Memory and intelligence following spontaneously arrested congenital hydrocephalus. This study describes two cases of spontaneously arrested congenital hydrocephalus whose educational progress appears normal. They were found on examination to have a reduced performance IQ, but a normal verbal IQ. They showed a significant impairment in immediate free recall, which was specific to the secondary memory component. It is concluded that congenital hydrocephalus may produce an organic disorder which manifests itself in later life as an impairment of verbal memory.


Anxiety, extraversion and smoking.

Anxiety, extraversion and smoking. In previous large-scale studies, smoking has been found to be associated either with extraversion or anxiety, though not both. Using a large population of adult American males, anxiety and extraversion scores were examined in groups of never smokers, former light, former heavy, current light and current heavy smokers to test the hypotheses that smokers would be both more extraverted and more anxious than non-smokers. Two independent measures of both traits were used. Heavy current smokers were seen to be significantly higher than non-smokers on both measures of neuroticism or anxiety; there were no differences between groups in extraversion. The small magnitude of reported relations led to the suggestion that future research focus on more meaningful classification of smokers and more specific facets of personality.


Visual interaction in schizophrenic patients: the timing of looks. Previous research has suggested that schizophrenic patients engage in very little Looking and eye-contact, at least in "personal" conversations. As yet, however, we know nothing about the precise timing of their Looks, even though this has important clinical implications. Data from three studies are presented and no evidence of abnormality is found. It is concluded that, taken together, findings from visual interaction suggest not that schizophrenic patients behave in a socially unskilled way as has sometimes been argued, but simply that they are embarassed by "personal" conversations and, like perfectly healthy people who are embarrassed, respond by averting the gaze.


Iliotibial tract friction syndrome in athletes--an uncommon exertion syndrome on the lateral side of the knee. An uncommon exertion pain on the lateral side of the knee is described in 88 patients, in four of whom it was bilateral. The disorder is a result of the friction of the iliotibial tract over the lateral femoral epicondyle. The syndrome is the iliotibial tract friction syndrome of ITFS. All the patients in the material were active athletes or middle-aged joggers in regular training. The cases were seen over four years and four months. The mean age of them was approximately 25 years, and there were only nine women in the series. Th pain appeared usually after running and was localised on the outer femoral condyle, and often radiated downwards along the iliotibial tract. Conservative treatment and changes in training habits cured most cases. The disorder has not often been described in the literature, and seems to appear only in physically very active people, such as athletes or military recruits.


Serum insulin and glucose response to graded exercise in adults. Part I: the influence of fitness status. The effect of acute exercise upon serum immunoreactive insulin levels (IRI) and serum glucose concentrations (GC) was studied in groups of middle-aged men of contrasting physical fitness status. Two groups of subjects, one active and one sedentary (both N = 11, mean age 44 years), performed a graded cycle ergometer exercise test in the post-absorptive state. Venous blood samples were taken at rest, during low and high work intensities, and after recovery. The response of serum IRI to exercise was similar in both groups of subjects with significant increases observed during exercise followed by a return to resting values during recovery. However, the magnitude of serum IRI response was lower in the active group. In contrast, the sedentary group demonstrated little or no change in serum GC during exercise, whereas significant increases in serum GC were observed during exercise in the active group.


A study of potential Olympic swimmers. Part 2. Changes due to three months intensive training. Anthropometric and physiological measurements were recorded for a group of exceptional young swimmers undergoing an intensive training programme over 3 months. The observed changes are presented and are discussed in relation to the training undertaken, and are compared with expected changes due to normal growth. Some of the physiological parameters measured showed marked changes: average physical work capacity decreased significantly, while the physical fitness index improved. Many of the anthropometric changes were small, but a significant increase in lean body mass occurred in both boys and girls, and in both groups the average weight gain was greater than that expected. In individuals subjected to rigorous training significant changes in anthropometric and physiological parameters over and above the expected changes due to normal growth and development occur relatively quickly within a period of 3 months.


A comparison of physical efficiency between Indian physical education and medical students. The recovery pulse and respiration were analysed to determine the level of physical fitness among the physical education and medical students of Banaras Hindu University. The analysis of the data suggested that physical fitness as measured by recovery rate was better in physical education students than in medical students. Following questionnaire method, it has been noted that the daily activity of physical education students was more than the medical students and probably the reason for higher efficiency in them.


Standards on age, height and weight in Olympic running events for men. The Olympic champions, finalists and participants are well differentiated on age, height and weight (adjusted for height) in each of the eight running events. Height for height, the champions in sprinting events are heavier than other participants but the trend is reversed in long distance events. Physiological reasons for these differences are discussed.


Intraoperative management of phaeochromocytoma with sodium nitroprusside. Sodium nitroprusside (SNP) is a powerful, peripherally acting hypotensive agent with a rapid onset but short duration of action. It is highly effective for hypertensive episodes in patients with a phaeochromocytoma and may be used safely with adrenoceptor-blocking agents. Two cases are described that illustrate its effectiveness in this condition, even in the presence of exceptionally high circulating concentrations of catecholamines. A simple and reliable regimen for preparing these patients for surgery may be based on oral adrenoceptor-blocking medication (phenoxybenzamine and propranolol) to provide "background" hypotensive and antiarrhythmic cover. SNP by infusion is then used as the principal intraoperative hypotensive agent, dysrhytmias being controlled with additional intravenous propranolol if required.


Prevalence of multiple sclerosis in north-east Scotland. An epidemiological study of multiple sclerosis (MS) in north-east Scotland was carried out based on data correct on 1 December 1970. The prevalence of MS was 127 cases/100 000 population, which is greater than in any other surveyed area with a comparable population. The disease was not spread homogeneously within the region, and in one district one in 400 people was affected. The geographical distributions of MS and the presence of HLA antigens A3 and B7,which are associated with the disease, are remarkably similar, and the prevalence of B7 in north-east Scotland is higher than elsewhere. This may partly explain the high prevalence of MS in this area, but the essential additional environmental factor remains to be established.


Complications of ascending phlebography of the leg. Forty patients were studied prospectively for complications of ascending phlebography. The commonest immediate complication was pain at the site of injection and the commonest delayed complication pain in the foot or calf. Out of 30 patients with pain in the foot and calf, 15 had venous thrombosis. Review of 200 case notes disclosed only one recorded complication--namely, necrosis of the dorsal skin of the foot. Complications of the procedure reported by referring clinicians over 10 years comprised four cases of necrosis of the dorsum of the foot and two of gangrene of the foot, in one of which the gangrene spread to the leg. Major complications of ascending phlebography are rare, though when they occur may cause serious morbidity. If a scrupulous technique is used contrast phlebography remains the most accurate method of diagnosing venous disease of the leg.


Does adipocyte hypercellularity in obesity exist? Adipose tissue samples were biopsied from three subcutaneous sites in 80 obese and 27 non-obese patients. Additional samples were taken from intra-abdominal sites in 44 of the patients. There was a small increase in the calculated number of fat cells in the more obese patients, but there was no relation between fat-cell number and obesity of childhood onset. Omental fat cells were one-third the size of subcutaneous cells. Thus the calculated number of fat cells, usually based solely on subcutaneous samples, is an underestimate of the true number, and most obese patients can accommodate their fat without needing to recruit new cells. The diagnosis of "hyperplastic" obesity--that is, an excess number of fat cells--is unreliable and its relation to infantile obesity doubtful.


Heparin-like activity in uterine fluid.

Heparin-like activity in uterine fluid. Uterine fluid was collected from a group of normal patients and a group of patients with menorrhagia. Heparin-like activity was detected in 34 out of 38 samples using an anti-Xa heparin assay. The heparin-like activity in uterine fluid was inhibited by adding the heparin antagonist hexadimethrine bromide to the assay. Concentrations of fibrinogen-fibrin degradation products (FDPs) were measured in five samples of uterine fluid. FDPs in the concentration detected had no effect on the anti-Xa assay. Heparin-like activity was higher in the group with menorrhagia, although the differences were not significant. Heparin-like activity increased throughout the menstrual cycle and decreased during menstruation, suggesting a possible cyclical variation in activity. There was no correlation between mast cell numbers in the endometrium and myometrium and heparin-like activity in uterine fluid and no correlation between the numbers and the stage in the menstrual cycle. In a few patients with intrauterine contraceptive devices (IUCDs) heparin-like activity was increased.


Cerebral blood flow in diabetes mellitus: evidence of abnormal cerebrovascular reactivity. Cerebral blood flow (CBF) was studied at normocapnia and after a challenge with 5% CO2 in 59 diabetic patients and 28 controls. There was a significant age-related decline in CBF in both groups, which suggests that diabetes does not affect the rate of decrease of CBF with age. After CO2 challenge CBF increased in most of the controls; in the patients CBF increased in 23, decreased in 26, and remained stable in 10. Thus the reactivity of cerebral blood vessels in diabetics is altered. Diabetics have diminished cerebrovascular reserve and are thus at increased risk of cerebrovascular disease because they are unable to compensate when necessary with an increased CBF.


Renal failure in otherwise uncomplicated acute viral hepatitis. Twelve patients with otherwise uncomplicated acute viral hepatitis (two were HBsAg-positive) developed renal failure. Apart from dehydration due to repeated vomiting in one patient, no factor responsible for precipitating renal failure could be identified. The clinical course was characterised by renal failure with plasma urea concentrations reaching maximum values of 26-69 mmol/l (175-416 mg/100 ml). Ten patients needed dialysis for up to two weeks. Seven patients recovered completely, while the other five died from sepsis. The types of renal failure were similar to those described in fulminant hepatic failure and cirrhosis--namely, functional renal failure in five patients and acute tubular necrosis in seven. Two of the patients with functional renal failure later developed tubular necrosis. The mechanism responsible for renal failure in acute viral hepatitis is uncertain, though endotoxaemia may contribute.


