Tumor of the follicular infundibulum.

A histopathologically unique tumor originating from the infundibular portion of vellus hair follicles is presented and the clinical and microscopic features of such a case are described. A superficial subepidermal shelf of trichilemmal structure differentiates the lesion from the lobular acanthosis of trichilemmoma.


Regional assignment of human genes TPI1, GAPDH, LDHB, SHMT, and PEPB on chromosome 12.

Karyological analysis was performed on a series of human-Chinese hamster cell hybrids containing deletions of human chromosome 12. Chromosome breakage was produced by treatment of the cells with either X-rays or 5-bromodeoxyuridine and near-visible light. The hybrid clones were analyzed for the presence or absence of the following five human gene markers known to be located on chromosome 12: triosephosphate isomerase-1 (TPI1),  glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase-B (LDHB), serine hydroxymethyltransferase (SHMT), and peptidase-B (PEPB). Based on the correlation between the isozyme markers and karyological analysis of these clones, a regional map of the five human genes on chromosome 12 was established. The linear order for these genes is: pter-TPI1-GAPDH-LDHB-centromere-SHMT-PEPB-qter. The locations of these genes are: TPI1, GAPDH, LDHB: pter leads to p12; SHMT: q12 leads to q14; PEPB: q14 leads to qter. Statistical analysis similar to that of Goss and Harris (1975, 1977a, b) has been performed on the segregation data in the hybrid clones. The statistical map, in general, agrees with the cytogenetic map and further localizes PEPB to 12q21.


Incidence of nondisjunction in mouse oocytes.

The chromosomes of more than 3000 ovulated mouse oocytes from strains C3H/Han, NMRI/Han, and (101 X C3H)F1 have been analyzed after spontaneous and hormonally induced ovulation. No significant difference in the incidence of nondisjunction was observed among the three strains with or without hormonal pretreatment. The incidence of nondisjunction was estimated to be 0.47% in NMRI/Han, 0.62% in C3H/Han, and 0.81% in (101 X C3H/F1. The incidence of chromosomal imbalance after the first meiotic division was slightly higher after adding the events following presegregation. Diploidy-spontaneous and hormonally induced-reached a significant leve in NMRI/Han. This may be interpreted as a consequence of hormonal interference with a genetically defined malfunction of gene product(s) during the late phase of oogenesis.


Breeding studies reveal segregation of a canine Robertsonian translocation along Mendelian proportions.

Six matings of golden retriever-type mongrel dogs with a 13/23 Robertsonian translocation were studied. Three matings between normal dogs and dogs heterozygous for the translocation produced 12 normals and 11 heterozygotes. In three matings between heterozygotes, the distribution of normal, heterozygous, and homozygous proteny was Mendelian (8:12:5). No gross phenotypic anomalies were observed with the exception of congenital inguinal hernia in two female homozygotes. Nondisjunction in the form of trisomic or monosomic individuals for either autosome 13 or 23 was not observed.


The effect of dexamethasone on the karyotype of A9HT cells.

In the majority of glucocorticoid-resistant receptor containing variants of A9HT cells, the numbers of dot chromosomes was found to be significantly higher than in the parent cells. The higher number of dot chromosomes, however, did not always correlate with the resistance of L cells to dexamethasone. The formation of dot chromosomes was not the consequence of dexamethasone-induced chromosome breaks. Dot-chromosome formation could not be induced by dexamethasone in human diploid cells. It seems likely that dexamethasone can select for A9HT cells with higher number of dot chromosomes.


Chromosome studies on a human liposarcoma cell line.

Numerical and structural chromosome analysis of a human retroperitoneal liposarcoma cell line maintained under standard cell culture conditions revealed a very stable hypodiploid mode. If the cells were not trypsinized for several generations, a near-triploid stemline, which was generally a duplication of the hypodiploid mode, emerged. Some chromosomes appeared to be relatively stable pairs (1, 2, 7, 9, and 12), but most had "lost" one homolog or both (4 and 21) or were rearranged into "new" marker chromosomes. Quantitation of the genetic material showed a loss of 12.0 +/- 3.7% per spread. Only one characteristically long marker chromosome, which is present in every cell, could be identified with certainty as a translocation between chromosomes 4 and 11. Several of the marker chromosomes showed interstitial negatively staining regions with the trypsin-Giemsa method.


Pattern of segregation of chicken HPRT phenotype in Chinese hamster-chick red blood cell hybrids.

The pattern of segregation of hypoxanthine phosphoribosyltransferase (HPRT, E.C. 2.4.2.8) was determined in synchronized Chinese hamster-chick red blood cell hybrids. Three hybrid lines were synchronized at the G1-S boundary. Bromodeoxyuridine pulses were subsequently applied throughout the S phase, and the frequency of the segregant clones was determined. It was found that the segregation of the chicken-specific HPRT phenotype associated with the loss of a chromosome was potentiated by bromodeoxyuridine administered during the first hour following release of the block.


Studies on isolated cloned populations from irradiated human embryonic cell cultures.

The recovery of substrains with stable chromosome aberrations from irradiated fibroblast culture are reported. Four human fetal cell strains were exposed to 600 rad of gamma rays at 200 rad/min. The efficiency of recovering viable cloned subpopulations was approximately 87%, and the frequency of clones with abnormal chromosomes was 40/100 colonies. G-band chromosome analyses for 34 abnormal substrains are described. Karyotypes of some of the clones with complex rearrangements are also presented. Analyses of a total of 47 aberrant events in the 34 abnormal substrains revealed at 7:1 and a 9:1 translocation-inversion and translocation-deletion ratios, respectively. Five of the abnormal substrains were continuously cultured; all except one showed signs of sensecence toward the end of 44 +/- 10 doublings. Unusual prolonged proliferation capacity was observed in substrain FFS-1-9. The significance of this finding is discussed.


Retinoblastoma, chromosome 13, and in vitro cellular radiosensitivity.

Five diploid fibroblast strains from patients with deletions mapping in the long arm of chromosome 13 and three strains bearing partial trisomies of chromosome 13 were assayed for clonogenic survival following X-irradiation. Results of these experiments suggest the existence of a region on 13q14 which is related to increased sensitivity to cell killing in vitro by X-rays. This locus seems to be distinct from but close to the retinoblastoma locus, which has been associated with the same band.


Assignment of a gene for uridine diphosphate galactose-4-epimerase to human chromosome 1 by somatic cell hybridization, with evidence for a regional assignment to 1pter yields 1p21.

The presence of human uridine diphosphate galactose-4-epimerase (GALE) was found to correlate with the presence of chromosome 1 in somatic cell hybrids between man and mouse. The gene for GALE can therefore be assigned to human chromosome 1. Using a chromosome 1 rearrangement, we have been able to regionally assign GALE to the pter yields p21 region.


Progression of aortic stenosis.

We assessed progressive stenosis of the aortic valve in 11 adult patients (mean age of 48 years) with aortic stenosis who had undergone two cardiac catheterizations without intervening aortic valve surgery. The mean time between cardiac catheterization was 59 months (range 20 to 133). No patients had mitral valve disease. Two patients had coronary artery disease. The results showed that progressive stenosis of the aortic valve occurred in 10 of 11 patients with a significant decrease in the calculated mean aortic valve area from 1.2 +/- 0.2 sq cm to 0.7 +/- 0.1 sq cm (P less than 0.005); a significant increase in mean left ventricular peak systolic pressure from 149 +/- 8 mm Hg to 199 +/- 3 mm Hg (P less than 0.01), and a significant increase in mean left ventricular aortic pressure gradient from 31 +/- 4 mm Hg to 75 +/- 13 mm Hg (P less than 0.005). On an individual basis, the change in left ventricular pressure and the left ventricular-aortic gradient did not always reflect the decrease in aortic valve area because of variations in cardiac output. The shortest period of time in which progression of aortic stenosis occurred was 27 to 29 months. Thus, progressive stenosis of the aortic valve occurs in adults with isolated aortic valvular stenosis. Significant decrease in the aortic valve area can develop in as short a period as 27 to 29 months.


Variability in interpretation of pulmonary function tests.

We asked 26 pulmonary physicians to interpret results of ten consecutive pulmonary function tests from one laboratory. There was frequent disagreement in their assessment of respiratory impairment. This is likely due to the variety of criteria for grading the severity of obstructive and restrictive defects. Since the narrative interpretation of pulmonary function data may influence patient care, physicians should consider the numerical magnitude of the derangements, as well as the descriptive terms applied.


Spirometric testing. Number of tests required and selection of data.

To address the questions of whether three or five maneuvers for forced vital capacity (FVC) should be required for adequate spirometric testing and whether the largest or mean values for FVC and the forced expiratory volume in the first second (FEV1) should be used for analysis, we analyzed spirometric data obtained from approximately 3,000 people for each of three consecutive years. The following four algorithms for selection of data were tested: (1) the average of the best two of five measurements; (2) the average of the best two of the first three; (3) the best of five; and (4) the best of the first three. There were no significant differences between any two algorithms within a given year and no differences between any two years for any algorithm. We conclude that there is little to be gained by requiring more than three maneuvers for FVC or in using values other than the largest FEV1 and FVC.


Pulmonary hemodynamics in systemic hypertension. Long-term effect of minoxidil.

To assess the effect of minoxidil on pulmonary hemodynamics, we performed cardiac catheterization on ten patients, prior to the administration of minoxidil, at six months after its addition to their existing drug regimens, and on seven patients following 12 or more months of minoxidil therapy. Systemic blood pressure and systemic vascular resistance were significantly reduced at six months and following 12 or more months of minoxidil therapy. Before receiving minoxidil, nine of ten patients had elevated pulmonary vascular resistance. There were no significant changes in pulmonary vascular resistance following the initiation of minoxidil. The data suggest that pulmonary hypertension is common in patients with long-standing poorly controlled systemic hypertension, and that minoxidil, in doses sufficient to significantly reduce systemic blood pressure, does not cause or aggravate pulmonary hypertension.


The radiologic significance of the left pulmonary ligament. Experience with 26 patients.

Pathologic processes confined to or by the left pulmonary ligament present a confusing radiographic appearance. Such processes may simulate pleural scarring, parenchymal scarring, or even left lower lobe collapse. Radiologic awareness of this structure is limited because in the normal state, it is not visualized on either posteroanterior or lateral chest x-ray films. The absence of secondary signs of left lower lobe collapse, together with a process which may extend above the level of the left hilum, is valuable in confirming that such a triangular density seen behind the left cardiac border is disease in or confined by the pulmonary ligament, rather than left lower lobe collapse.


