Periodic sleep apnea: chronic sleep deprivation related to intermittent upper airway obstruction and central nervous system disturbance. Periodic sleep apnea may be due to repeated episodes of upper airway obstruction in patients who have a short thick neck and/or large jowls. Apnea due to complete cessation of breathing may occur to a lesser extent. Anaylsis of the sleep electroencephalogram shows that these patients rarely achieve deep sleep and have less stage 1-REM sleep than normal subjects of comparable age. They are chronically sleep-deprived, a manifestation expressed by daytime somnolence, chronic fatigue and often by personality disturbances marked by paranoia, agitated depression and hostility. The definitive diagnosis of this syndrome may be established by monitoring during sleep, the electroencephalogram, measuring abdominal excursions through a mercury-in-Silastic-strain gauge and recording air flow at the nose by means of a thermocouple. As demonstrated by other investigators, chronic hypoventilation during sleep leads to both pulmonary and systemic arterial hypertension, which may produce generalized cardiac enlargement and congestive heart failure. The abnormalities in the periodic sleep apnea syndrome are abolished by establishing a patent airway either through tracheostomy or weight reduction.


Xerotomographic diagnosis of central bronchogenic carcinoma. Xerotomography was used to examine 14 patients with substantial pulmonary opacities, in whom the diagnosis of bronchogenic carcinoma had been suspected. Xerotomography was valuable because it provided excellent delineation of the tracheobronchial tree, which assisted in differentiation of benign from malignant lesions. Malignancy was suggested by: 1) amputation, 2) eccentric narrowing of the bronchus, 3)irregularity of the bronchial wall, 4)presence of an intraluminal mass. Mediastinal and hilar node enlargement could also be assessed. The use of these criteria allowed a correct preoperative diagnosis in 12 of 14 patients. Due to the high radiation dosage, this method is not suitable for use as a screening procedure.


A new radiologic sign of subpulmonic effusion. A new radiologic sign of subpulmonic effusion is described. That is obliteration of the intrapulmonary blood vessels which are seen below the level of the diaphragmatic dome. One hundred normal chest films are reviewed as well as nine patients with subpulmonic effusions. In three of the patients with subpulmonic effusions, this sign was the first evidence of pleural effusion.


Bronchial brushing through the flexible fiberoptic bronchoscope in the diagnosis of peripheral pulmonary lesions. Bronchial brushing was performed concomitantly with transnasal flexible fiberoptic bronchoscopy in 44 patients with localized peripheral pulmonary lesions and absence of visible bronchial abnormality down to subsegmental level. Fluoroscopic confirmation of brush placement was obtained. A diagnosis of malignancy was made by bronchial brushing in 12 of 23 patients (52 percent) proved to have neoplasm, although diagnostic accuracy rose to six of seven patients (86 percent) in the final quarter of the study. There was no relationship between diagnostic accuracy and tumor location. Diagnostic accuracy was highest for squamous cell carcinoma, intermediate for adenocarcinoma, and lowest for undifferentiated carcinoma. A diagnosis of tuberculosis was made in two of 21 patients found not to have malignancy, and bronchial brushing was the only procedure to yield diagnostic material in these two patients. There were no false-positive cytologic examinations and no complications. Fluoroscopic control of placement of the bronchial brush passed through the fiberoptic bronchoscope allows a single, highyield, diagnostic procedure to be performed with minimal risk to the patient. In selected cases, thoracotomy may be avoided by this procedure.


Evaluation of skeletal muscle capillary basement membrane thickness in congestive heart failure. Although it has been demonstrated that during isotonic grip exercise patients with chronic congestive heart failure have an abnormally reduced forearm oxygen consumption resulting from a depressed forearm flood flow, there may be additional etiologies of this abnormality. To explore this possibility biopsies of the pronator teres muscle were taken in eight control subjects with normal cardiac hemodynamics and in seven severely decompensated chronic congestive heart failure subjects. Each sample was fixed, stained, and photomicrographs of the sections were obtained and the capillary basement membrane thickness determined. The control capillary basement membrane thickness was 3028 plus or minus 187 A (mean plus or minus SEM) compared to the congestive heart failure thickness of 4924 plus or minus 538 A (pless than .01). It is possible that the increased basement membrane thickness in congestive heart failure may result from or actually cause the depressed oxygen consumption by altering diffusion.


Use of artificial heart for basic cardiovascular research. Improved technology in artificial heart development and implantation studies in unanesthetized calves have stimulated a new model for cardiovascular research. Independent control of the left and right ventricles, replacement of the natural right atrium with an artificial atrium (with a compliant inner diaphragm) are illustrated as examples of new methods to study the cardiovascular system. Preliminary results in three calves suggest that synchronous ventricular pumping is not required for total circulatory maintenance. In four calves a passive artificial right atrium was shown to decrease outflow obstruction to the right ventricle. A compliant inner deiapragm demonstrated a reduction in the amplitude of the atrial C and V waves. The effects of volume and drug infusion on peripheral vascular response in the presence of controlled artificial heart pumping (which does not respond to direct neural or hormonal influences) further illustrate the efficacy of this preparation as a new model for cardiovascular research.


Percutaneous transfemoral coronary arteriography; prevention of morbid complication. During a six-year experience involving 3,089 selective coronary arteriograms (99 percent by the percutaneous transfemoral method), modifications of technique have reduced the incidence of morbid complications. Modifications have involved guidewire technique, systemic heparinization, attention to spontaneous catheter back-bleeding after guidewire removal, and caution in approaching sever main left coronary artery lesions.


Aneurysm of the body of the left atrium presenting with chest pain. A patient with aneurysm of the body of the left atrium presenting with angina pectoris and mild congestive heart failure, but completely normal coronary arteriograms, is reported. A deverticulum seen in the left ventricular angiogram, read as a ventricular diverticulum, was found at surgery to be an aneurysm of the body of the left atrium. The possible etiologics and complications of the left atrial aneurysm are briefly discussed.


Pulmonary artery compression due to acute dissecting aortic aneurysm: clinical and angiographic diagnosis. Clinical and angiographic features simulating acute massive pulmonary embolism, the result of compression of the right and main pulmonary arteries by a dissecting hematoma, are described in a 52-year-old white woman.


Prolapsed mitral valve associated with the Holt-Oram syndrome. The association of hypoplastic thumb and atrial septal defect, (Holt-Oram syndrome) with a prolapsed mitrial valve is described. Recognition of this association adds further support to the concept that the prolapsed mitrial valve syndrome is not necessarily an isolated cardiac disorder but may be part of a more generalized heritable disorder of connective tissue.


Transient eosinophilic pneumonia secondary to use of a vaginal cream. Various drugs have been implicated in the development of transient eosinophilic pneumonia or Loeffler's syndrome. We present such a case occurring in a woman who had been using a sulfanilamide-containing vaginal cream.


Second degree entrance block in intermittent ventricular parasystole. In a 21-year-old healthy man, there may be a second degree entrance block occasionally of 2:1 nature resulting in intermittent ventricular parasystole. The refractory period of the ventricular-ectopic (V-E) junction in this case was markedly longer than the ventricular muscle except the V-E junction, but much shorter than the whole length of the parasystolic cycle.


Mediastinal histoplasmosis with abscess. A mediastinal mass of clinically undetermined nature was found at autopsy to be an enormous abcess due to secondary infection in granulamatous caseating mediastinal nodes caused by Hitosplasma capsulatum. Other complications of mediastinal histoplasmosis are briefly reviewed.


Delayed opening of Beall mitral prosthetic valve detected by echocardiography. A 47-year-old woman in normal sinus rhythm developed frequent pulse deficits, immediately following mitral valve replacement with a Beall disc prosthesis. Emergency bedside simultaneous tracing of echocardiogram, phonocardiogram and arterial pulse revealed a delayed opening of the disc with various timing intervals in diastole, and suggested some form of interference with normal disc motion. An interfering papillary muscle remnant was later confirmed and corrected by reoperation.


Disseminated Actinomycosis.

Disseminated Actinomycosis. A patient with multiple subcutaneous abscesses was found to have disseminated actinomycosis. No predisposing cause was identified. No defects in immunity were found. His disease responded promptly to penicillin therapy.


Paradoxical septal motion in a patient with pulmonic stenosis. This case will demonstrate abnormal (paradoxical) septal motion in a 31-year-old woman with an isolated pulmonary valvular stenosis. The right ventricular volume overload was exluded by the shunt series, special angiographic studies and at surgery. The echocardiographic abnormality persisted during a restudy three months after surgery.


Scleroderma cerebritis, an unusual manifestation of progressive systemic sclerosis. A 42-year-old female with scleroderma experienced two exacerbations in which behavioral changes were the main clinical features. On both occasions she presented with paranoid delusions, perceptual aberrations, and disorientation. After treatment with corticosteroids, the patient's mental status returned to normal, and her electroencephalogram showed an increase in alpha wave frequency, which is consistent with a resolving delirium. Unlike systemic lupus erythematosus, scleroderma rarely involves the central nervous system. This case illustrates an unusual manifestation of progressive systemic sclerosis, primary cerebral involvement which presented as an acute organic brain syndrome. Connective tissue diseases, notably systemic lupus erythematosus, often present neuropsychiatric symptoms. Despite the fact that there appears to be a clinical and pathological continuum among the connective tissue diseases, an organic psychosis rarely occurs in progressive systemic sclerosis (scleroderma. Described here is a patient with scleroderma in whom behavioral abnormalities were the main features of two exacerbations of the disease.


The awareness of risk and personal relevance in alcoholics. From the perspective of health professionals, the estimated nine million alcoholics in America are engaged in repetitive health-avoidance behavior. The purpose of this study was to asses whether alcoholics were themselves aware of the risk-taking implications of their drinking, particularly in view of the denial clinically attributed to alcoholics. Horn's Smoker's Self-Testing Kit, modified to measure respondents' attitudes toward excessive drinking and its consequences, was administered to 61 alcoholic inpatients. This instrument evaluates awareness of the health hazards of excessive drinking, awareness of the seriousness of alcoholism as a health problem, awareness of its personal relevance, and the value of stopping, concern with mastery of the drinking problem, and belief in capability for stopping. The results indicated that during sobriety these alcoholics definitely acknowledged the health hazards of excessive drinking, the seriousness of the problem, its personal relevance, and the value of stopping. However, subjects generally anticipated great difficulty in making any significant change in their self-destructive drinking patterns.


