Intraventricular free wall dissection causing acute interventricular communication with intact septum in myocardial infarction. This report delineates a previously unrecognized complication of acute myocardial infarction, an intraventricular wall dissection producing interventricular communication without septal perforation. The clinical, hemodynamic, and pathologic features of this unique condition are documented, as well as the factors important in the mechanism of its production.


Patent ductus arteriosus with hypoplastic lung. A median sternotomy approach was used for closure of patent ductus arteriosus associated with a hypoplastic right lung. The anterior approach to the left ductus is indicated if left thoracotomy is contraindicated.


Nocardia infection in a bronchopulmonary sequestration. A case of intralobar bronchopulmonary sequestration is reported in which the sequestered lung was infected with Nocardia sp. Although recurrent pyogenic infections are common in pulmonary sequestrations, this is the first case report with documented nocardiosis.


Detection of covert myocardial sarcoidosis by scalene node biopsy. The antemortem diagnosis of myocardial sarcoidosis is rare in patients without overt signs of the disease. Two patients are presented to alert physicians to the value of early scalene node biopsy when sarcoidosis could be the cause of marked disturbances in cardiac conduction. The first patient, aged 29 years, had first, second, and third degree atrioventricular block and intermittent left and right bundle-branch block; the second, aged 59 years, had second degree atrioventricular block and complete right bundle-branch block. Both had diagnoses of sarcoidosis based on scalene node biopsy. The cardiac conductive disturbance improved, and the symptoms disappeared with steroid therapy.


Penetrating injury of the chest and coronary arteriovenous fistula. An unusual case of coronary artery fistula, due to a stab wound in the chest in a 17-year-old male patient, with a resultant acute inferior myocardial infarction is presented. At surgery, complete transection of the right coronary artery was found, which formed a fistulous communication with both the right atrium and the right ventricle. The development of a continuous murmur in the period immediately after the injury, the absence of hemopericardium, and multiple cardiac-chamber involvements were unique features of the case. The inferior myocardial wall was akinetic due to infarction and did not improve following revascularization surgery. A brief review of the literature is also presented.


Esophagopleural fistula after pneumonectomy. Rupture of the esophagus into the space left after pneumonectomy is a rare and often fatal complication. Esophagopleural fistulas occurred in three patients following pneumonectomy. After previous methods failed, two patients were successfully treated by using a one-stage procedure which included (1) suture closure of the fistula, (2) buttressing the repair with a viable, pedicled, two-rib intercostal-muscle flap, and (3) performing an extensive thoracoplasty with a continuous drip infusion of neomycin. Such a procedure offers the maximum opportunity for successful treatment of this catastrophic lesion.


Alternation of left ventricular performance with electrical alternans. Systolic time intervals (STIs) were measured in a patient with massive pericardial effusion and electrical alternans. The total electromechanical systole and the left ventricular ejection time (LVET) were significantly shorter in beats following the smaller QRS complexes, while the pre-ejection time (PEP) was longer and the ratio of PEP/LVET larger. This beat-to-beat difference in the STIs suggests than an alternation in left ventricular performance accompanied the electrical alternans. After evacuation of the pericardial fluid, electrical alternans and STI alternation disappeared.


Mycobacterium szulgai; a new pathogen causing infection of the lung. A case of infection with a newly described scotochromogenic mycobacterial species, Mycobacterium szulgai, is presented, and all the reported cases are summarized. The disease is characterized by its predominance in middle-aged men, the occurrence of cavitary pulmonary lesions, and a good response to triple-drug therapy. Sputum samples are usually positive on smear. Drug susceptibility studies show a greater degree of susceptibility to several antituberculosis drugs than the usual scotochromogen. Mycobacterium szulgai has frequently been confused with other atypical mycobacteria, but serologic and other laboratory characteristics are distinct and should allow proper identification.


Serial echocardiographic abnormalities in nonbacterial thrombotic endocarditis of the mitral valve. This report describes the clinical course and serial echocardiographic abnormalities in a patient with nonbacterial thrombotic endocarditis and repeated embolic episodes. Serial echocardiograms revealed a mass of abnormal echoes on the anterior mitral leaflet and progressive restriction of mitral valvular motion. Cineangiographic studies demonstrated a large filling defect in the area of the mitral valve. Surgical intervention confirmed the presence of a large vegetation on the mitral valve. The surgical specimen consisted of a sterile, partially organized fibrin thrombus. The echocardiographic abnormalities are described and discussed in relation to the clinical and pathologic findings.


Persistence of the third heart sound after resection of the native mitral and tricuspid valves. Evidence against the valvular theory of third sound origin. A patient is described with severe rheumatic mitral and tricuspid insufficiency in whom both atrioventricular valves with their chordae tendineae and papillary muscles were resected and replaced with Hancock porcine grafts. This would appear to be the second such patient reported and the first described in detail in whom the third heart sound persisted postoperation. This occurrence documents the fact that a third heart sound can occur in the absence of native atrioventricular valve leaflets and the major portions of the subvalvular supporting apparatus, and argues against the theory that the third heart sound is generated by either the valvular leaflets of the subvalvular apparatus.


Late thrombosis of the aortic Bjork-Shiley prosthesis. Its clinical recognition and management. Seven cases of massive thrombosis of an aortic Bjork-Shiley prosthesis were encountered among 433 valvular implants. Four patients died before treatment could be instituted, and three underwent repeat surgery successfully. Anticoagulation therapy was probably well maintained in four, and poorly maintained in three patients. These cases illustrated the need for a high index of suspicion and prompt recognition of this complication in patients with Bjork-Shiley prostheses. The diagnosis of massive thrombosis should be suspected with the rapid onset of (1) signs of congestive heart failure, (2) absence or attenuation of valvular clicks, (3) aortic regurgitation, or (4) hemolytic anemia. Salvage of these patients requires emergency replacement of the thrombosed prosthesis or removal of the thrombus.


A comparison of spirometric values with subjects in standing and sitting positions. Spirograms obtained from 235 subjects in standing and sitting positions revealed small differences for the forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). No statistically significant differences were found for the mean forced expiratory flow during the middle half of the FVC (FEF25-75%, or maximal midexpiratory flow) and FEV1/FVC. Sitting values were, on the average, higher for determinations greater than FVC of 2.14 L, FEV1 of 1.68 L, FEF25-75% of 2.16 L/sec, and FEV1/FVC of 75.7 percent. On the average, subjects with less than these values performed slightly better in the standing position.


Quantitative levels of immunoglobulin E in advanced tuberculosis. Quantitative levels of immunoglobulin E (IgE) were determined in samples of sera obtained from 29 patients with proven moderate to far-advanced tuberculosis. The sensitive radioimmunoassay test for IgE was used. Statistical analysis of the results revealed no difference in IgE values as compared to a control group of normal sera. In contrast to other chronic pulmonary infections, such as bronchopulmonary aspergillosis, the IgE level in pulmonary tuberculous infection is of no diagnostic significance. Simultaneous determination of levels of immunoglobulins G, A, M, and D (IgG, IgA, IgM, IgD) in these same sera by radial immunodiffusion showed elevated IgG and lowered IgM levels in the tuberculous patients, confirming previous studies. The significance of these alterations in immunoglobulin levels is unclear and may represent a secondary phenomenon rather than a primary host response.


Both direct and neurally mediated components of the chronotropic actions of aminophylline. Aminophylline was selectively perfused through either the sinus node or through the AV (atrioventricular) junction of 35 intact canine hearts in situ. The positive chronotropic action observed was equally powerful in accelerating either sinus rhythm (50 +/- 8 percent increment) or AV junctional rhythm (55 +/- 10 percent increment). This positive chronotropic effect has at least three distinct components: a major direct action on autonomic centers, a lesser effect due to local catecholamine release, and a part due to peripheral vagolytic action.


The diagnosis of pleural effusion by ultrasonic and radiologic techniques. The value of the A-mode ultrasonic technique and the radiologic method in the diagnosis of pleural effusion was assessed in 116 patients with diseases of the pleura. Ultrasonic and radiologic examinations, as well as needle punctures, were performed, and the results were compared statistically. The pleural fluid was detected by ultrasound in 93 percent (74) and by radiologic examination in 83 percent (66) of the 80 cases with such fluid. The absence of fluid was established by ultrasound in 89 percent (32/36) and by radiologic examination in 61 percent (22/36). For the first time the superiority of the ultrasonic method over the radiologic one was demonstrated, and the difference was most obvious in cases of small pleural effusion. Ultrasound permitted the detection of very small amounts (even 3 to 5 ml) of loculated pleural fluid. In contrast to the radiologic method, ultrasound permitted easy differentiation between loculated pleural fluid and pleural thickenings. The ultrasonic method appeared especially useful in the accurate localization and precise indicating of the site for needle aspiration of even the smallest fluid collections. It made possible thoracocentesis in 94 percent (154) of 163 instances. The practical value of the ultrasonic method, both in establishing diagnosis and in treatment, is emphasized.


Pleural calcification associated with exposure to chrysotile asbestos in southeast Turkey. In this study, pleural calcifications prevailing in the inhabitants of some villages and towns around Diyarbakir, a city in southeast Turkey, have been found to be caused by the inhalation of chrysotile asbestos, the mineral commonly used indiscriminately to paint the walls and floors of houses. There were no industrial establishments in the area, except some local mining, and asbestos deposits were even not included on the mining map of the country. Chest roentgenograms from the Chest Hospital and the tuberculosis dispensaries were screened: and, additionally, 15,239 photofluorograms were obtained during a survey. Of all these, 511 patients were found to have pleural calcifications, some with pericardial and diaphragmatic involvement. Forty-four percent (28) of the 64 patients who had examinations of samples of their sputa had asbestos bodies, and asbestosis was also induced in rabbits by administration of the raw material.