Necrotizing sarcoid granulomatosis.

Twelve cases of necrotizing sarcoid granulomatosis are presented as a retrospective study. The population of patients consisted of ten women and two men, with an average age of 50 years. Nine patients initially had a variety of pulmonary and nonpulmonary complaints, while three were asymptomatic. Chest roentgenograms demonstrated bilateral nodules in seven patients, solitary nodules in four, and a miliary pattern progressing to nodules in one. Enlarged hilar nodes were found in six. Histologically, all biopsies showed a combination of individual granulomas, confluent masses of granulomas which formed the nodular masses seen on the roentgenograms, a variable amount of necrosis of tissue and hyalinization, and a granulomatous vasculitis. Follow-up periods ranged from four months to 11 years. Eleven patients are alive and asymptomatic. The sole death occurred in a patient treated with an immunosuppressive agent (cyclophosphamide). We conclude that the clinical behavior of necrotizing sarcoid granulomatosis is not similar to that of the other angiocentric granulomatoses and that most patients with this disease can be left untreated or be treated with steroids alone. We suggest the possibility that necrotizing sarcoid granulomatosis may be the histologic counterpart of so-called nodular sarcoid.


Doxapram hydrochloride: a respiratory stimulant for patients with primary alveolar hypoventilation.

Four patients (ages 43 to 51) with primary alveolar hypoventilation (PAH) syndrome were studied to characterize the pharmacologic augmentation of ventilation with intravenous doxapram hydrochloride. Doxapram hydrochloride evoked a rapid ventilatory increase of 50 to 100 percent in all four subjects with a consequent decrease in arterial CO2 tension. Blood pressure and heart rate measurements showed small increases during the doxapram infusion. These responses, however, were only sustained during the infusion, decreasing to their predoxapram level when the drug was discontinued. The ventilatory response to the drug was more marked in the pressence of hypoxia than during high O2 breathing, suggesting that the carotid bodies are a site of action for this drug in man. Doxapram hydrochloride can be an effective respiratory stimulant in patients with PAH.


Bacterial colonization, tracheobronchitis, and pneumonia following tracheostomy and long-term intubation in pediatric patients.

Serial tracheal cultures for aerobic and anaerobic bacteria were obtained from 27 pediatric patients during one year of follow-up. The patients had required tracheostomy and prolonged intubation for periods ranging from 3 to 12 months (average, 7 1/2 months). Cultures of tracheal aspirates yielded 1,508 isolates of pathogenic aerobic (969 isolates) and anaerobic (539 isolates) bacteria. The most frequent aerobic isolates were Streptococcus pneumoniae and Staphylococcus aureus. The predominant anaerobes were anaerobic gram-positive cocci, Fusobacterium nucleatum, and Bacteroides fragilis. Replacement of one pathogen by another occurred frequently. Tracheobronchitis occurred in 24 patients, all of whom had episodes of pneumonia. The data suggest that anaerobic bacteria are a part of the bacterial flora in colonization, tracheobronchitis, and pneumonia in patients with tracheostomy and prolonged intubation.


Determination of static pulmonary volumes after bronchodilator therapy.

Increased (more positive) end-expiratory and decreased (more negative) end-inspiratory values for intrapleural pressure (PpI) invariably accompany acute bronchoconstriction. We hypothesize that both the increase in vital capacity (VC) and the decrease in residual volume (RV) observed after dilation of the central airways in patients with reversible obstruction of the airways result, in part, from a restoration of normal PpI during unforced exhalation. To test this hypothesis, we examined the end-expiratory PpI during breathing at rest in ten emphysematous and eight asthmatic subjects before and after inhalation of isoproterenol. The VC increased by 0.38 L after therapy, and the specific airway resistance and the RV decreased by 6.8 cm H2O.sec and 0.63 L, respectively. Total lung capacity was unchanged. The response of the VC to administration of isoproterenol is an important sequel to dilation of the large airways. Bronchioles close at a critical PpI during exhalation. Because PpI normalizes with administration of isoproterenol, this closure may be delayed to a lower pulmonary volume even if improvement in the function of peripheral airways does not occur.


Failure of surgery in preexcitation. Correlation with pathologic findings.

A 37-year-old man with mitral stenosis and recurrent drug-resistant paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and preexcitation, underwent two surgical attempts to ablate an anomalous pathway (AP). Electrophysiologic study demonstrated a left posterior AP with a short antegrade refractory period. Epicardial mapping at the time of mitral valve replacement (left lateral thoracotomy) suggested a posterior right AP. Mitral valve replacement and incision of the left atrial wall failed to cure preexcitation. Epicardial mapping at a second operation (median sternotomy) demonstrated a subepicardial left posterior AP. Right atrial and atrial septal incisions failed to cure preexcitation. Serial section of the atrioventricular rings and conduction system demonstrated an intact left posterior anomalous atrioventricular muscle bundle with surgical incision placed above the plane of the mitral anulus.


Tricuspid and pulmonic valve echoes in tricuspid and pulmonary atresia.

An echocardiographic pattern of normal tricuspid valve motion in a patient with tricuspid atresia, and pulmonic valve motion in a patient with transposition of the great vessels and pulmonary atresia were documented. The recordings of the valve motion resulted in an initial erroneous diagnosis. Although M-mode echocardiography is very useful for the initial diagnostic evaluation of critically ill newborn infants with complex congenital heart diseases, on occasion recording of valvular echoes may result in conflicting clinical and pathologic correlation.


Echocardiographic indices of left ventricular function. A comparison.

Multiple M-mode echocardiographic indices of left ventricular function are currently in use, but their reliability is disputed. Therefore, we correlated echo ejection fraction (EF) using quadratic (Q) and cubic (C) formulae, percentage of minor axis shortening (%S), mean velocity of circumferential fiber shortening (mVCF), and peak VCF with angiographic EF in 37 subjects, including 10 normal subjects. None had echocardiographic segmental wall motion abnormalities. Significant linear correlations were found between angiographic EF and EFc (r = 0.78), %S (r = 0.77), EFQ(r = 0.68), peak VCF (r = 0.68), and mVCF (r = 0.58). However, for all indices, the scatter was too great to permit reliable quantitative estimations of angiographic EF based on echo date. Peak VCF was qualitatively the most reliable predictor of ventricular function, being greater than or equal to 2.00 circumference per second in 23 of 25 patients with angio EF greater than or equal to 55 percent and less than 2.00 circumferences per second in 11 of 12 with EF less than 55 (sensitivity [sens] 92 percent, specificity [spec] 92 percent). Mean VCF (sens 83 percent, spec 80 percent), %S (sens 50 percent, spec 96 percent), EFC (senc 58 percent, spec 96 percent), and EFQ (sens 58 percent, spec 92 percent) were less satisfactory. We conclude that echo indices are reliable only as qualitative parameters of ventricular function. Peak VCF appears to be the most sensitive and specific qualitative index now available.


Relation between pulmonary transvascular fluid filtration rate and measured Starling's forces after major burn.

Our purpose was to determine the reliability of the currently used measurements of pulmonary vascular hydrostatic and oncotic pressures in monitoring pulmonary water after a major burn. The flow of pulmonary lymph, a reliable indicator of the rate of filtration of pulmonary transvascular fluid (Qf), was measured before and for 72 hours after a third-degree burn over 40 to 55 percent of the total body surface in sheep. Changes in Qf were correlated with measured changes in pulmonary microvascular (Pmv), plasma colloid osmotic pressure (pi p), and interstitial colloid osmotic pressure (pi i), as measured in the pulmonary lymph. The periods from 0 to 24 hours (resuscitation), from 24 to 48 hours (early mobilization of fluid), and from 48 to 72 hours (early recovery) were compared with baseline. Regression equations and correlation coefficients for Qf vs Pmv, Qf vs Pmv minus pi p, and Qf vs Pmv minus (pi p -ph i), the oncotic gradient, were calculated. There were significant differences in slopes between the periods of time, with all three comparisons indicating that the response of the microcirculation to the same changes in pressure was different in each of the periods. The correlation between Qf and the comparisons of pressures was clearly best in the period from 48 to 72 hours. The comparison of Pmv minus pi p was not better than Pmv alone, while the comparison of Pmv minus the gradient (pi p -- pi i) was significantly better than either of the other comparisons in predicting Qf.


Pericardial effusions in sarcoidosis.

A case of sarcoid pericarditis is presented. The associated pericardial effusion was a transudate with a low complement level. Investigating the prevalence of pericardial effusions in sarcoid by echocardiography, we found small effusions in 19 percent of 48 consecutive patients with sarcoid. Additionally, ten previously reported cases of symptomatic parietal pericardial sarcoid are reviewed.


Swallowing-induced supraventricular tachycardia.

A rare form of paroxysmal supraventricular tachycardia (SVT), associated with swallowing solid food, is described. Repeated triggering of the arrhythmia during esophagoscopy was produced by mechanical stimulation of the anterior esophageal wall, 30 cm from the incisors. Treatment with verapamil abolished this tachycardia. Esophagoscopic examination, the first of its kind in this setting, aided the investigation.


Elimination of Mycobacterium intracellulare from sputum after bronchial hygiene.

Three cases are presented, each of which had more than 20 positive cultures of sputum for Mycobacterium intracellulare, infiltrations, and a history of bronchiectasis. Two had complete and the third nearly complete, sputum conversion during a program of bronchial hygiene without chemotherapy. It is probable that these cases were only noninvasive colonizations in previously diseases lungs. Recommendations are given for a therapeutic approach in such cases.


Disseminated echinococcosis with repeated anaphylactic shock. Treated with mebendazole.

A 46-year-old man, who was twice operated on for echinococcosis and who suffered from recurrent angioneurotic edema, was hospitalized with anaphylactic shock. Chest x-ray examination showed round lesions in the lungs; Casoni, immunofluorescence and hemagglutination tests for echinococcosis were strongly positive. With a diagnosis of disseminated echinococcosis, drug treatment with mebenzadole was given for 29 weeks (the last 22 weeks a dose of 1,200 mg daily). No side effects were observed, allergic manifestations disappeared, and the round lesions were noticeably reduced. The titer of hemagglutination fell gradually, and IgE concentration initially increased and later fell. Mebendazole is proposed as a drug of choice in the cure of disseminated hydatidosis; it may both alter the indication for operation and considerably improve the prognosis.


Partial right-sided congenital pericardial defect with herniation of right atrium and right ventricle.