Disproportionate reduction in tryptic response to endogenous compared with exogenous stimulation in chronic pancreatitis. The secretin-pancreozymin (SP) and Lundh-Borgström (meal) tests were compared in diagnosing chronic pancreatitis (CP). A range of normal values for each test was obtained in a control group of 22 patients without pancreatic disease. Seventeen patients with CP were given the tests on separate days. The peak concentration of bicarbonate after secretin was reduced in 14 of these 17 patients, post-secretin bicarbonate output fell in 13, while peak tryptic activity (PTA) in duodenal juice after pancreozymin was below normal in 10; the overall incidence of abnormal results in SP tests was 88%. The mean tryptic activity (MTA) in a two-hour collection of duodenal juice after the test meal was reduced below normal in 16 of the 17 patients.In the control group PTA after pancreozymin was closely similar to MTA after the test meal, but in the patients with CP MTA was significantly less than PTA. PTA and MTA correlated significantly in both the control and CP groups, and the slopes of the two regression lines were not significantly different. In each patient with CP the tryptic response to the test meal was only a third of the tryptic response to intravenous pancreozymin. This disproportionate reduction in tryptic response to endogenous compared with exogenous stimulation in CP accounts for the high success rate of the meal test, which equalled the SP test.The Lundh-Borgström test is a sensitive indicator of CP and is within the resources of most hospitals. The SP test is better suited to specialist centres and may provide valuable additional information in individual cases.


Corticosteroids and liver amoebiasis.

Corticosteroids and liver amoebiasis. Patients with amoebiasis who receive steroid treatment may suffer adverse affects including acute amoebic dysentery and exacerbation of the amoebiasis. In some cases the presenting symptoms are initially misdiagnosed and steroids prescribed, which provokes fulminating progression of hepatic amoebiasis. Repeated stool examinations often yield negative results. Any patient being considered for treatment with corticosteroids who has lived in the tropics should be investigated for amoebiasis serologically and by repeated stool examination. Even after negative results the possibility of amoebiasis should be reconsidered if diarrhoea or fever develops during or after steroid treatment.


Emergency geriatric surgical admissions. The emergency surgical work load created by patients aged 80 and over in a district hospital was assessed and the results of treatment examined. Over one year 248 patients aged 80 or over were admitted as emergencies, and the overall mortality rate was 21.8%. When terminal disease was excluded mortality rate was 12.5%. These elderly patients had an average length of stay in the acute surgical ward of 14.7 days compared with a mean of 8.4 days for all patients, and all but seven patients were discharged to their original place of referral.Elderly patients do exacerbate the bed shortage in acute surgical wards because they tend to stay longer than younger patients, but these elderly surgical patients imposed only a small load on the inpatient geriatric services, as 78% were discharged straight to their own homes and a further 17% went home after a period on the surgical convalescent wards.


Dorsal column nuclei in a prosimian primate (Galago senegalensis). II. Cuneate and lateral cuneate nuclei: morphology and primary afferent fibers from cervical and upper thoracic spinal segments. The morphology and brachial cord primary afferent projections of the cuneate and lateral cuneate nuclei have been studied in the lesser bushbaby. The cuneate nucleus was divided into three regions. From caudal to rostral these were the large cell, cell column and rostral regions. Primary afferents from C2, C4, C6, C7, C8, T1 and T3 terminated within distinct partially overlapping terminal zones in the ipsilateral large cell and cell column regions of the cuneate nucleus (CN) and the lateral cuneate nucleus (LCN). Segmentotopic was the greatest in the rostal region of the CN due to a more diffuse projection pattern. In the LCN, the transverse terminal fields appeared as curved mediolaterally oriented laminae. In each case, ascending fibers of passage from C4, C6, and C7 in the cuneate fasciculus were organized so that two distinct fiber laminae were present. The separation of fibers and the formation of the two ascending laminae were completed either within two segments rostral to their respective level of entry (for C6 and C7 lesions) or in the caudal medulla (for C4 lesion). For each of these segments, the laminae consisted of a small dorsomedial one and a large lateral one. The organization of primary afferents from one segment into two ascending fiber laminae in the cuneate fasciculus was reflected in a differential termination pattern within both the CN and LCN. The results of this study were discussed relative to earlier anatomical and physiological studies on the DCN in other animals.


The accumulation of DL-glutamate by the central nervous system of the snail Helix pomatia. Isolated snail ganglia are capable of maintaining their free amino acid levels steady for the first 60 min of incubation in physiological saline. Within this time the ganglia also possess an uptake mechanism for DL-glutamate which can be divided into sodium-sensitive and -insensitive components. The accumulation of DL-glutamate showed saturation kinetics typical of a carrier-mediated process. The Vmax value for the uptake is 1.5 x 10(-8) mole/g/min and the Km value 1.1 x 10(-4) M. The amino acid accumulation is quite specific towards L-dicarboxylic acids and insensitive to a number of metabolic inhibitors. It is unlikely to be due to a homoexchange phenomenon because the ganglia are capable of achieving a net uptake of glutamate and the efflux of DL-[3H]glutamate is not increased by the addition of non-radioactive L-glutamate to the incubation medium.


Vascular permeability alterations to horseradish peroxidase in experimental brain injury. Protein uptake and transport within the brain stem vasculature of mechanically brain injured cats was studied by means of both light and electron microscopy utilizing intravenously injected horseradish peroxidase as the protein tracer. In animals sustaining low grade head injuries not of sufficient intensity to elicit either microscopic, intraparenchymal hemorrhages or subtle, neuropathological responses, peroxidase extravasation was noted both in the vascular walls and in the surrounding parenchyma of the ventromedial aspect of the brain stem. At the ultrastructural level as early as 3 min after brain injury, occasional arterioles, venules and capillaries displayed peroxidase leakage. In serial sections large endothelial segments of these vessels revealed the peroxidase reaction product within numerous vesicles which often shared continuity with tubular and vacuolar profiles. Such vesicular activity apparently moved the peroxidase from the luminal surface to extrude it into the basal lamina. From the perivascular basal lamina, the reaction product flooded the interstices of the surrounding brain stem parenchyma where occasional neural, glial and pericytic elements incorporated the peroxidase within coated invaginations, vesicles, tubules and vacuoles. In that protein leakage was consistently observed despite the apparent integrity of both the endothelial tight junctions and their cell membranes, it is concluded that the vesicular transport of horseradish peroxidase across the endothelia of the brain stem vasculature represents a possible mechanism of blood-brain barrier dysfunction in mechanical brain injury.


Efferent projections of the gracile nucleus in the cat. The efferent projections of different portions of the gracile nucleus in the cat were studied using both autoradiographic and degeneration tracing methods. The results suggest that there are two aspects to the functional organization of these projections. First, the somatotopic organization of the gracile n. (GR) is maintained, but inverted, by the topographic organization of its projections to VPL1. Fibers from the lateral portions of GR terminate medially in VPL1; fibers from the dorsal portions terminate ventrally. These fibers, especially those from the middle and caudal portions of GR, terminate in dense, precisely located groups of clusters. Dorsally located clusters in VPL1 (predominantly from middle-ventral portions of GR) are significantly smaller than ventrally located clusters (predominantly from middle-dorsal portions). The second aspect of this organization, involving the projections both to VPL1 and to other brain stem targets, is that some kind of functionally relevant sorting process appears to occur as fibers leave different portions of the gracile n. The afferent projections of the rostral (GRr) and middle-ventral portions (GRmv) of the gracile n. are different from those from the other portions of the nucleus. Projections to VPL1 from GRr are less dense, less likely to form clusters, less clearly topographically organized, and extend further rostrally and dorsally in VPL1 than those from the rest of GR. The clusters are small, like those from GRmv. Similarly, although all portions of GR project to several other brain stem regions, these projections appear to be derived preferentially from GRr and/or GRmv. These brain stem regions involve certain portions of the inferior olive, inferior and superior colliculi, red n., zona incerta, pretectum, thalamic posterior group and the H field of Forel. This dual organization of efferent connectivity is similar to that of the cuneate n.20, and is consistent with many of the differences in cytoarchitecture, afferent connectivity and response properties of cells within different portions of the dorsal column nuclei.


Nerve endings in the choroid plexus of the fourth ventricle of the rat: electron microscopic study. Nerve fibers and nerve endings in the fourth ventricle choroid plexus of the adult rat were studied with the electron microscope. Nerve endings were found at two sites within the plexus: (1) on the smooth musculature of the blood vessels (i.e. vascular nerve endings), and (2) in the stroma between the choroidal epithelium and the fibrovascular core. Ultrastructurally all fibers were of the efferent type, and the majority were unmyelinated. No ganglion cell bodies were identified. Fibers ending in relation to the smooth muscle of the vessels presumably control the calibre of these vascular channels. Although the role of the stromal nerve endings is as yet unknown, these fibers may influence epithelial cell functions and thus indirectly regulate choroidal cerebrospinal fluid production.


A mapping of the distribution of acetycholine, choline acetyltransferase and acetylcholinesterase in discrete areas of rat brain. Acetylcholine (ACh) concentration, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in 60 discrete areas dissected from the rat forebrain. All 3 substances were detectable in every region examined. The range for ACh levels was approximately 9-fold, with highest levels in the striatal and mesolimbic areas. Wider ranges were found for ChAT and AChE. In addition to not having a uniform distribution ACh, ChAT and AChE did not always show proportional variations. ACh levels did not appear to relate to the activity of either enzyme in a simple manner. There was a better correlation (r = 0.902) between the activities of ChAT and AChE, with AChE activities always being higher. In some regions, AChE was disproportionately low or high relative to ChAT. In general, the biochemical results presented here are compatible with histochemical studies of AChE. Such measurements in small brain regions should prove valuable in future experiments designed to determine cholinergic function and localize cholinergic pathways.


Evidence for loss of Purkinje cell dendrites during late development: a morphometric Golgi analysis in the mouse. The late postnatal development of the Purkinje cell dendritic tree in mouse cerebellar vermis was investigated in Golgi preparations by morphometric techniques in order to determine at what age adult characteristics of the Purkinje cell are achieved in the rodent brain which grows continuously throughout adult life. B6D2F1 hybrid mice were sacrificed at 9, 15, 20, 35 and 250 days of age. "Hind-brain" weights (by direct weighing) and vermis volume (determined histometrically from Golgi sections), both increased rapidly from 9 to 20 days of age and continued to increase steadily with advancing age. The growth of Purkinje dendritic field areas, determined by planimetric measurements from Golgi sections paralleled the growth curves for vermis cross-sectional area, vermis volume and "hindbrain" weight. However, stereological determinations revealed an unexpected disparity between the growth of the Purkinje dendritic field areas and changes in the total length of dendrites of Purkinje cells. The total dendritic branch length per Purkinje cell increased sharply up to 20 days of age but thereafter declined with advancing age. Dendritic spine counts on Purkinje cells revealed no change in the number of dendritic spines per unit length of dendrites between 20 and 250 days of age, however, since the Purkinje cell total branch length declined-calculations suggest that the total number of spines per cell declined after 20 days of age. Thus, the size of the cerebellum and the Purkinje cell dendritic tree continued to enlarge during late postnatal development; however, the total dendritic surface area and the total number of dendritic spines on each Purkinje cell, after reaching a peak at 20 days of age, declined with advancing age. The data suggest that the late postnatal development of the Purkinje cell dendritic tree is characterized by resorption as well as dendritic growth. The functional significance of such developmental remodelling is unknown.


