of their drawings and pictures.(ABSTRACT TRUNCATED AT 250 WORDS)


[Acute and chronic respiratory insufficiency in diseases of the nervous system]. From the practical experience gained in a neurological intensive-care ward criteria and parameters which require specific consideration in long-term artificial respiration are reported. These empiric data were gathered in the reanimation of 490 patients suffering from different illnesses of the nervous system. Treatment was most efficient in the cases of acute poliomyelitis, polyradiculoneuritis, botulism and myasthenia gravis. A detailed account is given of the metabolic changes observed in the application of artificial respiration. The facts reported indicate that during long-term artificial respiration the blood gas metabolism changes and the vital regulatory centres adapt to the condition.


[Prognostic significance of myoclonias in aerospace altitude studies and others with acute hypoxia-accompanied status]. Motor phenomena - mostly in the form of myoclonus in the widest sense - are not rare in aeromedical studies conducted at flight altitudes and involving severe and acute hypoxia. At the same time medium to severe general changes can be observed in the EEG. When oxygen is supplied the motor phenomena stop after a few seconds, and the EEG results become normal again. These reversible changes are contrasted with clinical findings after anoxic coma conditions and hypoxic accidents which occurred during flights and where the myoclonus survives the coma, which is an extremely grave prognostic indication.


[Clinical and electroencephalographic follow-up of consciousness disorders]. A report is given of the experience gained in close-meshed neurological and electroencephalographic observations of unconscious patients suffering from acute and severe brain damage of different aetiology. Only in some cases can the neurological findings be assigned to the midbrain or bulbar brain syndromes - in our material this is possible only after skull-brain traumas and subarachnoid haemorrhage but least of all after hypoxic accidents and brain operations. The vegetative functions often show inconsistency and do not always correspond with the rest of the neurological findings. Selected examples are used to make an assessment of electroencephalography in the interpretation of severe and acute brain damage.


[Frequency of different prodromal signs in cerebrovascular insult]. 137 courses of illness were studied to determine, for different age groups, the incidence of early symptoms such as headache, dizziness, sleep disturbances, asynchronism, photism and singing and other sounds in the ear. The significance of prodromic signs, including uncharacteristic ones, in the overall diagnostic interpretation of cerebro-vascular insultus is indicated.


[Value of ophthalmodynamography and ophthalmodynamometry in acute cerebrovascular processes]. Methods of examination are briefly described and findings are then reported for cerebral vascular processes. The results have been assessed in comparison with the angiographic picture. The authors conclude that both ophthalmodynamography and ophthalmodynamometry can be used to record haemodynamic changes resulting from stenosing vascular processes in the extra-cranial cerebral vascular area. The two methods are non-operative and involve little stress on the patient during examination so that they may be used for preliminary diagnostic purposes.


[Lipids in serum and cerebrospinal fluid in acute cerebrovascular disorders]. The cholesterol and lipoid phosphorus levels in the serum and liquor' cerebrospinalis were studied in 40 patients suffering from ischaemic cerebral lesions. A chromatographic determination was also performed for eight sub-fractions of polar and neutral fats (lysolecithin, sphingomyelin, lecithin, phosphatidyl-ethanolamine, non-esterified fatty acids, cholesterol, triglyceride and cholesterol ester). Furthermore, five sub-fractions of cholesterol esters were prepared according to the degree of unsaturation in the individual fatty acids. The results were compared with a group of 25 control persons. No significant changes in the lipide sub-fractions were found in the serum. Total cholesterol was lower for cerebral haemorrhages, lipoid phosphorus was higher. In the liquor, no increase was found in total lipides but only a shift in some lipide fractions, the most pronounced being a lowering in triglyceride and an increase in free cholesterol and sphingomyelin. It would seem that a determination of lipides in the serum and liquor is not decisive for the diagnosis of acute vascular cerebral haemorrhages. These questions require thorough research and experimentation.