In an unusual case of right-sided pericardial defect with herniation of the right atrium and right ventricle, cardiac blood pool isotope imaging is introduced as a new, noninvasive diagnostic procedure. Surgery which consisted of excision of right-sided pericardium relieved the chest pain which was the only symptom the patient had prior to surgery.


Intracoronary anastomosis in the absence of obstructive lesions of the coronary arteries.

The patient had collateral flow from the right coronary to left circumflex coronary artery in the absence of proximal obstructive disease. This supports the hypothesis that the intercoronary collaterals seen in coronary atherosclerotic disease are present in the normal heart.


Concentration of thiamphenicol in the human prostate and testis.

The concentration of thiamphenicol in prostatic tissue, testicular tissue and serum after a single intravenous injection of 1 g thiamphenicol glycinate ester was investigated. The prostatic and testicular specimens were obtained by prostatectomy and plastic orchidectomy, respectively, from patients with adenomas and carcinomas of the prostate. 2 h after dosing, the prostatic tissue concentration ranged from 2.1 to 15.1 microgram/g (mean value 5.7 microgram/g) and the testicular tissue from 3.4 to 8.4 microgram/g (mean value 6.1 microgram/g). At the same time the thiamphenicol serum levels varied in the patients with prostate adenomas from 4.6 to 14.5 microgram/ml (mean 8.9 microgram/ml) and in the prostate carcinoma patients from 5.2 to 10.4 microgram/ml (mean 8.5 microgram/ml). Several factors influencing the diffusion of thiamphenicol into the prostate and testis are discussed. The levels of thiamphenicol in the prostate and testis suggest that the antibiotic may be valuable for the treatment of infections of the prostate and testis caused by gram-positive and gram-negative cocci, but is of questionable value for the treatment of infections caused by gram-negative bacilli.


On the mechanism of the antimycobacterial activity of isoniazid + prothionamide + dapsone (Isoprodian).

Increased antimycobacterial activity of Isoprodian (isoniazid + prothionamide + dapsone) may be due to (i) decreased mutation rate for INH resistance provoked in mycobacteria by DDS (in 2 of 3 strains tested); (ii) leakage of K+, Na+ or Ca++ caused by INH and/or by PTH (in all 3 strains tested), and (iii) indicating damages which may increase the low level penetration of DDS into the cell in sub-MIC concentrations as shown by phage proliferation changes (tested in 1 strain with 1 phage).


Cefazolin treatment of bacterial infections. In vitro and in vivo evaluation.

Cefazolin sodium was used to treat 20 serious bacterial infections in 19 patients, 11 of whom were infected by coagulase-positive Staphylococci. Clinical and bacteriologic success were initially obtained in 15 patients with 16 infections. 2 additional patients were cured after surgery for removal of foreign bodies and a second course of the antibiotic. 1 asplenic patient had bacteremia and died 5 days after initiating therapy with negative blood cultures and multiple abscesses. 1 patient with endocarditis relapsed 19 months after treatment with 6 weeks of cefazolin and prolonged oral antibiotics. Calculated median, trough, free drug levels were 1.5--15.3 times the minimum inhibitory concentration for 27 of 29 pathogens.


What can be expected from the surgical treatment of craniopharyngiomas in children. Report of 92 cases.

92 cases of craniopharyngiomas have been operated, 63 with a follow-up extending from 30 months to 20 years. The possibilities of the surgical treatment are mainly discussed on the basis of the anatomical location of the tumors. Simple intrasellar craniopharyngiomas can be operated by a transphenoidal approach with, sometimes, spectacular improvement (case of spontaneous normal pregnancy). The tumors most frequently seen are those with predominantly prechiasmatic expansion. A subfrontal approach is always required, aiming at radical excision. Microscopy can offer interesting possibilities for selective surgery. However, if the vital prognosis is excellent and recurrences rare, functional results remain very poor. In retrochiasmatic tumors involving the posterior hypothalamus, the principle of radical excision must be seriously discussed and sometimes challenged. The various combined approaches are described with their own limits and risks. Other therapeutic techniques are suggested. In many cases, selective neurosurgical dissection may raise some hope for better improvement of functional results.


Optic glioma in children. Review of 16 cases given megavoltage radiation therapy.

From 1967 to 1975, 16 consecutive children with optic-tract glioma were treated with postoperative irradiation. Clinical, surgical and pathologic findings have been summarized. Doses ranged from 4,000 to 6,000 rad. As of 1976, follow-up had been obtained in 13 of 16 children. 9 of 13 survived and 3 were lost to follow-up. We have been unable to relate survival to age, sex, pathologic grade, radiation dose of field size. Although all patients in our series were irradiated, it appears that survival is excellent for those with gliomas that are confined to the optic nerve or chiasm without hydrocephalus even if postoperative irradiation is not given. In patients with extension beyond the chiasm or with hydrocephalus, survival may be improved by the addition of irradiation. A staging system is proposed.


Adoption of Korean children by New York area couples: a preliminary study.

This paper reports on the first segment of a longitudinal study of the effects of transracial and transcultural transplantation into American families.


Childhood moyamoya syndrome. Postradiation pathogenesis.

The development of typical clinical and radiological features of moyamoya syndrome is described in 3 children following radiation therapy for a gliomatous tumor at the base of the brain. The effect of radiation therapy on the medium-sized arteries is discussed with a review of the literature. Radiation therapy as the causative factor for the narrowing or occlusion of the carotid siphon is discussed.


Lipoma of the corpus callosum: report of a case and review of the literature.

A case of lipoma of the corpus callosum associated with subcutaneous lipoma, whose symptoms were headache and trembling of the extremities, was reported. Roentgenograms showed characteristic findings and computerized tomography revealed a mass of very low density. The literature was reviewed and 15 cases not included in previous compilations were found. Clinical and radiological findings in 89 cases including the present case were analyzed.


Comparison of the effects of surgical decompression and resection of local edema in the therapy of experimental brain trauma. Investigation of ICP, EEG and cerebral metabolism in cats.

The effect of decompressive trepanation was compared to that of surgical resection of the traumatized tissue in the course of traumatic brain edema in standardized experimental brain trauma. Following a right parietal cold injury, the following parameters were monitored continuously in 12 cats: ventricular pressure, epidural pressure over both hemispheres, arterial and central venous pressure and heart rate. The EEG was evaluated continuously, using a computer (power spectra). After catheterization of the superior sagittal sinus, cerebral arteriovenous differences of glucose, lactate, O2 and CO2 were calculated. 6 animals were treated surgically when showing elevated intracranial pressure ICP and markedly altered EEG. In 3 animals, the right hemisphere was decompressed by extensive resection of bone and dura. In 3 further animals, the softened brain tissue of the cold lesion was resected and the skull defect closed. 6 untreated animals were used in controls. A decompression by skull hemiresection for ablation of the injured cortex abolished the high intracranial pressure, but only the latter method seemed to prevent further damage. This could be demonstrated by the EEG registration, and by the normalization of arteriovenous metabolite differences. Only animals treated with edema resection had a normal arousal reaction and survived the trauma. The results indicate, that only an ablation of the local injury will prevent further damage to the brain. After decompressive trepanation alone, the progression of tissue edema is not interrupted. As can be seen from the literature, the poor results obtained even from extensive decompressive operations in traumatic brain edema, indicate that the further development of edema is independent of the intracranial pressure, whereas the favorable results of resection of lobar contusions show an interruption of the spread of dysbolism.


A model for systematic child protective service training.

A model training program structured to provide basic knowledge and skills for child protective workers appears to be meeting its objectives.


[Topography and surgico-tactical principles of the mesocaval shunt].

The mesocaval shunt has special advantages. It can be applied also in patient with worse condition (Child B and C). The technically simple performance according to the original method of Drapanas is recommended provided that anatomical variants at the surgical trunk of the vena mesenterica superior are known. The anatomical situation should be investigated preoperatively by direct (umbilical vein catheter) or indirect mesentericography. The access via umbilical vein offers in addition the possibility of coronary vein embolisation in emergency patients.


Clinical illustrations of the sexual misuse of girls.

The sexual misuse of girls, usually incestuous, often results in profound psychological impairment, sometimes transmitted to the next generation.


[Prevention of postoperative pancreatic complications following duodenopancreatectomy using somatostatin].

Somatostatin was prophylactically administered to 10 patients who had surgery for pancreatic diseases. The postoperative course uncomplicated with no increase in serum amylase levels. Bile induced acute pancreatitis in six beagles was prophylactically treated with somatostatin. The results demonstrate that SRIF not only inhibits basal but also pancreatic-induced blood amylase and enzyme activities in the dog. SRIF-treated animals were in good general condition compared with untreated controls, macroscopic and histologic aspects of the pancreas were significantly improved.


[Clinical and morphological properties of cold nodules formed in the thyroid gland of patients treated with I-131 for hyperthyreosis].

The authors report on the clinical and morphological features of patients who had been previously treated for toxic adenoma with different doses of 131I isotope, and were then operated on for cold nodule. Progressive pseudoatypic and Hürthle-cell transformations, which are difficult to distinguish from different-type thyroid carcinomas, were revealed in one and a solid anaplastic carcinoma in another of the five patients during histological examination of operative specimens in serial sections. On the basis of these findings the authors support the function-protective operative treatment of single toxic adenomas, although the causal relationship between isotope treatment and consecutive carcinoma can not be verified unanimously.


[Studies on the effect of 4-methyl-umbelliferon (Hymecromone) in patients following surgical revision of the biliary pathways].

The effect of 4-methylumbelliferone (hymecromone) on postoperative gall volume and residual pressure, serum enzymes, and other parameters in 50 patients after cholecystectomy and choledochotomy with T-tube drainage is measured by a clinical double-blind study. There were several interesting findings: (a) significant less gall flowing from the T tube, (b) highly significant less activity of the enzymes basic phosphatase and of the gamma-glutamyltranspeptidase, and (c) fewer need of analgesics.


Preventing worker burnout in child welfare.

Awareness is growing that worker burnout is a serious problem in the child welfare field. This paper examines the multiple causes of the phenomenon, and suggests approaches to prevention.


[Man in old age: from the viewpoint of the surgeon].

The most important problems of surgery in the aged patient are: immediate recognition of risk factor (few, but reliable laboratory parameters in the sense of "searching tactics": status of blood, blood sugar, urea-N, creatinine, cholinesterase), careful procedural choice, immediate mobilisation postoperatively, subsequent rehabilitation, if necessary. The operation itself must be fast but careful and as restricted as possible.


