Influence of luminal Na+ on the intestinal absorption of sugars in vivo.

The effect of substituting Na+ with Tris, Li+, K+ or mannitol on the intestinal absorption of sugars, in successive periods of 1 minute duration, has been studied in rat and hamster in vivo. The absorption of 2 mM D-glucose, D-galactose, 3-0-methyl-D-glucose and D-fructose is clearly inhibited in the absence of Na+, up to 70-80%, and returns to its normal value of restoring Na+. The degree of inhibition varies with the sugar, increases on lowering Na+ concentration, reaches maximum values with mannitol as substituent, and minimum with Tris, D-arabinose absorption is not affected by Na+. These results prove once more how important Na+ is in sugar intestinal transport in vivo, while they reveal additional influences of the different substituents on the transport system.


Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs.

The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium.


Acute effects of acetaldehyde and ethanol on rat heart mitochondria.

The effects of acute exposure of rat heart mitochondria to ethanol (87, 65, and 45 mM) and acetaldehyde (3, 1, and 0.3 mM) were studied using both glutamate and pyruvate/malate substrates. Mitochondria assayed with pyruvate/malate substrate showed no apparent effects of acute exposure to or 30 min preincubation with ethanol at the three concentrations tested. With glutamate substrate, acute ethanol at 87  and 65 mM produced significant decreases in respiratory control ratio (RCR). With 65 and 45 mM acute ethanol, mitochondrial oxygen consumption (QO2) was significantly decreased. Acute acetaldehyde significantly decreased RCR and QO2 of mitochondria tested with both substrates. The depressive effect was more pronounced with pyruvate/malate substrate than with glutamate substrate. With pyruvate/malate substrate, the ADP/O ratio was also decreased with 3 and 1 mM acetaldehyde. Preincubation with acetaldehyde had no effect on mitochondrial function except for significantly decreased RCR after preincubation with 3 mM acetaldehyde followed by assay with glutamate substrate. The data indicate a depressant effect of acetaldehyde and ethanol on cardiac mitochondria that may contribute to abnormal cardiac biochemistry and function characteristic of alcoholic cardiomyopathy.


Alterations in arginine-induced pancreatic hormone release: influence of acute and chronic exposure to ethanol.

Acute oral administration of ethanol (150 and 750 mg/100g) to fasted rats produced dose-related inhibition of arginine-induced insulin (IRI) release, an elevation of plasma glucagon (IRG) levels and minor effects on blood glucose. In contrast, chronic consumption of ethanol for 10 weeks augmented arginine-induced hyperglycemia and hperinsulinemia. Thus, acute ethanol administration decreased plasma IRI levels at both doses, presumably by suppressing beta cell function; whereas, function of the alpha cell and plasma IRG levels were increased, but only by the high dose of ethanol. In these experiments the effects exerted by ethanol on the pancreatic endocrine responses to arginine infusion varied according to: dose of ethanol administered; duration of exposure to ethanol; and state of nourishment of the subjects.


Quantitation of isoproterenol-induced myocardial necrosis with 3H-tetracycline.

Methods currently used to quantitate myocardial damage and necrosis produced by chemicals are usually time consuming and subjective. These studies were conducted to evaluate the utility of 3H-tetracycline as a means of quantitating myocardial necrosis produced by isoproterenol. Male, Sprague-Dawley derived rats (180-200 g) were treated with (+/-)-isoproterenol HCl (0.1-100 mg/kg, s.c.) or equivalent volumes of saline. After 90 minutes, all rats received 50 uCi/kg of 3H-tetracycline. Rats were sacrificed 3 hours after 3H-tetracycline administration and the hearts were removed and rinsed free of blood. The degree of radioactivity of the heart as determined by liquid scintillation counting was directly proportional to the dose of isoproterenol. Propranolol pretreatment decreased the accumulation of radioactivity in a dose-dependent fashion. Determination of 3H-tetracycline accumulation appears to be a rapid and reliable method for quantitating isoproterenol-induced myocardial necrosis.


Short- and long-term effects of graduated doses of DL-6-OH-DOPA upon marsh mice.

The lethal effects in Marsh mice for a range of DL-6-OH-DOPA levels were ascertained and exceeded those previously reported for 6-OH-DA under comparable conditions. The addition of vitamin "C" to the 6-OH-DOPA solution given intraperitoneally increased the lethal effect, as did the intraperitionel route of injection over that of the subcutaneous. Increased water consumption developed the fourth day for those surviving toxic levels of 6-OH-DOPA given subcutaneously as compared with controls. For all mice initially surviving administration of 6-OH-DOPA, tumorigenesis and long-term survival were of the same order as that of the controls. The toxicity of 6-OH-DOPA relating to ferric heme formation more likely involves metmyoglobin than methemoglobin. The combination of direct damage to sympathetic adrenergic cardiac innervation and metmyoglobin formation appears sufficient to account for the lethal effects of 6-OH-DOPA.


Toxicity of digoxin in acutely and chronically heat-exposed rats.

Rats exposed acutely or chronically to high ambient temperatures (35 degrees C) were much more susceptible to digoxin toxicity than rats kept at 22 degrees C. LD 50 values were 8.8 +/- 1.8 mg/kg in the acute group and 10 +/- 5 2.5 mg/kg in the chronic group, which contrasted with 32.0 +/- 4.4 mg/kg in the control group. Toxic doses of digoxin cause marked hyperthermia in both the acute and chronic groups. Transferring the rats to 22 degrees C not only prevented the extreme hyperthermia, but also prevented death in the acute group (from the expected 100% to 0% mortality) and lowered the incidence of death in the chronic group (from the expected 78.5% to 30.7%). The suggestion is made that death may result from hyperthermia in the heat-exposed rats.


Radioimmunoassay for phencyclidine.

A sensitive and specific radioimmunoassay has been developed for the drug phencyclidine (PCP). Levels as low as 50 pg (200 femto-moles) of PCP can be detected. The specificity of the antisera has been investigated by inhibiting the [3H]PCP-anti PCP reaction with the parent drug, metabolites, and other related compounds. Three urinary metabolites, 4-phenyl-4-piperidinocyclohexanol, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine and 1-phenylcyclohexylamine inhibit 2,5, and 0.002% as effectively as PCP respectively. Plasma samples supplemented with PCP (1.2 to 10,000 ng/ml) can be analyzed directly by this procedure.


Single point clearance estimation.

Linear relationships were observed between the log of total body clearance (C1B) and simulated serum concentrations (Cmin) six hours after a test dose of chloramphenicol, as well as between C1B and the reciprocal of Cmin. Correlation coefficients for these relationships were 0.988 and 0.977, respectively. Clearance estimates obtained from a single serum sample following a test dose of a drug may prove to be a useful method of predicting dosage requirements for individual patients.


The effects of oleic acid, tolbutamide, and oxyphenbutazone on the binding of warfarin by human serum albumin.

Equilibrium dialysis studies showed that, at low levels, stearate, palmitate and oleate enhanced the binding of warfarin by human serum albumin, but at high levels of FFA, warfarin was displaced. Tolbutamide and oxyphenbutazone separately desplaced warfarin, and this dispplacement was reduced by the presence of low concentrations of oleate while at higher concentrations of oleate displacement occurred. Thus, the binding of warfarin was affected in a complex fashion depending upon the drugs present and the concentration of the FFA.


Immunonephelometric assay for urinary total protein and albumin in mice.

A quantitative immunonephelometric assay for measuring total protein and albumin in mouse urine has been developed. Antisera to whole mouse sera or to mouse albumin was added to aliquots of urine and the antigen-antibody complexes formed were measured by laser nephelometry. Sample volumes were small (20 microliters) and the assay time was 90 minutes. The assays were sensitive to 10 mg/L and within-day and day-to-day precision studies demonstrated coefficients of variation of less than 15%. Average urinary total protein and albumin concentrations for random urine specimens in female C3H mice (age 80-150 days) were 42 and 24 mg/L respectively. Urinary total protein and albumin to creatinine ratios were also determined.


Decreased pentobarbital sleeptime following a single intraperitoneal injection of cedar-derived sesquiterpenes.

Within one day after a single IP injection of cedar sesquiterpenes into mice, pentobarbital sleeptime was reduced by 40%. The estimated ED50 is 50 mg terpenes/kg body weight. The mice recovered from this terpene-induced reduction in the strength of hypnosis within 6 days after the terpene injection. The potency of the terpenes, the rapidity of their action, and the duration of their effectiveness in modulating a drug response suggest their usefulness as a pharmacological tool.


Cholesteryl iodide-125I as a diagnostic adrenal photoscanning agent. Part - I.

Cholesteryl iodide-125I was prepared and administered intravenously to rabbits. After six days, tissue distribution studies indicated a good target to non-target ratio with selective concentration in adrenal glands.


The sites in the duodenum of receptor areas which affect abomasal emptying in the calf.

Calves were prepared with abomasal and duodenal cannulae to assess the effects on abomasal emptying of duodenal infusates at different rates and different sites. In two calves infusions of isotonic NaHCO3 or 60 mM HCl 30 cm distal to the pylorus were as effective in controlling abomasal emptying as infusions of the duodenum from 5 cm distal to the pylorus, and in three other calves they were as effective as perfusing the whole duodenum including the most proximal 5 cm. Reducing the rate of duodenal infusion of 60 mM HCl from 10 to 2.5 ml/min diminished its effect from total inhibition of gastric emptying to slight or negligible inhibition. The stimulation of gastric emptying by duodenal infusion of isotonic NaHCO3 solution was undiminished by reduced rates of infusion. It is proposed that in the calf receptors which activate and inhibit gastric emptying are present throughout the duodenum.


Trichostrongylus colubriformis and Ostertagia circumcincta resistant to levamisole, morantel tartrate and thiabendazole: occurrence of field strains.

