A simple method for the differential measurement of 125I and 3H by liquid-scintillatin spectrometry. 1. A method is described for the differential radioactivity counting of 125I and 3H in a liquid-scintillation spectrometer without a separate gamma counter. 2. The sample was contained in a polyethylene miniature vial placed centrally in a standard 20 ml glass scintillation vial containing a tin-loaded scintillant. 3. A direct measure of the 125I radioactivity at an efficiency of 30% was then obtained by radioactivity counting in the pre-set 3H window of a scintillation spectrometer. No counts for 3H radioactivity were registered at this stage because of the barrier to the passage of the low-energy beta-particles provided by the wall of the polyethylene vial. 4. After mixing the sample and scintillant both 125I and 3H were detected at efficiencies of 73% and 29% respectively. Subtraction of the 125I contribution from the combined radioactivity count rate then gave the net 3H count.


Intractable peptic ulcer disease.

Intractable peptic ulcer disease. The intractable ulcer is usually complicated because of posterior penetration, obstruction, or postbulbar or channel location; or it is an atypical ulcer such as those occurring with the ZE syndrome, hyperparathyroidism, and the milk-alkali syndrome. The management of intractability depends upon finding the cause and initiating the appropriate therapy. Many abdominal diseases may masquerade as intractable ulcers, so every patient must be evaluated thoroughly to prove that his ulcer is indeed intracetable.


Community mental health centers and the decreasing use of state mental hospitals. To test the success of the Community Mental Health Centers Program goal of reducing state hospital utilization, changes in state mental hospital resident and admission rates were calculated, using 16 states, for counties wholly within or outside of catchment areas served by operating, federally funded community mental health centers. There was no consistent relationship between the opening of centers and changes in state hospital resident rates. However, counties with centers tended to decrease more (or increase less) in state hospital admission rates than areas without centers.


The paraprofessional as a referral link in the mental health delivery system. The role of the paraprofessional in the delivery of mental health services is often ambiguously defined. Even while performing the specific task of making a referral, the activities of the paraprofessional are subject to controversy. In this study the clients, the agency board members, and the community mental health agency workers all have different expectations of the qualifications, the knowledge, and the activities of the paraprofessional referral worker. It is suggested that the disparate views the participants bring to the referral situation make it unlikely that the paraprofessional will satisfy the expectations of all of them.


Social characteristics of patients admitted to the terminated from mental health centers. The assumption that terminations data represent a cross section of patients treated at mental health centers is investigated by comparing social characteristics of patients admitted to and terminated from mental health centers. The great majority of patient characteristics of the two groups are similar enough to make the above assumption safely.


The emerging role of sociological consultation in the field of community mental health. One of the most innovative features of the community mental health movement is its expansion to include other than the traditional mental health personnel. It seems most appropriate now that the sociologist be among the new manpower resources put to use by the various agencies concerned with the community mental health movement. In this regard, it is necessary that both professionals and lay people working in mental health be made aware of what the sociologist can contribute to the mental health movement. Sociological services relative to the comprehensive community mental health centers, to other mental health agencies, and to lay and professional persons concerned with mental health are described. The emergence of this role will not be without problems, several of which are described here.


Social workers' orientations toward community mental health concepts. Relations between ideological priorities in social work and community mental health were examined by a Likert-type questionnaire containing statements representing Caplan's Conceptual Models in Community Mental Health. Seventy social workers were sampled, with equal subsamples representing the five largest fields of practice in social work. This sample appeared to be highly representative of the national social work population by fields of personal service. By analyses of variance and correlation, significant differences were found between levels of approval for respective models by the total sample, but no significant differences were found by fields of practice, or any other professional or demographic attribute. This indicates a consensual integrity in the social work profession's community mental health orientation, and strong mutuality between social work and community mental health value orientations.


Treatment progress by objectives: Kiresuk's and Sherman's approach simplified. A simplification of Kiresuk's and Sherman's approach to the measurement of therapeutic success is proposed. Hypothetical cases are given as examples.


Program evaluation in the public interest: a new research methodology. For every social welfare or social control service program there are several parties, each with different interests: patients, clients, staff, management, and sponsors. Evaluation of such a program in the public interest must take the interests of these parties into account. To do so requires an untraditional methodology, that of a second-person, or communal, science, which is not above the conflict of parties and their interests in specifying the variables, staffing the research, balancing considerations of intrusion against those of bias, considering the action implications of the data, sequentially staging the research, or even publishing findings. This all makes evaluation in the public interest a highly political process often unlikely to be logically decisive about intervariable relationships, to yield generalizable results, or even to be completed.


The psychologist in the pediatrician's office: one approach to community psychology. This paper describes a community psychology program that was based in a pediatrician's office in a rural community. Three broad categories of psychological problems were encountered: (1) emotional disturbance, (2) developmental delay in children, and (3) ineffective child management procedures used by parents. The advantages and the problems involved in using the pediatric office as a setting to provide primary mental health care to children and families are outlined.


Psychological consultation to a police training academy: problems and opportunities. Police departments are systems of social regulation affecting the lives of many citizens. Psychological instruction to trainees can increase the armamentarium of police techniques in dealing with civil disturbances. Such instruction must be cognizant of attitudinal resistances toward new police instructors, particularly those with an intellectual or university orientation. Crisis situations that are handled by a proper balancing of coercive and negotiation types of techniques generate the most effective solution to disturbance situations. An approach is offered for effective teaching of a balanced-coercive alliance model.


The use of clemastine ("Tavegil') administered parenterally in acute allergic episodes. An open study was carried out in 41 patients, requireing an emergency doctor visit because of an acute allergic episode, to assess the effectiveness of an antihistamine, clemastine, given parenterally. The results showed that a single intramuscular injection of 2 mg clemastine was 'fully effective' in relieving the sumptoms of 19 (46.3%) patients, and gave 'some relief' in 20 (48.8%). Two (4.9%) patients failed to respond. No side-effects of treatment were reported.


Pulmonary function study in old age.

Pulmonary function study in old age. A study was carried out in 100 patients aged between 70 and 90 years to investigate pathological and respiratory function changes in old age. Vitalograph and peak flow meter measurements were made, but blood gas analysis was only carried out in 6 patients in view of the technical difficulties. Analysis of the results showed that there was a definite, moderate, restrictive type of defect in pulmonary function in almost all the patients, in those with generalized senile changes as well as in those with a pathological condition. Blood gas analysis showed a minimum degree of alteration in oxygen tension and saturation with normal carbon dioxide tension.


Long-term effects of an amiloride/hydrochlorothiazide combination ('Moduretic') on electrolyte balance. A study was carried out of plasma electrolyte estimations made before and after long-term use of a combination of amiloride and hydrochlorothiazide in 23 patients. The mean duration of use was 20.3 months. No significant differences were found in plasma potassium, sodium, bicarbonate or urea from baseline levels.


Changes in plasma and urine magnesium following subcutaneous insulin. In 7 of 13 patients given subcutaneous insulin as part of the assessment of their endocrinological status, serum magnesium levels fell below the lower limit of the normal range for the laboratory 1 to 2 hours after insulin administration. This relative hypomagnesaemia was not accompanied by any change in the red cell magnesium concentration, and did not bear a close relationship to the degree of hypoglycaemia developed. During the 2 1/2 hour period following insulin therapy there was renal conservation of magnesium ion.


Translocations of acrocentric chromosomes and their implications in the evolution of sheep (Ovis). Cytogenetic evidence suggests that the caprids (sheep and goats) evolved from a common ancestor with a 2n=60 karyotype. Although goats (Capra) retained the primitive 2n=60 karyotype, sheep (Ovis) underwent a sequential reduction in the number of chromosomes by means of acrocentric translocation. The formation of the first metacentric autosome (M1) occurred in the aoudad (Ammotragus) and urial (O. vignei), resulting in a 2n=58 karyotype. The G-bands are homologous, which implies both genotypes arose from a common ancestor, possibly a rupicaprid. Based on G-bands, acrocentric chromosomes 1 and 7 of the 2n=60 karyotype formed the M1. The X chromosome, which is the second longest acrocentric in the 2n=60 karyotype, became the longest acrocentric in Ammotragus and Ovis (2n=58). The second pair of metacentrics to evolve, which is ranked in the M3 position of the 2n=54 karotype, resulted from the translocations of acrocentric chromosomes 4 and 14 or 15 in the 2n=60 karyotype. The M2 was the third pair of metacentrics to be formed and resulted from the translocations of acrocentric chromosomes 3 and 12 or 13 in the 2n=60 karyotype. The G-bands of all 2n=54 karyotypes are homologous, which indicates origin from a common ancestor. Evidence is presented that suggests a prezygotic selection is bringing about a reduction in diploid chromosome numbers. The possible roles of fission and fusion in the karyotypic evolution of Ovis are discussed.


Spontaneous triploidy in the California roach Hesperoleucus symmetricus (Pisces: Cyprinidae). A single triploid individual (3n = 75) of the Calfornia roach, Hesperoleucus symmetricus, was identified among a sample of nine specimens from the Russian River, California. The diploid number of H. symmetricus, as revealed by the karyotypes of the remaining eight specimens, is 50. Aside from the all-female triploid unisexual fishes, this is the first report of a triploid fish from the wild, and the second report of a triploid in a bisexual fish species. The most likely origin of the triploid was probably fusion of a haploid sperm with an unreduced ovum.


Nondisjunction in aging female mice.

Nondisjunction in aging female mice. Oocytes from CBA mice varying in age from 2 to 11 months were cultured to the metaphase II stage of meiosis and the chromosomes analyzed. The oocytes from three maternal age groups were compared with respect to the mean number of oocytes obtained per mouse, the frequency of maturation to metaphase II, and the frequency of numerical chromosomes abnormalities. Both the mean number of oocytes obtained per mouse and the frequency of maturation decreased markedly with maternal age. The frequency of chromosome abnormalities in the oocytes increased with maternal age from the young to the middle-aged mice but dropped off in the oldest maternal age group. No hyperploid (n + 1) oocytes were observed in the young or old group of mice, but 5.2% hyperploidy occurred in the middle-aged group. It is suggested that the lack of hyperploid oocytes in the old CBA females might be due to a threshold effect in which oocytes that are damaged by the number of univalents present at metaphase I become atretic and do not progress to metaphase II. The frequency of diploid (2n) oocytes was 1.7% and was not maternal-age dependent.