Cellular density of normal corneal endothelium.

With the aid of the specular microscope photographs were made of the endothelium of 72 subjects, 41 men and 31 women, aged from 24 to 86 years. The number of endothelial cells was counted by projecting the photographs and counting the cells in a given area. The average variation per eye was 4.9% with a standard deviation of 3.7. A difference in magnification associated with differences in the thickness of the cornea was not found. There was a significant negative correlation (Pearson) between age and cell density: correlation coefficient 0.395, significance P = 0.001. Regression analysis of this correlation gave the following equation: CL = 3081 - 8.8 L, where CL = cell density at age L. The error is 97 cells more or less than this figure.


Iatrogenic endothelial damage during cataract extraction.

Morphological changes in the endothelium of rabbits' corneas after rinsing with Ringer's solution, chymytrase 0.05% or acetylcholine could not be demonstrated by vital staining with nitroblue tetrazolium. Local lesions caused by manipulations in the anterior chamber were conspicuous. Endothelial lesions due to manipulations with an intra-ocular lens were studied in the same way.


Continuous lavage in (chemical) corneal lesions.

In a small number of patients with severe chemical corneal damage and in a few patients with corneal ulcers, continuous lavage of the conjunctival sac with a mixture of the patient's own serum, tissue culture fluid and various medicaments was carried out with great success.


Pathologico-optic approach to cataract and lens.

From the weight of the lenses of patients with senile cataract, ultrasonic measurements of the eyes of patients with acute diabetic refractive changes, and calculations on the basis of Legrand's theoretical eye, it appears that the conclusion can be drawn that these refractive changes are due to alterations in the refractive indices of the lens.


Lens injury in children treated with irido-capsula supported intra-ocular lenses.

The treatment of lens injury in children with irido-capsula supported intraocular lenses is described. A consecutive series of 73 children is analyzed as to the functional results and complications. Surgery and anaesthesia are discussed in detail. Guidelines are given for future straightforward management of eye injury in children, using this promising possibility of visual rehabilitation.


The superior oblique: a challenging extraocular muscle.

Isolated paralysis of one or both superior oblique muscles in a consecutive series of 43 patients was found to occur most often by indirect injury to the skull. The etiology in the group of spontaneous cases was mostly vascular. With rare exceptions the latter recovered spontaneously. Those with traumatic palsy may be due to "contrecoup" trauma at the decussation of the nerves or by decompensation of the cerebral fusional mechanism, with dissociation of the images of the two eyes and subsequent vertical deviation. The traumatic cases never recover spontaneously and recession or myectomy of the ipsilateral inferior oblique with or without recession of the contralateral inferior rectus is recommended but only in cases of more than 8 diopters squint, and in cases which do not adapt themselves by minor head-tilting.


The influence of clonidine on intraocular pressure.

In order to study the influence of clonidine on intraocular pressure (IOP), the drug was administered via different routes. The experiments were performed on chloralose-anaesthetized cats. The rise in IOP observed after administration of clonidine into the external carotid arteries was subjected to a pharmacological analysis. Our experiments suggest that the increase in IOP is due to the contraction of eyelids and extraocular muscles, mediated by the influence of clonidine on alpha-adrenoceptors. The IOP-lowering effect of clonidine was more pronounced after its infusion into the left vertebral artery than after its intravenous injection. This difference would suggest that the clonidine-induced decrease in IOP may be mediated via a central mechanism.


Tobacco amblyopia: the effect of treatment on the electroretinogram.

In seven recently diagnosed and untreated patients with tobacco amblyopia the light and dark adapted electroretionograms were recorded together with visual acuity, central fields and the Farnsworth-Munsell 100-Hue test. After 3 months treatment with injections of hydroxocobalamin all these tests were repeated. An improvement in visual acuity resulted in all cases. A significant reduction in the Farnsworth-Munsell total error score of the seven patients was noted (p less than 0.01). A significant increase in the amplitude of the light adapted b-wave of the ERG was found (0.01 less than p less than 0.02) following the course of hydroxocobalamin injections. No other significant changes in the ERG were demonstrated. It is suggested that the ERG changes demonstrated an improvement in an abnormal biochemical state in those bipolar and perhaps Müller cell of the inner nuclear layer of the retina which make electrophysiological connnections chiefly with foveal cones.


S.I. units in ophthalmological practice.

The introduction of S.I. units internationally means that an adaptation of the use of certain units in ophthalmological practice will have to be considered. This has important consequences, especially for the measurement of intra-ocular pressure. A survey is given and some suggestions are made for the practical use of an adapted unit for intra-ocular pressure measurement.


TV pattern evoked cortical responses without and with film mixing.

To obtain measurable TV pattern evoked cortical responses of children, the alpha-rhythm of the EEG must be suppressed. In our study, mixing pattern stimuli and film proved to be an effective way of doing this.


[Diagnosis of leucocytes in urine by means of a test-strip (author's transl)].

A test-strip for diagnosing urinary leucocytes (Cytur) was evaluated by 11 centres, on a total of 1985 voided urine specimens. Results were compared with chamber counting of uncentrifuged urine, as well as by microscopic examination of spun sediment. With a reaction time of 15 minutes the test-strip compared well with the other two methods. When urine is allowed to stand, the lysis of leucocytes exaggerates the colour reaction of the test-strip. Red blood cells, bacteria, sperm and nitrite in urine do not influence the results, except Trichomonas which increases the reaction. Ascorbic acid and albumin slightly inhibit the reaction.


[Fibrinolytic treatment with urokinase of post acute phlebothromboses (author's transl)].

Standardised urokinase-heparin treatment was administered to 32 patients one to six weeks after deep-vein thrombosis. Treatment generally continued over 7-14 days. Complete recanalisation occurred in six, partial in 18 patients. In eight patients there was no evidence of thrombolysis in the phlebogram.


["Plica disease" (synovial folds) of the knee-joint: arthroscopic and histological findings, with suggestions for treatment (author's transl)].

A mediopatellar plica (synovial fold) of the knee-joint may develop without recognisable cause in adolescents or young adults, predominantly females. It leads to pain on pressure over the medial knee compartment, sudden or "springing" intraarticular movements and pseudolocking of the joint. Similar plicae occur after traumatic joint contusion, with meniscus disease, or more rarely with arthrosis deformans. Histologically they are characterized by band-like fibrosed evaginations of the synovial membrane and of the synovial fat and connective tissue into the joint spaces. The following therapeutic suggestions, based on the personal experience of 15 cases, are made in the knowledge that significant inflammatory or proliferative arthritic changes can be excluded: the plica can be cut through under arthroscopy; chondromalacial defects, directly or indirectly caused by plical rubbing, of the medial femoral condyle and the medial patella can be removed, also under arthroscopic control, with an electric razor. Arthrotomy is no longer needed in most cases.


[Danazol treatment of hereditary angioneurotic oedema (author's transl)].

Danazol, an attenuated androgen, was administered to four patients with hereditary angioneurotic oedema, with rapid and complete response without side-effects. The follow-up period has now been up to 17 months. In all patients there was an indirect indication that their hormonal state influenced the course of the disease.


[Local recurrences of carcinoma of the breast (author's transl)].

Distant metastases were sought for in 90 patients with local recurrence of breast carcinoma. Only 11 patients had demonstrable spread of the disease at the time of referral. Two-thirds of all local recurrences presented within two years of the primary operation. In 66 out of 90 patients the recurrence was in the chest wall, in 11 cases it was in the chest wall and in the lymphatic system and in only 13 cases was it primarily in the regional lymph nodes. The recurrence rate depended mainly on the previous treatment of the primary tumour: 42 recurrences were found in those cases treated only by surgery, 46 in cases treated surgically and with low-dose post-operative irradiation and only two in patients treated with over 4500 rad to the area of subsequent recurrence.


[Bronchodilator effect of methylxanthine derivatives (author's transl)].

The bronchodilator effect of theophylline ethylenediamine was compared with that of a combination of the methylxanthines theophylline, diprophylline and proxyphylline, after administration of slow-release capsules. At an initial dose of twice two capsules the two drug preparations produced similar, therapeutically significant, effects. When reducing the dose to twice one capsule, during long-term treatment, there was a clinically and statistically significantly greater bronchodilator effect among those patients receiving the combined methylxanthine preparation.


[Interaction of rifampicin with phenprocoumon (author's transl)].

Prothrombin time and plasma phenprocoumon levels were serially controlled, at short intervals, in three tubercular patients receiving both tuberculostatic drugs and phenprocoumon. The required phenprocoumon dose was continuously adapted to the prothrombin time values. During and after treatment with rifampicin optimal levels of prothrombin time were difficult or even impossible to achieve in two of the three patients. This confirms the known loss of effectiveness of the coumarins induced by rifampicin. This action has a slower onset and disappears more gradually than after acenocoumarol or warfarin. It is, therefore, likely that these two latter drugs are more suitable in patients treated with rifampicin than phenprocoumon.


[The effectiveness of cervical cytology screening for cervical cancer (author's transl)].

Cervical cytology screening was performed, between July 1971 and the end of 1976, on 503,870 specimens from 226,428 women. During this period the rate of positive or suspicious findings fell from 2.6% to 0.9%. The number of specimens judged suspicious for invasive carcinoma, carcinoma in situ or with severe dysplasia (among those women who had undergone serial examinations) was 5 per thousand for the first specimen, 2 per thousand for a subsequent second specimen, and 1.6 per thousand for a subsequent third specimen. The screening programme detected (later confirmed histologically) 272 cases of invasive carcinoma and 948 of carcinoma in situ or severe dysplasia. Related to the number of women screended at various ages, the frequency of carcinoma in situ and severe dysplasia had a peak between the 25th and 29th year of life, with a second, lower peak at around the 65th year. For invasive cervical carcinoma the frequency remained high into old age. The proportion of histologically proven cases of invasive carcinoma fell continuously from 1963/66, at 3.6 per thousand, until 1976, at 1.6 per thousand.


[Does low-dosage heparin treatment require serial haematological controls? (author's transl)].

Blanket serial controls are not necessary in low-dosage heparin treatment. It would, in any case, be difficult under normal clinical conditions and would run counter to the whole conception of low-dose heparin treatment. However, in problem cases with an increased thrombo-embolic risk, sensitive methods for monitoring the heparin effect are recommended. A study on 150 patients has indicated that the most sensitive method is the use of chromogenic substrates. Thrombin time, using low-concentration thrombin solution of 1.5 NIH units/ml, thrombelastogram and activated partial thromboplastin time are less sensitive. Antithrombin III levels should be determined in all cases of increased heparin tolerance. With reduced antithrombin III levels and higher body weight an increase of the standard dose from 5000 U.S.P. units heparin t. i. d. subcutaneously to 7500 U.S.P. units t. i. d. should be considered.