Treatment of phenothiazine induced bulbar persistent dyskinesia with deanol acetamidobenzoate. The late manifestation of neuroleptic-induced dyskinesia (persistent dyskinesia) is an irreversible complication of long-term treatment that is poorly understood and difficult to treat. Recently, a theory of dopamine receptor hypersensitivity in the dopaminergic-cholinergic system has suggested an explanation of choreiform movements and, thus, an implication for the management of persistent dyskinesia. The case presented is that of bulbar persistent dyskinesia in a patient who had been prescribed a phenothiazine derivative for eleven years; his symptoms improved with the use of deanol, which probably converts to acetylcholine after crossing the blood brain barrier. This improvement suggests that deanol may shift the neuroleptic-induced dopaminergic-cholinergic system unbalance toward equilibrium by matching predominant dopaminergic effect or by enhancing deficient cholinergic action in the dopaminergic-cholinergic system. This isolated finding needs to be confirmed by more research in neuropharmacology.


Determining what heroin means to heroin addicts. For purposes of treatment, description, typological and psychological instrumentation, agreement judgements were obtained from 20 heroin addicts and 51 normal controls on data matrices constructed from sentences obtained from the heroin addicts. Correlations demonstrate controls are similar to one another and qualitatively different from addicts. Multidimensional scaling techniques and perspective summary maps demonstrate these differences and provide the technology for developing a typology of addicts for future studies. Heroin addicts have an inability to tolerate frustration, a depressive core, a negative sense of identity and a sense of futility and isolation. Heroin addicts deviate from normals at well beyond the p less than .001 level of significance in using heroin to handle problems that normals handle in other ways. For treatment of the addict, the drug must be withdrawn and new ways of coping with old needs must be taught. This matrix qualitatively demonstrates and pinpoints the deficiencies and excesses of the addict which need treatment. The epidemiology of drug use relating narcotics, delinquency, and social policy has been well documented (Chein, 1964). One major problem posed by narcotic addition is the problem of getting people to stay off drugs (withdrawal). Another major problem is the alleviation of the human misery that motivates drug use (rehabilitation). (Jaffee, 1970, Chein, 1964). In addition to the above, a problem of recent importance has been the key question of whether or not the Vietnam addicts differ basically from addicts socialized in the drug culture in the united States. (Walsh, 1971). Numerous investigators have discussed personality and addiction (Chein, 1964; Eddy, 1965, Jaffee, 1970) usually from the vantage point of the investigators. This study attempted to describe the personalities of heroin addicts from the vantage point of the addicts using instruments borrowed from descriptive semantics. (Goodenough, 1967; Stefflre, Reich, Wendell, 1967). The purpose of the pilot study was to: 1) determine where heroin positioned in the conceptual frames of reference of heroin addicts and non-addicted control subjects, 2) to establish a classification procedure for determining subtypes of heroin addicts, and 3) to demonstrate the usefulness of a linguistically based instrument in application in clinical psychiatry.


On the learning process in medical students disturbances as a symptom and a disease. The role of emotional factors in the learning process has been recognized by the student as well as the educator in medicine. The medical student may develop disturbances in learning under appropriate circumstances. These disturbances may be the symptom of a disease but not the disease itself, or the disease but not the symptom, or the disease and the symptom at the same time. The most frequently encountered symptoms of the disturbance among the medical students include: loss of interest in studying; decrease in motivation for medicine; difficulties in concentration and retention; student's difficulty in applying himself; selective disturbance in learning certain subjects within medicine; impairment in the capacity to discriminate relevant from irrelevant data; and the tendency toward obsessive thinking and compulsive actions. The role of fantasies in these disturbances is explored. The development of the capacity to learn and some etiological considerations in its disturbances are formulated.


The portrait of a murderer.

The portrait of a murderer. A portrait is presented of an impulsive, violent and paranoid young murderer. A review of the psychiatric literature for indicators which address themselves to predicting murderous behavior yields a broad spectrum of theories and observations. The portrait presented includes a composite of many of the indicators which the various authors have described. The patient presented is felt to represent a discernable stereotype, and the predisposing factors which are viewed as contributiing to his murderous behavior are offered and given priorities.


Brain damage associated with chronic alcoholism. Three hypotheses were discussed concerning the nature of the neurological and psychological disorder in chronic alcoholics. The evidence was not supportive of a diffuse or generalized deficit. The hypothesis that the right hemisphere of the brain is more vulnerable than the left hemisphere to disruption from chronic alcohol abuse was also considered. Although provocative, there existed significant findings which did not coroborate this notion. The third hypothesis considered maintained that chronic alcoholics suffer from an anterior-basal focus of impairment. The evidence in support of this notion was substantial from both the neurological and psychological research, suggesting that alcoholics exhibit a pattern of disorders similar to that manifested by more deteriorated persons suffering from the Korsakoff psychosis.


Demorgraphic characteristics in affective disorders. One hundred and fifty four consecutively evaluated new and return psychiatric outpatients were examined by the same interviewer using a detailed, precoded questionnaire based on the diagnostic criteria for psychiatric research proposed by Feighner et al. Affective disorders were present for 75% of the patients and were associated with older age, divorce and a shorter duration of marital status. Race, sex, education and income levels were not related to the presence of affective disorders. Sixty patients with diagnoses of primary affective disorders and 56 patients with diagnoses of secondary affective disorders were identified and studied. Secondary affective disorders were found to be associated with males, younger age (under 34), unmarried marital status, and lower income levels. Primary affective disorders were associated with higher annual incomes (over +4,000) and fewer individuals with a "some high school only" education. Forty one patients with diagnoses of unipolar primary affective disorders were examined. Sex, race, age, marital status and duration of marital status did not vary for the two groups and were not associated with polarity of affective disorders. Lower education and annual income levels both were demonstrated for patients with bipolar primary affective disorders.


[A case of "miliary" Crohn's disease (author's transl)]. A case of "milary" Crohn's disease in a 53-year-old woman is described. There were numerous epithlioid-cell, non-caseous serosal granulomas in the jejunal and terminal ileal regions. There were, furthermore, immediately adjoining the epithelioid-cell granulomas, granuloma-like collections of brown fat tissue, a previously undescribed coexistence.


[Goodpasture's syndrome (author's transl)]. Goodpasture's syndrome occurred in six patients (four men and two women) aged 18-32 years. Haemoptysis, anaemia and abnormal urinary findings with erythrocyturia were the first signs of the disease in five instances, in one the renal signs predominated. In five patients the disease took a malignant course with uraemia developing within six weeks. One patient is in a spontaneous remission eleven months after the onset of the disease. Three patients died of recurrent haemoptysis (non-nephrectomised), two nephrectomised patients are still alive half a year and three and a half years later, respectively. A typical linear IgG-, beta1A, alpha2D and beta1E deposition along the glomerular capillaries was demonstrated immunohistologically in all subjects. Of three lung biopsies one also had typical IgG and beta1A-positive linear fluorescence along the alveolar basal membrane. Immunoglobulins with basal membrane antibody activity were eluted from renal homogenates in two patients, basal membrane antibody activity in serum was demonstrated only in one of three patients.


[Recurrences of agranulocytosis (author's transl)]. Since agranulocytosis is in principal a curable condition with modern treatment, recurrences must be reckoned with in sensitized patients. They are relatively frequent. Recurrence occurred in eight of 17 patients. One patient had three recurrences, the last one 18 years after the first. In an Italian woman nine recurrences due to aminophenazone occurred within six years. Since sensitization does not disappear spontaneously, a recurrence may also occur in patients who have had one episode of agranulocytosis. Sensitizing drugs must be strictly avoided to prevent such recurrences: their presence in drug mixtures must be guarded against. But once a patient is sensitized he may react with agranulocytosis to various types of drugs.


[Thyroid tumours with a long clinical course: diagnostic and therapeutic aspects (author's transl)]. Thin-needle biopsy allows morphological examination which is free of complications. It is, therefore, suitable as a routine out-patient diagnostic measure in diseases of the thyroid. A biopsy should be taken whenever there is the slightest indication, so that clinical changes which have existed for prolonged periods can be included, even if there is no suspicion of tumour.  In this way, thyroid tumours with an unusually long course will be diagnosed cytologically. Three such cases are reported: a papillary adenocarcinoma, a medullary carcinoma and a Hürthle-cell tumour.


[Total thyroidectomy in progressive endocrine exophthalmos (author's transl)]. In 26 patients with progressive endocrine exophthalmos thyroidectomy was performed after conservative treatment had failed. This treatment was successful in all but two patients. The success of therapy depended on the complete removal of all thyroid tissue. If the ophthalmic changes were more than a year old or if there had been preoperative irradiation of the orbit regression of the exophthalmos was less satisfactory.


[Thiamine and thiamine pyrophosphate in obsese patients during partial and total fasting (author's transl)]. The development of vitamin B1 (thiamine) deficiency was investigated in 17 obese patients in the course of a 1000 calory diet or during total fasting for a fortnight. Compared with normal persons no changes of concentrations of total thiamine, TPP, and pyruvate in the blood; thiamine excretion in the urine, or activiation coefficient of the eryhrocyte transketolase (alphaETK) were observed during the reducing diet. However, during a fortnight's total fasting all values decreased significantly to those of thiamine deficiency. The thiamine pyrophosphate (TPP) levels in the blood dropped from the 1st to the 14th day, whereas the alphaETK rose accordingly and the pyruvate levels showed a delayed rise. Total thiamine content of the blood and thiamine excretion in the urine only showed significantly different values when comparing the 1st and the 14th day. There was no dependency of thiamine excretion on urinary output. Clinical symptoms of thiamine deficiency could be demonstrated in no case.


[Serum level and urinary excretion of 14C-thiamozol in patients with hyperthyroidism (author's transl)]. 2-(14C) Thiamazol (Favistan) was administered intravenously in a therapeutically subthreshold dose to seven control subjects and five patients with hyperthyroidism. In both groups the reduction of plasma radioactivity occurred with at least two exponentials. Half-life was calculated to be 35 minutes for the faster and 28 hours for the slower process in the control group, and 12 minutes and about 20 hours, respectively, in the hyperthyroid patients. Forty-eight hour urinary excretion of the injected radioactive material was about 80% for the hyperthyroid patients and 87% for the control subjects. Maximal activity in urine occurred about six hours after injection. There was practically no demonstrable plasma-protein binding of the drug in in-vitro experiments. As the pharmacokinetics of the drug are not influenced in thyroid disease, there is apparently no need to adapt thyrostatic dosage in hyperthyroid states.