Hydrocephalus in infancy and childhood. Our experience of CSF shunting. A surgical series of 346 children with nontumoral hydrocephalus shunted in the period January 1957 to December 1973 is presented. The etiological factors, preoperative clinical and anatomical status of the patients, their surgical career, the reasons for revision operations and causes of death, are analyzed and discussed in relation to each of the four groups constituting the series: tetraventricular communicating hydrocephalus, triventricular hydrocephalus, obstructive hydrocephalus from ventriculocisternal block and postmeningocele or postmyelomeningocele hydrocephalus. 141 patients required 218 revision operations. 16 patients died after the first operation, 27 on revision and 38 sometime later. 41 patients were lost to follow-up. A recent clinical and instrumental review of the physical, neurological and mental status of the remaining 224 patients showed that 136 (60.7%) are well or very well, 68 (30.3%) have residual deficits likely to regress with treatment and 20 (8.9%) are severely handicapped. These long-term results and the surgical aspects of the problem are discussed in the light of the literature.


X-linked hydrocephalus, with aqueductal stenosis, mental retardation, and adduction-flexion deformity of the thumbs. Report of a family. A new family is reported of a Bickers-Adams-Edwards syndrome. This family has been studied up to three generations. Two female carriers are known. Among the six male children who are affected, four are severely mentally retarded, have spasticity of the legs, and survived with a mild macrocephaly, and two show a more severe and rapid progression of head enlargement. A partial aqueductal stenosis, with remarkable ventricular dilatation, has been demonstrated by pneumoence-phalography in three boys. A deformity of the thumbs links these six children together. One of them has been treated by a ventriculoperitoneal shunt, when 18 months old, without any improvement in the neurological condition. The mental deficiency is much more severe than could be expected from the degree of hydrocephalus, at least as estimated clinically by the macrocephaly. Hydrocephalus is precocious, and the ventricular dilatation very advanced when seen by PEG studies. Recognition of the female carriers is not possible.


Hydrocephalus secondary to intracranial hemorrhage in premature infants. Premature (low birth weight) infants are particularly susceptible to intracranial hemorrhage. This frequently arises from the subependymal area and may dissect into the brain or into the ventricles. If the infant survives, hydrocephalus is a frequent sequela. Because of major improvements in the care of premature infants in recent years and the proliferation of intensive care nurseries, increasing numbers of low birth weight infants are surviving and developing hydrocephalus. Seven cases are described of infants who developed hydrocephalus following intracranial bleeding. Initially, ventricular and lumbar punctures were done to attempt to control head growth but this was unsuccessful. Two were treated with temporary external ventriculostomy which did not permanently control the hydrocephalus. Definitive treatment included ventriculo-atrial shunts using an expandable 'telescopic' cardiac catheter in two and ventriculoperitoneal shunts in five. The pathogenesis and management of the condition are discussed.


Hydrodynamics of shunt valves.

Hydrodynamics of shunt valves. A study of differential pressure valves (DPV) used in the treatment of hydrocephalus was undertaken to determine their pressure-flow characteristics and compatability with the antisiphon valve (ASV). DPV could be classified into two groups: low resistance valves (LRV) and high resistance valves (HRV). The LRV maintains intraventricular pressure (IVP) near the closing pressure (CP) of the valve by permitting a high flow whenever CP is exceeded. The HRV regulates IVP by attempting to match inflow with some point on the pressure-flow curve of the valve. These characteristics were lost unless valve outlet pressure was maintained at atmospheric pressure. This could be accomplished by using a proximal DPV with an ASV at the DPV outlet, thus converting the DPV into a gauge pressure valve and preventing the 'siphon effect' seen with the use of a DPV alone.


Clinical and radioisotopic follow-up study of 'Moyamoya'. 24 children with 'moyamoya' had average follow-up periods of 5 years and 9 months. The following factors were noted to influence the prognosis for mental function: early onset, repeated transient ischemic attacks followed by residual neurological deficit, symptoms suggesting bilateral or dominant hemispheric lesions, and angiographically widespread occlusion. Futhermore, radioisotopic procedures could replace angiography for follow-up studies of patients with Moyamoya.


[Total shoulder endoprosthesis design St. Georg]. Experiences with shoulder replacement in 40 cases since 1966 and the development of a nonblocked total prosthesis are described. The replacement of both joint surfaces according to the principles of low friction arthroplasty ist needed to obtain relief of pain. The nonblocked system corresponds in a high degree to physiologic conditions. The shape of the implant and the meticulous reconstruction of the inner and outer rotator cuffs reduce the danger of dislocation considerably. Only small bone resection is necessary. In cases of dislocated compound fractures and of painful posttraumatic and rheumatic arthrosis, total replacement could be an alternative to resection of the humeral head as well as to shoulder arthrodesis.


[Total replacement of humerus including shoulder and elbow joints]. A case of total alloplastic replacement of the humerus, including the neighboring joints, is reported. The method may be used for treatment of large defects of the humerus due to tumor, osteomyelitis, or trauma. The alloplastic replacement seems superior to autoplastic fibula transplantation.


[Partial replacement of the humerus].

[Partial replacement of the humerus]. Based on twelve cases, this paper reviews the possibilities of partial replacement of the humerus. In 6 cases an interpolation was successfully performed replacing a resected part of the humeral shaft while maintaining the shoulder and elbow joint. The interpolated material is polyethylene, centrally reinforced by metal. A resection of up to 17 cm was performed. The longest period of observation is more than 2 years. This operative procedure is preferred to the methods so far used in cases of extensive destruction of the humeral shaft. Primarily, osteolyses are an indication for this type of operation.


[Results in the implantation of total or partial prosthesis in the knee joint]. A report of the results achieved by treating of corrosive diseases of knee joint by partial and total endoprosthesis. A total of 74 knee joints were operated on. Improvement of movement and stress capability was achieved in 93% of all cases. Complications are presented and discussed. Follow-up and summary of all cases reveals that the total endoprosthesis is increasingly indicated. The replacement of a sliding endoprosthesis by a total endoprosthesis has since become necessary in three cases and resulted in marked improvement of function. One patient is not free of complaints, and an exchange operation is indicated. The indications for implantation of a sliding endoprosthesis will in the future surely be much more closely drawn. Follow-up reveales that increasing reactive changes of the knee joint cause pain of increasing measure. An initially painless interval is followed by a period of increasing pain. Results of follow-uthesis may be extended. The continued pain that totally operated patients in part by the high-grade and progressive changes in the femoro-patellar joint.


[Chondropathy of the patella. Experiences with 100 medializations]. After a brief reference to the biomechanics of the patellofemoral joint, the anamnesis and the clinical and the radiologic symptomatology of chondropathia and the possibilities of its therapy are described. Patellofemoral arthrography is very helpful for the diagnosis. The technique of our operation is also described. After close study of current available literature and careful control of our 100 medialization cases, the results after 6, 12, 24, and 36 months are shown in tabular form. The operation is recommended for primary chondropathia patellae with lateroposition or lateral-tipped patella.


[Ultrasonic welding of bones. Preliminary results]. Experiments with ultrasonic applied welding, a method first developed in the USSR are reported. In standardized isolated bone preparations stability values could be obtained of 10% [and in one case of 40% (!)] of the stability of the nonfractured bone. With these values the requirements of the method of osteosynthesis are met. Results of in vivo experiments are expected.


[Serum enzymes in seriously injured patients]. In 45 patients with multiple injuries due to trauma, admitted consecutively to our clinic, the following enzyme activities were studied, beginning at the onset of treatment: SDH, GPT, GLDH, and acid phosphatase. The mean levels of SDH rose in all patients between 2 and 24 h after trauma. The mean values of GPT were above normal between 2 and 48 h after trauma; this rise was more pronounced and statistically significant in those patients who eventually died of trauma than in the less severely injured ones. Twenty-four hours after trauma, the levels of GLDH were 16 times higher in the first group of patients than in the less severely injured group. These results lead us to the conclusion that through serum level measurements of these enzymes particularly of GPT it is possible to evaluate the degree of tissue damage and the general state of this group of patients.


[Ganglioneuroma of the small intestine]. The ganglioneuroma is a rare, benign tumor of the small bowel. The clinical symptomatology and morphology of the tumor are presented in detail. The differences in histopathology between ganglioneuroma and eosinophilic granulomatous polyp are discussed. Therapy should be resection of the tumor.


[Preoperative determination of the probability of a pulmocardiac insufficiency after resection of the lung]. Pneumonectomy is endangered above all by pulmocardial insufficiency. Its probability can be calculated in advance by a simple formula and a nomogram. With the help of a special mathematical method the most important functional parameters have been investigated and the formula and nomogram have been derived. The safety of the prediction comes up to the demands of biostatistical significance.


[Radiation load of patients and radiation-exposed personnel in the endoscopic retrograde cholangio-pancreaticography]. Measurements of radiation in 54 patients and examiners during endoscopic-retrograde cholangiopancreaticography (ERCP) were analyzed. The values of radiation were relatively low and were compared favorably with those of gastroenterologic x-ray diagnostics. With greater experience it can be lowered further. Dangerous exposition to radiation was not found in patient or in examiner. The values obtained are far below the maximum dose permitted by radiation legislation. The question of a danger from repeated examination is not important, on the contrary, due to minimal exposition, the frequency of ERCP can be increased.


[Clinical problems of the breast carcinoma in situ]. A report of carcinoma in situ of the breast, including problems of diagnosis and treatment. Over a 6-year period cut of a total of 743 carcinomas of the breast, 77 carcinomas in situ were observed. The difficulties of diagnosis are reviewed. Treatment consisted of simple mastectomy. In view of the inadequate therapeutic results it is recommended that a modified radical mastectomy should also be done in all cases of carcinoma in situ of the breast. The pros and cons of postoperative radiation are discussed.


[Therapy and prognosis of cardia carcinoma. Study on 225 cases]. From 1955 to 1974, 225 patients with cardia carcinoma were treated at the Department of Surgery in the University of Göttingen. The resection rate was 46,6%. Only 35 of our 105 patients who underwent resection, were operated on radically; in all other patients a palliative resection was done. In 59% of the resection cases a abdominothoracic approach was performed, whereas in 21% an abdominal, and in 20% a thoracic approach was preferred. The abdominal approach seems to be less effective, since a radical operation in most cases was not guaranteed. In 62% of the resected cases, postoperative complications occurred, mainly of pulmonal origin. The postoperative lethality was 18.1%. The prognosis depends on the degree of tumor metastases. The mean survival rate of the radically operated patients was 36.2 months, compared to 9.7 months of the palliatively resected cases. The 5-year survival rate of the resected patients was 12.2%. An improvement of the results can only be achieved by increasing the resection rate and earlier detection of the tumors.