[The diagnosis of phaeochromocytoma: sensitivity of vanillylmandelic acid and urinary catecholamine determination and the Katecult test (author's transl)].

Tumour weight was compared with maximal vanillylmandelic acid and catecholamine excretion in 24-hour urine in 21 patients with phaeochromocytoma. The tumour weight correlated both with vanillylmandelic acid (r = 0.805, P less than 0.001) as well as urinary catecholamine levels (r = 0.725, P less than 0.001). Normal vanillylmandelic acid excretion was found in seven patients; urinary catecholamine levels were abnormal in all patients. The Katecult test was additionally performed in ten patients, with nine positive results.


[Effect of a 2 mg thyroxine bolus on the hypophyseal-thyroid axis (author's transl)].

The effect of a single dose of 2 mg L-thyroxine on central and peripheral parameters of the hypophyseal-thyroid axis was studied on ten euthyroid and ten hypothyroid patients, and ten with euthyroid goitre. Without the occurrence of hyperthyroid symptoms, the T4 serum level was raised for five days in the euthyroid group, for 11 days in the hypothyroid ones. During this time the T3 serum level did not alter. Suppression of iodine uptake by the thyroid and TSH secretion of the hypophysis persisted longer, both for basal and TRH-stimulated liberation, than the substitution effect. Even when the T4 bolus has to be at a higher total T4 dose for the same therapeutic effect than with daily small single doses, it is a comparable alternative to present-day forms of treatment. It is of particular advantage where there are medical reasons for widely spaced drug intake or rapid normalisation of the T4 serum level is deemed desirable.


[Noninvasive screening of cerebral death by Doppler sonography (author's transl)].

Directional Doppler sonography of the supratrochlear and extracranial cerebral arteries was performed on 16 patients without any cerebral flow, as confirmed angiographically. The findings were inconsistent for the supratrochlear artery, but the internal carotid and vertebral arteries had characteristic changes in the Doppler curve with clearly diminished systolic flow velocity and flow reversal during diastole. These results were never seen in arteriosclerotic occlusion, hypoxaemic or toxic cerebral oedema. Doppler sonography thus helps to formulate indications for early cerebral angiography.


[Possibilities of radiation-dose reduction in the treatment of Hodgkin's disease. I. Exclusion of the mediastinum from the radiation field in primary high-cervical or infradiaphragmatic involvement and stage I or II (author's transl)].

A retrospective analysis on 482 patients with localised Hodgkin's disease revealed that none of those with primary high-cervical or primary infradiaphragmatic involvement had any infiltration of the mediastinum, either at the time or later. As a result, prophylactic mediastinal radiation was not practised if high-cervical or infradiaphragmatic lymph-nodes had been affected first. None of these patients had any mediastinal recurrence after at least seven years.


[Bacteria of the campylobacter species as cause of enteritis (author's transl)].

In an eight-year-old boy who had acute gastroenteritis, examination of the faeces with specific isolation technique revealed Campylobacter fetus subspecies jejuni as the responsible pathogen. This is the first observation in the Federal Republic of Germany of an enteritis caused by Campylobacter.


Individualisation of oral anticoagulant therapy.

The hepatic synthesis of vitamin K dependent coagulation factors is modified by oral anticoagulant drugs, resulting in the release of functionally deficient coagulation factors into the circulation and consequently anticoagulation. Since their introduction into clinical medicine over 30 years ago, both clinical and scientific evidence has demonstrated the value of oral anticoagulants in the treatment and prophylaxis of venous thrombosis. In the treatment of arterial disease, however, both the indications for and usefulness of oral anticoagulants remain very much in doubt despite their widespread use in the 1950s and 1960s and in numerous clinical trials. The initiation and continuation of oral anticoagulant therapy is a co-operative venture involving the patient, the clinician and the laboratory. The clinician must have a thorough knowledge of the indications for and contraindications to the use of these drugs, and regular, accurate laboratory control is essential if haemorrhage, the major side effect, is to be avoided or reduced to a minimum. The patient must bear the responsibility for regular clinic attendance, abstinence from proprietary medications, and must immediately seek medical advice if any sign of haemorrhage occurs.


Nomifensine: A review of its pharmacological properties and therapeutic efficacy in depressive illness.

Nomifensine is a tetrahydoisoquinoline antidepressant which is chemically unrelated to the tricyclic or tetracyclic antidepressants, the monoamine oxidase inhibitors or the recently introduced agents. Nomifensine resembles the tricyclic antidepressants in many of its pharmacological effects in animal models of depressive illness, but differs from them in that it strongly inhibits the re-uptake of dopamine as well as noradrenaline and is a relatively weak inhibitor of serotonin uptake. It has an overall efficacy comparable with that of imipramine and amitriptyline in depressive illness, but at dosages which have achieved a similar overall clinical improvement, nomifensine causes little or no sedation, fewer and milder anticholinergic side effects, and also appears less likely than these drugs to cause serious cardiotoxicity on overdosage. Nomifensine may aggravate the psychopathology of patients with schizo-affective disorders and intensification of the psychosis may require neuroleptic therapy. Nomifensine also has antianxiety activity, but its role in treating anxiety associated with primary depression has still to be clarified. Nomifensine appears to be well tolerated by the elderly.


[Disorders of cognitive activity in schizophrenics].

4 tests are exploring the cognitive activity of 3 groups of persons: normal, mental patients of various types, schizophrenics, homogeneous as far as the I.Q. is concerned (above 110) and education (secondary school, or university). Whereas normal and mental patients give identical results, except that they are worse for the latter, schizophrenics have better success than other patients in two tests of logic-mathematical reasoning and obviously worse in two tests of experimental logic. These results are interpreted in the frame of Piaget's theory as demonstrating the discordance of the very dynamics of schizophrenic thinking whose cognitive activity is at the same time too near to the object by adherence to the perceived structure (too concrete) and too far from it by adherence to formal reasoning schemes acquired under genetic development (too abstract). These results are coherent with clinical features showing that autistic thinking is not only discordant by its contents and its meaning, but also by the formal dynamic patterns of its modus operandi.


[Abnormal movements induced by psychotropic drugs].

The abnormal movements produced by the psychotropic drugs are related to various physiopathological mechanisms: -- dopaminergic receptors blockage provokes neuroleptic parkinsoniam tremor; -- neuroleptic-induced tardive dyskinesia is similar to 1. Dopa abnormal movements; tardive dyskinesia is due to denervation induced hypersensitivity of the dopamine receptor; the 1. Dopa dyskinesia is probably related to altered responsiveness of these receptors due to an increase in dopaminergic receptor sensitivity; -- antidepressant drugs, particularly lithium, provoke tremor, alleviated by beta blockage; it is probably caused by an abnormal sensitivity of the beta noradrenergic receptors.


[The psychosis-epilepsy relationship in children].

From four cases studied both clinically and with the help of repeated and prolonged electroencephalograms, the problems raised by the association psychosis-epilepsy in children are reconsidered. The difficulties in evaluating: the actual weight of the "epilepsy" component; the role of the epileptic discharge for the subject's psychic economy; the role of drug therapies, are particularly underlined.


[Contribution of radiography and gammagraphy to the monitoring of the development of psychoses].

The authors emphasize the frequency of intracranial tumors in psychiatric patients. They make a distinction between the rare cases of psychiatric patients with intracranial tumors and the even most-frequent cases of tumors that express themselves through psychiatric disorders. According to the authors, the most important detection-tests are the brain scan and, more recently, the EMI scan or tomodensitometer.


[Mental disorders and prolactin secretion].

Recent reports suggest that selective endocrine disturbances are often associated with mental disease, and that hormonal responses to treatments with antipsychotic drugs can be related to their clinical efficiency. The importance of central monoamine neuron systems for both hormonal control and mental disease probably accounts for these correlations. Measurement of prolactin, a hormone primarily regulated by hypothalamic dopaminergic neurons, provides a useful tool which can help to define the symptomatology of schizophrenic or depressed patients, to calibrate drug therapy and to obtain advance warning of therapeutical side effects. The hormone can also be used as an excellent index for screening dopamine agonist or antagonist properties of new drugs.


[Psychiatric and postsurographic approach in the study of post-concussion syndromes following head or whiplash injuries. Correlation and additional aspects].

Purpose of this paper is to point out the interest in case of post-concussional syndroma following an head or whiplash injury to practice both: a posturographic examination objectiving the functioning of the different sensori-motor systems who maintain the body equilibrium giving an approach of the possibility of an organic etiology, psychiatric one giving the psychogenic aspect. Different therapeutics are proposed in regard of this double approach. Four cases illustrate this purpose.


Depot neuroleptics in the treatment of acute psychoses.

The data reported in the present study are derived from clinical records of 43 acute inpatients treated with the depot neuroleptic F.D. during a one year period, at the Psychiatric Institute of the University of Pisa. The criteria of selection of acute patients of schizophrenic, manic and schizoaffective type are reported. With such treatment it was possible to eliminate the stressful forced repeated drug administrations without any particular side-effects and the drug combinations were greatley reduced. However the clinical observations of this study need further confirm.


[An epidemiologic approach to psychoses].

This study is an epidemiological approach of psychoses based on morbidity statistics from french psyschiatric hospitals for the years 1968, 1971 and 1975. It compares some of the most interesting census and first admission data for the following categories: manic-depressive psychoses, chronic schizophrenia and paranoid states on the one hand, neurotic conditions, personality disorders and non-psychotic depressions on the other. Major trends are analysed. Two of them seem particularly interesting: 1) the decreasing number of cases classified as manic-depressive psychoses; 2) the diminishing proportion of females in most instances. Some explanatory hypotheses are suggested.


Studies of the biological and immunological properties of parathyroid hormone, labeled selectively on the methionine residues by [3H]methyl exchange to high specific activity.