[Lymphogranulomatosis of the recto-sigmoid region: a rare primary manifestation and localization (author's transl)]. In a 46-year-old patient lymphogranulomatosis was found localized exclusively in the rectosigmoid region. The stenosing tumour was removed by resection of the sigmoid colon. No further evidence of abdominal Hodgkin's disease was found at a second operation when splenectomy and careful searching for affected lymph nodes were performed.


[Basal and reactive proinsulin and insulin secretion in overweight women (author's transl)]. Serum proinsulin and insulin levels were measured on 55 normal or overweight women before and after oral glucose administration. The proinsulin proportion of basal total insulin was 70% in women of normal weight. With increasing overweight the relation shifted in favour of insulin. After stimulation with glucose, proinsulin levels were significantly raised, analogous to total insulin, but les marked than the latter. The increased total insulin excretion in obesity was, therefore, largely due to insulin and less to proinsulin. The greater the overweight the later maximal insulin levels were reached after oral glucose administration: proinsulin peaks occurred later than insulin peaks. Measurement of areas from single values and corresponding times for proinsulin and insulin, after stimulation, indicated their significant correlation with the degree of overweight. In women of more than 70% overweight (Broca index), reactive proinsulin and insulin excretion decreased again despite an increase in body weight. They had a definitely reduced carbohydrate tolerance. After reduction in body weight previously increased proinsulin levels fell again. The significance of higher proinsulin levels in fasting subjects, which increased after stimulation and with overweight but were in percentage terms less than those of reactive insulin, remains unexplained.


[Serum lipase activity and endoscopic retrograde pancreatography in chronic pancreatitis and pancreatic neoplasm (author's transl)]. Serum lipase activity was measured in 360 patients with the clinical suspicion of chronic pancreatic disease, 60 of them also having the lipase evocation test (serum lipase activity before and after pancreatic stimulation with secretin and pancreozymin). Of 48 with chronic pancreatitis (40 confirmed at operation) the diagnosis was made by endoscopic retrograde pancretography in all but one. Serum lipase activity was abnormal in 38. Without those cases associated with pancreatic insufficency, serum lipase activity-spontaneously and after the evocation test-was abnormal in 46 patients. Nine of 10 patients with papillary stenosis had the diagnosis confirmed at surgery, the pancretographic findings co-inciding with the surgical ones in all instances. All the five patients with abnormally high serum lipase activity also had chronic pancreatitis on pancreatography. In all of the 18 patients with pancreatic neoplasm pancreatography gave the same results as operation or post-mortem findings. In eight of these serum lipase activity was spontaneously elevated. The lipase evocation test was shown to be most effective if 2 C.H.R.- U/KG-h each of pancreozymin and secretin were administered. Serum lipase results were falsely positive in 17 of 300 patients with clinical suspicion of pancreatic disease but normal pancreatographic findings.


[A case of Behcet's disease with multiple intestinal ulcerations(author's transl)]. A case is reported of Behçet's disease in a 41-year-old man, in the course of which colitis with perforation developed over two years, with fatal results. This is a rare complication of Behcet's disease and must be differentiated from ulcerative colitis and Crohn's disease. Blood transfusions have a limited therapeutic value in the terminal phase of the disease, which among others is characterized by a generalized depression of response of peripheral lymphocytes to stimulation.


[Treatment of renal hypertension by nephrectomy in persons over 40 years of age]. 42 patients aged over 40 years at the time of nephrectomy (between 1961 and 1972) for unilateral renal disease and arterial hypertension were re-investigated. The WHO criteria for normotensive and hypertensive blood pressure levels were used. Systolic and diastolic pressures returned to normal after nephrectomy in 15 patients, systolic pressure alone in nine. Systolic and diastolic pressures remained unchanged in twelve. When grouped by histological criteria, only patients with small pyelonephritis kidney improved significantly, while those with pyelonephritis, arteriolosclerosis and renal-artery stenosis did not. It is concluded that patients aged over 40 years who have hypertension associated with unilateral renal disease may benefit from nephrectomy, especially if they have a small pyelonephritic kidney.


[Constitutional narrowing of the cervical spinal canal. Radiological and clinical findings]. A constitutional narrowing of the cervical spinal canal was seen in 31 patients with neurological disorders. The ratio of the inner diameter of the spinal canal to the diameter of the vertebral body was smaller than 1 (normal greater than 1). Clinical signs were observed from 45 years upwards where reactivedegenerative changes cause additional narrowing. The majority of patients were male, predominantly heavy manual labourers. There is often a trauma preceding. On myelography multilocular deformations of the spinal subarachnoid space and nerve roots are seen. On the mechanical narrowing of the spinal canal a vascular factor supervenes, caused by exostoses, intervertebral disc protrusions, and fibrosing processes. Clinically a chronic progressive spinal transection syndrome (cervical myelopathy) dominates besides a multilocular root involvement. Posterior column sensibility is predominantly lost. Pain in the extemities and the cervical column is an early symptom. Non-specific CSF changes occur frequently. In case of root involvement the electromyogram is pathological. The prognosis is bad. Operation can only remove reactive processes but not the constitutional anomaly.


[Acute necrotizing angitis with eosinophilic myocarditis in bronchial asthma(author's transl)]. In a 34-year-old patient asthma had developed as an allergy to infection. He died suddenly from cardiac and respiratory arrest following parenteral penicillin and sulphonamides. At autopsy necrotizing angiitis of the myocardial vessels as well as eosinophilic myocarditis were shown. These findings are probably the expression of a drug allergy.


[Influence of cytostatic combination therapy with vincristine sulphate and iphosphamide on blood coagulation]. Disorders of blood coagulation were investigated before and during a cytostatic combination therapy with vincristine sulphate and iphosphamide (Asta Z 4942) in 12 patients with malignant tumours or haemoblastoses.  Thromboplastin time, partial thromboplastin time, thrombin time, heat-dependent fibrin, clot retraction, and clotting factors II, V, VIII, IX, X, and the platelet count were determined. A change in the plasmatic coagulation system attributable to the combination therapy could not be demonstrated in any patient.  The influence of the cytostatic combination on the platelet-dependent haemostasis was small; a decrease in platelet count could be observed in only one patient, in whom an additional causative damage to thrombopoiesis due to the underlying disease could be assumed.  Regardless of the cytostatic therapy there were indications of a hypercoagulability in 10 patients.  This explains the increased susceptibility of such patients for thromboses or consumption coagulopathy.


[Fatal vitamin D intoxication].

[Fatal vitamin D intoxication]. A 43-year-old man with alopecia maligna was treated for 4 weeks with a total of 130 mg vitamin D3. Two weeks later, after intensive exposure to the sun, he developed a hypercalcaemic crisis and died 5 weeks later of acute cardiac failure.  The hypercalcaemia proved treatment-resistant despite good diuresis.  Causes other than vitamin D intoxication were excluded clinically and on histopathological investigations.  It is suggested that vitamin D should be administered only on the strictest indications and with regular control of the patient.


[Observations in vitamin D and dihydrotachysterol poisoning]. In three women intoxication with vitamin D or dihydrotachysterol occurred.  Two patients died from complications despite successful lowering of the serum calcium, the third died after a pulmonary embolus during hypercalcaemia 5 months after cessation of vitamin D.  Correct observation of the narrow therapeutic range of vitamin D preparations appears most important in the treatment of hypoparathyroidism and other indications.  Particular attention should be given to the prophylaxis of over dosage.  Apart from regular serum calcium estimations instruction of the patient and relatives as to the dangers and symptoms of intoxication is recommended.  The issuing of a therapy identity card would meet these requirements.


Adrenal steroidogenesis in the spontaneously hypertensive rat (SHR). Adrenal vein catheterizations were done in SHR and control rats at different ages during the development of hypertension. All SHR became hypertensive by 15 weeks of age. The secretion rate of aldosterone was significantly reduced at 8 weeks of age, 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) at 12 weeks of age, deoxycorticosterone (DOC) at twenty weeks of age, and corticosterone (B) at 12 and 20 weeks of age. Secretion data suggest either an enzyme block, or increased conversion of known steroids to an unknown steroid product. Reduced secretion of corticosterone could explain the adrenal hyperplasia observed in SHR which may be important to the development of hypertension in these animals.


Regulation of FSH secretion: use of hydroxyurea to deplete germinal epithelium. Hydroxyurea, a chemotherapeutic agent that prevents mitosis by inhibiting DNA synthesis, was administered to adult male rats for 70 days. Plasma FSH and LH showed no systematic trend although severe germinal cell depletion was produced. These data suggest that the cell(s) of the seminiferous tubule involved in FSH regulation must be either the type A spermatogonium or the Sertoli cell.


Ovarian and placental origins of plasma progesterone following fetectomy in monkeys (Macaca mulatta). Fetectomy, either alone or combined with ovariectomy, was performed in 17 monkeys. Following fetectomy alone in 8 animals, progesterone values were maintained at normal pregnancy levels (1.0 ng/cc plasma or more), until expulsion of the placenta, which frequently occurred at a time well past normal term. Values declining toward but not reaching the nonpregnancy range were observed in some animals in the 2 to 6 weeks preceding expulsion; no similar decline occurs preceding normal labor. In all cases, after the placenta was expelled, progesterone values fell below 1 ng/cc plasma within 2 days. When ovariectomy was superimposed on 3 animals previously fetectomized, plasma progesterone values fell abruptly to nonpregnancy levels, and the placenta was expelled in an average of 6.3 days. The source of the progesterone in these fetectomized animals was, therefore, the ovaries, not the placenta damaged by a preceding fetectomy. However, the ovarian progesterone production after fetectomy was dependent on the continued presence of the placenta. In 6 animals following ovariectomy, and with an intact fetus and placenta, plasma progesterone levels were usually maintained at normal pregnancy levels. When fetectomy was superimposed in these animals with a preceding ovariectomy, plasma progesterone levels fell into the nonpregnancy range in an average of 4.8 days, and placental expulsion occurred after an average of 30.8 days. We believe this reflected a deteriorating ability of the fetectomized placenta to produce progesterone, which was capable only transiently of maintaining plasma values, but later of exerting sufficient local effect to maintain uterine quiescence for a longer time.