Doppler ultrasonic assessment of aortic stenosis by analysis of axillary arterial blood velocity upstroke time. Rate-corrected velocity upstroke time (VUT) was calculated from analogue Doppler ultrasound recordings of axillary artery blood flow velocity in 25 patients with aortic stenosis documented by cardiac catheterization and in 14 normal individuals. The mean VUT in normal individuals was 0.11 +/- 0.02 second (+/- 1 SD), which was significantly lower than that of patients with aortic stenosis: 0.15 +/- 0.05 second (P less than 0.005). The VUT correlated with the aortic valve index and the aortic valve mean pressure gradient with correlation coefficients of 0.62 and 0.64, respectively (P less than 0.005). Arterial blood flow velocity assessment by Doppler ultrasound may be a useful noninvasive technique to evaluate patients with aortic valve disease.


Aortico-left ventricular tunnel. Recognition and repair in infancy. An infant with an aortico-left ventricular tunnel underwent surgery at the age of five months. There was clinical and electrocardiographic improvement, and postoperative cardiac catheterization demonstrated obliteration of the aortic end of the tunnel, normalization of systemic pulse pressure, mild residual aortic valvular insufficiency, and a decrease in the left ventricular end-diastolic volume index. Early surgery may limit the progression of aortic valvular insufficiency secondary to turbulent aortic-root blood flow.


Severe coarctation of the aorta with pulmonary edema. An unusual presentation of a traumatic aortic aneurysm. A patient with an unrecognized rupture of the ascending aorta developed severe pulmonary edema three weeks following the initial injury. This is a distinctly unusual manifestation of this injury. Emergency resection of the traumatic aneurysm was required to reverse the rapidly deteriorating clinical situation. The early recognition and surgical treatment of this lesion would have avoided this complication.


Esophagocolic anastomotic stricture repaired twelve years after original interposition. Successful resection of a long, tight, unyielding cervical esophagocolic anastomosis with mobilization of the colon interposition transplant through a sternal splitting incision 12 years after the primary surgery is reported. The colon transplant with its vascular bundle was dissected with less difficulty than expected and 5 cm of increased length was obtained to make a new neck anastomosis without tension.


Atrial fibrillation developing in the acute phase of myocardial infarction. Prognostic implications. Atrial fibrillation was observed in 39 (11 percent) of 350 instances of acute myocardial infarction. The mortality among these patients was 41 percent (16/39). Atrial fibrillation was more common in patients with undetermined infarctions and in older people. As opposed to death rates close to 50 percent among patients with anterior, combined, and undetermined infarctions, the presence of atrial fibrillation did not affect the mortality among patients with inferior infarctions (10 percent, 1/10). Ventricular rates higher than 120 beats per minute and duration of the arrhythmia longer than six hours were not associated with increased mortality. Hemodynamic failure was present in almost all of the cases and preceded the arrhythmia in most of them. It is concluded that different mechanisms are responsible for the production of atrial fibrillation in the setting of acute myocardial infarction, and the prognosis of the patient is related to the mechanism of production and not to the arrhythmia itself.


Subepicardial infarction, myocardial impression, and ventricular penetration by sutureless electrode and leads. Postmortem examination two weeks following implantation of a demand pacemaker with sutureless electrodes demonstrated that (1) the loops of intrapericardial electrode leads indented the myocardium and produced a circumscribed area of subepicardial necrosis, and (2) one of the electrode coils protruded into the right ventricular cavity. The use of extrapericardial electrode leads and left ventricular implantation sites should avoid these problems.


Systemic arteriovenous fistula simulating severe valvular aortic stenosis. A patient with a renal arteriovenous fistula is described. She was though to have valvular aortic stenosis because of a history of rheumatic fever, symptoms of congestive heart failure and syncope, and the presence of a harsh systolic murmur with a thrill in the aortic area. Cardiac catheterization revealed a left-to-right shunt of 8.7 L/min. Ligation of the fistula resulted in complete relief of the symptoms and attenuation of the murmur.


Pneumonitis due to Corynebacterium equi. Corynebacterium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a child with pneumonitis and leukemia. Clinical improvement followed the administration of chloramphenicol, and cultures of sputum specimens were sterile until relapse occurred after antibiotic therapy was terminated. Cure was achieved with a second course of chloramphenicol therapy. Corynebacterium equi was not isolated from 1,181 samples of sputum from other immunosuppressed children with cancer.


Echocardiographic diagnosis of a stuck Bjork-Shiley aortic valve prosthesis. A 55-year-old man who had been asymptomatic after replacement of his aortic valve with a Bjork-Shiley prosthesis, suddenly developed heart failure. The clinical suspicion of prosthetic malfunction was not only confirmed, but specified as being a stuck disc secondary to a large thrombus. Surgical removal of the clot resulted in restoration of normal function and return to the expected findings on echocardiogram. The value of echocardiography in such instances, as well as in routinely following-up patients with prostheses postoperatively, is emphasized.


Periodic review of foster care: a brief national assessment. A survey of statewide public agencies shows that a majority of states have some form of judicial or administrative periodic review, although few have both. The organizational level of authority and degree of foster care specialization of agencies are positively correlated with administrative review and negatively correlated with judicial review.


Percutaneous third ventriculostomy: experience and technique. A series of stereotaxic percutaneous third ventriculostomies has been carried out on 46 shunt-dependent hydrocephalic children. The technique and results are presented. The advantages of this procedure over the open craniotomy type are discussed. There has been low morbidity and one mortality. The necessity of preoperative shunting to provide a 'slack brain' is emphasized.


Measurement of respiration in Arnold-Chiari malformation. Respiratory distress occurs in infants with myelomeningocele and Arnold-Chiari malformation. It is difficult to measure it because of the small volume exchanged and the lack of cooperation of infants. Existing equipment had to be modified to do so by decreasing the dead space and reducing the bulkiness of the sensing device. In infants with tracheostomies, a continuous flow of gas was applied to reduce the dead space. In infants without tracheostomies, a continuous flow of gas was applied, but the mask was too bulky to seal around the baby's face. A nose-piece pneumotachograph was developed to alleviate the problem. Respiration was measured in 15 patients with myelomeningocele and hydrocephalus from 1 day to 5 months of age. After gas was administered, they breathed 38.5 times a minute with a tidal volume of 6.25 ml/kg, producing a minute ventilation of 0.2541/min/kg. After administration of 5 per cent CO2-95 per cent O2, respiratory frequency rose to 47 breaths a minute, with a tidal volume of 8.8 ml/kg, producing a minute ventilation of 0.4101/min/kg, comparable to that of normal infants.


Diagnosis and management of skeletal metastases from cerebellar medulloblastoma. Four cases of cerebellar medulloblastoma with skeletal metastases have been described. Extracranial metastases from this tumour are extremely rare but the skeleton is the site most commonly involved. The metastases did not occur after ventriculo-atrial shunting, but in one of the cases, the diagnosis was made from the check X-ray taken on the day a shunt was introduced. The influence of vincristine sulphate and cyclophosphamide on the radiological appearances and management of the cases has been described. After the diagnosis of skeletal involvement was made three of the children survived over a year with cytotoxic drug treatment; the other case did not respond satisfactory and died from widely disseminated metastases of the central nervous system, 4 months after starting treatment.


Computerised axial tomography. Particular applications and advantages in paediatric neurosurgery. The first year's experience of computerised axial tomography (the EMI scanner) in a department of neurosurgery is described, and those features of particular importance in the younger age group are emphasised.


Midline commissurotomy for the treatment of some cases of intractable epilepsy. Preliminary report. When epilepsy is localized, limited excisions can be very effective for control of seizures without increased neurological deficit. Van Wagenen found that a seizure discharge confined to one hemosphere would not produce an unconscious state, so he treated his patients with partial or complete sections of the corpus callosum with more success with complete sectioning. Erickson showed that total callosal section was necessary to stop the spread of cortically induced seizures from one hemisphere to the other. Luessenhop reported on four patients treated by divisions of the corpus callosum. Midline commissurotomy is an effective operation for the control of major seizures when the seizure discharge begins in the cortex of one hemisphere and becomes generalized. The procedure is equally applicable to patients with or without major neurological deficit.


Intracranial pressure monitoring in Reye's syndrome. Reye's syndrome is difined as fatty degeneration of the viscera with encephalopathy. The signs are change in consciousness after recovery of a viral illness, vomiting, high fever, and progresseve deterioration of the level of consciousness. Signs of brain stem involvement quickly follow. The clinical findings are: mild elevations of serum transaminases (SGOT and SGPT), normal to slightly elevated bilirubin, abnormal blood-clotting functions, normal to low blood glucose, high blood ammonia, and normal cerebrospinal fluid which may be under increased pressure. Death is due to increased intracranial pressure. Therapy is used to stabilize these signs. It includes: infusion of hypertonic glucose followed by insulin, peritoneal dialysis, and exchange transfusion. Intracranial pressure was monitored continually to determine when therapy should be administered.


Pinealoma in children.

Pinealoma in children. The author has a high incidence of pinealoma in his series of intracranial neoplasms. In order to make a diagnosis of pinealoma of the pineal region and of the chiasmal region, pneumoencephalography or ventriculography is very useful in addition to the neurological findings and the plain radiographic findings. The author emphasizes the usefulness of the Millipore filter-cell culture of the cerebrospinal fluid and of the ventriculofiberscopy for the diagnosis of pinealomas in children. The reported cases were treated by a combination of radiation and surgery.


Development of a liposarcoma out of the capsules of a hygroma. We treated a patient who had a very rare finding: the development of a malignoma out of the capsules of the subdural hygroma covering the right occipitotemporal brain. Lumbar encephalography and arteriography confirmed the fact that surgery was necessary. A subdural-auricular shunt was performed and revised 2 years later. During the second operation, the external and internal capsules were removed in addition to the shunt. 3 years later the hygroma and large capsules were removed again and a ventricular-subdural drainage performed. 1 year later once more a subdural-auricular shunt was performed. 10 months later a tumour was found to be a pseudomucinous liposarcoma with large hyperchromatic  nuclei and oval cells with large vacuoles of neutral fat. Renewed growth of the tumour led to the child's death. The histological and macroscopic findings of the capsules suggest the development of a malignoma within the last 3 years.


Transient loss of recent memory following deep midline cerebral operations. We have drawn attention to a post-operative complication of deep midline cerebral operations where operative manipulation occurs to structures associated with memory mechanisms. In the cases presented, the deficit was not permanent probably because the lesions were unilateral, or in conduction pathways.


