Epidemiology of adverse drug reactions to phenformin and metformin. Adverse drug reactions (ADRs) to phenformin and metformin reported to the Swedish Adverse Drug Reaction Committee during 1965--77 were analysed in relation to sales and prescription data. The biguanides accounted for 0.6% of all reported adverse drug reactions but for 6% of the fatal cases (all phenformin). Sixty-four ADRs to phenformin and eight to metformin were classified as causal relation "probable" or "not excluded." Fifty-one of these reactions (71%) were lactic acidosis, all but one being reactions to phenformin. After 1973 phenformin was prescribed less in Sweden and metformin became predominant. A nationwide prescription survey during 1975--6 disclosed no differences in age and sex between patients receiving phenformin and metformin. The mean daily doses prescribed in 1976 were 74 mg of phenformin and 1.5 g of metformin. The numbers of ADRs to the two drugs reported during 1975--7 were related to use. The relative incidences of ADRs reported for phenformin and metformin did not differ. Significantly more cases of lactic acidosis and deaths were reported for phenformin.


Measurement of capillary blood glucose in filter-paper spots: an aid to the assessment of diabetic control. A method of measuring glucose in capillary blood spotted on to filter paper was evaluated. Between-batch reproducibility was about 6%, and the glucose remained stable in the spots for up to four days. Adoption of the method should improve control of diabetes, particularly insulin-dependent forms.


Lack of proliferation of circulating white blood cells in patients with syphilis before and after a Jarisch-Herxheimer reaction. The occurrence of lymphoblasts in peripheral blood, measured by incorporating tritiated thymidine ([3H]dThd), was studied before, during, and after a Jarisch-Herxheimer reaction in patients with early syphilis. No difference in [3H]dThd incorporation into peripheral white blood cells was found between five patients with syphilis and 19 healthy controls, whereas in 20 cord blood samples [3H]dThd incorporation was significantly increased.


Lymphocyte reactivity in patients with gonococcal urethritis. Lymphocyte reactivity to virulent gonococcal antigen T2 and the non-pathogenic Neisseria pharyngis (NPN) has been studied by using the 14C-thymidine uptake in cell cultures from 42 patients with gonococcal urethritis and from 18 controls. The DNA synthesis in cell cultures with T2 antigen was higher in 21 female patients than in the 18 controls. No differences in DNA synthesis were observed in antigen-stimulated cell cultures from patients with single or multiple infections, from patients with urogenital complication, or from controls. Gonococcal antibodies in the serum were detected by the gonococcal complement-fixation test (GCFT). A study of the possible correlation between the outcome of the serological test and the cellular response to gonococcal antigen showed that 14C-thymidine uptake in lymphocyte cultures from male patients with negative GCFT, stimulated with T2 antigen, was much lower than the thymidine uptake in stimulated cell cultures from all the other male and female patients (P less than 0.001). The DNA synthesis was higher in cell cultures from seronegative women than from seronegative men (P less than 0.01). A significant difference (P less than 0.01) was also noted in the lymphocyte reactivity to gonococcal antigen between controls and all patients, except in those men who gave negative results to the serological tests. There were no differences between these two groups with respect to the thymidine uptake in NPN-stimulated cell cultures.


Talampicillin and probenecid compared with ampicillin and probenecid for the treatment of gonococcal urethritis in men. Two hundred and ten men suffering from uncomplicated gonococcal urethritis were treated with one of two treatment schedules. Of 109 patients treated with 3 g ampicillin and 2 g probenecid (group A) there were two recurrences in the first week after treatment and none in the second week. Of 101 patients treated with 1.5 g talampicillin and 2 g probenecid (group B), there were three recurrences in the first week and none in the second week. Both antibiotics were well tolerated, but one patient vomited two hours after taking talampicillin. The sensitivity pattern of Neisseria gonorrhoeae to penicillin at The London Hospital has shown an increase in the proportion of more sensitive strains during the last three years. Talampicillin given in a single dose with probenecid is satisfactory in the treatment of acute gonococcal urethritis but, apart from the smaller dosage, it does not offer any advantage over ampicillin with probenecid.


Changes in the incidence of acute gonococcal and nongonococcal salpingitis. A five-year study from an urban area of central Sweden. The incidence of acute gonococcal and nongonococcal salpingitis for a five-year-period (1970--74) was studied retrospectively in an urban area of central Sweden. The investigation was undertaken to see if the reported decrease of gonorrhoea in Sweden had been followed by a change in the incidence of gonococcal salpingitis--the most common complication of gonorrhoea. The study showed that the relative incidence of acute gonococcal salpingitis had decreased even more than urogenital gonorrhoea and these findings thus indicate a real decrease of gonorrhoea. At the same time there were more patients with nongonococcal salpingitis. During the period of the study the gonococcal complement-fixation test (GCFT) gave positive results in 40% to 80% of the patients with gonococcal salpingitis. The yield with this test was only 4% in patients with nongonococcal salpingitis during 1970 but it increased successively and was 23% in 1974. This increase was statistically highly significant (P less than 0.001).


Chlamydia trachomatis in non-specific urethritis. Chlamydia trachomatis was isolated from 58.5% of 159 patients with non-specific urethritis (NSU) using irradiated McCoy cell cultures. Patients with persistent Chlamydia-positive NSU remained Chlamydia-positive each time they were examined before treatment and patients with Chlamydia-negative NSU remained Chlamydia-negative during the course of the illness. Neither the duration of symptoms of urethritis nor a history of previous urethritis affected the chlamydial isolation rate significantly. Of 40 patients with severe discharge 30 (75%) harboured C. trachomatis. One-third of the Chlamydia-positive patients had a severe urethral discharge, while this was present in only 15% of Chlamydia-negative patients. Complications--such as conjunctivitis, arthritis, and epididymitis--were more severe in men with Chlamdia-positive NSU than in those with Chlamydia-negative NSU. Of 64 men matched for sexual promiscuity but without urethritis, none harboured C. trachomatis in his urethra. This differs significantly (P less than 0.001) when compared with patients with NSU. C. trachomatis was isolated from the urogenital tract in 24 (42%) out of 57 female sexual contacts of patients with NSU. The presence of C. trachomatis in the women correlated significantly (P less than 0.001) with the isolation of the agent from their male contacts. These findings give further evidence for the aetiological role of C. trachomatis in non-specific urethritis and its sexual transmission.


Spectral interactions in horizontal and ganglion cells of the isolated and arterially-perfused rabbit retina. Intracellular and extracellular recordings in the arterially-perfused eye cup of pigmented and albino rabbits show the presence of blue cones, green cones and rods. Among the ganglion cells, a fraction shows spectral opponency. Two main types were found. In one, on-depolarizing responses and on-hyperpolarizing responses receive antagonistic input from different cone types ('B/G'); in the other, on-depolarizing responses receive input from both blue and green cones wheras off-depolarizing responses receive input either from blue or from green cones ('BG/G','BG/B'). Two types of horizontal cell responses have been found, both receiving mixed green cone and rod input; one type is cone-dominated while the other is rod-dominated. Neither type shows C-type responses or obvious input from blue cones, either synergistic or antagonistic, with intense selective chromatic adaptation of green cones and rods. Mass b-wave responses show a spectral sensitivity suggestive of antagonistic interactions between blue and green cones signals to inner nuclear layer neurones, which were not seen in action spectra based on a-wave or PIII component responses. It is argued that although blue cone signals contribute to spectral interactions at the ganglion cell and inner nuclear layer cell levels, they do not seem to contribute significantly to such interactions at the receptor or horizontal cell levels.


Patterns of output firing generated by a many-input neuronal model for different model parameters and patterns of synaptic drive. A relatively simple neuronal model with a large number of 'synaptic' inputs is described. The model has been extensively studied in order to investigate the influence which patterns of presynaptic firing may have upon the pattern of output firing. The model has been studied in two versions. In one the threshold remained constant, while in the other the threshold was increased following an output firing. This increase in threshold decayed with time and was analogous to the after-hyperpolarization of a real neurone. The effect on the frequency of output firing of changes in the threshold and of the overall input rate were studied in detail. The pattern of output firing was studied for two patterns of input firing. In one, each presynaptic input fired steadily, each at a different rate; in the other, the input firings were randomly distributed in time, being generated by a Poisson process. It was found that, for a given total input rate, the pattern of output firing was markedly more regular when the input processes were regular, even though the mean rate of output firing was not appreciably different for the two different distributions of input firings. It is shown that, with suitable parameters for the model, it is possible to mimic very closely the discharge of tonically discharging motoneurones under different experimental conditions. This suggests that the more general properties of the model may have considerable relevance to the way in which real neurones integrate their synaptic input.


Protein and enzyme distribution in microsomal and myelin fractions from rat and Jimpy mouse brain. The protein, glycoprotein and enzyme composition of myelin and myelin-related fraction (SN 4) from rat forebrain was compared with that of microsomal fractions. Acetylcholinesterase was largely confined to the microsomal fractions, wheras 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP) showed a high specific activity in myelin and SN 4 fractions. Nevertheless, the total specific activities of CNP present in microsomal membranes and in a water-soluble form were not negligible, and suggest that this enzyme has a wide distribution among subcellular particles. A high molecular weight protein was identified in myelin and all the other fractions studied. This protein (X), which co-migrates with the major myelin glycoprotein, was present in myelin and in fractions lacking typical myelin components as well as in fractions from a myelin deficient mutant, the Jimpy mouse. The results suggest that the X protein is probably a contaminant in isolated myelin, although the occurrence of this protein as an intrinsic component of several different membranes cannot be ruled out. Despite substantial overlap in density upon zonal centrifugation between SN 4 and microsomal fractions, the enzyme patterns of the fractions were different.


Modulation of ACh turnover in the septal-hippocampal pathway by electrical stimulation and lesioning. The septal-hippocampal cholinergic pathway of the rat was either electrically stimulated or lesioned in order to study whether or not acetylcholine turnover rate (TRACh) changes with the activity of the cholinergic neurons. Appropriate electrical stimulation of the septum selectively increased the TRACh in the hippocampus in nonanesthetized and in barbiturate-treated animals. The ACh content of the hippocampus increased by approximately 30% 1 h after fimbria lesions, but decreased by about 80% 9 days after fimbria lesions. Acute fimbria lesions decreased the TRACh in the lesioned side by approximately 85%, but the TRACh in the intact side and in the cortex was unchanged. The same was true in rats with chronic fimbria lesions. In conclusion, the hippocampal TRACh increases or decreases proportionally to the activity of the cholinergic neurons; therefore the measurement of this parameter is of particular value in understanding how postynaptic cholinergic neurons are modulated by putative neurotransmitter released from afferent nerve terminals.


