Two abnormalities of glucose-induced insulin secretion: dose-response characteristics and insulin sensitivity. To characterize the defect of insulin secretion in diabetes, the response to different iv glucose loads has been studied in women who have had gestational diabetes and are, by definition, latent diabetic (LD). Women who have produced a large-for-dates baby, but who were not known to have been diabetic (LFD), have been investigated to determine if they have abnormal metabolism. Both groups were found to have raised fasting plasma glucose concentrations. Only the LD had glucose intolerance, which was associated with a reduced first phase insulin response to all glucose loads with a decreased maximal secretory capacity (low V max). The LFD women appeared to include a distinct abnormality in which the beta cells had decreased sensitivity to glucose (high Km), with diminished secretory response to small but normal response to large loads. Whereas the LD probably have disordered beta cell function, some of the LFD women may represent the upper end of the normal range of the glucose "set" of beta cell function. Neither group had insulin resistance, as measured by the hypoglycaemic response to an iv insulin bolus. A woman who has produced a LFD, but who was not known to be diabetic, does not necessarily have a diabetic tendency.


The androgens in the guinea-pig foetus throughout the embryonic development. Testosterone (T) and dihydrotestosterone (DHT) content and concentration were measured by radioimmunoassay in plasma, gonads, adrenals, and sexual ducts of 235 male and 214 female guinea-pig foetuses at various stages of gestation after gonadal and adrenal differentiation occurred. In the male foetus, a sharp increase in the content and concentration of T and, to a lesser degree of DHT, is observed in the testis, the plasma and the ducts at the time of sexual differentiation between days 28 and 36. Thereafter androgen concentrations in these tissues decrease and rise again after day 52. In the female foetus, levels of T and DHT in the ovary are low throughout foetal life and do not account for the relatively high concentrations found in the plasma; in sexual ducts, T concentrations decrease at the time of differentiation. DHT levels are low at every stage. In both sexes, T and DHT are present in the adrenal. No sexual dimorphism is observed in the evolution of T and DHT adrenal content and concentration.


Effect of human chorionic gonadotrophin on phagocytic activity and proliferative capacity of rat peritoneal macrophages in culture. Human chorionic gonadotrophic hormone (hCG) decreased phagocytosis of rat peritoneal macrophages in culture and also inhibited their capacity to be stimulated by an inflammatory exudate. Both effects were related to the concentration used. These experimental results suggest that elevated levels of hCG may play a role in the prevention of the rejection of the foetal allograft by the maternal host.


Effect of endogenous thyroid stimulating hormone levels on the secretion of thyroid hormones in man. The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.


The behaviour of the thyroidal iodide trap after subtotal thyroidectomy for thyrotoxicosis and its implication for the T3-suppression test. It is important to distinguish between symptomatic response and immunological cure in thyrotoxicosis because it has been suggested that surgery, in addition to providing a rapid symptomatic response, may also cause the disappearance of thyroid-stimulating antibodies. The evidence, however, is based largely on suppression tests which we argue may not be valid in the post-operative period. Seventy thyrotoxicosis patients were treated for 6 months with a standard course of carbimazole and T3, at the end of which each patient was classified as suppressor (S) or non-suppressor (NS) according to the fall in radioiodine uptake. Group I (18 patients) and group II (18 patients) were then randomly selected for immediate surgery while group III (34 patients) continued on antithyroid drugs. All groups were reviewed every two months from the 6th month for 12 months, during which time group I was drug-free and groups II and III received T3. Twenty-min iodide uptakes were performed in all patients at each visit to compare the serial changes in mean iodide trapping capacity between treatment groups. Despite 10-fold differences in TSH levels between groups I and II, and irrespective of suppressibility before surgery, the mean uptakes in both these groups remained basal (less than 4%) throughout the period of study, while the serial mean uptakes in group III S (no TSH, by implication no TSAB, but intact iodide trap) were consistently higher than those of group I NS (high TSH, by implication TSAB as well, but reduced iodide trap size). The data points to an absence of dose-responsiveness between TSH and the surgical-remnant's iodide trap, implying that post-thyroidectomy suppression tests (at least during the first year) cannot measure changes in iodide trapping, and therefore do not measure the same phenomenon after subtotal thyroidectomy as they do before operation when the thyroid is intact. We therefore question the validity of comparing suppressibility before and after surgery and basing the frequency of surgical cure on the result.


Tiapride-induced chronic hyperprolactinaemia: interference with the human menstrual cycle. Four regularly menstruating volunteers were submitted to an oral treatment, for 3 consecutive cycles and starting on the first day of a cycle, with tiapride at daily doses ranging from 1 x 100 mg to 2 x 100 mg. The first and the last cycle under treatment, as well as a prior control cycle, were thoroughly studied by means of daily measurements of blood concentrations of LH, FSH, prolactin (PRL), oestradiol and progesterone. Tiapride, a benzamide derivative with dopaminergic blocking activity at the level of the lactotrophes, increased mean PRL secretion in each subject but a permanent hyperprolactinaemia above 700 uU/ml was attained only in one subject. Despite these widely fluctuating PRL levels in most subjects, the resulting overall hyperprolactinaemia induced in all cases a progressive deterioration of the function of the corpus luteum: 5 cycles showed luteal phases reduced by 2--5 days, one cycle was characterized by some slight luteinisation but questionable ovulation and the 2 remaining cycles were anovulatory. The interruption of drug intake one week after the onset of menses led thereafter to a cycle with a likely inadequate luteal phase but of normal length. It is concluded that even a non-permanent hyperprolactinaemia can impair the normal function of the hypothalamo-pituitary-ovarian axis, as well as exhibit some effects in a cycle consecutive to the normalization of PRL. With the exception of the impaired luteal progesterone secretion, the pooled hormonal data from the short luteal phase cycles under tiapride-induced hyperprolactinaemia exhibit very little significant differences, as compared to the corresponding values in the control cycles. Some delay in the onset of follicular maturation, however, should be assumed since the follicular phase had been lengthened by 1 to 31 days in 5 of the 6 cycles with luteinisation during treatment. The present results are compatible with a double impact -- both at the ovarian and the hypothalamo-pituitary levels -- of hyperprolactinaemia in its mechanisms of impaired function of the hypothalamo-pituitary ovarian axis.


Oxytocin determination by radioimmunoassay in cattle. I. Method and preliminary physiological data. A radioimmunoassay for oxytocin in cow plasma is described. Antisera were raised in rabbits against synthetic oxytocin coupled to bovine thyroglobulin. Iodinated oxytocin free of unlabelled oxytocin and most likely also free of diiodo-oxytocin was used as radioactive tracer. The tracer showed a high degree of purity, and was stable on storage. It could be used in the assay for 2--3 months. The assay showed very little cross-reactivity with vasopressin. Acetone was used for the extraction of oxytocin from plasma as well as from standards made of synthetic oxytocin in pooled cow plasma. Inhibition curves obtained with plasma collected from cows at parturition were parallel to those obtained with the oxytocin standard preparation. The mean recovery of oxytocin added to cow plasma was 106% (SD = 14). The within-assay coefficient of variation (CV) varied from 5.2 to 10.9%, and the between-assay CV was in the order of 13%. The assay sensitivity was 1 pg (0.5 uU) per tube, corresponding to 3 pg/ml plasma. Around the time of milking the plasma oxytocin profile showed a strong response to the preparation for milking, and a further effect releated to the attachment of the teat cups of the milking machine. Peak concentrations were in the range of 15--50 pg/ml. During parturition there was a peak of oxytocin (65 pg/ml) coinciding with the expulsion phas. After this peak levels decreased but remained measurably elevated until the expulsion of the placenta. The plasma disappearance curve for immunoreactive oxytocin after the infusion of 100 IU oxytocin over a period of 1 h showed two components with apparent half-lives of 7--7 and 25 min, respectively.


Effect of exercise on thyroid parameters and on metabolic clearance rate of antipyrine in man. Serum concentrations of thyroxine, triiodothyronine, free-thyroxine-index, free-triiodothyronine-index and reverse-triiodothyronine (r-T3) were followed in nine normal men, aged 18 to 22 years, during a nights rest and during nine hours march (4.6 km/h). In addition antipyrine elimination was measured in the same periods after iv injection of 1 gram of antipyrine. No significant differences were found in any of the thyroid parameters during exercise except for a small increase in serum r-T3 after 3 hours. During rest a small but significant decrease was found in serum r-T3. Otherwise no significant differences were found except for a significant increase in free-T3-index after 3 hours rest. The mean value of total body clearance of antipyrine was identical at rest and during exercise. Prolonged exercise does not change the metabolic clearance rate of antipyrine and does not elicit any major change in the serum concentrations of the thyroid hormones.


Regulatory hyperparathyroidism in a pig breed with vitamin D dependency rickets. A radioimmunoassay for porcine parathyroid hormone has been developed and applied to measure immunoreactive parathyroid hormone (PTH) in plasma of pigs with hereditary vitamin D dependency rickets (VDDR) (pseudovitamin D deficiency rickets). Levels of 25-hydroxycholecalciferol (25-(OH)-D3) in plasma were measured by a protein binding assay. Both plasma concentrations of PTH and 25-(OH)-D3 showed an approximately 4-fold increase compared to normal pigs. PTH levels increased with duration of the disease. Daily dosing of the animals with 1--4 micrograms of 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3) reduced PTH concentrations and resulted in clinical healing. Iv administration of 10 micrograms of 25-(OH)-D3/day did not alter PTH concentrations nor the clinical symptoms. The results suggest that these animals suffer from regulatory hyperparathyroidism. The metabolic defect could be due to a failure of the kidney to convert 25-(OH)-D3 to 1,25-(OH)2-D3.