Testosterone and 5alpha-reduced androgen secretion by rabbit testes-epididymides perfused in vitro. Mass spectrometric determinations confirmed that testosterone, 5alpha-androstan-17betaol-3-one, 5alpha-androstan-3alpha, 17beta-diol and 5alpha-androstan-3beta, 17beta-diol were present in venous effluent of in vitro perfused rabbit testes-epididymides. Testosterone, dihydrotestosterone, 3alpha-androstanediol and 3beta-androstanediol were secreted at 3.1 plus or minus 0.9, 0.7 plus or minus 0.2, 0.4 plus or minus 0.1 and 0.6 plus or minus 0.1 mug/h when testes-epididymides were perfused with an artificial medium containing 2.5 ng/ml NIH-LH-S17, ovine. Surprisingly, testosterone constituted only 64% of the total mass of the four androgens secreted. These results probably reflect in vivo androgen secretion since hourly collections of spermatic vein blood from anesthetized rabbits contained 2.7 plus or minus 0.9, 0.8 plus or minus 0.3, 0.15 plus or minus .04 and 0.5 plus or minus 0.2 mug of testosterone, dihydrotestosterone, 3alpha-androstanediol and 3beta-androstanediol, respectively. Once again testosterone constituted only 64% of the total mass of the four androgens.


Pancreatic beta cell culture: preparation of purified monolayers. Procedures were developed for preparing partially purified beta cell monolayer cultures. Neonatal rat pancreases were dissociated with a trypsin-collagenase solution. Beta cells were separated from denser acinar cells by centrifuging the initial suspension in a two layer discontinous Ficoll gradient (20, 25%). Resultant cultures, highly enriched in beta cells, were further purified by incubation with cystine-free medium. This caused necrosis of the majority of fibroblastoid cells within two days, while beta cells were considerably less affected. The resultant cultures contained an average of 72% beta cells compared to 10% in untreated control cultures. Insulin release by purified monolayers remained responsive to changes in the glucose concentration of the culture medium.


Persistent pancreatic glucagon but not insulin response to arginine in pancreatectomized dogs. Effects of total pancreatectomy on plasma glucagon, insulin and glucose responses to arginine were determined in 5 dogs. Portal vein and femoral artery samples were obtained in response to an arginine infusion (10 g/30 min) prior to, 1 h, 1 day and 1 week after pancreatectomy. Glucagon was measured using pancreatic-specific antiserum 30K (Unger, Dallas). Before pancreatectomy arginine significantly increased portal vein glucagon from 373 plus or minus 36 to 595 plus or minus 31 pg/ml and femoral artery levels from 233 plus or minus 28 to 342 plus or minus 74 pg/ml. Portal vein and femoral artery insulin concentrations of 74 plus or minus 21 and 17 plus or minus 3 muU/ml increased significantly to 173 plus or minus 64 and 31 plus or minus 7 muU/ml. Glucose levels did not change. One h after pancreatectomy, portal vein glucagon decreased to 121 plus or minus 15 pg/ml but increased to 230 plus or minus 42 pg/ml after arginine. Elevated blood glucose and the necessity for insulin treatment established the adequacy of pancreatectomy. Furthermore portal vein insulin levels were undetectable and unresponsive to arginine or a combination of glucose, glucagon, and tolbutamide 1 week after pancreatectomy. One day after pancreatectomy arginine significantly increased portal vein glucagon from 343 plus or minus 42 to 776 plus or minus 152 pg/ml. One week after pancreatectomy basal glucagon values were 374 plus or minus 30 in the portal vein and 360 plus or minus 49 in the femoral artery and responded to 1226 plus or minus 641 and 825 plus or minus 270 pg/ml, respectively, with arginine. Chromatography of plasma from one pancreatectomized dog on Sephadex G-50 after arginine stimulation revealed that much of the material cross-reacting with antibody 30K was eluted from the column earlier than either 125I-insulin or 125I-glucagon. In contrast, peak glucagon activity in plasma obtained from a normal human given arginine eluted from the column between the peak of 125I-insulin and 125I-glucagon; glucagon added to human plasma also was recovered in this same area between the 125I-insulin and 125I-glucagon peaks. These results suggest that some of the material that reacted with 30K antibody and which increased after pancreatectomy in response to arginine has a molecular weight greater than pancreatic glucagon. At autopsy no pancreatic tissue could be identified. Thus, after pancreatectomy, validated by absent insulin responses, the glucagon response to arginine was normal or increased. Since arginine is not thought to increase intestinal glucagon-like immunoreactive material, the source and nature of the material measured as glucagon after pancreatectomy is unknown, but may be important to any understanding of plasma glucagon measurements.


Progesterone, androstenedione, testosterone, estrone, and estradiol synthesis in hamster ovarian follicle cells. Isolated granulosa cells and theca from proestrous hamsters alone and in recombination, were cultured in order to study steroidogenic capacity of this tissue. Cells from medium size antral follicles (100-300 mum diam.) and large preovulatory follicles (500 plus mum diam.) were used. Steroids were measured by radioimmunoassay. Cultures of cells derived from both sizes of follicles made significant amounts of progesterone for up to 6 days in tissue culture. The preparations from the medium sized antral follicles synthesized little or no estrogen. Of the cells harvested from the preovulatory follicles, the granulosa and theca made moderate amounts of estradiol-17beta while the recombined system made similar to 5 times the estradiol-17beta made by theca or granulosa alone. The results indicate that in the in vitro system used: 1) The hamster follicle cells are similar to other species in that they spontaneously luteinize in culture and secrete large amounts of progesterone, 2) Androgen accumulation is greatest in media from cultured theca of preovulatory follicle, 3) A synergism between theca and granulosa of the large preovulatory follicle exists to effect maximal estrogen synthesis, and 4) Estrogen synthesis is short-lived in vitro in contrast to continued progesterone production.


Inhibition by somatostatin of glucagon and insulin release from the perfused rat pancreas in response to arginine, isoproterenol and theophylline: evidence for a preferential effect on glucagon secretion. To determine whether somatostatin inhibits glucagon secretion directly at the pancreatic level and to study quantitatively the relative effects of somatostatin on glucagon and insulin secretion, the effects of various concentrations of somatostatin on glucagon and insulin release from the in vitro perfused rat pancreas in response to arginine (14.2 mM), isoproterenol (2 mg/ml) and theophylline (10 MM) were studied. Glucagon and insulin responses to arginine were progressively inhibited by somatostatin over a concentration range from 0.1-100 ng/ml. At all doses, somatostatin caused greater inhibition of glucagon secretion than of insulin secretion. Approximately 4 ng/ml somatostatin reduced glucagon responses 50%, whereas 90 ng/ml was required to produce comparable inhibition of insulin responses. Glucagon responses to isoproterenol, an activator of adenylate cyclase, and to theophylline, a phosphodiesterase inhibitor, were completely abolished by 100 ng/ml somatostatin. Isoproterenol did cause insulin release in this system, but insulin responses to theophylline were diminished by somatostatin. The present studies thus indicate that somatostatin is a potent inhibitor of both glucagon and insulin secretion and indicate that it acts directly on the pancreatic alpha and beta cells. Glucagon secretion is approximately 20 times more sensitive to the inhibitory effects of somatostatin than is insulin secretion. Furthermore, the present results suggest that somatostatin may act by modifying cAMP-dependent systems rather than by altering cAMP levels.


The effect of abrupt lengthening of the photoperiod on the onset of ovulation in gonadotrophin-treated immature rats. Immature female rats exposed daily to a-14 h photoperiod were induced to ovulate precociously by administering pregnant mares' serum gonadotrophin (PMS) at 30 days of age (day 30). In these rats ovulation occurs on day 33 between 0130 and 0330 (midpoint of photoperiod equals 1200). The acute effect on the timing of ovulation of abruptly lengthening the photoperiod by 6 h was investigated in this preparation. When compared with controls kept on a 14-h photoperiod, adding 6 h of light to the beginning of the daily photoperiod (i.e., AM light) advanced ovulation by 2 h; adding 6 h of light to the end of the photoperiod (i.e., PM light) delayed ovulation by 5.5 h; adding 3 h of light to the beginning and to the end of the photoperiod delayed ovulation by 2 h. These results suggest that the time of release of an ovulatory quota of pituitary gonadotrophin may be advanced by exposure to AM light and delayed by exposure to PM light, but the PM light appears to have a stronger effect on the time of gonadotrophin secretion.


Measurement of plasma and tissue triiodothyronine concentration in the rat by radioimmunoassay. This paper reports a radioimmunoassay method for triiodothyronine (T3) and the application of this assay to the study of plasma and tissue T3 concentration in the rat. Several antisera formed to a T3-bovine fibrogen complex in guinea pigs and T3-thyroglobulin complex in rabbits are shown to have low or no cross reactivity with T4, monoiodotyrosine, diiodotyrosine, tetraiodothyroacetic acid (TETRAC) and reverse T3. Cross reactivity with T3 derivatives, triiodothyroacetic acid (TRIAC), and triiodothyropropionic (TRIPROP) was variable, some antisera differentiating moderately well and others not at all. An extraction method is described which removes approximately 85% of added 125I-T3 or unlabelled T3 from tissues and in the final step represents 57% of total tissue T3. Mean plasma T3 in 5 normal male rats was 58 plus or minus 6.0 ng/100 ml (SEM), in liver 769 plus or minus 56 ng/100 g, and kidney 627 plus or minus 39 ng/100 g. Tissue to plasma concentration gradients for liver and kidney were 13.3 and 10.8, respectively.


Duration of chorionic gonadotropin production by the placenta of the rhesus monkey. Concentrations of macaque chorionic gonadotropin (mCG) in placenta, blood and urine of rhesus monkeys have been measured by both radioimmunoassay and bioassay throughout gestation. mCG was easily detected and quantified in these specimens for a brief period in early pregnancy, but was not detectable between the 40th day of pregnancy and term in placental extracts, serum, or 40-fold urine concentrates. The apparent absence of mCG after the 40th day of pregnancy makes these macaques a valuable model for pregnancy research, where the absence of chorionic gonadotropin is experimentally desirable. Unlike women and some higher primates, the functional status of the fetal, placental and maternal endocrine compartments of macaques can be studied in the absence of circulating chorionic gonadotropin during mid and late gestation.