Induction of chronic epileptiform activity in the rat by an inhibitor of cholesterol synthesis, U18666A. Earlier work in our and other laboratories suggest that alteration of brain lipids, primarily sterols, could be a precondition for the development of epileptiform activity. The present study further tests this hypothesis by attempting to produce chronic epileptiform activity in the rat by a drug which impairs biosynthesis of cerebral cholesterol. Starting one day after birth, weekly injection of the rat with U18666A, 3-beta(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride (10 mg/kg, s.c.), produced a reduced seizure threshold to flurothyl ether and a recurrent, spontaneous seizure state by the sixth and tenth weeks of life, respectively. These conditions were not seen if treatment was delayed until rats were about 4 weeks old. The seizure pattern, as seen by continuous ECoG and EMG recordings, consisted of a 3--5 sec burst of high voltage spiking and corresponding increases in muscle activity. However, major motor seizures were not produced. The total episode lasted 10--15 sec. Seizure frequency ranged from 5 to 21 per day. U18666A decreases cholesterolsynthesis, presumably by inhibiting enzymatic reduction of desmosterol to cholesterol. After the first two weeks of treatment, cerebral cortical cholesterol levels decreased to about 50% of control cortical levels. However, the concentration of cerebral total sterols did not change because desmosterol levels reciprocally increased. In spite of continued drug dosage, cholesterol and desmosterol levels of treated rats approached those of controls by 8 weeks of age. These observations, plus finding that a seizure-prone state did not develop in rats when the onset of drug treatment was postponed until about 4 weeks of age, suggest that alterations of brain sterols early in development of the mammalian brain can result in development of a chronic, epileptiform condition later in life.


Ontogeny of (--)-[3H]norepinephrine uptake properties of synaptic storage vesicles of rat brain. The ontogeny of[3H]norepinephrine uptake mechanisms has been examined in synaptosomes and storage vesicles isolated from rat whole brain. The [3H]norepinephrine accumulated by synaptosomes was low in neonates, but reached adult levels by 15 days of age. In contrast, development of[3H]norepinephrine uptake into isolated rat brain storage vesicles was not complete until 38 days of age. Kinetic analysis of the developing vesicular uptake mechanism revealed no change in Km, while maximal uptake increased progressively from birth to maturity. Storage vesicles from immature and adult rats exhibited similar energy requirements for uptake as determined by their dependence on ATP-Mg2+ concentration; furthermore, the degree of inhibition of [3H]norepinephrine uptake by other amines was the same in both vesicle preparations. Thus, storage vesicles isolated from adult and developing rats display an in vitro[3H]norepinephrine uptake mechanism with properties that are kinetically and pharmacologically similar. The results suggest that, while the number of storage vesicles in the central nervous system increases during development, those vesicles that are present possess a fully functional amine uptake system.


Observations on the commissural projection to the dentate gyrus in the Reeler mutant mouse. The commissural projection to the displaced granule cells of the dentate gyrus in Reeler mutant mice has been examined with autoradiography, and light and electron microscopy. Commissural terminals in Reeler are confined to the hilar region, in contrast to normal littermates in which this projection is restricted to the inner part of the molecular layer. Granule cell somata in Reeler, but only exceptionally in normal littermates, are invested with spines, which have postsynaptic specializations, but no spine apparatus, and are contacted by presynaptic terminals. Between 20 and 30 h after destruction of the commissural fibres in Reeler, degenerating terminals can be found contacting both somatic and dendritic spines in the hilus; 30 h after decommissuration the number and length of spines on the somata and proximal dendrites of Golgi impregnated cells is greatly reduced, while spines on the distal parts of the dendritic tree are unaffected. A similar pattern of degeneration after decomissuration is found in the inner molecular layer of normal littermates. These results are discussed in terms of factors controlling the normal development of afferent projections. The paper concludes with an analysis of a potential methodological hazard. A change in mean spine length will of itself result in a change in the number of visible spines in golgi material. A quantitative assessment of the relation between spine length and the number of visible spines is developed for spherical cell bodies and cylindrical dendrites.


Neuronal differentiation in somatosensory cortex of the rat. I. Relationship to synaptogenesis in the first postnatal week. Newborn (P-0 and P-1) through 6-day-old (P-6) rats were studied using light microscopic (Golgi) and ultrastructural methods. Previous studies demonstrated that early-formed synapses are concentrated at specific cortical depths, i.e. in strata. The present study shows that the synaptic stratum in the marginal zone corresponds to a dense fiber plexus and few somata (Cajal-Retzius cells). Axons in this zone almost exclusively form synapses on distal branches of dendrites originating in deeper lamina. In newborn neocortex there is a second synaptic stratum located deep to the cortical plate. It contains numerous axosomatic and axoproximal dendritic synapses as well as the most highly differentiated somata and proximal dendrites. By age P-6 there are 3 synaptic strata; one each in the marginal zone, cortical plate and 'subplate' layers. For all 3 strata a neuron's most differentiated dendrites are directed towards, traverse or run within, the nearest synaptic stratum. We conclude that, throughout the first postnatal week, the most mature dendrites of a given neuron generally occur at depths where synapse density is highest. At P-0 the most mature somata are similarly related to synaptic density.


Use of cortical circuits during focal penicillin seizures: an autoradiographic study with [14C]deoxyglucose. Autoradiography with [14C]deoxyglucose was used to study the architectural pattern of glucose utilization in the motor cortex of rats during focal penicillin seizures. The seizure focus was characterized by a well circumscribed area whose metabolic activity was increased 2-3 times normal. This was tightly surrounded by cortex that was normal or slightly depressed. The posterior third of the focus showed an increase in glucose utilization in a columnar pattern with particular accentuation of activity in lamina V. There was a loss of normal activity in lamina IV within the focus and in somatosensory and occipital cortex far behind the focus. This depression was particularly prominent in the ipsilateral barrel field. Increased metabolic activity was found in a small area in contralateral homotopic cortex, in lamina Vb with columns extending above this from lamina IV to the surface. Glucose utilization was accentuated 1.2-1.8 fold in the ipsilateral secondary somatosensory area, but was normal in the contralateral cortex. The intensity of focal seizures was increased by the intracortical injection of more penicillin or by giving intravenous metrazol. Both of these methods resulted in an increase in the size of the focus as determined with [14C]deoxyglucose. This was most prominent on the lateral border in lamina I-II and V. In addition, there was an accentuation of the columnar pattern in the posterior part of the focus, ipsilateral somatosensory cortex, and contralateral motor cortex. The architectural pattern of glucose utilization in the cortex during focal seizures is discussed with reference to corticocortical, commissural, and corticothalamic circuits that have been identified by others in anatomical studies. Superimposed on this structure are physiological principles of recurrent excitation, lateral spread, and surround inhibition that characterize basic electrophysiological mechanisms of epilepsy, and influence the intensity of activity within the architectural design.


Kindling of neuroanatomic pathways during recurrent focal penicillin seizures. Sequential changes in convulsive phenomena have been studied using intracortical injections of penicillin as a kindling agent. Rats given 25 units of penicillin every 4 days had a progressive increase in the frequency of contralateral muscle jerks. Unilateral tonic-clinic events began after the third injection, and bilateral jerks of both upper extremities began subsequent to that. No generalized convulsions occurred, and further changes in focal convulsions stopped after 7 injections. The seizure events occurring in this kindled state could be seen in rats given a single injection of 100 units of penicillin. Rats subjected to daily injections at this dosage did not develop more intense seizures, and afterdischarges essentially stopped after the first injection. Animals studied with deoxyglucose autoradiography during kindling with 25 units showed an increase in the size and intensity of metabolic activity in the seizure focus. In addition there was an increase in size and intensity of most transynaptic sites, with new activity appearing in contralateral basal ganglia. A comparison of these findings with the autoradiographic results of animals receiving 100 units of penicillin suggests that the major change during kindling takes place in the focus itself. The appearance of new activity in contralateral basal ganglia is probably an expression of activity in crossed corticostriate pathways from the focus as well as pathways descending from the homotopic cortex in an obligatory input-output response. Use of these pathways is not dependent on kindling, but is available on a first come basis if the intensity of discharges from the seizure focus is strong enough.


Study of cardiac sympathetic and vagal efferent activity during reflex responses produced by stretch of the atria. (1) In chloralose anesthetized dogs, effects of the left and the right atrial stretch were studied in the same animal. Stretch of the sino-atrial region of the right atrium produced acceleration of the heart rate during, and reversal of response at the termination of, the stretch. Stretch of the left pulmonary vein-atrial junctional region evoked an initial decrease followed by an increase in heart rate. The responses were similar in all animals, despite initial heart rates ranging from 120 to 200 beats per minute. (2) Activity in vagal and sympathetic nerve branches innervating the heart was recorded simultaneously. Care was taken to identify the vagal fibers innervating the heart, and record their activity without contamination of sympathetic impulses. The right atrial stretch evoked an augmentation of sympathetic activity which reached its peak at 20 sec after the beginning of stimulus. The stimulus slightly increased the vagal activity; this change occurred slowly and reached its peak in about 40-60 sec after stretch. At the release of stretch, sympathetic activity generally showed a reversal of response, i.e. activity was inhibited for 30 sec. (3) Stretch of the left atrium produced biphasic changes in cardiac sympathetic nerves; their activity was strongly inhibited for the first 15 sec, then augmented throughout the remainder of the stretch. This effect lasted 30 sec after the cessation of stimulus. Effects on vagal cardiac nerve fibers were smaller; mild augmentation in activity was produced. The onset of this effect was faster than that seen in case of the right atrium stretch. (4) Reciprocal action between vagal and sympathetic cardiac nerves was obvious only in the early phase of left atrium stretch. Effects on the heart were determined by balances in activity of these antagonistic nerves. In contrast with what occurred in cardiac reflexes, carotid sinus distension even in the same animal produced a large increase in vagal activity, and near complete inhibition of sympathetic nerve activity. Thus, good reciprocal action between the two sets of nerves was demonstrated. A difference in the two types of reflexes was thus revealed. (5) Stretch of the right atrium evoked during carotid sinus distension caused an increase in heart rate from the new low level which was produced by baroreceptor activation. Vagal activity which was greatly augmented by sinus distension was decreased by atrial stretch, while previously inhibited sympathetic activity due to sinus distension was augmented by stretch of the atrium. The effect of stretch on vagal activity seems to depend to a degree on the prestimulus level. It is of interest that the powerful baroreceptor reflexes do not mask the cardiac reflexes studied. (6) The relative importance of sympathetic and vagal efferents to atrial stretch reflexes was discussed.