[Clinical aspects and diagnosis of the occlusion of upper mesenteric arteries]. Acute mesenteric vascular occlusion is associated with an extremely high mortality. Only the early diagnosis may be helpful in this condition. A directed anamnesis and close observation of clinical signs and symptoms associated with metabolic acidosis, significant base deficit, elevated white blood count, and arteriography could shorten the time period between vascular occlusion and operation. This is the way, which possibly leads to more gratifying results.


[Diffuse, nodular-polypous lipomatosis of the small intestine]. One case of diffuse nodular lipomatosis of the small intestine is reported. Four other cases from the literature are revied. Symptomes and signs, diagnosis and differential diagnosis, as well as surgical treament, are discussed.


[Cryosurgical treatment of tumors].

[Cryosurgical treatment of tumors]. In 84 out of 164 carcinoma patients, admitted from June 1974 to September 1975 -- altogether 98 cryosurgical operations were performed according to the stage of the tumors. This was done as additional treatment to radical operation, as monotherapy, as additional treatment to palliative resection, or as a mono-palliative-therapy. After a discussion of the method, and a critical evaluation of the advantages and disadvantages (including new application areas) cryosurgery is proved to be superior to the conventional method in the destruction of tumor, e.g. in the liver, pancreas, roof of mesentery, and iliac region. The same is true when it is used as a palliative treatment in processes where access is difficult. On the other hand it seems that tumor-freezing shortens the life of patients, weakened through inanition.


[Results of spincteromyotomy in anal-spincter achalasia. Histology and postoperative continence]. Electromanometric studies were performed in a serie of 149 chronically constipated children. One third of the cases showed manometrically an organic and spincter achalasia. In the other two thirds the constipation was functional or psychogenic. In 73 patients a sphincter myotomy was performed. In 50 of these cases the histology of the internal anal sphincter taken by biopsy revealed a close relationship to the electromanometric results. Patients electromanometrically diagnosed at having an organic cause of the achalasia showed histologically in all except one, severe chronic inflammation, fibrosis, hyperplasia of the smooth muscle, or an absence of the ganglion cells in the upper part of the sphincter muscle. In 17 cases with a functional or psychogenic cause only one showed histopathologic findings. Of the 73 patients who were operated upon, 66 had excellent results. In 7 cases encopresis and constipation persisted. The reasons for this are discussed. Pre- and postoperative electromanometric measurements were performed in 30 children, postoperative measurements alone in 59 others. The most important electromanometrically criteria in evaluating the results of the sphincteromyotomy are normalisation of the anorectal pressure profile and the return of regular anorectal fluctuations. Signs of incontinence could not be observed.


Chronobiology in 1975.

Chronobiology in 1975. A spectrum of rhythms with several frequencies importantly characterizes not only the central nervous system but also the neuroendocrines and endocrines, other structures and organs, beyond the level of the cell to subcellular structures; it has a wide bearing since chronobiologic methods and facts relate to both basic research and its bearing on major problems of our day. Perhaps most important, computer analysis of data series allows study of temporal structure, progressive and rhythmic variations in life processes and in their responses to environment and drugs. By such methods coupled to modern data collection and/or self-measurement, chronobiology is particularly promising in the following areas, cited as illustrative rather than comprehensive examples: 1. Work hygiene: optimization of work schedules by adjustment of regular schedules and in particular of shift-work to the individuals' physical and mental rhythms. Experimentally, differences in manner of schedule change can account for the difference between the life span shortening and lengthening. 2. Population control: improved methods for detecting the neural as well as neurohormonal regulation of ovulatory cycles should aid efficient family planning by the recognition of a spectrum of rhythms and its synchronization with socio-ecologic factors acting, perhaps, via olfactory and/or other sensory modalities; 3. Nutrition: optimizing the utilization of ever scarcer food supplies and also the benefit from both oral and parenteral medications by meal timing; 4. Education: providing a do-it-yourself system for monitoring individual health in the context of secondary and adult education and as the basis for preventive health care; and, in another context, taking individual mental rhythms as well as morningness-eveningness into account in teaching and learning; 5. Health care: Any risk, e.g., from blood pressure rhythm alteration (perhaps preceding by years intermittent labile elevation) will be detected earlier and more efficiently by multiple measurements readily obtained by autorhythmometry. Results of such an endeavor provide at any one time indices that can be compared with an individualized rhythmometric reference standard as well as peer group rhythm parameters. The rhythm-determined average is more reliable than the single measurement. Other individualized characteristics of a rhythm, such as measures of extent of change or timing of change, may constitute an early warning signal and could be monitored by self-measured or preferably automatically-collected data. Timely and timed treatment can then be sought to prevent, in the case of blood pressure, elevation and consequent debilitating disease such as coronary infarction and stroke. 6. One can strive toward the more specific correction of any pathogenic rhythm alteration when such can be recognized by modern methods of data collection and data analysis...


Chronobiologic and inbred strain differences in blood hemoglobin of the mouse. Hemoglobin concentration in mouse blood exhibits differences as a function of inbred strain, age and circadian rhythm. The detection of an age-effect can depend upon the circadian stage chosen for sampling.


Effect of fasting on the circadian rhythm of serum insulin levels. The effects of 29 hrs of fast on gastric content, serum glucose and IRI levels were studied twice in normal mice. Both experiments showed a circadian rhythm of all parameters studied in control animals. Fasting in both experiments was unable to modify the circadian rhythm of gastric content and serum glucose levels, in spite of substantial modifications in their absolute values. Conversely, while the rhythm of serum IRI levels was not changed in one experiment, the other showed a variation with no level of significance. The latter coincides with the greatest decrease of both gastric content and serum glucose levels. Therefore, circadian IRI levels should be only within some range under the control of food intake. This suggests the possible existence of a threshold for absolute glucose and/or gastric content variation under which serum IRI level rhythm is unable to reach the level of significance.


The 24-h pattern of human prolactin in serum. Radioimmunoassay determinations of serum prolactin every 2 hrs in twelve healthy subjects (six women and six men), aged between 22 and 34, reveal that several episodes of hormone secretion occur over a 24-h period. The two episodes displaying significant oscillations have 24-h and 8-h periods, with maxima occurring respectively at 04(30) and at 07(00), 15(00) and 23(00). Accordingly, the highest prolactin levels in serum occur during the night, but oscillations are present throughout the day. The observation schedule adopted leads us to conclude that the main secretory rhythm is synchronized with sleep. The 8-h periods seem to be rather dependent on the course of time.


Circadian rhythms in blood, urine and gastric acid secretion of presumably healthy volunteers. The mean conisor technique reveals statistically significant circadian rhythms for serum concentrations of iron, chloride, cortisol, PBI, the fibrinolytic activity of blood, urinary iron excretion and gastric acid secretion in studies covering a 24-h span for presumably healthy subjects. Quantification of these rhythms provides internationally comparable reference values both for the conventional clinical laboratory and for any special chronobiologic applications.


Volvulus of the colon--a continuing surgical problem. Twenty-six cases of colonic volvulus from the University of Kentucky Medical Center and the Lexington Veterans Administration Hospital, covering a ten-year period, are presented. Overall mortality was 19 per cent (5 of 26 patients). Cecal volvulus carried the greatest mortality, 30 per cent (3 of 10 patients), whereas sigmoidal volvulus had relatively low mortality rate of 7 per cent (1 or 15). A single patient who had volvulus of the transverse colon died. The most significant factor leading to death was not necrotic bowel but the necessity for emergency operation in these generally debilitated patients. A plan of management with the major aim to convert emergency situations into elective or urgent ones is presented with the expectation that the mortality rate can be improved.


Intraoperative Chaffin sump recto-colonic irrigation. A simple method for intraoperative rectocolonic irrigation using the time-honored Chaffin sump drain is recommended. It assures an empty particulate matter-free bowel for anastomosis, washes out malignant cells, and provides proof of the integrity of anastomosis and decompression of the proximal bowel when indicated.


Management of focally malignant pedunculated adenomatous colorectal polyps. A hospital record review identified 59 patients whose sole colorectal pathology was a pedunculated, adenomatous polyp with a focus of malignancy confined to the head of the tumor. Thirty-one patients had polyps with in-situ carcinoma, and 28 patients had foci of invasive carcinoma. Sixteen patients who had lesions in situ underwent laparotomy, and not a single instance of metastasis was found. Twenty patients who had carcinoma in situ received only local treatment, and 15 are alive and well. None of the patients treated locally has developed subsequent colorectal cancer, and 12 have survived at least five years following treatment. Of the 28 patients who had invasive carcinoma confined to the head of an adenoma, 19 are alive and well, and 17 have lived five years or more following treatment. There was one instance of lymph-node metastasis, which occurred in a patient who had a malignant lesion extending to the neck of the tumor and tumor cells in the lymphatics in the head of the polyp. All of the eight patients treated locally are alive and well, and five have lived at least five years following treatment. The results of this study, coupled with the rarity of reported metastasis from focally malignant, pedunculated, adenomatous colorectal polyps, strongly suggest that local treatment is sufficient for the vast majority of these lesions. Evidence from the literature suggests that resective therapy should be considered when 1) lymphatics within the head of the polyp contain tumor cells; 2) the cancer is highly undifferentiated; 3) the pedicle is extremely short and malignant changes extend to the neck of the adenoma.


A comparison of the results of extraperitoneal and intraperitoneal techniques for construction of terminal iliac colostomies. In a series of 251 patients followed for at least two years after abdominoperineal excision for carcinoma of the rectum, those given extraperitoneal iliac colostomies were found to have significantly lower incidences of pericolostomy herniation, prolapse, and recession than those given intraperitoneal colostomies. There was no difference between the frequencies of mechanical intestinal obstruction.