Disorganization of myelinogenesis in tissue culture by anti-CNS antiserum. The presence of decomplemented anti-CNS antiserum profoundly affects myelinogenesis in cultured mouse embryo spinal cord. Light and electron microscope study has shown that oligodendroglia differentiate and produce an abundance of cell processes which surround the oligodendrocytes in a chaotic, disorganized array. Where the cell processes chance to meet, they form a kind of aberrant swollen myelin. Rarely, the oligodendroglial processes ensheath axons. For the most part, the available axons remain unmyelinated. On removal of the decomplemented antiserum, oligodendroglia differentiate and form normal myelin around the available axons. Myelination of peripheral nervous system (dorsal root ganglion) axons in the same preparations is unaffected by the presence of the antiserum. Thus, under these circumstances, the message from the neuron to the oligodendrocyte to make myelin is apparently intact, yet there is interference with the ability of the oligodendroglial cell process to find, attach to and encircle CNS axons with a normal myelin sheath.


Topographical distribution of dopaminergic innervation and dopaminergic receptors of the anterior cerebral cortex of the rat. The quantitative topographical distribution of the dopaminergic innervation and the DA-sensitive adenylate cyclase were estimated in the anterior cerebral cortex of the rat. The high affinity uptake of [3H]DA and endogenous levels of DA were used as markers of the dopaminergic innervation. [3H]DA uptake, DA levels and DA-sensitive adenylate cyclase were estimated in microdiscs of tissues punched out from frozen serial frontal slices. The uptake of [3H]DA was measured on sucrose homogenates prepared from such microdiscs. The ventral part of the frontal cortex contained the highest DA concentration and DA-sensitive adenylate cyclase activity; the other structures rich in DA and in DA receptors were the cingular (close to the corpus callsoum) and the rhinal cortices. All of these cortical areas were rich in [3H]DA uptake sites. However, curiously, the dorsal part of the frontal cortex, which contained only moderate amounts of DA and of DA-sensitive adenylate cyclase, presented the highest number of [3H]DA uptake sites. Nevertheless, the uptake of [3H]DA in this region decreased by 60% after bilateral electrolytical lesions of the ventral tegmental area (A10 group). The parietal cortex was practically devoid of dopaminergic innervation and of DA-sensitive adenylate cyclase. The activity of the DA-sensitive adenylate cyclase in the frontal, cingular and rhinal cortices was 10-fold higher than that found in the striatum when compared to their respective DA levels.


A pictorial representation of endogenous brain ATP by a bioluminescent method. The layering of a luciferin-luciferase solution on brain slices makes endogenous ATP visible. Rat brains, frozen in situ and sliced at 16 micrometer thickness at a temperature of--15 degrees C, were fixed by a ternary mixture of ethanol, formalin and dioxane at--20 degrees C for 15 min, and dried at 40 degrees C for 12 h. Luciferin, luciferase and a small quantity of magnesium sulfate were dissolved into an arsenate buffer solution containing 1% polyvinylpyrrolidone, 2% gelatin and 1% glycerol. The solution was then frozen into a column, sliced at 40 micrometer thickness at--15 degrees C and placed on the precooled brain slice. A luminiferous luciferin-ATP reaction begins when the brain slice reaches room temperature and persists for more than 10 min. This technique therefore makes possible the optical and/or photographic determination of the endogenous concentration of brain ATP. Capability of the technique is also demonstrated.


Centrifugal influence on olfactory bulb activity in the rabbit. (1) Regions which exert centrifugal influences on the olfactory bulb activity were studied by applying systematic stimulation to various areas of the ipsilateral telencephalon in the rabbit. By delivering electric stimuli to the anterior commissure (AC), the deep lying structures in the projection areas of the lateral olfactory tract (LOT) and the medial forebrain bundle situated between the lateral hypothalamic area and the lateral preoptic area, negative field potentials were evoked in the granule cell layer (GCL) of the bulb. (2) Intracellular recordings from the mitral cells and the GCL neurons in the olfactory bulb were performed in order to clarify the modes of the centrifugal influences on the olfactory bulb neurons. (3) EPSPs were recorded in the GCL neurons by stimulation of the deep-lying structure of the prepiriform cortex as well as by stimulation of the AC. The onset time and duration of the EPSPs corresponded well to those of the negative field potentials in the GCL. Thus, it was suggested that these negative potentials were caused by the EPSPs of the number of granule cells. (4) In almost all of the mitral cells, IPSPs were recorded by stimulation of the AC and the deep-lying structures of the LOT projection areas. The onsets of the IPSPs were found with delays of several milliseconds from those of the negative field potentials in the GCL. (5) It was postulated that the excitation of the centrifugal system mainly exerts a depressive influence on the activity of the mitral cell, and that the GCL neuron (presumably the granule cell) seems to be an inhibitory interneuron interpolated between the extrinsic fibers from the telencephalon and the mitral cell.


Potentiation of a cardioinhibitory reflex by hypothalamic stimulation in the rabbit. Repetitive stimulation of an area within the lateral hypothalamus, near the mammillothalamic tract, evoked pressor responses with bradycardia in anaesthetized rabbits. With weak stimulation (cathodal pulses below 75--150 microamperemeter, 1 msec duration, 60--100 per sec for 5--9 sec) the pressor responses were accompanied by bradycardia similar in intensity to that evoked by i.v. administration of noradrenaline. Stronger stimulating currents evoked an intense bradycardia that could not have arisen solely through the baroreceptor reflex. With these stronger currents the heart rate sometimes fell, transiently, to less than 20% of the resting rate. After denervation of the 4 main buffer nerves (sinus and aortic nerves), hypothalamic stimulation could not readily evoke bradycardia, although the pressor, respiratory and other effects remained. When the baroreceptor afferents were activated, either by evoked pressor responses in rabbits whose buffer nerves were intact or by electrical stimulation of the central ends of divided aortic nerves, strong hypothalamic stimulation augmented the bradycardia evoked reflexly from these baroreceptor afferents. This evidence suggests that electrical stimulation of this area in the hypothalamus may facilitate the cardioinhibitory component of the baroreceptor reflex in the rabbit.


Microperoxisomes in the central nervous system of the postnatal rat. The distribution of catalase-containing microperoxisomes was studied in the central nervous system of rats during the early postnatal period when the processes of myelination and cell differentiation are active. The regions selected for study included a region previously found in adult animals to contain substantial numbers of reactive microperoxisomes, as well as areas where few such bodies were seen. Microperoxisomes were relatively numerous in all areas during the first two postnatal weeks; at later times they occurred less frequently, or, in some areas, were almost entirely absent. In early postnatal CNS, catalase-positive microperoxisomes were found in all cell types in all regions studied. Neurons of both cerebrum and cerebellum contained catalase-positive microperoxisomes during the first two postnatal weeks; few such neuronal bodies are found in these areas after the third postnatal week. During the period of active myelination, catalase-positive microperoxisomes were found in oligodendrocyte cell bodies, and also in oligodendrocyte processes associated with forming myelin sheaths in all areas. In several areas during the first 3 postnatal weeks, catalase-positive bodies were seen in synaptic terminals, a location where they are seldom observed in mature tissue. Cells of postnatal choroid plexus also were found to contain modest numbers of reactive microperoxisomes.


Gastrin and cholecystokinin in human cerebrospinal fluid. Immunochemical determination of concentrations and molecular heterogeneity. To determine whether gastrin and cholecystokinin (CCK), recently found in the central nervous sytem, were present in cerebrospinal fluid (CSF), we studied human specimens by sensitive and specific radioimmunoassays for the two related polypeptide hormones. The concentration of gastrin in cerebrospinal fluid from 10 neurologically normal persons ranged from 1.5 to 8.0 pM (mean 3.4 pM), whereas the concentration of CCK ranged from 4 to 55 pM (mean 14 pM). The molecular heterogeneity of gastrin and CCK in CSF was determined by gel chromatography of concentrated fluid monitored by 3 gastrin radioimmunoassays specific for different sequences of gastrin17 and 3 CCK radioimmunoassays specific for different sequences of CCK33. Chromatography revealed that gastrin was present in molecular forms corresponding to gastrin34 ('big gastrin') and gastrin17. CCK was present in molecular forms corresponding to the COOH-terminal octapeptide amide of CCK33 and a fragment corresponding to sequence 25-29 of CCK33. Also, a peptide corresponding to COOH-terminal tetrapeptide amide common to both gastrin and CCK was found. The results indicate that true gastrin as well as CCK are present in CSF, and that both hormones display a molecular heterogeneity similar to that found in extracts of brain tissue.


Behavioral and physiological studies of non-narcotic analgesia in the rat elicited by certain environmental stimuli. These experiments characterized the analgesia resulting from exposure to certain noxious and/or stressful manipulations. Rats exposed either to electric grid shock (0.35-2.0 mA for 10-30 sec) or to 5 min of presumably non-painful centrifugal rotation (about 7.0 transverse g's) were analgesic as measured by tail-flick, hot plate and responses to applications of a calibrated paw pinch or alligator clip. Analgesia produced by shock (SA) or centrifugal rotation (RA) persisted after termination of these manipulations. Neither SA nor RA were attended by generalized sensory, attentional or motoric deficits. Intraperitoneal injection of hypertonic saline also increased tail-flick latencies. Exposure to brief ether anesthesia or horizontal oscillation, both of which have been reported to increase ACTH secretion (a commonly used indicator of stress), did not produce analgesia as measured by the tail-flick test. The use of classical conditioning procedures to pair shock with environmental stimuli resulted in increased tail-flick latencies. The narcotic antagonist naloxone (1 mg/kg, i.p.) did not reduce the tail-flick inhibition produced by shock, rotation, hypertonic saline or classical conditioning. Chlordiazepoxide (5 mg/kg, i.p.) also failed to antagonize the increased tail-flick latencies produced by shock or conditioning. Tail-flick inhibition produced by shock or rotation was markedly reduced by complete spinal cord transection at thoracic levels. These results suggest that: (1) the selective modulation of nociceptive input at the level of the spinal cord can be mediated by a supraspinal system or systems physiologically distinct from those involved in analgesia produced by the administration of opiates; (2) non-narcotic modulation of nociceptive input occurring within the spinal cord can be learned by exposure to classical conditioning procedures; and (3) noxious stimuli are sufficient but not necessary to produce a non-narcotic analgesia; stress alone, however, is not always sufficient to produce this analgesia.