Eledoisin, substance P and related peptides: intracranial dipsogens in the pigeon and antidipsogens in the rat. The undecapeptide eledoisin caused vigorous and copious drinking within a minute or two of injection into the pigeon forebrain. Systemic injections of the same doses were ineffective. The relative efficacy of eledoisin and angiotensin II as dipsogens in the pigeon was similar to that of carbachol and angiotensin II in the rat. The related peptides eledoisin hexapeptide, physalaemin and substance P also caused some drinking, but they were less effective than eledoisin. In the rat none of these substances caused drinking. On the contrary eledoisin and substance P were found to depress angiotensin-induced drinking, but carbachol-induced drinking was not depressed to the same extent by these peptides. The preferential depression of angiotensin II-induced drinking resembles the effects of other vasoplegic drugs on this response in the rat, and may be related to the potent vasodilator properties of these peptides.


Effects of 5-bromodeoxyuridine on development of Mauthner's neuron and neural retina of Xenopus laevis embryos. Bromodeoxyuridine (BrUdR) injected into Xenopus embryos at stages before, during or after the last period of DNA synthesis in Mauthner's neurons had no serious effect on differentiation of Mauthner's neurons. However, the BrUdR caused widespread cell degeneration in the central nervous system. The action of BrUdR on retinal neuronal differentiation depended on dose and stage of infection. At all doses (0.005-0.9 microgram per injection), and all stages (22-29), the main effect was retinal cell degeneration. The drug produced complete absence of differentiated retinal neurons only when given at early stages (22-24) and at the highest doses (0.5-0.9 microgram) that enabled the embryo to survive to stage 44. At stages 22-24 at lower doses (0.005 or 0.05 microgram per injection) and at stages 26-29 at all doses, some retinal neurons differentiated, although retinal cell degeneration was the main effect. In these two systems BrUdR did not selectively inhibit neuronal differentiation.


The influence of brain damage on locomotor behavior of mice selectively bred for high or low activity in the open field. Locomotor activity was measured in mice with lesions restricted to the neocortex, in animals with hippocampal damage, and in sham-operated control mice of the selectively bred high and low open-field activity lines developed by J. C. DeFries. Postoperatively, the high-activity animals with hippocampal lesions showed reduced activity relative to those with only neocortical damage, and their postoperative activity levels were uncorrelated with those obtained preoperatively. Testing the animals under reduced illumination enhanced locomotor activity, with the greatest increase demonstrated by high-activity mice with hippocampal damage. While increases in activity under low illumination did occur in the low-activity line, no significant group differences were observed. Amphetamine did not affect locomotor behavior of the high-activity control animals, whereas doses of 1.0 and 10.0 mg/kg reduced the activity of the low-activity mice. High-activity mice with hippocampal damage evidenced a significant increase in locomotor behavior after the 10.0 mg/kg dose. These results emphasize that the behavioral effects of brain lesions and pharmacological manipulations cannot be adequately assessed without regard to genotype of the animals under investigation.


Electron microscopic autoradiography of the uptake of [3H]GABA in dispersed cell cultures of rat cerebellums. I. The morphology of the GABAergic synapse. Dispersed cell cultures of rat cerebellums 21 days in vitro were incubated in saline containing 0.5 micrometer [3H]GABA for 5 min, fixed and prepared for electron microscopic autoradiography. Quantitative methods for analyzing the resulting autoradiographs were developed to distinguish lightly labeled neurons from heavily labeled (i.e. GABAergic) neurons. After a 3 week exposure, 2% of the presynaptic elements were found to be GABAergic. A longer incubation time of 15 min resulted in a greatly increased grain density over lightly labeled neurons, making it more difficult to distinguish them from the GABAergic neurons. When the concentration of [3H]GABA was increased to 1.0 micrometer, the grain densities over both GABAergic and other neurons increased to a similar extent. The morphology of the GABAergic synapses differed from that of the total population synapses. The GABAergic synapses had larger cross-sectional areas, lower densities of vesicles, greater numbers of vesicles, and thinner postsynaptic densities. Both the GABAergic and total population had similar lengths of the postsynaptic densities, cleft widths, vesicle sizes and types of postsynaptic elements. The morphology of the GABAergic synapse reported here is similar to that described for basket and stellate presynaptic elements in vivo.


CNS site of clonidine induced hypotension: a microiontophoretic study of bulbar cardiovascular neurons. To localize the central site and mechanism of clonidine induced hypotension, the drug was applied by the technique of microiontophoresis to neurons of the bulbar cardiovascular center in decerebrate cats. The excitatory and inhibitory cardiovascular neurons (CVN) were identified by their response to an increase in the arterial blood pressure induced by intravenous injections of small doses of norepinephrine (NE). Clonidine had an inhibitory effect on the spontaneous firing rate of excitatory CVN but had no effect on the firing rate of inhibitory CVN. At the same doses, it had no effect on the firing rate of NCVN recorded from the same area. Furthermore, clonidine had a blocking action on the excitatory response of CVN induced by microiontophoretic application of NE. It is concluded that clonidine produces its hypotensive response by acting on alpha-adrenergic receptors of bulbar CVN.


Sparing of function in rats with early prefrontal cortex lesions. Previous work has shown that medial frontal lesions in adult rats produce deficits on spatial reversals, delayed responses, and active avoidance, whereas more ventrolateral (orbital) lesions have little effect on these tasks. These findings were confirmed. However, when lesions were made at 2, 5 or 9 days of age, rats tested as adults showed dramatic sparing of function on all these tasks, whereas similar lesions inflicted at 35 or 40 days of age produced deficits on delayed responses and spatial reversals. Orbital frontal lesions failed to significantly alter behavior on any task at any age. The effects of the neonatal lesions are in striking contrast to the effects of juvenile or adult lesions, even though the infant lesions were considerably larger. Histological analysis revealed no retrograde degeneration in the dorsomedial thalamic nucleus of the rats operated in infancy unless the lesions were so large that the adjacent caudate-putamen was also damaged. The contrast between these results, and results obtained after similar lesions in adults may indicate the growth of sustaining collaterals after the infant lesions which might be involved in the observed behavioral sparing.


Functional organization of receptive fields in the cat somatosensory cortex. I: Integration within the coronal region. The receptive fields (RF) of the neurons in the coronal region of the first somatosensory cortex (SI) were studied in a preparation of unanesthetized paralyzed cats. The majority of units responded to simple light mechanical stimuli to the hairy or glabrous skin. There were units with slightly larger RFs and more complex properties, such as those preferentially responding to the moving skin stimuli with directional selectivity. The receptive fields tend to be larger in the more rostral (area 3a) or medial coronal (area 3b) region than in the caudal region (area 3b). The largest RFs intermingled among focal ones included other smaller RFs in the vicinity. Their configurations were different at different loci in the coronal region. It is suggested that the coronal SI region is organized in terms of multiple clusterings of units, each with particular receptive field characteristics. The representation of a single peripheral locus on the forepaw can thus be multiple, if it appeared in more than one of such clusterings of receptive fields.


Functional organization of receptive fields in the cat somatosensory cortex. II: Second representation of the forepaw in the ansate region. The receptive fields (RF) of the neurons in the ansate region of the first somatosensory cortex (SI) were studied in unanesthetized paralyzed cats. Along the ansate sulcus, the forepaw dorsum was represented laterally, and the ventral surface of the paw was represented medially. These representations of the distal forepaw were found to be different from those in the coronal region in that they take parts of the larger and elongated receptive fields along the forearm axis. The principle of multiple representation of the forepaw on SI proposed in the preceding paper was thus confirmed and extended in this study. Many units in the ansate region showed complex receptive characteristics different from those in the coronal region. The convergence of skin and deep submodality was observed in units recorded in area 2 in the deep fold along the ansate sulcus, border zone along area 5. The functional organization of SI in terms of its cytoarchitectonic differentiation and thalamocortical relationships was discussed.


Neurones with synchronous bursting discharges in organ cultures of the hypothalamic supraoptic nucleus area. Explants of the hypothalamic supraoptic nucleus area from newborn rats were cultured. Ultrastructural studies revealed the existence of typical neurosecretory granules in neuronal perikarya as well as in axons. Large nerve cells that were spontaneously active discharged at an average firing rate of 7.2 +/- 4.4 (S.D., n = 98) spikes/sec and 42% of these neurones displayed a phasic firing pattern as shown by the existence of peaks in their autocorrelograms. The firing of 59% of the neurones was synchronous with the activity of other nerve cells. In some neurones, only the onsets of bursts were correlated, whereas in others periods of high correlation alternated with periods of no correlation. The relative proportion of rhythmically or synchronously firing hypothalamic neurones was not altered when a neurohypophysial explant was co-cultured. Field stimulation in the cultures resulted in a short-latency excitation followed by an inhibition which was found to be bicuculline-sensitive. The existence of functional synapses was furthermore demonstrated by intracellular recordings of postsynaptic potentials.


Evidence for the movement of fluid, macromolecules and ions from the brain extracellular space to the CSF. This report examines the effect of decreasing serum osmolality on movement into the ventricular system of fluid and of test material injected into the brain. Trace quantities of 22NaCl and 125I-labeled cat serum albumin (CSA) were injected into cerebral white matter of cats. The rates of cerebrospinal fluid volume flow, and appearance of 22Na and 125I-CSA were measured in the effluent fluid using ventriculocisternal perfusion before and while serum osmolality was acutely decreased by the intravenous infusion of a 60 mOsm sucrose solution. As compared to the control period, at the end of the infusion serum osmolality decreased from 321 +/- 4.2 mOsm to 283 +/- 4.0 mOsm and CSF volume flow increased from 21.8 +/- 2.3 microliter/min to 54.9 +/- 4.1 microliter/min (means +/- S.E.). The slope of the regression line describing 22Na influx went from 1.04 to 1.79, while for 125I the slope went from 0 to 1.38. These results suggest that a common pathway may exist for the movement, through the brain and into the ventricular system, of water, ions and large molecules.