Plasma 1,25-dihydroxyvitamin D levels in pregnancy and lactation. Plasma concentrations of 1,25-dihydroxyvitamin D (1,25--(OH)2D), serum prolactin and serum parathyroid hormone (PTH) were followed during pregnancy and lactation in 16 women. High 1,25--(OH)2D was demonstrated in human pregnancy and lactation. A causative relationship between 1,25--(OH)2D and prolactin is discussed and a possible explanation of the mechanism of the augmented calcium absorption in human pregnancy and lactation is suggested.


HCS regulation in cultured placenta: action of glucose. The regulation of HCS secretion on placenta cultures in the presence of [3H] leucine was studied. When Eagle's medium containing 0.0055 M of glucose per liter is used, it is noted that the HCS increases regularly in the culture medium, whereas it diminishes in the explants. [3H] HCS represents about 50% of the [3H] proteins, and among these proteins HCS is preferentially secreted in the culture medium. The absence of glucose in the medium provokes a decrease in all of the cellular metabolism as well as a decrease in protein and HCS secretions, with an accumulation of preformed HCS in the tissues. An increase in the glucose level in the medium 0.011 and 0.027 M provokes a selective decrease of HCS secretion with an accumulation of preformed HCS in the tissues, determing a long term decrease in HCS synthesis. Insulin added in the mediums (60 microU/ml) does not change the results significantly. The use of structural analogues of the glucose shows that the point of impact of the HCS secretion regulation by the glucose is membranous; however, it seems that at a second stage one or some glucose metabolites also interven. There is no self regulation of HCS secretion in vitro.


[Action of metoclopramide bromide and metoclopramide chloride on the lower esophagogastric junction and the peristalsis of the lower 3d of the esophagus]. In 10 patients with esophageal hiatus hernia the effect of metoclopramide bromide and metoclopramide chloride compared with placebo, was studied by the double blind method. Both drugs produced an increase of the lower esophageal sphincter pressure and of the peristalsis of the lower third of the esophagus, only being statistically significative the action of metoclopramide chloride on the perstalsis. No significative side-effects were noted.


Perforation of the cecum, as a complication of pleural biopsy. A case of a rupture of the cecum following pleural biopsy in a patient with lung carcinoma complicated by inappropriate secretion of antidiuretic hormone is reported. We hypothesized that this unusual complication was caused by a neurogenic effect caused by the trauma of the biopsy causing an imbalance in the autonomic nervous system producing a sympathetic predominance leading to adynamic ileus and subsequent perforation.


[Pseudocysts of the pancreas. Considerations on 18 cases]. The authors present their experience in the study and treatment of 18 patients with pancreatic pseudocysts. Fifteen patients were operated on as follows: 6 external drainage 4 cyst-gastrostomy, 4 cystoyeyunostomy and one had distal pancreatectomy. Nine of the patients who were operated did well and 6 died in the postoperative course; one died after a prolonged period of time.


[Rectal tonometry in the differential diagnosis of constipation in pediatrics]. Based on the difficulties regarding the clinical, radiological, and histological diagnosis of colonic aganglionosis, we resorted the motility studies. Sixty-two children (15 days-10 years of age) were studied by means of rectal motility without knowing the results of the other auxilary methods. We obtained a clear difference between aganglionic and other group formed by constipated functional or psicogenic. We conclude that rectal motility studies have the advantage of being rapid and non-aggressive, besides avoiding rectal biopsy.


Clinical significance of estrogens in chronic aggressive hepatitis. For a long time, it has been assumed that stagnation of active estrogens in the blood gives rise to liver injury and causes a severe inflammatory process in the liver as well as affecting the clinical course of chronic aggressive hepatitis in women. During reproductive years, estrogen production, as gaged by the values of urinary excretion, follows a cyclic pattern. As the menopause is approached, urinary excretion of estrogens gradually diminishes and the cyclic fluctuation becomes more shallow. The titer continues to fall progressively in the post-menopausal years although some estrogen may be found even in aged women. Even though it must be assumed that estrogens are rarely produced in bilaterally ovariectomized women, chronic aggressive hepatitis is rather frequently encountered in practice in women after ovariectomy. To find a solution to the question of whether stagnation of active estrogen in the blood actually gives rise to liver injury, estrogen levels in the blood must be estimated in these patients. It will be desirable to estimate not the metabolites of estrogens in the urine but the estrogens or estrogenic substances themselves in the blood. The authors have estimated estrogens in the blood by means of radioimmunoassay and revealed a decrease in quantity of the estrogen values in the blood. Therefore, it can be stressed that the lack of estrogens in the blood must be taken into consideration because it has been pointed out that estrogens exert some form of liver-protecting influence against infection as well as the protracting factors of hepatitis.


Ischemic damage of the liver. Part I: In vitro investigation of the prevention of the ischemic lesion of the liver. In an isolated rat liver perfusion system the effects of normothermal ischemia on hepatic functions were investigated. After 30 minutes of anoxy bile production and BSP elimination capacity of the liver are significantly reduced. The quantity of secreted "ascites" from the surface of the liver several times high after anoxic damage, while oxygen consumption, portal venous pressure and ammonia elimination do not differ significantly from the controls. Pretreatment with insulin plus glucose, isoproterenol, hypoxanthine, chlorpromazine and glucagon (5 micrograms/100 g i.v., or 0.2 mg/100 g s.c.) does not reduce noticeably the normothermal anoxic lesion of the liver Glucagon (50 micrograms/100 g i.v.), allopurinol, dibenzyline, ATP-MgCl2 and aspartic acid enhance significantly the ischemia-tolerance of liver in vitro.


Ischemic damage of the liver. Part II: In vivo investigation of the prevention of the ischemic lesion of the liver. A new model for the study of ischemic liver lesion on rats has been worked out. Pretreatment with allopurinol, dibenzyline, methylprednisolone, glucagon, ATP-MgCl2 and aspartic acid reduced the overall mortality of ischemic liver injury. Administered after the anoxic hepatic lesion only glucagon and aspartic acid had beneficial effect on the survival rate. Under the influence of 30 minutes of normothermal ischemia the DNA synthetizing ability of the liver decreased. Aspartic acid, glucagon and ATP-MgCl2 significantly enhanced the regeneration of the ischemically damaged liver. These procedures might be suitable for donor pretreatment in liver transplantation, as well as for the treatment of other pathological states, causing a normothermal ischemia of the liver.


Follow-up study on patients with non-alcoholic and non-diabetic fatty liver. From a group of 424 patients with histologically verified fatty liver 92 patients without diabetes mellitus and alcohol abuse were subjected to follow-up examination for 3 1/2 years. 56 patients underwent second liver biopsy at this time; 20 of these patients had shown marked fatty liver at the initial liver biopsy examination. These 20 patients with marked fatty liver and 25 further patients with moderarte fatty liver could be followed up 5 and 7 1/2 years later; the clinical examination, the various liver function tests, liver scan and blind liver biopsy did not show any evidence of progression of fatty liver towards chronic inflammatory liver disorders or precirrhotic states. This clinical study therefore suggests the harmlessness of non-alcoholic fatty liver.


Intestinal sucrose assimilation in the rat after an Endogenous secretin release. Endogenously released secretin had no effect on the intestinal sucrose hydrolysis, the absorption of the sucrose split products, glucose and fructose, and the net water movement in the rat in vivo.


The effect of ethanol ingestion on plasma biochemistry and the pancreas in the rat. Intra-gastric ethanol given daily for 4 weeks caused transient elevations in plasma amylase and total protein with a fall in total calcium. Light microscopic examination of the pancreas at 4 weeks showed areas of acinar cell degranulation and necrosis without an inflammatory cell infiltrate. The pancreatic changes are unlikely to be an artefact, but rather a direct toxic effect of the alcohol as confirmed by the biochemical changes.


Effect of segmental epidural block on the course of labour and the condition of the infant during the neonatal period. Epidural block for vaginal delivery was given to 242 women during a 6-month period. Of these, 178 with a spontaneous start of labour and vaginal delivery were studied with respect to the effect of epidural block with bupivacaine-adrenaline on the course of labour and the condition of the infant in women with normal uterine activity and women with primary uterine inertia treated with oxytocin infusion. On average, the 178 women had already had a longer course of labour before the block was applied than women in control groups. The block per se had only a slight effect on the first stage of labour, but the effect on the second stage was more obvious, leading to outlet extraction in 50% of the primiparous women, compared to 12% of the controls. Transitory asphyxia at birth was observed in 4.5% of the infants of mothers with epidural block, but after 5 min, only 1% had an Apgar score of less than 7. Infants of mothers with epidural block were more often placed under observation or treated in the neonatal ward than infants in control groups.


Can postoperative pulmonary conditions be improved by treatment with the Bartlett-Edwards incentive spirometer after upper abdominal surgery? During the immediate postoperative course after upper abdominal surgery, pulmonary complications often occur, caused, inter alia, by reduced regional ventilation and by atelectases as a result of: (1) narrowing of the small peripheral bronchi, and (2) impaired respiratory function. Based on these pathophysiological mechanisms, an instrument (Bartlett-Edwards Incentive Spirometer) has been devised, which aims at giving the patient an opportunity of sustained maximal inspiration under standardized and controlled conditions. The use of this instrument has been followed by reports of a considerable reduction in postoperative pulmonary complications. In a controlled clinical investigation of the pre- and postoperative condition of the lungs, we were unable to show any beneficial effect of the instrument. In general, we have a low frequency of severe postoperative pulmonary complications, as compared with the results reported in the literature. We ascribe this to our very effective pre- and postoperative respiratory therapy.