Deflection of selected optic fibers into a denervated tectum in goldfish. In goldfish, one eye was enucleated, and after two or more weeks a select fraction of optic fibers from the remaining eye was deflected into the ipsilateral optic tectum. At varying intervals, the optic reinnervation of the ipsilateral tectum was measured by autoradiography and electrophysiologic mapping. Both methods indicated the deflected optic fibers not only innervated the appropriate region of tectum but also spread beyond this, occupying a total area that was several times greater than normal. Correlated with this spreading were low grain density in the autoradiograms and reduction in the number of amplitudes of units recorded electrophysiologically. The electrophysiology also revealed this projection to be almost devoid of topographic organization, showing only a crude but appropriate polarity.


Modulation of intracranial self-stimulation behaviour by local perfusions of dopamine, noradrenaline and serotonin within the caudate nucleus and nucleus accumbens. In order to examine the possible role of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in the control of intracranial self-stimulation behaviour (ICSS) a push-pull perfusion system was used to administer different consecutive doses of DA, NA and 5-HT to discrete regions within the caudate nucleus (CN) and nucleus accumbens (NAC) of rats during ICSS. Electrode placements supporting ICSS were in both the medial forebrain bundle (MFB) and the ventral mesencephalic tegmentum (VMT). Animals were allowed to determine the ICSS pulse train duration thereby permitting three measures of ICSS behaviour: (1) mean presses/min; (2) mean duration/press and (3) mean time pressed/min. Eleven electrode/cannula combinations were found to be responsive to both DA and 5-HT. The DA response profile was typified by a significant increase in mean presses/min, a significant decrease in mean duration/press and no significant change in the mean time pressed/min. The response profile for 5-HT was the converse of the DA pattern for the first two measures of ICSS, however, again there was no significant change in the mean time pressed/min. In addition, 8 electrode/cannula combinations were sensitive to NA; for 5 combinations the response pattern was similar to that of DA, however, the changes in ICSS were generally larger and of longer duration. For the remaining 3 combinations sensitive to NA there was no major change in mean presses/min but a dramatic increase in the mean duration/press and consequently, an increase in the mean time pressed/min. It is suggested that the central control of ICSS behaviour might depend, in part, upon a relative balance between DA and 5-HT systems within the CN and NAC. The operational characteristics of this balance may be subject to additional modulation by the activation of an adrenergic receptor.


A procedure for obtaining initial estimates of parameters appearing in steady-state rate or equilibrium binding equations. A "peeling" procedure is described for obtaining initial estimates of the parameters in the equation: formula: (see text), where P(x) and Q(x) are polynomials in x. The method is illustrated, in the context of enzyme kinetics, using data which are fitted to the following equation: formula: (see text), where v denotes the initial steady-state velocity at an initial substrate concentration S, and a1, a2, b1, and b2 are non-negative constants. The applicability and limitations of the method for data fitting in fields such as enzyme kinetics and ligand-binding studies are discussed.


Control of glucose transport in adipose tissue of the rat: role of insulin, ATP, and intracellular metabolites. The purpose of this study was to elucidate some of the mechanisms of control of the glucose transport step in adipose tissue. Glucose transport was studied by monitoring the conversion of [1-14C]glucose to 14CO2 in a system where glucose transport was made rate limiting by increasing the flux through the pentose phosphate pathway with phenazine methosulphate, an agent which results in rapid rates of reoxidation of NADPH. The maximum velocity for the apparent rate of glucose transport was increased significantly by insulin. There was no change in the glucose concentration required for half-maximal rates of 14CO2 production. Glucose transport was also monitored by directly measuring the rate of glucose uptake. Glucose uptake was increased by phenazine methosulphate. The intracellular glucose-6-phosphate concentration was decreased by phenazine methosulphate. These two agents, insulin and phenazine methosulphate, seemed to act by independent mechanisms as their optimal effects on glucose uptake were additive. The apparent rate of glucose transport was decreased by ATP which resulted in a decrease in maximal velocity but did not affect the affinity for glucose. This effect of ATP was seen in the presence of absence of insulin.


Studies on the preparation of rat liver plasma membrane fractions and on their polypeptide patterns. Plasma membrane and bile canalicular membrane fractions were prepared from rat liver using NaHCO3, NaHCO3--CaCl2, and K2HPO4-KH2PO4 buffers (all at pH 7.4). The amount (expressed as milligrams protein per gram liver) of plasma membrane fraction exceeded the amount of bile canalicular membrane fraction using each of these three media; the use of NaHCO3-CaCl2 afforded a substantially higher yield of both types of membranes. The two membrane fractions exhibited complex patterns of polypeptides (greater than 30) on sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis. Several reproducible differences in polypeptide patterns were observable between the two membrane fractions; in particular, components possibly corresponding to the heavy chain of myosin and to action were prominent in the  bile canalicular membrane fraction. The effects of incubation in the above three buffers and in Tris--HCl (pH 7.4) on the polypeptide patterns of both types of membrane were studied. Many polypeptides were released from each type of membrane in all of these media. Differential effects on the polypeptide patterns of either type of membrane fraction were observed among the various buffers. In terms of minimizing loss of polypeptides, in general, NaHCO3--CacCl2 appeared to be the best buffer and Tris--HCl the worst buffer. The significance of these results for the preparation and storage of liver cell plasma membrane fractions is briefly discussed.


Wheat embryo ribonucleates. XII. Formal characterization of terminal and penultimate nucleoside residues at the 5'-ends of "capped" RNA from imbibing wheat embryos. (1) N2,N2,7-Trimethylguanosine, not previously detected as a component of plant RNA, is shown to be present in the RNA which is isotopically labelled when dry wheat embryos imbibe water in a medium that contains[methyl-3H]methionine. (2) N2,N2,7-Trimethylguanosine and 7-methylguanosine are released as part of "capped" oligonucleotides when the isotopically labelled RNA from imbibing wheat embryos is subjected to hydrolysis by RNase T2. (3) By way of contrast with the "capped" RNA of animal cells, 5'-terminal "cap" structures (m7Gppp- and m32,2,7 Gppp-) in the "capped" RNA from the higher plant organism are not bonded to pneultimate O2'-methylnucleoside constituents. (4) In an allied study, it has been found that recovery of poly (A)-rich RNA from dry wheat embryos depends on the inclusion of sodium dodecyl sulphate (SDS) in phosphate-buffered (pH 6.8) phenolic emulsions. By way of contrast, recovery of poly (A)-rich RNA from dry wheat embryos does not depend on the inclusion of SDS in Tris (hydroxymethyl) aminomethane buffered (pH 9.0) phenolic emulsions.


[Control of argininosuccinate synthetase, argininosuccinase and arginase activities in the newborn rat]. Some factors influencing the postnatal development of three urea cycle enzyme activities, argininosuccinate synthetase, argininosuccinase, and arginase, in the liver of newborn rats, are studied. Premature and postmature birth change the developmental pattern of these enzyme activities, suggesting that the increase in enzyme activity after birth is initiated by the birth process. Starvation of newborn animals after birth has no effect on the postnatal development of the three enzyme activities. Bilateral adrenalectomy at birth causes a partial inhibition of the postnatal increase of argininosuccinase and arginase activities while injection of cortisol prevents the effects of adrenalectomy. It is suggested that presence of adrenal secretion is one condition necessary for the increased activity of the prematures.


Identification of the 5S RNA binding site in intermolecular complexes of wheat embryo ribosomal 5S and 18S RNA. The nucleotide sequence in wheat embryo ribosomal 5S RNA that binds by complementary base pairing to ribosomal 18S RNA has been identified. The 5S--18S RNA complex was formed in vitro and the interacting regions of the two RNA chains were isolated by a combination of nuclease digestion and electrophoresis on polyacrylamide gels. The binding site is close to the 3'-end of the 5S RNA molecule and contains a maximum of 24 nucleotides.


Bile acid synthesis in isolated rat hepatocytes. Normal adult rat hepatocytes were incubated for 48h and the concentration of total and individual bile acids in homogenized samples of the culture was measured at intervals during the incubation, using radiogas chromatography and isotope derivative assay. The net increase in bile acids over the value observed at the start of the culture was taken as synthesis. The results showed that bile acid synthesis was linear up to 24h of incubation, at a rate of 20nmol/g hepatocytes per hour, and that 85% of the newly synthesized bile acid was cholic acid. The bile acid synthesized was mainly conjugated with taurine. These results suggest that isolated hepatocytes cultured in the way described could be a useful in vitro model for the study of bile acid synthesis.


Investigation of polyene macrolide antibiotic-induced permeability changes in vesicles by 31P nuclear magnetic resonance. The permeability of egg yolk lecithin (EYL) vesicles to Pr3+ has been measured by 31P nuclear magnetic resonance (nmr) spectroscopy. Measurable Pr3+ leakage into the internal aqueous compartment of EYL vesicles at ambient (21 degrees C) temperature required the presence of small (7--10 mol%) amounts of dicetyl phosphate (DCP). The permeability of DCP-containing vesicles is decreased by incorporation of sterol (cholesterol greater than ergosterol approximately 5.6-dihydroergosterol greater than zymosterol) into the lipid bilayer. Addition of the polyene macrolide antibiotic, nystatin, to DCP-containing EYL vesicles with and without sterol resulted in increased Pr3+ permeability at the three temperatures studied (21--37.5 degrees C). Permeability changes observed upon addition of nystatin to sterol-impregnated, DCP-containing vesicles varied with sterol structure: ergosterol approximately 5,6-dihydroergosterol greater than cholesterol approximately zymosterol. These results are compared with other polyene macrolide induced permeability changes on model and natural membrane systems. Permeability changes induced by nystatin in sterol-free EYL vesicles were generally greater than for comparable sterol-containing vesicles. This is attributed to a nonspecific interaction of the antibiotic with the latter vesicles.