The differential effects of 5-hydroxytryptamine, noradrenaline and raphe stimulation on nociceptive and non-nociceptive dorsal horn interneurones in the cat. The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA) and stimulation of the inferior central nucleus of the raphe (RN) were examined on nociceptive and non-nociceptive spinal neurones in anaesthetized cats. 5-HT reduced excitation evoked by noxious stimulation, but increased spontaneous firing and firing evoked by DL-homocysteic acid (DLH) on both nociceptive and non-nociceptive cells. NA reduced spontaneous activity, DLH-evoked excitation and excitation evoked by a noxious stimulus on nociceptive neurones, but had little action on non-nociceptive units. RN inhibited spontaneous, stimulus-evoked and DLH-evoked firing of nociceptive cells and caused briefer inhibitions of non-nociceptive cells. Excitatory effects were also observed. Strychnine antagonized short-duration inhibitions from RN of non-nociceptive cells responding to hair movement, but failed to antagonize any of the other effects of RN. No antagonism of the inhibitory effect of RN was observed with phenoxybenzamine, phentolamine, sotalol, bicuculline or methysergide. However, methysergide antagonized some excitatory effects of 5-HT and RN, but also produced non-specific actions on some cells. It was concluded that, although glycine may mediate some of the brief duration inhibitions evoked by RN, the longer duration inhibitions were unlikely to have been mediated by either glycine or GABA. 5-HT may be a mediator of raphe-spinal actions but may have presynaptic inhibitory actions coupled with postsynaptic excitatory effects. NA could mediate some descending inhibition of nociceptive neurones.


Synaptic structures and quantification of catecholaminergic axons in the nucleus tractus solitarius of the rat: possible modulatory roles of catecholamines in baroreceptor reflexes. The synaptic organization in the nucleus tractus solitarius (NTS) of the rat at the level of the obex was examined by fluorescence and electron microscopy in 5 groups of animals: (1) normal control, (2) intraventricular injection of 5-OHDA, (3) intraventricular injection of 6-OHDA, (4) intracranial denervation of the IXth and Xth cranial nerves, and (5) intraventricular injection of 5-OHDA 48 h after intracranial denervation of the IXth and Xth cranial nerves. A dense network of catecholaminergic nerves was observed in the NTS and several catecholaminergic neurons were seen to be scattered in the lateral portion of the NTS. Nerve cells in the NTS were small in size (15-20 micrometer in diameter). In addition to ordinary axodendritic and axo-somatic synapses, serial synapses were occasionally encountered. The first presynaptic site in some of the serial synapses was identified as catecholaminergic by 6-OHDA treatment. After treatment with 5-OHDA, 2.4% of axon varicosities were identified as catecholaminergic by small dense-cored vesicles. After administration of 6-OHDA, 5.19% of dense degenerated axon varicosities were counted. After intracranial deafferentation of the IXth and Xth cranial nerves, 5.3% of dense degenerated axon varicosities were found. The total number of axon varicosities in 6800 sq.mum area was decreased by 9% after the injection of 6-OHDA and 11% after deafferentation of the IXth and Xth cranial nerves. At least 3 types of axons could be identified: (1) catecholaminergic axons with small dense-cored vesicles after 5-OHDA administration, (2) afferent axons from the IXth and Xth cranial nerves with small clear vesicles, and (3) axons with small clear vesicles probably originated from the supramedullary nucleus. The results of the present study suggest that catecholamines modulate reflex blood pressure regulation within the NTS of the rat.


Biochemical changes accompanying unilateral 6-hydroxydopamine lesions in the rat substantia nigra. The biochemical consequences of a unilateral 6-hydroxydopamine injection into the substantia nigra of the rat brain were investigated. Projections of dopaminergic neurons from the A8-A9-A10 regions to a number of forebrain areas were confirmed. No innervation to the hypothalamus, including the median eminence, or to the brain stem, could be found with the present techniques. No destruction of serotonergic or GABAergic fibers could be demonstrated in the lesioned substantia nigra. Increases in glutamic acid decarboxylase activity were found restricted to the caudate and zona compacta of the substantia nigra ipsilateral to the lesion, indicating the possibility of a physiological interaction between GABAergic and dopaminergic systems. The neuroanatomical localization of the nigral dopamine-sensitive adenylate cyclase was also studied. No change in enzyme activity was found after destruction of a great proportion of the dopaminergic cells, suggesting that this enzyme has an extradopaminergic localization in the substantia nigra.


Cerebral energy metabolism during recovery from carbon monoxide hypoxia-oligemia. The effects of 1 h exposure to 1% CO and right common carotid artery clamping upon the cerebral energy metabolism, perfusion and histology were studied in anesthetized (70%N(2)O) and unanesthetized rats following reoxygenation for 0-6 h. At 0 h recovery the clamped hemispheres showed decreases of ATP, PCr and glycogen, and increases of ADP, AMP, inorganic phosphate and lactate which indicated an advanced derangement of the tissues' energy homeostasis. Exposure in unanesthetized animals was associated with lower levels of ATP and glycogen, and with larger increases of lactate in the clamped hemisphere which suggested the presence of a more intense hypoxic-oligemic insult. The metabolic differences in the clamped hemisphere of unanesthetized and anesthetized animals became more marked after 1 h reoxygenation, with anesthetized animals showing large restitutions of ATP, PCr, glycogen and lactate, whereas in unanesthetized animals these metabolites showed severe persistent defects over the 6 h reoxygenation period. Since the arterial oxygen content and tension, and perfusion patterns were equivalent in the 2 series at 0 and 1 h recovery, it is concluded that even minor anesthetic agents such as 70%N(2)O or other non-hypoxic variables during exposure or recovery may cause significant alterations in the metabolic restitution of the hypoxic-oligemic brain.


Uptake of L-alanine, glycine and L-serine in the pigeon central nervous system. The uptake characteristics of L-alpha-alanine, glycine and L-serine into crude mitochondrial fractions from pigeon telencephalon, tectum and spinal cord were determined. Sodium dependent high affinity uptake systems were found for all 3 amino acids in all 3 brain regions, except for glycine in the telencephalon. The mutual inhibition of the high affinity uptake by the 3 amino acids was measured in the tectum. Alanine uptake was inhibited competitively by serine and glycine. The inhibition of serine uptake by alanine and glycine was also competitive. In contrast, glycine uptake inhibition by alanine and serine was incomplete and neither competitive, non-competitive nor uncompetitive. The effect of various chemicals on the uptake of the 3 amino acids was measured in the tectum at a substrate concentration of 10(-5) M. Four groups could be distinguished: (1) Substances with no effect on the uptake of all 3 amino acids, (2) substances which inhibited the uptake of all 3 amino acids to a similar degree, (3) substances which inhibited the uptake of alanine and serine more than glycine and (4) substances which inhibited glycine uptake more than alanine and serine uptake. From these results we conclude: Alanine and serine are probably taken up by the same transport system. This system can possibly also use glycine as substrate. Most of the glycine high affinity uptake, however, is due to a specific glycine transport system. This system was found only in tectum and spinal cord and is probably the same uptake system as known in the spinal cord of other vertebrates.


Chromatin binding of estradiol in the hypothalamus and cortex of male and female rats. Gonadal steroids are thought to act by activation of the genome following cytoplasmic binding, translocation of the hormone--receptor complex to the nucleus and chromatin binding at specific acceptor sites. This study examined the kinetics of chromatin binding of estradiol by hypothalamic and cortical cells of adult gonadectomized male and female rats. In both sexes binding was found to be limited to hypothalamic cells. The kinetics of binding differed between the sexes, estradiol being retained less well in males. In females hypothalamic chromatin binding was shown to be of limited capacity and to be competitively inhibited by unlabeled estradiol. Unlabeled testosterone inhibited estradiol binding when administered subcutaneously 3 h before the estradiol, but not by testosterone when administered either intravenously or concurrently with the estradiol. It was suggested that the observed sex difference in hypothalamic chromatin binding might underlie the relative insensitivity of the male to the lordosis-inducing properties of estradiol.


Morphological localization of PNS myelin proteins. The localization of PNS myelin protein was studied using two methods: (1) lactoperoxidase catalysed iodination of intraperiod band material, (2) solubilization of basic proteins with ammonium acetate--Triton X-100 solutions. When myelin was swollen in the presence of lactoperoxidase and subsequently submitted to lactoperoxidase catalysed iodination P0 and what appeared to be the X protein labeled with 125I. In specimens which were disrupted in 50% ethyl alcohol, the basic proteins P1 and P2 were also iodinated. When the lactoperoxidase was omitted, there was no labeling of proteins. Ammonium acetate--Triton X-100 solutions solubilized basic proteins from both whole nerve and purified myelin preparations. Electron microscopic changes which accompanied this modification included swelling and splitting of the main period band. These data indicate that the P0 and X proteins are available for iodination in the intraperiod band of swollen PNS myelin and that basic proteins are localized in the main period band.


Topography of the neurons responding to estrogen in the hypothalamic arcuate nucleus of immature female mice. The neurons in the hypothalamic arcuate nucleus (ARC) of 20-day-old female mice were examined by electron microscopy. The administration of estradiol-17 beta during 20 days from the day of birth resulted in the increase of dense-core vesicles (DCVs) in some neuronal perikarya of the middle region of the ARC (middle ARC), while, in the posterior region of the ARC (posterior ARC), the increase of DCVs was less marked. Topographical studies revealed that the neuronal perikarya containing few DCVs were assembled in the ventromedial area of the middle ARC in both control mice and mice given estrogen. Those containing 5 or more DCVs were found predominantly in the ventromedial area of the middle ARC in mice given estrogen. In the posterior ARC, however, the neuronal perikarya containing DCVs seemed to be scattered. The distribution patterns of the diameter of DCVs were significantly different between control mice and mice given estrogen. The administration of estrogen seem to bring about the enlargement in the size of DCVs. These results indicate that the neurons responding to estrogen are present in the ventromedial area of the middle ARC, and suggest that this area is a significant focus in estrogen feedback mechanisms.