Field strains of Trichostrongylus colubriformis and Ostertagia circumcincta, designated PF4 and PF5 respectively, were recovered from a farm on which the sole use of levamisole over a preceding 12 year period led to the development of anthelmintic resistance. The results of field observations and preliminary critical trials in both Merino and crossbred sheep showed that both species have varying degrees of resistance to three major anthelmintics; levamisole, morantel tartrate and thiabendazole. Mean worm count reductions for adult T colubriformis (PF4) for therapeutic doses of morantel tartrate, thiabendazole and levamisole in crossbreds were 45.7 per cent, 97.3 per cent and zero respectively, and for Merinos 80.7 per cent, 88.3 per cent and 92.0 per cent respectively. Against O circumcincta the corresponding reductions for crossbreds were 51.4 percent, 95.4 per cent and 20.3 per cent and for Merinos, 52.5 per cent, 73.1 per cent and 29.8 per cent. There was no statistically significant difference in the responses of both parasite species to either levamisole or morantel. This result suggests that resistance to the two chemically unrelated drugs may be co-inherited.


The efficacy of fenbendazole and albendazole against immature and adult stages of benzimidazole-resistant sheep trichostrongylids.

The efficacy of two recently introduced benzimidazole anthelmintics, albendazole and fenbendazole, was determined for six-day, 10-day and adult stages of resistant strains of Haemonchus contortus and Trichostrongylus colubriformis. Albendazole, at 3.8 mg/kg reduced H contortus worm counts by 92.4, 70.8 and 67.1 per cent while fenbendazole, at 5.0 mg/kg, reduced worm burdens by 51.7, 95.5 and 93.4 per cent against six-, 10- and 25-day-old parasites respectively. For T colubriformis, the corresponding reductions with albendazole were 97.7, 95.8 and 64.9 per cent and for fenbendazole 29.0, 66.3 and 33.4 per cent. Compared with susceptible strains of H contortus and T colubriformis, for which therapeutic doses of benzimidazole anthelmintics are generally highly active against all stages of development, the present results show that these drugs do not have a uniform level of activity against all developmental stages of resistant strains.


Effect of halothane on isometric contractile properties of muscle from stress-susceptible and stress-resistant pigs.

The effect of clinical concentrations of halothane on the isometric contractile properties of muscle in stress-susceptible and stress-resistant pigs was studied. Exposure to halothane initially increased the percentage of peak twitch tension in the muscle of stress-susceptible pigs whereas the tension gradually decreased in the stress-resistant group of pigs. Halothane may act as a potentiator of muscle contraction in stress-susceptible animals, but this effect is transitory.


The measurement of transplacental magnesium fluxes in the sheep.

Bi-directional transport rates of magnesium across the placenta of the ewe have been measured towards the end of pregnancy. The results indicated that approximately 0.042 and Mg/h/kg fetal body weight passed from ewe to fetus and that about 0.012 mg Mg/h/kg fetal body weight was transported back to the ewe. There was a significant, although small, positive gradient in plasma magnesium concentration from ewe to fetus.


Plasma phospholipid changes in tick infested N'dama cattle.

Plasma phospholipid composition and concentration of healthy and tick infested local cattle (N'dama) were studied. Phospholipid concentration was lower in the tick infested cattle. Phospholipid composition was also altered by the tick infestation. The phospholipids mainly affected are phosphatidyl choline, sphingomyelin and lysophosphatidyl choline and are absent from the plasma of tick infested cattle.


A survey of the aerobic bacteria in the droppings of captive birds of prey.

Fresh droppings were collected from six species of bird of prey (Falconiformes and Strigiformes). Bacteriological examination revealed that the birds' digestive systems were colonised by bacteria found widely in other species of animals. Throughout the survey no Salmonella species were isolated.


The identification of Moraxella bovis and Neisseria ovis from the eyes of cattle and sheep.

The cultural characteristics of Moraxella bovis and Neisseria ovis from eyes of cattle and sheep were examined to determine which tests precisely identified the isolates. The elongation test to distinguish the bacillary M vovis from the coccal N ovis, the nitrate reduction and the litmus milk tests were found to be the most reliable.


Trypanosomes in the lymph nodes of cattle and sheep infected with Trypanosoma congolense.

The prefemoral lymph nodes of two calves and a sheep infected with a stock of Trypanosoma congolense transmitted by Glossina morsitans were examined histologically for the presence of trypanosomes. Ten days after infection trypanosomes were found in the subcapsular sinuses of the nodes of a calf and the sheep but parasites were absent from the blood at this time. Trypanosomes were also detected in the prefemeral lymph node of the other calf on examination 30 days after infection, when parasites were also present in the blood. These observations provide further evidence that extravascular foci of trypanosomes develop in infections with T congolense and indicate that it should not be regarded as a strict plasma parasite.


The anthelmintic efficacy of oxfendazole and haloxon against arrested Haemonchus contortus larvae in sheep.

In a controlled trial with natural infection of Haemonchus contortus, oxfendazole at 4.53 mg/kg body weight was highly effective against arrested larvae, developmental stages and adult helminths. Haloxon at 40 mg/kg significantly reduced helminth burdens.


Adherence of Bordetella bronchiseptica to swine nasal epithelial cells and its possible role in virulence.

Bordetella bronchiseptica phase I organisms adhered well to swine nasal epithelial cells cultured in vitro, while phase III variants exhibited feeble adherence to the same cells. Similarly, firm attachment of phase I organisms and poor adhesion of phase III organisms to nasal epithelium were demonstrated in experimentally infected piglets. Electron microscopic observations of nasal mucosa infected with phase I organisms showed preferential adherence to the cilia of nasal epithelial cells; the association of bacteria and cilia appeared to be mediated by fuzzy or string-like surface appendages which extended out from the bacterial cell wall. The ability to attach to epithelial cells was significantly reduced by heating the bacteria at 100 degrees C for 1 h or by pretreatment with 1 per cent formalin. Trypsin digestion treatment did not greatly reduce the adherence. Rabbit antisera to living or formalinised phase I organisms markedly impaired the attachment of the bacteria. However, antisera to heated phase I organisms or living phase III organisms did not show inhibitory effects. These data indicate that the heat labile surface component which is specific to phase I organisms may function in the adherence of the bacteria to swine nasal epithelium.


Intracellular distribution of copper in the liver of normal and copper loaded sheep.

Thirteen sheep were dosed repeatedly with copper sulphate in order to induce chronic copper poisoning. Twelve similar sheep acted as controls. Three dosed sheep were killed before haemolysis, six at haemolysis and four after cessation of the haemolytic crisis. The subcellular distribution of Cu, Zn, Fe and lysosomal marker enzymes was investigated in the livers of normal sheep and copper loaded sheep. In control sheep the highest concentration of Cu was in the nuclear fraction. Copper loading increased the concentration of Cu in all fractions. The proportion of Cu in the nuclear fraction continued to increase while that in the heavy mitochondrial fraction decreased. Significant increase in lysosomal enzymes along with electron microscopic studies on pellets of fractions indicated: (a) proliferation of lysosomes, (b) possible localisation of Cu in lysosomes, and (c) sedimentation of the denser lysosomes on N and MH fractions in test sheep with the majority being in the N fraction. Thus the increase in Cu observed in the N fraction is at least partly due to the storage of Cu by lysosomes which sediment with the heavier nuclei. The excessive deposition of Cu in lysosomes and nuclei may lead to cell damage. With increase in hepatic Cu concentration the proportion of Zn and Fe in the cytosol decreased.


Distribution of cardiac output in anaesthetised horses.

The radioactive microsphere method was used to determine the distribution of cardiac output in six anaesthetised ponies. Simultaneous measurements of cardiac output allowed calculation of the tissue perfusions (ml/min/100 g). Allowing for the fact that measurements were carried out on animals under halothane anaesthesia and which had respiratory acidosis, the results were comparable with published values for other species.


The effects of repeated injections of adrenaline on the response of the fowl to further alarm stimulation.

Chicks, aged two weeks, were injected with either adrenaline (300 microgram/kg) or saline daily for seven days. One day after the seventh injection it was found that the birds treated with adrenaline had become hypolipacidaemic and hypocholesteraemic and that there had been adrenal hypertrophy and an increase in the adrenal store of cholesterol. Plasma concentrations of glucose and corticosterone were within the normal range. The two groups (adrenaline- or saline-treated) were further subdivided each into two subgroups and were now injected with either adrenaline or saline, and their responses measured over a 120 min period. A significantly shorter period of hyperglycaemia was found in the birds pretreated with adrenaline and given a further injection of the hormone. These birds also showed an enhanced lipacidaemic response but the corticosterone response was not altered.


Toxicity of Jatropha curcas in sheep and goats.

The sequential development of the clinical signs and lesions in the organs of desert sheep and Nubian goats dosed with Jatropha curcas seeds at 0.05, 0.5 and 1 g/kg/day was studied. Diarrhoea, reduced water consumption, dehydration, sunken eyes, inappetence and loss in condition were the important signs of J curcas poisoning in sheep and goats. The main pathological changes were haemorrhage in the rumen, reticulum, lungs, kidneys and heart, catarrhal and/or haemorrhagic enteritis, hepatic fatty change, pulmonary congestion and oedema and straw-coloured fluid in serous cavities. An increase in the concentrations of AST, ammonia, potassium and sodium and a decrease in total protein and calcium were detected in the serum. Haematological changes were haemoconcentration and leucocytosis.


Ruminal and salivary concentration of some sulphonamides in cows and their effect on rumen flora.

Sulphadiazine, sulphatiazole and sulphamerazine were shown to be excreted through the ruminal wall and salivary glands of cows. These sulphonamides had a slight inhibitory effect on cellulose digestion and on the activity of rumen infusoria. Acetylation of the sulphonamides occurred to a slight extent. Sulphatiazole was more acetylated (16.2 per cent) than sulphadiazine (7.0 per cent) or sulphamerazine (8.4 per cent). The rate of elimination of the three compounds, as indicated by their half lives, showed that sulphathiazole was the most rapidly excreted (2 h), whereas sulphadiazine and sulphamerazine were more slowly excreted, 5.4 and 7.1 h respectively.


A technique for sampling total rumen contents in sheep.

The paper describes the manufacture of an easily removable large rumen fistula closure for sheep and a restraining cradle which is used when sampling total rumen contents. Eight sheep have been fitted with the fistula and have been used regularly for nine months. The technique is rapid and simple and the closure is more reliable than other types which are often removed accidentally.


The role of elastase in the differentiation of Bacteroides nodosus infections in sheep and cattle.