Analysis of plant genomes. IV. Isolation and characterization of satellite DNA components from two dicotyledons cucumber (Cucumis sativus) and radish (Raphanus sativus). Satellite DNA fractions from cucumber and radish, two plants having low DNA contents and relatively small chromosomes, were isolated and characterized. Reassociation studies of satellite and total nuclear DNA showed that the satellite fractions in these two plants contain most of the rapidly reassociating DNA. Cucumber satellite I was found to contain one major component (70% of the total satellite) having a density of 1.706 g/cm3 and a Tm of 90.5 degrees C and a minor component with a density of 1.712 g/cm3 and a Tm of 93.5 degrees C. The complexity of the major component was estimated to be 3.8 X 10(5) daltons while that of the minor one was 12.9 X 10(7) daltons. Although cucumber satellite II banded as a single peak at a density of 1.700 g/cm3 in neutral CsCl gradients, it was observed to have a rather broad denaturation profile with a Tm of 86.5 degrees C. Its Cot curve was also broader than that of satellite I and one of its components (40% of the total) had a complexity of 5.8 X 10(5) daltons. Two satellite fractions were also observed in the case of radish DNA but only satellite I was isolated in a pure form and characterized. This radish satellite formed a sharp, symmetrical peak at a density of 1.698 g/cm3 in neutral CsCl gradients and underwent denaturation in a narrow temperature range of 6 to 7 degrees C. An analysis of the optical reassociation kinetics showed that this satellite contained a major and a minor component. The major component, which comprised 80% of the satellite, had a complexity of 12.9 X 10(5) daltons. Hybridization experiments revealed that the ribosomal DNA was present in satellite II.


Actin-like and tubulin-like proteins in synaptic junctional complexes. Synaptic junctional complexes (SJCs), isolated by a procedure which preserves presynaptic dense projections (PDPs) contain as their major component a polypeptide (P55) which comigrates with tubulin on sodium dodecyl sulfate - polyacrylamide gels and another major polypeptide (P45) which comigrates with muscle actin. We report here the characterization of P55 and P45 by two-dimensional polyacrylamide gel electrophoresis and by peptide mapping of the radioiodinated polypeptides. Our results indicate that P55 and P45 are homologous with tubulin and actin respectively, in terms of molecular weight, protein charge, and primary structure. Comparison of the sodium dodecyl sulfate - polyacrylamide gel electrophoresis patterns of SJCs and postsynaptic densities (PSDs) indicates that P55 and P45 are associated mainly with PDPs but are also found in the PSD.


A rapid method for the determination of CTP and phosphocholine in rat liver and baby hamster kidney 21 cells. A rapid and sensitive assay for CTP and phosphocholine was required for us to determine the concentration of these compounds in tissues and cell cultures. Such a procedure was devised with CTP:phosphocholine cytidylyltransferase, an enzyme which is highly specific for CTP and phosphocholine. The 0--22% ammonium sulfate precipitate of a cytosolic extract from rat liver was used as the source of the enzyme. The amount of CTP in an extract was estimated by the conversion of [3H]phosphocholine to 3H-labelled CDP-choline. Similarly, the concentration of phosphocholine was estimated by the formation of 3H-labelled CDP-choline from 3H-labelled CTP. The conversion of CTP and phosphocholine to CDP-choline was 90% when inorganic pyrophosphatase was added to the incubations. The formation of CDP-choline was linear between 1 and 10 nmol of CTP or phosphocholine. The concentration of CTP was determined in rat liver (62 nmol/g wet weight) and baby hamster kidney 21 (BHK-21) cells (161 nmol/g wet weight). The concentration of phosphocholine in rat liver was 1.16 mumol/g wet weight whereas in BHK-21 cells it was much less (69 nmol/g wet weight). By this procedure, it may be possible to establish the importance of CTP and phosphocholine in the control of phosphatidylcholine biosynthesis.


A study of the influence of the method of oral administration of ampicillin upon plasma drug levels in calves. Ampicillin was given orally to five Holstein calves using the following four different methods of administration: via stomach tube, mixed and fed in the calf starter ration, dissolved in milk and pail fed and administered orally as 400 mg commercial calf tablets. In addition, ampicillin was dissolved in milk and pail fed 20 to 30 minutes following intramuscular atropine. Ampicillin was only detected in the plasma of calves which had received the drug, pail fed in milk. Atropine administration slowed the appearance of the drug in the plasma but did not decrease the efficiency of absorption.


An agglutination test for the detection of Bordetella bronchiseptica infection in swine. An agglutination test with the use of formalin-killed antigen of the cell carrying the capsule was developed and used for the detection of antibody in swine naturally infected with Bordetella bronchiseptica. Under optimum antigen concentration and reaction temperature 210 or 60% of 342 serum samples tested from 42 conventional swine herds were positive for Bordetella infection. In contrast, only 34 or 10% of 342 nasal swabs from the same animals were positive for Bordetella by culture technique. The test was relatively free of cross-reactivity to related organism. However, 2.7 and 13.0% of sera from growing pigs and mature hogs, respectively, reacted with antigen of Pasteurella multocida. Because of this, only agglutinin reactions in 1:20 dilutions or higher to Bordetella were considered positive. The bulk of the antibody activity of selected sera tested from various age ranges of swine was mercaptoethanol sensitive, suggesting that serum antibody in Bordetella infection may be associated with immunoglobulin IgM. Because of the high agglutinability and stability of formalin-killed antigen the test may be useful as an auxiliary aid for the diagnosis of Bordetella infection where the organism cannot be identified by culture means.


On establishing reference values.

On establishing reference values. In order to establish a range of reference values for any characteristic one can use  Gaussian or nonparametric techniques, whichever are most appropriate. One  has the choice of calculating tolerance intervals or percentile intervals. A tolerance interval is said to contain, say 95% of the population with probability, say 0.90.  A percentile interval simply simply calculates the values between which 95% of the observations fall. If the data can be said to have a Gaussian distribution, the same precision can be obtained with smaller sample sizes than using the nonparametric techniques. In some cases, data which are not Gaussian can be transformed into a Gaussian form and hence make use of the more efficient Gaussian techniques. In both cases, the data should be checked for outliers or rogue observations and these should be eliminated if the testing procedure fails to imply that they are an integral part of the data.


Enigmatic resistance of sheep (Ovis aries) to infection by virulent Francisella tularensis. Tularemia in range sheep is an occasional cause of severe economic loss from mortality and unthriftiness as well as a hazard to persons in contact with the animals. Epizootics are unpredictable and explosive, therefore, prophylaxis is more practical than therapy. Live vaccine of proven value in man and in beavers was inoculated into mature ewes and elicited antibodies without harm to the sheep. However, challenge of immunity was not possible because virulent Francisella tularensis in large doses did not cause significant mortality in healthy, well managed, unimmunized sheep. Evidence suggests that a complex of stresses such as inclement weather, lambing and concomitant ectoparasitism render sheep more susceptible to tularemia.


Bovine erythrocytic, granulocytic and macrophage colony formation in culture. A preliminary report. Bovine erythrocytic colonies containing up to 300 cells each were produced by using a plasma clot technique with five percent CO2 at 37 degrees C. with high humidity and 2.5 units of sheep step III erythropoietin per milliliter. Erythropoietin was essential for colony formation. The number of colonies ranged from 24 to 823 per 10(5) nucleated marrow cells plated, in different animals. Some of the erythroid colonies were mixed with granulocytes. Granulocyte/macrophage colonies were produced in methyl cellulose cultures. Colonies contained up to 1000 cells and the number of colonies ranged from 13 to 981 per 10(5) nucleated marrow cells plated, from different animals. Glass adherent cells appeared to produce colony stimulating activity in culture. In both culture systems, there was a direct linear relationship between the number of nucleated marrow cells plated and the number of colonies produced.


Strongylus edentatus: development and lesions from ten weeks postinfection to patency. Pony foals inoculated with infective Strongylus edentatus larvae were examined at necropsy from ten to 72 weeks postinfection. At ten weeks postinfection larvae were visible retroperitoneally in the liver and flanks and were recovered from the ligaments of the liver. The fourth molt was detected at 16 weeks postinfection and larvae were also recovered from the wall of the cecum at this time. By 40 weeks adult S. edentatus containing eggs were found in the contents of the cecum and colon. While many larvae migrate to remote parts of the body, it is likely that only those that attain the base of the cecum are successful in establishing in the cecum and colon as adult forms. By 36 weeks postinfection no larvae were found in the liver and up to this time none were found in the peritoneal cavity. Larvae were not recovered from the parenchyma of the lungs. Adhesions and disruption of omental architecture were frequent changes observed throughout infection. Casts of necrotic eosinophils enclosing tracks and larvae were observed beneath the intima of major veins of the cecum and colon. The liver was rough and the capsule thickened at 16 and 20 weeks postinfection and the flanks remained edematous until 36 weeks postinfection.


The effect of thiopental sodium, methoxyflurane and halothane on the acid-base status in sheep. Experiments have been carried out on 20 adult fat-tailed ewes to determine the effects of thiopental sodium, methoxyflurane and halothane on acid-base status of the saliva loss during prolonged surgical anaesthesia. The rate of loss of base in saliva depends on the volume of saliva produced, which fell sharply at the onset of anesthesia with the volatile anaesthesia. Plasma pH and plasma pvCO2 excess were both increased by the volatile anaesthetics but fell sharply during thiopental anaesthesia. Plasma pH and plasma PvCO2 showed no consistent relationship.


The bovine alveolar macrophage. II. In vitro studies with Pasteurella haemolytica. Bovine alveolar macrophages were cultured in vitro and challenged with suspensions of live and dead bacteria. These cells showed severe cytotoxic morphological changes and a low rate of phagocytosis after exposure to live Pasteurella haemolytica type I was readily phagocytosed and produced only mild cytotoxic changes.


The removal of "nucleic acid" from an antigen present in the livers of chickens with erythroblastosis. The recovery of viral antigen in a pure form from tissue can be hindered by the small amount of antigen present relative to the remaining normal tissue constituents with which the antigen may form loose associations. An antigen from the livers of chickens with erythroblastosis had earlier seemed to be associated with nucleic acid.  The present work suggests that this material, which reacts with reagents for DNA and RNA but is soluble in 0.2N HClO4, is only a contaminant and not an integral part required for complete activity of the antigen. Treatment with 0.2N HClO4, together with precipitation of the active protein by 60% saturation of aqueous solutions with ammonium sulphate, removes the nucleic acid without destroying antigenicity. The procedure results in a marked degree of purification of the antigen (732-fold with respect to original liver protein) but contaminants still remain. A contaminant absorbing at 260 nm resisting extraction with 0.2N HClO4, can be partly eliminated if the solution is treated with ether-alcohol to remove lipid.