Dependence of the activity of interpositus and red nucleus neurons on sensory input data generated by movement. Cats performed flexion movements of the forearm, and the discharge of interpositus and red nucleus neurons was examined for relationships to the motion and to the EMG activity of agonist and antagonist muscles. It is shown that, over a wide range in the time course of the motion, the activity of the neurons is covariant with both the EMG and the movement parameters, in particular, the velocity. Also, the discharge of the interpositus neurons is modulated in phase with the velocity of passive movement. It is concluded that during fast, intentional movements, sensory input data generated by motion is a major determinant of the output of the interpositus nucleus. Furthermore, the results are consistent with the concept that this output provides a continuous modulation of spinal segmental mechanisms by way of the red nucleus and rubrospinal tract.


Relationships between sensory input, motor output and unit activity in interpositus and red nuclei during intentional movement. The relationship between unit activity in interpositus (8 units) and red nuclei (11 units) and the EMG activity of the biceps during intentional elbow flexion movements was investigated by means of cross-correlation analysis. This analysis showed that there were long-lasting (200 msec) changes in the probability of EMG activity both before and after a single spike in neurons which covaried with the motor output. The dependence of the activity of these units on sensory inputs was investigated by (1) calculating the quantitative relationship between angular displacement and unit activity and (2) recording unit activity after the sensory input from peripheral afferents had been eliminated by dorsal rhizotomy.


Afferent connections of the entorhinal area in the rat as demonstrated by retrograde cell-labeling with horseradish peroxidase. The entorhinal cortex (EC) of the rat has been divided into medial (MEA) and lateral (LEA) subdivisions. In order to analyze its afferent connections, small deposits of horseradish peroxidase (HRP) were placed at various loci within EC. The patterns of retrograde cell-labeling charted in 18 such cases suggested that EC is projected upon by several allocortical and subcortical structures and that there are differences in the afferent connections of the two subdivisions. Thus, although HRP injection of either division of EC led to cell-labeling in the hippocampal formation, most in ammonic field CA1 and the subiculum, several cells of the presubiculum were preferentially labeled by injection of MEA. Injections of LEA, but not those in MEA, resulted in substantial cell-labeling in the anterior piriform cortex of both hemispheres. Regardless of the location of its injection site within EC, the enzyme labeled cells in the diagonal band nucleus of Broca, amygdala and claustrum. The pattern of cell-labeling in the diagonal band nucleus extended into the ventrolaterally contiguous nucleus basalis after injection of LEA and into the dorsally contiguous medial septal nucleus after injection of MEA Whereas HRP deposits in either division of EC resulted in cell-labeling in the cortical and medial nuclei of the amygdala, only those deposits which involved LEA led to cell-labeling in the posterior part of the lateral nucleus. In the thalamus, labeled cells were found in the rostral part of the paratenial, periventricular and reuniens nuclei. Finally, at midbrain levels, numerous labeled cells appeared in the dorsal raphe nucleus, a few in the median raphe and locus coeruleus, and, only after rostral EC injection, in the ventral tegmental area.


Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Ascending projections from the caudal (general-visceroceptive) part of the nucleus of the solitary tract (NTS) were studied experimentally in the rat by the aid of the anterograde autoradiographic and the retrograde horseradish peroxidase (HRP) tracer techniques. Microelectrophoretic deposits of tritiated proline and leucine which involved the caudal part of the NTS, the dorsal motor nucleus of the vagus (dmX), and portions of the hypoglossal nucleus, nucleus intercalatus and/or nucleus gracilis were found to label ascending fibers that, besides going to numerous brain stem territories that included prominently the parabrachial area, could also be traced to serveral forebrain structures, namely, the bed nucleus of the stria terminalis (BST), the paraventricular (PA), dorsomedial (HDM) and arcuate (ARC) nuclei of the hypothalamus, the central nucleus of the amygdaloid complex (AC), the medial preoptic area (PM) and the periventricular nucleus of the thalamus (TPV). Smaller isotope injections almost completely confined to the NTS and dmX resulted in lighter labeling of a similar set of parabrachial and forebrain projections, whereas in another case, in which the deposit was almost exclusively limited to the nucleus gracilis, no label was seen in the aforementioned structures. In another series of experiments, aimed at further localizing the neurons of origin of the prosencephalic projections under consideration, small microelectrophoretic HRP injections confined almost totally to BST, PA, HDM, AC, PM or TPV, as well as both small and large injections involving ARC, resulted in labeled neurons situated in the dorsal medullary region, mainly in the medial portion of the NTS at the level of and caudal to the area postrema. Taken together, these observations indicate for the first time the existence of relatively direct conduction lines by which interoceptive information might be conveyed to limbic forebrain structures; some of the possible physiological correlates of these anatomical findings are discussed.


Visual field representation in the newborn rabbit's cortex. The representation of the visual field in the newborn rabbit's visual cortex appears on about the 10th day after the animal's birth coinciding with the time of its eye opening. Initially the visual response is obtained from a small anterolateral segment of the visual area of the cortex representing a few degrees of the extreme nasal vision of the animal. Even at this early stage, the visually responsive area of the rabbit's cortex seems to organize into V1 and V2 with the binocular response confined to V1 only. By the 15th day after the animal's birth, the visually responsive area in the newborn rabbit extends medially and posteriorly over the cortex, representing more of the animal's temporal and superior visual fields. By this time the binocular response is established over a narrow zone of the animal's visual cortex, representing a few degrees of the nasal visual field, on either side of the boundary between V1 and V2. Between the 16th and 17th day after the rabbit's birth, the cortical representation of the animal's visual field extends medially to the margin of the fissura sagittalis lateralis and caudally to the posterior pole of the hemisphere. In this visually responsive area of the cortex, the band-shaped visual field of the newborn rabbit is asymmetrically represented.


alpha-Bungarotoxin-acetylcholine receptors in the chick ciliary ganglion: effects of deafferentation and axotomy. alpha-Bungarotoxin (alpha-BuTX) binds in a saturable and practically irreversible fashion to membrane-associated receptors in the ciliary ganglion of the adult chick. The binding of toxin to receptors is competitively inhibited by nicotinic cholinergic ligands, and for these properties the receptors are regarded as acetylcholine receptors of the nicotinic type (alpha-buTX-AChRs). The rate constant of association (K1) and dissociation (K-1) of the toxin-receptor reaction has been estimated to be K1 = 7.4 x 104 M(-1) sec(-1) and K-1 = 9.6 X 10(-6) sec(-1), respectively. Light autoradiography shows that most, if not all, the receptors are related to surface membrane, probably to synaptic areas of both choroid and ciliary neurons. The choroid neurons contain more receptors than the ciliary ones. A single chick ciliary ganglion binds specifically 47 fmole of alpha-BuTX in situ corresponding to 2.83 x 1010 alpha-BuTX-AChRs/ganglion. No changes in number and distribution of the toxin receptors occur following preganglionic denervation. Conversely, postganglionic axotomy causes a rapid disappearance of the receptors in situ. Since binding experiments in vitro revealed a partial, instead of a total, loss of the receptors, it is suggested that the disappearance of the receptors in situ includes both a partial loss of the original receptors and the masking of the residual ones.


Reversible hyperphagia and obesity following intracerebral microinjections of colchicine into the ventromedial hypothalamus of the rat. Colchicine, a drug which produces a reversible inhibition of intraaxonal transport and synaptic transmission, was used as a reversible neural blocker to investigate the role of the ventromedial hypothalamus (VMH) in the control of ingestive behavior and body weight regulation. Male Sprague-Dawley rats received intracranial microinjections of colchicine into the VMH. Volume and concentration of the colchicine solution were varied to assess specificity of action and dose-response relationship. When colchicine (2 and 4 microgram) was microinjected bilaterally into the VMH, there was a dose-dependent increase in food and water intakes and body weight gain which lasted several days. The acute period of hyperphagia was followed by a marked depression in feeding which persisted until body weight was lowered to control levels. This suppression of feeding appeared to be a consequence of the preceding period of hyperphagia and obesity, since colchicine-treated rats which were pair-fed with controls to prevent obesity continued to maintain normal food intake and body weight gain when later fed ad libitum. The results of this study confirm the importance of the VMH in the long term regulation of feeding, and indicate that reversible neuronal blocking with colchicine is a useful technique for investigating the neural substrates of feeding and other behaviors.


Biotin deficiency and liver metabolism in relation to fatty liver and kidney syndrome. Varying degrees of biotin deficiency were induced by adding freeze-dried, raw egg white to the diet of broiler chicks. Aspects of liver metabolism were studied with reference to fatty liver and kidney syndrome. Mortality was low with 11.8 g egg white/kg diet, or less, but with 17.7 g/kg or more, mortality was very high. High mortality was observed with less than 0.33 microgram biotin/g liver. Associated with low concentrations of liver biotin were substantial increases in liver weight and lipid content in starved birds. The increased liver lipid content was not observed in birds fed ad libitum. The increased liver lipid content in biotin-deficient, starved birds was not reflected in the specific activities of hepatic lipogenic enzymes or hepatic lipogenesis in vivo measured by the incorporation of tritium from 3H-labelled water into liver lipid. Biotin deficiency affected the specific activities of the biotin-requiring enzymes, pyruvate carboxylase and acetyl CoA carboxylase, differently; the latter was unaffected whereas the former decreased concomitantly with liver biotin concentration.


The tryptophan requirements of young laying pullets. Two experiments were conducted with laying pullets between 32 and 47 weeks of age. In each trial 1728 White Leghorn and 1728 cross-bred pullets were used. A series of diets of increasing protein content was offered. Protein quality was identical in all diets and tryptophan was demonstrated to be the most limiting amino acid in the protein mixture used. The daily tryptophan requirement of the individual pullet was estimated, by indirect methods, to be 2.25 mg/g egg output plus 10.25 mg/kg body weight. Response curves for flocks of pullets are illustrated. Calculated optimum intakes of tryptophan for various ratios of costs of input to value of output are tabulated. It is estimated that for a flock of mean body weight 1.5 kg, producing 55 g egg mass/hen d and consuming 110 g food/hen d, the optimum dietary tryptophan concentration is 1.7 g/kg when the marginal cost of supplying 1 kg tryptophan is 20 times the marginal value of 1 kg egg output.


The effect of a single oral dose of nonprotein nitrogen from various sources on amino acid concentrations in the plasma and liver of the chick. Broiler chicks were fed normally for 21 d, then starved overnight and given a single oral dose of an aqueous solution of diammonium hydrogen citrate (DAHC), triammonium citrate (TAC), ammonium lactate (AL) or urea equivalent to 24.76 mg N. Controls were given water. The concentrations of free amino acids in the plasma were measured 2, 4 or 6 h after dosing. The only non-essential amino acid significantly affected was glutamine, which increased in chicks given DAHC or TAC (P less than 0.01). In another experiment, non-protein nitrogen (NPN) from the same sources was given at dosages of 124 mg N per chick. The concentrations of free amino acids in the plasma and liver were determined 2, 4 or 6 h after dosing. NPN from all sources increased the amount of glutamic acid and glutamine in both tissues (P less than 0.001), although the response to urea was delayed. The concentrations of plasma aspartic acid (P less than 0.05), plasma alanine (P less than 0.001) and liver aspartic acid (P less than 0.001) also increased. The results are discussed in relation to earlier studies with liver homogenates in vitro.


Interrelationships between dietary concentrations of sodium, potassium and chloride in laying hens. Twelve diets, representing the factorial combination of two concentrations of Cl- (0.8 and 1.4 g/kg), three concentrations of Na+ (0.5, 1.1 and 1.7 g/kg) and two concentrations of K+ (7 and 12 g/kg) were fed to groups of laying hens for 24 weeks and records taken of their productivity. Different concentrations of Na+, K+ and Cl- showed highly significant interactions which were always similar. Thus, a deficiency of Na+ (0.5 g Na/kg) was aggravated by the restriction of Cl- (0.8 g/kg), but was partly compensated for by supplementing the diet with K+ (12 instead of 7 g/kg). Without a sodium deficiency other interactions occurred; for example, the higher concentration of K+ became unfavourable if the other two ions were also supplied at the higher concentrations. These results show that, for the laying hen, the optimum concentrations of Na+, K+ and Cl- cannot be determined independently but depend upon the concentration of the two others in the diet.


The inheritance of tibial dyschondroplasia in broilers. A breeding programme to develop a line of chickens with a high incidence of tibial dyschondroplasia (TD) from Australian broiler stock is described. Despite the absence of a control flock, this programme has demonstrated that selection in a broiler population can rapidly increase the incidence of TD. There was consistent circumstantial evidence of the presence of a major sex-linked gene, the recessive allele of which is associated with an increased incidence of TD. The realised heritability estimates (obtained in the absence of a control flock) consistently exceeded 1.00, suggesting the presence of an environmental trend favourable to the onset of TD over the four generations of this investigation. There was a high maternal component or dominance genetic component, or both, for the inheritance of TD in the final generation, suggesting that environmental factors associated with the female parent line may influence the incidence of TD in broilers.


Studies on the avian shell gland during egg formation: the effect of acetazolamide on the composition of the mucosa. The effect of acetazolamide, an inhibitor of carbonic anhydrase activity, on the intracellular composition of the shell gland mucosa was determined. The normal cyclic hydration of the mucosal cells was found to be reduced when the egg was in the uterus and the partition of the water between the intra- and extracellular compartments was modified. Acetazolamide decreased the accumulation of Na+ within the cells, inhibited the Na+-independent movement of Cl- and reduced the transfer of Cl- linked with Na+. It is concluded that acetazolamide blocks the intracellular generation of HCO3- and the reabsorption of Cl-.


Studies on the avian shell gland during egg formation: the effect of acetazolamide on the transfer of ions to the albumen. Twenty-five laying hens were fed on a diet containing 100 mg acetazolamide/kg in order to determine the effects of a decrease in the activity of carbonic anhydrase on the transfer of minerals to the egg albumen. Treatment with acetazolamide decreased the rate of shell formation by 44%; reduced the concentrations of water and Na+ in the albumen at the beginning of the plumping stage but increased the accumulation of water during plumping; increased the concentration of Cl- in the albumen after the 6-h stage without any appreciable change in K+ and Ca2+ concentrations. The computed relationships between the concentrations of different ions also showed that the transfer of water and Na+ were linked during egg formation, that a water-independent, acetazolamide-sensitive reabsorption of Na+ occurred after the 10-h stage and that Na+ and Cl- moved simultaneously up to 14 h but with the ratio of Cl- to Na+ three times higher in the treated group. It is concluded that acetazolamide impairs the transfer of Na+ and Cl- between the albumen and the extracellular fluid and that secretion of Ca2+ into the uterine lumen seems to depend on Na+ and Cl- reabsorption.


Twisted legs in broilers.

Twisted legs in broilers. The effect of various factors on the incidence of leg abnormalities, with particular reference to twisted leg, in broilers was studied. The incidence of twisted legs was influenced by strain and for males was twice that for females. There was also a higher incidence in cages than on litter with the type of cage floor having an effect: broilers reared on floors of metal wire and perforated sheets had more leg problems than those reared on plastic mats and plastic-covered wire. Although vitamin and mineral supplementation had no effect on caged broilers, a restriction of metabolisable energy (ME) intake during the first 14 d after hatching halved the frequency of leg abnormalities compared with those fed ad libitum. Studies of cage size and location of water suggested that a lack of exercise increases the incidence of leg abnormalities.


Effects of age on the tryptophan requirement of laying hens. White Leghorn pullets which had been used for an assay of tryptophan requirement between 32 and 40 weeks of age were used for similar determinations between 63 and 73 and, after a moult, from 97 to 106 weeks of age. A tryptophan-limiting protein mixture was used and by dilution seven dietary protein contents were produced, supplying from 0.84 to 1.92 g tryptophan/kg diet. The diet of lowest protein content was also supplemented with free tryptophan. These diets were fed in experiments using 24 groups of 72 pullets at 63 to 73 weeks and 45 groups of 21 hens at 97 to 106 weeks. The relationship between egg output and tryptophan intake was the same in moulted hens as in young pullets, but pullets of 63 to 73 weeks of age yielded a different response curve; more tryptophan being needed for a given egg output. It is concluded that tryptophan required, per day, does not decrease during the first laying year, despite a decrease in rate of egg output.


Ultrastructure of the dolipore-parenthesome septum in Hirschiporus pargamenus (Polyporaceae). The septal complex in hyphae of Hirshioporus pargamenus (Fr.) Bond. & Sing. is generally similar to that described for other Homobasidiomycetes. A noteworthy distinction is the presence of imperforate parenthesomes. A dark line is frequently observed in the inner matrix of the parenthesome. We suggest that this line is an image produced by the overlapping of folded, opposing membranes differentiated from the wall endoplasmic reticulum.


Morphology microstructure, and development of colonies of Acetobacter xylinum. Development of the morphology and microstructure of colonies of Acetobacter xylinum growing on agar was studied by optical microscopy, and transmission and scanning electron microscopy. The mass of rapidly dividing cells surrounded by a sheath of cellulose microfibrils passes from a smooth spheroid to a flattened aggregate with a characteristic "pillowed" surface. This morphology is the result of a repeated extrusion of cells from the confirming sheath, followed by regeneration of a new portion of the sheath on the extrusion of cells from the confirming sheath, followed by regeneration of a new portion of the sheath on the extruded cell mass. Relations of this mechanism to others which produce similar shapes are indicated.


Isolation anc characterization of actinophages of Thermoactinomyces and Micropolyspora. Two new actionphages infecting thermophilic actinomycetes were isolated from lysogenic cultures of Thermoactinomyces candidus and Micropolyspora faeni. The physiochemical properties, morphology, host range, electron microscopy, and immunology of the two phages, phi-115A (ATCC 29680-B1) and phi-150A (ATCC 29681-B1), are reported.


Difference in generation times for mother and daughter cells in yeasts. Fruitless attempts to synchronize haploid yeast cells from the Phargmobasidiomycete Sirobasidium magnum led to the discovery that the mother and daughter cells (MDC) had greatly different generation times. Time-lapse photographic sequences of budding showed that the mean generation time for daughter cells was more than three times greater than that for mother cells. This growth characteristic could be determined by a spot check of the microcolony pattern on agar. Using such a check, yeast strains of Rhodotorula (Rhodosporidium) and Cryptococcus that were tested demonstrated relative MDC equivalence while those of Sporobolomyces, Bullera, and Tremella showed MDC non-equivalence in varying degrees.


Possible association of granulocyte mobilization to the peritoneal cavity with ZnCl2-induced protection against endotoxin. We have attempted to determine which components of the inflammatory response are responsible for ZnCl2-induced retention of endotoxin in the peritoneal cavity and enhancement of survival following challange with the toxin. ZnCl2 injected intraperitoneally into mice caused accumulation of granulocytes in the peritoneal cavity, but these cells were apparently not responsible for the trapping process. This contention in supported by our observation that reduction of hepatosplenic uptake of 51CR-labeled endotonxin was similar in unirradiated mice and in mice made by irradiation (1000 rad 60 Co) 1 rad = 10 (-2) J/kg). Hepatosplenic uptake was also depressed when untreated mice were injected with endotoxin suspended in cell-free plasma. Furthermore, zinc did not protect irradiated mice challanged with endotoxin, although it enhanced survival in urirradiated animals. Lack of protection in irradiated mice may be due to a deficiency in the cellular response in the peritoneal cavity.


The transport of microbial biomass and suspended material in a high-marsh creek. The transport of microbial biomass and suspended material in a high-marsh creek was investigated during four 40-h tidal studies throughout the year. Although considerable differences were noted between successive tidal cycles, overall the creek was found to be an exporting system and transported a mean concentration of ATP (-33g), chlorophyll a (-66g), particulate organic carbon (-31kg), total suspended material (-344kg), and fixed suspended material (-195kg) during each tidal cycle. This net outward flux of materials was associated with a net flow of water out of creek, while the net import of aerobic, heterotrophic bacteria (43 x 10(12)) and volatile suspended material (238kg) was generally due to higher mean concentrations of these materials per unit volume of water during the flooding tide. Also the latter generally were associated with increased amounts of suspended material suggesting an association between bacteria and suspended matter.


The microbial degradation of cyclohexanecarboxylic acid by a beta-oxidation pathway with simultaneous induction to the utilization of benzoate. The metabolism of cyclohexanecarboxylic acid by a bacterium, designated PRL W19, follows a pathway involving beta-oxidation of coenzyme A intermediates analogous to the classical oxidation of fatty acids. The organism appears to have the property for the constitutive metabolism of caproic acid, and cell extracts contain high levels of the enzymes required for the functioning of the fatty acid cycle. However, the metabolism of cyclohexanecarboxylic acid requires induction by growth or incubation with an appropriate substrate. Extracts of induced cells contain several enzyme activities which are synthesized in response to the induction process. These enzymes include cyclohexanecarboxyl-CoA synthetase, cyclohexanecarboxyl-CoA dehydrogenase, 1-cyclohexenecarboxyl-CoA hydratase, and trans-2-hydroxycyclohexanecarboxyl-CoA dehydrogenase. A characteristics feature of this organism is that it becomes induced for the metabolism of benzoate and catechol during growth on cyclohexanecarboxylic acid, but benzoate does not appear to be an obligatory intermediate in the metabolism of cyclohexanecarboxylic acid.


Lipopolysaccharides of the motile aeromonads; core oligosaccharide analysis as an aid to taxonomic classification. Twelve motile Aeromonas strains have been examined with respect to the hexose and heptose monosaccharide residures present in the core region of their cell wall lipopolysaccharides. These strains were divided into three distinctly separate groups on the basis of the various combinations of hexose and heptose residues. The assignment of a strain to any one of the three groups furnishes a distribution which is substantially the same as that recently reported in a computerbased numerical analysis. All strains tested which were previoulsy named A. liquefaciens fall into the same group.


Necrotrophic mycoparasitism of Ceratocystic fimbriata by Hirschioporus pargamenus (Polyporaceae). Necortrophic mycoparasitism by Hirschioporus parganenus (Fr.) Bond. & Sing. on selected non-basidiomycetous fungi is characterized by rapid necrosis of host cytoplasm. Invagination of the host plasmalemma is followed by the production of a conspicuous extraplasmalemmal wall deposit. Necrosis is the result of disruption of membrane systems and is followed  by the penetration of dead host cells. Pathogenesis involves an unidentified toxic substance excreted by the parasite. Contact is not essential.


The effect of compounds which degrade hydrogen peroxide on the enumeration of heat-stressed cells of Salmonella senftenberg. Greater than 90% of heat-stressed cells of Salmonella senftenberg failed to grow on trypticase soy agar. Adding to this medium compounds which are capable of degrading hydrogen peroxide allowed growth of the heat-injured cells. These compounds did not stimulate growth of heated cells of Streptococcus faecium, an organism which does not possess catalase.


Clinical experience with the newer hepatobiliary radiopharmaceuticals. Technetium 99m-labelled hepatobiliary imaging agents provide high resolution images not previously possible with rose bengal labelled with iodine 131. This has prompted a re-examination of the utility of these radioactive pharmaceuticals. We have found that the newer methodology provides a rapid, innocuous and accurate means of excluding acute cholecystitis from the diagnosis in patients with symptoms suggestive of this disease and of assessing surgically altered biliary anatomy. In the presence of moderate bilirubinemia, up to about 85.5 to 103 mumol/L [5 to 6 mg/dL], a definitive distinction can be made between medical and surgical jaundice.


Recurrent duodenal ulcer.

Recurrent duodenal ulcer. In the past 6 years 26 patients underwent operation for recurrent duodenal ulcer after what was considered to be an "adequate" initial operation. In such patients it is necessary first to demonstrate the recurrent ulcer and then to determine its cause. Endoscopy was the best means of confirming the diagnosis. The cause of recurrence was determined by tests for gastric acid secretion; 70% of patients had hyperacidity and 80% had positive results of the Hollander test. Treatment is always surgical but varies depending on the type of initial surgery, the primary cause of recurrence and the condition of the patient. Ten patients underwent vagotomy, 12 had vagotomy with antrectomy and 4 had antrectomy alone. There were no operative deaths but nine (35%) patients experienced 11 significant postoperative complications.


Reoperation following failure of aortoiliofemoral arterial reconstruction. Over a 19-year period, 729 primary arterial reconstructions for aneurysmal and occlusive disease of the aortoiliac arterial system were performed at the Health Sciences Centre, Winnipeg. During the same interval 49 of these reconstructions required reoperation and 6 additional cases were referred for secondary repair from other institutions. The authors reviewed these 55 cases to determine the reasons for reoperation and the cumulative results of secondary repair. Secondary arterial repair was performed in 11.5% of cases of occlusive disease and in 1.2% of cases of aneurysmal disease. The overall frequency of reoperation was 6.7%. The mean interval between primary and secondary operation was 31.5 months. Perioperative failure, false aneurysm, graft infection, progression of disease and late technical problems were the major reasons for reoperation. Of the secondary repairs the results in 83.6% were satisfactory at 30 days. At 5 years, 57% of secondary repairs at risk remained satisfactory. The operative mortality for secondary arterial repair was 5.4%. The authors believe that continued aggressive management of failed primary aortoiliac reconstructions is justified.


Role of Doppler ultrasonography in determining the hemodynamic significance of aortoiliac disease. Doppler ultrasound recordings from the common femoral artery were quantified by calculation of the pulsatility index (a number of related to the maximum oscillatory energy of the wave). To demonstrate that the index permits detection of hemodynamically significant aortoiliac stenosis, studies were carried out that led to the following conclusions: (a) in patients with aortoiliac occlusive disease and normal distal vessels, the index correlates with the ankle pressure ratio (the ratio of systolic blood pressure at the ankle to brachial systolic blood pressure) (r = 0.70); (b) the index allows distinction of subjects with significant aortoiliac disease, demonstrated arteriographically, from normal subjects; and (c) in patients with pure aortoiliac occlusive disease (no evidence of distal disease on arteriography) there is a strong correlation between the index and the percentage improvement (i.e., increase) in the ankle pressure ratio following operation (r = 0.80). When the femoral  pulsatility index was greater than 5, the ankle pressure ratio did not improve following operation, but when it was 4 or less, an objective improvement in ankle pressure ratio was demonstrated.


Oropharyngeal dysphagia in patients with oculopharyngeal muscular dystrophy. Sixteen patients with an established diagnosis of oculopharyngeal muscular dystrophy underwent clinical, radiologic and manometric assessment. Secondary pharyngo-oral and pharyngonasal regurgitations are usually associated with this condition and chronic aspiration with consequent bronchorrhea is common. Such patients may present with marked oropharyngeal dysphagia. Cineradiologic findings correlated well with the mamometric results. The pharynx showed very weak contractions of longer duration than those observed in normal subjects. The proximal esophageal sphincter had a normal resting and closing pressure; however, relaxation and coordination of the sphincter were substantially different from those in a control group. Eleven patients underwent cricopharyngeal myotomy. All had notable improvement of their symptoms. Surgery on the sphincter results in a substantial decrease in its resting pressure; pharyngeal contraction remains unaltered.


Antibiotics in surgery of the colon.

Antibiotics in surgery of the colon. In a randomized prospective study of patients undergoing elective colonic surgery the postoperative wound infection rate was 13% (early, 10%) in patients receiving systemic cephaloridine perioperatively and 12% (early, 7.3%) in those given oral neomycin and erythromycin base preoperatively. Wound infections were more frequent in patients with severe lymphopenia or hypoalbuminemia preoperatively, but the potential degree of wound contamination was the main determinant of postoperative infection.


Importance of a fifth parathyroid gland in the surgical treatment of hyperparathyroidism. Of 365 patients surgically treated for hyperparathyroidism at the University of Toronto hospitals, 3 had hypercalcemia due to an abnormal and ectopic fifth parathyroid gland. Autopsy studies have shown that a fifth gland may be present in 3% to 5% of patients with hyperparathyroidism. The possibility of an abnormal fifth gland as the cause of primary hyperparathyroidism should be considered when four glands of normal size and histology have been found in the neck, and such a gland should be sought in all patients with the diffuse hyperplasia of secondary hyperparathyroidism. The fifth gland is usually in the lower neck or upper mediastinum, frequently within the thymus. If present, it can usually be recognized and excised.


Aspiration and gastroesophageal reflux.

Aspiration and gastroesophageal reflux. Gastroesophageal reflux is the commonest esophageal cause of chronic intermittent aspiration. The authors investigated 1000 consecutive patients with reflux with reference to their medical history, and by barium esophagography, esophageal manometry and pH studies. In patients with respiratory complications, chest roentgenography and pulmonary function tests were also performed. Of the total number, 279 patients aspirated either by coughing and choking during swallowing or as a result of night reflux; of these, 159 had associated respiratory symptoms, which included cough, voice change, recurrent respiratory infection, bronchiectasis and asthma. Of the patients with aspiration, 120 had surgical correction of reflux because conservative management failed. This form of reflux control improved the symptoms of cough and voice change and the condition of patients with recurrent infections or bronchiectasis, but alleviated the symptoms in only 8 of 28 asthmatic persons.


The anterior interosseous nerve syndrome. A review of the literature pertaining to the anterior interosseous nerve (AIN) syndrome revealed that the diagnostic criteria for this syndrome need to be defined. The authors describe the etiology of the AIN syndrome and use two cases of their own and 52 cases reported in the English literature to draw up a definition of the diagnostic criteria. The recommended criteria are: (a) demonstrable weakness of muscles innervated by the anterior interosseous nerve; (b) electromyographic findings of marked denervation potentials and decreased or absent voluntary motor unit potentials of these muscles; (c) operative evidence of entrapment of, or injury to, the anterior interosseous nerve; and (d) improved power in the muscles and reversal of the electromyographic changes on follow-up after operation.


Renal artery embolism: diagnosis and treatment. A 59-year-old woman presented with flank pain, atrial fibrillation and a nonfunctioning left kidney. A diagnosis of renal artery embolism was made and she was treated successfully by embolectomy. A review of the literature reaffirms the role of embolectomy, even in cases with delayed diagnosis.


Cake kidney with abdominal aneurysm.

Cake kidney with abdominal aneurysm. The authors describe a case of cake kidney occurring in association with a ruptured abdominal aneurysm with special reference to preoperative evaluation by angiography. They discuss the need to prepare these patients for possible in-vivo or ex-vivo renal manipulation during the removal of the aneurysm and the placement of the Dacron graft.


Interstitial pregnancy following ipsilateral salpingo-oophorectomy. A case of interstitial pregnancy, which occurred 12 years after ipsilateral salpingo-oophorectomy, was managed by cornual wedge resection. Internal (transuterine) migration of the fertilized ovum is the most probable explanation for this ectopic gestation. During the past 10 years three other cases of interstitial gestation have been managed at St. Michael's Hospital, Toronto, an incidence of 3% of all ectopic pregnancies seen at the hospital during that period.


Total replacement of the hip joint affected by Paget's diseases. In seven patients with Paget's disease involving the bones about the hip joint, associated degenerative changes of the joint caused such severe pain and disability that total hip replacement was necessary. The results were uniformly satisfactory and no serious complications were encountered.


The paramedic ambulance: a Canadian experience. Prehospital critical care provided by specially trained ambulance attendants in New Westminster, BC during a 27-month period was studied. Although the most important benefit of the improved care was the prevention of sudden death in a large proportion of persons with crises due to coronary artery disease, the skills learned to provide basic life support are applicable to a wide variety of other disorders that can result in death before the patient reaches hospital.


Calcium infusion and pentagastrin injection in diagnosis of medullary thyroid carcinoma. Calcium infusion and pentagastrin injection were compared as tests to stimulate calcitonin secretion for the detection of medullary carcinoma of the thyroid. Plasma concentrations of immunoreactive calcitonin were measured by radioimmunoassay before and during both stimulation tests in 2 persons who had been found at operation to have medullary thyroid carcinoma, 1 relative in whom a cervical lymph node biopsy had shown medullary thyroid carcinoma and 36 asymptomatic relatives. The tests were carried out on separate days by intravenous infusion of calcium gluconate for 2 hours, to provide 3.75 mg/kg of elemental calcium per hour, and rapid intravenous injection of 0.5 microgram/kg of pentagastrin. Before stimulation immunoreactive calcitonin was undetectable in the plasma of 34 of the 36 asymptomatic persons; the 2 with elevated baseline concentrations of the hormone had a positive response to both tests. Seven others showed an increase in plasma immunoreactive calcitonin concentration only after pentagastrin injection. The two persons with initially elevated values and three of the seven with increased values after pentagastrin injection were found at subsequent operation to have focal medullary carcinoma and parafollicular cell hyperplasia; after the operation immunoreactive calcitonin was undetectable in the plasma, even after stimulation. Rapid injection of pentagastrin is more reliable than slow infusion of calcium as a stimulation test for the early detection of medullary thyroid carcinoma.


Prinzmetal's angina, normal coronary arteries and pericarditis. A woman with Prinzmetal's variant angina had spontaneous attacks of myocardial ischemia characterized by severe chest pain, hypotension, inferior ST-segment elevation, transient complete heart block and selective right ventricular dysfunction. Despite initial improvement following intravenous administration of atropine and sublingual administration of nitroglycerin she died of cardiogenic shock. Autopsy showed normal coronary arteries and acute pericarditis, more pronounced over the right side of the heart. It is postulated that the pericardial inflammation elicited severe spasm of the subjacent right coronary artery.


Carbon monoxide poisoning and nonoliguric acute renal failure. Carbon monoxide poisoning in a 37-year-old man was complicated by neurologic damage, skin changes, muscle necrosis and nonoliguric renal failure. The relation between nontraumatic rhabdomyolysis and acute renal failure in carbon monoxide poisoning is reviewed. Recognition of the acute renal failure in such cases is important, for this complication can be fatal; the prognosis is excellent, however, if proper medical management is provided.


Air transport of infants in Newfoundland and Labrador. Air transportation of 33 infants in small unpressurized aircraft over long distances is described. Twenty-six of the infants were transported more than 320 km in environmental temperatures varying from -35 to +21 degrees C. A commercially available incubator was used. Although more than half the infants had a rectal temperature within the normal range at the time of arrival at hospital, 12 infants had rectal temperatures above 37.5 degrees C as a result of efforts to diminish heat loss. Adequate oxygenation of infants at 3000 m in unpressurized aircraft can be difficult. Cold and vibration can affect equipment, and at high altitudes the readings from oxygen analysers may not be true. The use of an expanded transport team, which includes experienced nonmedical personnel, is particularly important in these cases.


Preservation of pre-excitation despite acute myocardial infarction complicated by complete heart block. In a 53-year-old man with ventricular pre-excitation (normal PR interval, QRS interval of 0.12 seconds and delta-waves) acute inferior wall myocardial infarction was complicated by, successively, first-degree atrioventricular block, second-degree atrioventricular block (Wenckebach type) and complete heart block. The QRS pattern of pre-excitation was preserved throughout these events. The classification of ventricular pre-excitation is reviewed and the correlation between the various electrocardiographic patterns (the Wolff-Parkinson-White syndrome and its variants and the Lown-Ganong-Levine syndrome) and the anomalous conduction pathways of Kent, James and Mahaim are discussed. In this case the best possible explanation for preservation of pre-excitation during complete heart block was the existence of accessory fibres of Mahaim.


Hypophosphatemia associated with coma.

Hypophosphatemia associated with coma. In three cases of severe hypophosphatemia profound coma was associated. Although the occurrence of hypophosphatemia appeared to coincide with a high rate of intravenous administration of glucose and water, two of the three patients had liver disease and the other had hypothermia. In two instances the neurologic status improved with intravenous phosphate therapy. These case reports emphasize the importance of early recognition and treatment of profound hypophosphatemia in critically ill patients.


Diagnostic efficacy of tests for the detection of iron overload in chronic liver disease. The value of tests for the detection of body iron overload was investigated in 8 patients with clinically manifest primary hemochromatosis, 12 patients with cirrhosis and iron overload and 20 patients with liver disease and low or normal iron stores. Iron overload was defined as the presence of stainable iron in more than 50% of hepatocytes in a liver biopsy specimen. The percentages of patients with a true-positive (abnormal) or true-negative (normal) result were: serum iron concentration 65%, transferin saturation 85%, serum ferritin concentration 78%, serum ferritin:serum glutamic oxaloacetic transaminase (SGOT) index 78%, percent iron absorption 58%, percent iron absorption in relation to serum ferritin concentration 80% and percent iron absorption in relation to serum ferritin:SGOT index 93%. The calculated predictive value of a normal test result for the exclusion of iron overload in patients with liver disease, a group with an assumed prevalence of iron overload of 10%, was 98% to 99% for transferrin saturation and serum ferritin concentration used alone and 100% for these measures used together; the predictive value of an abnormal result for the diagnosis of iron overload was less than 50% for all of the above measures used alone or in combination. Hence, in patients with an increased serum ferritin concentration or transferrin saturation, or both, determination of the hepatocellular iron content of a specimen from a percutaneous liver biopsy is required for the diagnosis of iron overload.


Person-to-person transmission of Giardia lamblia in day-care nurseries. In an outbreak of giardiasis at two day-care nurseries in metropolitan Toranto Giardia lamblia appeared to be transmitted person to person. No common source of infection could be found. The proportions of children infected in the two nurseries were 39% and 17%; infection was spread to 7% and 23% of their household contacts. Of the infected children and household contacts 26% and 30% respectively of those for whom detailed information could be obtained were symptomatic. Canadian children were more likely to be infected and symptomatic than were immigrant children attending the nurseries. The most susceptible ages for infection were 1 to 3 years. The results of this study suggest that all children in day-care nurseries who are infected with G. lamblia should be treated, regardless of whether they are symptomatic.


The staging and treatment of epithelial ovarian cancer. Recent advances in the staging of ovarian cancer have suggested that many patients with apparently localized (stage I or II) disease have occult dissemination within the abdomen. Approximately 20% of patients classified at laparotomy as having stage I or II ovarian cancer are found by lymphangiography to have abnormal retroperitoneal lymph nodes. In many other patients advanced disease is also detected by peritonescopy; with this technique metastases are often discovered on the undersurface of the right diaphragm. These findings may help explain the high rates of recurrence after surgical resection or pelvic irradiation, or both, in patients with localized disease. Studies are in progress to determine whether modification of the radiotherapy field to include the right diaphragm will improve survival. Along with improved staging, histologic grading of the degree of anaplasia of the tumour tissue may permit more precise determination of prognosis and therefore better design of therapy. Adjuvant radiotherapy has not yet been shown to improve the survival of patients with stage I disease, but the 5-year survival of patients with stage II disease is greater for those receiving postoperative radiotherapy than for those undergoing surgery alone. For most patients with advanced disease radiotherapy is palliative only and carries a high risk of long-term complications. Numerous chemotherapeutic agents used singly can produce an objective response by tumour. Preliminary data suggest that combination chemotherapy can increase the rate of objective response, but a longer follow-up period is necessary to determine whether this form of therapy can improve survival.


Diagnosis of schizophrenia.

Diagnosis of schizophrenia. Case records of ninety consecutive first lifetime admissions with a hospital diagnosis of schizophrenia were examined for Schneiderian first rank symptoms, the Feighner diagnostic criteria, and the New Haven Schizophrenia Index. Diagnostic exclusion criteria were developed and applied. It is concluded that the hospital diagnosis of schizophrenia is likely to be too broad. Each diagnostic system can increase accuracy of diagnosis, but their exclusion criteria are too vague and the system would be improved by using those given here. Each diagnostic system selects similar groups of patients, and can be applied retrospectively to adequate case records.


University students, mental health and development. University students of the late 1960s and 1970s have been included in a study of factors affecting their mental health and academic functioning in many countries and cultures. Social change and intergenerational conflict were seen to be almost inseparable as social, economic and political concerns involve both students and their countries. Results of studies at Dalhousie University, six British universities, and the University of Singapore are examined in light of the socioeconomic problems existing at the time. High unemployment of university graduates, a growing factor in developing and developed nations, is pointed to as a major stress during a university education in the late 1970s.


The superior-mesenteric-artery syndrome: cause or complication of anorexia nervosa? The so-called superior-mesenteric-artery syndrome is not mentioned in psychiatric journals or books. Yet two variations of the condition have been described. In its acute form, it can be mistaken for psychogenic vomiting in anorexic patients, while its chronic intermittent form is readily misdiagnosed as anorexia nervosa. The case report is of a 16 year old boy admitted for investigation and treatment of severe weight loss. He initially responded to a modified behaviour program, but within days developed an acute small-bowel obstruction. Superior-mesenteric-artery syndrome was diagnosed and he improved with appropriate medical management. This condition needs to be considered by the psychiatrist who otherwise might not differentiate it from the symptoms of anorexia nervosa.