Eighty-seven Bacteroides nodosus isolates were examined for elastase production by clearing of elastin particles in TAS agar medium. These included 54 ovine virulent isolates, 28 ovine benign isolates and five bovine isolates. In addition 22 ovine virulent, 16 ovine benign and two bovine isolates were examined for decline in proteolytic activity over a 13-day period in the degrading proteinase test using hide power-azure as substrate. There was a remarkable correlation between elastase production, relative stability of proteolytic activity in the hide powder-azure test and virulence of B nodosus. Ovine virulent isolates invariably produced elastase whereas ovine benign isolates and bovine isolates were elastase negative. Bovine isolates produced only mild lesions in the feet of challenged sheep.


Resting hemodynamics and oxygen transport in unanesthetized adult cats.

Characteristics of blood, oxygen transport were determined in seven adult female cats with inlying catheters in the pulmonary artery and a carotid artery. Measurements were made without anesthesia. Cardiac output averaged 167 ml.kg-1.min-1. Blood oxygen capacity averaged 11.6 ml.dl-1. Mean arterial oxygen saturation was 94% and mixed venous oxygen saturation was 49%. Mean oxygen tensions were 97.3% and 36.9 mm Hg in arterial and mixed venous blood, respectively. Mean arteriovenous oxygen concentration difference was 5.1 ml.dl-1, yielding a calculated oxygen consumption of 8.4 ml.kg-1 min-1, 5% higher than the value obtained by spirometric measurements on four of the animals. These data, when compared with previously reported values from species ranging widely in body size, show that the increased oxygen consumption per kg associated with decreasing body size is provided by progressive increases in cardiac output per kg and in arteriovenous oxygen concentration difference. Mixed venous oxygen tension is held within narrow limits in resting, unanesthetized animals.


Observations on the avian pulmonary and bronchial circulation using labelled microspheres.

Domestic fowl, ducks, geese, Guinea-fowl, quail and pigeons were anaesthetised with intravenous pentabarbitone sodium. Carbonised microspheres (40,000-60,000), 15 micrometer +/- 5 micrometer in diameter and labelled with 85Sr (3M Company) were injected into the cannulated right atrium. After spontaneous breathing of room air the birds were killed and the radioactivity measured in the spleen, kidneys, brain, lungs and extrapulmonary primary bronchi. Small pieces of lung tissue were removed from the beginning (costal region), middle (costovertebral region), and the end (vertebral region) of the paleopulmonic parabronchi, in the direction of air flow. Microspheres found in samples of parabronchial tissue indicated the relative perfusion rates of the three regions. Thermal panting was induced in six domestic fowl and six pigeons, followed by injection of microspheres. No arteriovenous anastomoses were found to exist across the pulmonary bed in any of the species examined at rest or in the panting domestic fowl and pigeons. The extrapulmonary primary bronchus was found to be well perfused from the pulmonary artery in the domestic fowl and to a lesser extent in the other species. The perfusion of the parabronchi in the domestic fowl and pigeons at rest decreased in the direction of ventilatory gas flow. This blood flow gradient was significantly increased during thermal panting in the domestic fowl, but not in the pigeon.


The interaction between the diaphragm, intercostal/accessory muscles of inspiration and the rib cage.

During Mueller maneuvers (MM), the volume change of rib cage, delta Vrc, and abdomen, delta Vab, are equal and opposite. Thus delta Vrc = -delta Vab. Substituting delta Prc.Crc for delta Vrc and delta Pab.Cab for delta Vab yields: delta Prc = - delta Pab.Cab/Crc, where delta Prc, delta Pab, Crc and Cab are applied pressures and compliances of rib cage and abdomen respectively. MM performed solely with the diaphragm permits calculations of Prc in terms of observed changes in Pab and pleural pressure, Ppl. Three trained subjects performed MM with no evidence of inspiratory intercostal or abdominal muscle contraction. During the diaphragmatic MM delta Pab was positive and delta Prc negative. The magnitude of delta Prc/delta Pab was 2-6 times greater than that of delta Ppl/delta Pab. We conclude that neither Pab nor Ppl by themselves displace the relaxed rib cage during Mueller maneuvers. A model in which the diaphragm acts both in parallel and in series with the rib cage, and in which Prc is the sum of Pab and a pressure lying between Pab and Ppl explains these results as well as the hypothesis that Pab displaces the relaxed rib cage during quiet breathing.


A mathematical and graphical analysis of inspiratory muscle action.

In this paper a mathematical and graphical analysis is presented for the action of the diaphragm and the intercostal/accessory muscles of inspiration, in terms of the pressure developed, the volumes displaced and the work performed by each set of muscles. An analogous model is described which behaves according to the analysis. The critical variable by which the action of the diaphragm and intercostal/accessory muscles can be measured is the change in abdominal pressure Pab. When delta Pab = 0 it is assumed that the diaphragm has contracted isometrically and is acting as a fixator preventing an expiratory displacement of the abdomen. When delta Pab greater than 0 the diaphragm shortens and acts as an agonist. When delta Pab less than 0 the diaphragm lengthens as it contracts, performs negative work and the abdomen is displaced in an expiratory direction. For a given change in lung volume, as delta Pab diminishes, there is progressive recruitment of intercostal/accessory muscles and a progressive increase in the work of breathing over and above that required to produce the same change in lung volume by contraction of the diaphragm alone. For values of delta Pab greater than 0 the sum of diaphragm and intercostal/accessory muscle work is less than the total work, because of an increase in the elastic energy stored in the rib cage. For Pab less than 0 there is a decrease in the elastic energy stored in the rib cage leading to a marked increase in work performed and pressures developed by the intercostal/accessory muscles.


Mechanisms controlling inspiration studied by electrical vagal stimulations in rabbits.

Electrical stimulations of either constant (step) or linearly increasing (ramp) stimulus frequency (F) were applied with different timing during inspiration to the central ends of cut vagi of anaesthetized rabbits. Integrated diaphragmatic activity (Ad) time course during stimulation, after a period of common path (Tu) with control, increased at reduced rate for a substantial period before end-inspiration (Ti). With stimulations maintained into early expiration, the higher F, the shorter Tu and Ti and the smaller end-inspiratory Ad. Delaying the onset of stimulation or using ramp instead of step stimulations, shifted rightwards both F vs. Tu and F vs. Ti relationships which became steeper. With increasing delay, Ad at Ti or Tu became eventually independent of F. Short stimulations ineffective to shorten Ti, prolonged Ti beyond control, end-inspiratory Ad being smaller, the smaller Ti prolongation. (a) vagal input, beyond a time dependent threshold, exerts a graded inhibitory effect on central inspiratory output (CIO); (b) vagal input undergoes a certain degree of integration; (c) vagal inspiratory inhibitory effects are independent of CIO; (d) vagal input prevents some centrally generated activity inhibiting CIO.


Experimental control of the diaphragm and laryngeal abductor muscles by brain stem arousal systems.

The effect of mesencephalic central tegmental field (FTC) stimulation in barbiturate anesthetized cats on the activity of the diaphragm and the laryngeal abductors was studied. With brief stimulus trains, two effects were observed: (1) a short latency, stimulus-specific activation of these muscles and (2) phase-switching of the respiratory cycle. The characteristics of short latency driving were as follows: (1) the latency and threshold for activation of the laryngeal abductors was less than for activation of the diaphragm; (2) driving continued for the duration of the stimulus only; and (3) during expiration, the threshold for short latency driving was lowest in the early part of the phase and progressively increased throughout it. Phase-switching had these characteristics: (1) expiration-to-inspiration (E-to-I) phase-switching was obtained in all cases and, in 17% of the cases, stimulation of the same FTC site also produced I-to-E phase-switching; (2) phase-switching was a function of stimulus intensity and the time of stimulation; and (3) during expiration, phase-switching showed a threshold profile opposite to that for short latency driving. These effects could be obtained after bilateral dorsolateral pontine lesions, bilateral vagotomy, and transection at the C8 level. It was concluded that the FTC could influence breathing by two systems. One is relatively direct to respiratory motoneurons and the other engages the oscillator.


Breathing in the potassium depleted rat: the role of metabolic rate and body temperature.

Rats with dietary potassium (K) depletion have an altered breathing pattern compared to age matched control rats. The K depleted rats also have a decreased body weight gain, basal metabolic rate and body temperature. In this study, age matched controls are underfed (UFC) to match for body weight gain and metabolic rate and controls are exposed to different ambient temperatures to alter metabolism and body temperature. Compared to UFC rats with the same body weight and basal metabolic rate the K depleted rats breathe slower and with a larger tidal volume in the basal state and in response to hypercapnia and hypoxia. With heat stress body temperature is increased in K depleted rats as is metabolic rate. While frequency is increased it is still slower than in controls at the same ambient and body temperatures. We conclude that the low metabolic rate and body temperature of K depleted rats is not the cause of the altered breathing pattern. In addition, it is shown that the hypothermia of K depletion is present only at ambient temperatures below the thermoneutral zone and that is is apparently due to an inability of the K depleted rat to increase metabolic heat production with cold stress.


Arterial pH, airway caliber and response to acetylcholine and catecholamines in vivo.

Direct assessment of tracheal circumference, which permits evaluation of constriction and dilatation in vivo, was made continuously in intact, pentobarbital-anesthetized, spontaneously breathing dogs. Immediate response to induction of hypercapnia included tracheal constriction and cessation of normal, vagus-dependent rhythmicity of airway tone. The characteristic constrictor response to acetylcholine was exaggerated significantly during hypercapnic acidosis and returned to normal when arterial pH, but not CSF pH, was corrected by NaHCO3 infusion. Epinephrine produced significant tracheal dilatation (infrequently followed by constriction) and isoproterenol produced only dilatation at normal pH. The catecholamine-induced dilatation was decreased significantly during hypercapnic acidosis, but improved after NaHCO3 infusion. Responses to acetylcholine and epinephrine were the the same as control during alkalemia, whereas the response to isoproterenol was unexplainedly diminished. Thus alkalemia may inhibit the action of isoproterenol; acidemia enhances parasympathomimetic constriction and reduces sympathomimetic dilatation; and correction of arterial pH returns these responses to normal, even if hypercapnia and CSF acidosis persist.


[Acute pseudobulbar palsy related to bilateral infarction of a part of the anterior choroidal arteries territory; a case report (author's transl)].

A 73 year old man had a pure, acute pseudobulbar syndrome. The pathological study showed only two infarcts of different ages. They involved uncompletely the territories of both anterior cohroidal arteries. On semi-serial sections, both cortico-bulbar tracts were destroyed whereas the cortico-spinal tracts were spared.


[Mortality and morbidity after complete surgical removal of 162 intracranial arteriovenous malformations (author's transl)].

A series of 162 arteriovenous malformations (A.V.M.) surgically removed is reported. All patients had a post operative control angiogram showing that the lesion had been totally excised. Supra and infra tentorial A.V.M. are included in the series as well as conscious and comatous patients. The overall mortality has been 11.1% and the mortality in conscious patients has been 6.9%. Mortality is higher when the volume of A.V.M. is over 60 cm3 and when a rupture has occurred. The influence of the operation on epileptic seizures, motor, speech or visual fields deficits has been reviewed in 109 patients who answered to the survey. Morbidity has been higher in patients with a cerebral heamorrhage, therefore the authors advise to operate these patients before the rupture when, for instance, seizures represents the only clinical picture. C.A.T. scan in these epileptic patients is a remarkable investigation to track down A.V.M.


[Does posterior internuclear ophthalmoplegia exist? A report on eleven cases and the results of oculography (author's transl)].

Based on the anatomical and clinical findings in the very rare cases reported, recent experimental data, and the results of oculography, the authors consider that this condition merits definition as an individual entity. It is usually associated with other disorders of oculomotility which may mask clinical signs, and oculography is necessary to establish the diagnosis. Terminologically, it would appear logical to retain the terms; abduction internuclear ophthalmoplegia (and not, posterior), and adduction internuclear ophthalmoplegia (and not, anterior).


[Macrosaccadic oscillations in a case of paraneoplastic myoclonic encephalopathy (author's transl)].

Abnormal ocular movements were observed in a patient with myoclonic encephalopathy secondary to branchial carcinoma. Clinical, cinematographic, and oculographic studies demonstrated the presence of rapid, large amplitude, conjugated, horizontal movements which occurred in bursts. They had a tapered appearance and were triggered by fixing vision and jerking movements, while they were abolished by rest and closing the eyelids. These features are similar to those seen in macrosaccadic oscillations. Other types of oscillating ocular movements are discussed as well as the physiopathological features of this disorder.


Ventral hippocampus spikes during sleep, wakefulness, and arousal in the cat.

The relationship between high amplitude (100--300- micro V) spike potentials (50--100 msec duration) in the ventral hippocampus (VH) and sleep-wakefulness stages was investigated. Forty-eight hours of continuous recordings taken from 5 chronically implanted cats were quantitatively scored for stage by digitized outputs of integrated EEG and electromyographic signals and for VH spikes by automatic devices. (1) A very strong relationship was observed between VH spike rates and EEG stage. Spikes were rare during wakefulness and paradoxical sleep (PS). They were always most frequent during nonrapid eye movement (NREM) sleep stages, progressively increasing through drowsiness, moderate amplitude slow wave activity, and high amplitude slow wave activity. (2) VH spike rates varied inversely with level of behavioral arousal within wakefulness. Rates were lowest during the presentation of novel experimental stimuli, higher during spontaneous movement, and highest during quiet wakefulness. (3) VH spikes anticipated stage changes independent of the quantified EEG. Spike rates increased from previous baseline levels in the 30 sec epoch of waking immediately preceding NREM sleep onset and in the transition period between PS and NREM sleep. They decreased significantly from previous base-line levels in the 30 sec epoch of NREM sleep preceding either waking or PS. These results show that the VH spike is a potentially useful noncortical indicator of NREM sleep. Within wakefulness and in the anticipation of stage changes it can be a more sensitive indicator of sleep processes or arousal level than the EEG.


[Strümpell Lorrain's familial spasmodic paraplegia. An anatomical and clinical review and report on a new case (author's transl)].

The authors describe the anatomical and clinical findings in a case of the pure form of Strümpell Lorrain's familial spasmodic paraplegia. This hereditary condition of the dominant autosomic type has very monomorphic pathognomonic features which are found in all patients affected. The slowly progressive isolated spastic hypertonia appears exclusively in the upright position and the extent of the disease can be ascertained by clinical observation during walking. The myelino-axial degeneration which is strictly limited to the spinal cord has an elective localization in the crossed pyramidal tracts, is less evident in the direct tracts and is mainly predominant in the lumbosacral and low dorsal regions of the cord. The extension of the process beyond the limits of the extrapyramidal tracts confirms the generally accepted unity of spinocerebellar degenerations. In this case the spinocerebellar tracts were less involved than the lumbar spinal ganglia, as well as their distant axial continuation to Goll's tracts only at the cervical level and until the bulber nucleus gracilis.


Effect of flurazepam, pentobarbital, and caffeine on arousal threshold.

After laboratory and procedure adaptation, 6 normal subjects were randomly administered 30 mg flurazepam (twice), 100 mg pentobarbital (twice), 400 mg caffeine (once), and placebo (twice) on nonconsecutive nights. On each night subjects were aroused from standard segments of stage 2 sleep five to eight times with an ascending series of 1,000 Hz tones produced by an audiometer. Arousal threshold and awake threshold after each arousal were measured. Both thresholds were increased by flurazepam and pentobarbital and decreased by caffeine. All of the drugs appeared to modify arousal threshold in a time course fashion such that extreme effects were found during the first half of the night. However, the modifications of waking threshold by caffeine and flurazepam continued throughout the sleep period. The method may be a means of measuring the behavioral time course of drug activity during the sleep period.


[Anatomical and clinical correlations in a case of alexia without agraphia (author's transl)].

The authors report the anatomical and clinical findings observed in a case of alexia iwthout agraphia due to left posterior cerebral artery infarction, in which there were lesions of the occipital and thalamic regions, the splenium of the corpus callosum, and the hippocampus. They discuss, more particularly, the memory difficulties, and the objects naming trouble.


[Measurement of multiregional blood volumes: a cerebral vascular autoregulatory phenomenon (author's transl)].

The variations in regional cerebral blood volume (RCBV) during controlled severe hypotension induced by sodium nitroprusside were studied in a series of 29 patients with aneurysms (14), meningiomas (6) and arteriovenous malformations. Two characteristic variations were noted. The RCBV and mean blood pressure (MPB) vary inversely, this type of variation being known as "Active variation". When pathological lesions are present the RCBV and MBP are modified in the same direction in the regions affected and this is called "Passive variation". A quantitative study in 21 patients showed that in the healthy regions there was a change from the active to the passive mode of variation for a MBP situated between 44 and 52 mm of mercury.


Sleep onset facilitation by tones.

In five successive sessions the effect on sleep latencies of three sound stimuli (silence, continuous sound, and an intermittent tone), as well as the combination of a tone plus counting or eye closing, were compared. Tests were conducted under a condition of "artificial insomnia": the subjects attempted sleep in the morning after a full night's sleep. No condition approached the latencies after a night of sleep deprivation. The intermittent tone and the tone plus counting were most effective and showed a differential sessions effect. The tone plus eye opening and closing was counterproductive.


Effect of growth hormone on memory in mice.

In order to determine the effects of growth hormone (GH) on long term memory, two experiments were carried out, all involving a common paradigm. Mice were given massed training on a discrimination task and were injected with GH or control substances before and/or after training: retention was measured 4 weeks later. In Experiment 1, different groups of mice were injected with either GH or saline at five different time points relative to original learning (OL): 90, 30, and 5 min before, and 5 and 30 min after. The results showed a significant quadratic trend, in the form of a U-shaped curve for the GH-injected groups at retention. Maximal retention was observed at the 90 min pre-OL and the 30 min post-OL injection groups. Poorest retention was shown by the 5 min pre-OL injection group. In Experiment 2, GH, saline, and thyroid-stimulating hormone (TSH) were administered at 90 and 5 min pre-OL. In addition, a "state dependency" hypothesis was tested using additional groups of mice. The results again showed a severe drop in retention when GH was administered 5 min before OL; differences between the two pre-OL GH injection groups were less marked than in Experiment 1; TSH did not have the same action as GH; and finally, a state dependency interpretation was ruled out. Together the two experiments present results that indicate a selectively GH-induced suppression of memory when GH is administered in close proximity to OL. As the time lapse between the injection of drug and the learning task increases, the inhibitory effect on memory is reversed.


[Present day concepts of the cerebral organization of language based on findings in bilingual Oriental patients with crossed aphasia (author's transl)].

Two right-handed bilingual (English and Cantonese) Chinese patients were observed to have crossed aphasia. A preliminary study of a multiracial population with left hemiplegia did not show a higher incidence of aphasia in Chinese subjects. These two extremely rare cases are interesting examples of a particular type of cerebral organization of language.


Excitatory-inhibitory processes in parietal association neurons during reticular activation and sleep-waking cycle.

Excitatory-inhibitory processes of parietal association neurons were studied during reticular-induced EEG activation and natural sleep-waking cycle. The probability of antidromic invasion in long-axon cells is enhanced following midbrain reticular stimulation and during both waking (W) and desynchronized sleep (D) states compared to slow-wave sleep. The thalamically elicited inhibitory phase occurs with a shorter latency following reticular stimulation and during W and D states; this is due to the reduced duration, during all these experimental conditions, of secondary excitatory processes. The duration of the inhibitory period is shorter during reticular activation; the postinhibitory rebound occurs at shorter latencies and is sharper following reticular stimulation and during W and D states. The similarity between reticular effects and changes during both W and D states is discussed.


Motoneuronal excitability during wakefulness and non-REM sleep: H-reflex recovery function in man.

Comparisons were made in 13 normal young adults of alpha motoneuronal excitability during non-rapid-eye-movement (NREM) sleep (stages 2--4) and wakefulness based on a study of the recovery cycle of the H-reflex after a conditioning stimulus. During sleep, excitability was generally decreased and a peak of secondary facilitation, which characteristically occurs 100--300 msec after the conditioning stimulus during wakefulness, was reduced or absent. A variety of mechanisms, including long-loop reflexes and afferent discharges from reflex muscle contraction and cutaneous fibers, has been proposed to account for this phase of facilitation in the waking recovery curve. However, since studies to date indicate the absence of tonic presynaptic or postsynpatic inhibitory influences acting on the monosynatpic reflex pathway during NREM sleep, but report tonic reduction in fusimotor activity at this time, it is suggested that a primary factor underlying the absence of facilitation during sleep is a reduction in central excitability deriving from depressed fusimotor activity.