[Acute cerebrovascular disorders caused by ovulation inhibitors]. Cerebral circulatory disturbances occurred in 42 women between the ages of 17 and 52 who were taking oral contraceptives. The disturbances were primarily in the form of cerebral haemorrhages. The symptoms ranged from ephemeral neurological deficiencies to massive hemi-syndromes. Complete remission occurred in 16 patients, partial remission in 24 patients, two patients died. The patients were subdivided into two age groups, one comprising 31 persons between 17 and 39, and the other 11 persons between 41 and 52 years of age. The aim was to ascertain facts which were related to the possibility of haemorrhage in women taking ovulation inhibitors. The first finding, statistically significant, was that the possibility of a cerebro-vascular disturbance increases with the period during which the pill is taken and that this possibility is especially great in the presence of migraine which may also be existent in the family, and in the case of hypertension. The second finding, not significant however, was that the risk was higher in the presence of several factors in one person. These factors include familial factors with a predisposition to migraine and thrombosis, past illnesses of the peripheral vascular system, a predisposition to allergic reactions, obesity and kidney damage. Should one of these situations or both prevail, the patient will be advised to stop taking the pill, and the contraceptive will be discontinued if certain prodromes are observed in a general form, or if focal symptoms occur.


[Experiences in intensive therapy of apoplectiform pictures of cerebrovascular insufficiency]. Our observations indicate that attention should be paid primarily to the following, in the sequence given, when applying intensive therapy to patients suffering from apoplectiform phenomena of cerebro-vascular insufficiency: keep the respiratory passages open, prevent inflammatory processes, especially bronchopneumonia, give an optimum supply of calories, water and electrolyte to patients in the comatose state, compensate for disturbances in the central regulation of respiration and circulation, combat disturbances of the acid-base balance and prevent cerebral oedema and hyperthermia from central causes. The report was to emphasize the gasometric results of our studies which indicated that 65 per cent of the patients in this group suffer from significant hypoxia and that respiratory alkalosis occurred in 34 per cent. The cause seems to be a disturbance in the respiratory passages which leads to hyperventilation and to subsequent respiratory alkalosis.


[Detection and monitoring of high-risk children]. The authors first describe problems related to the lowering of infant mortality and deal with the terms "high-risk factor" and "high-risk baby". As a result of the dangers presented by prenatal and perinatal noxae the need arises for low-risk births and optimal care of new-born babies. The public health system must be suitably organized so that babies with case history details can be supervised and others with cerebral motor disturbances without pathological data can be registered in the case history. In the registration of the latter group child-welfare centers have an important role to play. The way in which consulting hours for high-risk children are organized is described. Between 1973 and 1977 regular examinations were made of 1.500 high-risk babies, in three groups (150 premature infants without any additional load factors, 118 premature infants showing dyspnea syndrome, 80 new-born babies with prenatal dystrophy). Of these, the 118 premature infants with dyspnea syndromes had the highest overall percentage of border-line and clearly pathological findings in all examinations. Reference is made to symptoms which point to disturbed development, and to the importance of early diagnosis and therapy in the case of cerebral motor disturbances.


[Neurologic, electro- and echoencephalography studies of former high-risk children and control children]. First results of neurological, electro-encephalographic and echo-encephalographic examinations obtained from three different groups consisting of former high-risk babies (about two thirds) and control children (about one third) are presented. As was to be expected, the control group showed remarkably fewer findings which differed from the physiological variation width. The comparatively high proportion of individual results without pathological findings obtained from high-risk children indicates that reliable diagnostic conclusions can be drawn only if the results of various examination techniques are summarized. The analysis of a neurological longitudinal study of former high-risk infants reveals a trend toward recession of the neurological peculiarities over the observation period which lasted until the sixth year of age. This particularly applies to light phenomena of a neurological character which do not have syndrome character and are pathologically irrelevant. As a result of different interpretations of what "high risks" are, considerable problems can arise when the results of examinations performed on groups of high-risk children by various workers are to be compared.


[Follow-up studies of high-risk children at the time of entering school in comparison with a normal group]. Somatic, neurological and psychological follow-up examinations performed on 54 high-risk children for school enrollment gave no significant differences in comparison with a randomized equal number of normal control children, with regard to physical development and maturation as indicated by carporadiograms. So far as neurological development was concerned, there was a slightly more frequent occurrence of minimal defects and, anamnestically, a marked retardation in the mastering of static functions (running) and speech development in the high-risk group. The results were in correlation with the psychological test findings. Here, too, a more frequent occurrence of impaired intellectual functions was found, which led to a greater number of deferments, conditional enrollments and transfers to special schools. Prospective examinations afford better opportunities of etiologically classifying and registering defects, including light forms. In this connection problems of screening are also discussed.