A direct radioimmunoassay of corticosterone in rat serum. A direct radioimmunoassay of corticosterone is described requiring as little as 1-2 mul of rat serum. After methanol inactivation of CBG, serum was assayed with a relatively specific antibody raised against corticosterone-21-hemisuccinate. While this antibody has a significant cross-reaction with cortisol, prior purification is not necessary since cortisol is not produced in the rat.


Conversion of [125I]growth hormone into high molecular weight forms in vivo. [125I]-growth hormone, injected in rats, was converted into high molecular weight forms (70,000 to over 200,000 daltons) as judged by gel filtration of blood serum samples collected after the injection. These forms were reactive with antisera against growth hormone, although their immunoreactivity was only 50% of that of control, single component [125I]growth hormone. Their molecular weight was not affected significantly by denaturation with sodium dodecyl sulfate. Incubation of [125I]growth hormone with blood serum in vitro did not result in the production of high molecular weight forms.


Compensatory renal hypertrophy in the absence of androgen binding. As a direct test for a role of androgens, compensatory renal hypertrophy was studied in normal male mice, in androgen-insensitive Tfm/Y mice, and in sibling normal female mice. Fifteen days after unilateral nephrectomy, although the kidneys of the normal male mice were larger, relative increases in renal weight were similar in all groups (33-43%). The magnitude of the increase and the contents of protein, RNA, and DNA were the same in the Tfm/Y mice and the female mice. Androgens are not essential to compensatory renal hypertrophy, but they promote larger mice with larger kidneys.


Differences in the enzymatic inactivation of arginine vasopressin and oxytocin by rat kidney homogenate. Arginine-vasopressin and oxytocin, both 14C-labeled in the glycine residue, are enzymatically inactivated by rat kidney supernatant. Production of radioactive metabolites of each hormone was followed as a function of time. Both oxytocin and vasopressin are degraded by an enzyme which cleaves their Pro-X bonds, to release Leu-Gly-NH2 from oxytocin and Arg-Gly-NH2 from vasopressin. In addition, oxytocin alone is degraded rapidly by a chymotrypsin-like enzyme which directly releases Gly-NH2 from the hormone. The direct release of Gly-NH2 from vasopressin in the homogenate is of minor importance, but there occurs a transient formation of an uncharacterized fragment in significant amounts. The data are interpreted to indicate that the difference in the overall mechanism of inactivation of the two hormones by the rat kidney extract is a result of the high level of the enzymic activity which releases Gly-NH2 directly from oxytocin, compared to the low level of activity releasing Gly-NH2 directly from the antidiuretic hormone. This allows, in the case of arginine vasopressin, a greater expression of the activity of enzyme(s) giving rise to uncharacterized fragment(s) and of the Pro-X cleaving enzyme.


Reduced level of uterine norepinephrine transmitter during hCG-induced pseudopregnancy in the rabbit. The bulk of rabbit uterine norepinephrine is present in short adrenergic neurons which have unique functional properties. Pseudopregnancy was induced in adult nulliparous rabbits by a single injection of 1,500 IU of human chorionic gonadotrophin (hCG). By the 6th day of pseudopregnancy, the total uterine content of norepinephrine was reduced to a level only 40% of that found in untreated controls. At 12 days after the injection the amine level was greater than at 6 days but still significantly less than in controls. By 18 days, when the progestational proliferation of the endometrium had subsided, the levels in uteri of control and injected animals were similar. The findings support previous findings indicating the presence of a peripheral neuro-endocrine mechanism influencing uterine motor function.


Radioimmunoassay of canine growth hormone: enzymatic radioiodination. A sensitive radioimmunoassay is described for the measurement of plasma concentrations of canine growth hormone (cGH) as low as 0.25 ng/ml. The assay utilizes enzymatically iodinated cGH and the double antibody technique. The mean plasma concentration of growth hormone in the normal dog after overnight fast is 1.75 plus or minus .17 ng/ml. Exogenous cGH was cleared from the plasma of both the normal and hypophysectomized dog with a mean half-life of 25.6 plus or minus 1.0 min and was distributed in a volume equal to 8.9% of the body weight. Insulin hypoglycemia produced a 3- to 5-fold increase in plasma GH in 4 of 6 dogs and arginine infusion failed to produce a statistically significant rise.


Structural and mechanical properties of tendon related to function. Tendon normally fulfills its primary role as a flexible force transmitting element very effectively and yet failure of this passive tissue leads to great disability. As a connective tissue its structure is relatively simple and the peculiar helical arrangement of collagen fibres confers highly non-linear as well as time-dependent mechanical properties. Functional significance cannot be attributed to any facet of mechanical response until the physiological pattern of loading is established. In particular the rate of deformation and the minimum force experienced by tendon in normal locomotion have yet to be elicited. Most published values of maximum forces transmitted by tendon fall short of the measured quasi-static rupture strength. The fact that some estimates exceed this ultimate force illustrates the errors incurred in indirect assessment. Direct measurement techniques, which have now been demonstrated to be practicable, should yield valuable information when applied to tendons susceptible to spontaneous rupture. Other proposed mechanical functions of tendon are clearly of secondary importance. Much has yet to be learned of the response of muscle to rapid loading and extension before these hypotheses can be tested fully. With our scant knowledge of normal tendon function it is indeed fortunate that the techniques of repair and treatment of damaged tendon are rapidly advancing.


The indirect measurement of arterial blood pressure in the horse. An accurate modified auscultatory technique for the indirect measurement of arterial pressure in the horse is described. Limitations of the method were sensitivity to external motion in nervous, conscious horses, and the failure to detect Korotkoff sounds in shocked, anaesthetized surgical cases. The apparatus required for the method is expensive and is probably impractical for routine monitoring during anaesthesia.


Enzyme activity in the serum of thoroughbred horses in the United Kingdom. This paper records the concentrations of aspartate amino transferase (A.A.T.), creatine kinase (C.P.K.), sorbitol dehydrogenase (S.D.H.), alpha-hydroxybuturate dehydrogenase (alpha-H.B.D.) and alkaline phosphatase (A.P.) activity observed in the sera of Thoroughbred horses in the United Kingdom, at rest and during training. The methods of analysis have been selected to achieve the optimum precision when used for horse serum. During training A.A.T., C.P.K. and alpha-H.B.D. are related and demonstrate intermittent periods of increasing activity. S.D.H. remains unchanged but demonstrates increases associated with raised titres to equine rhinopneumonitis virus in the serum during the period in which the animal is clinically normal.


Abnormal flexion of the corono-pedal joint or "contracted tendons" in unweaned foals. A condition frequently misnamed "contracted tendons" is described in unweaned foals. Various theories regarding its aetiology are examined. Overfeeding and lack of exercise are suggested as being the most likely causes, leading to excessive growth of the long bones. An effective method of treatment is described. "Contracted tendons" in yearlings are also discussed.


Osteoporosis in a six year old pony.

Osteoporosis in a six year old pony. A case of what can be presumed to be secondary nutritional hyperparathyroidism, due to high phosphorus diet, in a six year old pony is discussed. The findings are compared to those found when the disease occurs in young growing horses.


Primary ocular melanoma in a young horse. The clinical features and pathology of an ocular melanoma in a young born-grey mare are described. The tumour, possibly arising on the cornea, invaded the eye and extra-orbital muscles. Histologically; it consisted predominantly of spindle-shaped and polygonal cells containing melanin.


Response of the elasmobranch utricle to maintained spatial orientation, transitions and jitter. 1.  The spike discharges of single first order afferents from the utricle were recorded in the isolated head of the guitarfish and tested for responses to maintained spatial orientation, to transitions and to a small positional jitter representing natural perturbations.  Sensitivity to maintained orientation is referred to as "tonic", and to transitions and jitter as "phasic".  2.  Most responsive cells were either phasically, or phasically and tonically sensitive.  A few were exclusively tonic.  Tonic responsiveness implied that maintained orientation was associated with a stationary discharge which differed from one position to another; it sometimes differed also from one station to another at the same position.  Transitions from one position to another evoked a rate change that later adapted to the level of the tonic response.  Opposite transitions evoked rate changes in the opposite sense.  The phasic rate change was usually larger for transitions that increased the rate.  Many units were non-responsive.  The prevalence of phasic over tonic sensitivity is stressed, and the remarkable heterogeneity of utricular afferents confirms that the macula is not uniform, probably coding a wide variety of head accelerations.  3.  The jitter increased the ongoing scatter of intervals and binrates, changing, complicating, or abolishing their periodicity.  The jitter could influence the effects of maintained orientation, increasing, decreasing, inverting or even revealing directional sensitivity.  It could also force previously independent units into an orientation-dependent correlation; hence, between-cell correlation is potentially useful in coding of spatiel orientation.  Naturally occurring perturbations may sonstitute a significant issue of normal operation.  4.  Certain afferents from the horizontal semicircular canal showed a slow tonic response to maintained spatial orientation.


The direct spinal area of the inferior olivary nucleus: an electron microscopic study. Identification of the direct spinal areas (portions of the dorsal and medial accessory nuclei) within the opossum inferior olivary complex was accomplished by mapping the location of the terminal degeneration by the Fink-Heimer technique subsequent to cervical cord lesions.  Following similar lesions, sampling of these same regions for electron microscopic study was assured by examination of transversely oriented, 1 mu plastic sections prior to thin sectioning.  The first evidence of electron dense axon terminals was found at a survival time of 24 hours.  At survival times of 36, 48 and 72 hours, degenerating presynaptic profiles shrink, become irregular in shape and are totally or partially surrounded by glial processes.  Spinal terminals average 1-2 mu in their greatest dimension, contain round, clear synaptic vesicles and generally contact small diameter (0.4--1.8 mu) dendritic shafts or occasional spiny appendages.  The spiny dendritic appendages make up the central core of the olivary glomeruli and these juxtaposed dendritic processes exhibit gap junctions.  At longer survival times (5, 7 and 9 days) many presynaptic profiles with either round or pleomorphic synaptic vesicles remain normal in appearance and contact dendritic shafts or the spiny appendages within glomeruli.  Afferents from other sources (possible including intrinsic neurons) must terminate within the direct spinal portion of the nuclear complex to account for the numerous axon terminals which retain normal morphology after such long survival times.