The pathology of the appendix in ulcerative colitis. Sixty-five patients who had the documented histologic diagnosis of chronic ulcerative colitis were selected in order to study appendiceal involvement in this disease. There were 28 males and 37 female patients with an average age of 30 years. The incidence of appendiceal involvement involving the right colon was found to be 47 per cent. In all of these cases the appendiceal involvement occurred in association with the disease process in the cecum or the right colon. In seven patients a classic picture of ulcerative appendicitis in active phase was found. In 78 per cent of patients a similarity between the disease stages in the colon and in the appendix was observed.


Motor neuron disease: retrospective study of associated abnormalities. In a retrospective study of the charts of 39 patients who had motor neuron disease we found that over 50 percent of patients had radiographic abnormalities of bone and over 20 percent had serum calcium concentrations out of the range observed in normal controls. Statistical analysis indicated that, in respect to serum calcium levels, patients who have motor neuron disease are a separate population. These findings, which might reflect a disturbance in bone or calcium metabolism in patients with motor neuron disease, are of interest in view of the known ability of divalent ions other than calcium, such as lead and mercury, to simulate motor neuron disease, and the discovery that patients with proven primary and secondary hyperparathyroidism may have features of amyotrophic lateral sclerosis.


Intravenous chlorimipramine and depressive subtypes. An open clinical trial with intravenous chlorimipramine was carried out on twenty depressed inpatients, diagnosed as primary or secondary affective disorders following a classificatory scheme for use in psychiatric research. Eleven of twelve patients with primary affective disorders had a significant decrease in symptoms of depression at the end of two weeks. In contrast, eight patients with secondary affective disorders did not show such significant improvement. Changes in physiological parameters (systolic blood pressure) were significantly greater in the primary affective disorders than in the secondary ones. It is inferred from the results of this trial, that intravenous administration of chlorimipramine is a safe and feasible procedure, which may compare to electroconvulsive therapy in the treatment of severe unipolar and bipolar depressions.


Ballistic movements of the arm in systemic lupus erythematosis. The case of a 24-year old woman with systemic lupus erythematosis and central nervous system disease manifested by ballistic movements of the left arm is presented. She also had bilateral cerebral infarcts with pseudobulbar palsy. Ballismus is not generally known to be a manifestation of systemic lupus although there have been been reports of chorea in this disease which has responded to treatment with corticosteroids. In the present case, the ballismus disappeared when very large doses of steroids were given. This suggests that massive doses of corticosteroids may be needed for effective treatment of central nervous system lupus.


Deviation of the rectosigmoid colon simulating a presacral tumor: report of a case. The rectosigmoid colon has a potential for a great deal of mobility and variation of position. This is partially due to the wide variation in length and distal attachment of the sigmoid mesocolon. When anterior or lateral deviations of the distal sigmoid and rectum are found on barium-enema examinations, the possibility of anomalous fixation of the rectosigmoid should be considered.


Further examination of a biochemical test for suicide potential. The use of biological data, especially adrenal cortical activity, to enhance the assessment of suicide potential has been suggested and briefly argued in the literature. In this report data is presented on two suicide patients. One patient suicided 8 months after her 4-month hospitalization during which time her 17-hydroxycorticosteroid (17-OHCS) excretion remained at low levels. The second patient suicided on his thirteenth hospital day; his 17-OHCS excretion was moderately elevated, but consistent with his high anxiety and depression ratings. One case is used to support the previous findings that low 17-OHCS affords the clinician no reassurance regarding suicidal risk in the future. The other case illustrates the difficulty in interpreting moderate elevation in arousal sensitive endocrine systems in light of clinically manifest anxiety and/or depression.


New developments in electroconvulsive therapy. Recent legal limitations on the availability of electroconvulsive therapy (ECT) are discussed in relation to the constitutional rights of the doctor-patient relationship. Technical factors which may contribute to the debate about ECT are presented. Improved methods of administration and documentation are proposed.


Hyperpyrexia in catatonic states.

Hyperpyrexia in catatonic states. A patient with an underlying brain disease and catatonia associated with fever of unknown origin, who responded to ECT is presented. The role of dopamine in the basal ganglia in the etiology of catatonic states and its possible relationship to the symptomatology of the patient and his response to ECT is discussed.


[Investigations into urea elimination in patients with advanced chronic renal failure during forced diuresis]. Controlled balance studies were performed in 12 oedema-free patients with advanced chronic renal failure with optimal dietary pretreatment. Forced water diuresis did not result in a significantly increased urea excretion as compared with spontaneous diuresis. Furosemide diuresis resulted in a significant increase (P less than 0.05) which was irrelevant therapeutically. The serum urea may even increase slightly under furosemide due to massive fluid loss. During thirst-regulated diuresis of advanced chronic renal failure urea back-diffusion is probably already reduced to a minimum. Normal hydration provided, forced water diuresis (oral or parenteral fluid) is useless and irresponsible as it poses additional risks in such patients. Furosemide in high dosage in over-hydrated patients is an effective diuretic even in advanced renal failure. The slightly significant increase in urea excretion during furosemide treatment does not result in important benefits in dietetically well treated patients.


[Scanning in progessive pulmonary failure (shock-lung): preliminary results of a clinical study]. Lung scanning was performed on five patients with shock lung. It gave no evidence of morphological (pre-capillary) arterio-venous shunts or of increased pulmonary arterial pressure. Nor was there evidence of perfusion-ventilation inequality in the scan. The cause of the progressive pulmonary insufficiency was most likely due to maldistribution of gases in the microscopic region and to diffusion abnormalities.


[Use of muscle aspiration biopsy needle for diagnostic purposes]. The needle for aspiration biopsy of skeletal muscle, previously developed for biochemical and physiological purposes, has been introduced in the diagnosis of muscular and vascular diseases. Evidence is presented that this needle is a useful tool for routine evaluation of such disorders.


[Normal cholesterol and triglyceride levels in serum: comparison of enzymatic and colorimetric methods (author's transl)]. Three methods were used to determine the normal ranges for cholesterol and triglyceride in serum of 385 blood donors (289 men, 96 women, aged 18-50 years). Enzymatically determined cholesterol levels had an upper normal range to 6.73-6.99 mmol/l (2.6-2.7 g/l), i.e. lower than with the colorimetric method. The upper range for the triglycerides was 2.28-2.85 mmol/l (2.0-2.5 g/l). Both variables were age and sex-dependent. It is suggested that in assessing lipid levels they should be divided into normal, border-line and definitely abnormal values.


[Intragastric titration, a method for clinically testing the effect of antacids]. Intragastric titration can be used not only for the quantiative assessment of gastric secretion in healthy subjects and patients with peptic ulcer, but also for differentiating disorders in the regulation of HCI secretion. It is useful foe evaluating the effect of antacids after stimulation of acid secretion with  a test meal. The duration of action of an antacid taken about one hour after a meal was much greater than when taken on an empty stomach. Results in 12 healthy subjects indicate that frequent small meals (6 to 8 daily) and antacids between meals greatly reduce gastric acidity. Whether these findings hold true for patients with peptic ulcer remains to be determined.


[Embolic occlusion of the left renal artery with a non-functioning right kidney]. In a 69-year-old patient with absolute arrhythmia and a rightsided non-functioning kidney embolism occurred in the left renal artery. Despite 2 1/2 days of anuria embolectomy was successful. Fastest possible restoration of renal perfusion is critical for organ preservation.


[Isoenzymes of creatine kinase in extracardiac disease and after various diagnostic and therapeutic procedures]. Creatine kinase MB isoenzyme was measured (using antibody inhibition) in serum of patients with exogenous intoxication, acute pancreatitis, cerebrovascular accidents, meningitis, encephalitis, skeletal muscle disease, shock, postoperative states and after coronary arteriography, cardiac catherisation of cardioversion. CK-MB activity was revealed only in sera of patients with exogenous intoxication (severity III and IV), polymyositis, scleroderma, after operation or after coronary arteriography, cardiac catherisation or cardioversion. As it is not possible to differentiate between CK-MB and CK-BB using inhibiting antibodies against CK-M subunit, CK-isoenzyme activity was determined in parallel, using precipitating antibodies. No CK-BB was found in any case. The determination of CK-MB isoenzyme after blocking of the CK-MB subunit by means of inhibiting antibodies is suitable  for clinical diagnosis. The method significantly increases the value of creatine kinase measurement.


[Regional contraction of the left ventricle in congestive cardiomyopathy]. Regional analysis of ventricular angiograms obtained at diagnostic cardiac investigation was undertaken in 22 patients with congestive cardiomyopathy and 16 healthy subjects. Applying the concept of radial motion, directed towards the centre of the left ventricle, akinetic zones of 20 to 50% of left ventricle circumference were found in more than half the cases of congestive myopathy. The greater the area of regional abnormal motion, the greater the reduction in haemodynamic variables and left ventricular function. The clinical status of nearly all patients with large akinetic areas deteriorated in the subsequent period of observation (6-48 months, averaging 26 months). But in patients without additional abnormal regional wall motion the clinical condition remained stable. A large akinetic area in congestive myopathy indicates severe reduction in left ventricular function and is an unfavourable prognostic sign.


[Recto-vaginal fistulae: causes, treatment, results (author's transl)]. Among recto-vaginal fistulae in 41 patients 22 were due to radiotherapy, 6 to inflammatory disease, 4 occurred as a postoperative complication and 9 were carcinomatous fistulous tracts. Passage of stool or air per vaginam is a pathognomonic sign. The fistula can usually be diagnosed by routine gynaecological examination. Barium enema, barium meal with follow-through or colpography often demonstrate the fistula. Except for a few cases in which the fistula closes spontaneously (most frequently those which occur postoperatively), treatment is surgical. Intestinal resection is often necessary in the inflammatory fistulae and those after radiotherapy. In fistulae due to carcinoma colostomy will improve symptoms: radical removal of the tumour is rarely possible. 31 of the 44 women are cured, while in two a fistula has persisted.


[Pathological perfusion scintigram of the myocardium in angina pectoris patients with normal coronary angiograms (author's transl)]. In patients aged 24 to 45 years with angina pectoris, pathological changes in the exercise electrocardiogram and a normal coronary angiogram, a disturbance of the pattern of myocardial perfusion could be demonstrated in addition by scintigraphy. The cause of this disturbance of myocardial perfusion is unknown. Myocardial scintigraphy is indicated (1) to demonstrate an otherwise undetectable disturbance in the blood flow of the myocardium with a morphologically normal coronary system, (2) in subtotal coronary stenosis before the decision to perform a coronary bypass operation is made, (3) in cases of anginal syndrome with normal coronary angiograms.