Lack of an effect of dietary selenium on serum albumin, glucose and urea nitrogen in ewes. The results of a study on the effect of dietary selenium administered with vitamin E on serum levels of albumin, glucose and urea nitrogen in ewes are reported. In October, at the onset of breeding, after ten months on a dystrophogenic diet, mean serum levels of albumin (g/dl), glucose (mg/dl) and urea nitrogen (mg/dl) were respectively 3.5, 52.9 and 12.8, in 65 Se-deficient ewes and 3.6, 51.7 and 14.3 in 65 Se-adequate ewes. Despite a significant difference in the serum level of urea nitrogen between Se-deficient and Se-adequate groups, no consistent effect of dietary selenium was apparent.


Perfusions of the posterior hypothalamus of cats with various ions and saccharides: effects on body temperature. Alterations of the ionic constituents of solutions perfused through the tissue of the posterior hypothalamic region in conscious cats elicited changes in body temperatures. Increasing the (Ca2+) to (Na+) ratio of the perfusion solution elicited falls in body temperature which were accompanied by changes in posture and vasomotor tone which assisted the heat loss. The magnitude of the fall was dependent on the ratio of (Ca2+) to (Na+) and was not related to the osmolarity of perfusion solution. The addition of dextrose to the perfusion solution attenuated or abolished the response produced by an increase in the (Ca2+) to (Na+) ratio. This dextrose effect could be attributed to its role as an energy substrate. These data are consistent with and extend previous suggestions that the set point for body temperature may be dependent on the inherent ratio of the ionic constituents of the posterior hypothalamic area. Further, they suggest that these ionically induced alterations can be overriden by increasing the available energy substrate.


Differential impairment of thermogenesis in the pigeon after chemical sympathectomy. A dose-controlled chemical sympathectomy with 6-hydroxydopamine (6-OHDA) did not disrupt thermostasis in the pigeon at +38 degrees C. At +6 degrees C, thermogenesis was impaired, but the lower body temperature and oxygen consumption were stable and vasoconstriction was normal. The stability may partly be explained by a massive release of adrenaline from the adrenals (50% in 20 min). Despite a deficit in heat production both after sympathectomy and after acute 6-OHDA, no change in muscle electrical activity was observed. Plasma free fatty acid (FFA) concentration was significantly elevated after sympathectomy, but no changes occurred in blood glucose or plasma lactate levels. The results indicate a major compensatory role for the adrenals in avian thermogenesis. They also suggest a sympathetically mediated auxiliary thermogenic mechanism independent of muscle electrical activity and coupled to FFA metabolism.


Adrenal-regeneration hypertension in Wistar-Furth rats. The susceptibility of young virgin female Wistar-Furth (W/Fu) rats to adrenal-regeneration hypertension (ARH) was evaluated by comparing the blood pressure of adrenal-enucleated, mononephroadrenalectomized, salt-loaded rats with that of similarly treated rats having one intact adrenal over a period of 5 weeks. Hypertension began to appear in animals of the first group by the 3rd week, affected all of them by the 4th week, and increased in severity during the 5th week. Control rats remained normotensive during the study. Hypertensive rats developed marked enlargement of the heart and kidney, which frequently displaced myocardial scarring and nephrosclerosis, respectively. These studies do not support the contention that W/Fu rats display heightened resistance to ARH to which, in fact, they appear to be just as susceptible as are most other strains.


The rabbit mesenteric vein: a specific bioassay for substance P. The anterior mesenteric vein of the rabbit responds to substance P with dose-dependent contractions and is among the vascular smooth muscles most sensitive to this peptide. In spite of its high sensitivity to numerous other agents, including angiotensin and bradykinin, the rabbit mesenteric vein can be made selective for substance P by the use of specific inhibitors that will prevent the myotropic effects of acetylcholine, catecholamines, histamine, 5-hydroxytryptamine, and of the two above-mentioned peptides, without modifying the contractions elicited by substance P. It appears that this peptide acts directly on specific receptors and not through the release of neurotransmitters. Interference by intramural prostaglandins is excluded because substance P is equally active on tissues pretreated with indomethacin or untreated. Dose-response curves obtained with substance P are close to the theoretical curves predicted by the mass action law. The rabbit mesenteric vein contains a new type of receptor for bradykinin, recently identified (REGOLI, D., MARCEAU, F., and BARABE, J. 1978. De novo formation of vascular receptors for bradykinin. Can, J. Physiol. Pharmacol. 56, in press.). The action of bradykinin on this receptor can be prevented with the use of specific and competitive inhibitors and, therefore, the mesenteric vein will distinguish between peptides of the kinins or of the substance P types.


Absence of Na+--H+ barrier function in mucosa of canine small bowel. The study was designed to determine whether the special Na+--H+ barrier function of the gastric mucosa is present in the mucosa of the small bowel and whether a gastric mucosal barrier breaker (hexanoic acid) would accelerate the fluxes of sodium in duodenum-jejunum and ileum as in the stomach. The observations were made in healthy conscious dogs with Thiry-Vella fistulae of the small bowel or Heidenhain pouches of the gastric corpus. These barrier characteristics of the stomach were completely absent in the small intestine where bidirectional Na fluxes were 5--10 times greater than in the stomach and were not accelerated by hexanoic acid as they were in the stomach. A comparison was made between the rates of absorption of hexanoic acid, sodium hexanoate, and HCl from the pouches and fistulae. The lipid-soluble fatty acid was transported at all sites more rapidly than its water-soluble sodium salt. In the stomach and ileum the H+ of HCl and sodium hexanoate were absorbed at similar slow rates. The duodenal-jejunal mucosa, however, transported H+ at rates nearly identical to those of hexanoic acid. In our tests HCl was not neutralized in duodenal contents while large quantities were neutralized in the contents of ileum.


The effects of vasodilators in the perfused hind limbs of spontaneously hypertensive and normotensive rats. The vascular effects of isoproterenol and nitroprusside were evaluated in the perfused hind limbs of age-matched normotensive Wistar (NW) and spontaneously hypertensive (SH) rats. The vasodilating effects of these two compounds were assessed in the presence of concentrations of noradrenaline sufficient to raise the basal perfusion pressure to 85--110 mmHg. The sensitivity of the hind limb vessels of SH rats to the vasodilating action of isoproterenol (2.4 x 10-6--1.0 x 10-4 M) was slightly greater than that of the hind limb vessels of NW rats. On the other hand, the sensitivity to the vasodilating effect of nitroprusside (1.7 x 10-7--3.3 x 10-5 M) was similar in the hind limb vessels of both groups of rats. Propranolol (7.6 x 10-6 M) inhibited to a similar extent the isoproterenol-induced dilation of NW or SH hind limb vessels, but did not modify the vasodilating effect of nitroprusside in these preparations, thus suggesting that the vasodilating action of isoproterenol was due to the stimulation of vascular beta-adrenergic receptors. These results do not support the hypothesis suggesting the existence of a deficient vascular relaxation in hypertensive rats.


Epileptiform seizures in domestic fowl. VIII. Anticonvulsant activity of primidone and its metabolites, phenobarbital and phenylethylmalonamide. Primidone is an effective anticonvulsant against seizures induced in epileptic fowl by exposure to intermittent photic stimulation. Epileptic fowl metabolize primidone to phenobarbital. Pretreatment of epileptic fowl with SKF 525A to prevent the metabolism of primidone to phenobarbital indicated that primidone itself had anticonvulsant activity. Phenylethylmalonamide, a second metabolite of primidone, did not have anticonvulsant activity when administered at the same dose as primidone.


Tectospinal and tectoreticular cells: their distribution and afferent connections. Experiments on chloralose-anaesthetized cats have shown that cells in the superior colliculus may be antidromically activated either from the pontomedullary reticular formation or the ventral cervical spinal cord, or from both sites. In tests on 111 units this has provided a basis for differentiating between cells of origin of the tectospinal tract and the tectoreticular system within the superior colliculus. Tectospinal cells may be activated both by spinal and pontine stimulation; tectoreticular cells cannot be activated by spinal stimulation. Both tectoreticular and tectospinal cells respond to visual and muscle afferent stimulation. The afferent connections may be strongly inhibitory as afferent input to the superior colliculus ofter prevented subsequent antidromic invasion. This was more commonly seen in tectospinal cells than tectoreticular cells. The distribution of the two cell populations within the superior colliculus was also found to be dissimilar. Evidence has also been obtained to suggest that the tectoreticular system, in part, consists of collaterals of the tectospinal tract.


Spontaneous hydrolysis of heroin in buffered solution. Electron-capture gas-liquid chromatography was used to study the spontaneous hydrolysis of heroin in phosphate buffer (pH 6.4 and pH 7.4) at 23 degrees C. Aliquots of solution were taken over a 24-h period. After extraction at pH 8.9 into propan-2-ol (10%)-ethyl acetate, deacetylated products were made into hepafluorobutyrate derivatives which were analyzed quantitatively using nalorphine as the internal standard. Heroin decomposes to 06-monoacetylmorphine (06-MAM) under these conditions. Further decomposition to morphine was not observed. Spontaneous hydrolysis was faster at pH 7.4 (first-order rate constant, 9.6 x 10-5 min-1) than at pH 6.4 (first-order rate constant, 3.0 x 10-5 min-1). In 24 h, the decomposition to 06-MAM was 13 and 4%, respectively.


Acute tolerance to ethanol on the release of acetylcholine from the cat cerebral cortex. Ethanol (1 g/kg, iv) produced a peak depression of acetylcholine release from the cat sensorimotor cortices within 30 min of the ethanol administration but recovery to control levels occurred in the following 30 min. However, the concentrations of ethanol in the blood and in the solution bathing the cortex remained stable during this recovery period. This example of acute tolerance to ethanol is possibly related to the well-known acute tolerance that develops to the behavioural effects of ethanol.


Chronotropic and inotropic effects of neurotensin on spontaneously beating auricles. Synthetic neurotensin (NT) was shown to exert a potent positive inotropic and chronotropic action in spontaneoulsy beating guinea pig and rat auricles and to be inactive in the rabbit auricles. The positive inotropic effects of NT in guinea pig and rat auricles were detected at concentrations as low as 3.0--6.0 x 10-10 M. Maximal concentrations of NT (3.1 X 10-7 M) increased the amplitude of contractions by 135 and 55% in guinea pig and rat auricles, respectively. On the basis of ED50 values, NT was found to be 20--30 times more potent than epinephrine in increasing the force of contraction in guinea pig and rat auricles. The results suggested that the positive inotropic and chronotropic actions of NT are species dependent. The potential usefulness of NT in the treatment of experimentally induced heart failure is underlined.