[Catamnestic findings in breech-presentation births]. Connections exist between the delivery technique for breech presentation cases and the intellectual development of infants. Extracted infants show lower development quotients (EQ) than others delivered with a modified Bracht. Diagnostic symptoms of early brain damage are found in either group. No symptom combination appears to have a significant effect on the EQ level. A prospective delivery technique should be selected in the case of breech presentation on the basis of specific criteria.


[Value of the orthopedic examination of newborn infants with regard to the diagnosis of hip dislocation]. Out of a total of 10,617 new-born babies examined, 11.1 percent required supervision as a result of clinical signs pointing to a congenital dislocated hip joint, and 6 percent as a result of anamnestic indications. X-ray follow-up examinations after four months showed pathological hip joint findings in 27.7 percent of the patients under supervision. Out of a total of 1,587 new-born babies without pathological findings (both clinical and anamnestic), 1.2 percent showed pathological hip findings in an X-ray examination performed at the age of four months. The overall incidence of congenital dislocated hip joints was found to be 5.8 percent. The results point to the importance of regular and thorough hip examinations in child-welfare centers even after earlier checks on new-born babies which revealed no pathological findings.


[Development of dentition 4 to 6 years of age]. A longitudinal study has been made of the incidence of caries and malocclusion in 361 high-risk children and 180 control children aged between 4 and 6 years. A comparison of the findings obtained from the two groups showed no remarkable differences in the two areas of examination.


[Significance of early detection and early treatment of the development of children with phenylketonuria]. The amino acid l-phenylalanine (PA) accounts for 3-6 percent of all food proteins. Its breakdown is mainly through change into tyrosine. This irreversible metabolic step which makes PA an essential amino acid occurs in the liver and is catalyzed by PA-hydroxylase. In the autosome-recessive phenylketonuria syndrome (PKU, medium incidence rate 1:10,000) there is no PA-hydroxylase activity in the hepatic tissue. Infants suffering from PKU are born without any visible damage, but the untreated disease leads to irreversible brain injury. In the GDR legislation for early screening has been in force since 1971, so that the disease is recognized in all new-born babies. Brain damage can be prevented by dietetic treatment which starts during the first month but not later than the second month of life. The results of examinations performed on 107 infants suffering from PKU, with different onsets of dietetic treatment, underline the fundamental importance of early recognition and treatment for optimal development.


[Concentration of amino acids in synaptosomes of the rat brain in the preconvulsive phase of experimentally-induced seizures]. In the synaptic vesicae of rat brains the free amino acids were determined for control animals and experimental animals during the preconvulsive phase of induced cerebral spasms. Especially high concentrations were established for taurine, glutamic acid, asparaginic acid, gamma-aminobutyric acid and valine. Prior to a cerebral spasm the glutamic acid concentration is lowered in the synaptosomes.


[Social development of epileptic children and adolescents]. A report is given on 162 cases (90 men, 72 women) ranging in age from 22-27 years, where the course of the disease, school performance, integration into professional life and social achievement has been followed over periods between 10 and 20 years. Of these patients 60 percent are free from attacks, and half of them have been for more than 10 years. Among those still suffering from attacks the great majority have psychomotor and combined fits. One quarter of the patients experienced a change in the type of attack in the course of the disease. The school performance and professional achievement of the patients are viewed in relation to the type of attack, duration of the disease and the period of freedom from attacks, and discussed. About 75 percent of the group had had satisfactory achievements at school and experienced smooth integration into working life, but only half of this percentage were still working in the occupation for which they were trained at the time of a follow-up examination. About 10 percent had to take up some other employment on account of the disease, whereas the rest gave various reasons. Social development was favorable for the majority of the patients. More than half of the women and one third of the men have married in the meantime. The crime rate was 3 percent.


[Effect of post-traumatic epilepsy on the development of the child's personality]. A comparison is made between the intellectual development and school performance of children suffering from posttraumatic attacks and children who suffered brain traumas of comparable severity but no attacks afterwards. Retarded intellectual development is comparatively frequent in children suffering severe and medium brain traumas, but clearly more frequent in children showing posttraumatic attacks as opposed to those not experiencing these late complications.