Erythrocyte damage caused by the Haemotherm microwave blood warmer. Blood units (59) were warmed with the Haemotherm microwave blood warmer and seven units were warmed in a water bath for comparison. The influence of the final blood temperature, the size and the hematocrit of the units on the erythrocyte lesion was studied. Extracellular hemoglobin and potassium, hematocrit, osmotic fragility and mean cellular volume were used as indicators of red cell damage. Warming in the water bath caused no erythrocyte damage at temperatures below +46.8 degrees C. Higher temperatures caused progressive morphological changes and hemolysis. Units of red cells in saline warmed to temperatures above +46.3 degrees C with the Haemotherm showed intense hemolysis and changes in all parameters used. Below this temperature no erythrocyte damage occurred. When the amount of blood warmed was less than 300 g or when the hematocrit exceeded 0.70, the blood mixing mechanism became insufficient, leading to local overheating and hemolysis. Therefore, erythrocyte concentrates in a Fenwal blood bag should never be warmed by the Haemotherm. The mean plasma hemoglobin increase of the ten whole blood units warmed by the Haemotherm to +36.0-36.8 degrees C was 123 mg/l. The results of the present study indicate that microwaves per se are not harmful to erythrocytes but that poor penetrance of microwaves, together with insufficient blood mixing during warming, are the critical factors leading to hemolysis.


Circulatory pattern and duration of action of naloxone in dogs with and without opioid pretreatment. We investigated the circulatory pattern of naloxone reversal after high-dose fentanyl infusion in dogs. Within 1 min there was a sudden decrease in total peripheral resistance with a concomitant increase in stroke volume index. All other parameters changed back in direction of pre-fentanyl values in various degrees with peak effects in about 3-7 min. The persistency of reversal was different for individual parameters, but 20 min after injection of naloxone almost all changes induced by antagonisation of narcotic activity had returned to pre naloxone levels. In a control series with animals not pretreated with opioid, naloxone was shown to have no specific pharmacologic action of its own.


A new transducer for respiratory monitoring. A description of a hot-wire anemometer and a test procedure for general use. A respiratory transducer based on the constant temperature anemometry principle has been developed for respiratory monitoring, and as a tool for bedside evaluation of pulmonary function. The transducer is characterized by a dynamic range from 0-2.5 1/s and an upper limiting frequency of 50 Hz. It is designed with a view to a low pressure drop of 2.5 mbar/1/s and a minimum dead space of 5 ml. The transducer has been tested using a generally applicable procedure which includes both static and dynamic test set-ups. The influence of variation in gas composition, temperature and pressure, together with variations in tidal volume and respiration rate, have been investigated. The results show that the transducer registers the immediate value of gas flow-rate with a mean error less than 5-10% in all situations which are predictable in clinical use. The mean error can be reduced to less than 5% when systematic errors are eliminated.


"Hyperfrontal" distribution of the cerebral grey matter flow in resting wakefulness; on the functional anatomy of the conscious state. Regional cerebral blood flow was measured with the intra-arterial 133 Xenon clearance technique using a multidetector device in 11 patients undergoing carotid angiography (with normal findings). During the flow studies the patients were awake and strict resting conditions were observed. The patients did not move or speak, and sensory stimulation were kept at a minimum. It was confirmed that the distribution of the grey matter blood flow showed a hyperfrontal pattern, the flow in frontal regions being significantly (20-40%) higher than in postcentral, occipital and temporal regions. There were no technical factors or morphological features of the telencephalon which could explain this difference. It was also shown that the distribution of the white matter flow and the relative weight of the grey matter corresponded in general to hemisphere morphology. Since in normal nervous tissue the blood flow is regulated by the neuronal activity, the following interpretation is given of the main finding. The hyperfrontal flow distribution of the grey matter (cortical) flow during resting wakefulness shows that there is a high activity in frontal "efferent" (motor-behavior) regions. At the same time there is a low activity in post-central and temporal "afferent" (sensory-gnostic) cortical areas. The high frontal activity suggests that in the resting conscious state--unaccompanied by movements, speech or behavioral reactions--the brain is active with an anticipatiory "simulation of behavior". The low postcentral flow, on the other hand, may possibly be related to a global inhibition of the sensory input. Several clinical as well as general biologic arguments are forwarded to support this interpretation. It is further pointed out that the hyperfrontal distribution of the resting activity in the cerebral cortex correlates to the resting EEG, in which lower frequencies (the alpha rhythm) predominate in postcentral and temporal regions where there is a low flow/activity, and high frequencies in frontal areas where the blood flow is high. This is in agreement with the finding that the blood flow and metabolism of the brain correlate to the EEG frequency content.


Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs. Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.


Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen and intracranial pressure during and after severe prolonged arterial hypoxia in dogs. The role of dopamine in the deep hypoxic state. The effect of extreme, prolonged arterial hypoxia on cerebral blood flow, oxygen uptake and intracranial pressure was studied in anesthetized dogs. The experiments were performed along two lines. Both started with a period of hypoxia of about 40 minutes to 2 hours. Thereafter normoxia was restituted in one group and the animals were studied for another 1-2 hours. In the other group with continued hypoxia dopamine was administered. During the hypoxic period the cerebral blood flow decreased mainly as a result of vasoconstriction after an initial marked flow increase. Cerebral oxygen uptake was reduced. Intracranial pressure increased, largely in proportion to blood flow changes, and no indication of important brain edema appeared. In the "recovery" period at normoxia the cerebral oxygen uptake showed an increase during the observation time. The blood flow, initially high, returned to the control level within the observation period. Dopamine infusion during continued hypoxia induced a vasodilatation, with reduction of vascular resistance to the values found at the induction of hypoxia, and with an increase of the cerebral oxygen uptake. An important role of endogenous dopamine in the hypoxic vasodilatation is suggested.


Chronic diphenyl hydantoin encephalopathy in mentally retarded children and adolescent with severe epilepsy. An account is given of chronic diphenyl hydantion (DPH) encephalopathy in 21 mentally retarded epileptics with increasing psychomotor deterioration, choreiform hyperkinesia, deposits of immunoglobulins in the skin, and changes in serum immunoglobulins. Three months after withdrawal of DPH the condition proved partially reversible, from the clinical as well as laboratory point of view. Eleven patients have been followed for 1 year after discontinuation of DPH, and the findings were largely unchanged from the 3-month follow-up examination. Before the drug was withdrawn, seven patients exhibited deposits of immunoglobulins at the dermo-epidermal junction and in vessel walls. At the end of 1 year such deposits were found in only three patients, all of whom were on another antiepileptic drug.


A numerical scoring system for the classification of multiple sclerosis. A simple, numerical system for the classification of multiple sclerosis into probable and definite categories is proposed. This system is based upon the analysis of the clinical symptomatology of 111 autopsy-proved cases of the disease from England, Norway and the United States. It is not designed to be used as an aid in the diagnosis and should be applied only to those cases where multiple sclerosis is suspected. It permits the incorporation of data obtained by means of evoked responses studies, psychological evaluations and other methods for confirming anamnestic information or delineating some asymptomatic lesions. The numerical system also provides a means for plotting the temporal evolution of the disease strictly in terms of the appearance of new signs and symptoms since recurrences of previously experienced symptoms cannot be scored; thus it has the advantage of not allowing so-called exacerbation due to physiological or psychological factors to falsely suggest disease progression or activity. The major use of this scoring system is to provide a reasonably reliable means of comparing epidemiologic data from different investigators by more clearly defining the probable and definite categories.


Study of epidemiological and etiological factors of amyotrophic lateral sclerosis in the province of Florence, Italy. An epidemiological survey of amyotrophic lateral sclerosis (ALS) based on 83 patients living in the province of Florence (central Italy) showed an incidence of 0.714 X 100,000 inhabitants and a prevalence of 2.142 X 100,000 inhabitants. The disease was found to be more prevalent in males (sex ratio 1.3--1). Average age of onset was 59 years (57 +/- 4 for males and 61.6 +/- 3 for females). No particular geographical distribution was noted. 59 % of the patients presented the conventional amyotrophic form, while 10 % and 30 % were those with the bulbar and polyneuritic type, respectively. A survey of the social and economic status showed ALS to be more frequent in manual workers (P less than 0.001). Among all patients 31 % presented evidence of trauma; however only in 15 % of them could the trauma be chronically and topographically related to the onset of ALS. The presence of other diseases associated with ALS was examined but the combination found may be only casual.


Association of glycerol to dexamethasone in treatment of stroke patients. A prospective study of 93 acute stroke patients randomly selected by type of antiedema treatment given (hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke.


Clinical, psychometric and radiological signs of brain damage in chronic alcoholism. A total of 34 male inpatients with advanced chronic alcoholism and a clinical picture of impaired working capacity were examined by pneumoencephalography and 29 of them by psychometric tests. All or almost all (depending on the criteria chosen) showed degenerative changes in the cerebrum and about one-third showed degenerative changes in the cerebellum. All 29 patients who were psychometrically investigated showed signs of cerebral dysfunction. The correlation between the single pneumoencephalographic and psychometric variables was at most 0.46 and abnormalities of the third ventricle showed the highest correlation to the psychometric variables. An overall assessment of the degree of degenerative changes in the cerebrum (pneumoencephalographic findings) and the degree of cerebral dysfunction (psychometric findings) resulted in a correlation of r = 0.54 (P less than 0.001).


The healing of experimental fractures by compression osteosynthesis. I. Torsional strength. Biomechanical properties of osteotomized rabbit tibio-fibular bones fixed with 6-hole stainless steel AO/DCP plates were investigated with torsional loading 3 to 24 weeks postoperatively. During the first 9 weeks maximum torque capacity, energy absorption and torsional rigidity increased, reflecting progressive bony union between the fractured bone ends. From 9 to 24 weeks the values of torque capacity and energy absorption decreased, whereas torsional rigidity seemed to reach a steady state without further significant changes. For the three parameters considered, the mean percentage differences between the osteotomized plated bones and their paired-sham-operated controls were 69, 64 and 80 per cent, respectively. The results suggest that internal fixation of fractured bones provides conditions for undisturbed fracture healing, but that subsequently the rigid nature of the implant has an adverse effect on the cortical bone, which slowly loses strength. Thus the optimal time for removal of the plate seems to be shortly after the fracture has healed and before the bony tissue had been weakened by secondary changes, such as cancellous transformation and spatial rearrangement of the tubular bone.