Effects of sleep deprivation on sleepiness, sleep intensity, and subsequent sleep in the rat.

The effects of 24 hr of sleep deprivation on cortical EEG and ventral hippocampus EEG recordings, ventral hippocampus spike rates, sleep stages percentages, and bout length measures were studied in rats. Two groups, differing only in the rate and distance they were forced to walk during deprivation by the water wheel method, were recorded continuously (23 hr per day) for one baseline, one deprivation, and two recovery days. During deprivation, microsleeps, increased hippocampal spike rates, and increased amplitude of the EEG recordings all suggested the intrusion of sleep processes. Nonetheless, there was no evidence to support the idea that these animals were not substantially deprived of sleep. No important differences were found in the recovery data of the two groups, even though one group walked three times as far as the other during deprivation. This supports the idea that, in conjunction with large amounts of sleep deprivation, changes in exercise and energy depletion may have little effect on sleep measures. During recovery, increased hippocampal spike rates and bout lengths, as well as increases in EEG amplitude, were interpreted in terms of increased sleep "intensity." High amplitude NREM sleep rebounded first, followed by rebounds in both paradoxical sleep and low amplitude NREM sleep. This pattern was compared to patterns previously reported for humans, cats, and rats. Finally, the tendency for some measures to fall below their baseline levels after an initial rebound was discussed in terms of "sleep inhibition" and servomechanism theory.


Sleep apnea in normal kittens.

Apneic episodes in normal 10-, 20-, and 40-day-old kittens were assessed with polygraphic recordings. End expiratory apneas, usually preceded by somatic activity and/or augmented breaths, with durations less than 10 sec were observed in quiet sleep, active sleep, and transitions between states in all age groups. The highest apnea density was found at state transitions. Heart rate decelerations occurred before, during, and following apneas, but decelerations were not related to apnea duration. Combined central and obstructive components were associated with 9% of apneas in normal kittens.


[Prevention of streptococcal infections and post-streptococcal complications].

Starting from the particularities of the streptococcal infections, and the possibilities for fighting acute forms and the immediate and late complications, multiple aspects are discussed that should be implied by the prophylaxis of this infection in the present stage. Aspects of primary prophylaxis are treated separately, that are related to the limiting of the circulation of the etiologic agent, especially in view of preventing the epidemic forms of the disease. Also aspects of secondary prophylaxis are discussed, aimed at preventing streptococcal re-infections in subjects in whom complications such as rheumatic fever or acute glomerulonephritis have occured. "Primary prophylaxis" represents the key to the limitation of the streptococcal infection on the one hand, and of the transformation of acute articular rheumatic fever, of rheumatic carditis and of acute glomerulonephritis in "rarely encountered" diseases, on the other.


[Results of the use, for a period of 3 years (1974-1977), in pilot districts, of the complex program of measures for prevention of streptococcal infections and their complications].

Starting with the year 1974 a total 11 pilot units have been organized, in as many counties in which a complex program of surveillance of streptococcal infections was applied, that had the following objectives: 1. Prevention and fight against acute streptococcal infection ; 2. Prevention of severe complications of acute rheumatic fever of rheumatic carditis and acute glomerulonephritis ; 3. Prevention of relapses of acute rheumatic fever. The establishment and verification of methods for clinical and laboratory diagnosis was followed, as well as of therapeutic techniques and dispensarization. The analysis of results obtained after the application for a period of 3 years of the program in high-risk collectivities, and in the conditions of an intensive circulation of some epidemic strains of streptococcus has shown the decrease each year of the incidence of scarlet fever, the increased efficiency of detection of acute non-eruptive (non-rash) streptococcal infections, as well as a significant decrease in the number of cases that developed a first attack of acute rheumatic fever and acute glomerulonephritis. A significant decrease was also obtained in the number of relapses and of severe evolution of rheumatic carditis, due to active detection, continuous evidence, prophylaxis and periodic control of cases with acute rheumatic fever.


[Antibiotic prophylaxis of immediate and late complications of scarlet fever].

Patients with scarlet fever were followed by clinical and laboratory investigation (bacteriologic and immunologic reactions, etc.), in relation with the early application, and the duration of penicillin therapy. The patients were also followed for a period of 30 days after discharge from the hospital. The results show a decrease in the number of early and late complications, as well as a reduction in the number of carriers of beta-haemolytic streptococcus in those patients in whom penicillin treatment was applied early, and when it was prolonged in the recovery period. The clinical and statistical data stress the pathologic morphology of scarlet fever, and the restructuration of complications when penicillin treatment is applied.


[Streptococcal infections in adults].

The paper presents the morbidity through streptococcal angina, acute rheumatic fever and acute glomerulonephritis in two industrial enterprises with different working conditions. This study was performed between 1968 and 1977. In enterprise A, where rheumatogenic conditions were present, streptococcal angina had an yearly attacks vaeried between 0,13 and 0,7 percent, and acute glomerulonephritis between 2,3 and 5,4 percent. In enterprise B, with usual working conditions, angina showed an yearly variation between 2,3 and 5,8 percent, acute rheumatic fever varied between 0,0 and 0,84 percent and there were no cases of acute glomerulonephritis. In two units (collectivities of students) where angina was detected by active methods and prophylactic measures were applied rigurously no post-streptococcal complications were recorded. The authors stress the effects of morbidity through streptococcal infections in adults and recommend an extension of targeted prophylactic programs in high-risk units.


[Diagnosis of primary chronic rheumatic carditis in adults].

The authors maintain that in some cases one can note the so-called primar chronic rheumatic carditis, or apparently primary rheumatic carditis. Streptococcal infections can be held responsible for the eventuality of a sub-clinical evolution of rheumatism, and there which develops as a clinical form of latent rheumatism, and there is the possibility of ulterior development of valvular cardiopathy without a clear history of acute rheumatic fever in the antecedents. One of the groups subjects with maximal exposure to repeated streptococcic infection is represented by the teaching personnel working permanently in school or pre-school children collectivities or with teen-agers, which are both carriers and disseminators of the rheumatogenic streptococcal infection. Of a total of 50 cases of apparently primary chronic valvular cardiopathies that have been followed by the ASCAR personnel, 48 had tonsillary infections in their antecedents, 8 had arthralgia and 4 cases were detected by chance. In school collectivities at high risk prophylaxis with penicillin should be mandatory, both for the students and for the teaching personnel.


One man's view of Hodgkin's disease.

Despite its many heterogeneous features, Hodgkin's disease is most likely a single neoplastic disorder in which some common viral agent of low virulence and infectivity might be of etiologic importance. Family factors such as birth order influence age of initial exposure, a major determinant of the outcome of infection - clinical disease versus immunity. The various epidemiologic patterns for this lymphoma observed internationally are probably a reflection of different levels of natural immunity acquired in childhood. Host factors might be responsible for the male excess of Hodgkin's disease, particularly in childhood.


Some clinical considerations on congenital anomalies of the nose.

The diagnosis and treatment of nasal cysts and fistulas are reviewed on the basis of a material of 16 cases. Definite evidence of cyst size is often unobtainable. Surgery of nasal cysts and fistulas should be done as early as possible to assure unimpaired nasal growth. In secondary fistulas re-operations may be quite problematic. Bifid noses vary substantially in terms of severity. Severity, in fact, will dictate the surgical techniques to be employed, i.e. decortication or external incisions. Saddling, which is a consistent finding can be corrected by preserved cartilage. The results thus obtainable are satisfactory by follow-up evidence. Congenital flat nose is a rare anomaly. Eight cases were encountered in the past 10 years. The techniques of columellar lengthening and strutting of the nasal tip are reviewed.


Studies on the tryptophan load test in man.

Studies on the tryptophan load test were carried out by measuring the urinary excretion of 10 tryptophan metabolites via the kynurenine pathway in 25 healthy men and 20 women after oral L-tryptophan loading with dosages of 2 g. 50 mg/kg or 75 mg/kg body weight. With increasing doses of the amino acid, a difference was found between the male and female groups in the pattern of excretion of the tryptophan metabolites. In both groups, kynurenine and kynurenic acid were the metabolites excreted in the greatest amounts. The results indicate that the most useful loading dose of L-tryptophan for both men and women is 50 mg/kg body weight, as with 2 g L-tryptophan the excretion of the metabolites is too low and varies too much between the two groups of male and female subjects. On the other hand, the load with 75 mg/kg body weight can cause an overloading, particularly in women. No significant variations in the levels of the metabolites were found in the urine of two female subjects at different stages of the menstrual cycle after loading doses of 2 g and 50 mg/kg body weight. On the basis of the determination of the serum tryptophan levels, the period of urine collection was established as 10 h.


Results of surgical treatment of choanal atresia.

During a period of 19 years we have treated 65 infants with choanal atresia. Thirty of them showed a bilateral atresia, thirty-five a unilateral (29 left-sided, 6 right-sided). Fifty patients were girls, fifteen boys. In 27 cases the abnormality was combined with other anomalies. Most infants have been operated upon in the first six months of their life by a transpalatinal approach in general anethesia. From the results the following conclusions can be made: early treatment is the method of choice; restoration of nasal permeability, although minimal, allows normal nutrition and diminishes a number of respiratory infections, due to choking. The transpalatinal approach permits a direct control of the surgical area. It does not inhibit the growth of the hard palate and the function of the soft palate. Failures are caused by difficulties to keep the new passage open.


Corrective procedures in harelip nose deformities.

The author describes his method of surgical corrections of the hare lip nose which is based on publications in the literature. In addition he has developed his own technique of modelling the nasal top through intracartilagenous incisions and a special technique of stair-step-rim-nasal incision in order to prevent a linear contraction of the enlarged nostril.


Leukocyte behaviour in chronic uraemic patients undergoing regular dialysis.

A review of the literature is followed by the presentation of data obtained during a study of white blood cell kinetics in patients undergoing regular dialysis treatment. It was found that contact between white blood cells and the dialyzer results in a very prompt 'neutropenia-neutrophilia' stage and the deposition of billions of white blood cells on the membranes at the end of each treatment. A comparison of intradialytic leukocyte behaviour and the mean baseline white blood cell values was made in a total of 49 patients subdivided in four groups: 1. patients using coil and parallel flow dialyzers; 2. patients using dialyzers of different surface area; 3. patients of different dialytic age; 4. patients employing monoused or re-usable filters. No differences were noted in groups 1 and 4. In contrast, employing large dialyzers and the increasing dialytic age led to a variety of white blood cell patterns. Contrary to the information in the literature on leukocyte adhesion, it was observed that the cell deposits on the membranes and on the bubble trap filters, while predominantly composed of neutrophils, also contained monocytes and lymphocytes in proportions similar to those of the normal differential blood count.