A technique is described for labeling bovine parathyroid hormone (bPTH) with tritium by [3Hmethyl exchange. The methionine residues were first methylated with [3H]methyl iodide at pH 4, and the reaction products were separated by cation exchange chromatography. The major peak consisted to hormone in which both methionines were converted to [3H]methyl methionine sulfonium iodide (3H-methylated bPTH). This product was then demethylated with 2-mercaptoethanol (6 M) at pH 8.6 to regenerate the hormone in an unmodified but tritiated form ([3H]bPTH), with a specific activity of 1.7 Ci/mmol. High pressure liquid chromatographic analysis showed that 96% of the radioactivity was incorporated into the methionine residues. There was no evidence of any alteration in the primary structure, as [3H]bPTH was found to run in the same position as unlabeled bPTH on cation exchange chromatography and disc gel electrophoresis and to have an identical absorption spectrum in the 240- to 330-nm range. Moreover, [3H]bPTH had full biological activity, as measured by an in vitro bioassay based on activation of rat renal cortical adenylate cyclase, although 3H-methylated bPTH was almost completely inactive. Similarly, while 3H-methylated bPTH had reduced potency in a RIA specific for antigenic sites in the 1--34 region of the sequence, [3H]bPTH was found to have full activity. The preparation of labeled bPTH was repeated using [14C]methyl iodide, with similar results, although [14C]bPTH was found to have somewhat reduced immunological and biological activities. While [3H]bPTH had a lower specific activity than can be obtained by various other techniques for incorporating tritium or 125I into peptides, biosynthetic labeling is at present the only alternative method for preparing biologically active, labeled bPTH without altering the primary structure. By comparison with this technique, the present method gave a product of a much higher specific activity which was labeled specifically in the biologically essential amino-terminal region. The same simple chemical procedures are clearly of wide potential application to the preparation of other labeled peptides.


Neonatal estrogen treatment alters sexual differentiation of hepatic histidase.

Hepatic histidase was used as an enzyme marker for the study of neonatal programming in intact rats. Diethylstilbestrol (DES) or 17 beta-estradiol (E2) treatment for days, 2, 4, and 6 post partum resulted in decreased histidase activities in the adult female, but no effect was seen in prepubertal male and female rats or in adult males. In contrast, similar neonatal doses of testosterone propionate (TP) had no effect on histidase. Dose-response experiments demonstrate a 3-fold greater neonatal sensitivity to DES than to E2. The action of neonatal estrogen treatment is demonstrated to be permanent and irreversible. Neonatal treatment with E2, DES, or TP resulted in decreased uterine wet weights in adult females (E2 less than DES less than TP less than controls). Circulating sera estrogen levels were lower in adult E2- and DES-treated females than in TP-treated and control females. Our results suggest that these alterations may be due to direct toxic effects on the postnatal development of the female reproductive tract and endocrine system and/or to organizational effects on nerve endings in the hypothalamus that result in programming for altered sexual differentiation of hepatic metabolism.


Ether releases large amounts of prolactin from rat pituitaries previously "depleted" by short term suckling.

The effect of ether inhalation upon plasma PRL levels was assessed in lactating rats whose pituitary stores of the hormone first had been depleted by a short term (10-min) period of suckling in comparison with those whose PRL stores had not been depleted by prior suckling. Ether, unlike suckling or handling-decapitation stress, did not deplete pituitary PRL and caused only a small increase (36 to 52 ng/ml) in the plasma concentration of the hormone. However, when ether was given 10, 60, or 120 min after the plasma concentration had subsided from a prior 10-min period of suckling, the plasma concentration of PRL in each instance rose within 5--10 min to 200--250 ng/ml and was sustained at that level for the remainder of the 30-min exposure period. The amplitude and profile of the plasma PRL concentration after ether inhalation were similar to those obtained when a second suckling, rather than ether, was administered after the short term suckling. These data support the hypothesis that releasable PRL derives from depleted PRL and also indicate that, once it is formed, releasable PRL remains available for discharge into the circulation for a relatively long period of time.


Rapid inibition of basal and glucose-stimulated insulin release by xylazine.

Xylazine is a tranquilizer that is widely used in both biomedical research and veterinary medicine. We now report that in dogs, clinically effective doses of xylazine both markedly decrease basal insulin levels and completely abolish the rise in insulin produced by iv glucose. These changes in insulin levels lead to elevations of fasting plasma glucose and glucose intolerance. In contrast, glucagon levels are unchanged. These studies suggest that xylazine may be a useful agent in the study of glucose metabolism and beta-cell function.


The effects of metergoline and other serotonin receptor antagonists on serum corticosterone in rats.

Metergoline antagonized the elevation of serum corticosterone by quipazine in rats. The ED50 of metergoline was less than 0.1 mg/kg, ip, and the effects of a 3 mg/kg dose persisted for more than 24 h. Metergoline did not antagonize the elevation of serum corticosterone by theophylline or ketamine (i.e. did not prevent corticosterone release nonspecifically) and did not affect the concentration of quipazine in the brain. Since quipazine is a serotonin receptor agonist, the antagonistic effects of metergoline may have been due to competition with quipazine at serotonin receptor sites in the brain. Some other agents capable of blocking serotonin receptors also antagonzied the elevation of serum corticosterone by quipazine. These included LY53857, which gave complete blockade at 3 mg/kg, and cyproheptadine and spiperone, which gave significant but incomplete antagonism at 1 mg/kg. Methysergide at 3 mg/kg did not alter the effect of quipazine. Metergoline did not antagonize the elevation of serum corticosterone by other agents throught to act via serotoninergic mechanisms, namely fluoxetine, fenfluramine, L-5-hydroxytryptophan, N,N-demthyl-5-methoxytryptamine, and 1-(m-trifluoromethylphenyl)piperazine. Thus, the interactions between metergoline and quipazine may have occurred at receptors that are not serotonin receptors or that represent a subset of serotonin receptors not mediating the actions of serotoninergic agents other than quipazine.


Vitamin D-dependent calcium-binding protein of rat intestine: changes during postnatal development and sensitivity to 1,25-dihydroxycholecalciferol.

To study the role of the vitamin D-endocrine system during the perinatal period, we monitored vitamin D-dependent calcium-binding protein (CaBP) in rat intestine by radial immunodiffusion and polyacrylamide disc gel electrophoresis. Small amounts of CaBp were present 2 days before birth; these levels increased 74-fold by day 38 after birth. Approximately 80% of the increase in CaBP concentration occurred in a 5-day period at the time of weaning (days 17--22 after birth). Before this period, the concentration of CaBP was comparable to that found in rachitic (adult) rats. Administration of 1,25-dihydroxycholecalciferol to suckling rats on days 15 and/or 16 was followed by a premature increase in the amount of intestinal CaBP. These data demonstrate that although vitamin D-dependent CaBP is low in preweaned rats, the rat intestine is responsive to exogeneous 1,25-dihydroxyvitamin D3 at least as early as day 15 after birth. The close temporal correspondence between the increases in CaBP and previously reported changes in calcium transport and vitamin D metabolism suggest that the vitamin D-endocrine system plays a role in postnatal intestinal maturation and adaptation during the weaning period.


Mechanism of the dipsogenic action of tetradecapeptide renin substrate in dogs.

Dogs with chronically implanted third ventricular cannulae showed significant drinking responses to central injections of angiotensin II and tetradecapeptide renin substrate (TDP). The threshold dose for angiotensin II was 1 pmol and for TDP was 70 pmol. Although central injections of TDP led to drinking and appearance of angiotensin II in cerebrospinal fluid, renin substrate prepared from dog cerebrospinal fluid had no effect. The dipsogenic action of TDP was blocked by prior administration of converting enzyme inhibitor SQ20881 (P less than 0.01) but was not affected by either pepstatin or N-acetyl-pepstatin. Thus, converting enzyme acts directly on TDP to produce angiotensin I and then angiotensin II. The results of the present study do not provide evidence for the presence of an enzyme in the brain with renin-like activity.


The development of gonadotropin and steroid hormone patterns in male and female hamsters from birth to puberty.

Male (1--60 days old) and female (1--30 days old) hamsters were decapitated and serum levels of LH, FSH, PRL, progesterone, androgens (males), and estradiol (females) were measured by RIA. Males and females had similar levels of LH until 15 days of age and of FSH until 12 days of age, at which times gonadotropin levels increased significantly in females. Peak levels for females occurred on days 19--21 for LH and on days -2--24 for FSH, later than the times reported for female rats. Adjusting female gonadotropin peaks for gestation length places these peaks for hamsters and rats at the same time in postmating age. In female hamsters, large variations occur in LH between 16--25 days of age, as reported for female rats. Males reached peak serum levels of LH and FSH on day 40, just before the first motile epididymal sperm. Serum PRL levels were identical in male and female hamsters until at least day 30. PRL levels sharply increased in both sexes after day 18 and remained elevated until at least day 30. In males, serum androgens were low until 30 days of age, in contrast to high levels reported for infantile rats. Androgens rose sharply in male hamsters after day 30 to peak levels on day 50. Progesterone in males also remained low until after day 30. Serum estradiol in females did not attain the extremely high elevations seen in rats. Some fluctuations occurred between 10--30 days of age, which presumably represent maturational changes in the ovary. Serum progesterone in females followed a pattern of development similar to estradiol.


Estrogen receptor in the thymus of the castrated mice.

Sucrose density gradient ultracentrifugation and dextran-coated charcoal adsorption permitted us to characterize the estrogen-binding proteins in cytosols obtained from the thymus, spleen and mesenteric lymph node of the castrated male and female mice of C57BL strain. The thymic cytosol from both sexes incubated with 3H-estradiol-17 beta in the presence of excess unlabeled steroids showed a specific estrogenbinding 4 S protein with its binding capacity of 10(-14) moles/mg protein for males and 4 x 10(-15) moles/mg protein for females, respectively. The dissociation constant was of 4 x 10(-10) M for males and 3 x 10(-10) M for females, respectively. No specific binding was, however, found in the cytosols of the spleen and mesenteric lymph node. Steroid analysis by thin-layer chromatography of the thymic cytosols after incubation of them with 3H-estradiol-17 beta showed that a fair amount (around 60%) of radioactivity was from the undegradated radioactive steroid still bound to 4 S binder in both sexes. Enzyme study and heat experiment revealed that the estrogen specific 4 S binding component in the thymic cytosols bears at least protein in nature and is of heat-labile nature. These results strongly suggest that the thymus of the castrated mice contain a specific estrogen receptor, the nature of which is in part protein and heat-labile.


Comparison of human calcitonin secretion after a 1-minute calcium infusion in young normal and in elderly subjects.