The healing of experimental fractures by compression osteosynthesis. II. Morphometric and chemical analysis. The effects of rigid plate fixation on the structure and chemical composition of bones during healing of experimental fractures were studied by morphometric and chemical analysis at intervals of 3 to 24 weeks after attachment of six-hole AO plates to osteotomized rabbit tibiae. After fracture union gradual porotic transformation could be observed from 9 weeks onwards, with rapid excavation and breakdown of the cortical wall. During the study over 24 weeks the degree of porosity increased from 9.0 +/- 4.8 per cent to 37.5 +/- 10.2 per cent (P less than 0.001). This osteoporosis was accompanied by formation of new subperiosteal bone. The changes in the tubular bone led to a progressive increase in overall diameter and in the area occupied by the medullary cavity throughout the experiment. In the osteotomy area increased values were found for the content of hexosamines and the ratio of hexosamines to hydroxyproline at 3 weeks, indicating formation of connective tissue in the fracture area. Later on, no chemical signs of callus formation could be detected. In spite of the slight increase in the content by hydroxyproline, reflecting the formation of new bone subperiosteally, the chemical composition of the unresorbed cortical bone remained unchanged.


Fracture healing in rabbits after osteotomy using the CO2 laser. Fracture healing was studied in 28 rabbits after their femurs had been osteomized using the carbon dioxide laser. Twenty rabbits whose femurs were osteotomized by means of a Gigli saw served as the control group. Fracture healing was initially delayed in the laser cut femurs, yet after 60 days no significant difference between the groups could be detected. The initial delay was caused by thermal damage to the laser cut bone edges. Further fragmentation of the damaged bone occurred during the immediate postoperative period.


Assessment of fracture healing by vibration. The wave signal from percussion of a bone (i.e. percussion-note) has been used to evaluate the extent of bony consolidation after fracture. Forty-one cases with a fresh tibial fracture and eight cases of delayed union of the tibia were investigated. The medial malleolus of the tibia was struck with a tapper and the vibration signal was picked up at the medial region of the tibial tuberosity. The changes in the signal waveform of the percussion-note with time were investigated. As healing proceeds, the signal waveform of the fractured bone approaches that of intact bone. In cases of delayed union, the character of the wave does not improve sufficiently with time. The authors are convinced that this is a promising new method for the early diagnosis of delayed union.


The vascularization in the amputation stumps of rabbits. A microangiographic study. With the aid of microangiography the vascularization in the amputation stumps of 108 rabbits was studied, both in extremities with normal circulation and in those supplied with collaterals. It was found that the vascularization of the normal leg was altered by amputation, with the development of newly-formed, pathological, spirally-twisted vessels. Closure of the stump with myoplasty, however, counteracted this vessel formation, and hypervascularization took place through normal arteries. After amputation of extremities supplied with collaterals, the influence of amputation on collateral function and vascularization in the amputation stump was dependent on the time interval between arterial occlusion and amputation.


A late neurologic complication of scoliosis surgery in connection with syringomyelia. A case of scoliosis in connection with syringomyelia is described. Theories are proposed to explain the progression of the neurological symptoms after surgical correction and fusion of the deformity. Special points are emphasized that will aid in the recognition of syringomyelia in scoliosis patients. i) Abnormal neurology, in particular a dissociated disturbance of pain and temperature in the upper extremity. ii) Abnormal localization of a scoliosis curve. iii) Rapid progression of the scoliosis. iv) Bony anomalies of the upper cervical spine. v) Increased diameter of the cervical spinal canal.


Controlled hypotension in hip joint surgery. An assessment of surgical haemorrhage during sodium nitroprusside infusion. Controlled hypotension, combined with light balanced anaesthesia, was employed during total hip replacement operations on 25 patients. Sodium nitroprusside (Nipride, Roche), in the form of a 0.01 per cent (100 micrograms/ml) infusion, was used as a hypotensive agent. The mean arterial blood pressure (MABP) was lowered from 108 to 64 mmHg (range 60--70) (P less than 0.001). The average blood loss during the operations was 212 ml and none of the patients required homologous blood transfusion. In comparison with 25 normotensive patients undergoing similar surgery, the difference in the mean volume of haemorrhage between the two groups was 826 ml (P less than 0.001). The difference in the total haemorrhage, however, between the same two groups was 518 ml (mean) (P less than 0.01). The results were compared with those of another investigation in which epidural anaesthesia was used to diminish bleeding during surgery on the hip.


Osteosynthesis of displaced fractures of the femoral neck. A comparison between Smith-Petersen Osteosynthesis and sliding-nail-plate osteosynthesis -- a radiological study. Smith-Petersen osteosynthesis has been compared with sliding-nail-plate osteosynthesis in a prospectively planned, randomized, follow-up study of 197 cases of displaced medial fractures of the femoral neck. A total of 131 patients were followed for more than 2 years. After Smith-Petersen osteosynthesis 66 per cent of the fractures united and after sliding-nail-plate osteosynthesis 77 per cent united. The results showed that the choice of fixation devices is of minor importance compared with exact reduction of the fracture and optimal positioning of the nail.


Subcapital fractures of the femur. Re-operations with internal fixation. Over a period of 5 years, 55 re-operations with internal fixation were performed on 51 patients. The re-operations constituted 9.2 per cent of all operations employing internal fixation for subcapital fractures of the femur during that period. The indications for re-nailing were penetration of the nail through the femoral head, or slipping of the nail, with or without dislocation of the fracture. Only 26 per cent of the re-nailed fractures healed. Seventy-three per cent showed avascular necrosis and 61 per cent non-union.


Total hip replacement by the Müller-Charnley prosthesis. A follow-up study of 238 operations after 2 to 7 years. A prospective study of 238 total hip replacements, with the Müller prosthesis, is presented. The complications in the total material and the results in 216 hips with follow-up times from 2 to 7 years are described. Eighty-four per cent of the hips were free from significant pain and 64 per cent had a total range of motion exceeding 160 degrees. Aseptic loosening of the femoral component, entailing reimplantation, has occurred in 6.7 per cent and, in addition, 9.2 per cent show radiological evidence of deterioration of the fixation of the femoral component. No deep infection has been encountered. None of the hips has ended as an excision arthroplasty.


Significance of free-dorsiflexion of the toes in walking. Dissection reveals that the ball of the foot contains a connective tissue framework with transverse, vertical, and sagittal fibers, all connecting the skin with the proximal phalanges of the toes. Dorsiflexion of the toes tightens the framework and thereby restricts passive movements of the skin, enabling shear forces to be transferred to the skeleton. An electromechanical oscillator was constructed that applied oscillatory shear forces of constant amplitude (+/- 0.2 N) to the skin and at the same time measured the resulting motions. It was found that the toes should be dorsiflexed by 35--40 degrees to restrict skin mobility to 50 per cent and by 50 degrees to restrict it maximally. The results were compared to actual dorsiflexions of toes during walking. These dorsiflexions were measured on slow motion film and with still pictures with light tracks formed by light emitting diodes. Maximal dorsiflexion during push off was found to be 60 degrees for feet walking without shoes, 45--50 degrees for feet walking in soft shoes, and 25--30 degrees for feet walking in a stiff shoe of the minus-heel type. Dorsiflexion was further found significant for arch support and for the mechanics of the forefoot during push-off.


Hair cell condition and auditory nerve response in normal and noise-damaged cochleas. Histological and physiological data are presented from cats born and raised in a low-noise environment and from cats with long-standing, noise-induced threshold shifts. Even after a 1 1/2-year survival from acoustic trauma, there were threshold elevations of roughly 40 dB in the response of single auditory-nerve fibers which could not be correlated with significant loss of hair cells. An attempt was made to correlate these threshold differences with differences in the condition of the sensory cells as seen in a light-microscopic examination of epon-embedded surface preparations. Of all the histological features evaluated, the orderlines of the stereocilia, on both inner and outer hair cells, showed the closest correlation with single-unit thresholds. In the final analysis, most of threshold shift in the noise-exposed ears could be accounted for by loss or damage to sensory cells clearly visible under the light microscope.


Structural changes in the organ of Corti of the guinea pig after obstruction of the arterial blood flow to the inner ear. Forty-one young guinea pigs were studied after obstruction of the anterior inferior cerebellar artery in order to ascertain the effects on the surface specimen of the organ of Corti. Most of the animals had damage in the third and fourth turns (22) and a minority of these had dizziness and destruction nystagmus (3). Our hypothesis is that one of the causes of Meniere's disease is an interference with the inner ear circulation, and our plans for testing this hypothesis are given.


Further studies of the membrane potential of the stria cells of the guinea pig in vitro. Negative membrane potentials from the stria vascularis of the guinea pig have been recorded in vivo.  Stable negative membrane potentials from the stria cells have also been recorded for as long as 2 minutes in vitro.  They varied from -20 mV to -49 mV, irrespective of whether the stria vascularis was immersed in Ringer's solution for in K-Ringer's solution (approximately to the composition of an endolymph). Labelling of the inserted stria cells from which the membrane potential had been recorded demonstrated that the microelectrode tip was inside the cell. These cells will continue to show electrical activity for some time when immersed in suitable media.


The effect of cerebrospinal fluid pressure on perilymphatic flow in the opened cochlea. Scala tympani of guinea pigs was perfused with elevated potassium solutions whose concentraus recovery, the concentration curve showed a 'break' approximately 3 min after perfusion ceased. When the CSF pressure was released by opening the cisterna magna, cochlear flow was markedly reduced, and the recovery curve became smoothly exponential, following a much slower return to control levels. This finding lends support to the idea proposed by Moscovitch, Gannon & Laszlo (1973) that longitudinal flow of CSF contributes to perilymph efflux in the patent cochlea.