Cellular allergy - one way to ozena? Rhinomanometry and histology in animal experiments compared with clinical aspects.

Based on rhinorheomanometric examinations supplemented by rhinoscopic and histological findings, evidence could be provided that an allergy of type IV in the Coombs and Gell classification can be challenged in the nasal mucous membrane as well. The tuberculin reaction in guinea pigs was used as test model. A critical evaluation of test results, immunological literature and some related challenge tests as to delayed reactions in human medicine are the reason for assuming the clinical symptoms of hypertrophy preceding ozena to be the clinical correlation to a type IV reaction. This correlation to clinical symptoms is not only borne out by animal experiments but also by years of experience in intranasal challenge tests, in rhinorheomanometry including the preparation of allergens for intranasal challenge.


Plasma renin activity in essential hypertension (a critical approach to its significance).

A study of the frequency distribution of plasma renin activity (PRA) in 123 patients with essential hypertension (EH) produced no evidence of a distinct subpopulation with low renin levels, whether the samples were taken from supine or upright patients. Applying an arbitrary classification criterion, however, low PRA levels were found in 30.1% of patients. There were no significant differences in mean blood pressure, 24-h sodium excretion, and age when groups with low, normal or high PRA levels were compared. The incidence of PRA hyporesponsiveness was similar in the three groups of patients, but increased with age. In the female there was apreponderance of low PRA levels. It is concluded that EH with low PRA levels is not a separate diagnostic entity and, when PRA is low in a hypertensive subject, the possible effects of age, blood pressure, and sex ought to be taken into account before other causes of low PRA are postulated.


Insulin binding to target cells (general survey, problems and results in spontaneous obesity).

Following Yalow and Berson's basic research on the binding of polypeptide hormones to plasma proteins, an integrated picture of hormone-receptor interaction and biological activity has been proposed for insulin in experimental models and in man. The extracellular interaction of the insulin molecule with the cell membrane structure modifies the intracellular metabolism, and it has been suggested that this occurs through the activation of a second messenger or the transduction of an insulin fragment into the cell. The use of monoiodoinsulin has made it possible to perform a series of experiments on cells isolated from the blood (monocytes) or from the tissues (adipocytes) and on plasma membranes prepared by ultracentrifugation. The existence of specific receptor sites for insulin in all cases, both in animals and in man, has been confirmed by mathematical analysis of the binding curves; their non-linear course, as plotted by Scatchard's method, may depend on negative cooperation or on different classes of receptor. From an evaluation of recent studies on human obesity, particularly on adipocytes and circulating monocytes, a new approach to the problem of 'insulin resistance' in obesity has been proposed, and this has shown that a reduction in the number of receptors on the target cells may contribute to peripheral insulin insensitivity. This phenomenon, which seems to be characteristic of the static phase of obesity, is reversible during fasting or weight reduction and may be a compensatory mechanism for hyperinsulinaemia. These results are an example of the significance and applicability of the experimental method of detecting insulin binding to target cells, and suggest a wide application in different endocrinological fields.


On nasobronchial reflex in asthmatic patients.

In 27 asthmatic patients a single cold stimulus into the nose resulted in a sudden increase of airway resistance, measured continuously by a new forced-oscillations-technique. The effect could be blocked by previous intrabronchial application of an anti-cholinergic drug. In laryngectomised patients, who no longer have a connection between the upper and the lower airpathways, cold stimuli into the nose caused a bronchoconstriction just as it did in the asthmatics. So the cold effect must be based on a reflex mechanism.


Effect of human leukocyte enzymes on tracheal mucosa and its mucociliary activity.

Human neutrophil granulocytes contain proteolytic enzymes. In purulent bronchial and paranasal secretions these enzymes have been found extra cellulary in complex with enzyme inhibitors as well as in free form indicating saturation of the inhibiting capacity. Isolated human leukocyte enzymes, elastase and neutral protease, were found to arrest the mucociliary activity and subsequently cause superficial tissue destruction. Elastase was found to be the most potent of the enzymes. Experimental studies with elastase together with specific inhibitor indicated the importance of the enzyme inhibitors for the integrity of the mucous membrane.


Determination of serum progesterone levels using a direct 125I-radioimmunoassay.

A new conventional simple and direct 125I-radioimmunoassay (RIA) for serum progesterone is described. In comparison with the classical tritiated assays which are preceded by extraction, the assay is more simple, less time-consuming, less subject to error and hence less expensive. In normal cycling females the serum progesterone range during the follicular phase was 0.9 to 5.5 ng/ml (mean 2.5 ng/ml). Levels above 12 ng/ml occurring during the luteal phase are indicative of adequate luteal function. The actual progesterone levels assayed with this method are significantly greater than those found using the classical tritiated technique, and the reasons for this discrepancy are discussed. The assay is also capable of being used to assess the response to treatment for infertility, thus indicating that, in spite of the higher values obtained, there is no impairment in diagnostic sensitivity.


[Epidemiological investigation on epilepsy in children of school age (author's transl)].

An epidemiological investigation was carried out in 1976-77 on all children attending the fourth year of primary education (9-10 years old) in Venice. The method of analysis was a questionnaire similar to that proposed by Rose (Epilepsy 1973) and by Meighan (Epilepsy 1976). Out of 1838, 1350 answered the questionnaire. The questionnaire synthesises various symptoms of epilepsy in 30 questions starting from the most severe ones. In a second phase the answers were divided into 8 groups: the hypothesis was that the percentage of children with epilepsy in groups 1-3 (high probability to have epilepsy) would be significantly higher than in groups 4-7. In order to test this hypothesis and to assess the discriminating quality of the questionnaire, a random sample of 114 children was submitted to clinical and EEG examination. The final classification in: A) epilepsy; B) febrile convulsions; C) minimal brain disfunction (M.B.D., according to Rose's definition); D) normal, was agreed upon including the heterogeneous information derived from history, neurological examination and EEG interpretation. A statistical elaboration of the findings has shown that the weighted average prevalence rate resulted to be 8.7%; the one relating to febrile convulsions was 27.93%; the one of M.B.D. was 5.2%. The high incidence of apparently positive cases may be explained because of difficulty in understanding some of the terminology used in the questionnaire; such cases, however, have been identified and discarded after a fuller history and neurological examination had been obtained. The problem of false negative cases seems however more important since it may also be caused by prejudice and by the reluctance of many people to accept the idea of epilepsy. For the appraisal of the incidence of this phenomenon we have examined all children (about 90) in two schools of the city indipendently from the answers in the questionnaire: no case of epilepsy was found. Further investigation is being carried out through an inquiry in EEG laboratories, hospitals and private phisicians in order to find out the real number of epileptic children. The incidence of epilepsy estimated with other methods appears similar to our data (Cooper 1965 - Huser and Kurland 1975). As a conclusion the questionnaire survey approach can be effectively used in studies on epilepsy together with epidemiological investigations in the assessment of cases of epilepsy not yet diagnosed as such.


[Incidence of chondrocalcinosis in a series of 1,000 surgically excised intervertebral disks].

This study is based on the histological examination of a series of 1000 intervertebral discs which were excised surgically for a painful spinal or nerve root syndrome. The authors observed in 31 cases (18 men and 13 women) a chondrocalcinosis that was not found clinically (small circumscribed deposits of crystals identified as calcium pyrophosphate after examination in compensated polarized light microscopy). The frequency is higher than that of chondrocalcinosis observed in the menisci excised surgically from the knees of subjects with the same average age; but it is lower than that for the menisci taken from autopsy material of subjects with a higher average age. The histological examination of all surgically excised discs would permit the findings of signs of chondrocalcinosis, thus emphasizing the risk for the patient of a further evolution to arthropathies (spinal or peripheral). This can offer bases for statistical longitudinal studies.


[Preliminary results of arthroplasty of the hip, using a pair of sealed double cups].

Arthroplasty of the hip with a pair of locked cupolas uses a metal cupola and a polyethylene cotyloid cupola. Ancillary instrumentation and 3 sets of protheses allow an acrylic fixation using a thin layer of cement. The authors report their experience with 75 surface replacement arthroplasties. The initial complications seem related to errors made in at the outset in drilling the femur, thereby compromising the solidity of the neck and the vascularization of the head. These results can be transposed upon the case of total conventional prothesis. The indications, which principally incluse centered coxarthrosis, have been widened to comprise necrosis limited to the femoral head, to rheumatoid polyarthritis, to ankyloses of the hip in a bad position, and to re-setting of non cemented cupolas. These encouraging results should be tempered by their short follow-up period (less than 2 years), and the present uncertainty as to the future performance of the lock joints and the wear of the polyethylene.


[Cervical arthrosic myelopathies. Study of a series of 35 cases. Pathogenetic and therapeutic reflections].

A series of 35 myelopathies was studied. The clinical characteristics are detailed. Gaseous myelography remains the best contrast test for establishing this diagnosis, making it possible to distinguish between spinal cords with constriction by stages and "trestle spinal cords" these two conditions often seem related. The medical treatments are disappointing, and one can improve the lesional syndrome but rarely the post-lesional syndrome. Surgery by posterior laminectomy gives in the long run only 45 per cent of improvement. On the basis of these observations, the authors state the opinion that the majority of the cases combining a cervicarthrosis and melyopathy after the age of 55, reveal of mixed, vascular and mechanical pathogeny. Surgery appears most useful in young patients whose spinal cord is congenitally constricted and shows sings of clinical distress.


[Local osseous blood flow measured with radioactive microspheres: correlations with intra-medullary pressures].

The authors studied in the dog, using radioactive microspheres, the blood bone outputs of the trochanter, the femoral diaphysis and the tibial diaphysis, and measured, in a simultaneous fashion, the intra-medullar pressures in these bone regions. A same hierarchy of outputs is consistently found in all animals : the trochentarian outputs are always the highest, and next come, in decreasing order, the outputs of the femoral diaphyses and the tibias. On the other hand, the intra-medullar pressures, although differing according to the bone regions, always have rather superposable rates, so that the neighboring intra-medullar pressures always correspond to radically different outputs. It is thereby demonstrated that the intra-medullar pressures, as an isolated parameter, cannot accurately reflect the rate of bone output.


[Axial osteosclerosis with autosomal dominant transmission: a new entity?].

The authors report on the case of a 26-year-old woman and three members of her family suffering from a benign condensing osteopathy, of dominant autosomic transmission, characterized mainly by a non homogenous hyperopacity of the spine and the pelvis, without alcaline hyperphosphatasemia, and which seems to them different from the condensing ostepathies described up to now.


[Diagnostic criteria in rheumatic pelvispondylitis without radiological sacro-iliac signs. Proposals for updating].

The authors propose a limited number of changes and additions to criteria for diagnosing spondylitis without the radiological sacro-iliac signs established by Sèze and Lequesne in 1961, taking into account the evolution of the diagnostic means that have appeared since this date, especially the attempt to locate HLA 27 leucocyte antigen, now a common practice. The application of these revised criteria in 75 cases, including 41 with certain or probable spondylitis, appeared satisfactory.


[The patella and the femoro-patellar joint during rheumatoid polyarthritis].

The authors report 2 series of cases of rheumatoid arthritis, one prospective of 115 cases, the other retrospective of 72 cases, and note the frequency of clinical and radiological patellar and femoro-patellar involvement during this disease. Signs of active rheumatoid disease in the patella were present in 31 cases. The most common lesions of the femoro-patellar joint space are narrowing and lateral dislocation of the patella. The femoro-patellar lesions evolve in parallel to the femoro-tibial lesions, but dissociation is possible. The early detection of a femoro-patellar syndrome permits effective treatment by isometric rehabilitation of the quadriceps. On the most advanced lesions, and when pain is limited to the femur and patella, an operation of reaxation of the patella may provide remarkable functional improvement.


[Comparative pathology of vertebral hyperostosis].

The changes seen in vertebral hyperostosis are due to a slow ossification of the perivertebral connective tissue causing osteophytic spurs and/or bridging of intervertebral ankylosis. The same changes seen in man are also seen in all land and aquatic mammals. This confrontation of comparative pathology emphasizes certain essential points in common. There is a relation between the vertebral hyperostosis and local anatomic and physiologic conditions linked to a ligament insertions. It occurs in bipodisis or tetrapodisis as well as in an aquatic environment. It must be distinguished from an osteoarthritic intervertebral remodeling and the evolution of its bone tissue is dissociated from that of the adjacent vertebral bone tissue. It is frequently observed in relation to general conditions (aging -- diabetes in man -- dietary imbalance in the animal). This example emphasizes the interest that comparative pathology can have for the rheumatologist.


[Lymphocyte populations in the blood and synovial fluid in rheumatoid polyarthritis. Importance of cell electrophoresis].

We have studied the synovial and blood lymphocyte populations of 18 patients with rheumatoid arthritis. Two methods have been used: the membrane markers (E rosette, active E, EA, EAC) and lymphocyte electrophoresis. The authors find no significant difference beteween the blood populations of the patients with the PR and that of the controls. On the other hand, the study of the synovial fluid shows a large number of lymphocytes T forming active rosettes having an electrophoretic mobility of about 1,10. In order to explain the presence of lymphocytes with high affinity for sheep red cells, and having a reduced electric charge in the synovial fluid, we propose two explanations: the first one is a selective filtration through the synovialmembrane of a physiological T subpopulation; the second one is a general modification of the lymphocyte membrane in relation with a stimulation or an intraarticular cellular alteration. In the discussion we report the arguments in favour of the two hypothesis.


[Silicon, bone tissue and immunity].

The authors study the activity of a soluble salt of silicium on the evolution of the trabecular bone volume (TBV). They note a significant increase in the TBV, both in drinkable and in injectable form, in relation to a control population not receiving osteotrope medication. They moreover note, in a series of patients treated with silicium compared to a control group, a net increase in circulating lymphocytes and immunoglobulins (especially IgG).


Ultrastructural pathology of the adrenal gland in Cushing's syndrome.

Authors studied the ultrastructural pathology of Cushing's syndrome. Some specific features correlated with the pathological aspects of the adrenals could be found. In the hyperplastic adrenal cortex the cytoplasm contains a rich smooth endoplasmic reticulum and numerous mitochondria. Increased lipid-pigment complexes were also found. The clear cell adenomas showed large lipid vacuoles. In the compact cell adenomas the mitochondria are of variable size and the smooth endoplasmic reticulum is well developed; the pigment bodies are frequent. The nuclei and especially the nucleoli are increased in size. In the adrenal carcinoma the nuclear and nucleolar alterations are still more evident. A marked pleomorphism of mitochondria was noticed. The behaviour of the steroidogenic activity in both tumoral and hyperplastic adrenal glands can be assessed using the ultrastructural picture of the agranular endoplasmic reticulum and of the mitochondria as functional parameters.


Studies on the purification of the antigonadotropic melatonin-free pineal extract.

Partial purification of a melatonin-free extract obtained from bovine pineal and showing an antigonadotropic activity was studied. The following methods were utilized: Sephadex gel filtration, ultrafiltration, precipitation by alcohol, ammonium sulphate and trichloracetic acid. The fractions obtained by all these procedures as well as the dialysed extract were biologically tested through the mouse uterine test. The protein contents in all the substances studied were assayed by Lowry's method. The results showed that in the extract studied, the antigonadotropic activity was present both in the fraction under 10,000 and in the fraction above 10,000, the latter containing 72% of the proteins from the total extract.


Effects of crinofizin administration in experimental diseases with protein anabolism disorders. Studies in the rat.

The effects of the treatment with Crinofizin, a pineal peptide extract, on certain parameters of the protein metabolism, altered in rat by prolonged deficiency of endogenous insulin (study on animals with streptozotocinic diabetes) or by administration of large doses of cortisone, were studied. The results demonstrated the anabolic effects of the pineal extract treatment which improved the diabetic syndrome and counteracted some catabolic effects subsequent to insulin deficiency, such as weight loss and decrease in the nucleic acid concentration in the liver, or to cortisone excess, such as nitrogen loss. The data obtained open new prospects for the use of Crinofizin in the management of degenerative endocrine diseases through anabolizing hormones failure or catabolizing hormones excess.


Persistence of circadian rhythms of RNA, DNA and protein in the rat adrenal and thyroid under continuous darkness conditions.

Continuous darkness regimen applied to rats for 30 days did not significantly alter the patterns of the circadian rhythms of RNA, DNA and total protein in the thyroid and adrenals. These results show that the dominant role of light as a "Zeitgeber" cannot be generalized in the case of the biorhythms studied.


The effect of acetyl salicylic acid and dipyridamole on thromboembolic complications in splenectomized patients with myelofibrosis.

The effect of combined treatment with acetyl salicylic acid and dipyridamole on thrombic phenomena was studied in splenectomized patients with an aggressive form of myelofibrosis. 3 of these patients had thrombotic episodes, shortened platelet survival and an abnormal platelet aggregation pattern. The treatment with antiplatelet drugs resulted in a decreased platelet utilization as evidenced by clinical improvement and an increasing platelet concentration.


The level of urinary and plasma steroids after oral administration of cyclofenil to hirsute women with menstrual disorders and obesity.

Cyclofenil 600 mg/day was given to 10 women with excessive skin hair and marked excretion of urinary androgens. The urinary values of androgenic metabolites as well as the plasmatic values of radioimmunoassayable testosterone remained unaltered. A significant increase was noticed in the radioimmunoassayable plasma estradiol. Urinary total estrogens could not be assayed in the women under cyclofenil because of a non-specific color reaction. It was concluded that the estrogenic effects of cyclofenil are mediated, at least partly, by release of gonadotropins from the hypophysis.


RIA measurement of insulin antibodies in human sera using the polyethyleneglycol separation technique.

A radioimmunological method for the detection and measurement of insulin antibodies in human sera was developed using polyethyleneglycol (PEG) as separation agent. Studies were performed on 150 sera of nondiabetic subjects and on 27 sera collected from diabetic patients treated with insulin. The per cent binding of 125I-insulin in normal sera ranged similarly to control free-insulin serum while in sera from insulin-treated patients8 the binding was significantly greater. The technique is quick (24 hours) and the intra-assay precision (correlation coefficient for replicates) varies from 0.87 to 0.99%. The separation technique using PEG for the precipitation of the antigen-antibody complexes may be extended to the measurement of antibodies for any other substance of lo, molecular weight (under 10,000 daltons).


Serum iron and transferrin saturation in women with special reference to women with low transferrin saturation. The population study of women in Göteborg 1968-1969.

Serum iron and total iron binding capacity (TIBC) were determined in a population sample of 1462 women in age strata between 38 and 60. Serum iron and TIBC values were similar in the various ages studied but with a slight trend towards higher serum iron and lower TIBC values in the upper ages. Transferrin saturation was used to divide the material arbitarily into women with and without iron deficiency. The dividing point chosen was 16%. The women thus defined as iron deficient had lower mean haemoglobin values than women in the total population sample and were more often anaemic. They had also lower MCV, MCH and MCHC indices than women in the total population sample. Of these indices, MCH seemed to discriminate the state of iron deficiency better than MCV and MCHC. Except for an increased mean menstrual blood loss no obvious cause of iron deficiency could be found in these women with low transferrin saturation.


Factors interfering with the cell morphology in smears.

Factors interfering with the cell morphology in smears were studied. The following artifacts were observed: Lysis of cells with release of granules, cytoplasmic and nuclear proteins; fern-like structures due to detachment of protein from glass; rupture of the surface of smears; crystal formations; leakage from cells interfering with the surrounding medium; cell shrinkage, vacuolization; and aggregation of cells caused by gammaglobulins. The concentration and type of plasma protein in the medium greatly influenced the type of artifacts. The technique by which the least artifacts occurred, was cytocentrifugation of cells suspended in a cell protecting medium.


The effect of combined administration of L-proline and glycine on GH and IRI release in healthy prepuberal children.

Proline (100 mg/kg b.w.) was given per os and after 30 minutes 10% glycine was i.v. injected to 25 healthy children of both sexes. A positive response (an increase of over 5 ng/ml of serum level of GH) was found in 21 of the 25 children. The insulin test showed a positive response in 24 of the 25 children. It was concluded that the decrease in glycine dosage from 250 mg/kg b.w. (earlier reports by the same authors) to 100 mg/kg b.w. (present data) is generally compensated by l-proline priming. The IRI serum levels were almost unchanged. By l-proline priming, the glycine test can also be applied to subjects with body weight over 40 kg, in doses of 100 mg/kg b.w. for exploring the secretory reserve of the somatotropic axis.


Platelet heterogeneity. Relationship between buoyant density, size, lipid peroxidation and platelet age.

Human platelets were separated into 2 density populations by repeated centrifugations of platelet-rich plasma at increasing gravitational force. The heaviest platelet fraction was rich in larger platelets. The lightest platelet fraction was rich in smaller platelets. In both fractions and in the platelet button, lipid peroxidation (malonaldehyde-MDA-production after addition of thrombin) was measured at basal condition, on the 1st, 3rd, 5th, 7th and 9th day after aspirin ingestion. At basal conditions and after ingestion of aspirin, MDA production was higher in the heavy-large platelets than in light-small ones, but a parallel increase of MDA production was observed in the light and in the heavy population and in the platelet button. The data are not compatible with the hypothesis that platelet density and size are age-related. Aspirin inhibits platelet lipid peroxidation by permanently acetylating their cyclooxygenase and if the heaviest platelets were the young ones, lipid peroxidation should reappear sooner in them.


Glucagon secretion in subjects with prediabetes, diabetes mellitus and obesity.

The blood glucagon concentration (fasting and in insulin hypoglycemia) was determined by radioimmunoassay in diabetic patients, relatives of diabetic patients with a normal glucose tolerance test, patients with obesity and a group of normal weight subjects. The index of glucagon rise above the fasting level and glucagon release rate were estimated. In relatives of diabetic and obese patients the initial blood glucagon concentration did not differ from that of healthy subjects. However, during insulin hypoglycemia, glucagon secretion was significantly reduced, and in relatives of diabetic patients it also proved to be delayed. A comparison of glucagon and somatostatin changes in the above mentioned patients allows to suggest participation of the somatostatin mechanism in disorders of glucagon secretion.


Circulating megakaryocytes in patients with pulmonary inflammation and in patients subjected to cholecystectomy.

30 patients with pulmonary inflammation and 17 patients subjected to cholecystectomia à froid were investigated for circulating megakaryocytes in a cubital vein using the saponin-haemolysis leucoconcentration technique. The number of circulating megakaryocytes was significantly higher in patients with pulmonary inflammation than in healthy humans. In 15 patients with bronchitis, bronchopneumonia, and leucocytosis the arithmetic mean was 15.6 megakaryocytes per 1.5 ml blood (range 3 to 47). In 15 patients with bronchitis and a normal leucocyte count the arithmetic mean was similarly 14.1 megakaryocytes per 1.5 ml blood. After cholecystectomy a significant maximum increase in the number of circulating megakaryocytes to 3 times the preoperative value was found on the third postoperative day but not on the other postoperative days. Of the observed megakaryocytes 99% had only a narrow rim of cytoplasm or were naked nuclei.


Familial erythrocytosis.

Erythrocytosis was found in 3 generations of an English family. The red cell mass was only moderately increased in some of the affected members but was accompanied by an unusually low plasma volume. Oxygen affinity of Hb was normal. Changes in serum and urinary erythropoietin showed an essentially normal pattern throughout a series of venesections. Venesection produced some transient clinical benefit in the older patient but there was no obvious change in the younger ones.


The diffusion chamber technique as an in vivo assay in mice for the effectiveness of antitumor agents.

The diffusion chamber (DC) technique has been applied to the culture of L1210 cells in view of determining their sensitivity to chemotherapic agents. The surviving fraction of L1210 cells cultivated in DC's 4 d after i.v. injection of the host mice with 10 mg/kg of daunorubicin or daunorubicin-DNA was 40% and 9% respectively. The results suggest that the DC technique could be a useful in vivo predictive test for cancer chemotherapy.


High level of human growth hormone (HGH) in cerebrospinal fluid patients with pituitary tumors.

Six patients with suprasellar extension of pituitary HGH-secreting tumors showed the cerebrospinal fluid (CSF) content in human growth hormone (HGH) to be very high, i.e. 164.3 +/- muU/ml (mean +/- SEM) (range 8.4--413.8 muU/ml) as compared to ten patients with uncomplicated acromegaly whose values were 50-fold lower, i.e. 3.4 +/- 0.5 muU/ml (range 0.6--7.0 muU/ml), and nine patients with suprasellar extension of other pituitary tumors, showing also low levels of HGH in the CSF, i.e. 2.9 +/- 0.8 muU/ml (range 0.6--7.2 muU/ml). A control group of 29 normal patients without pituitary or brain diseases showed extremely low values of HGH in the CSF (1.9 +/- 0.2 muU/ml), one third being below the sensitivity limit of the assay method. Another control group of 70 patients with hypothalamic diabetes insipidus (n = 18), brain traumatisms (n = 10), brain surgery (n = 20), as well as various brain diseases (n = 22), also showed low HGH levels in the CSF, like the normal control group. It is shown that a high level of HGH in the CSF has a potential usefulness in the diagnosis of suprasellar extension of the pituitary mass in acromegaly.


Evaluation of the activated whole blood clotting time (ACT) in vitro.

The activated whole blood clotting time (ACT) was analyzed in vitro using blood samples from normal individuals and from patients with heart disease, scheduled for open heart surgery. The ACT was found to be normally distributed in a group of normal individuals with a mean of 135 sec. In patients with heart diseases, the average ACT was slightly shorter than in normal individuals. A linear relationship between ACT and heparin concentrations was established. Haemodilution and depletion of platelets did not significantly influence the ACT. When a clean venipuncture with disposable needles is used, ACT is a reliable, uncomplicated bedside technique by which heparinisation can be monitored.


[Heparin treatment. Comparison between intravenous and subcutaneous administration].

48 patients with acute deep venous thrombosis of the lower limbs were treated with sodium heparin. In 23 patients heparin was injected subcutaneously (s.c.) twice a day and in 25 patients heparin was given by continuous intravenous perfusion (i.v.). Pain and edema disappeared after 8.7 days (s.c.) and 11.7 days (i.v.) respectively. One non fatal pulmonary embolism occurred in each group. A second venography was performed in 24 patients after 7 days of treatment and revealed no difference between the two groups. As judged by repeated thrombin time determination, anticoagulation was ineffective on at least one day in 39% of patients treated subcutaneously and in 60% of patients treated intravenously. The two pulmonary embolisms occurred in patients with ineffective anticoagulation. It is concluded that heparin  may be used either intravenously or subcutaneously in the treatment of acute deep venous thrombosis. Thromboembolic complications occurred with both methods of treatment when anticoagulation was ineffective.


Classification of opioids on the basis of change in seizure threshold in rats.

Twenty opioids have been subdivided into four classes by using flurothyl-induced seizures in rats to measure dose-response relationships, stereospecificity, naloxone sensitivity, and tolerance-cross-tolerance. The data support current theories of multiple opiate receptor types. Since the receptors involved mediate effects that are antagonized, enhanced, or unaffected by naloxone, the model is uniquely suitable for detecting novel narcotic antagonists that can then be used to differentiate opiate receptors in other systems.


Reading without a fovea.

A visual mask moving in synchrony with the eye obliterated foveal vision during reading under certain conditions. When foveal vision was masked, reading became difficult. In another condition, a window of readable text moved in synchrony with the eye, and parafoveal vision was masked on each fixation. The results point out the importance of foveal and parafoveal vision in reading.


Phenylethylamine in paranoid chronic schizophrenia.

Phenylethylamine (PEA) is an endogenous amine that is structurally and pharmacologically related to amphetamine. Urinary PEA excretion is significantly higher in paranoid chronic schizophrenics than in nonparanoid chronic schizophrenics and normal controls. Diet, hospitalization, and medication do not account for differences in PEA concentrations. These findings offer some indication that PEA may be an endogenous amphetamine.


Cholecystokinin octapeptide: continuous picomole injections into the cerebral ventricles of sheep suppress feeding.

Cholecystokinin octapeptide decreased food intake in a dose-related manner when injected continuously into the lateral cerebral ventricles of sheep that had been deprived of food for 2, 4, 8, or 24 hours. In sheep deprived of food for 2 hours, as little as 0.01 picomole per minute suppressed feeding 35 percent 1 hour after beginning injection. Pentagastrin also decreased feeding in the 2-hour group, but only at a much higher dose range. Secretin had no effect. These findings support the hypothesis that cholecystokinin octapeptide acts on central nervous system structures that are involved in control of food intake.


Stimulation of abducens nucleus supports classical conditioning of the nictitating membrane response.

The acquisition and terminal performance of a classical conditioning group compared with a control group indicated that extension of the nictitating membrane elicited by direct electrical stimulation of the abducens nucleus was successfully conditioned to a previously neutral stimulus. The conditioning so obtained was associative and not due to such nonassociative factors as sensitization, pseudo-conditioning, or alteration in base-rate responding.


Gamma rays: further evidence for lack of a threshold dose for lethality to human cells.

In experiments designed to measure human cell survival sith +/- 2 percent accuracy it was found that low doses (21 to 87 rad) of gamma-rays inactivated the colony-forming ability of cultured human cells with a probability of 0.00226 +/- 0.00012 per rad. There appears to be no threshold for the lethality of radiation to human cells in vitro.


Movement disorders of aged rats: reversal by dopamine receptor stimulation.

When placed in a tank of water, aged rats (24 to 27 months old) showed marked impairments in swimming. Compared with young adult rats (3 to 4 months old), the older animals moved their limbs less vigorously and were less successful in keeping their heads above water. The young, but not old, rats maintained a position nearly horizontal to the water surface and planed across it. These movement dysfunctions of aged rats resemble those seen in young adult animals that have sustained injury to brain dopamine-containing neurons. The swimming impairments of the aged rats were reversed by the dopamine receptor stimulant apomorphine and by the biosynthetic precursor of dopamine, L-dopa. Thus, age-related alterations in brain dopaminergic systems may be responsible for some of the movement disturbances associated with senescence.