[Etiology and rehabilitation of lip, jaw, palate and velum clefts]. The heredity rate among the patients treated by the authors (527 cases) was 14.4 percent. Most of the schistases were caused by exogenic noxae. Of 271 children affected, 83.1 percent entered school at the normal age and 14.7 percent later, whereas 2.2 percent were found not educable. A total of 88.5 percent went to ordinary schools and 9.2 percent to special schools. At the elementary stage 10 children (6.1 percent) had to repeat a year once. The most important task in rehabilitation is the full social integration of patients, and special attention must be devoted to the early recognition of developmental disturbances and their treatment through specific advancement measures.


[Catamnestic studies of normally intelligent encephalopathy patients among children and adults]. Our studies show that the special features in the psychic development of encephalopaths showing normal intelligence consist in delayed motor, intellectual and educational progress. While motor retardation is reduced with age, as a result of such factors as rhythmical and psychomotor musico-therapy, individual intelligence test results drop more frequently at school age. The drop is less marked in students attending special classes, although they go back to their original schools after grade 4. The trend toward deterioration in intellectual development is reduced with age, i.e. when educational progress as encouraged by society, slows down. Despite their normal performance with regard to intelligence these students markedly lag behind their healthy contemporaries as far as performance at school is concerned.


[Neurogenic disorders of bladder emptying in children]. Disturbed micturition of the neurogenic type is found in children suffering from spinal tumors and anomalies of the vertebral column. The most frequent cause is the so-called myelomeningocele. Myelodysplasia can occur in 1-2 out of every 1,000 new-born babies. Operative treatment is available today (closing the celes immediately after birth and drainage of the associated hydrocephalus) so that these children survive and their fate essentially depends on the early diagnosis and therapy of the neurogenic micturition disturbance. Urodynamic examinations and the determination of the urethra pressure profile are vital for diagnosis. Using the results four different groups can be established each requiring a specific therapy. Individual therapies must also be selected for each individual case. Apart from operative treatment, drugs and electrostimulation can be used on a large scale. The authors present their own experience and results with regard to diagnosis and therapy.


[Psychologic development of children with surgically treated myelodysplasias, craniostenoses and hydrocephalus]. The authors present the results of psychosomatic follow-up examinations performed on 40 children after myelodysplasia, hydrocephalus and craniostenosis operations. A total of 60 percent showed average intelligence (suitable for ordinary schools) despite considerable motor disturbances, and 27.5 percent could attend special schools. Psychic and somatic development was further differentiated using such criteria as concentration, vocabulary, running, incontinence and social conditions.


[Objective evaluation of the cerebral organic-psychiatric axis syndrome--experiences with the encephalopathy questionnaire]. This supplements the publication on "A standardized questionnaire for behavior typical of encephalopathy" (Meyer-Probst, 1978) which dealth with content validation and provisional calibration. The paper is concerned with external validation and, under such headings as "Axis syndrome and milieu factors", "Axis syndrome and school performance" and "Axis syndrome and age", presents the results from questionnaires of an extreme group comparison to illustrate the clinical and diagnostic value of the axis syndrome concept acc. to Göllnitz. Relations of dependence and the usefulness of assessment procedures are discussed, as well as the concept of the axis syndrome in connection with newer trends in specialized psychopathology research.


[Behavior of the Berger effect in boys brain-damaged in early childhood and in brain-healthy boys in a conditioning trial]. Berger effect behavior was tested in a group of 15 boys with early brain damage and a control group of 15 boys without an anamnesis of brain damage, with a view to development, conditioning ability and habituation. In the group of brain-damaged test persons the proportion of BE-positive subjects was markedly less in all trials. Habituation occurred earlier and in a larger percentage. The conditioning capacity was worse in each series. The phenomena observed suggest that subjects with early brain damage suffer from a disturbance in the general reticular action system.