[Use of alloplastic material on the extrahepatic bile ducts]. Dogs (20 kg body weight) were laparotomized and the choledochous duct was ligated. Pre- and postoperative laboratory-parameters such as bilirubin, GOT, GPT, and alcaline phosphatase were controlled. Then, 8 days later, a patch-widening-plasty was performed after incision of the stenosis in 10 dogs. In the 10 other dogs the stenosis was resected and the defect was bridged over with a Teflon prosthesis. A few days later laboratory parameters became normal. Histologic investigation showed that after 4 weeks the Teflon prosthesis was covered with a bile duct-epithelial layer. In one of 3 patients with normal laboratory findings who have a Teflon patch, the operation took place 2 years ago.


[Ureteral lesions after abdomino-perineal resection of the rectum]. Three ureter lesions in abdominoperineal rectum amputations are described. The surgical literature on this subject is discussed. Particularly dangerous points in the procedure of abdominoperineal rectum amputation concerning injuries of the ureter are accentuated. Possibilities of avoiding and recognizing early ureter injuries are indicated. More attention should be given to intraoperative lesions of the ureter.


[Spigelian hernia].

[Spigelian hernia]. Spigelian hernia is very rare. Together with the direct inguinal hernia which emerges between the inferior epigastric artery and the edge of the rectus muscle, it is more frequent. Congenital openings in the aponeurosis of the transverse muscle permit the hernia either above or under the inferior epigastric artery. Due to neglect of this type of hernia and absence of herniation, the diagnosis can be difficult. Complaints are often uncharacteristic. Surgical intervention is indicated.


[Peculiarities of acute appendicitis in women]. A complete documentation of the clinical and operative findings and a comparison of these with the histologic diagnosis in nearly 900 appendectomy patients from a period of more than two years is presented. In this publication an account of the specific results of nearly 500 women is given. The influences of age, menstruation, and gynecologic illnesses are reported in detail. Sixty-five percent of all women were treated unnecessarily with appendectomy. However, the indications for this operation should not be limited on these grounds.


[Problems of a suitable pressure-measuring technic for the esophagus and its sphincter]. The functional analysis of the esophagus and its lower sphincter requires an adequate procedure of pressure measurement. The value of studies on the motility and the terminal closing segment, using different pressure transducers, is examined. The pressure measuring device, constructed by us, makes possible the investigation of the mechanical behaviour of the closing muscular segment by means of extension under gradual increases in pressure.


[Temporary gastrostomy as an alternative procedure for nasogastric suction]. Based on personal experience with 70 cases of temporary tube gastrostomy - used as an alternative procedure to nasogastric suction in 50 cases and as a double-purpose tube in 20 cases of radical esophagectomy - pertinent problems concerning indication, technique, advantages, and possible complications are presented. The results indicate that temporary gastrostomy is a safe procedure, reduces cardiopulmonary disorders, and increases the patient's comfort. The procedure is therefore strongly recommended for patients with poor cardiopulmonary reserve and for the age group above 60 years. Temporary gastrostomy is also indicated in younger patients, if prolonged gastric distension with the necessity of decompression is anticipated.


[Gastrointestinal anastomoses and carcinoma in the operated on stomach]. This study examines the question of which type of gastroenteral anastomosis is predisposed to carcinoma of the gastric stump. Evaluation of operative or autopsy reports of 72 patients with carcinomas of the gastric stump following ulcer resection was undertaken. The interval after resection for ulcer was on the average 23 years. In 69 cases a Billroth II resection with retrocolic anastomosis (Polya type) had been performed; 7 patients had a Billroth II resection with enteroanastomosis (Braun's type); only 3 cases of Billroth I resection were found in the whole collective. From the results it may be concluded that carcinoma of the gastric stump develops predominantly in the remaining stomach following Billroth II resection with retrocolic anastomosis (without Braun's enteroanastomosis). When retrocolic anastomosis is performed, the duodenogastric reflux definitely passes through via atrophic gastritis to the development of a stump carcinoma. However, when Billroth I resection or Billroth II resection with enteroanastomosis is performed, the duodenogastric reflux is low or is quantitatively derived into the jejunum.


[Problems in the therapy of central arterial ectasias and elongations in long-lasting arteriovenous fistulas]. Acquired arteriovenous fistulas should be surgically cured as soon as possible after the diagnosis. In all the patients we treated, the arteriovenous fistula had existed for quite a long time, i.e. up to 26 years. These arteriovenous fistulas were surgically closed by the separation-method, the resection of the vessels and vascular reconstruction, or by the transvenous technique. - Arteriovenous fistulas, which have been in existence for quite a long time, result in cardiac dilatation, which can be cured after closure of the arteriovenous fistula. Furthermore, there can be pathologic changes of the vein and artery wall: chronic venous insufficiency and arterial ectasia can result. - After closure of the arteriovenous fistula our patients no longer complained of venous reflux disturbances. Even after closure of the arteriovenous fistula, an arterial ectasia is not reversible. The reasons for this are discussed. Symptoms, which occur after the closure of an arteriovenous fistula, which had existed for a long period and had produced a severe arterial ectasia, are looked upon as an autonomous disease. During the progress of this disease many complications can occur, even the rupture of the ectatic artery. The question is therefore discussed, whether it is justified to resect the ectatic arterial segment together with the arteriovenous fistula and to implant an alloplastic vascular graft in its place during the initial operation.


[Amyloid tumors in soft tissues of the neck]. Tumorous amyloid deposits in the neck region of a 31-year-old man caused difficulties in the preoperative differential diagnosis of a tumorous process of the thyroid gland. Several tumorous amyloid deposits compressing and eroding the left nevus vagus and having no connection to the trachea or thyroid gland were removed. Such isolated tumorous amyloid deposits in the neck region have not been described before. Histologically no thyroid tissue was found. A medullar cancer of the thyorid gland that has to be excluded in such cases was not found.


[Injuries of the central base of the skull]. In different types of lesions, especially in frontobasal and laterobasal ones, the central base of the skull is injured, too (in about 20% of severe frontabasal lesions). Surgical treatment is necessary. Examination of intra- and infrabasal structures and localized intracranial operations may be performed by transthemoidal-transphenoidal or transpyramidal approaches. Main problems are the treatment of dura lesions, the control of hemorrhages, the examination of the optic nerve, and the compensation of disturbances of central regulation. The above experiences we gathered from patients in the ORL Clinic of Jena University.


[Sequelae of injuries on the lower urogenital system]. A description of aetiology, symptomatology, and diagnosis of traumatic lesions of the bladder, urethra, and genital organs is followed by a critical discussion of therapy. Contributions to these topics coming from round-table discussions, held at several international urological meetings during the past few years, are considered. Important points concerning traumatic lesions of the bladder, and the male, female, and infant urethra are stressed. Consideration is given to diagnostic methods and to surgical methods relative to localisation, degree, and age of urethral lesion. Complications resulting with and without therapy are laid down.


Colonic anastomosis-a new approach: preliminary report. The exact incidence of colonic anastomotic breakdown is difficult to assess. The low incidence reported on the basis of clinical observation only is misleading, since it has been demonstrated that leakages occur without clinical manifestation. Better evaluation of the rate of incidence will require meticulous postoperative investigation, as shown by Goligher. A new colonic anastomosis was performed in 24 cases of high and low anterior resections. The principal of forming a seromuscular cuff has been employed. The encouraging results merit further trial.


A metachronous colorectal tumor: report of a case. A patient with a cancer of the colon or rectum is at increased risk for developing subsequent cancer of his remaining large bowel, particularly when associated polyps and papillomas are present, and when the initial resection is for two or more growths. Patients who develop signs and symptoms of large-bowel tumors following colonic resections for carcinoma should be completely evaluated for another primary tumor. If it is assumed that these patients simply have recurrences of their initial cancers and therefore they are not treated, many patients would be denied a potentially curative operation. All investigators agree that this group warrants long-term follow up, ideally with regular and double-contrast enema studies and sigmoidoscopy. Earlier diagnosis of a second colorectal cancer should improve the resectability rate and prognosis. Those patients with intact cell-mediated immunologic responses seem to do better after surgical treatment.


Combination preoperative radiation and chemotherapy in adenocarcinoma of the rectum: preliminary report. The plausibility of preoperative chemotherapy and radiotherapy in the treatment of patients with carcinoma of the rectum is demonstrated. The finding of specimens with no tumor along with a higher proportion of Dukes' A lesions than expected was most encouraging. Whether this is a false impression because of the small number of patients, or whether it demonstrates upgrading of pathologic staging by preoperative adjuvant therapy, remains to be determined.


Purulent pericarditis occurring in a patient with cecal carcinoma: report of a case. We report the unusual concatenation of cecal carcinoma complicated by bacteremia and purulent pericarditis. The organism responsible for the pericarditis was not definitely established. The pericarditis was successfully managed by surgical drainage and antibiotic therapy. Colonic surgery followed eradication of the pericarditis.


Clinical evaluation of acupuncture in 129 patients. The scope of effectiveness of acupuncture in relieving pain was tested in an Acupuncture Clinic for nonemergency care: 129 patients were treated, mainly for intractable pain associated with a wide variety of conditions. Only mechanical stimulation was used. Acupuncture anesthesia was not evaluated. Response was excellent or good in 87 patients. Acupuncture was most effective in conditions attributable to musculoskeletal or visceral muscle spasm. In some situations it inhibited pain recurrence, such as menstrual cramps in subsequent periods. It did not mask pathology: pain recurred promptly if underlying stimulus persisted. Relief of pain was usually immediate; side effects were negligible. Neurophysiologic principles appear to offer a basis for explaining the mechanism of action. Acupuncture is sufficiently promising as an adjunct to standard medical methods to deserve clinical and theoretical investigation.


Adenocarcinoma of the cecum manifesting as intussesception in a 16-year-old patient: report of a case. A 16-year-old Negro girl underwent exploratory laparotomy for ileocecal intussusception and was found to have moderately well-differentiated mucin-producing adenocarcinoma of the ileocecal valve. Specific aspects of this disease in children are discussed and an appeal for early diagnostic studies in cases of children who complain of weight loss, chronic constipation, and abdominal pain is made. Finially, on the basis of the natural history of the disease, a "second-look" operation is recommended.


Central core disease--a congenital myopathy. A case is reported of a 28-year-old woman with central core disease who prior to muscle biopsy was diagnosed to have muscular dystrophy. Histologic evaluation confirmed a diagnosis of central core disease, a nonprogressive or slowly progressive disorder of voluntary muscle belonging to a group of muscle diseases called benign congenital myopathies. The clinical and pathologic features fo this benign disorder are reviewed. Two sons were examined and found to be normal.