[A new method of demonstrating the regional lymph nodes of the urinary bladder (author's transl)]. Pedal lymphography as used up to now does not fully demonstrate the lymphatic drainage of the bladder. A new method is presented in which Lipiodol-Ultra-Fluid is injected into the submucosal layer of the bladder wall under endoscopic vision. In 27 endovesical lymphographies the following lymph nodes could be demonstrated: the anterior, lateral and posterior vesical, the obturator, the external and internal iliac and the common iliac nodes.


[Diabetes mellitus in idiopathic haemochromatosis (author's transl)]. In 28 out of 40 patients with idiopathic haemochromatosis manifest diabetes mellitus could be demonstrated 19 patients required insulin. Treatment of diabetes with or without insulin was problem-free. In only two patients there was an insulin resistance which required high doses of insulin some of the time. There was a family history of diabetes in eleven patients. Minimal diabetic retinopathy in two patients was the only typical complication specific to diabetes. Severe forms of microangiopathy are seldom seen in haemochromatosis diabetes. This form of diabetes is probably mainly of genetic origin. Liver cirrhosis and fibrosis and possibly pancreatic siderosis are additional factors to be considered. A sufficiently long and intensive venesection treatment leads to clinical improvement in the diabetes in only a small fraction of the haemochromatosis patients.


[On amnesic episodes (author's transl)]. Amnesic episodes occur suddenly out of full health and pass off spontaneously after about three to six hours. Consciousness and customary speech and action are maintained during these periods, but powers of acute observation and memory for preceding weeks are lost. But amnesia persists only for the events during the amnesic episode. Temporary and circumscribed ischaemia in the limbic system is thought to be the case. Three case reports are presented to illustrate precipitating circumstances.


[Liver damage in chronic alcoholics with and without delirium tremens (author's transl)]. 371 males admitted to a special hospital for withdrawal treatment of alcoholics were investigated on admission and repeatedly controlled during a follow-up of 3-6 months. In only 15% of all patients without delirium tremens there were no signs of liver disease on admission. 62% showed evidence of moderate or severe liver disease. 2-6 months after admission the percentage with moderate or severe liver disease had decreased (26%) while normal findings were obtained in 49%. On admission no correlation between frequency or degree of liver damage and the duration of alcohol abuse or daily intake of alcohol was demonstrated. Following abstinence of 2 months or more incidence of severe liver changes was nearly unchanged (16%) in patients drinking for more than 20 years, while it dropped distinctly in the groups with shorter duration of abuse (abuse less than 10 years: 5%). Histological alterations were distinctly more frequent in patients with abuse of more than 15 years (pronounced fibrosis 26%, cirrhosis 20%), as compared to alcoholics who drank less than 15 years (5 and 9%, respectively). In the patients with delirium tremens signs of severe liver disease were more frequent than in those without delirium. The trend towards normalisation of liver function tests was less in the former than in the latter (marked pathological findings following 2 months of alcohol abstinence in alcoholics with delirium tremens: duration of alcoholism less than 10 years: 16%; 11-20 years: 33%).


[Results of 201thallium myocardial scanning in coronary heart disease (author's transl)]. Quantifiable 201Tl scanning of the myocardium was performed in 23 patients with coronary heart disease and 10 without heart disease. Taking into consideration normal relative minimal storage of 201Tl in different regions of the myocardium (five projections), decreased 201Tl uptake in underperfused myocardium (acute myocardial infarction, coronary artery stenoses with hypo-, dys-, and akinesia) was recognizable according to extent and localisation (iso-impulse rate scan). The lowest relative 201Tl storage was found in dyskinesia or akinesia (37.6-54.1%) in the region of the anterior wall, as well as in acute myocardial infarction (50%). In the period after myocardial infarction persistence and normalisation of underperfusion could both be demonstrated. 201Tl scan as a non-invasive test is an appropriate means for demonstrating relative regional perfusion in the myocardium, with myocardial capacity for active uptake of potassium-like thallium being determined at the same time.


[Human coronary arterial patterns (author's transl)]. Limits of the supply area of the three large coronary arteries (right, left descending and left circumscribed branches) were determined by post-mortem angiography of 400 human hearts. The largest variation was demonstrated in the region of the posterior ventricular wall and the apex. Most frequently the border of the supply region between right and left circumflex branches extended across the middle of the left posterior wall. Hearts in which the left ventricular posterior wall was supplied from both right and left circumflex branches (normal type) constituted 82% of all cases. In the right-coronary dominant type (10%) the left ventricular posterior wall, at least at the base, was supplied by the right coronary artery, while in the left-dominant type (8%) the right coronary artery did not supply any part of the left posterior wall. At the apex the left descending branch rose dorsally by about 0.2-5.0 cm in 70% of cases, while the posterior interventricular branch only rarely supplied the apex (1.1%). The left coronary artery showed most variations in the anterior wall. It divided into two in 41%, into three with an additional diagonal branch in 53% and into four in 6%.


[Acute febrile neutrophilic dermatosis Sweet's syndrome]. Acute febrile neutrophilic dermatosis was diagnosed in three middle-aged women. It started characteristically one to three weeks after infection of the upper respiratory tract with sudden fever and painful, inflammatory, multiform skin lesions. There was marked leucocytosis and neutrophilia. The disease is characterized by dense, perivascular, neutrophil-granulocytic infiltrates associated with lymphocytic-histocytic reactions at the margins. Site and dynamics of the histological changes suggest an immune-complex disease. However, direct immunofluorescence has not given any characteristic findings. In general the prognosis is good, the disease rapidly responding to systemic glucocorticoids. But there are also spontaneous remissions, as in two of the described cases.


[Plasma aldosterone during haemodialysis in patients with terminal renal failure]. In 14 patients with terminal renal failure who underwent dialysis with a solution containing potassium in a concentration of 2 mmol/l, the aldosterone concentration in plasma decreased significantly during haemodialysis. On the other hand a clear increase of plasma aldosterone was observed during haemodialysis in two patients who were dialysed with a solution containing potassium in a concentration of 4 mmol/l. This observation demonstrates the importance of plasma potassium for the regulation of plasma aldosterone concentration during haemodialysis. It suggests that the renin-angiotensin system has no major role in the regulation of aldosterone despite sodium and fluid losses.


[Allergic agranulocytosis due to promethazine]. An allergic agranulocytosis developed after promethazine administration to a 34-year-old man with a compulsion neurosis. Promethazine-specific leucocyte antibodies were demonstrated in the antiglobulin consumption test. Four similar cases, reported in the literature, are discussed in relation to this personal case. The findings are contrasted to the majority of cases of toxic "phenothiazine agranulocytosis".


The prevalence of hypertension in the United States today. The simplest response to the question, what is the prevalence of hypertension in the United States today?, is given by a currently popular slogan: 23,000,000 Americans have hypertension. It is clear that the problem is large in scale, but this figure alone is an insufficient guide to many practical issues. The prevalence ratio underlying this estimate is about 15% for adults 18 to 79 years of age. Actual prevalence ratios may vary widely in specific sub-groups of the population and in accordance with differing methods and criteria of ascertainment. For example, the actual numbers of hypertensives in the general population of the US, detectable by two-stage screening, may be closer to 8 or 9 million. On the other hand, the current failure generally of detection of hypertension would suggest that the entire adult population must be screened periodically - and this number is greater than 126 million. The implications of these considerations for undertaking screening and management programmes are discussed briefly.


Clinical use of immunosuppressive drugs: part II. In haematological diseases, insufficient data has been accumulated to evaluate the efficacy of immunosuppressive drug treatment in patients with erythroid aplasia or sideroblastic anaemia. Cyclophosphamide may be efficacious in inhibiting circulating anticoagulants in patients who need continued replacement of clotting factors. Azathioprine, 6-mercaptopurine, cyclophosphamide and vincristine have been used successfully in treating patients with idiopathic thrombocytopenic purpura, and some patients with auto-immune haemolytic anaemia may benefit from the addition of purine analogues. However, the use of immunosuppressive therapy seems to accelerate the presence of haematological malignancies in patients with macroglobulinaemia. In gastro-intestinal diseases, uncontrolled studies have shown nitrogen mustard, 6-mercaptopurine and azathioprine to be of modest benefit to patients with ulcerative colitis and Crohn's disease. In a controlled trial azathioprine plus prednisone proved more effective than prednisone alone in sustaining remission in patients with Crohn's disease. In patients with either chronic active hepatitis or primary biliary cirrhosis, however, there seems to be no benefit from immunosuppressive therapy for primary treatment of these diseases. Cyclophosphamide, azathioprine and methotrexate have all been used with some success in treating patient with uveitis, and in a controlled trial cytarabine has been shown to be beneficial to patients with herpes ophthalmicus. However, no benefit has been shown to patients with the eye changes of Graves' disease with either azathioprine or methotrexate. Patients with Paget's disease appear to be helped by mithramycin. Cyclophosphamide, chlorambucil and azathioprine are ineffective in treating patients with multiple sclerosis. 6-Mercaptopurine, azathioprine, methotrexate and cyclophosphamide have all produced some benefit in patients with myasthenia gravis, and some patients with idiopathic pulmonary haemosiderosis have responded to azathioprine, 6-mercaptopurine and cyclophosphamide. Alkylating agents have proved useful in treating some patients with asthma and in treating frequent relapsers among children with the nephrotic syndrome. In adults with membrano-proliferative glomerulonephritis some patients have responded to combination therapy with cyclophosphamide, azathioprine and corticosteroids. Immunosuppressive therapy is also indicated in prolonging graft survivals in patients receiving organ transplants. Drug toxicities of immunosuppressive agents are discussed. Their long-term effects, including mutagenic potential, have as yet not been fully elucidated.