The uptake of methyl mercury in guinea pig cochlea in relation to its ototoxic effect. Guinea pigs were treated for 7 days by daily subcutaneous injection of methyl mercury chloride labeled with 14C, the total dose of which was 17 mg Hg/kg. In these animals the cochlear microphonics and whole-nerve action potentials were suppressed in the basal turn but there was no marked losses in the third turn of the cochlea. The endocochlear potential was not decreased in magnitude. At the end of the treatment there was no accumulation of mercury in the perilymph, endolymph and cerebrospinal fluid. Uptake and elimination of mercury in the cochlear fluids were studied in guinea pigs which were treated by a single intravenous injection of 203Hg-labeled methyl mercury, the dose of which ranged from 0.2 to 17 mg Hg/kg. The results indicated that mercury concentration ratio of the blood relative to cochlear fluids was comparable with the blood to plasma ratio reported previously. In contrast to lack of accumulation in the extra cellular environment, it is likely that tissues of the sensory end organs in the cochlea accumulated methyl mercury.


Extracorporeal preservation. Organ culture of the post-natal mammalian inner ear. Postnatal (newborn and mature) inner ear organs from CBA/CBA mouse and guinea pig were analysed concerning hair cell survival in an in vitro system. After only a few days in the artificial surroundings a transformation of hair cell characteristics occurred, in the form of either loss of sensory hairs (cochlear hair cells) or hair fusion (vestibular hair cells), although the hair cell itselt survived for a considerably longer time. Intracellular myelin figures became evident after 2--3 days in culture. However, a considerable individual variation among hair cells was observed concerning the ultrastructure of the cell at this stag in vitro. Completely normal hair cells could in rare cases be recognised after 1 week in organ culture (cochlear inner hair cells of the CBA/CBA mouse). Loss of the surface structures of the hair cells is likely to constitute an irreversible transformation not in agreement with the true hair cell characteristics.


Perennial atopic rhinitis as an early stage of bronchial asthma. Etiologic factors and incidence of bronchial hyperreactivity as a 'stigma' of bronchial asthma were studied in 237 patients suffering from perennial atopic rhinitis. All pateints underwent detailed laryngologic and allergologic examiniation and pulmonary function tests at rest, after exercise, and after histamine inhalation. Most often the patients were sensitized tungal allergens. Bronchial hyperreactivity, typical of bronchial asthma, was observed in 48.52% of patients. Results were analysed statistically. It was concluded that early institution of causal therapy can cure the symptoms of rhinitis and prevent evolution of the disease into atopic bronchial asthma in patients already suffering from bronchial hyperreactivity.


Postural variations in nasal resistance and symptomatology in allergic rhinitis. Variations in nasal resistance (NR) which was induced by positional change of the head were examined in 15 normal subjects and 15 patients with allergic rhinitis. Nasal symptoms were also observed in 15 patients and nasal symptom scores were calculated. Concerning the postural variations of NR, patients with allergic rhinitis showed much more remarkable change than normal subjects. Nasal symptom scores of all patients decreased after nasal insufflation of Beclomethasone Dipropionate for 2 weeks. Coincidence between improvement in postural variations of NR and that of nasal symptom score was not always seen in each patient. However, as a mean value of 15 patients, postural variations of NR improved after nasal insufflation of Beclomethasone Dipropionate.


Endoscopic examination of the nasopharynx. Endoscopic examination of the nasopharynx is a simple and rapid procedure. The inspection can be made through the nose. This method is recommended for screening. If abnormalities of the nasopharynx are disclosed and are to be studied in detail, and particularly if such abnormalities are to be documented photographically, it is necessary to inspect them through the oropharynx while the soft palate is drawn forward. It is possible under direct vision to take representative biopsy specimens, and it is easy to take photographs for the purpose of documentation, comparison and education. This procedure can to a great extent replace diagnostic excision of tissue from the nasopharynx under general anaesthesia. Especially with a view to early diagnosis of malignant disease of the masopharynx, it is important to extend the use of this method, which can be performed with little discomfort to the patient.


Rhinoscopical findings in nickel workers, with special emphasis on the influence of nickel exposure and smoking habits. Rhinoscopy and X-ray examination were performed on 318 nickel workers and 57 controls, to study the significance of these methods in detecting cancerous and precancerous mucosal changes. The clinical and radiological findings were compared with histopathological data and mucosal nickel concentrations determined in nasal biopsy material from the middle turbinate, with duration of nickel exposure, and with tobacco smoking habitl changes (43%) than the controls (26%), (0.01 less than P less than 0.02), mainly due to differences in frequency of hyperplastic rhinitis. Thirteen nickel workers (4%) had nasal polyps. Two of these cases, both employed at the nickel refinery for 28 years, appeared to have nasal carcinoma, according to histological examination. No distinct association was established between rhinoscopical findings and epithelial dysplasia found by histological examination. The explanatory values for the rhinoscopical findings of different factors, such as working category age, duration of nickel exposure, grams tobacco smoked per week, and nickel content of nasal mucosa, were evaluated by applying a stepwise multiple regression analysis. Number of years from first employment at the nickel refinery and tobacco consumption were the only explanatory factors that showed a statistically significant correlation to the rhinoscopical findings. The radiological examination revealed few characteristics findings. Chemical analysis of cigarettes handrolled by nickel workers showed high nickel concentrations compared with non-contaminated cigarettes.


Carcinoma occurring in branchial cleft cysts. In order to find histological data in the differentiation between branchial cleft carcinomas and metastatic carcinomas, the specimens from 154 patients with branchial cleft cysts and 7 patients with an isolated tumour in the neck with unknown primary tumour were reviewed and compared with 10 normal lymph nodes. Absence of lymph node structures as peripheral lobulation, internodular trabeculae and perinodular sinuses in branchial cleft cystc, are found valuable for distinguishing primary carcinoma of branchial cleft cysts from metastases. A correct diagnosis of this rare tumour is important in order to avoid overtreatment of these patients, who have a good prognosis if treated with surgical excision only.


Inherited congenital bilateral atresia of the external auditory canal, congenital bilateral vertical talus and increased interocular distance. Six out of twenty descendants of a reportedly affected grandfather have congenital bilateral symmetrical and isolated subtotal atresia of the external auditory canal. Four of the six affected descendants have bilateral foot anomalies--two affected cousins having congenital vertical talus. All of the three affected boys in the third generation have increased interocular distance. Short fifth fingers, bilateral single transverse palmar creases, pyloric stenosis and congenital exotropia were found infrequently and are considered coincidental features. Apart from the atresia, oto-rhinolaryngologic examination, mental function, dermatoglyphics, IgA, kidney function and heart function of the affected descendants were all normal. The karyotype of four affected descendants examined was normal. An autosomal dominant inheritance with variable expressivity is suggested.


Congenital unilateral lower lip palsy.

Congenital unilateral lower lip palsy. Thirty-nine cases of congenital facial asymmetry, in which one corner of the mouth does not dip downward symmetrically with the other, are presented. The author has termed this condition 'congenital unilateral lower lip palsy' (CULLP). CULLP was the most frequent condition in congenital facial anomalies seen in our clinic. Complaints were purely cosmetic. No functional disorders in pronouncing labial sounds or in suckling were noticed. As for pathogenesis, an insufficiency of the unilateral depressor labii inferior muscle is the most likely cause. An important point is that the lower lip, when drawn down, is normal, whereas the contralateral lip is paralysed. As far as facial asymmetry is concerned, CULLP is a minor deformity. Nevertheless, possible association with other anomalies must be seriously considered when examining patients, especially neonates. As for treatment, selective facial nerve blocking is successfully done in our clinic.


The pharyngo-oesophageal sphincter after laryngectomy. A manometric investigation. The function of the pharyngo-oesophageal sphincter in patients subjected to total laryngectomy has been evaluated by manometric measurement, and the results related to the patient's ability to speak with an oesophageal voice, as well as to the occurrence of dysphagia. Seventeen totally laryngectomized patients were studied. The intelligibility of the patient's oesophageal voice was classified according to the scale: good (group IV), middle (group III), poor (group II) and unintelligible (group I). The manometric investigation was carried out with a continuously perfused low compliance system with three side holes, and the results of the patient investigation were compared with those from a normal material. It was possible in three patients only to demonstrate a resting tone corresponding to the pharyngo-oesophageal sphincter. The pressure was lower in these patients than in the normal material. No correlation was found between any of the three parameters: sphincter pressure, intelligibility, and the presence of dysphagia.


[Stereophonic apparatus: our hearing aid test]. The authors wanted to verify the advantages produced by binaural amplification in the loudness and in the speech identification. To value the improvement in speech identification they used the Jerger's test (1976); and to value the loudness improvement they measured, gain characteristics of the aid with monoaural and binaural amplification. They executed the test on 50 hearing aid users, chosen among 10 and 84 years old, suffering from sensorineural bilateral hearing loss between 40 and 80 dB. It results that : 1. The gain obtained by the use of binaural amplification is 5 dB lower than the one obtained by monoaural. 2. The binaural amplification permits a remarkable advantage in speech identification, the advantage is directly proportionated to deafness. The authors conclude that the described test is valid, simple and that it is possible to apply it by cheap instruments.


[Vestibular testing in Ménière's syndrome]. Extensive vestibular examination was done in fifty patients with unilateral Menière's disease in the interval between the attacks of vertigo. Horizontal and vertical eye-movements were recorded by electro-oculography. In 80% of the significant difference was found in the slow phase velocity of the nystagmus due to caloric stimulation between the normal and pathological ear (mean difference 41% +/- 24,2). A spontaneous nystagmus was found with closed eyes in 58% of the patients with a mean value of 2,5 degrees/sec +/- 1,6 and a positional nystagmus in 76% with a mean value of 2,3 degrees/sec +/- 1,5. Also in the silent phase (between the vertigo-attacks) distinct abnormalities can be found in the vestibular examination tests.