Receptive field characteristics and plastic properties of visual cortical cells in kittens reared with or without visual experience. The functional organization of visual cortical cells was studied in two groups of five week old kittens: one group normally reared, the other reared in total darkness from the third day after birth.  The following results were obtained: 1. The cells of the normally reared kittens were similar to adult cells except for some aspects of immaturity.  In contrast, the cells of the dark-reared kittens were totally non-specific.  Their receptive field showed neither orientational nor directional properties. 2.  The distribution of cells according to the ocular dominance was not different in either group and was similar to that previously described for "adult" cells.  3.  A few hours of visual experience was sufficient to provide specific receptive field properties to the cortical cells of a dark-reared kitten. 4.  Conditioning exposure with an oriented grating induced changes in orientational sensitivity in normally reared kittens but not in dark-reared kittens.


[Quantitative study of autoradiographic marking in the rat nervous system.  II.  Final characteristics of the adult animal brain: interpretation rules and concept of cortical chronoarchitecture]. In this work a statistical study is made of the final outcome of the quantification of the nerve cell labelling in the adult, after prenatal injection of tritiated thymidine. This outcome is presented in the form of histograms which are the superposition of elementary Poisson distributions.  A theoretical model, based on Probability theory, has been developed explaining the experimental outcome.  Studying the final histograms of a defined region, according to this model, we can find out the number and the importance of the constitutive cell generations (chronology).  From the graphic study of the percentage of labelled cells and that of the average of grains, the characteristics of the stratification of the neuronic populations/architectony) can be defined.  All these notions have been gathered into a new concept: chronoarchitectony.  This concept has also been applied to the neocortex.  The results show that there is a strong interpenetration of the different cell generations in a given layer.  The cortical neuronic production is a continuous phenomenon and there is no correspondence with the discontinuity of the cortical layers.


Modification of single neurons in the kitten's visual cortex after brief periods of monocular visual experience. Kittens were deprived of form vision by suturing the lids of both eyes, except for a brief period (1, 6 or 20 hours) on the 29th day when the right eye was opened. 6 space and 20 hours of monocular vision produced a distinct shift in the ocular dominance of visual cortical neurons towards the experienced eye, and an increase in the proportion of cells with obvious orientation selectivity.  These modifications in the visual cortex were enhanced by a period of "consolidation": they were somewhat less obvious if recordings were taken immediately after the exposure but were complete 2 days later.  Although remarkably little visual experience was needed for these changes, the results contrast with the effects of rearing in an environment of vertical stripes, where only 1 hour of exposure produces much more striking effects.  A normal visual environment may have a less powerful organizing influence on cortical neurons than such an environment containing only one orientation.


Labyrinthine influence on cat forelimb motoneurons. 1.  Intracellular responses in forelimb motoneurons to electrical stimulation of the whole labyrinth and of individual semicircular canal nerves were studied in decerebrated, unanesthetized cats.  2.  Stimulation of the whole labyrinth typically produced EPSPs, usually bilaterally, in forelimb extensor (LON, LAT, MED) and shoulder (SI) motoneurons and bilateral IPSPs in forelimb flexor (BIC) motoneurons.  3.  Latencies of PSPs indicated that most of those in extensor motoneurons were trisynaptic and many seen in flexor motoneurons may involve four synapses.  4.  In the cells sampled, stimulation of the anterior, horizontal or posterior canal nerves often evoked EPSPs in extensor and IPSPs in flexor motoneurons, both ipsi- and contralaterally.  Responses to canal stimulation were weaker and more variable than those to stimulation of the whole nerve.  5.  Transection of the MLF in the lower medulla had no effect on PSPs evoked in forelimb motoneurons.  Lesions in the medulla in the area of the LVST greatly  reduced the occurrence of contralateral EPSPs in extensor and IPSPs in flexor motoneurons.  The pathway linking labyrinths to forelimb motoneurons therefore appears to include the LVST.  Hemisection shows that the pathway to contralateral motoneurons descends in the cord on the side of the stimulated labyrinth before crossing to influence these cells.  6.  Labyrinthine control of forelimb motoneurons is less direct than control of neck and back motoneurons.  It is suggested that the interneuron in the pathway to forelimb motoneurons is the site of integration of labyrinthine with other reflexes.


The structure-activity relationship of 9-(X-phenyl)guanine inhibitors of xanthine oxidase. A correlation analysis of the structure-activity relationship in the 9-(X-phenyl)guanine inhibitors of xanthine oxidase has been made. The following equation (see article) has been formulated for 30 derivatives having substituents in the 2-, 3- and 4-positions of the 9-phenyl moiety. C in this expression is the molar concentration of inhibitor causing 50% inhibition of xanthine oxidase. MR-3,4 is the combined molecular refractivity of substituents in the 3- and 4-positions. Molar refractivity is a measure of the polarizability of the substituents; it is assumed in the present instance to be a measure of the dispersion forces between the substituent and the enzyme. The positive coefficient with this term roughly indicates that the greater the number of electrons and the greater their polarizability in the substituent, the more inhibitory are the substituents. Es-2 and Es-4 are Taft steric parameters for functions in the ortho and para positions. The positive coefficients with these two terms indicate that bulky groups in the 2- and 4-positions do not make good inhibitors. This is a proximity effect and is related to the enzymic region near the ortho and para positions. No sigma term occurs in this equation which indicates the lack of importance of the electronic effect of substituents on the phenyl ring as it pertains to inhibitory power. Since the hydrophobic parameter pi was not found to be important, it is assumed that these inhibitors are not binding to hydrophobic space in or on the enzyme; rather, they are interacting with polar space. The implications of this equation for the design of better inhibitors are discussed.


[Iodo-derivatives of 2-aminobenzensulfonamide and 1,2,4-benzothiadiazine-1,1-dioxide]. A series of iodo derivatives of 2-aminobenzensulfonamide and its derivatives has been prepared by reaction with iodine chloride in N,N-dimethylformamide or N,N-dimethylacetamide. The structure of each compound was confirmed by transformation with formic acid into the corresponding 1,2,4-benzothiadiazine and comparison with the same compounds prepared via the Sandmeyer reaction starting form amino derivatives of known structure. It was found that the iodination reaction in N,N-dimethylformamide, can lead, depending on the nature of the starting material, to the formation of benzothiadiazine derivatives apparently generated from sulfonamide via a formylation reaction due to N,N-dimethylformamide.


[Pyrazino (1,2-a)- and 1,4-diazepino(1,2-a)indoles. II. Synthesis of 1-substituted 10-phenyl-3,4-dihydropyrazino(1,2-a)indoles and of 11-phenyl-4,5-dihydro-4H-diazepino(1,2-a)indoles]. The AA. describe the synthesis of some 1-substituted 10-phenyl-3,4-dihydropyrazino(1,2-a)indoles and 11-phenyl-4,5-dihydro-3H-1,4-diazepino(1,2-a)indoles. Preliminary pharmacological tests indicate that these products, have lower sedative and antiadrenergic activity than the compounds reported in our previous paper.


[Salts and betaines with quaternary ammonium function derived from sulfanilamide and from p-aminobenzoic and p-aminosalicylic acids]. The preparation of quaternary ammonium derivatives of sulfanilamide and of tertiary amines containing an aliphatic chain up to c-18 is described. Some members of this series show greater antimicrobial activity than the parent substances. This is found also in comparison with other analogous series which have been prepared.


Synthesis and properties of 1,3-bis-salicyloyl-5,5-diethylbarbituric and 1,3-bis-salicyloyl-5,5-diethyl-2-deoxybarbituric acids. 1,3-Bis-salicyloyl-5,5-diethylbarbituric acid and 1,3-bis-sacilcyloyl-5,5-diethyl-2-deoxybarbituric acid have been synthesized and found not to isomerize spontaneously. 1,3-Bis-salicyloylbarbital undergoes thermal decomposition giving 2,3-dihydro-4H-benzoxazine [1,3]dione-2,4, carbon monoxide and cyclopentane.


[New esters of prednisolone and triamcinolone acetonide and their anti-inflammatory activity]. Seventeen acids with diphenylyl and cyclohexylphenyl groups were esterified with the hydroxyl group at position 21 of prednisolone and triamcinolone acetonide. Some of these esters showed marked activity against carrageenin edema and Selye spots in the rat, especially on local application.


[Preparation and pharmacological study of some N-substituted amino-1,8-naphthyridines]. The synthesis of N-substituted amino-1,8-naphthyridines is described. Some products were subyected to pharmacological screening and the resulting data are reported.


[Derivatives if imidazol (1,5-a) pyridin-3(2H)-one]. Numerous imidazo[1,5-a]pyridin-3(2H)-one derivatives having one or two electron-attracting substituents in positions 1 or 2 have been prepared starting from substituted 2-aminomethyl-pyridines and phosgene or ethyl chlorocarbonate. Attempts to obtain unsubstituted imidazo[1,5-a]-pyridin-3(2H)-one were not successful.


Cholinergic compounds. II - Synthesis and biological activity of epi- and allo-desethermuscarines. To obtain further clarification of structure-activity relationships of cholinergic substances, which would give better understanding of cholinergic receptors, the carbocyclic analogs of epi-muscarine (I) and allo-muscarine (II) were prepared starting from 6-methyl-3-oxo-2-oxabicyclo[2.2.1]heptane (IV). Pharmacological tests show that these two compounds possess lower muscarinic activity than the carbocyclic analog of muscarine (desethermuscarine), the allo isomer being from 5 to 500 times more active than the epi isomer. Therefore, the activity in the carbocyclic series follows, for these receptors, the same pattern as the oxygenated one. As far as nicotinic activity is concerned. (I) is 2.5 times more active than (II), the effective doses being from 40 to 100 times higher than that of Ach. These results suggest a steric rather than an electronic influence for the ether oxygen, whose principal role seems to be that of contributing to the rigidity of the molecule. For most receptors assayed, an inverse relationship between the potency ratio of the isomers and the sensitivity towards Ach has been observed.