Action of propranolol on arterial pressure and on cardiovascular reflexes. In the rabbit, administration of 500 mug (+/-) propranolol into the lateral cerebral ventricle resulted in rapid leakage of drug into the blood. The drug produced a small reduction in blood pressure at 2 and 4 hours after injection but because of the rapid leakage, this could have been due to its peripheral actions. To investigate possible central mechanisms of action which were independent of peripheral effects, we tested the action of intravenously administered propranolol on the reflex rise in TPR evoked in rabbits by graded Valsalva-like manoeuvres. This was performed in unanaesthetised rabbits with Doppler flowmeters for measuring cardiac output. Graded expiratory pressures (EP) were applied to the inlet and outlet tubes of the tracheotomised animal's respiratory valve and to the cuff around their thorax and abdomen. Administration of propranolol at two levels (168 +/- 35 ng/ml, and 240 +/- 33 ng/ml) for 1 hour had no effect on slope and threshold of the EP-TPR relationship. By contrast to the minimal effects on the reflex with propranolol, the EP-related rise in TPR was attenuated by clonidine. We conclude that propranolol does not lower blood pressure in the rabbit by attenuating sympathetic constrictor activity.


Blood pressure in middle-aged people in Albury and Melbourne - implications for screening. Prevalence rates of hypertension and its treatment in two population samples of middle-aged people, one in Albury and one in Melbourne, are described. On average, Italian-born subjects had lower pressures than their Australian-born neighbours. The proportions of Australian-born people in the two centres who had been previously diagnosed were respectively 22% and 32% and the proportions with diastolic blood pressure greater than or equal to 110 mm Hg were 13% and 9%. About one half of the latter had never been told they had high blood pressure. Postal follow-up in the second post-survey year indicated that treatment rates had nearly doubled, many people with relatively low survey pressures stating they were now on therapy. Screening may precipitate over-use of antihypertensive drugs. The recent finding that 80% of middle-aged people in Albury had been to a doctor in the previous 12 months and that in a high proportion the blood pressure had been measured suggests that control of hypertension in Australia may be best achieved by developing surveillance in the context of ordinary medical practice.


Morbidity and mortality in hypertension. There is substantial evidence of increased mortality and morbidity in hypertension. There is also clear evidence that antihypertensive treatment reduces the incidence of stroke and reduces the incidence of heart failure, but leaves myocardial infarction as a major cause of death and disability.


Hypertension and strokes.

Hypertension and strokes. Strokes are the third major cause of death in developed countries and are probably the major cause of severe chronic disability. Hypertension is the most important condition predisposing to strokes, and treatment of hypertension is of great importance in stroke prevention. The relationship of strokes to the degree of hypertension, and to age, sex, race and drug treatment is discussed.


Morbidity and mortality in untreated and treated hypertension: results from the Göteborg 50-year-old men study. Total mortality, and mortality and morbidity from myocardial infarction, have been followed in one-thrid (n = 855) of a totoal male population from the age of 50 to the age of 60. An initial screening examination was performed in 1963 when the participants were 50 years old. Mortality data were gathered from death certificates and autopsies. Fatal and non-fatal myocardial infarction was followed by means of an infarction register. The participants were divided into four groups according to blood pressure in 1963 and the mortality and morbidity data in these 4 groups were compared with those who had been on antihypertensive treatment from 1963 to 1973.


Mortality patterns in treated hypertension: results from Sydney Hospital. A group of hypertensive patients, diastolic blood pressure 110 mm Hg or more and under the age of 60 years at the time of presentation, has been followed at the Cardiovascular Clinic, Sydney Hospital since 1955. Changes in the causes of death have been observed during the twenty-year period of observation. Patients with severe and treatment-resistant hypertension are likely to die of cerebro-vascular accidents, patients presenting with advanced retinopathy with papilloedema and established renal failure die predominantly of uraemia. The fate of patients with moderate degrees of blood pressure elevation, without papilloedema and with normal renal function, seems to be to succumb to the complications of ischaemic heart disease.


New instruments for measuring blood pressure. The development of the conventional indirect method of blood pressure measurement was essentially complete by 1905, 70 years ago. The method has certain shortcomings, but these can be offset to a large degree by control over conditions of measurement, provision of proper apparatus, and intensive training of observers. Still, there are potential advantages which might be met by an acceptable automated device. An experimental evaluation of five such devices led to rejection of each  of them on grounds of inadequate measurement performance, mechanical failures, or both. Only the Random-Zero device (Hawksley) among the instruments tested, gave good performance in comparison with the conventional method and was free of serious mechanical disadvantages. Evaluation of new devices will continue to be of great importance, and proposed guidelines for such studies are reviewed.


Pre-treatment workup for antihypertensive treatment. The prevalence of primary and secondary hypertension and of heart and kidney involvement was thoroughly studied in 689 hypertensive subjects derived from a blood pressure screening examination of a total population sample of Swedish men (n = 7,452). The prevalence of secondary hypertension was found to be only 5%, the prevalence of surgically curable hypertension being even lower. Left ventricular hypertrophy and slight heart enlargement were each found in about one-third of the hypertensive patients, while severe heart enlargement, left ventricular hypertrophy on ECG, proteinuria, abnormal serum creatinine and urinary sediment were each found in about 5%. On the basis of these findings, a minimum pre-treatment workup in uncomplicated hypertension is proposed.


The problem of non-compliance in long-term antihypertensive therapy. Of 1,593 subjects admitted to the Australian National Blood Pressure Study 1 to 2 years ago, a substantial number (391 or 24.5%) ceased attending, in 85% of cases voluntarily. Withdrawal rates were very high in the first 4 months, settling to 5% per annum by the second year. Extrapolation to clinical practice is hazardous but contibutory factors elicited by questionnaire suggest certain management strategies: maximisation of efforts to enlist subject co-operation at the onset of treatment; management of treatment by family doctor or health centre with appointments flexible in time and infrequent in number; minimisation of doctors' ambivalence about treatment effectiveness and the withholding of information from the subject. It is inevitable that a proportion of subjects will reject long-term drug treatment. This adds further weight to the need for research on alternatives such as low salt diets.


[Epithelial proliferations in organ cultures of mouse lung treated with urethane and 3,4-benzopyrene]. The authors carried out some series of experiments under the conditions of organ cultures of lungs of mice, treated with urethane and 3,4-benzpirene. They succeeded lung culturinf up to 14-th and 21-th day. Growths of bronchial and bronciolar epithelium manifested at various degree were obtained in the lung extracts from mice, treated with urethane and 3,4-benzpirene. The most manifested proliferation was observed in extracts, treated with urethane at a dose of 10 mg/ml and 3,4-benzpirene -- 64 gamma/ml.


[Comparative studies of the vascularization of the posterior vena cava in some laboratory animals]. The author examined the posterior caval vena in four various areas in a rat, guinea pig, rabbit, cat and dog by applying Indian inkgelatine injection and subsequent preparation of histologic and total brighter preparations. The established differences in the vascularization were determined by the thickness of the true venous wall. The later increased with an increase of the body of the examined kind of animal on behalf of the adventitial longitudinal muscular layer at comparatively small differences in the thickness of the circular muscular layer in the media. There were no capilearies in the adventicial muscular layer of a rat and guinea pig. This layer was vascular, when the thickness of the true venous wall surpassed 70 microns. The most deeply penetrated capillaries were located almost equaly from the vascular lumen: 25 microns in the rabbit and 30 microns in the cat and dog.


[Method for obtaining bile from rats in a chronic experiment]. The authors make a critical review of the methods, described in the literature for multiple samples of bile from rats under the conditions of a chronic experiment. They present their own method. The results from the follow-up of the dynamics in the bile cholinesterase activity in one of the rats canulated by this method are described.


[Effect of cardiac glycosides on isoprenaline-induced heart changes]. The authors carried out studies on rats to examine the influence of preliminary treatment with strophanitine G on myocardial necrosis, induced by isoprenaline, evaluated by the changes in the number of leucocytes, erythrocyte sedimentation rate and the activity of SGPT in the peripheral blood, by the changes in the cardiac frequency and ECG as well as by the histologic and histochemical changes in the myocardium. It was established that strophanitine G potentiated the cardiotoxic action of isoprenaline, evaluated by hamatological, biochemical, electrocardiographic and histologic changes. The authors discuss the possible mechanisms of this interaction between digitalis glucoside and isoprenaline.


[Determination of the noradrenaline content and the noradrenaline metabolic rate in the brain of rats treated with lonetil]. Lonethyl1,2-methyl-3(para-etoxy-phanyl)-hynasolone-4, is an original Bulgarian preparation from the group of the tranquilizers. The authors examined its influence on the content of brain noradrenaline as well as on the velocity of noradrenaline exchange, which was the best index of sympathicus tonus. They used nonisotopic method of examining the velocity of noradrenaline exchange, which was based on measuring dimnution of the enodgenous mediator after blocking its biosynthesis. The studies were caried out on rats. The authors did not find changes both in the tissue concentration and in the velocity of noradrenaline exchange of animals, treated with lonethyl, which gave them foundation to include the preparation into the group of tranquilizers.


[Phagocytic function of the macrophages in leukemic animals]. The author carried out studies on 292 mice with transplantation leucosis. It was established that after alogenic transplantated leucosis the phagocytosis and digestion of the phaged objects by the peritoneal macrophages were enhanced. This effect lacked under syngenic conditions. The peritoneal cells of leucemic animals had higher phagocytosis of the purified peritoneal macrophages.


[Scanning electron microscopy of the lung in experimental collapse]. The author induced experimental lung collapse by means of ligating a bronch of a dog. The material was divided into six groups and was examined by a scanning electrone microscopy. Two phases in the development of the collapse were found. She indicated the advantages of the scanning electrone microscope in comparison with the light and the remaining electrone optical systems.


[Electron microscope studies of the kidney after its preservation at low temperatures]. Fragments the renal cortical part of white rats were frozened in two solutions: saline and 15% of glycerol. The preservation was made in liquid nitrogen (--196 degrees) for a period of 24 hours. The obtained results from the electrone microscopic examination showed that when freezing was performed without protective media, the intactness of the cells and their ultrastructural organization were destroyed. The nuclei preserved their intactness. When protective media (15% of glycerol) was used, then greater stability to low temperatures revealed the epitheleal cells, forming the glomerulus and intersticial tubules, but the most sensitive were the epithelial cells in the main part of the nephrone.