Vertigo, particularly of vascular origin, treated with flunarizine (R 14 950). The antivertiginous properties of flunarizine were evaluated in three consecutive studies --- two open and one double-blind --- in an total of 99 patients showing definite vertigo. Dosage was two tablets (= 20 mg) t.i.d. for three days in Study I (50 patients), 20 mg. t.i.d. for two months in study II (31 patients), and weekly decreasing doses of four, three, two and one (maintenance) tablets of flunarizine or placebo for three months in study III (9/18 patients with vertigo of recent origin). Improvement of vertigo was significant both objectively and subjectively in studies I and II. In study III, objective tests were always clearly in favour of flunarizine, but subjectively, flunarizine was superior only by month two. Vertigo of vascular origin seemed to be a preferential indication for flunarizine treatment. No major side-effects were found in these studies.


[Salivary scintigraphy and sialography. Comparison of results in various common disorders]. We recommend the association of scintigraphy and sialography in salivary glands pathology. The obtained results of both methods are very often complementary or convergent. In case of sialadenitis or dry mouth, it happens that results diverge, but these differences can be explained if one remembers the anatomo-physiological alterations. To prevent a false positive result of atrophy. The scintigraphy must always be realized before sialography. N.B. "Scintigraphy" means isotopic sialography. "Sialography" means conventional sialography.


Valvular structure at the branching portion of the human aorta. The Valvular structure developing at the site from which an artery was given off was examined. The valvular structure consisted mainly of smooth muscle cells, and was found at the openings of such small arteries as the intercostal and lumbar arteries. It was a crescent membrane-like structure extending from the peripheral edge of the opening to the downstream edge. This structure was indistinct in newborn infants, became gradually distinct in infants and stood out in teen-agers. It became rather thick and rounded in human beings more than 20 years of age. With further advance in age, the smooth muscle cells became degenerated and hyalinized with some disappearing eventually. In the valvular structure smooth muscle cells running longitudinally in the same direction as the blood stream were arranged in such a manner as a Venetion blind. This arrangement seemed to suggest that the valvular structure might have some function to adjust the blood stream at the branching portion of the aorta.


Ultrastructural study of benign osteoblastoma of the maxilla. The ultrastructure of benign osteoblastoma of the maxilla in a 14-year-old boy was studied. Morphologically, the tumor tissue was composed of abundant osteoid of a trabecular form, and cellular and vascular connective tissue. The cellular components were osteoblasts, osteoclasts, osteocytes entrapped within the osteoid, and small perivascular cells of two types. The small cells of one type were ovoid and had a relatively large nucleus and a dark cytoplasm. The cells of the other type were elliptical and had a clear cytoplasm. The former seemed to be a preosteoblast and the latter could not be identified. The osteoblast was the predominant cell in this lesion and was characterized by the presence of abundant rough-surfaced endoplasmic reticulum and several Golgi complexes. These characteristics indicated the pronounced activity of collagenous fiber synthesis and the matrix of the osteoid tissue.


Collision tumor of the stomach with carcinosarcoma and tubulo-papillary adenocarcinoma. The present case is an autopsy case of a 66-year-old male who developed a collision tumor in the stomach which originated from carcinosarcoma of Borrmann type II in the gastric antrum and from papillary adenocarcinoma of Borrmann type III in the corpus. The carcinosarcoma consisted of tubular carcinoma and sarcomatous transformation of stroma from the carcinoma.


Destruction of Toxoplasma gondii by HC1 solution. It was shown that the destruction of Toxoplasma gondii by pepsin-HCl solution was due to the acid only. Endozoites were destroyed faster by hydrochloric acid than cystozoites. Furthermore, endozoites were stained faster than cystozoites in an alkaline solution of methylene blue. For this reason, endozoites were assumed to have a higher permeability than cystozoites. The action of hydrochloric acid was used for demonstration of cystozoites in mouse peritoneum cavity. No cystozoites were found after inoculation of virulent parasites.


Ochratoxin A contamination of foodstuffs in an area with Balkan (endemic) nephropathy. Ochratoxin A is a nephrotoxic fungal metabolite (mycotoxin) occurring in foodstuffs. The compound is causally associated with mycotoxic porcine nephropathy, a disease comparable with a human kidney disease, Balkan (endemic) nephropathy. A survey of 768 samples of foodstuffs (cereals and bread), locally produced in an area of Yugoslavia where Balkan (endemic) nephropathy is prevalent, has revealed that ochratoxin A is constantly present in parts of foodstuffs. The mean frequency of ochratoxin A contamination of cereals in the study period was 8.7 per cent, but a pronounced annual variation was encountered, with frequencies of contamination up to 43 per cent. These contamination frequencies are higher than those reported elsewhere for foodstuffs for human consumption. Thus further evidence is provided to support the hypothesis that ochratoxin A might by a disease determinant of Balkan (endemic) nephropathy.


Electron microscopy of a filamentous, segmented bacterium attached to the small intestine of mice from a laboratory animal colony in Denmark. A filamentous, segmented bacterium was observed in the small intestine of the SSC:AH stock of mice from the Statens Seruminstitut (Denmark) animal colony but was absent in golden hamsters and guinea pigs from the same colony. The bacterium is attached to the epithelial cell by a special segment (holdfast) and causes specific changes in the epithelial cell at the site of attachment. Once attached the bacterium appears to undergo a complex life cycle which involves the development of a long filament divided into a number of segments within which holdfasts or spores are formed. This organism is morphologically identical to a bacterium found in mice and rats in the USA, but this is the first report of such an infection in Europe.


Genetic control of the spontaneous hypertension in the NZB/Cr strain of mice. Immunogenetic considerations. NZB/Cr mice spontaneously develop a high blood pressure. This hypertension is developed during the first two months of age. F1-hybrids between NZB/Cr and C57/B1/6J (a normotensive mouse strain which does not spontaneously develop hypertension) also develop a high blood pressure, showing that the phenomenon is inherited as a dominant trait. The gene(s) responsive for the phenotypic high blood pressure is localised outside the MHC of the mouse (the H-2 complex). However, H-2 typing of backcrosses and F2-hybrids gave a weak evidence that genes located in or closely linked to the H-2 complex do influence the spontaneously developed high blood pressure in the NZB/Cr strain of mice. It is emphasized that further studies in larger populations of mice is necessary to establish the importance of linkage of genes to the H-2 comlex for the spontaneous hypertension in the NZB/Cr strain of mice.


Formation of germinal centres during neonatal tolerance in the chicken. Chickens were made tolerant to BSA at the time of hatching. During the tolerance, antigenic stimulation with BSA resulted in poor germinal centre formation as compared to normal immunized control birds. The tolerance persisted for at least 6 weeks. Its breakdown had hardly started at the age of 12 weeks, both IgM and IgG antibody responses against BSA remaining negligible. Stimulation with the unrelated antigens SRBC and Brucella abortus resulted in good antibody responses, but the number of germinal centres was smaller in the tolerant birds than in normal controls.


Clonidine increases the rate of blood pressure recovery from splanchnic nerve stimulation. Clonidine reduced both the pithed rat heart rate and blood pressure responses to low frequency sympathetic nerve stimulation. Marked shortening of the blood pressure response but not of the heart rate or of the responses to injected noradrenaline was found. This shortening effect was independent of the number of impulses in the train (4--120 impulses) and of the impulse frequency. It lasted for more than 1 hour and was found to affect only the late part of the pressor decay curve. Nerve stimulations at 2 Hz simulating bursts of different periodicity in the splanchnic nerves showed that the cumulation of the blood pressure between bursts was affected only when these were applied at intervals of more than 10 sec. The effect could not be influenced by antagonists to several known transmitters, by ligation of the renal arteries or by adrenalectomy and does not seem to be mediated by pre-or postjunctional alpha receptor stimulation.


Effects of digoxin in isolated human pulmonary vessels. In isoalted human pulmonary arteries and veins the contractile response to noradrenaline (1.8 X 10(-5)M) was 33 +/- 7.4% and 20 +/- 4.5% (Mean +/- S.E.M.) of that induced by potassium (127 mM). A variable degree of spontaneous contractile activity was recorded in the vein preparations. This activity was abolished by nifedipine (2.9 X 10(-6)M). Digoxin (10(-6)M) induced contractions in pulmonary vessels. In the arteries, the digoxin contraction developed slowly and reached a maximum amplitude of 90 +/- 4% (Mean +/- S.E.M.) of the potassium evoked contraction. In the veins, the amplitude of the digoxin contraction was 32 +/- 5% of that induced by potassium. Digoxin (10(-6)M) also increased the maximum response to noradrenaline and potassium in both arteries and veins. In the arteries, the noradrenaline and potassium contractions increased to 211 +/- 6.8% and 145 +/- 8.9 of control, and in the veins to 169 +/- 13.5% and 163 +/- 9.9%, respectively. Nifedipine in concentrations which completely relaxes arterial and venous preparations contracted by potassium, had only a slight relaxing effect on digoxin induced contraction. It is concluded that digoxin increases the tension in pulmonary arteries and veins, and increases the maximum response to noradrenaline and potassium in both types of vessels. The digoxin induced contraction is highly resistant to blockade of extracellular calcium influx.


Reproductive and teratological studies with a new aminoglycoside: netilmicin (Sch 20569). Reproductive and teratological studies were undertaken with netilmicin (Sch 20569), a new semisynthetic aminolgycoside antibiotic structurally related to sisomicin. The administration of 32 and 80 mg/kg/day, by the intramuscular route, in the rat prior to and during pregnancy and lactation did not affect the fertility of animals, the resorptions rate and the vitality of the litters until the second generation. Also in the rabbit, the dose of 32 mg/kg/day by intramuscular route during pregnancy did not cause any embryotoxic effect. No gross malformations were observed in both species. The minor skeletal malformation, described as "wavy ribs", was observed at a significant level only in the rat foetuses generated by dams treated with a dose as high as 80 mg/kg/day by the intramuscular route.


Relaxant effects of nifedipine on isolated, human myometrium. Myometrial tissue was obtained from non-pregnant women subjected to hysterectomy because of various gynaecological disorders, and from women undergoing caesarean section. Strip preparations were dissected and isometric tension was recorded. Nifedipine (2.9 X 10(-8)--2.9 X 10(-6)M) inhibited spontaneous contractile activity, mainly by reducing the amplitude of contraction in both non-pregnant and pregnant myometrium. The drug also inhibited potassium induced contractions in a concentration dependent manner. This effect seemed to be more pronounced in pregnant than in non-pregnant tissue. In preparations of pregnant human myometrium, normally polarized or potassium depolarized, oxytocin induced a contractile activity that was effectively inhibited by nifedipine. Nifedipine also relaxed contractions induced by vasopressin in isolated non-pregnant myometrium. It is concluded that the relaxant effect of nifedipine on isolated pregnant and non-pregnant human myometrium can be explained by inhibition of calcium influx. The results thus support the view, that calcium influx is an important step in the initiation of contractile activity in human uterine smooth muscle.


Absorption of diazepam in man following rectal and parenteral administration. Serum concentrations of diazepam and N-desmethyldiazepam were measured in six adult patients following administration of 10 mg diazepam in solution by the rectal, intravenous, and intramuscular routes. Maximum serum concentrations of 121--200 ng/ml were recorded from 10 to 20 min. after the rectal instillation, whereas following intramuscular injection the levels rose slowly and irregularly, reaching a maximum (62--186 ng/ml) in 1 to 24 hours. The bioavailability of diazepam given by rectal instillation was found to be 50 +/- 17 per cent (mean +/- S. D.) as compared with the intravenous administration. The possible reasons for the low bioavailability are discussed. It is concluded that administration by rectal tube provides a useful alternative to the tablets (and intramuscular injections) when a rapid onset of effect of the drug is wanted, and when intravenous administration is not applicable or practical.


The role of blood coagulability and axial streaming of erythrocytes in determining F cells-value and TPR. Experiments were performed in anaesthetized and splenectomized dogs to influence the intravascular distribution of erythrocytes and plasma within the vascular bed. Blood volume was determined by double-isotope labelling of red cells and plasma. A significant decrease of F cells-value was found after posthaemorrhagic haemodilution and after haemodilution induced by homologous plasma. The administration of epsilon-amino caproic acid and bovine thrombin was followed by a significant increase of F cells-value. An interdependence of coagulability and F cells-value is suggested. The increase of haematocrit was followed by an increase of TPR, which, however, was only half of the value that would have been anticipated on the basis of the increase of viscosity when measured in normal-bore viscometers. This points to the possibility that blood flowing in the resistance vessels undergoes a certain spontaneous separation of cells and plasma and its haematocrit will be lower than in the large vessels. Cell separation in different organs having different haematocrit values and blood volumes probably affects total body haematocrit and F cells-value.


Stimulation of renal tubular transport by ethacrynic acid in rats of different ages. The transport system for organic acids in the kidney is not fully developed in the neonatal period. The effect of repeated administrations of ethacrynic acid on the renal excretion of p-aminohippurate (PAH) was studied in rats of different ages. Pretreatment with ethacrynic acid was followed by an increase in the renal excretion of PAH in 33-, 55-, 105- and 240-day-old rats but not in newborn rats. In 55-day-old rats the increase in renal excretion of PAH after pretreatment with ethacrynic acid was not associated with any consistent change of the glomerular filtration rate. It is concluded from these results that the stimulation of transport processes in the kidney by ethacrynic acid and some other drugs is linked with their affinity to tissue proteins.


The connection of plasma triiodothyronine levels with the sex-dependent body weight loss after bilateral pallidal lesion in rats. Previous data showed that after bilateral pallidal lesion (GPL) the weight loss of animals is higher in males than females. Data in the literature have called attention to the possible involvement of thyroid hormones. The sex dependence of weight loss was prevented by neonatal castration. In the present experiments, plasma triiodothyronine level was determined in neonatally castrated and non-castrated male and female rats on the 4th day after GPL. Body weight changes in food and water deprived male and female rats were compared after 4 days of T3 administration. A positive correlation between weight loss and T3 levels was found but there was no difference in mean T3 values between male and females. In the non-castrated group, T3 levels were higher in lesioned than in food and water deprived animals. In neonatally castrated animals no such difference was found. T3 administration caused a uniform weight loss in both sexes. It seems that while they play a role in the mechanism of weight loss after GPL, the sex-dependence is not due to changes in factors involved in regulation of the thyroid hormone level.


Comparative study on the metabolism and filtrability of red blood cells of the calf and adult cattle. Filtrability of calf and adult cattle red blood cells was studied to characterize their durability; to compare their metabolism, lactate dehydrogenase, glucose-6-phosphate dehydrogenase and glutamate-oxalacetate transaminase activity and ATP-content were determined. The activity of the enzymes declined gradually with age. The most pronounced decline of activity, particularly in the case of lactate dehydrogenase, was observed 6--8 weeks after birth. ATP content of calf red blood cells was ten times higher than that of the adult cattle, however, it proved to be less stable. Filtrability of fresh calf and adult cattle red blood cells was identical, while following incubation for 15--24 hours the decrease of filtrability was more pronounced in calf red blood cells indicating a lower filtrability and, consequently a shorter expected lifetime.


Dynamic phase-shifts between theta generators in the rat hippocampus. Winson [13] reported on two independent phase-reversed generators in the rat hippocampus. In the present study the synchrony between the two generators was investigated during the sleep-wakefulness cycle and during a behaviour-dependent discriminative learning task. Electrical activities derived from the CA 1 region and dentate gyrus were in phase during slow wave sleep but phase-reversed during the awake state and paradoxical sleep. The degree of phase-reversal was significantly higher during running than during lever pressing. These findings demonstrate that substantial changes occur within the hippocampal circuitry during dynamic shifts of behaviour.


Metabolic effects of ethanol in the rat liver. The NADPH is one of the cofactors in ethanol metabolism. The aim of the study was to investigate the effect of ethanol on a NADPH generating enzyme (G6P-DH) and on some metabolic parameters of the liver. After a 2-day starvation period rats were fed a lipid free diet for three days. During this refeeding period the animals were divided into three groups; they received a single daily dose of 4 g per kg b.w. ethanol, isocaloric aqueous glucose solution or water by gastric tube. In response to ethanol the activity of hepatic G6P-DH decreased. The amount of triglyceride remained unchanged, certain changes occurred in the fatty acid composition of total lipid. The liver glycogen content was elevated. In female rats treated with ethanol the activity of glucose-6-phosphatase increased.


Oxotremorine-tolerance: muscarinic blockade or homeostatic adaptation? Tremorine pretreatment of mice induces tolerance to some effects of oxotremorine. In the state of tolerance even the highest doses of oxotremorine did not cause antinociception, this blockade being insurmountable. Oxotremorine decreased motility and amphetamine hypermotility, and both effects were diminished by tremorine pretreatment. Amphetamine hypermotility increased in the tolerance state. The increase of cerebral acetylcholine level due to oxotremorine was diminished by tremorine pretreatment. It is suggested that a special blockade of cerebral muscarinic receptors might play a role in the tolerance phenomenon, moreover it is possible that some excitation develops in the CNS. A homeostatic adaptation may be involved a role in this kind of tolerance.


Effect of ovarian steroid hormones on superficial activator calcium in the rabbit uterus. Effect of oestradiol (E2) and progesterone (P) on activator calcium binding was studied in the rabbit uterus. Superficial Ca-binding of isolated uterine strips was characterized by determining the rate of loss of isometric tension evoked by low (2.4 V/cm) field strength electrical stimulation in Ca-free Krebs solution. Intramuscular injection of 10 mg P increased superficial Ca-binding significantly in the postpartum and E2-treated virgin uterus with a latency period of 8--12 hours. Bilateral ovariectomy on the 25th day of pregnancy decreased superficial Ca-binding progressively, which could be avoided by P-substitution. 72 hours after ovariectomy P-treatment failed to increase Ca-binding. Local application of cycloheximide increased Ca-binding in the E2-treated virgin uterus. The results suggest that a high P-level plays an important role in the induction and maintenance of a strong binding of superficial activator calcium in the rabbit uterus. Progressive disappearance of the strong binding near term and after bilateral ovariectomy correlates well with P-withdrawl in this species.


Effect of testosterone and thyroxine on corticosterone and transcortine plasma levels in different bird species. Effect of testosterone and thyroxine on corticosterone and transcortine plasma levels has been investigated in photostimulated (18L--6D) Peking duck, domestic pigeon, Japanese quail and cock. In all these bird species corticosterone and transcortine plasma levels increased following castration, while restitution with testosterone decreased them in the castrated animals. Thyroidectomy and thyroxine supplements in thyroidectomized birds failed to influence plasma corticosterone and, apart from cock, transcortine levels. It is suggested that in case of high testosterone levels the effect of thyroid hormones on the function of the adrenal cortex can partly or completely be masked by the dominancy of the testocorticoid interrelation.


Organization of blood pressure reflexes elicited by low intensity stimulation of cutaneous and muscular afferents in cats. The incidence and patterns of blood pressure reflexes elicited by sustained (3--4 min) low intensity electric stimulation (0.5--4 V, 0.1 ms, 4 Hz) of cutaneous and muscular afferents of high or low spinal segmental input levels were investigated in immobilized (gallamine) and artificially ventilated conscious or anaesthesized (chloralose-urethan) cats. In a part of the experiments, subconvulsive doses of picrotoxin and/or strychnine were used as pharmacological disinhibitors. The results suggest that (1) the variability of the responses in conscious animals may be due to the varying degree of spinal inhibition, especially of that associated with cutaneous inputs; (2) intraspinal irradiation of excitation plays an important role in the integration of the reflexes; (3) the preferred direction of irradiation seems to be different in the projection zones of cutaneous and muscular afferents. Comparison of the results with previous data points to the possibility that the different response patterns seen after intense stimulation might be the result of the suppression of spinal inhibitions, due to C-fibre activation.


Localization of the change in intensity of a visually pursued light target. The aim of the subjects was to track a moving light target and to locate the change in its intensity (its disappearance or dimming). It is shown experimentally that: (1) mislocation of target disappearance is smaller than mislocation when the target is dimmed three times; (2) the distance at which the eyes move after the target is darkened does not influence localization. The data disprove possible influence of "overtracking" on localization. They are in favour of the hypothesis about the dependence of localization on stimulus intensity.


Recognition of changes in the dimensions and categories of visual objects. The aim of the present work is a comparison between recognition with changes in the dimensions of the objects and recognition with changes in the category of the objects. After preliminary training under tachistoscopic ocnditions, to a control set of different contour drawings are added: (1) the same drawings increased or desreased several times; (2) different new drawings with the same size. The percentage of recognized drawings is determined for such exposure time which is needed for the recognition of 60--80 per cent of the drawings in the control set. Recognition is found to be deteriorated in the case of changes both in the dimensions and in the category of the objects, the deterioration being double for the objects with changed category. This fact serves as a basis for rejecting the hypothesis that considerable changes in the dimensions could create new objects for the visual system. It was also found that recognition of pre-trained drawings is either not influenced or comparatively least influenced by the changes in the dimensions and categories. This result is probably due to the specificity of recognition of long trained objects. The results obtained do not contradict the assumption of the participation of spatial consecutive scanning of the iconic memory in the recognition of the spatial properties of visual objects.


Motor estimation of short time intervals under the effect of some psychotropic drugs. A study is made of the human ability to estimate short time intervals (up to 1 s) by a simple motor response under the effect of stimulants (Amphetamine, Caffeine) and depressants (Chlorazin, Diazepam, Phenobarbital). Of all psychotropic drugs used only Chlorazin causes a statistically significant increase in the mean values of the reaction time of all subjects compared with the controls. The psychotropic drugs in the doses used have no influence on the ability of the subjects to produce a light interval of a given duration. In the task requiring reproduction of a 900 ms interval, Amphetamine schortens significantly the response times, which is explained by earlier organization of their motor responce and lack of feedback.


Scintigraphic and radiocirculographic studies on the effect of As2 on cat cerebral circulation. Various well-known agents with a favourable influence on cerebral circulation were used as a basis for creating new methods to asses the effects on this vascular region in experimental animals. A technique was worked out for radiocirculography and simultaneous radiometry, as well as for scanning and simultaneous radiometry of cat brain. Radiocirculography, followed by scintigraphy, proved to be among the best methods used for assessment of the effect of As2 on cerebral circulation. Simultaneous radiometry with the methods mentioned above had only orientational value. Radiocirculographic and scanning data after application of As2 in a dose of 10 mg/kg are close to those for nicotinic acid in a dose of 1 mg/kg. Similar to the data of the isotopic methods after application of As2 in a dose of 5 mg/kg are the results obtained with 5 mg/kg cinnarizin, which suggests a similar machanism of action.


Studies on the dense-core vesicles in the ontogenesis of locus coeruleus. II. Method of statistical reconstruction of the diameter distribution of the dense-core vesicles. A statistical method for reconstruction of the distribution of the diameters of spheres according to their planar image obtained from ultrathin sections, is proposed. The method can be applied for casses when the thickness of the section is commensurate with the diameter of the spheric objects studied. The formulae worked out in the work are based on the assumption that the diameters of the spheres are with discrete distribution in geometric order. The method is elaborated in connection with the problem of the changes in the diameters of the dense-core vesicles in monoaminergic structures during development.


Studies on the dense-core vesicles in the ontogenesis of locus coeruleus. III. Statistical reconstruction of the diameter distribution of the dense-core vesicles in locus coeruleus during rat ontogenesis. The method for statistical reconstruction of the diameters of dence-core vesicles, described in the previous work, is applied for studying the changes of these vesicles in the perikarya, the axonal boutons and the neuropile of the rat locus coeruleus during ontogenesis. The data obtained show the presence of the population during the embryonal development and of two populations of dense-core vesicles after birth in the structures studied. This finding is interpreted in connection with the different function of the dense-core vesicles and of the transmitters, respectively, in the development and function of the main noradrenergic nucleus in the brain of mammals -- locus coeruleus.


Diminished adrenergic response to 2-deoxy-D-glucose after prolonged, exhausting physical exercise in dogs. Effect of 2-deoxy-D-glucose (2DG) on plasma adrenaline, glucose and free fatty acid concentrations was studied in dogs under control conditions and after prolonged, exhausting physical exercise. The increase in all three variables in response to 2DG was significantly reduced following the exercise. The results suggest diminished responsiveness of adrenal medulla to the glucopenic stimulus after exhausting exercise.


The effect of prolonged restriction of physical activity on exercise performance in dogs. 2-months restriction of physical activity of dogs markedly reduced their capacity for prolonged running. The rate of exercise-induced Tre increases was significantly higher in the cage-confined dogs in comparison with controls. At the point of exhaustion blood glucose concentration and muscle glycogen content were similar in the control and cage-confined animals, in spite of the much shorter time of exercise until exhaustion in the latter. The exercise-induced increases in plasma FFA concentration were considerably lower in dogs after prolonged inactivity period in spite of the greater activation of the adrenergic system. It is concluded, that there are several factors which may contribute to the reduction of the ability of cage-confined dogs to perform prolonged physical exercise. The most important seems to be the diminished muscle glycogen content, modifications in exercise metabolism and exercise-induced hyperthermia.


The hypothalamic and neurohypophysial vasopressin content as influenced by diphenylhydantoin in dehydrated rats. Rats dehydrated up to 8 days were treated with diphenylhydantoin given intraperitoneally in daily doses of 10 mg/100 g of the initial body weight. The single dose of diphenylhydantoin diminished the vasopressin content in the hypothalamus and neurohypophysis of normally hydrated rats. Under conditions of severe dehydration (8 days), DPH treatment resulted in a more marked decrease of vasopressin in the hypothalamo-neurohypophysial system.


Age-related changes in the content of fibrous proteins in the rat tissues. An attempt was made to establish a relationship between the content of elastin and collagen in the rat tissues during the process of aging. The content of collagen fractions and elastin in the rat liver, lung and skin, as well as the elastolytic activity of blood serum were determined. It was found that the concentration of elastin as well as the elastolytic activity of blood serum are increasing during the maturation of rats and the total collagen content is increasing too. After the animals reached the age from twelve to twenty four months--above mentioned values began to decrease. It is concluded that the changes in the content of the two fibrous proteins of the connective tissue depend on age.


Effect of potato inhibitor of proteolytic enzymes on activity and morphology of the rat pancreas. The effect of the inhibitor of proteolytic enzymes present in potatoes on morphology and activity of the rat pancreas was investigated administering the inhibitor with drinking water in doses of 50 and 100 mg to two groups of rats for 20 days. On the 21st day the exocrine activity of the pancreas was evaluated by the method of duodenal perfusion after previous hormonal stimulation of pancreatic secretion (secretin and cholecystokinin-pancreozymin 1 U CHR/100 g body weight), while morphology of the organ was assessed by histological methods. It was found that the inhibitor exerts a trophic effect on the rat pancreas, causing hypertrophy of acinar cells and raising the exocrine activity of the gland. The higher dose of the inhibitor had a more pronounced trophic effect.


Cardio-respiratory adaptation to physical exercise and hypoxia after a high-altitude expedition. Seven young, male subjects were tested before and immediately after 6 weeks high-mountain expedition. Cardio-respiratory measurements were performed at rest and during standard physical excercise (10 min, 100 W) when breathing atmospheric air or hypoxic mixture (14% O2 in N2). After the expedition an increased V o2 max (16% an average) and diminished heart rate response to submaximal exercise were found. This was observed during air and hypoxic mixture breathing. There was significant increase in stroke volume and cardiac output during the exercise. No significant differences in ventilatory parameters were found nor at rest or during exercise under condition of breathing atmospheric air or hypoxic mixture. No changes in erythrocyte count or haemoglobin concentration in the blood were found. The physiological changes which developed during high-mountain expedition were more dependent on physical that hypoxic training.


The analgesic action of some flavonoids in the hot plate test. Albino-Swiss male mice were tested in the hot plate test. Oligomeric procyjanidin (OL-1), rutin, quercetin, hyperoside and vitexin rhamnoside were administered intraperitoneally in doses 3.5 and 10 mg/kg. It was found that OL-1, rutin and hyperoside but not vitexin rhamnoside exert analgesic action, whereas quercetin even decreases the pain threshold level. The mechanism of the analgesic action of flavonoids remains to be explained.


Relationships between peak force, action potential duration and stimulus interval in rabbit myocardium. Isometric force and membrane action potential were recorded simultaneously in rabbit papillary muscles (36.5 degrees--37.5 degrees C). One to three test stimuli were given at various intervals (0.20--10.0 s) after a series of control contractions at constant stimulation intervals (1.0--1.5 s). Optimum peak force always occurred when the preceding test interval was 0.80 s. When this interval was greater than 0.80 s, time to peak force was a linear function of the action potential duration. Furthermore, under these conditions the action potential duration (AP1) and peak force (F1) of the test contraction could be used to predict peak force (F2) of the subsequent contraction elicited after a fixed interval (0.80--1.50 s) according to the equation (regression plane): F2 = BAPAP1 + BFF1 + A. Constants BAP and BF are interpreted to provide information about calcium influx during the action potential and of the recirculation of calcium between contractions, respectively. F2 deviated towards higher values than predicted from the equation when the preceding test contraction was triggered to occur at an interval less than 0.80 s. This may be due to an intensified calcium transport into the cell during the action potential after these short intervals. The action potential duration was inversely related to both the inotropic state of the muscle (representing a feed-back mechanism) and the preceding stimulation interval.


A new non-steroidal drug for long-acting contraception. A new contraceptive compound had been prepared with the common ingredients and it was applied in female rats. The efficacy and toxicity tests of this compound showed that this drug has along-acting contraceptive value not causing any side-effects.