[Disorders of psychological performance in mentally normal school children]. The authors deal with such psychic factors as weaknesses in concentration, reading and spelling which are to a major degree responsible for failure at school. These factors often occur in combination and may indicate early brain damage, in complex interaction with milieu conditions. Ample evidence of this is given in a literature survey. Principles of concentration training and a diagnostic verification procedure are then outlined, which have been derived from an analysis of attention requirements made at school. A therapy for reading and spelling weaknesses is dealt with, followed by a presentation of the results of training and catamneses. Using the method of Kossow mistakes were reduced by 78 percent and spelling marks improved considerably, after the children had returned to their original schools. In conclusion information is given on future projects for better assistance and prevention in the case of reading and spelling weaknesses at the elementary stage.


[Personality structure and child-rearing behavior of parents of children with psychologically defective development]. The personality structure and educational methods of parents exert considerable influence on the emergence of psychic defects in children. Tests have been conducted with a group where cerebro-organic damage but no psychic defects occurred, another group of children showing psychic defects and previous cerebro-organic injury, and a third group with psychic defects. In the last two groups there was a marked recurrence of traits from the personality structure of the parents, and a larger number of misguided attitudes and educational activities occurred.


[Methodology of parent group therapy (experiences with a social training program for parents of children and adolescents requiring psychotherapy)]. An analysis is made of the socio-psychological status of parents and their problems with regard to intrafamiliar social behavior, and then the aims of parent groups are defined. This is followed by a critical assessment of such methods as information groups, conventional training groups and dynamic group psychotherapy, all of which are unsuitable for this population. Then follows a discussion of the experience gained and results achieved, with a social training program for parents of children needing psychotherapy, where the disturbance in the child is an expression of family-neurotic disturbances. The accent is on the formation of motivations, sensitization to emotional signals, self-experience, feedback exercises and the mastering of partner-oriented conflict management behavior. The aim is to resolve neurotic family arrangements, so that the child is no more needed as a carrier of symptoms. The new attitudes and conflict management behavior should also be available in genuine educational situations. During the third phase of the program of exercises which consists of three parts, concrete problem situations are dealt within psychodramatic manner. As a conclusion special requirements for leading such groups are discussed with a view to therapists treating parents and children at the same time.


[Comments on a concept of clinical child psychology]. Arguments in favor of establishing clinical child psychology as an independent subject are first discussed, and then the discipline itself is defined as a comparatively autonomous domain of psychology. Using three examples (research on reading and spelling weaknesses, the development of the memory and social interaction in ecological fields) it is shown that clinical child psychology can and must develop also through the utilization of fundamental research. The examples are closely related to aspects of the "Defective child" research project.


[Intelligence findings in children and adolescents with congenital cataract]. In children and young people with congenital cataracts the verbal intelligence quotient gives higher values than the perceptive-practical IQ. Longitudinal studies show the IQv reduced, but not the IQH. Connections exist between visual acuity and the IQ value, and the causes can be assumed to be disturbances of verbal information processing.


[Factor structure of psychopathologic symptoms in the pre-school age]. The authors present a factor analysis of 49 psychic and physical peculiarities found in 294 children in creches, most of them high-risk children; these were perinatologically classified at the time of birth, and an examination was performed by neuropsychiatrists and a follow-up clinical and psychological examination made, at the age of 2.0-2.3 years. The following two problems were of interest: 1. Can psychosyndromes be detected in creche children and, if so; 2. Does the psychosyndrome obtained through factor analysis contain vegetative symptoms? Results - The peculiarities can be grouped as follows: (table; see text) This is the first time that the existence of a pre-school chronic psychosyndrome has been detected using a multivariate method. Its basic structure is as described by Göllnitz. A discussion follows of its position within the symptom variability in damaged and disturbed children, and of rough brain localization analogies.


[Initial reports on experiences in working with special groups in child day care centers]. A decisive condition for advancement at an early stage is the detection of physical damage. In this connection the GDR Ministry of Public Health has published guidelines for the establishment of special groups for infants suffering from physical damage, at ordinary creches (Verfügungen und Mitteilungen 15/1976). In 1976/77 a total of eight special groups with 64 children were set up at creches in the city of Erfurt. The criteria for assigning children to such groups were age and the type/degree of damage, with the aim of having homogeneous group structures. Advancement was through an all-day teaching process, in which parents were involved by giving them guidance, inviting them for discussion evenings and calling on their homes. A description is given of the approach to teaching and methods and planning (written timetables for specific months, weeks and days), all of which are essential in creating adequate educational conditions taking into account individual differences in the level of performance and the prevailing primary damage (e.g. disablement, impaired hearing, marked milieu damage).


[Effect of the hypotrophy factor on the prognosis of the development of premature and newborn infants from the neurologic and psychologic viewpoint]. Neurological and psychological examinations have been conducted of prematurely born babies in good bodily condition and hypotrophic new-born infants (including control groups) as part of a not yet concluded longitudinal study. The hypoplastic premature infants showed a comparatively high proportion of statomotor retardation and neurological disturbances, which were also found in premature infants in good bodily condition with a pregnancy duration of 26-30 weeks. Cerebral motor disturbances were found primarily in hypoplastic new-born babies and especially in premature infants. The EQ (development quotient) for the premature infants in good bodily condition with a pregnancy duration between 26 and 30 weeks, and for the hypoplastic premature infants was lower than for other high-risk groups. These two groups were also responsible for the larger proportion of children showing light and medium psychic retardation. Behavioral peculiarities were, however, distributed also over other high-risk groups, and some were even more frequent there. It was also found that speech development was delayed. The study shows the necessity of following the development of high-risk babies and using individual therapies.


Phosphoenolpyruvate and 2-phosphoglycerate: endogenous energy source(s) for sugar accumulation by starved cells of Streptococcus lactis. In the absence of an exogenous energy source, galactose-grown cells of Streptococcus lactis ML3 rapidly accumulated thiomethyl-beta-D-galactopyranoside (TMG) and 2-deoxyglucose to intracellular concentrations of 40 to 50 mM. Starved cells maintained the capacity for TMG uptake for many hours, and accumulation of the beta-galactoside was insensitive to proton-conducting ionophores (tetrachlorosalicylanilide and carbonylcyanide-m-chlorophenyl hydrazone) and sulfydryl group reagents including iodoacetate and N-ethylmaleimide. Fluorimetric analysis of glycolytic intermediates in extracts prepared from starved cells revealed (a) high intracellular levels of phosphoenolpyruvate (13 mM; PEP) and 2-phosphoglycerate (approximately 39 mM; 2-PG), but an absence of other metabolites including glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-diphosphate, and triosephosphates. The following criteria showed PEP (and 2-PG) to be the endogenous energy source for TMG accumulation by the phosphotransferase system: the intracellular concentrations of PEP and 2-PG decreased with concomitant uptake of TMG, and a close correlation was observed between maximum accumulation of the beta-galactoside and the total available concentration of the two intermediates; TMG accumulated as an anionic derivative, which after extraction and incubation with alkaline phosphatase (EC 3.1.3.1) formed the original analogue; fluoride inhibition of 2-phospho-D-glycerate hydrolyase (EC 4.2.1.11) prevented the conversion of 2-PG to PEP, and uptake of TMG by the starved cells was reduced by 80%; and the stoichiometric ratio [TMG] accumulated/[PEP] consumed was almost unity (0.93). In cells metabolizing glucose, all intermediates listed in (a) and (b) were found. Upon exhaustion of glucose from the medium, the metabolites in (b) were not longer detectable, while the intracellular concentrations of PEP and 2-PG increased to the levels previously observed in starved cells. The glycolytic intermediates in (b) are all in vitro heterotropic effectors of pyruvate kinase (adenosine 5'-triphosphate:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from S. lactis ML3. It is suggested that the capacity of starved cells to maintain high intracellular concentrations of PEP and 2-PG is a consequence of decreased in vivo activity of this key regulatory enzyme of glycolysis.


Characterization of Pseudomonas aeruginosa derepressed R-plasmids. A genetic study of conjugal transmissibility of two R-plasmids was undertaken in Pseudomonas aeruginosa. Conjugally derepressed mutants of the R-plasmids were isolated, and examination of 11 independent mutants revealed that 10 were recessive to the wild-type transfer repressor, whereas 1 mutant was cis dominant. Cross-repression was observed between the two R-plasmids, suggesting that they have functionally equivalent systems for regulating the expression of tra loci. The derepressed R-plasmid mutants exhibited several characteristics, in addition to derepressed transfer, that were not expressed by the parental plasmids. These included sensitivity to certain donor-specific phages, inhibition of multiplication of a transducing phage, and, in the one case examined, a high degree of entry exclusion. The coexpression of these different functions suggests that their respective genetic loci are controlled by the same regulatory system as that of tra, or else that they are part of the tra complex.


Functional capacities and the adenylate energy charge in Escherichia coli under conditions of nutritional stress. Functional capacities in Escherichia coli cells starved for glucose were examined by comparing protein synthesis, utilization of new substrates, and maintenance of viability with the adenylate energy charge of the culture. When growth ceased because of glucose exhaustion in an E. coli culture, the energy charge dropped from 0.90 to about 0.80. During this time, the viable-cell count and the capacity for protein synthesis and for induction of new enzymes were maintained only if other substrates were available in the medium. The culture could be maintained for many hours without growth or death if glucose was added slowly; the energy charge in this case stabilized at about 0.80. A consistent transient decrease in the energy charge to around 0.80, accompanied by a decrease in protein synthesis, was also observed during the adaptation from glucose to other substrates during diauxic growth on glucose and glycerol or lactose.


Analysis of plasmid deoxyribonucleic acid in a cariogenic strain of Streptococcus faecalis: an approach to identifying genetic determinants on cryptic plasmids. Streptococcus faecalis strains ND539 and OG1 have been previously shown to be cariogenic in gnotobiotic animals. Deoxyribonucleic acid analyses have revealed the presence of a single 26-megadalton plasmid designated pAM539 in the former strain, whereas the latter strain was found to be plasmid-free. By gene transfer experiments, it was possible to construct isogenic pairs of strains that differed only with regard to the presence or absence of pAM539. Comparative studies of isogenic pairs showed that the presence of pAM539 conferred bacterial sensitivity to a bacteriocin produced by S. faecalis strain 5952.


Bacterial mutation affecting plasmid maintenance in Pseudomonas aeruginosa. A bacterial mutation, risA, in Pseudomonas aeruginosa caused growth inhibition at 43 degrees C of risA strains containing P2 plasmids. Incubation at 43 degrees C resulted in selection for clones that had lost P2 plasmids.


Characterization of plasmids determining hemolysin and bacteriocin production in Streptococcus faecalis 5952. Two plasmids designated pOB1 and pOB2 were isolated from Streptococcus faecalis strain 5952 and found to have molecular weights of approximately 46 X 10(6) and 28 X 10(6), respectively. pOB1 was found to determine hemolytic activity and was transmissible, whereas pOB2 appeared to determine a bacteriocin that is specifically inhibitory to S. faecalis strains harboring the 26-megadalton plasmid pAM539.


Nephrogenic diabetes insipidus due to demethylchlortetracycline hydrochloride in a child. Nephrogenic diabetes insipidus occurred in a 7-year-old child who had received a high dose of demethylchlortetracycline hydrochloride (DMC). The patient had a relatively elevated urinary sodium concentration in addition to isosthenuria. The nephrogenic diabetes insipidus was completely reversible within one month after cessation of DMC administration.


In vitro activity of piperacillin, a new semisynthetic penicillin with an unusually broad spectrum of activity. The in vitro activity of piperacillin (T-1220), a new semisynthetic derivative of aminobenzylpenicillin, was investigated. The majority of streptococci and pneumococci were inhibited by 0.12 micrograms/ml; the staphylococci and enterococci were inhibited by 2 micrograms/ml. Piperacillin was slightly more active against Neisseria and Haemophilus influenzae than was ampicillin. Piperacillin was active against all members of the Enterobacteriaceae including the Klebsiella, 58% of which were inhibited by 8 micrograms/ml. The activity of piperacillin was at least equivalent, but generally superior, to that of ampicillin or carbenicillin on species susceptible to these drugs. Most striking was its activity on Pseudomonas aeruginosa: 50% were inhibited by 2 micrograms/ml, and 83% were inhibited by 4 micrograms/ml. The minimum bactericidal concentrations were very close to the minimum inhibitory concentrations, and in most species only a slight inoculum effect was observed on the minimum bacterial values except for certain P. aeruginosa strains. A complete parallel resistance exists between piperacillin and ampicillin or carbenicillin. However, the clinical importance of this is largely mitigated by the intrinsically higher activity of piperacillin.