Volvulus of the transverse colon, a long-term complication of hemicolectomy: report of a case. A redundant limb of ileum left after a hemicolectomy is postulated to be the causative factor in a case of volvulus of the transverse colon and distal ileum after hemicolectomy 20 years before. A case is presented and the etiology of volvulus briefly discussed.


Detachment of the continent ileostomy poucn from the anterior abdominal wall: report of two unusual cases. The cases of two patients with continent ileostomies are presented. These illustrate the problems encountered with detachment of the pouch from the abdominal wall resulting in angulation of the efferent loop of the pouch in relation to the nipple valve and difficulty intubating the pouch. Both patients required operative correction of the separation. Several suggestions are made in order to prevent or decrease the incidence of the complications. Removal of a peritoneal strip around the efferent loop of the pouch appears to facilitate adequate fixation of the pouch to the anterior abdominal wall.


Subcutaneous emphysema, pneumoretroperitoneum, and pneumomediastinum following rectal surgery: report of a case and review of the literature. A case of retroperitoneal, mediastinal, and subcutaneous emphysema following rectal surgery is described. This complication has not been reported in medical literature. Treatment was based on the fear of a more extensive and irreversible situation, because on the basis of the single case, it could not be demonstrated that the intestinal gas was not associated with infection.


[Treatment of hyperuricaemia with a combination of allopurinol and benzbromaron (author's transl)]. Three patients with gout and seven with hyperuricaemia, previously untreated, took a single dose of 100 mg allopurinol and 20 mg benzbromaron (as a combined preparation) each morning. There occurred a highly significant decrease in serum uric acid concentration from 430.7 mumol/l (72.4 mg/l) to 268.6 mumol/l (45.2 mg/l), without any significant increase in urinary excretion of uric acid.


[Heterologous grafts (from calves) in peripheral arterial reconstruction (author's transl)]. A new collagen graft from calves was used in 45 patients with a variety of peripheral arterial occlusions. Favourable early results were obtained in two-thirds of cases, but late results are not yet available.


[A new immunochemical tube test for pregnancy using the latex-agglutination inhibition reaction. II. Clinical results (author's transl)]. In a multi-centre study 1117 morning urine samples were tested using the new immunochemical pregnancy tube test (Roche), based on the principle of indirect latex-agglutination inhibition. The test proved to be both qualitatively and semi-guantitatively suitable for demonstration of HCG in urine. There was only one false-negative result among 320 pregnancy tests (after 50th postmenstrual day). In 94 early pregnancies (test done before the 50th day) there were only two false-negative results. No false-positive result were seen. In the prognosis of threatened abortion, diagnosis of incomplete abortion, hydatid cyst, or chorionepithelioma the semiquantitative performance of the test was clinically useful and especially suitable because the result of the agglutination-inhibition reaction is unequivocal.


[Duodenogastric reflux and stress ulcer (author's transl)]. Duodenogastric reflux in 14 patients in an intensive care unit was compared with that in 12 healthy controls. In addition, intragastric bromsulphalein concentration was measured up to 60 minutes after intravenous administration. Reflux was much more frequent in the intensive-care patients and correlated with the incidence of gastric erosions and stress ulcers. Reflux is apparently one of three factors (in addition to ischaemia and HCl) which synergistically lead to stress-induced lesions of the gastric mucosa.


[Total parathyroidectomy and autologous parathyroid transplantation in secondary hyperparathyroidism (author's transl)]. In a 17-year-old female patient with marked secondary hyperparathyroidism and progressive bone changes all four parathyroid glands were removed. Part of the endocrine tissue was reimplanted into the muscles of the forearm. The transplant took successfully and showed a satisfactory function. Total parathyroidectomy and autologous parathyroid transplantation has a number of advantages as compared with subtotal parathyroidectomy: The function of the transplant can be directly observed and tissue can be easily removed in the further course of the disease. It is thus possible to regulate parathormone secretion over long periods in patients with chronic renal failure.


[Significance of the size of an acute infarct for left ventricular haemodynamics (author's transl)]. Acute infarct size was estimated from serial determinations of creatine-kinase (CK) activity. In 15 patients the infarct size was obtained post-mortem, using nitro-blue-tetrazolium stain. There was good correlation between the two measurements (r = 0.98). The relationship between the calculated infarct size and haemodynamic values was obtained in 50 patients (end-diastolic pulmonary arterial pressure [PAEDP], cardiac output, stroke volume, stroke volume/filling pressure of left ventricle [SVI/PAEDP]). On average there was a tendency towards impaired left ventricular haemodynamics with increasing infarct size. Among the survivors the infarct size (51 g) was significantly less (P less than 0.05) than that of those who had died (83 g). PAEDP at 24 mm Hg was significantly higher in those who died than in the survivors (17 mm Hg), cardiac index was 2.95 l/min-m2 in the survivors compared with 2.14 l/min-m2, while SVI/PAEDP was 2.4 ml/m2-mm Hg in the former and 0.9 ml/m2-mm Hg in the latter. However, in individual cases the infarct size sometimes did not correlate with haemodynamic values. Taking into account infarct size and haemodynamics, four classes could be distinguished: (a) infarct size less than 65 g with good haemodynamics (PAEDP less than 18 mm Hg, normal cardiac index); (b) infarct size greater than 65 g with PAEDP greater than 18 mm Hg and markedly reduced cardiac index). Only 10% of those a to c had previously had infarcts, compared with 60% of those in class d (infarct less than 65 g, PAEDP above 18 mm Hg). Small infarcts with markedly impaired haemodynamics thus indicate that there has been previous damage to remaining myocardium.


[Bleeding times in haemophilia patients treated with lyophilised antihaemophilic globulin (AHG) (author's transl)]. Tests on 16 patients with haemophilia A confirmed earlier studies that bleeding times may be prolonged after treatment with antihaemophilic globulin (AHG). Despite adequate factor VIII substitution by AHG, treatment effect was unsatisfactory in all 16 patients and there were abnormally prolonged bleeding times after several AHG infusions. But determination of bleeding times after single AHG infusion provides no pointer to possible later problems.


[Spontaneous rupture of the oesophagus (author's transl)]. During the last 4 years three so-called spontaneous perforations of the oesophagus were treated, twice by surgical intervention 12 anys after the rupture. Two patients survived. The classical history of retching or vomiting and retrosternal splitting pain is indicative, wht medium, amidotrizoate sodium (Gastrografin), from the oesophagus. Prognosis depends decisively on the time of operation after the rupture. Direct suture of the rupture with plastic coverage of the defect by sewing on of the gastric fundus or by plication of the fundus have proved valuable.


[Successful zinc treatment of a severe case of acrodermatitis enteropathica (author's tteropathica]. A 24-year-old patient treated with hydroxychinoline preparations without cure for acrodermatitis enteropathica since he was nine years old was given zinc oxide orally, at first 50 mg three times, later twice daily. Zinc concentrations in blood plasma, whole blood and sputum were serially determined. At the start of treatment they were significantly below that in four healthy controls. One week after starting zinc therapy the blood level had returned to normal and with it the changes in skin, hair and nails had regressed, as had the emotional disturbances.


[A highly sensitive C-terminal specific radioimmunoassay for human parathormone as a routine method (author's transl)]. The basis for the radioimmunoassay of parathormone (PTH) as a routine method is a new sheep antiserum and a labelled PTH stabilised by a modification of the purification technique. The antiserum is obtained by immunisation with pig and cattle parathormone, it is C-terminal specific and is used in the assay in a final dilution of 1:35000. The affinity to human PTH is markedly greater than of the antisera used up to now. Two purification steps of 125J labelled bovine PTH lead to a tracer with a nonspecific binding of approximately 5% which increases to approximately 10% within 6 weeks. All normal sera investigated so far were measurable quantitatively (normal range 0.7 to 2.5 mul/equiv.). The lower sensitivity range was at 0.3 mul/equiv. All patients with chronic renal insufficiency and dialysis patients have an increased PTH concentration (3.9 to greater than 20 mul/equiv.). This also applies to patients with primary hyperparathyroidism (2.9 to greater than 20 mul/equiv.).


[Haemodynamic effect of dobutamine in cardiac failure (author's transl)]. Dobutamine, a new catecholamine with a positive inotropic action, was given by infusion to 9 patients with cardiac failure in a dosage of 5 and 7.5 mug/kg-min over a period of 15 minutes. An improvement of left ventricular function was proven by an increase of cardiac output by 33%, a reduction of end-diastolic pressure from 21 to 14 mm Hg, an improvement of left ventricular ejection fraction from 29 to 39% and of the mean circumferential fibre contraction velocity from 0.4 to 0.8 circ/s. The systolic aortic pressure increased by a mean of 14% (5 mug/kg-min) and 23% (7.5 mug/kg-min). However, the resistance of the systemic circulation decreased from 1858 to 1439 and 1444 dyn-s-cm-5. Cardiac frequency remained unchanged with a dosage of 5 mug/kg-min and increased by a mere 7 beats/min with a dosage of 7.5 mug/kg-min. There was no increased tendency for arrhythmia. Dobutamine thus appears to act relatively selectively on myocardial beta-1 receptors. Results so far indicate therapeutic success in patients with severe cardiac failure, particularly in the low-output syndrome.


[On the method of indirect electrogastrography and its diagnostic applicability (author's transl)]. The cutaneous recording of the gastric electrical activity according to the modified method of Sobakin was utilized. In fasting individuals changes in potential occured between 2 and 5 per min., in most of the cases after standard breakfast the frequency increased while lower amplitudes appeared. The frequency of electrical waves from the duodenum increased remarkably. It could be demonstrated that the peristalsis recorded by gastroscopy was synchronous with the electrogastrographic potentials. The applicability of the method for clinical diagnostic purposes is limited at the present time, because a "normal" electrogastrogram has not yet been established. Specific changes of the electrogastrogram have not been observed in various gastric diseases, which may be verified by routine diagnostic procedures.


[Paradoxical effects of neuroleptics].

[Paradoxical effects of neuroleptics]. Paradoxical effects of major tranquillizers are discussed by the author about his observation on two patients, above all in connection with the sedative and stimulating properties of these drugs. These two observations concern a treatment with Haloperidol at high dosages giving surprising effects: syndrom of excitement with an increase in delusive activity along with hallucinations and a touch of depressive mood. From this point of view, a few questions can be raised about the correlation between the antipsychotic activity of the major tranquillizers and these sedative or stimulating effects. The author has also discussed the stress upon mood.


[Present status of narcissism].

[Present status of narcissism]. From the book "The Analysis of the self" by Heinz KOHUT, recently translated into French, the author studies how several notions coming from the psychanalysis of those cases may be used in practical psychiatry, more particularly the notions of: self-object, grandiose self, double cleavage, independance of the development of the libido and narcissim.


[An apperture effect in hypochondria].

[An apperture effect in hypochondria]. It is usual to consider hypocondriac patients as jailed in their own bodies; of course, this jail may be a protection against declared paranoiac or paranoid states. However, our experience has shown us that in certain cases, there are some possibilities of aperture if we feel ourself free enough with our medical identity and if we keep silent as long as the patient is not able to hear us. A step is then allowed to him. Our prudent remark concerns the story which is then gradually revealed: it is often the story of the secret of maternal suffering which is enclosed in his own body.


[The psychiatric examination as the first "therapeutic act"]. The author thinks that psychiatric examination (asked by the judge) can be a therapeutic act: the first. The expert should not think he is a therapeutic man, nor should he say he is, but he must create by his intervention the circumstances that are necessary for a therapy.


[Blood level of tryptophan in psychiatric diseases]. The dosage of the free tryptophan and of the total tryptophan is interesting in psychiatric diseases when a possible role of serotonin is suspected: endogenous melancolia, schizophrenia, sleep disorders. The dosage of tryptophan is made by ultracentrifugation and separation then spectrofluorimetry by increasing 15 times the native fluorescence of tryptophan. The data are given for 16 healthy volunteers and 12 schizophrenics treated and not treated. The methodology of sampling is described and must be strictly standardized to get interpretable data.


[Regional medico-psychologic centers].

[Regional medico-psychologic centers]. The intervention of the psychiatrist in the prison world is a comparatively recent phenomenon, since it has been actually effective only since 1945 onwards, at least in France. It is not until 1959 that the Penal Regulations have provided for the setting up of Regional Medical and Psychological Centers (C.M.P.R.). Among the main duties of these centers, the following two are of paramount importance: -- The supervision and treatment of patients who, although they are free from mental disorders calling for institutionalization, show behavioral troubles which may create difficulties, or danger, if they are remanded in normal custody; -- Psychiatrist's advice and, if required (albeit not compulsorily), prescription of medicines. Psychiatrist's advice may be sought either at the request of the inmate (which is the most common procedure), or of the other medical staff of the prison, or required by the Judicial Authority or Administration. The major cause of concern currently challenging the C.M.P.R. is the always unsufficient, and sometimes underqualified, staff.


[Grandmothers in child psychiatry].

[Grandmothers in child psychiatry]. Presenting three case-histories, the author stresses on the importance of grand mother psychopathology-- There upon he discusses some special aspect relevant in child psychiatry.


[From N-doep to psychodrama].

[From N-doep to psychodrama]. The interest taken in traditional African Therapies was classically supported by a system of anthropological eurocentric references, motivated amongst other things by a folkloric curiosity. The socio-political evolution has progressively modified the vision of ethnologic teams of psycho-sociologists and psychiatrists. COLLOMB and LAMBO permitted recognition of a psycho-pathology which integrates with the cultural reality of the Africans and the Negros. The O.M.S. at present is supervising a number of enquiries into traditional African medicine. Obviously, such an ideological mutation imposes on occidental psychiatry the conceptualisation sociometry of certain traditional group therapies, distinctly making n'doep the forerunner in morenian psychodrama, and putting the healer in the position of leader in certain domains of modern psychiatry. Should occidental Europe be listening to the African Models?


[Influence of psychotropic therapy on thrombogenesis and platelet functions. A propos of 4 cases of thromboembolic accidents occurring in patients treated by neuroleptics and antidepressants]. Thromboembolic complications secondary to psychiatric therapy are known but relatively rare. Four pulmonary embolisms happening in a few months' time in our services have lead us to reconsider the incidence of psychotropes on thrombogenesis, and more particularly on the aggregability of blood-platelets. We have found hyperaggregability curves for a significant number of cases in patients undergoing treatment in comparison with reference patients undergoing no treatment. We have tried to explain the difference in the results of works concerning the aggregability of blood-platelets and psychotropes by problems of dosage and of level of action of these medications and of their metabolites, the effects often oposite for a limit dose, the danger of extrapolating in vivo the results found in vitro, finally the complexity and numerous unknown elements in the working of aggregation of blood-platelets.


[Chemotherapy of melancholia by sequential neuroleptic-viloxazine association]. Viloxazine administered as a unique antidepressant may in some cases cause an aggravation of anxiety and agitation or manic states. In order to control this effect, we thought of administering neuroleptics and anxiolytics: 1) Before Viloxazine for a few days. 2) Then during antidepressant treatment. The results were as follow: 1) Quick and efficient upon melancholic states in manic -- depressive psychoses. 2) Irregular and questionable upon other depressions.


[Pharmacokinetic profile of perphenazine enanthate]. Publications on blood kinetics, biotransformations, excretion and tissular distribution of Perphenazine and its enanthic ester were analyzed. They allowed to make the pharmacokinetic profile of Perphenazine Enanthate, a long-acting neuroleptic, and to draw some information concerning its therapeutic use.


[The use of rating scales for the study of diagnostic models: recognition of the uncertainties in classification principles]. In a cross cultural comparison of diagnostic concepts, we obtained from 45 expert italian psychiatrits symptom rating profiles, in terms of B.P.R.S., of the 12 most used diagnostic categories. While for 11 diagnostic concepts agreement was reasonably good, for cycloïd psychosis the variability of results supported the conclusion that this diagnostic concept is rather non specific among italian psychiatrists.


Circadian variations of the urinary excretion of catecholamines and electrolytes. Concomitant measurements of circadian variations in the urinary excretion of dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), epinephrine (E) as well as of creatinine, sodium and potassium under controlled dietary conditions during relative physical and emotional rest in 13 volunteers have shown that maximum excretion of all these substances occurred in the afternoon period between 14:30h and 18:00h, and minimum excretion in the morning between 4:00h and 5:00h. The changes were in some cases progressive from one collection period to the other, and synchronized for NE and E. DA and HVA excretions fluctuated from subject to subject. Excretory rhythms of sodium and potassium were found to be similar to those of the catecholamines. This can be explained by diurnal changes in renal blood flow and different renal excretory mechanisms of catecholamines. None of the catecholamines correlated with the urinary volume but urinary NE and E positively correlated with urinary creatinine, urinary NE and E with urinary DA and urinary sodium with urinary E. There are some common patterns in the diurnal rhythms of catecholamines and electrolytes but their interrelationship is different for individual catecholamines.


Effects of human chorionic gonadotropin preparations on amino acid uptake and incorporation into protein in vitro. Human chorionic gonadotropin preparations were tested for their effect on protein metabolism by cultured fibroblasts. Commercial preparations of HCG strongly inhibit amino acid uptake and incorporation into protein by a variety of human adult and fetal fibroblast lines, whereas, highly purified HCG is without such an effect.


Action of prolactin on ornithine decarboxylase activity in mammary gland explants of mice. Prolactin stimulated ornithine decarboxylase activity in mammary gland explants from midpregnant mice. The enhanced enzyme activity occurred in explants which were preincubated for 1 day in medium containing insulin, hydrocortisone, insulin plus hydrocortisone, or in medium containing no hormones. The largest prolactin effect was observed in tissues which were pretreated with insulin plus hydrocortisone; a greater than ten-fold increase in ornithine decarboxylase activity was observed when these tissues were incubated with prolactin for 2 hours. An effect of prolactin on ornithine decarboxylase activity was also observed in explants prepared from lactating mouse mammary glands.


Influence of serum, estrogen, and gonadotropins upon growth and progesterone secretion by cultures of granulosa cells from small porcine follicles. Granulosa cells from small (less than 2mm) antral porcine follicles were grown in culture to study the effects of various hormones on growth, morphology and progesterone secretion. Culture medium 199D + 4% serum was found to be most suitable since it maintained a fairly constant cell population. Estradiol (1mug/ml) and human FSH stimulated cell growth. LH and FSH stimulated progesterone secretion and induced morphological changes associated with luteinization. Estradiol (0.1 mug/ml) inhibited progesterone secretion by granulosa cells.


Unconjugated estradiol in the myometrium of pregnancy. By chemically digesting myometrium in a mixture of NaOH and sodium dodecyl sulphate, estradiol could be recovered almost completely by extraction with ethyl acetate. The concentration of estradiol-17beta (E2) in the extracted samples could reliably be determined by radioimmunoassay. Compared to its concentration in the plasma, E2 in the pregnant human myometrium was very low, and as a result, the tissue/plasma estradiol concentration ratio was less than 0.5. In the pseudopregnant rabbit, this ratio ranged between 16 and 20.


Gastric A-cell function in insulin-deprived depancreatized dogs. To determine if gastric A-cells are a major source of the glucagonemia of insulin-deprived depancreatized dogs and to examine their secretory behavior, immunoreactive glucagon (IRG) was measured simultaneously in plasma from the inferior vena cava (VC) and from a gastric vein (GV) draining the fundus. Basal GV IRG averaged 205 +/- 35 pg/ml, significantly above the VC level of 71 +/- 30 (P less than 0.001) and rose to 1417 +/- 498 1.5 minutes after the start of an arginine infusion, exceeding VC IRG at all points (P less than 0.01). Measurement of IRG in gastric, jejunal, and ileal veins and vena cava revealed an IRG gradient only across the stomach. Measurement of glucagon-like immunoreactivity (GLI) revealed no gradient across the stomach, jejunum, or ileum, thus excluding cross-reaction with GLI as the cause of the GV hyperglucagonemia. Intragastric arginine elicited a near doubling of GV IRG within 1.5 minutes and this persisted for at least 120 minutes, ranging from 142 to 623 pg/ml above the VC level. Infusion of insulin at a physiologic rate lowered GV IRG from 665 +/- 66 to 151 +/- 49 pg/ml in 20 minutes and abolished the GV-VC gradient within 60 minutes, whereas intravenous and intragastric glucose administration without insulin did not alter GV IRG. It is concluded that: 1) in the insulin-deprived depancreatized dog, the stomach is a major source of IRG; 2) gastric IRG secretion is somehow stimulated by intravenous and intragastric arginine administration; 3) it is not influenced by intravenous or intragastric glucose administration; and 4) its release is suppressed by physiologic levels of insulin.


Metabolic clearance of immunoreactive vasopressin and immunoreactive [131I]iodo vasopressin in the hypophysectomized dog. Fourteen acutely hypophysectomized, anesthetized dogs were given a constant infusion of arginine vasopressin (AVP) and 131I-labeled arginine vasopressin ([131I]AVP). After 90 min, 3 blood samples were collected at 15 min intervals for determination of total body clearances of immunoreactive AVP and immunoreactive [131I]AVP. Seven dogs were then nephrectomized. Ninety minutes later, a second set of 3 blood samples was collected at 15 min intervals for clearance measurements in these and the 7 time-control dogs. Prenephrectomy AVP clearance averaged 5.1+/-1.0 ml/min-kg (mean +/- SE, n=7), and the 210-240 min postnephrectomy AVP clearance average 4.9+/-0.8. The 90-120 min average clearance in the time-control dogs was 6.1+/-0.9 ml/min-kg (n=7) and AVP clearance in these dogs increased (P less than 0.01) with time to 7.3+/-0.9 ml/min-kg during the 210-240 min period of constant infusion. Although the postnephrectomy AVP clearance was not significantly changed from prenephrectomy levels, it was significantly lower (P less than 0.05) than the 210-240 min average clearance in the time-controls. Clearance of [131I]AVP was 3.3+/-0.2 ml/min-kg (n=7) before nephrectomy and 2.9+/-0.2 ml/min-kg after nephrectomy. This was a significant 12% reduction (P less than 0.01). [131I]AVP clearance in the time control dogs was 3.9+/-0.3 during 90-120 min of infusion and 3.9+/-0.4 during 210-240 min of infusion. [131I]AVP clearance before nephrectomy was 79+/-12% of AVP clearance (P less than 0.005) and afther nephrectomy was 74+/-16% of AVP clearance (P less than 0.05). Although these results might suggest that [131I]AVP clearance is at least a qualitative indicator of AVP clearance, there was no significant correlation (P less than 0.20) between AVP clearance and [131I]AVP clearance.


Uterine norepinephrine levels as related to plasma and tissue progesterone in pseudopregnant rabbits. Pseudopregnancy was induced in rabbits by a single iv injection of 100 IU of human chorionic gonadotrophin (hCG). Uterine norepinephrine, located exclusively in adrenergic nerves, was markedly reduced (fluorometric determinations) during the first 6 days of pseudopregnancy and then returned towards pre-injection values. Plasma progesterone (measured by radioimmunoassay) was found to be elevated at days 3,6, and 12 of pseudopregnancy as compared to the very low values of the untreated controls. Although tissue progesterone also increased during pseudopregnancy (fourfold at day 6), there was a somewhat paradoxical relationship between plasma and tissue progesterone. In spite of unchanged plasma levels, tissue progesterone decreased considerably between days 6 and 12. The uterine/plasma progesterone ratio was very high (approximately 28) in non-pregnant (control) animals and ranged between 1 and 3 during pseudopregnancy. These results suggest that there is a causal relationship between the high levels of progesterone in the uterus and the reduced amount of norepinephrine transmitter in the adrenergic nerves in this organ, and that plasma progesterone concentration and the changing progesterone receptor levels regulate uterine progesterone concentration.


Biotransformations of pituitary luteinizing hormone in serum and urine. I. Association with serum components. In the effort to elucidate the nature of luteinizing hormone (LH) in the circulation, studies in adult male rats have been conducted using a highly purified and well-characterized tritiated and methylated ovine pituitary LH, a derivative which retains full biological activity. Following an intravenous injection of the radioactive hormone, serum chromatograms (molecular exclusion chromatography) are characterized by three radioactive components. The first one, a rapidly formed high molecular weight heterogeneous fraction, involves the non-covalent interaction of the hormone with one or more circulating proteins. These high molecular weight complexes are cleared rather slowly from the circulation, relative to the non-associated hormone. A second component co-chromatographs with control hormone and is rapidly cleared from the circulation. These two fractions retain full biological activity judged by their ability to stimulate testosterone production in Leydig cell suspensions. A third component is observed in the circulation about 15 minutes after injection and was shown to represent tritiated amino acids. The lag period for the appearance of the labeled amino acids in the circulation correlates with the kinetics of hepatic and renal uptake and subsequent lysosomal catabolism of [3H]methylated-LH. The high molecular weight fraction may represent a physiologically important circulatory storage form for LH by conferring a relatively long circulatory half-life. This appears to be brought about mainly by reduced urinary excretion, presumably due to its high molecular weight.


Biotransformations of pituitary luteinizing hormone in serum and urine. II. Evidence for reduced potency following urinary excretion. The renal clearance of tritiated and methylated ovine pituitary luteinizing hormone (LH) has been determined in mature male rats, and the urinary product has been characterized with regard to molecular size, charge, and heterogeneity. [3H]Methylated-LH was found to have a renal clearance of 0.17+/-0.03 ml/min/100 g body weight, compared to a value of 0.99+/-0.18 for tritiated inulin. This indicates that LH is not secreted and that much of the filtered hormone is reabsorbed from the tubular lumen. Evidence is presented which shows that urinary ovine [3H]methylated-LH is not extensively degraded; yet, the biological potency is only 10-20% that of pituitary and serum LH. The large reduction in potency is a result of excretion since the in vitro incubation of LH with urine does not produce the same effect. The biotransformation occurring during excretion results in charge heterogeneity of LH; this may arise from either inhibitor binding or enzymic alterations.


Interactions of the light-dark cycle, adrenal glands and time of steroid administration in determining the temporal sequence of LH and prolactin release in female rats. The purpose of this study was to determine the effects of the light-dark cycle, adrenal glands and steroid treatment schedule on LH and prolactin release in rats. Rats maintained in either a 14 h light: 10 h dark schedule (LD) or constant illumination (LL) were ovariectomized (Ovx) or ovariectomized and adrenalectomized (Ovx-Adx). Three weeks later at 1000 h, animals received a SC injection of estradiol benzoate (EB 10 mug/100 g BW) or oil. Three days after EB administration, rats were given a 2 mg injection of progesterone (P) or oil at either 0200, 0500, or 0900 h, and were sequentially bled at four-hour intervals until 1700 h. P administered at all three times increased the amplitude of the plasma LH surge and advanced it, though by no more than 4 hours, in LD. In LL, P was more effective in advancing the time of LH release, although peak plasma LH levels were considerably less than those observed in LD. Adrenalectomy increased the sensitivity of Ovx rats to the effects of EB and P on LH release. P administration at either 0200, 0500 or 0900 h advanced prolactin release in EB-primed Ovx and Ovx-Adx in LL and LD, but only in LL did P increase the amplitude of the plasma prolactin surge. The lighting conditions did not alter the effectiveness of P in advancing prolactin release. Our study demonstrates that the light-dark cycle and adrenal steroids interact to synchronize the timing of LH release in rats, but the regulatory mechanism controlling prolactin release is less strictly cued to these environmental factors.


Levels of testosterone in the plasma, gonads, and adrenals during fetal development of the rabbit. Testerone (T) concentrations in the plasma, gonads, and adrenals were measured by radioimmunoassay in 188 male and 160 female rabbit fetuses. Determinations were performed daily from the 20th to the 31st day of gestation and were correlated with the maternal plasma concentration of T. The T content of both testes remained relatively constant from the 20th (3040 pg) to the 26th day (3940 pg), and subsequently decreased until the 31st day (1630pg). the concentration of testicular T fluctuated only slightly from the 20th (1040 pg/mg) to the 23rd day (783 pg/mg), and thereafter decreased until the 31st day (138 pg/mg). The T levels in plasma of males (132-361 pg/ml) were significantly higher than those of females (21-116 pg/ml). Plasma T levels in males were relatively constant and did not exhibit any rise, which is similar to observations of the testis during differentiation of the genital tract. Testosterone concentrations were low in the adrenals (3.5-12.3 pg/mg) of both sexes and in the ovaries (1.5-20.4 pg/mg) of fetuses. These data provide the first evidence for testicular T secretion at the time of genital differentiation in the rabbit.


Androgen and estrogen receptors in the developing mouse brain. Specific binding of the androgens, 5alpha-dihydrotestosterone (DHT) and testosterone, and of 17beta-estradiol by brain cytosol from mice at 3-5,9-11, and 18-23 days of age was measured by charcoal assay and glycerol gradient centrifugation and analyzed by Scatchard plots. The immature mouse brain contains putative receptors for these steroids which migrate at 8 S in gradients at low ionic strength and at 5 S in 0.5 M KCl. Investigation of estradiol binding was complicated by the presence in cytosol from 3-5 day-old mice, and to a lesser extent from 9-11 day-old mice, of the high capacity, fetoneonatal estradiol binding protein (FEBP) which is no longer detectable at 3 weeks. The rapid dissociation of the FEBP-estradiol complex under non-equilibrium conditions probably led to over-estimation of free steroid concentration and thus to an apparent increase in the affinity of 8 S receptor for estradiol with age (for female brain cytosol KD=9.5 X 10(-10)M at 3-5 days and 2.7 X 10(-10)M at 18-23 days). The number of estradiol binding sites remains relatively constant during the first 3 weeks at 7-9 fmol/mg protein, while the number of DHT binding sites in female brain increases from 3.2+/-0.3 to 6.6+/-0.9 to 9.6+/-0.3 (mean+/-SE) fmol/mg protein in the 3 age groups. Dissociation constants and numbers of sites for both DHT and estradiol binding are similar in brain cytosol from male and female mice. Testosterone and DHT compete for the same binding site, but its affinity for DHT is about twice that for testosterone. The high affinity of the brain receptor for DHT (KD=4-5 X 10(-10)M) may reflect the slow metabolism of DHT to 5alpha-androstanediols, amounting to less than 10% after 2 h at 0 C. Binding of DHT and estradiol to cytosol from brain regions was also investigated. DHT receptors increase in parallel in various regions with age; the concentration of sites in the hypothalamus-preoptic area (HPOA) is 1.2-3.4 times that in the cerebral cortex (C). The concentration of estradiol binding sites in HPOA to that in C increases about 12-fold from neonatal to adult stages, reflecting both an increase in HPOA sites and a decrease in C sites, while the concentration in the remainder of the brain shows little change. Androgen and estrogen receptors in brain cytosol from immature mice can be distinguished by their different specificities and developmental patterns in whole brain and brain regions. The presence and properties of these receptors in the brain of neonatal mice are discussed with respect to their possible role in sexual differentiation of the brain.


Androgen receptors in the anterior pituitary and central nervous system of the androgen "insensitive" (Tfm) rat: correlation between receptor binding and effects of androgens on gonadotropin secretion. The cytosol fractions of the anterior pituitary, hypothalamus, preoptic area and brain cortex of androgen "insensitive" (Tfm) rats possess androgen receptors. However, in the Tfm rats the androgen binding per mg protein was only 10-15% of that in the corresponding normal littermates (Nl). The physicochemical properties of the androgen receptors in the anterior pituitary of the Tfm rat were indistinguishable from those of the normal rat. Thus, no distinctive differences were observed with regard to electrophoretic mobility in 3.25% polyacrylamide gels, isoelectric point (pI=5.8), binding affinity (KD=1.5 X 10(-9)M), temperature stability, sulfhydryl dependence and steroid specificity. It is, therefore, likely that the very low androgen binding capacity by the anterior pituitary and the central nervous system is due to an extreme reduction in the receptor number rather than to the presence of abnormal receptors. Since in the Tfm animals the androgen receptor number is reduced by 85-90%, it is to be expected that very high doses of androgens would be required to achieve hormonal effects. In fact, low doses of 5alpha-dihydrotestosterone propionate (50 mug/100 g body weight) given sc daily for 12 days had no effect on serum levels of LH and FSH. However, very high doses (2 mg/100 g body weight) of testosterone propionate and 5alpha-dihydrotestosterone propionate, which maintained circulating androgen levels above 20 ng/ml, significantly reduced serum gonadotropin levels in castrated Tfm rats. In normal littermates both low and high doses of the androgens suppressed gonadotropin secretion to low levels. These findings strongly indicate that androgen receptors are essential to androgen action on the anterior pituitary and central nervous system in the rat. The serum levels of testosterone (7.7+/-0.15 (SE) ng/ml) and 5alpha-dihydrotestosterone (0.37+/-0.06 ng/ml) were significantly higher in intact Tfm rats than in normal littermates (2.6+/-0.03 and less than 0.1 ng/ml, respectively). The failure of the elevated concentrations of serum androgens to reduce the high serum levels of LH and FSH in intact Tfm rats is most likely due to the extreme reduction of the androgen receptor number and the consequent insufficient hypothalamic and/or pituitary response to androgens.


Dose-dependent prolactin releasing activity of arginine vasotocin in intact and pinealectomized estrogen-progesterone treated adult male rats. Estrogen-progesterone (EP) treated adult male rats were injected intravenously (iv) with 0.1, 1 or 10 mug arginine vasotocin (AVT) or Ringers lactate solution. A significant dose-related rise in plasma prolactin was evident 10 min after injection with AVT. In a second experiment, sham-operated or pinealectomized EP-treated male rats were injected iv with 0.1 or 1 mug AVT or diluent. Plasma prolactin was significantly elevated in both sham-operated and pinealectomized groups at both 10 and 20 min post-injection of 1 mug AVT. These results indicate that AVT has prolactin-releasing activity and that this activity is not dependent upon the presence of an intact pineal gland.


Serum immunoreactive relaxin and softening of the uterine cervix in pregnant hamsters. Serum immunoreactive relaxin levels and ripening of the cervix were measured throughout pregnancy in hamsters. RIA relaxin rose from an undetectable level on day 7 to a maximum value of 29 ng/ml on day 15 of gestation and then fell prior to parturition. The cervix became progressively more dilatable from the 12th to the 16th day of pregnancy. It is suggested that the endogenous relaxin measured by RIA may induce the cervical softening. The absolute levels of immunoreactive relaxin appear to be 10 to 15-fold higher than those previously observed in rats, mice and guinea pigs.


Enzymatic sulfation of steroids: II. The control of the hepatic cortisol sulfotransferase activity and of the individual hepatic steroid sulfotransferases of rats by gonads and gonadal hormones. Ovariectomy has relatively little effect on hepatic cortisol sulfotransferase activity (HCSA) in female rats, diminishing it only 30%. On the other hand, castration more than doubles HCSA in males. HCSA is due to 3 steroid sulfotransferases, STI, STII, and STIII. Its dimunition in ovariectomized rats is due to decreased STI and STII. Castration of males results in elevation of STII. Thus, ovaries appear to stimulate STI and STII production and testes appear to inhibit production of STII and perhaps STI. Studies with testosterone and estradiol-17beta support a role for sex hormones as mediators of gonadal effects on HCSA, by stimulating or inhibiting production of the individual enzymes. Estradiol-17beta administration reverses the effect of ovariectomy on HCSA. Testosterone administration to intact or castrated females decreases HCSA by 60-70%, due to disappearance of all STI and most STII activity. Thus, androgen administration appears to suppress both STI and STII production. In intact males testosterone administration elevates HCSA 70-80% due to increased STIII. Estradiol-17beta administration to intact or castrated males elevates HCSA 9-10-fold. In intact animals this is due to elevated STI and STII but not STIII. In castrates all three enzymes are elevated by the estrogen.


Androgen receptor dependent and independent activities of testosterone on hepatic microsomal drug metabolism. Administration of testosterone for 6 days to intact female and castrate male BALB/cJ mice stimulated hepatic microsomal ethylmorphine N-demethylase activity and cytochrome P-450 content by 50-75%. Testosterone also stimulated hepatic microsomal NADPH-oxidase activity, but to a lesser degree. To probe the mechanism of this effect of androgens, two antiandrogens (cyproterone acetate and flutamide) were employed. Since cyproterone acetate was a potent stimulator of hepatic microsomal ethylmorphine N-demethylase activity and cytochrome P-450 content, no antiandrogenic activity of this steroid could be detected. By contrast, flutamide alone had little effect on either ethylmorphine N-demethylase activity or cytochrome P-450 content. However, this drug effectively blocked the stimulatory effects of testosterone on ethylmorphine N-demethylase activity and cytochrome P-450 content but not on NADPH-oxidase activity. This effect was not species specific, since flutamide also prevented androgen stimulation of ethylmorphine metabolism in adult castrate and prepubertal male Fisher rats. The testosterone-induced increase of hepatic weight and microsomal protein content was not affected by the administration of flutamide. The observations are consistent with the hypothesis that androgens have two distinct effects on the liver. First, testosterone may act as a general, nonspecific stimulant of  liver weight and microsomal protein content which is independent of the androgen receptor. Secondly, testosterone action in the liver may be expressed via an androgen-specific or androgen receptor-dependent mechanism which controls, in part, the cytochrome P-450-dependent demethylase system.


Secretion of a bone resorbing factor by chick thyroid glands in organ culture. The ability of the thyroid gland to secrete a bone resorbing factor in vitro was studied using glands obtained from 20-day-old chick embryos. The glands were incubated in a modified BGJ medium containing 1 mg/ml bovine serum albumin under 5% CO2-40% O2 at 37 C. The culture media were assayed in vitro by measuring the stimulation of the release of previously incorporated 45Ca from cultured 19-day fetal rat bone shafts over a 48 h period. The glands secreted a stimulator of bone resorption which did not appear to be parathyroid hormone (PTH). The dose-response curve for the thyroid gland factor was not parallel to that obtained using PTH and secretion was not under calcium control. Neither thyroxine (T4) nor triiodothyronine (T3) produced a marked stimulation of bone resorption over a wide range of doses. Bone resorption stimulated by the thyroid gland factor was inhibited by calcitonin (CT). Concentrations of TH and thyroid gland factor which were minimally effective when tested separately, produced a marked synergistic response when added together. This synergism was not seen when T4, T3, PGE1, or PGE2 were tested with PTH. Media obtained by culturing explants of embryonic chick liver, heart and muscle did not have bone resorbing activity. Secretion of the bone resorbing factor by thyroid glands was blocked by Indomethacin (10(-5)M) but the effects of the factor on bone were not blocked by this agent. These results suggest that the thyroid gland is capable of secreting a stimulator of bone resorption, possibly a prostaglandin, which is capable of synergizing with PTH, and which may represent a tissue factor which under certain circumstances may exert an influence on bone.


Dopamine/neuroleptic receptors in basal hypothalamus and pituitary. In order to determine whether the basal hypothalamus or the pituitary (or both) is the likely locus of action of the tuberoinfundibular (TI) dopamine neurons, these regions were examined for dopamine and neuroleptic receptors. High affinity receptors for haloperidol and dopamine were found in the rat pituitary while none were detected in rat basal hypothalamus. The relative ability of two neuroleptics, chlorpromazine and haloperidol, to displace (3H)haloperidol from the receptor in monkey pituitary is similar to that for rat striatum. The lack of receptors capable of binding (3H)haloperidol or (3H)dopamine in the basal hypothalamus strongly suggests that the TI neurons do not produce postsynaptic effects in this region. The pituitary receptors for (3H)haloperidol and (3H)dopamine have the characteristics of a functional system. The presence of neuroleptic/dopamine receptors in the pituitary and lack of such receptors in the basal hypothalamus supports the hypothesis that dopamine may act directly as a prolactin release inhibiting factor (PIF) rather than releasing PIF from adjacent nerve terminals in the median eminence.


Decreased pancreatic somatostatin (SRIF) concentration in spontaneously diabetic mice. Spontaneously diabetic C57BL/6J obob and C57BL/Ks dbdb mice have been shown to have significantly decreased immunoassayable pancreatic somatostatin concentrations compared to lean littermate controls at 11-12 weeks: obob 1.06+/-0.15 pg/mug protein (n=10) vs control 1.94+/-0.-6 pg/mug protein (n=10) (mean +/- SE; p less than 0.005); dbdb 0.7+/-0.2 pg/mug protein (n=8) vs control 1.5+/-0.2 pg/mug protein (n=8) (mean +/- SE; p less than 0.005). An inverse relationship between circulating insulin levels and pancreatic SRIF concentration is suggested.


Comparison of the changes in plasma human growth hormone (HGH) and immuno-reactive glucagon (IRG) after intravenous and subcutaneous injection of glucagon. Ten healthy male volunteers were studied to compare the effectiveness of intravenous and subcutaneous injections of 1 mg of glucagon on HG secretion. Plasma HGH level rose to a peak of 6 ng/ml or greater 120 minutes after the subcutaneous injection of glucagon (sc glucagon) in all subjects, whereas the intravenous injection of glucagon (iv glucagon) caused comparable increments in plasma HGH in only six out of ten subjects. Furthermore, in comparison to those in sc glucagon the periods required to show maximum responses were less consistent in iv glucagon. Plasma IRG levels reached a peak of 102.4+/-22.6 ng/ml at two minutes following iv glucagon, and a peak of 3.33+/-1.08 ng/ml at 15 minutes following sc glucagon. These fell to initial levels at 60 minutes and at 180 minutes, respectively. There was no definite correlation either between the magnitudes of changes in plasma IRG and HGH levels or between the velocities of decrement in blood sugar and HGH responsiveness. Judging from its simplicity and reproducibility it may be concluded that sc glucagon is more suitable for a clinical provocative test of HGH release than is iv glucagon. In regards to the mechanism of glucagon-induced HGH release, neither glucagon per se nor the fall of blood sugar after hyperglycemia was assumed to play any major role. The sustained elevation of plasma IRG for a certain period might be responsible for the glucagon-induced HGH release.


Direct inhibitions of basal and arginine-induced plasma gastrin secretion by somatostatin in anesthetized dogs. Effect of somatostatin on plasma gastrin levels was investigated in anesthetized dogs. Somatostatin was infused into the right gastroepiploic artery and plasma gastrin levels in the right gastroepiploic, superior pancreaticoduodenal and peripheral veins were measured by radioimmnuoassay. Somatostatin suppressed basal gastrin level promptly in the right gastroepiploic vein and impaired the normal gastrin secretion in response to intravenous infusion of arginine. The inhibitory effect of somatostatin on the plasma gastrin secretion was quite clearly demonstrated in the right gastroepiploic vein. It appears likely that the inhibition of gastrin secretion by somatostatin resulted in direct action on the gastrin secretory cell.


Determination of triiodothyronine in red blood cells by radioimmunoassay. This study was undertaken to determine T3 content in red cells by radioimmunoassay. T3 in red blood cells was solubilized fairly from the stroma by hemolysis and red-cell T3 content could be determined directly by radioimmunoassay of the lysate. After hemolysing red cells with an equal volume of distilled water, 0.4 ml of the hemolyzate was used for the assay. The red-cell T3 content was expressed as ng/ml of red-cell volume. The normal T3 range in red cells was 0.20-0.45 ng/ml, and the Mean+/-SD was 0.32+/-0.10 ng/ml. The limit of detectability was 0.2 ng/ml. In hyperthyroid patients, the red-cell T3 content was more than 0.50 ng/ml with a Mean +/-SD of 1.35+/-0.65 ng/ml. In hypothyroid patients, red cells contained less than 0.25 ng/ml of T3, and there was an overlap from 0.20 to 0.25 ng/ml in the content of red-cell T3 in hypothyroid and euthyroid subjects. The patients with T3 toxicosis showed a high or normal level of red-cell T3. A positive correlation was noted between the red-cell T3 content and the serum T3 level (r=0.66). The correlation between the red-cell T3 content and the free T4 index (expressed as T7) was also positive (r=0.67). From these experiments, it is suggested that the red-cell T3 is low in comparison with the serum T3 levels, and depends on two factors; serum T4 and serum T3 levels.


A female case of the HCG-producing ectopic pinealoma associated with precocious puberty. A female case of precocious puberty associated with HCG-producing ectopic pinealoma was reported. The patient, a 5-year-old girl, was referred to the hospital because of headache and choked discs. Physical examination revealed normal physical growth with breast enlargement. Endocrinological study revealed a high plasma HCG concentration of 1192 ng/ml with a normal FSH level. None of HCG, LH and FSH did respond to the LH-RH test. A partial resection of the tumor and an external X-ray irradiation relieved the symptoms and breast enlargement subsided with a remarkable decrease in the plasma HCG level. Histological examination revealed two-cell-pattern pinealoma and electron microscopic findings showed abundant secretory granules in the dark cells. HCG content in the tumor was as high was 400 ng/mg of acetone dried tumor tissue, but no FSH was detectable. Hitherto, all of the reported cases of precocious puberty associated with pineal tumors have been exclusively boys. A normal level of plasma FSH concentration with a somewhat elevated prolactin level might be a contributory factor for the development of precocial sexual development in the present case.


Effect of a spironolactone derivative (SC 14266) on Plasma renin activity in adrenal regeneration hypertension. The effects of treatment with a spironolactone derivative (SC 14266) for 9 experimental weeks on blood pressure and plasma renin activity (PRA) were investigated in unilaterally nephroadrenalectomized rats drinking 1% saline ("unilater nephrectomy"), unilaterally nephroadrenalectomized and contralaterally adrenal-enucleated rats drinking 1% saline ("adrenal enucleation") and intact rats drinking tap water ("normal"). The development of hypertension in "adrenal enucleation" rats was prevented by treatment with SC 14266 and the drug did not significantly affect the blood pressure in either "unilateral nephrectomy" or "normal" rats. SC 14266 did not influence a low level of basal PRA and the blunted response of PRA to furosemide administration in either "unilateral nephrectomy" or "adrenal enucleation" rats. On the other hand, PRA after furosemide administration in "normal" rats receiving SC 14266 was significantly higher than that in those rats treated with vehicle. The results suggest that the mineralocorticoid(s) secreted by the enucleated adrenal has a hypertensogenic property but no effect on the suppression of renin secretion under a high sodium intake and the unilateral nephrectomy.


The simultaneous assay of progesterone, 17-hydroxyprogesterone, and deoxycorticosterone in human plasma by competitive protein binding. A method is described for the simultaneous measurement of prosterone (P), 17-hydroxyprogesterone (17-OHP) and deoxycorticosterone (DOC) in plasma by competitive protein-binding assay. After extraction, these steroids were purified by Sephadex LH-20 columns. The methods described here is sensitive enough to detect the above-mentioned steroids in as little as 5 ml of plasma under physiological conditions. The mean physiological plasma level (ng/100 ml) of P, 17-OHP and DOC are 18.2+/-1.6 (SE), 136.5+/-11.7, and 8.6+/-1.0 in men, 14.7+/-1.7, 61,2+/-3.6 and 6.0+/-1.2 in women in the follicular phase, and 645.0+/-108.1, 155.2+/-16.9, and 7.5+/-1.2, in the luteal phase of the menstrual cycle. By this method and others, the responses of plasma levels of 7 adrenal steroids (P, 17-OH, doc, corticosterone, deoxycortisol, cortisol and aldosterone) to ACTH infusion (25U i.v. over 8 hours) were investigated in healthy men. The increase of DOC was more pronounced than that of the other steroids.


Effects of age and diseases on human serum 25-hydroxycholecalciferol determined by competitive protein-binding assay. Competitive protein-binding assay of 25-OH-D was developed by the use of specific vitamin D-binding proteins from vitamin D-deficient rat serum. Ether extract of serum sample which was dried and dissolved in ethanol, or standard solution of 25-OH-D3, was incubated with 3H-25-OH-D3 and vitamin D-binding protein for 2 hours at 4degreesC. Free and bound 3H-25-OH-D3 were separated through dextran-coated charcoal. The sensitivity of the assay system was 0.22 ng/tube. Percent cross reaction in the assay was 2.18% in vitamin D3, 0.70% in 1, 25-(OH)2-D3, less than 0.28% in 1alpha-OH-D3, and less than 0.06% in dihydrotachysterol, cholesterol and cortisol. Human serum 25-OH-D is 28.9+/-2.9 ng/ml in 19 normal subjects. Serum 25-OH-D in the old-age group (50-70 years of age) was significantly decreased, compared with that in the young-age group (20-40 years of age). Serum 25-OH-D was significantly decreased in gastrectomized and osteoporotic patients as well as in the patients with liver cirrhosis, in comparison with their age-controls.


p-Nitroanilides of 3-carboxypropionyl-peptides. Their cleavage by elastase, trypsin, and chymotrypsin. Fourteen 3-carboxypropionyl-tripeptide-p-nitroanilides of the general formula 3-carboxypropionyl-alanyl-alanyl-Y-p-nitroanilide (Y = glycine, norvaline, S-methylcysteine, valine, norleucine, S-ethylcysteine, methionine, leucine, isoleucine, phenylalanine, tyrosine, S-benzylcysteine, Calpha-phenylglycine, and proline) were synthesized and their cleavage by elastase, trypsin, and chymotrypsin (Km, kcat and kcat/Km) was determined. The significance of amino acid residues in the position of Y was evaluated firstly with respect to their structure (topographically), and secondly with respect to their free energy (thermodynamically). The alanine residue substrate was cleaved best by elastase, the phenylalanine substrate by chymotrypsin. Trypsin cleaved two substrates only, that is those containing a phenylalanine and a tyrosine residue. The optimum length of the elastolytic substrates was studied in a series of N-3-carboxypropionyl-(Ala)n-p-nitroanilides (n = 1, 2, 3, 4, 5), N-3-carboxypropionyl-(Gly)n-p-nitroanilides (n = 1, 2, 3), and in p-nitroanilides of fatty acids with two to seven carbon atoms. Elastase cleaved tri, tetra, and pentapeptides of alanine. p-Nitroanilides of the glycine series, as well as p-nitroanilides of fatty acids were not cleaved. 3-Carboxypropionyl-tetra-alanine-p-nitroanilide was the most suitable substrate so far found for elastase cleavage; it is not cleaved by trypsin nor chymotrypsin. The optimum distance between Y and the terminal anionic carboxyl residue was found to be 1.8 nm in elastolytic substrates.


Characterization of collagen and its precursors synthesized by  rabbit-articular-cartilage cells in various culture systems. Rabbit articular cartilage synthesizes type II collagen, comprised of alpha1(II) chains, in vivo or in vitro. Chondrocytes from the same tissue have the ability to produce type I chollagen with the chain composition 2alpha(I)-alpha2 or type II collagen, depending upon the culture systems in which they are maintained. Type I collagen and its precursors have been identified in the medium of monolayer cultures. Upon transfer from monolayer to suspension cultures, the cells synthesize type II collagen in the medium devoid of CaCl2 and type I collagen and its precursors in the complete medium.


Isolation and partial characterization of elastase from dog granulocytes. 1. An elastolytic enzyme has been isolated from dog granulocyte leukocytes. The purification procedure included preparation of the granula fraction, chromatography on Sephadex G-75 and ion-exchange chromatography on SP-Sephadex C-50 at pH 6.0. 2. The elastase isolated was homogeneous in analytical disc electrophoresis and showed in sodium dodecylsulfate electrophoresis a single protein component with the molecular weight of 24800. The enzyme lacked tyrosine and lysine and the N-terminal amino acid was phenylalanine. No carbohydrate or sialic acid were detected. 3. The dog granulocyte elastase showed similar activities as human granulocyte elastase on elastin and fibrin. The Km value for 3-carboxypropionyl-L-alanyl-L-alanyl-L-alanyl-p-nitroanilide was 2.50 mM and the pH optimum 8.5. The elastase preparation obtained was 99.5% active as judged from active-site titration. 4. The enzyme is a cationic protein and shows pronounced trailing on agarose gel electrophoresis. 5. A monospecific antiserum against the purified enzyme was produced in rabbits.