Human calcitonin (hCT) response to a 1-minute calcium infusion was studied in 6 male and 4 female young normal subjects and in 6 male and 6 female elderly subjects. In the young subjects plasma hCT levels increased significantly (p less than 0.01) from mean basal value of 82.3 +/- 48.7 pg/ml to maximum level of 407.5 +/-198.0 pg/ml in the male, while it increased from 96.3 +/- 89.2 to 216.3 +/- 89.1 pg/ml p less than 0.05) in the female. In the elderly subjects, it increased from 80.3 +/- 56.9 pg/ml to maximum level of 229.2 +/- 130.6 pg/ml (p less than 0.05) in the male, while it increased from 109.2 +/- 43.7 to 163.3 +/- 55.7 pg/ml (p less than 0.005) in the female. There was no significant difference in the basal hCT level of these 4 groups. In both the young and the elderly, however, mean increment of hCT level was significantly (p less than 0.05) higher in the male than in the female of the same-aged group. In both the female and the male subjects, it was significantly (p less than 0.05) higher in the young than in the elderly of the same sex. A 1-minute infusion of calcium can be used as a reliable provocative test for hCT secretion in human subjects.


Thyroglobulin and microsomal antibodies in patients with insulin dependent diabetes mellitus and their relatives.

The sera for 88 parents and 9 siblings of 73 patients with insulin dependent diabetes mellitus in childhood and 437 controls matched in age and sex, were tested by the thyroglobulin and microsome-coated tanned red cell hemagglutination test (Fuji-Zoki Co. Tokyo). None of 73 children with diabetes mellitus had antithyroglobulin antibodies, whereas twelve (16.4%) had antimicrosomal antibodies compared with the incidence of 0.4% and 1.1%, respectively, in 437 controls. In the parents and siblings of these probands, thyroid antibodies were also found in increased incidence. The incidence of antimicrosomal antibodies in the 68 mothers was significantly higher than in controls matched for age and sex, but the incidence of the positive thyroid antibodies in the 20 fathers and 9 siblings was not significantly different from that in control populations. The incidence of thyroid antibodies tended to be higher, though not significant, in parents and siblings of diabetic children with positive thyroid antibodies than in those of diabetics with negative ones. These findings suggest that immunogenetic factors may be responsible for the pathogenesis of some cases of diabetes mellitus in childhood.


Effects of vasoactive intestinal peptide on glycogenolysis in cultured liver cells.

When isolated rat liver cells were incubated in the presence of vasoactive intestinal peptide at the concentrations ranging from 0.2 microgram to 2 micrograms per ml, glycogenolysis was maximally stimulated within 15 min. However, somatostatin inhibited the liver glycogenolysis. The combined addition to the incubation medium showed that insulin and somatostatin inhibited the stimulated glycogenolysis induced by vasoactive intestinal peptide, while vasoactive intestinal peptide plus secretin showed no additive effect on glycogenolysis, as compared with single the addition of vasoactive intestinal peptide. On the other hand, the additon of glucagon to vasoactive intestinal peptide showed additive effects on glycogenolysis. These results suggest that the receptor site for vasoactive intestinal peptide may be distinguishable from that for glucagon. Extracellular calcium ions were demonstrated to play an important role in the modulation of vasoactive intestinal peptide-induced glycogenolysis. The evidence presented in this paper indicates that glucose metabolism may be partly regulated by the direct action of vasoactive intestinal peptide on hepatocytes, which is referred to as an enterohepatic axis and that the axis is inhibited by insulin and somatostatin.


The stimulatory roles of catecholamines and acetylcholine in the regulation of gonadotropin release in ovariectomized estrogen-primed rats.

Injections of 2 mg of progesterone into ovariectomized estrogen-primed rats significantly increased serum LH and FSH concentrations 3, 5 and 8 hr later. Receptor blockers of noradrenaline (NA), dopamine (DA) or acetylcholine (ACH), phenoxybenzamine (20 mg/kg body weight), pimozide (1mg/kg body weight) or atropine (700 mg/kg body weight), respectively, prevented the progesterone-induced gonadotropin release. On the other hand, none of them blocked the gonadotropin release following unilateral electrochemical stimulation (100 microA for 60 sec) of the medial preoptic area which occurred 0.5 and 1.5 hr later, although pimozide or atropine reduced serum LH concentrations at 4.0 hr after stimulation. Furthermore, the sites of action of NA, DA and ACH with respect to LH release were examined by intracerebral implantation in ovariectomized estrogen-primed rats DA or ACH, when implanted unilaterally into the medial preoptic urea, induced a significant increase in serum LH 5 hr later, whereas NA decreased LH levels. Implantations of NA or ACH into the bed nucleus of the stria terminalis or the medial amygdala increased serum LH although the effect of NA into the latter was not statistically significant. Only implantations of NA among the three substances into the lateral septum induced LH release. These results suggest that all of NA, DA and ACH play stimulatory roles in the regulation of gonadotropin secretion, and that there are regional differences of their effectivenesses in releasing LH within the limbic-preoptic area.


Effects of hypothalamic deafferentation on hormonal facilitation of lordosis in ovariectomized rats.

Lordosis response in estradiol benzoate (EB)-progesterone (P) primed castrated female rats was studied after 4 types of deafferentation of the medial hypothalamus. Tests were started 4-5 weeks after the brain surgery and ovariectomy. Anterior deafferentation (half-dome cut) at the level behind the suprachiasmatic nucleus (AD-I) and island isolation of the medial basal hypothalamus (MBH island) were highly effective to suppress lordosis response in EB-P primed females. However, the cuts placed dorsal (AD-II) or posterior (AD-III) to the AD-I were without apparent suppressive effect on the EB-P induced display of lordosis. These results suggest that the anterolateral fiber connection with the MBH may participate in lordosis facilitatory mechanisms in EB-P primed females. When reserpine (R) was injected instead of P to EB-primed rats, R effectively facilitated lordosis response in rats with or without the deafferentation (AD-I or MBH island). This suggests that the MBH is not necessary to facilitate lordosis in EB-R primed rats. The site of action of R in the central nervous system for facilitating lordosis may not be the same as that of P.


The release and metabolism of pancreatic hormones after major hepatectomy in the dog.

Major hepatectomy in the dog induced a 50% decrease in peripheral serum glucose, a 11-fold increase in portal plasma glucagon and a 36-fold increase in the portal glucagon/insulin ratio 3 hr after operation. Peripheral serum glucose levels were inversely correlated to the logarithmic value of portal plasma glucagon (r = -0.50, p less than 0.01) and that of the portal glucagon/insulin ratio (r = -0.85, p less than 0.01) for 1-6 hr after operation. The ratio of peripheral to portal plasma glucagon was also inversely correlated to the logarithmic value of portal plasma glucagon (r = -0.59, p less than 0.01). In case of glucose infusion, plasma glucagon levels were not elevated after major hepatectomy. The data suggest that glucose deficiency after major hepatectomy in the dog may cause hyperglucagonemia with an enhanced glucagon requirement.


Insulin and glucagon relationships during aging in rats.

Oral glucose tolerance tests were performed under pentobarbital anesthesia in 43 male Wistar rats 2 to 18 months of age in order to determine if insulin and glucagon secretion are altered with aging. Although any linear correlation was not demonstrated between aging and blood glucose, plasma insulin or glucagon levels, post-glucose levels of blood glucose were significantly suppressed and those of plasma glucagon were significantly elevated at 4 to 6 months of age. No significant difference was found between young (2 months of age) and aged rats (12 to 14 and 17 to 18 months of age) in either blood glucose or plasma insulin levels during oral glucose load. On the other hand, post-glucose plasma glucagon levels of the aged rats were significantly higher than those of the young ones. Furthermore, comparisons of various kinds of indices among the different age groups, such as insulinogenic index, insulin/glucagon and so forth during oral glucose tolerance tests also indicate the significant alteration of glucagon secretion during aging process. It is concluded from the present data that glucose tolerance does not apparently deteriorate during aging process in rats but that glucagon responses to oral glucose administration are elevated with aging.


Effects of oral administration of positively charged insulin liposomes on alloxan diabetic rats: preliminary study.

Insulin encapsulated in liposomes of various lipid compositions were prepared. The amount of insulin trapped in these liposomes increased in the order, negatively charged liposomes less than neutral liposomes less than positively charged liposomes. In positively charged liposomes, the amount of insulin trapped increased with increase in the amount of amphiphile stearylamine. Under the conditions tested, the highest insulin content (about 50%) was obtained with liposomes composed of phosphatidyl choline/cholesterol/stearylamine in a molar ratio of 7/2/2.25. These liposomes were stable on incubation for 3 hr at 37 degrees C in solutions of pepsin, trypsin, and pancreatin, and after these incubations, a considerable amount of insulin was still associated with the liposomes. However, the liposomes released almost all the insulin into the medium on treatment with bile. When the liposomes were administered orally to rats in the 3rd phase of acute alloxan diabetes, reduction of the blood glucose level was observed in 7 of 11 animals, the reduction persisted for several hours and was ranging from 30 to 75%. In alloxan diabetic rats showing hyperglycemia for 3 to 6 months, the liposomes also increased the glucose tolerance in half the animals tested.


Sex hormones metabolism in the brain: influence of central acting drugs on 5 alpha-reduction in rat diencephalon.

Rats after adrenalectomy-testectomy showed a gradual increase in diencephalon 3-oxo-5 alpha-steroid: (acceptor) delta4-oxidoreductase (5 alpha-reductase) activity for 3 days. The activity then returned near to the normal range on the 4th postoperative day. When rats were given testosterone propionate (TP) 3 days after adrenalectomy-testectomy, diencephalon 5 alpha-reductase activity returned to the preoperative range 2 hr after TP administration. Diencephalon 5 alpha-reductase activity showed a highly significant increase (p less than 0.01) after a single administration of carbamazepine, reserpine, diazepam, phenytoin, phenobarbital or disulfiram. A significant increase (p less than 0.05) was also found after a single administration of methylphenidate, caffeine or methamphetamine. Plasma testosterone decreased concurrently after administration of all these agents, except diazepam. Diencephalon enzyme activity decreased significantly after repeated disulfiram administrations (p less than 0.01) but increased significantly after methamphetamine administrations (p less than 0.05). Plasma testosterone showed a tendency to decrease after repeated methamphetamine administrations but tended to increase after repeated disulfiram administrations.


Effect of parathyroid hormone on the increase in serum glucose and insulin levels after a glucose load to thyroparathyroidectomized rats.

Thyroparathyroidectomy (TPTX) caused a significant increase in serum glucose and a corresponding fall in serum calcium in both fed and fasted rats. The increase in serum glucose, induced by TPTX, was markedly potentiated by a single intraperitoneal administration of calcium (2 mg/100 g BW) which caused a significant elevation of serum calcium in thyroparathyroidectomized rats. Parathyroid hormone (PTH; 20 U/100 g BW) administered subcutaneously to thyroparathyroidectomized rats, caused a significant decrease in serum glucose (0.1 g/100 g BW) to sham-operated rats significantly increased both serum glucose and insulin. The rise of serum glucose produced by a glucose load was markedly potentiated by TPTX, but the increase in serum insulin was not promoted significantly. The administration of PTH decreased both serum glucose and insulin levels increased by a glucose load to thyroparathyroidectomized rats, in a dose-dependent manner. The administration of calcitonin (80 MRC mU/100 g BW) significantly prevented the effect of PTH to decrease serum glucose after a glucose load to thyroparathyroidectomized rats, and calcitonin increased serum insulin. These results suggest that the effect of PTH on serum glucose does not involve insulin secretion.


Changes in fat content and some characteristics of lipolytic activity during pregnancy and lactation in mouse mammary gland.

The amount of free fatty acid in the mouse mammary gland continuously increased throughout pregnancy and lactation, while the amount of triglyceride which had been stored in the gland rapidly decreased after parturition. Higher lipolytic activity in the gland was observed in pregnancy than in nonpregnant and lactating animals. The optimum pH of the activities before and after parturition were about 6 and 7, respectively, and the activities did not decrease at high ionic strength in contrast to the ion dependent inactivation described in lipoprotein lipase. Incubation of the enzyme extract of the lactating mouse mammary gland at 50 degrees C for 10 min led to a remarkable increase in the lipolytic activity measured at pH 6.0, suggesting the existence of either an inactive form of the lipase whose optimum pH is 6.0 or some heat sensitive inhibitor(s) or inactivator(s) of the enzyme in the lactating mammary gland. The triglyceride stored in the gland in pregnancy will be consumed within the first 3rd days after parturition, and the lipases play an important role in the decomposition of the triglyceride.


Effect of somatostatin on plasma renin activity.

Intravenous infusion of somatostatin in mongrel dogs caused a significant decrease in the peripheral plasma renin activity (PRA) enhanced by pentobarbital sodium anesthesia or furosemide treatment. However, the inhibitory activity vanished within 10 min after termination of somatostatin infusion. Intrarenal arterial infusion of somatostatin decreased furosemide-enhanced PRA in renal vein by 24.0%, 16.6% and 8.6% in dose of 0.1, 0.5 and 1.0 microgram, respectively. On the other hand, high doses of the peptide (50-200 microgram) failed to decrease. The changes in PRA occurred in the absence of any alteration in blood pressure during the intravenous infusion under furosemide treatment. In an in vitro study, the addition of somatostatin in doses of 0.01 and 0.05 microgram suppressed the renin release in dog renal cortical cell suspension by 74.3% and 53.6%, respectively. Therefore, in both intrarenal arterial infusion and the cell suspension system, somatostatin was increasingly effective in decreasing renin release towards the lower end of the dose range tested. These results suggest that the effect of somatostatin on hyperreninemia may involve an inhibition of renin release at the cell level in the kidney.


Possible role of brain norepinephrine in the hypothalamic hypophyseal adrenal system.

Intracisternal injection of bethanidine in rats decreased brain norepinephrine turnover without affecting its endogenous level, and increased both cardiac norepinephrine turnover and serum corticosterone level. A negative correlation was observed between brain norepinephrine turnover rate and serum corticosterone level. On the other hand, when cardiac norepinephrine turnover was suppressed by intraperitoneal injection of bethanidine, serum corticosterone did not change significantly. Next, ether inhalation was added after intracisternal injection of bethanidine. Then, serum corticosterone increased more even brain norepinephrine turnover was suppressed only slightly. These data may indicate that serum corticosterone increases by selective decrease in brain norepinephrine turnover via the humoral route; from the hypothalamus down to the adrenal cortex. Inversely, intracisternal injection of corticosterone increased brain norepinephrine turnover. These results suggest that brain norepinephrine may play an inhibitory role in the tonic regulation of CRF-ACTH secretion in the higher center than the hypothalamus and there may be a closed-loop feedback system between brain norepinephrine and serum corticosterone.


Effects of chlorpromazine and estradiol benzoate on prolactin secretion in gonadectomized male and female rats.

The effects of chlorpromazine (CPZ) and estradiol benzoate (EB) on serum prolactin (PRL) levels were studied in gonadectomized male and female rats. In both sexes CPZ (25 mg/kg body weight) produced an elevation of PRL when measured 2 hr after the injection, but the elevated levels were higher in ovariectomized rats than in orchidectomized rats. These results reconfirm a sexual difference in the regulatory mechanism of PRL secretion in response to the dopamine receptor blocker. Pretreatment with 5 microgram EB 48 hr before CPZ injection abolished this sexual difference in serum PRL concentration.


Kindling phenomenon: impairment by auditory stimuli.

By coupling kindling stimuli with tones, it is shown that kindled epileptiform activity is not easily classically conditioned such that it can be evoked by an auditory stimulus. On the contrary, a tone presented 400 msec before and during the kindling stimulus impedes the rate of kindling.


An electrophysiological analysis of the anticonvulsant action of cannabidiol on limbic seizures in conscious rats.

The effects of cannabidiol (CBD) on electrically evoked kindled seizures were studied in conscious, unrestrained rats with chronically implanted cortical and limbic electrodes, and the results were compared with those of delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin (PHT), and ethosuximide (ESM). All drugs were anticonvulsant, but there were marked differences in their effects on afterdischarge (AD) threshold, duration, and amplitude. CBD, like PHT and delta 9-THC, elevated the AD threshold; in contrast, ESM decreased the threshold but suppressed AD spread. CBD, however, also resembled ESM inasmuch as both drugs decreased AD duration and amplitude. Electrophysiologically, the antiseizure effects of CBD were a combination of those of PHT and ESM. The combination of effects may account for the observation that CBD was the most efficacious of the drugs tested against limbic ADs and convulsions. Other properties of CBD were also noted: For example, compared with delta 9-THC, it is a much more selective anticonvulsant vis-à-vis motor toxicity. CBD also lacks the CNS excitatory effects produced by delta 9-THC, PHT, and ESM. These characteristics, combined with its apparently unique set of electrophysiological properties, support the suggestion that CBD has therapeutic potential as an antiepileptic.


Hemispheric asymmetry of pentamethylenetetrazol-induced wave-spike discharges and motor imbalance in rats.

An intrinsic asymmetry of nigrostriatal dopamine system postulated to be responsible for motor imbalance in normal rats (Glick et al., 1976) is believed to create asymmetry of arousal-sensitive wave-spike discharges. In the present study, bilaterally recorded pentamethylenetetrazol (PMZ)-activated wave-spike discharges were correlated with circling behavior in intact rats. Thirteen naive rats (10 male, 3 female) were implanted with electrodes symmetrically placed over the visual cortices, and their rotation directionality was assessed in the rotometer subsequent to administration of d-methamphetamine sul-ate, 1.5 mg/kg, i.p. In 9 rats a PMZ injection, 20 mg/kg, i.p., revealed asymmetric wave-spike bursts. All of them reliably rotated in the dirction opposite to the hemisphere with lower amplitude wave-spike discharges. It is believed that the nigrostriatal dopamine system plays a major role in modulating the asymmetry of wave-spike seizures. The findings are discussed as they relate to asymmetric generalized wave-spike dischanges found in certain petit mal patients.


Cortical modification of an epileptogenic focus.

The influence of cerebral cortex on penicillin-induced spikes in striate cortex was studied with the technique of hypothermic block. Direct cooling of the involved or contralateral striate cortex markedly reduced seizure activity. Significant reduction in seizure activity was also seen with cooling of ipsilateral and contralateral visual association cortex. None of the other cortical areas tested had a reproducible effect on the frequency of seizures. These findings are discussed in term of local and remote factors influencing the epileptogenic focus.


Metabolism and disposition of trimethadione in pregnant rats.

The metabolism and disposition of a suspected human teratogen, trimethadione (TMO), was studied in pregnant rats following administration of the drug at doses of 60 and 240 mg/kg/day during 6 to 15 days of gestion, with a view to understanding the fetotoxicity of the drug. Following the last dose, animals were sacrificed at 6, 12, and 24 hr, and the fetuses were removed by caesarean section. The concentrations of TMO and its N-demethylated metabolite, dimethadione (DMO), were determined by a specific GLC procedure in maternal plasma, urine, brain, and liver, as well as in placenta and whole fetus. The plasma and liver concentrations of TMO and DMO suggested that the parent drug is rapidly converted to DMO. Total 24 hr urinary recoveries of the unchanged drug and the metabolite were 61 and 82% following 240 and 60 mg/kg/day doses of TMO, respectively. The DMO concentrations in brain and all other tissues analyzed were far greater than those of TMO. The fetus to maternal plasma concentration ratios of TMO suggested that the placental transfer of the drug was greater than the clearance from the fetus over the periods examined, whereas the transfer of the metablite seemed to be independent of dose. Furthermore, the rate of decline of DMO in fetus was far slower than that of the placenta and maternal plasma, causing accumulation of DMO in the fetus. The results suggest that the fetotoxic effects produced by TMO when given to pregnant rats could be due to accumulation of DMO in fetus.


Flow-dependent salivary primidone levels in epileptic children.

In 36 epileptic children treated with primidone alone or in combination with additional anticonvulsants, salivary drug levels were compared in resting (I) and in flow-stimulated (II) saliva and were related to the corresponding serum levels. Primidone levels in saliva I and saliva II were highly correlated (r = 0.97) but were significantly (p less than 0.001) lower in saliva II; the mean difference was -38%. Serum primidone levels were highly correlated to salivary primidone levels both in saliva I (r = 0.92) and in salvia II (r = 0.91). A significant negative correlation could be established between the salivary flow rate and the saliva/serum ratio of primidone, especially in saliva I (r = 0.61; p less than 0.001). The mean saliva I/serum ratio was 1.115, reflecting drug accumulation in resting saliva. The reason primidone accumulates remains unclear. When salivary flow was stimulated, the mean saliva/serum ratio decreased to 0.7, indicating the development of a drug concentration slope from blood to saliva. This is explained by the limited permeation of the drug through cellular membranes due to its rather low lipid solubility. From the data it can be concluded that saliva is suitable for monitoring primidone levels provided the conditions of sample collection are standardized.