Site visits for the review of grant applications to the National Institutes of Health: Views of an applicant and a scientist administrator. The review of applications to the National Institutes of Health for individual research projects and complex programs of research may involve a visit to the applicant institution. The site visit is a review technique that is used only when information necessary for the scientific and technical review cannot be obtained satisfactorily by other means. The agenda for the visit must be carefully planned, particularly in the case of large research programs, since adequate time must be allowed for the presentation and discussion of the more complex components of the proposed research. All of the participating investigators associated with the proposal should get together for a thorough and critical rehearsal a few days before the visit. The impressions conveyed to the site visitors are transmitted to the initial review group usually through a site-visit report. The final recommendation of the visitors, which is based on the scientific merit of the proposed research, the competence of the investigators, and the suitability of the institutional setting, results from a thorough discussion of the strengths and weaknesses of the proposed program. The initial review group, in turn, uses the information obtained at the site visit in arriving at their recommendation to the appropriate National Advisory Council.


Covalent modification of nuclear proteins during aging. An in vitro assay system has been established to study acetylation and phosphorylation of nuclear proteins from isolated nuclei. Phosphorylation of neclear proteins reached a peak within 5 min while maximum acetylation occurred about 10 min later. The rate of acetylation of liver nuclear proteins in 15 min incubation was significantly higher in "old" mice (29 mo) than in "young" mice (2 mo), while there was no difference in phosphorylation. When nuclear histones were fractionated by polyacrylamide-urea electrophoresis the acetylation of histone F3 was increased in "old" mice to 129% and F2al to 112% of the values in "young" mice. Acetylation of phenol-soluble nuclear acidic proteins was increased to 250% and phosphorylation to 138% in "old" mice as compared to "young" mice. This increase in covalent modification of acidic proteins was found in tow specific fractions when separated by SDS-polyacrylamide gel electrophoresis. By contrast, the labeling of nucleoplasmic proteins, soluble in 0.14 M NaCl, showed no significant difference between the two ages.


Effects of aging on ionic movements of atrial muscle. The effect of age on ion concentrations and fluxes in cardiac muscle was examined. Left atria from rats of 1, 3, 6, 12, 24, and 28 months of age were analyzed for content of total water, sodium and potassium, for 14C-inulin space and for 22Na  and 42K influx and efflux rates. Animals of 3 and 24 months of age showed a small but significantly greater water content than those of the other age groups. The inulin space, after a small nonsignificant fall between 1 and 3 mo, increased significantly at 6 mo, then leveled off through 28 mo. Intracellular sodium (Na)1, and potassium (K)1 concentrations were calculated. (Na)1 showed a significant increase from 1 to 3 mo, decreased significantly at 6 mo, and then leveled off. (K)1 exhibited an initial significant decrease from 1 to 3 mo followed at 6 mo by a significant increase which remained unchanged through 28 mo. Trend analyses of the Na influx rates showed that a significant increase with age occurred, except for a decrease at 24 mo. Potassium influx rates remained relatively constant at all ages. Sodium efflux appeared to be multiexponential, with at least two distinct rate constants (k1 and k2). Potassium efflux steadily decreased as a function of age. The results are discussed with reference to possible consequences of aging on cardiac physiology and reactivity to pharmacological agents.


Drug and chemical residues in domestic animals. Given the large number of chemical substances that may find their way into the food supply, a system is needed to monitor their presence. The U. S. Department of Agriculture's Meat and Poultry Inspection Program routinely tests for chemical residues in animals coming to slaughter. Pesticides, heavy metals, growth promotants (hormones and hormonelike agents), and antibiotics are included. Samples are taken statistically so that inferences as to national incidence of residues can be drawn. When a problem is identified, a more selective sampling is designed to help follow up on the initial regulatory action. In testing for pesticides, only DDT and dieldrin are found with any frequency and their levels are decreasing; violative residues of any chlorinated hydrocarbon are generally a result of an industrial accident rather than agricultural usage. Analyses for heavy metals have revealed detectable levels of mercury, lead, and others, but none at levels that are considered a health hazard. Of the hormone or hormonelike substances, only diethylstilbestrol has been a residue problem and its future is uncertain. The most extensive monitoring for veterinary drugs is on the antimicrobials, including sulfonamides, streptomycin, and the tetracycline group of antibiotics that constitute the bulk of the violations; their simultaneous use prophylactically and therapeutically has contributed to the problem in certain cases. A strong, well-designed user education program on proper application of pesticides, chemicals, and veterinary drugs appears to be one method of reducing the incidence of unwanted residues.


Clinical implications of the presence of drug residues in food. Untoward clinical effects in man of drugs or chemicals as food residues might occur from direct pharmacological action, stimulation of hypersensitivity, or effects on cell regulatory processes. Antimicrobial residues might also influence the normal bacterial microflora of the skin, mucous membranes, and gastromintestinal tract. No direct evidence exists to incriminate antimicrobial drug food residues in any of these events. The permissible residues of antimicrobial substances are so low and the assay procedures for detecting them so sensitive that adequate surveillance should preclude harmful effects in man from these agents. Problems still remain with respect to potential carcinogenicity of drugs and chemicals as food residues.


Varicocelectomy as therapy in male infertility: a study of 504 cases. Over a ten-year period, surgical correction of varicocele was performed on 504 selected subfertile men. They were followed up for at least one year after surgery. Semen quality was improved in 71% and 55% of the wives became pregnant. Statistically, the results were better in terms of semen quality improvement and pregnancy for patients who had preoperative sperm counts over 10 million/ml (88% improved, 68% pregnancy rate) than for patients who had preoperative sperm counts of less than 10 million/ml (33% improved, 23% pregnancy rate). The empirical use of postoperative human chorionic gonadotropin therapy in this latter group improved results significantly (56% improved, 44% pregnancy rate).


Circulating antispermatozoa immunoglobulin G in men after vasectomy. The sera from ten vasectomized men produced immobilization and agglutination of human spermatozoa and positive passive hemagglutination tests. Immunoglobulin G fractionated from the samples of sera produced similar effects. In these men, it appears that a circulating antibody, immunoglobulin G, was produced against spermatozoa after vasectomy. The sera from 22 men who had not undergone vasectomy did not cause spermatozoa immobilization or agglutination, and produced a negative passive hemagglutination test.


Circulating sperm-agglutinating antibodies in azoospermic men with congenital bilateral absence of the vasa deferentia. Congenital bilateral absence of the vasa deferentia has been found to be the cause for azoospermia in 101 patients who have been examined in our urologic practice since 1956. This represents approximately 2% of the 5112 patients seen during that time because of problems relating to infertility. Of these 101 men, 29 have had their sera tested for the presence of circulating sperm-agglutinating antibodies. The Shulman15 modification of the macroscopic gelatin sperm-agglutination test of Kibrick et al6 was used. None of these patients had had testicular biopsy. Significantly high titers (1:32 or greater) of antibodies were found in 18 (62.1%) men, low titers (1:16 or less) in five (17.2%), and no antibodies in six (20.7%).


Inhibition of rat spermatogenesis and seminiferous tubule growth after short-term and long-term administration of a monoamine oxidase inhibitor. Seminiferous tubules from rats killed 24 hours after injection of pargyline, a monoamine oxidase inhibitor, did not grow well in tissue culture when compared to control tubules. Treated tubules showed severe tubular degeneration and loss of cellular detail after nine days in culture. Animals injected with pargyline for ten days had varying degrees of semi-niferous tubule degeneration with depletion of the spermatogenic elements. It is suggested that pargyline has a detrimental effect on spermatogenesis. Pargyline possibly acts by decreasing MAO levels which, in turn, may increase potentially damaging amines which may be responsible for the testicular damage.


The development of rabbit ovarian follicles following copulation. The morphologic development of rabbit ovarian follicles was studied by means of light and electron microscopy 0, 2, 4, 6, 8, and 10 hours after copulation. The progressive changes at the apex of the follicle included extensive edema, hyperemia, and rupture of blood vessels, and then rupture of the follicular wall. Ovulation occurred when the cohesive forces in the cellular layers of the follicular apex became less than the physical forces within the follicle. Most of the morphologic changes in the follicle as it approached ovulation could be related to the effects of locally produced estrogens.


Clinical experience with ethinyl estradiol and d-norgestrel as an oral contraceptive. One hundred eighty-one women received 30 mug of ethinyl estradiol plus 150 mug of d-norgestrel as an oral contraceptive for 21 days and then received no tablets for the next seven days for a total of 1,488 cycles. There were no pregnancies. Cycle control was good to excellent. Menstrual cycles lasted 25 to 32 days in 96.2% of treatment cycles. Menstruation lasted three to five days in 93.2% of the cycles, and it began three to five days after the last day of medication in 79.1%. The menstrual flow was moderate in 87%. Breakthrough bleeding occurred in 2.0% of treatment cycles, spotting in 0.1%, and amenorrhea in 0.8%. The incidence of adverse subjective symptoms was minimal and significant increases compared with the pretreatment cycle were noted only for nausea in the first two cycles and for nervousness in the second cycle of treatment. Overall incidence of nausea was 3.2% of treatment cycles.


Menstrual regulation in the United States: a preliminary report. The efficacy and safety of vacuum aspiration on an outpatient basis without anesthesia or cervical dilatation within 14 days of a missed menstrual period was evaluated in 1,009 women. Among those patients in whom pregnancy could be documented (54.8%), 4.2% were still pregnant after the procedure. Potentially serious complications were pelvic infection (0.4%), bleeding requiring a repeat curettage (0.3%), and prolonged bleeding (0.7%). For comfort, 26.7% received local anesthesia or analgesia. To allow selection of a higher proportion of pregnant patients, the probability of pregnancy was derived for patients with either a positive or negative pregnancy test at each length of amenorrhea. To determine the best vacuum pressure and source, and the cannula size and type at each duration of pregnancy, a more extensive (large, controlled, comparative) study is required.


Prostaglandin content of human endometrium. Prostaglandin levels in 46 human endometrium specimens were determined and expressed as both total uterine content and on a dry weight basis. Concentrations of PGF2alpha and PGE did not differ significantly between specimens obtained during the proliferative or secretory phases of the menstrual cycle. There was, however, a fourfold higher total uterine content of prostaglandins during the secretory phase. There was also a more than fourfold higher level of PGF2alpha than of PGE during the secretory phase. The two types of prostaglandins were present in nearly equal amounts during the proliferative phase. Atrophic endometrium was characterized by a high concentration of prostaglandins, but a low total amount consisting of nearly equal amounts of PGF2alpha and PGE.