[Clinical and biochemical considerations on depressive states occuring during parkinsonian syndrome treated by L-Dopa]. From 17 observations of depressive illness occuring to parkinsonians treated with L. Dopa alone or associated with an inhibitor of peripheral decarboxylase, several types of depressive illness can be distinguished according to their date of appearance, their evolution with or without tricyclic anti-depressant drugs tertiary amine. According to the characteristics of these depressive illness, to the related locomotive state and to various monoamingeric hypothesises that are suggested both in the genesis of affective disorders and the mechanism of action of two biochemically related depressive aspects, a distinction already considered by other authors for endogeneous depressions.


[Ectoparasites delusions in old age (Ekbom syndrome)]. The writers present the case of a patient diagnosed as suffering from a typical delusion of parasitosis which is also called "Ekbom's Syndrom". They remind the characteristics of an encapsulated delusional system. They try to show the particular role of semantic significations played by the words "parasitis" and "skin" as a defense against a death or inferiority anxiety in old patients.


Effects of bone in vitro of bovine parathyroid hormone and synthetic fragments representing residues 1-34, 2-34 and 3-34. The biological activities of bovine parathyroid hormone (BPTH) and fragments comprising portions of its amino-terminal sequence have been compared in three different assay systems using embryonic rat bone in vitro. Whereas the 3-34 fragment was without significant activity the 1-34 fragment caused all the actions characteristic of BPTH 1-84, extending to bone previous evidence that the amino-terminal residues are sufficient for expression of the biological effects of intact parathyroid hormone. However, the relative potencies of the fragment and the intact hormone were different in the various systems. BPTH 1-34 showed relatively low osteolytic activity and induced anabolic effects in both osteoblasts and cartilage cells of cultivated embryonic mouse radii which were not evoked by the intact hormone. Further work is required to determine the mechanisms responsible for these interesting alterations in relative potency of fragment and native hormone.


The differential response of prostatic nucleolar and extra-nucleolar protein phosphokinase activities following androgen deprivation. Protein phosphokinase activities of nucleolar and extra-nucleolar compartments of rat ventral prostate nuclei were measured using the model acidic phosphoprotein, dephosphophosvitin, as substrate. Following orchiectomy, the activity in both of these fractions declined; however, the kinase activity of the nucleolus decreased at a much greater rate than that in the extra-nucleolar portion of the nucleus. Testosterone maintenance of castrated animals prevented this decline in activity. The regulation of protein phosphokinases which phosphorylate prostatic nucleolar acidic proteins may be an important mechanism in the androgen mediated activation of the nucleolus in this target tissue.


Rapid chromatography for quantitation of radioimmunoassayable 5alpha-androstane-17beta-ol-3-one and testesterone in ram, bull and boar serum. A rapid technique for the simultaneous determination of serum 5alpha-androstane-17beta-0l-3-one (DHT) and testosterone (T) was developed and validated. The procedure incorporates a chromatographic step prior to binding with a T-3BSA antiserum. Anakrom columns used to separate DHT from T also isolate other steroids quickly and efficiently. Utilizing this procedure, levels of both androgens have been measured in the intact ram, bull and boar. Concentrations of DHT and T expressed as mean +/- SE in ng/ml were respectively: ram, 0.14 +/- 0.03 and 4.96 +/- 0.80; bull, 0.10 +/- 0.01 and 3.92 +/- 0.80; boar, 0.71 +/- 0.11 and 5.58 +/- 0.64. Whether these minute quantities of serum DHT play important physiological roles, particularly in the boar, is unresolved. Monitoring DHT under varying experimental or pathological conditions may allude to its importance in the domestic male.


The mechanism of action of the thioureylene antithyroid drugs. A model incubation system containing purified thyroid peroxidase (TPO) was used to study the mechanism of action of the thioureylene anti-thyroid drugs--propylthiouracil (PTU), methylmercapto imidazole (MMI) and carbimazole. Two general types of experiments were performed: a) measurement of the inhibitory effects of the drugs on TPO-catalyzed iodination and on TPO-catalyzed oxidation of guaiacol, and b) studies of the metabolism of PTU and MMI by the TPO model system. The major observations can be summarized as follows: 1) The thioureylene drugs are potent inhibitors of TPO-catalyzed iodination of protein and tyrosine. Their potency increases greatly as the concentration of I- decreases. 2) The thioureylene drugs are also potent inhibitors of TPO-catalyzed oxidation of guaiacol, a reaction that does not involve iodide. 3) MMI and PTU are readily oxidized in the model incubation system when iodide is present but not in the absence of iodide. The rate of oxidation increased as the iodide concentration was increased from 10 to 100 muM. 4) Oxidation of PTU and MMI by the model incubation system is inhibited by relatively slight increases in the concentration of PTU and MMI. These drugs are capable of inhibiting their own and each other's metabolism. 5) Inhibition of iodination is competitively antagonized by iodide at low drug concentrations, but not at higher drug concentrations. 6) Inhibition of iodination by MMI and PTU may be either reversible (low ratio of drug to iodide), or irreversible (higher ratio of drug to iodide). In reversible inhibition the iodination is inhibited for a period which may be as brief as 2 min or as long as 20 min, but thereafter, iodination begins, and there is escape from inhibition. During the lag-period there is extensive metabolism of the drug. In the case of irreversible inhibition of iodination is inhibited completely or almost completely for 60 min, and drug oxidation during this period is relatively low. 7) Irreversible inhibition may be transformed into reversible inhibition by increasing the concentration of TPO or the concentration of iodide. However, increasing the concentration of H2O2 or of tyrosine does not overcome irreversible inhibition. On the basis of these findings and of current views concerning the mechanism of enzymatic iodination, a scheme is proposed for the mechanism of inhibition by thioureylene drugs of TPO-catalyzed iodination of protein and tyrosine.


The influence of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin in ovariectomized, estrogen-treated rats. The effects of systemic administration of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin was investigated using ovariectomized, polyestradiol phosphate (PEP)-injected rats bearing aortic catheters. Basal prolactin levels were elevated and similar after PEP administration for a period of 5 weeks, and an afternoon surge in plasma prolactin persisted for a period of 3 weeks before the magnitude of the surge diminished. The plasma estradiol levels were significantly higher for the 1100 and 1300 h samples than for the 1500 and 1700 h samples. Cornified vaginal epithelia were predominant in the vaginal smears of all animals throughout the 49-day experimental period. The cholinergic agonists arecoline, nicotine, and carbachol significantly inhibited the afternoon surge of prolactin. The muscarinic antagonist atropine resulted in a partial inhibition of the surge while the nicotinic antagonist mecamylamine did not have any inhibitory effect. The alpha-adrenergic blockers phenoxybenzamine and phentolamine and the beta-blocker propranolol inhibited the prolactin surge, with phenoxybenzamine being most effective. The administration of the serotonergic antagonist methysergide resulted in only a partial blockade of the afternoon prolactin surge. The data suggest that both the adrenergic and serotonergic systems may have a positive input in the afternoon surge of plasma prolactin. It appears that the cholinergic system does not play a significant role in the afternoon surge.


Progesterone and estrogen control of uterine prostaglandin dehydrogenase activity during deciduomal growth. Prostaglandin, dehydrogenase activity was determined in deciduomal and myometrial tissues during growth and regression of the deciduoma during pseudopregnancy. The hormonal control of prostaglandin dehydrogenase activity in these tissues was determined in experiments with ovariectomized pseudopregnant rats. Prostaglandin dehydrogenase activity for both prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in deciduomal and myometrial tissues increased during the growth of the deciduoma and decreased during the regression phase. No prostaglandin dehydrogenase activity was detected in non-decidualized pseudopregnant rat uteri. In ovarictomized pseudopregnant rats, progesterone and estrogen increased prostaglandin dehydrogenase activity for PGE1 in the deciduoma and myometrium; no synergistic action of the hormones was observed. Progesterone increased prostaglandin dehydrogenase activity for PGF2alpha in the deciduoma, but had no effect in the myometrium. The increases during decidualization in dehydrogenase activity for PGE1 and PGF2alpha, and the enhanced inactivation of these luteolytic substances would provide an explantation for the prolonged pseudopregnancy which results from decidualization of the uterus.


Relaxin concentrations in pig plasma following the administration of prostaglandin F2alpha during late pregnancy. Concentrations of relaxin in peripheral plasma were measured following the injection of 10 mg of PGF2alpha to pregnant sows on day 112 of gestation. The mean concentrations of relaxin before injection of PGF2alpha were less than 13 ng/ml. Relaxin concentrations increased sharply to a mean of 104 ng/ml by 45 min following injection of PGF2alpha and then fell rapidly to a mean of 40 ng/ml 4 h later. Following this initial peak of relaxin, there was a gradual rise and fall of relaxin concentrations during the day preceding parturition. The levels of relaxin during this period were also influenced by PGF2alpha administration since the mean levels of relaxin were significantly lower from the 22nd through the 10th h before parturition in pigs given PGF2alpha, than in pigs given saline.