De novo formation of vascular receptors for bradykinin. Two different types of receptors for bradykinin have been found in isolated veins of the rabbit. The first receptor is a stable component of the smooth muscle membrane and it is found in the jugular vein, while the second is generated de novo during incubation in vitro and it is present in the mesenteric vein. Actinomycin D and cycloheximide block the generation of receptors in the mesenteric vein, without exerting any action either on receptors for other agonists (e.g. substance P) in the same tissue, or on the other receptor for bradykinin in the jugular vein.


Effect of hydrocortisone on phenylhydrazine-induced Heinz-body anemia. The effect of hydrocortisone on phenylhydrazine-induced anemia has been examined in adrenalectomized rats. The extent of hemolysis in adrenalectomized rats treated with phenylhydrazine was significantly higher than in normal and adrenalectomized rats supplemented with hydrocortisone.


Hepatic parasympathetic neural effect on glucose balance in the intact liver. Sympathetic nerves to the intact liver of the cat were selectively destroyed by injection of 6-hydroxydopamine into the portal vein 1 week prior to the experiment. Glucose output was calculated from the product of the arterial-venous glucose difference and hepatic blood flow. Hepatic blood flow was monitored by an electromagnetic flowmeter using a hepatic venous long-circuit. Stimulation of the parasympathetic nerves isolated from around the common hepatic artery produced a rapid reduction in hepatic glucose output to one-quarter of control levels by 2 min and to zero by 10 min of nerve stimulation. The data show that hepatic glucose balance is readily influenced by the hepatic parasympathetic nerves.


Acetic acid and hydrogen metabolism during coculture of an acetic acid producing bacterium with methanogenic bacteria. Two microorganisms originally existing as a mixed culture obtained from an anaerobic digester fluid were separated for pure and coculture studies. One of these was motile, Gram-negative, and non-sporeforming, and it required yeast extract for growth and acetic acid production. This isolate produced H2 and did not need H2 and (or) CO2 for growth and acetate formation. The other isolate was a methanogen whick resembled Methanobacterium arbophilicum in morphology and substrate specificity. Coculture growth of the two isolates in yeast extract broth (80% N2--20% CO2 gas phase) indicated that the non-methanogen produced up to four to five times more H2 than when grown separately. Although the growth of the non-methanogen was not enhanced by the removal of H2 by the methanogen, the hydrogen produced was essential for the growth of methanogen. Similar results were obtained when the non-methanogen was cocultured with Methanospirillum hungatti GP1. Cultivation of the non-methanogen in the presence of M. hungatti GP1 (under abundance of 80% H2--20% CO2) indicated that the acetate produced was consumed by M. hungatii, without inhibiting the growth of the other culture.


The metabolism of carbohydrates by extremely halophilic bacteria: the identification of lactobionic acid as a product of lactose metabolism by Halobacterium saccharovorum. Nongrowing cells of Halobacterium saccharovorum oxidized lactose to a product identified as lactobionic acid by thin-layer, paper, and column chromatography, and by identification of the galactose and gluconic acid produced from it after acid hydrolysis. Growing cells oxidized lactose to a product that was identical with lactobionate except that it did not serve as a substrate for galactose oxidase. While the identity of this compound has not been established, it is suggested that the product is lactobionic acid in which the galactose moeity is in the furanose form. Neither lactobionate nor the product produced by growing cells was further metabolized, suggesting that lactose oxidation is not coupled to growth.


Growth characteristics of three bacterial isolates from an arctic soil. Three bacterial isolates, a Pseudomonas sp., a Bacillus sp., and an Arthrobacter sp., commonly isolated from a hummocky sedge-moss meadow at Devon Island, N.W.T., Canada, were selected for further taxonomic characterization and for a study of the effects of temperature and limiting carbon source on growth. Pseudomonas M216 resembled P. putida and Bacillus M153, B. carotarum. Arthrobacter M51 had growth-factor requirements which were more complex than those of any named species of that genus. The temperature ranges of growth indicated that Pseudomonas M216 and Arthrobacter M51 were psychrotrophic while Bacillus M153 was mesophilic. Growth in batch culture at limiting glucose concentrations enabled the calculation of Ks and Y values for each isolate. These were similar to those obtained for other organisms and Pseudomonas M216 and Bacillus M153 showed a high affinity for glucose. The nutritional versatility of Arthrobacter M51 and its ability to grow at low temperatures and the high growth rates and affinity of Pseudomonas M216 for low substrate concentrations may account for their competitive abilities in the natural environment, while the inability of Bacillus M153 to grow at low temperatures may limit its activity in tundra soils.


The interaction of cholera toxin subunit A with cultured adrenal cells. Subunits A and B of cholera enterotoxin were isolated by chromatography on a Bio-Gel P-60 column in the presence of 4% formic acid. The purity and biological activity of the isolated subunits was assessed by polyacrylamide disc gel electrophoresis and mouse adrenal cell assay, respectively. The specific uptake of isolated 125I-labeled subunits A and B, peptides A1 and A2 and bovine serum albumin (BSA) by cultured adrenal cells was investigated. The results indicate that iodosubunit A, or peptide A1 or A2, traverses the plasma membrane and is released to the cell cytosol. A significant portion of bound iodosubunits A or B was associated with the plasma membrane, suggesting the presence of specific membrane receptors. The biological acitivity of subunit A was determined by the mouse adrenal cell assay. The purified subunit caused a characteristic cellular change from epithelioid to rounded morphology. A 30-fold higher concentration of subunit A (on a mole/mole basis) as compared with native toxin was required for a maximum morphologic response. These results extend previous observations related to the bioactivity of subunit A of the cholera enterotoxin molecule.


Estimation of bacterial production in fresh waters by the simultaneous measurement of [35S]sulphate and d-[3H]glucose uptake in the dark. Sulphate uptake in the dark by phytoplankton constitutes a severe limitation to the determination of bacterial heterotrophic production from sulphate-uptake rates. Consequently a modification to the 35S-method has been developed involving size fractionation to separate the algae from the bacteria. Both the whole water sample and the algae-free filtrate are incubated in the dark with trace quantities of [3H]glucose, whereas the filtrate alone is incubated with 35SO4. The experimental determined ratio (whole sample glucose assimilation: filtrate glucose assimilation) is used to correct the measured sulphate uptake (filtrate) and yields an estimate of bacterial sulphate uptake in the whole sample. A potential filtration artefact has been demonstrated in the 35SO4 uptake methodology. Excision of the outer edge of the membrane filter and counting of the inner wetted circle alone eliminated this problem and significantly improved the analytical performance of the method: coefficient of variation approximately 5%, detection limit approximately 2 ng S l-1 h-1. The modified [35SO4]-[3H]-glucose method was applied to samples from an English chalk stream: bacterial sulphate uptake was higher during the spring diatom maximum (10.6 ng S l-1h-1) than 3 weeks later when detritus dominated the seston (4.9 ng S l-1h-1). We estimate the corresponding rates of formation of particulate (bacterial) carbon to be 0.53 and 0.24 microgram C l-1h-1 respectively.


Mycoviruses of Penicillium stoloniferum: influence of carbon-nitrogen nutrition upon replication. Carbon-nitrogen ratio experiments indicate that limiting nutrition not only hinders Penicillium stoloniferum host proliferation but reduces total PsV-F and PsV-S virus replication. Results of C-N experiments show a pH-induced autolysis and virus release at minimal C levels. Maximal PsV-F levels and biomass were obtained with glucose and sucrose as C sources. Oleic acid also yielded high biomass and PsV-F yields. Yeast extract was an excellent N source; 2.83 g dry weight biomass and 87 A260 units PsV-F after 96 h of growth. Other nitrogen sources, including amino acids, supported only minimal growth and virus replication. The autolysis phenomenon is pH, not viral-induced. High C and N will support maximal growth and unrestricted virus replication with no cellular lysis. Under low C growth conditions, the replication of PsV-S is favored coupled with high pH and autolysis.


Spiroplasma associated with flowers of the tulip tree (Liriodendron tulipifera L.). Spiroplasmas were isolated and cultivated from nonsurface-sterilized petals and bracts excised from flowers of Liriodendron tulipifera L. (tulip tree) in Anne Arundel, Charles, and Prince George's Counties in Maryland, and East Lyme County, Connecticut. All isolates grew at 30 and at 37 degrees C. Morphology of colonies on solid agar (1%) medium containing serum differed among isolates: some isolates formed highly diffuse, barely visible colonies; others formed distinct colonies with granular centers surrounded by minute surface or submerged 'satellite' colonies. Cellular morphology and motility of organisms in broth and in agar culture were typical of the spiroplasmas pathogenic in plants and insects. In viscous media containing methylcellulose, spiroplasmas freely suspended in the medium swam, and organisms in contact with glass slide or coverslip "crawled" across the solid surface. Frowth inhibition, metabolic inhibition, and organism deformation tests failed to reveal a serologic relationship between spiroplasma strain 23-6 from tulip tree flowers and spiroplasma strain AS 576 from honey bee.


[Demonstration of extrachromosomal DNA in Rhizobium meliloti]. Seven effective (nitrogen-fixing) strains of Rhizobium meliloti have been studied. By sedimentation analysis of their alkaline lysates in alkaline sucrose gradients, a plasmid was found in four strains. In a strain (2011 str 3) which gave no result with this method, supercoiled DNA was detected by CsCl-dye buoyant density gradient centrifugation. That result was confirmed by analytical Cs2SO4-Ag+ density gradients, which showed a heterogeneity in the average base composition of the DNA extracted from three strains, including the 2011 str 3 strain. Two of those last strains seemed to contain an extrachromosomal DNA of very high molecular weight.


Nutritional characteristics of Megasphaera elsdenii. Megasphaera elsdenii B159 (formerly Peptostreptococcus elsdenii; Rogosa 1971) is able to grow in a chemically defined medium containing minerals, NH4+ as the sole nitrogen source, sulfate as the source of sulfur, acetate and glucose as the carbon and energy sources, and the vitamins biotin, pyridoxine, and calcium pantothenate. When lactate serves as the carbon source, with cysteine present as the reducing agent, acetate is not required. Valine and threonine appeared to be required although direct inoculation of unwashed cells into media lacking these amino acids permitted growth in their absence after an extended incubation period. Sulfur sources utilized included sulfate, sulfide, thiosulfate, cysteine, and glutathionine; methionine was utilized less readily. When glucose was autoclaved in the medium, the generation time of M. elsdenii was 170--200 min, but increased to more than 400 min when glucose was autoclaved separately and added to the cooled sterile medium. When fructose, which had been sterilized separately, was utilized as the carbon and energy source, the generation time was 200 min.


Partial characterization of a cubic Bacillus phage. Partial characterization of a cubic Bacillus phage. Can. J. Microbiol. 24: 986--993. Phage Bam35 is an icosahedron of about 63 nm in diameter. It has a double capsid with spikes at the vertices, and a tail which seems to appear upon nucleic acid ejection. The phage contains DNA and, probably, lipids which seem to be located in the inner coat. The phage is Bacillus-specific, UV- and lipase-resistant, and sensitive to heat, chloroform, and ether. The latent period is 50 min and the burst size is 39. Page Bam35 belongs to a new virus group which includes a phage of B. anthracis and four phages of gram-negative bacteria harboring drug-resistance plasmids.


Investigations into the kinetics and stoichiometry of bacterial oxidation of covellite (CuS) using a polarographic oxygen probe. "Oxygraph" apparatus was used to measure quantitatively the kinetics of oxidation of synthetic covellite (CuS) in the presence and absence of Thiobacillus species. The expected stoichiometric relationship between oxygen consumed and cupric sulphate produced was verified by atomic absorption assays of cupric ion and sulphate ion. Thiobacillus cultures markedly increased the oxidation rate. The dependence of each oxygen-uptake rate on oxygen concentration was also measured. Sterile controls and some bacterial cultures showed first-order kinetics while other cultures showed zero-order kinetics. Addition of biological inhibitors to reacting slurries revealed that cultures showing first-order kinetics did not oxidize CuS itself but merely oxidized elemental sulphur formed by non-enzymic oxidation of CuS. Cultures showing zero-order kinetics oxidized CuS in a way that resulted in all oxygen reduction being enzymic. This mechanism possibly involves the cyclic oxidation and reduction of soluble iron.


Bacterial endocarditis of the mitral valve associated with annual calcification. Bacterial endocarditis, caused mainly by Staphylococcus aureus, was found at autopsy in five patients who had a calcified posterior mitral valve annulus. Clincopathologic correlation indicates that the infection should be suspected in elderly patients with a calcified mitral annulus, the murmur of mitral insufficiency, fever, anemia, polymorphonuclear leukocytosis and a positive blood culture, regardless of evidence of peripheral embolism or of another disease that could cause the last four features. Pertinent pathologic findings are a calcified mitral valve annulus, vegetations of bacterial endocarditis towards the base of the posterior leaflet associated with leaflet perforation and an annulus abscess, and no other valvular disease. The infection may develop on the atrial aspect of a leaflet ulcerated by the calcium mass or may begin on its ventricular aspect, subsequently perforating the leaflet and infecting its atrial surface.


Assessment of the technical quality of electrocardiograms. The technical quality of 600 electrocardiograms (ECG's) was assessed for missing leads and clipping, and graded from 1 to 5 for each of noise, lead drift and beat-to-beat drift. Three subgroups of 200 ECGs each were studied: group A, those obtained by emergency department staff (non-technicians); group B, records obtained by ECG technicians; and group C, telephone-transmitted records obtained by technicians performing all the laboratory work at a smaller, outlying hospital. Records with missing leads, clipping, grade 4 or 5 noise, grade 5 lead drift or grade 5 beat-to-beat drift were classified as unsatisfactory or rejected. With these stringent criteria the rejection rate was 71.0% for group A records, 58.5% for group B and 44.5% for group C. The proportions of records with peak quality (no missing leads or clipping, and grade 1 noise, lead drift or beat-to-beat drift) were 4.5% for group A, 5.5% for group B and 23.0% for group C. Suggested revisions in the grading of technical quality of ECGs are presented.


Stuttering: recent developments in theory and in therapy. When parents are concerned about the development of stuttering in their child they often consult their pediatrician or family physician. Theories on the development of stuttering are briefly examined in this article, and guidelines are provided to help the physician determine if the child's dysfluencies are within the normal range. Referral to a speech therapist should be considered when any of the following are noted: excessive repetition of the first syllable of words; tremor of the muscles of mouth or jaw, increase in pitch or loudness, or evidence of fear or emotion as the child struggles with a word; evidence that the child avoids certain words or situations; and excessive concern of parents, teachers or the dysfluent individual. Two approaches to therapy, traditional and behavioural, are described. The latter has resulted in significant gains in fluency among stutterers.


Detection of pericardial effusion by chest roentgenography and electrocardiography versus echocardiography. To determine the sensitivity and specificity of chest roentgenography and electrocardiography in the detection of pericardial effusion, echocardiography was used as the diagnostic standard. Chest roentgenograms and electrocardiograms of 124 patients, 57 of whom had pericardial effusion, were read without knowledge of the echocardiographic interpretation. The sensitivity of roentgenographic diagnosis was low (20%), as was that of diagnosis from decreased voltage on the electrocardiogram (26%). The specificity of the chest roentgenogram was 89% and that of the low-voltage electrocardiogram 97%. The high specificity of the low-voltage electrocardiogram may have been due in part to the exclusion of obese and emphysematous subjects from the study. When cardiomegaly detected roentgenographically or a low-voltage electrocardiogram or both were considered as evidence of pericardial effusion, sensitivity improved to 82% but specificity declined to 29%. It is concluded the chest roentgenography and electrocardiography are unsatisfactory as screening investigations for the detection of pericardial effusion.


Hereditary angioneurotic edema and Charcot-Marie-Tooth disease in the same family. In one family two genetic diseases were transmitted as autosomal dominant traits; hereditary angioneurotic edema was inherited from the paternal side and Charcot-Marie Tooth disease from the maternal side of the family. The conditions occurred separately in 8 and 11 members respectively and together (an exceedingly rare occurrence) in 3. Of six siblings, two girls and four boys, all had Charcot-Marie-Tooth disease, and three, the two girls and one of the boys, also had hereditary angioneurotic edema.


Unusual fractures associated with osteoporosis in premenopausal women. Two premenopausal women (aged 40 and 34 years) and multiple undisplaced, often asymptomatic fractures of the femurs, ribs, metatarsals and other bones. The fractures, which appeared on roentgenograms as transverse radiolucent zones with variable callus formation, healed slowly or not at all despite treatment with calcium and vitamin D. They resembled pseudofractures (Looser's transformation zones) radiologically, but the biochemical and histologic findings were those of idiopathic osteoporosis rather than osteomalacia. Since neither patient had been subjected to unusual stress it was concluded that the fractures had resulted from normal activity in abnormal bone.


Patterns of relapse in advanced Hodgkin's disease treated with combination chemotherapy. One hundred sixty-one patients with advanced Hodgkin's disease achieved complete remission after combination chemotherapy. Of these, 52 (32%) have subsequently relapsed and the patterns of relapse have been studied. The probability of relapse increases with increasing stage and particularly with the presence of systemic symptoms. Patients with Nodular Sclerosis histology are more likely to relapse than those with other histologies. Patients relapse primarily (92%) in sites of previous disease and particularly in nodal sites (75%). Nodal sites most frequently involved at relapse are the central nodal areas and the left supraclavicular area. When patients relapse in new sites they tend to be either adjacent to sites of previous disease which relapse or to be contiguous with previously involved sites of disease. In the small number of patients who received prophylactic radiation therapy to sites of nodal disease after complete remission, the pattern of relapse was not significantly altered.


Future prospects in lymphoma and leukemia. Possible advances in leukemia and lymphomas can, in my opinion, derive from continued consideration of viral etiopathogenesis, possibly demonstrated by therapeutic impact of antiviral therapy. Terminology is in constant flux, and a classification based on biochemical (such as asparagine dependence) and immunologic (such as surface marker) characteristics should displace older terms such as chronic and acute. There is a constellation of neoplasms of lymphoid cells and their derivatives--leukemias, lymphomas, and plasmacytomas which need an integrated taxonomy. New diagnostic tests, new strategies of adapting therapy to tumor cell kinetics perturbed by the preceding treatment, and interesting clinical and preclinical combination of drugs provide new basis for favorable expectations. Immunotherapy is just emerging as a potent therapeutic tool. A technique for standardizing clinical results of different institutions to the age and sex of the population who develop the disease in question is much needed. Controls in trials of leukemias and lymphomas are found to be dispensable if one is measuring qualitative differences; for quantitative assessment of remission frequency or response duration, however, controls are requisite.


Chronic lymphocytic leukemia.

Chronic lymphocytic leukemia. Chronic lymphocytic leukemia (CLL) is the commonest type of leukemia seen in Western countries. It affects an older group of individuals than most other varieties of leukemia, and men more often than women, in a ratio of 2:1. The incidence of CLL is significantly increased in some families. In most instances, CLL is due to the overgrowth or accumulation of immunoglobulin producing B lymphocytes. Hypogammaglobulinemia is a common feature, and anomalous immunoglobulin components occur in 3 to 5% of patients. The early symptoms and signs of CLL include fatigue, reduced exercise tolerance, enlarged lymph nodes, and splenomegaly. Fever, weight loss, and impairment of bone marrow function, with anemia, bleeding and susceptibility to infection are characteristic of severe or advanced disease. In the great majority of patients, the disease can be controlled for 6 to 10 or more years with simple regimens using chlorambucil or cyclophosphamide, often in combination with prednisone. Radiotherapy and splenectomy are useful in some instances. The terminal phase of the disease is characterized by exacerbation or increasing severity of the leukemia and the development of opportunistic infections associated with immunodeficiency.


Induction of thyroid follicular adenomas and carcinomas by N-nitrosobis(2-oxopropyl)amine. Subcutaneous injection of N-nitrosobis(2-oxypropyl)amine (BOP) induced thyroid follicular adenomas and carcinomas in MRC rats. The tumor yield was 50% following a single dose and 60% after weekly treatment for life. In males the tumor incidence was slightly higher and the latency period shorter, while in females, the tumors were larger. Sites of origin, size, multiplicity and morphologic patterns of tumors were analyzed in relation to dose and sex. The possible mechanisms involved in tumorigenesis are discussed.


The effects of orally administered L-arginine HCl on the development of myeloma tumors in BABL/C mice following the injection of single cell suspensions, cell aggregates or tumor fragments; and on the growth of two ascites tumour cell lines. When arginine-HCl was added to the drinking water of Balb/c mice the formation of subcutaneous tumours following the injection of single cell suspensions of MPC-11 cells was prevented, however, tumours did develop after injecting tumour fragments or aggregates of suspension-cultured cells. Arginine-HCl had no inhibitory effect upon the production of Krebs II and 6C3HED lymphoma ascites tumours in Balb/c and C3H mice respectively.