The effect of orally administered androgens on sperm motility. The administration of oral androgens increased sperm motility to normal in 30 (52%) of 58 men whose impaired motility was the only defect in their semen quality. Their ejaculate volume, sperm count, and morphology were not benefited. Suppression was infrequently seen and appeared to be transient. Pregnancies were documented in 15 (26%) of the 58 couples studies. However, communication regarding this matter was made with only 39 of the 58 couples. The benefical effect from a single course of androgen is likely to persist. However, if a pregnancy does not ensue, semen analysis should be repeated to determine if additional medication is necessary. Pretreatment serum testosterone determinations were not helpful in determining those men who would most likely benefit from therapy. No appreciable benefit was noted in the semen quality of the 35 subfertile men identically treated who, in addition to poor sperm motility, had other defects in their semen.


Comparative glycolytic metabolism of sperm from normal, asthenospermic, and oligoasthenospermic men. The glycolysis of spermatozoa from normal, asthenospermic, and oligoasthen ospermic men was studied using a respirometry technique to measure glucose utilization by the production of 14CO2 from glucose 14C (U-L). Lactate and pyruvate were measured by a spectrophotometric method using DNA as reference. Human spermatozoa preferred glucose to fructose as the glycolytic substrate when concentrations of these hexoses did not exceed normal concentrations in the blood. Spermatozoa from oligoasthenospermic men produced an average of 3.5 times more 14CO2 (345, 457 dpm/mg DNA/hour) than did spermatozoa from asthenospermic (88,837 dpm/mg DNA/hour) and normal men (96,595 dpm/mg DNA/hour). They also formed four times more lactate (9.63 mumoles/mg DNA/hour) than spermatozoa from normal men (2.33 mumoles/mg DNA/hour) and 6.4 times more pyruvate (2.90 mumoles/mg DNA/hour compared to 0.45 mumoles/mg DNA/hour). Spermatozoa from asthenospermic men formed amounts of lactate (3.01 mumoles/mg DNA/hour) and pyruvate (0.63 mumoles/mg DNA/hour) similar to those produced by spermatozoa from normal men.


Serotonin and 5-hydroxyindoleacetic acid in fertile and subfertile men. High levels of serotonin and 5-HIAA were found in the urine of a group of 102 oligospermic and azoospermic men. These levels were significantly higher than those of normal fertile men.


Plasma testosterone, luteinizing hormone, and follicle-stimulating hormone after vasectomy. Plasma testosterone, LH, and FSH were measured in 24 healthy subjects prior to and after bilateral vasectomy. No significant changes were noted in any of the hormones 42 and 87 days after surgery; this indicated that normal testicular function persisted during the period of study.


Plasma testosterone response to short-term human chorionic gonadotropin administration in men with follicle-stimulating hormone suppressed by exogenous estrogen. In order to investigate the role of FSH in Leydig cell function, six men were given four daily injections of HCG (4,000 IU) while receiving oral ethinyl estradiol. The peak testosterone levels in these subjects were contrasted to the results obtained in seven men who received HCG without additional exogenous steroid treatment. Urinary and plasma FSH was suppressed to 26% and 50%, respectively, of basal values by the estrogen treatment. Peak plasma testosterone determinations following HCG did not differ in the two groups of subjects. Additionally, an early pubertal boy had a normal HCG-induced testosterone rise while his urinary FSH was suppressed by estradiol to lower than prepubertal levels. The data indicate the short-term FSH suppression does not alter testicular responsivity to short-term HCG administration. A role for FSH in Leydig cell testosterone production in men has yet to be demonstrated.


Selective ovarian sympathectomy in the rabbit. Evidence implicates the ovarian nerves in the regulation of hormonal and ovulatory functions. A technique for selectively denervating the in situ rabbit ovary is therefore of considerable investigative value. The ovarian artery was stripped of its adventitia and nerve bundles. Three weeks later, fluorescent histochemistry confirmed the complete absence of adrenergic nerves in the vessel walls and ovarian stroma of the experimental ovary, as compared to the abundant fluorescent structures present in the contralateral control ovary. The surgically treated ovaries demonstrated no significant ischemic or trophic change on gross and routine histologic examination.


Studies on the function of the denervated rabbit ovary: human chorionic gonadotropin-induced ovulation. The described method for selective sympathetic denervation of the in vivo rabbit ovary involved stripping the ovarian artery of its nerve bundles and adventitial tissue. The ovary was then entirely free of fluorescent-staining adrenergic nerves. This technique was used to study the effects of ovarian denervation on HCG-induced ovulation. After HCG was administered to 22 rabbits which had previously undergone unilateral ovarian denervation, the ovaries were observed for follicular maturation and rupture. Control ovaries demonstrated a mean of 5.6 stimulated follicles/ovary; denervated ovaries had a mean of 5.4. An average of 3.5 follicles/control ovary ruptured; an average of 3.1 follicles/denervated ovary ruptured. Furthermore, the time course of ovulation after HCG did not differ between denervated and intact ovaries. These results indicate that HCG-induced ovulation in the rabbit is not interrupted by ovarian denervation.


Effects of theophylline on glucose kinetics in normal and sympathectomized rats. The influence of intraperitoneal administration of aminophylline on the rate of hepatic glucose production and peripheral uptake (Ra and Rd) was studied in normal and in adrenodemedullated and reserpinized rats by using the primed constant infusion of Glucose-2-3H. In normal rats, the dose of 100 mg. per kilogram of aminophylline produced a marked increase of Ra and Rd. Since Ra rose more rapidly than Rd did initially, hyperglycemia developed. Thereafter, glucose production and uptake increased to nearly the same extent, and a new steady state was reached at plasma glucose levels almost twice those of the baseline. Smaller and transient modifications were observed after the administration of 20 mg. per kilogram of aminophylline. With the higher dose, insulin levels markedly rose (reaching a tenfold peak above the basal value) while minor increments were observed with the lower dose. In a group of normal rats which were given glucose (10 mg. per kilogram per minute) in order to achieve a degree of hyperglycemia comparable to that brought about by the higher dose of aminophylline, an almost identical enhancement of glucose uptake was recorded. However, insulin levels were much higher in aminophylline-treated rats as compared to normal rats. From these finding it was concluded that aminophylline induces resistance to insulin effect. When aminophylline was injected into demedullated rats pretreated with reserpine, at the dose of 100 mg. per kilogram, a marked enhancement of Ra, and consequently of glycemia, was recorded initially; later, severe hypoglycemia developed depending on both a progressive exhaustion of hepatic glucose production and a marked increase of glucose utilization. Insulin levels dramatically increased in these experiments. These results suggest that aminophylline directly increases glucose production by the liver and insulin secretion. The simultaneous activation of the sympathetic system blunts the insulin response and counteracts the restraining effect of insulin on the liver and the stimulatory effect of insulin on overall glucose uptake as well.


Production of chylomicron-like lipoproteins from endogenous lipid by the intestine and liver of diabetic dogs. Pancreatectomized dogs developed hypertriglyceridemia. This probably resulted from a lack of insulin rather than a lack of glucagon, as it did not develop either in pancreatectomized dogs maintained on insulin, or in dogs with all but the uncinate process of the pancreas removed. The increase in plasma triglycerides was preceded by a decrease in post-heparin lipolytic activity (PHLA) and an increase in FFA. As the hypertriglyceridemia developed in fasted dogs who had previously been on fat-free diets, the triglyceride fatty acids (TGFA) were nondietary. These endogenous TGFA originated from adipose tissue rather than from de novo synthesis. The composition of the lipoprotein TGFA was identical to that of adipose tissue. Furthermore, nicotinic acid blocked the FFA increase and the development of the hypertriglyceridemia. However, it did not prevent the fall of PHLA. Although their TGFA were entirely nondietary, the lipoproteins in these diabetic dogs resembled chylomicrons in their electrophoretic mobility, size, density, and composition. Surgical, histological and tracer studies suggested that in addition to the liver, the intestinal mucosa makes these lipoproteins. The tracer studies also suggested that circulating FFA might enter the intestinal mucosal cells directly and be esterified.


Responses to arginine of the perfused pancreas of the genetically diabetic Chinese hamster. Nonketotic, genetically diabetic Cinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose. To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM). Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabectics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics. Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon. These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.


Capillaries of South African diabetics. IV. Relation to retinopathy. The muscle capillaries of diabetic subjects, with and without retinopathy, have been measured. The groups with retinopathy had significantly thicker laminae than those without the fundal changes. No significant difference was found between the group with proliferative retinopathy and the group with nonproliferative retinopathy. The focal and segmental nature of the basal lamina thickening was confirmed by the increasing standard deviation of the measurements within and among capillaries. This study also confirms the fact that, at least for muscle capillaries, an apparent relationship exists between the thickness of the basal lamina of these vessels and the presence of clinical retinopathy.


Effect of glucose priming on insulin response in the premature infant. Our paper deals with premature infants in the first twenty-four hours of life and reports the effect of a preinfusion of glucose on glucose administration. Glucose infusion (2.5 gm.) resulted in a slight elevation of serum insulin. When this administration of glucose was preceded by a two-hour infusion of glucose, there was a striking increase in serum insulin.


Clinical and epidemiological significance of the HBSAg (Australia antigen): carrier state. One hundred fifteen asymptomatic Australia antigen (HBSAg) carriers, discovered by routine testing of volunteer blood donors in Toronto, were investigated and followed for up to 30 months. The carrier state seems to be largely host-dependent, and its prevalence is modified by ethnic origin, sex, and age. A high prevalence of carriers was found in persons coming from Mediterranean countries and the Orient. The carrier state was 3 times more common in males than in females, and the majority of the carriers were under 30 years of age. Family clustering of HBSAg-positive individuals was observed. All carriers were asymptomatic and only one gave a history of jaundice in the past. Seven gave a history of intravenous drug use. Four had moderate hepatomegaly. Fifty-four had some abnormality in their liver function tests. The SGPT was the most frequently abnormal test and correlated best with the histological findings. Twenty of 29 liver biopsies showed features of chronic benign persisting hepatitis. All patients remained well during the follow-up period. In no patient was there evidence of deterioration or progression in either their clinical state, liver function, or pathological findings. Only 1 of the 115 carriers became HBSAg-negative over the period of observation.