Actions of angiotensin II antagonists upon aldosterone production by isolated adrenal glomerulosa cells. The biological activities of angiotensin II antagonists upon basal and angiotensin II-stimulated aldosterone production were evaluated in an isolated canine glomerulosa cell preparation. The most potent competitive antagonist of angiotensin II-stimulated aldosterone production was the [Sar1, Ile8]derivative of angiotensin II. However, this peptide was also a partial agonist at concentrations required to inhibit the steroidogenic effect of angiotensin II on dog adrenal cells, and never reduced aldosterone production to basal levels. On a molar basis, the [Sar1, Ala8] and [Sar1, Gly8]derivatives of angiotensin II were relatively less potent as competitive inhibitors of angiotensin II-stimulated aldosterone production. However, the [Ala8] and [Gly8]-analogues did not exhibit significant agonist activity and were therefore more effective antagonists of angiontensin II-stimulated aldosterone production. These results suggest that increased length of the aliphatic side chain at the C-terminus of angiotensin II antagonists is accompanied by enhanced affinity for the receptor site, but also by increased agonist activity upon aldosterone synthesis. The actions of angiotensin II and [Des-Asp1]angiotensin II upon aldosterone production were inhibited identically and completely by [Sar1, Ala8]angiotensin II, and identically, though incompletely, by lower concentrations of [Sar1, Ile8]angiotensin II. The heptapeptide antagonist [Des-Asp1, Ile8]angiotensin II was much less potent than [Sar1, Ile8]angiotensin II as an inhibitor of the actions of both the heptapeptide and octapeptide agonists. The antagonist activity of six angiotensin II analogues at the adrenal level, determined by the concentration required for 50% inhibition of maximum aldosterone secretion, correlated well with their antagonist activity measured upon isolated smooth muscle. These observations demonstrate that the octapeptide antagonists are more effective than the heptapeptide antagonists upon angiotensin II-stimulated aldosterone production, and that angiotensin II receptors in smooth muscle and adrenal cortex exhibit generally similar responses to angiotensin II antagonists. Also, these results do not support the proposal that the [Des-Asp1]heptapeptide is an important intermediate in the action of angiotensin II upon adolesterone production in the adrenal glomerulosa cells. The production of aldosterone by dispersed zona glomerulosa cells in vitro provides a highly sensitive and biologically appropriate response for evaluation of the agonist and antagonist properties of angiotensin II analogues upon the adrenal gland.


Lack of gonadotropic activity in the rabbit blastocyst prior to implantation. Recent reports of an LH-like hormone in the rabbit preimplantation blastocyst and of elevated serum progesterone levels in the presence of unimplanted blastocysts prompted us to characterized further the biological activity of the presumed gonadotropin. Progesterone was measured by a highly specific radioimmunoassay in sera obtained from pregnant and pseudopregnant rabbits after mating (day 0) to fertile or vasectomized males. On days 3, 4, 5, and 6, which represent the preimplantation period, mean progesterone concentrations (ng/ml +/- SE) were 4.3 +/- 0.7, 5.1 +/- 0.5, 6.8 +/- 1.1, and 9.0 +/- 1.9 in 5 pseudopregnant rabbits and 4.1 +/- 0.4, 6.7 +/- 0.6, 5.9 +/- 0.9, and 7.0 +/- 0.8 in 7 pregnant rabbits. In a separate experiment, serum progesterone concentrations in 6 pseudopregnant and 8 pregnant rabbits were 10.1 +/- 0.7 ng/ml and 13.7 +/- 1.1 (P less than 0.02), respectively on days 11-12. Thus, serum progesterone concentrations were not different in pregnant and pseudopregnant rabbits before the time of implantation (day 7), but were higher in pregnant rabbits after implantation. Blastocysts obtained on day 6 and incubated with a cell suspension of immature rat ovaries failed to stimulate the accumulation of progesterone in medium, in contrast to hCG, which was active even in the presence of blastocysts. Day-6 blastocysts also failed to stimulate the accumulation of testosterone from decapsulated rat testes and of progesterone from rabbit ovarian tissues in vitro. A gonadotropic effect of the conceptus can be observed in the rabbit within 4 to 5 days after implantation. However, we find no evidence for the existence of an LH-like hormone in the preimplantation blastocyst which stimulates the rabbit ovary to secrete progesterone.


Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus. The metabolism of [4-14C]androst-4-ene-3,17-dione, [4-14C]5alpha-androstane-3alpha,17beta-diol and [1,2-3H]5alpha-androstane-3alpha,17beta-diol, 3,17-disulfate in the 105,000 X g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally "feminized" (increased 5alpha-reduction and decreased 6beta- and 16alpha-hydroxylation of 4-androstene-3,17-dione, decreased 2alpha-, 2beta-, 18- and 7beta-hydroxylation of 5alpha-androstane-3alpha, 17beta-diol and induced 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol,3,17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of "feminizing factor" from the female pituitary that is responsible for the "feminization" of the basically "masculine" type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary "feminizing factor" is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens.


Effects of ovariectomy and season on plasma luteinizing hormone in mares. Six pony mares were ovariectomized (OVX) on day 16 of diestrus during June and July, 1972, to study short term changes in plasma luteinizing hormone (LH) concentrations. Plasma LH was higher (P less than .05) 3 days after OVX (1.76 ng/ml) than the day after OVX (1.01 ng/ml), and a gradual increase occurred over the first 2 weeks. Elevated plasma LH concentrations similar to mid-estrus levels were present from the 2nd to 11th week post-OVX. In another experiment, the same 6 OVX mares were bled once a month from February, 1973, to January, 1974, to study long-term changes in plasma LH in relation to the anestrous (November-April) and breeding seasons (May-October). Mean monthly plasma LH concentrations in OVX mares during all months of the anestrous season were lower (P less than .05) than mean monthly plasma LH during the months of June-September of the breeding season. During the transition from anestrous to breeding seasons (April, May) and breeding to anestrous seasons October, November), mean plasma LH concentrations were not significantly different between April and May (1.39 vs 1.84 ng/ml) and between October and November (3.02 vs 2.56 ng/ml), but April and May levels were lower (P less than .05) than October and November levels. Mean monthly plasma LH levels in OVX mares during the anestrous season were similar to those in intact mares during the anestrous season and at mid-diestrus during the breeding season. Mean monthly plasma LH levels in OVX mares during the breeding season were similar to plasma LH levels at mild-estrus in intact mares. These data indicate the presence of inhibitory (most likely progesterone) and stimulatory (most likely estrogen) influences from the ovary which modulate the endogenous LH pattern in mares during the breeding season.


Enzymatic sulfation of steroids: I. The enzymatic basis for the sex difference in cortisol sulfation by rat liver preparations. Liver cytosols from female rats contained 6-8 times as much cortisol sulfotransferase activity as those from males. The reaction product, with both sexes, appeared to be cortisol-21 sulfate. Liver cytosols from male and female rats showed different substrate preferences when tested with cortisol, estradiol-17beta, testosterone, and dehydroepiandrosterone, suggesting that they contained different steroid sulfotransferases. Fractionation of cytosols from female rats on DEAE Sephadex A-50 columns resolved 3 steroid sulfotransferases, or families of steroid sulfotransferases (STI, STII, and STIII). These enzymes exhibited different substrate preferences. STI and STIII had the greatest preferences for cortisol, although none of the enzymes was restricted to the glucocorticoid. Fractionation of cytosols from males resolved 2 sulfotransferases which eluted at salt concentrations identical to STII and STIII from females. Study of the development of cortisol sulfotransferase activity with age showed little enzyme activity in rats of either sex at 2 days after birth. Enzyme activity developed in parallel in both sexes until 30 days after birth. Then the sulfotransferase activity began to rise in females and to drop in males. By day 50-55 both sexes attained adult enzyme levels. STII was the major enzyme in all immature animals. STIII was also present, but STI was absent. In male rats STIII activity began to rise by day 30. Soon after, STII activity began to drop. By day 55 adult male patterns developed. STI was the major enzyme in females by day 30. In ensuing days all 3 enzyme levels rose, until by day 50 adult enzyme patterns and levels were attained. The data suggest that the ovaries stimulated production of all 3 sulfotransferases and that the testes suppressed production of STII (and perhaps STI). Preliminary studies with gonadectomized rats supported the suppressive role of the testes, but suggested that the ovaries were not the only factor controlling sulfotransferase production in female rats.


Sex differences in the effects of surgical isolation of the medial basal hypothalamus on linear growth and plasma growth hormone levels in the rat. The effects of surgical isolation of the medial basal hypothalamus (MBH) on linear growth and plasma growth hormone (GH) levels were studied in adult male and female rats. Whereas MBH isolation resulted in reduced linear growth in males, increased growth resulted in females. These effects were apparent in males 4 weeks after surgery and in females at 10 weeks. The altered growth rates persisted throughout the 28 weeks of the study. MBH isolation in both sexes led to increased food intake, obesity, and atrophy of reproductive tract organs. Non-stress plasma GH levels were unchanged at 4 weeks in both sexes but were elevated at 10 and 26 weeks in females and at 19 and 26 weeks in males. Serial samples of tail vein blood were obtained at 4-h intervals for 44 h from MBH-isolated and shamoperated females at 17 weeks postoperatively, and from similar groups of males at 19 weeks. GH levels were elevated in MBH-isolated rats of both sexes during the afternoons and evenings. Only sham-operated females showed evidence of a 24-h rhythmicity in circulating GH levels. The amplitudes of trough to peak excursions were similar in MBH-isolated and control females, but these excursions were reduced in MBH-isolated males. Although opposite effects on linear growth were noted in the two sexes, the resulting growth rates of operated males and females were similar, suggesting that MBH isolation disrupts mechanisms that normally regulate sex-specific growth patterns. Despite the sex difference in growth responses, MBH isolation caused an eventual increase in plasma GH levels in both sexes. Therefore, it is unlikely that the sex difference in growth responses is attributable exclusively to corresponding changes in circulating GH levels. A reduction in levels of circulating gonadal steroids may be an important factor. The elevations in plasma GH levels observed in both sexes suggest that MBH isolation interferes with mechanisms which inhibit GH secretion.


Pulsatile growth hormone release in the rat: failure to demonstrate a correlation with sleep phases. Concurrent 5-hour profiles of growth hormone (GH) secretion and sleep phases were obtained in 7 rats chronically implanted with right atrial cannulae, and electroencephalographic electromyographic, and electroculographic electrodes. Hormone profiles confirmed pulsatile secretion of GH. Secretory GH episodes occurred every 3 to 4 hours and peaks generally exceeded 100 ng/ml, and, in 14 of the 21 troughs recorded, GH was unmeasurable (less than 1 ng/ml). The comparison of hormone profiles and concurrent sleep patterns excluded a temporal relationship between episodic GH secretion and sleep cycles, while scattergrams of hormone values plotted against preceding sleep phase durations also failed to demonstrate a relationship.


Selective suppression of FSH by testicular extracts. Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH.