Saturating summation of the afterhyperpolarization conductance in spinal motoneurones: a mechanism for 'secondary range' repetitive firing. Summation of the potassium conductance (GK) changes underlying the spike afterhyperpolarization (AHP) has been studied in cat spinal motoneurones. Cells were directly activated by one to five short current pulses at constant rate, each evoking an action potential. The analysis was restricted to cells displaying an approximately exponential decay of the AHP conductance. In these neurones the AHP conductances given by successive spikes were found to summate in a non-linear manner. This nonlinear summation seemed well described by a neurone model based on modified Hodgkin-Huxley equations. From the model equations the total AHP conductance in motoneurones could be calculated from values of GK measured experimentally at different times during the summation process. Adaptation and steady-state firing in motoneurones are assumed to be governed by summation of AHP conductance. The same model was then utilized for simulating neuronal repetitive firing in response to current steps. Such simulations were performed after substitution of the model parameters with values measured in individual motoneurones which had also been fired repetitively by intracellular injection of long-lasting current steps. The amount of adaptation and the shape and slopes of the steady-state frequency-to-current relation were found to coincide in the model and in the corresponding motoneurones.


Effects of intraventricular injections of norepinephrine on brain-pituitary-ovarian function in the rabbit. In estrous estrogen-primed female rabbits with electrodes chronically implanted in various subcortical regions of the brain, the intraventricular injection of an ovulation-inducing dose of norepinephrine (NE) stimulated a prolonged episode of high amplitude 40-60 cps electroencephalographic (EEG) activity in the olfactory bulb (OB) and its projections. This activity, which started usually between 30 and 60 min after NE injection and was maintained continously for periods up to an hour thereafter, was regularly absent in the same rabbits when they were pseudopregnant and non-ovulatory to NE. Similar OB-EEG activity and ovulation had been observed earlier in response to intraventricular histamine under light pentobarbital anesthesia. The ovulatory response to histamine was eliminated by massive midbrain lesions or removal of the olfactory bulb, but intraventricular NE still induced ovulation after such losses. The ovulatory effectiveness of NE was blocked, however, by low doses of pentobarbital or high doses of atropine, neither of which inhibited the ovulatory response to intraventricular epinephrine. Atropine and alpha-adrenergic blocking agents also prevented the ovulatory response to intraventricular histamine. It is suggested that histamine activates pituitary-ovarian function by stimulating central noradrenergic elements and that NE has more of the physiological-pharmacological characteristics of a natural central nervous activator of luteinizing hormone-releasing hormone than has epinephrine.


Postnatal development of retinogeniculate, retinopretectal and retinotectal projections in the opossum. The postnatal development of retinogeniculate, retinopretectal and retinotectal projections has been studied by the anterograde transport of proline-labeled proteins in 20 pouch young opossums aged from 10 to 60 days. Radioautographical findings suggest delayed development of uncrossed as compared to crossed projections. There is a phase of overlapping projections from both eyes in thalamic and tectal target sites. Partial segregation of projections to the dorsal lateral geniculate nucleus (GLD) is preceded by differential distribution of crossed and uncrossed terminal fields along its dorsoventral axis (at age 23 days). The quasilaminar pattern of projections in the dorsocaudal region of GLD pars alpha is incipient by 42 days and is fully established at 60 days of age, as eye opening starts. The mature pattern of projections to the ventral lateral geniculate nucleus (GLV) is established much earlier, at 23 days of age. The development of retinopretectal projections is assessed mostly from the analysis of the olivary pretectal nucleus (PO). Distribution of silver grains into discrete areas coextensive with PO is relatively delayed (by 23 days of age) as compared to the nuclei of the lateral geniculate body. Soon after, however, the mature pattern of projections to PO is established (at 33 days of age). The early development of retinotectal projections (from 10 to 23 days) is compatible with an initial tangential course of crossed optic fibers in the superior colliculus (CS) but other alternatives remain open, such as a sequential outside-in arrangement of terminal fields of deeply coursing fibers. Arborization of uncrossed fibers is delayed at extreme rostromedial and caudolateral portion of the territory of the main uncrossed retinotectal projection. Segregation of uncrossed projections at different depths of CS is nearly complete by 42 days. Differences in the development of terminal fields in different target nuclei or in regions of a given target site are discussed in relation to retinal and local factors.


Postnatal hippocampal granule cell agenesis in the rat: effects on two types of rhythmical slow activity (RSA) in two hippocampal generators. Hippocampal slow wave activity was studied in rats which were normal or had been subjected to denate gyrus granule cell agenesis by focal X-irradiation starting at birth (0-day group) or two days (2-day group) of age. X-irradiation reduced adult brain weight, abolished most (2-day) or all (0-day) granule cells in the lower (endal) blade of the dentate gyrus, and reduced granule cell density by up to 70% in the upper (ectal) blade of the dentate gyrus. X-irradiation did not affect pyramidal cells of the hippocampus proper. Tracking with microelectrodes in urethane anesthetized rats given eserine, sensory, or brain stimulation showed two foci of hippocampal rhythmical slow activity (theta or RSA), one in stratum oriens of CA1 and one in stratum moleculare of the dentate gyrus. These were opposite in phase by approximately 180 degrees and separated by a null zone and phase reversal point occurring at stratum radiatum. There were no significant differences in the amplitude, frequency, null, or phase reveral points in the normal or X-irradiated groups. However, the width of the RSA amplitude peak in the ectal blade was reduced, correlated with the reduction in the length of the ectal blade, and the RSA amplitude peak in the lower blade was absent, correlated with the absence of the lower blade. The fast activity recorded in the hilus of normal rats was absent in the X-irradiated groups. RSA recorded during spontaneous movement (walking) had identical amplitude, frequency, anatomical foci, and phase in both the hippocampus proper and dentate gyrus in normal and X-irradiated rats. Antimuscarinic, but not antinicotinic, agents abolished anesthesia-related RSA, but not movement-related RSA, in all groups of rats. The results are discussed in terms of their relevance to the two-generator hypothesis of RSA.


Dopamine receptors and ergot drugs. Evidence that an ergolene derivative is a differential agonist at subcortical limbic dopamine receptors. The actions of a new type of ergolene derivative, MPME ((5R, 8R)-8-(4-p-methoxyphenyl-1-piperazinyl methyl)-6-methylergolene), have been evaluated on central catecholamine (CA) neurons in the rat by means of a combined biochemical, histochemical and behavioural analysis. The evidence suggests that this ergolene derivative is a preferential agonist at subcortical limbic dopamine (DA) receptors and at DA receptors belonging to the neostriatal DA islands. (1) MPME does not change the DA and noradrenaline (NA) levels 4 h after the injection in doses ranging from 0.1 to 5 mg/kg. MPME significantly reduced DA turnover in doses from 0.5 to 5 mg/kg, whereas the NA turnover was increased in the same dose range. (2) Histochemically, using quantitative microfluorometry, DA levels were unchanged, except in the islands of the nucleus caudatus following administration of MPME. The drug selectively reduced DA turnover in the subcortical limbic regions (tuberculum olfactorium and nucleus accumbens) and in the DA terminal islands of the nucleus caudatus in doses of 1-5 mg/kg, whereas the large diffuse DA terminal systems of the nucleus caudatus were unaffected. Using this ergolene derivative the islandic small neostriatal DA system can be excellently demonstrated also in the adult rat. The effects of MPME on DA turnover, are blocked by haloperiodol but not by methergoline (which blocks 5-HT receptors). (3) Studies on uptake of tritiated DA in the nucleus caudatus and tuberculum olfactorium reveal a weak inhibition of DA uptake and retention only in high concentrations (10(-5)-10(-6) M). Such actions therefore can probably not explain the changes in DA turnover observed. (4) Behavioural effects of MPME were evaluated in the rotometer model of Ungerstedt25. This model will reveal actions on supersensitive striatal DA receptors. MPME was found to mimic the action of apomorphine and cause a prolonged rotational behaviour towards the nonoperated side in doses of 0.25-0.5 mg/kg. A marked potentiation of the action of MPME was obtained by means of pretreatment with phosphodiesterase inhibitors suggesting that the effect of MPME might be mediated by cyclic AMP. Studies with the DA receptor blocking agent pimozide indicated a high affinity of MPME for the supersensitive striatal DA receptors, since only very high doses of pimozide (15 mg/kg) were capable of blocking the actions of MPME. (5) Studies on the effect of MPME on DA sensitive adenylate cyclase in the nucleus caudatus and the subcortical limbic system (mainly tuberculum olfactorium and nucleus accumbens) suggested that MPME is a partial DA receptor agonist with different intrinsic activity on the DA receptors of the subcortical limbic system and of the nucleus caudatus, the effects in the subcortical limbic system being considerably larger than in the nucleus caudatus. Thus, the present paper gives evidence that the various DA receptor populations in the brain are sufficiently different to allow their preferential activation by drugs.


Independent masculinization of neuroendocrine systems by intracerebral implants of testosterone or estradiol in the neonatal female rat. Small pellets of testosterone (T) or estradiol (E2), but not cholesterol (CH), when implanted into the brain of neonatal female rats on day 2 or day 5 of life, produce masculinization of the adult regulation of gonadotropic hormone (GTH) release, female sexual behavior or masculine sexual behavior, specific to the site and time of implantation and the hormone implanted. Site specificity: There appear to be specific neuronal sites where implantation of T or E2 produces independent masculinization of GTH, female sexual behavior or masculine sexual behavior patterns. Implants of T or E2 placed in the dorsal preoptic area (POA) perinatally increase the amount of masculine sexual behavior displayed by adults. On the other hand, the ventromedial hypothalamus (VMH) is the only area in which neonatal implants of T or E2 produce GTH acyclicity in adults. Female sexual behavior is affected in opposite directions by hormonal implants in two different areas. Neonatal implants of T or E2 in the POA increase adult behavioral responsiveness to estradiol benzoate (EB) alone, whereas implants in the VMH decrease adult responsiveness to EB plus progesterone therapy. Temporal specificity: The most effective time for augmenting masculine sexual behavior is before day 5, since hormone implants on that day produce marginal effects on male sexual behavior, whereas day 2 implants in POA results in substantial increases in both mount and intromission patterns. GTH release in masculinized equally well by implants of hormones on either day 2 or day 5. Female sexual behavior is affected only by neonatal implants on day 2. Hormone specificity: Estradiol is as effective as T in masculinizing all three neuroendocrine parameters. In any particular neural site in which T implants produce an alteration in the neuroendocrine response, a similar effect is produced by E2 implants in the same site. It is suggested that independent masculinization of GTH, female sexual behavior and masculine sexual behavior patterns is produced by the action of T and/or E2 on separate neural areas, and that these neural areas may be susceptible to the action of hormones at different times.


Prosencephalic pathways related to the paleostriatum of the pigeon (Columba livia). Afferent connections of the avian paleostriatal complex were traced by means of anterograde and retrograde transport of horseradish peroxidase (HRP). The paleostriatum augmentatum (PA), a cell field comparable to mammalian caudate nucleus and putamen, was found to receive projections from a distinct population of elencephalic neurons in the temporal-parietal-occipital (TPO) and lateral cortical (CDL) areas of the neostriatum. TPO neurons, in turn, were found to receive projections from the contralateral ventral archistriatum (Av) and from neurons in the ipsilateral frontal neostriatum adjacent to the rostral portion of the ectostriatum (e). the paleostriatum primitivum (PP), comparable to globus pallidus, receives projections from the small cells of PA, and from neutrons in the anterior nucleus of the ansa lenticularis (ALa). ALa appears similar to the mammalian subthalamic nucleus on the basis of its afferent and efferent connections. In addition, PA was also found to receive extensive projections from the nucleus tegmenti pedunculopontinus of the midbrain, a dopamine-containing cell group. Evidence of projections from the nucleus dorointermedius posterior (DIP), a cell group receiving both cerebellar and paleostriatal afferents, to the rostral telencephalon was also found.


Identification of the cells of origin of a central pathway which sprouts following lesions in mature rats. Following unilateral destruction of the entorhinal cortical region of the adult rat, the denervated granule cells of the dentate gyrus are reinnervated as a result of the proliferation of a pathway from the surviving contralateral entorhinal area. The present study investigates the cells of origin of this lesion-induced pathway. Following HRP injections into the reinnervated dentate gyrus, heavily labeled cells were evident in layers II and III of the contralateral entorhinal area, in marked contrast to the pattern of labeling in normal animals, where labeled cells are restricted almost entirely to layer III. The atypically labeled cells in the operated animals were found predominantly in the dorsal half of the entorhinal area, and were concentrated in the medial most portion of layer II. These atypically labeled cells in layer II of the operated animals were an average of 16% larger than their unlabeled neighbors in the same lamina. This was not related to the loading with HRP, however, since in normal animals, cells in layer II which are labeled with HRP were no different in size than unlabeled cells. The atypically labeled cells in layer II of operated animals could also be identified at the electron microscopic level, and could be distinguished from the cells in layer III which normally project to regio superior of the contralateral hippocampal formation. While labeled cells were evident in layers II and III following injections into the reinnervated dentate gyrus, no labeled cells were found in the presubiculum or parasubiculum. In combination, these results suggest (1) the pathway which reinnervates the dentate gyrus from the contralateral entorhinal area originates predominantly, if not exclusively, from the cells in layer II, (2) these cells in layer II have the same preferential distribution within the entorhinal area as the rare lightly labeled cells which can be found contralateral to an injection in normal animals and (3) cells which participate in the reinnervation are larger than their unlabeled neighbors which presumably do not give rise to fibers which reinnervate the contralateral dentate gyrus. Since the cells in layer II which sprout following lesions can be identified at both the light and elctron microscopic level, a potentially valuable model system is available in which to analyze cellular changes during sprouting.


Abnormal recrossing retinotectal projections after early lesions in Syrian hamsters: age-related effects. If the superficial layers of the right superior colliculus (SC) of a newborn hamster are removed, fibers from the left eye not only terminate in the surviving deeper layers of the right SC, but also cross the tectal midline and terminate in the medial third of the left SC. If the right eye is also removed at birth, the abnormally recrossing fibers from the left eye will spread over the entire surface of the left SC31. In this series of experiments, we ablated the right SC of hamsters at birth, but enucleated the right eye on different days postnatally in order to examine the spreading of the axon terminal pattern as a function of age. When the animals were young adults, the pattern of retinofugal projection of the left eye was traced using the Fink-Heimer technique or with autoradiography. It was found that the projections from the left eye continue to spread over the entire left SC when the right eye was removed up until day 10, though their distribution was more sparse when the eye was removed on days 7-10 than when it was removed on days 0-6. When the removal of the right eye was delayed until day 12, the lateral spreading of recrossing axons was markedly reduced. When the right eye was removed on day 14, the distribution of the projections from the left eye was restricted to the medial third of the left SC, just as if no early eye removal had been performed. It appears that after a critical age is reached, even when terminal space is available the axons and axon terminals will not move, at least not over any appreciable distance.


Replacement of receptor neurones after section of the vomeronasal nerves in the adult mouse. Eight days after vomeronasal nerve section or removal of the accessory olfactory bulb, the majority of receptor cells of the vomeronasal neuroepithelium degenerate and disappear, leaving a regular framework consisting of supporting cells and their radial processes. The cell clusters at the boundaries of the epithelial sheet (which have been shown to be actively dividing in the normal, unoperated adult mouse) are also spared. The epithelium is subsequently repopulated by receptor cells appearing first in the basal part of the receptor cell layer and later occupying the full width of the receptor layer. These cells are anatomically fully differentiated receptor cells with normal sensory dendrites. Their axons form conspicuous intraepithelial neuromatous masses. Administration of [3H]thymidine on days 10-20 postoperatively labels some clusters of supporting cells and virtually all of the receptor cells, indicating that the repopulation of the epithelium is due to new formation of receptor cells.


Electrophysiological evidences of mutual modulatory influences on the retinal activity of the crayfish Procambarus bouvieri (O). Electroretinographic evoked potentials (ERGs) were recorded in dark adapted crayfish by the application of pulses of light (0.09 Cd/ft2) presented every 2.5 min. Heterolateral illumination (HI) for sixty min (0.06-0.3 Cd/ft2) induced up to 50% decrease in ERG after a latency of 12-25 min. ERG depression was proportional to the intensity of HI and also showed a circadian rhythm. During the alpha phase the ERG recovery started 3-10 min after HI was turned off. In contrast it started only after 10-20 min during the rho phase. The time course of the ERG depression, which was abolished in splitbrain animals, strongly suggests that a mutual modulatory influence, probably of neuroendocrine nature, is present in the crayfish visual system.


Space-time correlations of neuronal firing related to memory storage capacity. Most viable theories of memory require some form of synaptic modification dependent on the correlation of pre- and postsynaptic neuronal firing (which we will denote as the Hebb hypothesis). We show here that a possible consequence of this hypothesis is that the storage capacity of a network of highly interconnected neurons is related to the number of synapses and that this implies that the network can be excited into many different time sequence of firing patterns of assemblies of neurons. The important role played by the assembly (as defined by E. R. John) is discussed in detail. A modified Hebb hypothesis is proposed. The crucial experiments to test the model involve the use of two (or more) extracellular microelectrodes to record, simultaneously, the firing activity of several neurons and thus determine the spatial and temporal cross correlations after presenting a mature animal with a variety of stimuli.


Effect of visceral afferent activation on leg extension induced by sciatic afferent stimulation. In cats under light chloralose and sodium pentobarbital anesthesia the effects of electrical stimulation of various visceral afferent nerves on leg extension induced by sciatic afferent stimulation were studied. Stimulation of the central end of the cervical vagus and stellate ganglion produced inhibition of induced leg extension while stimulation of the distal end of the thoracic vagus, coeliac ganglion, and splanchnic nerves produced facilitation. Decortication slightly reduced the inhibitory effect and greatly reduced the facilitatory effect. Additional decerebration greatly reduced the inhibitory effect and almost abolished the facilitatory effect. Spinal transection at C1 completely abolished the inhibitory and facilitatory effects on induced leg extension. These results suggest that visceral afferents facilitate sciatic induced leg extension principally through the cortex while they inhibit extension through the midbrain and hypothalamus.


Elevations in nociceptive thresholds following locus coeruleus lesions. Serotonin depletion or lesions of the midbrain dorsal raphe nuclei attenuate both morphine-produced and stimulation-produced analgesia. In contrast, norepinephrine depletion enhances both types of analgesia. To extend these findings, the effects of destruction of the noradrenergic locus coeruleus (LC) upon nociceptive flinch-jump thresholds were investigated. after four preoperative baseline sessions, lesions were placed in the LC bilaterally and nociceptive thresholds were determined for up to five weeks postoperatively. The lesions were localized by monoamine histofluorescence procedures together with conventional histological staining techniques. In 9 of 13 animals, the LC or its ascending dorsal noradrenergic bundle sustained either bilateral or unilateral damage, evidenced by green fluorescent back-up caudal to the lesions. Eight of these animals demonstrated significantly increased jump thresholds. In the remaining four animals, both lesions spared the LC and nociceptive thresholds were either unchanged or significantly decreased. In three of the four, raphe damage was noted, evidenced by yellow fluorescent back-up. The results suggest apparently contrasting roles of norepinephrine and serotonin in nociception.


The influence of the conventional microflora on the body temperature of the chick. 1. Deep body temperature was measured daily in germ-free and conventional chicks from 1 to 16 of age. 2. The temperature of germ-free chicks rose rapidly during the first 4 d and thereafter only slowly, whereas that of conventional birds increased gradually throughout. 3. Body temperature attained by the germ-free birds was about 0.3 degrees C higher than that of conventional birds.


Maternal effects on embryonic and postembryonic growth in poultry. 1. It was found that the environment determined by the hen, namely protein, fat and moisture, had no effect on the growth of the embryo during the first 14 d of development. 2. The amount of protein available influenced growth during the last week of incubation but the amount of fat and water had no effect. 3. The regression of embryo on egg weight for the pooled data of large (mean 62 g) and small (53 g) eggs was 0.85 +/- 0.06 at day 20. 4. Embryos from large eggs were significantly heavier than those from small eggs on day 20: this difference persisted to the end of the experiment at 56 d of age when it had increased to 100 g. 5. A 1-g difference in egg weight was reflected in about a 10-g difference in chick weight at 56 d of age.


Taste responsivity of amygdaloid units in behaving rabbit: a methodological report. A technique is described for studying unit electrophysiology of taste in the behaving animal. Preliminary observations on response patterns by amygdaloid units to four putative basic types of taste qualities (represented by sucrose, saline, acid, and quinine), which also vary in motivational properties, revealed evidence of units with exclusive or highly differential response to either sucrose or saline in food-deprived animals. Small quantities (0.3 ml) of these palatable tastants injected intra-orally evoked neural responses lasting 5-8 sec that did not relate directly to the characteristics of the oro-lingual reaction as detected electromyographically; such sensorimotor relations were found in units sampled in the globus pallidus. Some amygdaloid units displayed differential excitatory and inhibitory modes of response to different tastants. Other cells exhibited more phasic patterns of response lasting 1-2 sec to 2 or more tastants, including unpalatable acid and quinine. The results underscore the sensitivity of the technique to stimulus parameters of taste-processing, which is basic to the study of all neurobehavioral functions of taste stimuli.


Endogenous uric acid and urea metabolism in the chicken. 1. Four chickens were used in nine successive experiments using a single injection radioisotope dilution technique to study the kinetics of endogenous uric acid and urea metabolism. 2. Starvation lowered uric acid and urea entry rates, but elevated the extent of degradation of these compounds. 3. Urea turnover time and the extent of urea pool degradation were higher, and urea excretion rate was lower than that of uric acid. 4. In colostomised chickens, the extent of uric acid and urea degradation were lower than in non-colostomised birds. 5. The average uric acid and urea entry rates in chickens fed on a diet containing 200 g protein/kg were 7.32 and 2.6 mumol/h g liver, respectively. 6. It is concluded that the contribution of uric acid and urea to the nitrogen economy of the birds is negligible.


Mesencephalic multiple-unit activity during acquisition of conditioned pupillary dilation. Multiple-unit recordings were obtained from the interstitial nucleus of Cajal, nucleus of Darkschewitsch and the superior colliculus of the cat during acquisition of classically conditioned pupillary dilation. Multiple-unit responses in all regions were enhanced by conditioning procedures. However, only the acquisition functions for the accessory oculomotor nuclei, i.e., interstitial nucleus of Cajal and nucleus of Darkschewitsch, were significantly correlated with the acquisition of conditioned pupillary dilation. These results were discussed in relation to the mechanism of autonomic control of conditioned pupillary dilation. It was concluded that inhibition of parasympathetic pupillomotor efferents via the accessory oculomotor nuclei may play a role in the acquisition of conditioned pupillary dilation.


Construction of wire leads and electrodes for use in slow wave recording in small animals. Techniques are described for the construction of wire electrodes and leads for use in recording slow wave activity in chronic animal preparations. Advantages of the technique include durability, lightness and absence of significant interference with animal movement.


Effect of restraint upon hypothalamic and adrenal catecholamines in Japanese quail. 1. Changes in catecholamine concentration after periods of restraint up to 48 h in male Japanese quail have been measured. 2. Hypothalamic catecholamines decreased after 10 min restraint. Dopamine concentration increased after 4 h and persisted to 48 h. 3. Plasma catecholamines increased after 10 min, remained high for 2 h and then decreased despite continuing restraint. Catecholamine content of adrenals slightly decreased during restraint. 4. The activity of adrenal phenylethanolamine-N-methyl transferase increased from the 4th hour of restraint.


Transient heterosynaptic depression in the hippocampal slice. Two independent, excitatory, monosynaptic afferent fiber systems projecting onto basal and apical dendritic layers of the CA1 sub-field of the hippocampus were tested for interactive effects. Long-term potentiation of either of the pathways was accompanied by a transient depression in the other pathway. Similar transient depression could be elicited by antidromic stimulation of the CA1 cells. No long-term heterosynaptic effects were observed.


Entrainment of oviposition in the fowl using light-dark cycles. 1. Fourteen experiments were performed to determine the minimum photoperiod and minimum scotoperiod needed for entrainment of oviposition in hens exposed to 21-h, 24-h and 30-h cycles. Entrainment was measured by the proportion of total eggs laid in a modal 8-h segment of each cycle. 2. In a 24-h light and dark cycle, a 15-min photoperiod or a 5-h scotoperiod produced essentially the same degree of entrainment as 6 h light, 18 h darkness (6L : 18D) or 14L : 10D, which were used as control treatments. Under 21-h light and dark cycles a minimum 3-h photoperiod or a minimum 9-h scotoperiod was needed to achieve full phase setting. When the cycle length was increased to 30 h a minimum 8-h photoperiod or a minimum 12-h scotoperiod was required for full entrainment. 3. This study demonstrates that photoperiod is a stronger signal than scotoperiod for the purpose of phase setting oviposition. It also shows that a stronger signal is required to achieve entrainment when the length of the light-dark cycle is several hours shorter or longer than the natural period of 24 h.


Entrainment of oviposition in the fowl using bright and dim light cycles. 1. Nine short trial, involving 96 different treatments, were used to investigate the critical intensities and duration of bright and dim periods of lighting needed to entrain oviposition in cycles ranging from 21 to 30 h. 2. Entrainment was shown to depend upon the contrast between bright and dim lighting, and to be independent of the absolute light intensity. 3. A bright: dim ratio of 13:1 fully entrained oviposition in cycles of 25 h and 27 h. For 23-h and 28-h cycles a 30:1 ratio was required. Twenty-one-hour cycles required a ratio of 300:1 and with 30-h cycles a ratio of 1000:1 was needed to achieve full entrainment of oviposition. 4. In 24-h cycles, 1 h of bright lighting at 02.00 h was sufficient to override other environmental signals and cause eggs to be laid in the late evening, but a minimum bright period of 6 h was needed to cause full phase setting with 21-h cycles. 5. Circadian periodicity can easily be imposed on hens by providing a short exposure to bright light with a background of continuous dim light; but the signal must be increased (by providing a greater contrast between bright and dim lights and/or a longer period of bright lighting) to entrain oviposition when the cycle deviates markedly from the natural period of 24 h.


Acetylcholine content in different regions of the rat brain. Acetylcholine content of different rat brain regions was measured. A correlation between acetylcholine content and cholineacetyltransferase (ChAc) activity in discrete brain regions was found. However there are regions such as cerebellar nuclei, cerebellar hemisphere, caudal medial forebrain bundle, zone incerta, nucleus vestibularis lateralis where the acetylcholine content is relatively much higher than the ChAc activity, and regions such as n.cochleares, n.motor n.V., N.motor N.VII., n.motor, n.XII where ChAc activity was high and the content of acetylcholine is relatively low.


The relative importance of sunrise and sunset for entrainment of oviposition in the fowl. 1. A series of four "sunset" signals, without associated sunrises, was given to laying hens by reducing light intensity in steps from 190 lx to 63, 21, 7 and 2 lx at 24-h intervals. Four "sunrises" were given by reversing the process. Treatments involving single "sunrises", single "sunsets" and combinations of sunrises and sunsets at 12-h intervals were also tested. 2. Only treatments which included one or more sunset signals were found to give full entrainment of oviposition, as judged by the proportion of eggs laid in a modal 8-h segment of each 24-h cycle. Full entrainment was achieved if the sunset occurred between 16.00 h and midnight, but not if the sunset occurred in the morning hours. Treatments involving only sunrise signals did not fully entrain oviposition but did have effect on the timing and distribution of ovipositions. Sunrises given in association with sunsets increased the degree of entrainment achieved, as compared with the sunset signal alone. 3. This study indicates that sunset is a potent synchronising agent for phase setting oviposition and, presumably, for phase setting the endogenous circadian rhythm of the fowl. Sunrise can also exert a modifying influence.


The effect of growth retardation and of osteomalacia on the uptake of albumin by bone. 125I-labeled rat albumin injected intravenously into rats was taken up by growing bone. Some of this radioactive albumin could be removed from bone by washing with saline, the proportion so removed decreasing from 82.5% at 1 day to 7.4% at 8 days. Both the total radioactivity, and that remaining in bone after saline wash, were reduced when growth was slowed by alteration or restriction of the diet. Although the amount of 125I albumin in rachitic bone was reduced, autoradiography showed that radioactivity was present in rachitic osteoid. Immunoprecipitation using anti-rat-albumin serum showed that about half of the radioactivity released from normal bone by EDTA was still attached to albumin. These results suggest that albumin plays some part in the growth of bone.


The crystal sheaths from bivalve hinge ligaments. The aragonite crystals in the molluscan bivalve hinge ligament are surrounded by an organic sheath which is distinct from the remainder of the ligament matrix. Methods have been developed to isolate these sheathed crystals from the ligaments of Spisula solidissima and Mercenaria mercenaria employing a papain digestion of the matrix protein. The sheathed crystals from Spisula have a CaCO3/protein ratio of 11.1 and those from Mercenaria a ratio of 29.6. The sheathed crystals and the empty crystal sheaths have been examined by electron microscopy for structural integrity. The sheath proteins exhibit much smaller proportions of the amino acids glycine and methionine than the hinge ligaments. These are characteristic amino acids of high concentrations in the hinge ligaments of both species. The concentrations of acidic and basic amino acids are increased about two fold in the sheaths over those of the ligaments. Otherwise there is little similarity in the amino acid composition of the sheaths in the two species. However, SDS electrophoresis shows the sheaths of both to contain a major protein component with a molecular weight of about 25,000. The sheath protein from the Mercenaria ligament contains about 5% carbohydrate and that of Spisula sheaths less than 1% carbohydrate.


Prostaglandin PGE2: a possible mechanism for bone destruction in calcinosis circumscripta. A patient showed evident osteolysis in phalanges and heavy periarticular calcium deposits of the fingers, wrists and toes which avidly took up 47Ca. The dense, white, tooth-paste like fluid contained in the periarticular calcium deposits has been studied by two different X-ray diffraction methods, by Ubatuba's bioassay for prostaglandin, by thin layer chromatography and by mass spectrometry. The calcium deposits were hydroxyapatite and prostaglandin PGE2 was detected in them. The bone resorption stimulating activity of PGE2 would be expected to result in increased bone destruction with release of calcium salts and this could be a working hypothesis of the pathogenesis of calcinosis circumscripta.


Failure of heterotopic osteogenesis by epithelial mesenchymal cell interactions in xenogeneic transplants in the kidney. Transitional epithelium of the guinea pig and rabbit and an established WISH cell line, when grafted under the kidney capsule of cortisone treated mice, survived and proliferated, but never induced bone formation. On the contrary, when grafted intramuscularly into the same recipients, readily induced cartilage and/or bone.


Scanning electron microscopical study on the fluorosis of enamel in rats. Sixteen 28-day-old male rats of Wistar strain, with a mean body weight of 179 g, were divided into two equal groups. Each group of eight animals was maintained for 70 days on drinking water, ad lib., containing no fluorine (control group) and 100 ppm of fluorine (experimental group). All specimens examined were obtained from the incisal portions of the incisors. The following types of enamel specimens were prepared for scanning electron microscopy: (1) acid-etched specimens; (2) acid-etched specimens followed by low temperature microincineration; and (3) fractured specimens. The enamel formed during high fluoride exposure showed marked hypocalcification, that is, the crystallite density in the prism core and interprismatic region was lower than that of control animals. The organic substances appeared to increase in these regions. The changes were prominent in the outer and middle enamel layers. Such changes following fluoride administration appear to indicate an inhibition of enamel maturation, that is, an inhibition of the mineral deposition and/or an inhibition of organic matrix withdrawal.


Influence of phenobarbital and diphenylhydantoin on the healing of rickets in the rat. Male weanling Sprague-Dawley rats were administered phenobarbital or diphenylhydantoin (phenytoin, dilantin, DPH), or a combination of the two drugs, while receiving a high calcium, low phosphorus vitamin D-deficient diet. A Line Test evaluation for calcification of the distal end of the radius was performed to determine the presence of rickets and the healing of the disease. After a period of 16 days, rickets had developed in a uniform manner in all groups regardless of drug treatment. Four I.U. of vitamin D3 were then administered to each animal and they were sacrificed either 3 or 9 days later. Three days after the administration of D3, bone calcification had started in all groups, with the greatest response being observed in the control group. Nine days after D3 administration, bone calcification was clearly impaired in PB and PB-DPH treated animals and slightly impaired in the DPH treated group when compared to controls. Weight gain was also impaired after PB and combined PB-DPH treatments. Based on these observations, it is suggested that anticonvulsant drugs, and in particular PB, inhibit, in a yet undetermined fashion, the normal calcification of the growth cartilage which accompanies a single physiological dose of cholecalciferol in the rat.


Recharacterization of fungal dinucleoside polyphosphate (HS3). Three polyphosphorylated dinucleosides given the pseudonyms of HS3, HS2, and HS1 that were erroneously described as diguanosine polyphosphates (LéJohn, H. B., Cameron, L. E., McNaughton, D. R. & Klassen, G. R. (1975) Biochem, Biophys, Res, Commun. 66, 460-467) have been repurified and partially recharacterized. They have proved to be extremely complex molecules; chemical (HCl and KOH hydrolysis), physical (ultraviolet-light spectral analysis and ion-exchange chromatography), and enzymic (nucleotide pyrophosphatase and bacterial alkaline phosphatase hydrolysis) studies showed that (i) all three HS compounds are uracil rich and (ii) only HS3 contains a purine nucleoside and glutamate. The partial structure of HS3 was deciphered as a moiety of ADP--sugar X--glutamate (the mode of attachment of glutamate is obscure) that is covalently linked to another moiety composed of UDP, mannitol, and four phosphates. Sugar X had chromatographic characteristics of ribitol, but the chromatographic isolate also contained a ninhydrin-sensitive entity presumed to be an amino group. Sugar X, THEREFore, may be an amino sugar polyol. Only the general chemical compositions of HS2 and  HS1 were determined. Each contained two uridines and HS2 had 10 phosphates whereas HS1 had 12.


Glucose transport in Achlya: characterization and possible regulatory aspects. The freshwater fungus Achlya transported D-(+)glucose (glucose) and 2-deoxy-D-glucose (deoxyglucose) by an energy-related system. Their transport4 was inhibited by uncouplers of metabolic energy such as 2,4-dinitrophenol, cyanide, azide, and carbonylcyanide-p-chlorophenylhydrazone. Besides inhibiting each other, glucose and deoxyglucose transport was inhibited by D-(+)galactose, D-(+)mannose, and D-(+)xylose. Many other sugars tested failed to inhibit glucose transport implying a certain degree of specificity. Glucose transport was pH (optimum at 6.5) and temperature (optimum at 30-40 degrees C) dependent. Glucose transport was also inhibited by citrate, N6-substituted adenines (cytokinins), and iodine. None of these agents penetrated the cell membrane within the brief (1-3-min) period in which glucose transport was measured. In every case, transport was inhibited within 10 s (the shortest time in which measurements could be made). When cells were osmotically shocked to release a cell-wall membrane phosphorylated proteoglycan (PPG), they became incapable of transporting glucose for several hours until new PPG material was reisolable from the membrane by osmotic-shock treatment. The osmotically shocked cells could not transport glucose or deoxyglucose. No glucose-binding protein was detected in the shock fluid. Practically all of the glucose transported within 1-2 min was recovered as glucose-6-phosphate. No other phosphorylated sugar was detected suggesting that glucose may be phosphorylated in transport. Related studies have shown that citrate removed calcium bound by PPG; N6-substituted adenines were bound by PPG while three polyphosphorylated dinucleosides, HS3, HS2, and HS1, were displaced from it. Iodine formed stable complexes with the HS compounds. All of these agents inhibited glucose transport without entering the cell. It is therefore possible that HS compounds, calcium and PPG may be involved in maintaining the cell membrane in proper form for glucose transport.


Age, breed and seasonal patterns in the occurrence of ten dairy cow diseases: a case control study. A total of 5,990 occurences of the diseases abomasal displacement, cystic graafian follicles, endometritis, hypocalcemia, ketosis, mastitis, metritis, ovarian hypofuction, pyometra and retained placenta were included in a case control study. The study was based on a hospital population of Holstein, Ayrshire, Guernsey and Jersey cows who were at least two years of age. The data were retrieved from computer storage of material abstracted for the Veterinary Medical Data Program. The transcription of data from original case records to these abstracts was examined as a source of error. An attempt was made to define each of the diseases by reference to random samples of the clinical records. Using the log-odds method, trends were noted for the youngest cows to be at increased risk of the reproductive diseases and for the Guernsey cows to be at increased risk of the uterine diseases. There was a tendency for peaks in disease occurrences in the winter (as opposed to summer) months.


Bovine allergic pneumonitis: an acute outbreak associated with mouldy hay. An outbreak of acute bovine atypical interstitial pneumonia is reported in association with feeding mouldy hay. Results of serological investigation and of provocation challenge indicated a hypersensitivity pneumonitis due to allergens of Micropolyspora faeni. Macroscopic and microscopic pulmonary changes were predominantly those of oedema and emphysema. These lesions were contrasted with more chronic changes reported in allergic pneumonitis of housed cattle.


Manganese status of pasturing ewes, of pregnant ewes and doe rabbits on low manganese diets and of dairy cows with cystic ovaries. Four experiments were conducted to obtain information on the manganese (Mn) status of ewes, doe rabbits and dairy cows with cystic ovaries. Manganese was not concentrated specifically in any one tissue or organ but the use of 54Mn has indicated that the isotope was retained by the liver for a longer time. Significantly lower (P less than 0.01) levels of Mn were observed in the liver, kidney and blood of pregnant ewes fed a synthetic diet containing low levels (5 ppm) of Mn than those that were supplemented with 60 ppm Mn. It would appear that the determination of blood Mn concentration would provide a valuable diagnostic tool for the assessment of the Mn status of the pregnant ewe and could be more reliable than data based on tissue (liver, kidney, ovary) levels of Mn. The cortical stroma of dairy cows with cystic ovaries had lower Mn contents than those cows that were without cystic ovaries. The data on blood suggests that cystic ovaries cannot be diagnosed by blood Mn levels if Mn was indeed a contributing factor of the development of this condition. The doe rabbit responded to supplemental dietary Mn in a manner analogous to the ewes.


Experimental induction of an immunohaemolytic anaemia in the chicken with Salmonella gallinarum endotoxin. The possibility that the extreme refractoriness of the chicken to injected endotoxin would permit the buildup of sufficient free endotoxin in the circulation to immunologically modify the erythrocytes in vivo and thereby cause them to be eliminated from the circulation was investigated. It was shown that a moderately severe immunohaemolytic anaemia accompanied by a mild spenomegaly could be induced in chickens by single (large) or multiple injections of Salmonella gallinarum endotoxin (SgE). Varying degrees of reticulocytosis, with corresponding decreases in haemoglobin and haematocrit values, were observed from the tenth day after the injection of the SgE. All the injected animals also showed significant immune responses to SgE, peak haemagglutinin titres occurring coincidentally with the peaks of the haemolytic episodes. A similar injection schedule in specifically immune chickens also showed the anaemia appearing much earlier, persisting longer and being much more profound in intensity. It is considered that the in vivo erythrocyte sensitization induced by SgE injection initiates the erythrocytic changes observed and that the underlying mechanism responsible for the subsequent development of the haemolytic anaemia is immunologically mediated.


Intraperitoneal immunization against necrobacillosis in experimental animals. Experiments employing recently developed mouse models indicated that intraperitoneal immunization with the cytoplasm (intracellular fraction) of Fusobacterium necrophorum protected the animals from a lethal challenge of the pathogen. The critical immunization schedule needed to achieve complete protection involved six weekly intraperitoneal doses of the intracellular antigen. Livers of immunized mice were cleared of infecting fusobacterial within 24 hours whereas those of nonimmunized mice harboured increasing numbers of hte bacteria. Sera from both groups did not protect recipient mice form developing liver abscesses after challenge. Sheep immunized intraperitoneally with 20 mg of cytoplasmic protein given in three doseases were protected against the development of abscesses induced by F. necrophorum.


Blood serum tocopherol levels in calves born from cows winter fed hay or grass silage. Blood serum tocopherol was determined in 44 calves born in the spring from cows that had been fed either timothy grass silage or timothy hay produced in Norther Ontario. On all sampling dates (at birth and at eight, 21, 35 and 60 days of age), calves from the silage group had higher average tocopherol levels than those from the hay group. Studies on serum tocopherol distribution in cows and their calves obtained 60 days after birth from the silage group showed that alpha-tocopherol averaged 85% and beta +  gamma-tocopherols 12%. Only trace quantities of delta-tocopherol were detected in the serum of cows but none in those of calves.


Effect of prednisolone treatment on selected respiratory parameters and cardiac output in prematurely delivered neonatal lambs. Lambs were delivered by hysterotomy on days 142 and 143 postcoitum and were assigned to either a control group or a prednisolone-treated group (10 mg/kg daily for four days). On days 1 through 3 of life erythrocyte 2,3-diphosphoglycerate values were significantly increased in the treated group. Prednisolone treatment did not result in significantly increased P50 values. Mean plasma corticoid values in the control group decreased gradually postpartum. The prednisolone-treated lambs compared to the control lambs had depressed corticoid values, differing significantly on day 4. Body weight gains were significantly depressed by treatment and this effect lasted beyond the treatment period. On day 1 of life (24 hours postinitial treatment) oxygen consumption and cardiac output were significantly elevated in the treated group.


Radioimmunological study of rat uterine extract. A radioassay was used to demonstrate the high affinitiy of a crude rat uterine extract for tritiated estradiol-17B. Although no other chemical procedures were employed to further characterize the extract, it may contain the estrogen binding protein isolated by others. The isolate was antigenic in rabbits and administration of immune serum to female rats significantly lowered the in vitro retention of tritiated estradiol-17B in the rat uterus. It is thought that this immune serum could be successfully used to study the estrogen binding activity of rat uterus.


Bordetella rhinitis in pigs: serum and nasal antibody response to Bordetella bacterins. The nasal and serum antibody response of two groups of pigs, vaccinated with adjuvant containing formalinized or sonicated Bordetella bronchiseptica bacterins was compared with the response of a nonvaccinated group. The tube agglutination test was used to determine agglutinin titers. Following vaccination, all pigs were challenged intranasally with the vaccine strain of Bordetella, after which the nasal Bordetella flora of vaccinated and nonvaccinated pigs was investigated. Sera and nasal secretions from both vaccinated groups exhibited markedly higher agglutinin titers than the control group and serum titers were higher than those in nasal secretions. No differences in agglutinating antibody response were evident between the two vaccines. Serum antibody titers exceeded nasal titers and persisted over a longer period of time. Systemic vaccination resulted in an increased nasal clearance of the vaccine strain by the groups of pigs vaccinated with sonicated or formalined bacterin, whereas no such clearance was evident in the nonvaccinated control group.


Prevalence of Toxocara spp. and other parasites in dogs and cats in Halifax, Nova Scotia. Several cases of visceral larva migrans syndrome in children led to an investigation of the ova of Toxocara spp. and other species in stool specimens from stray dogs and cats in Halifax, Nova Scotia. Fecal samples from 474 stray dogs and 299 stray cats were examined. Ova of Toxocara canis or cati were present in stools from 26.6% of the dogs and 25.1% of the cats. In dogs the prevalence of Toxocara canis was noticeably greater in puppies (56.1%) than in mature animals (11.9%).


Control of the time of parturition in sows with prostaglandin F2alpha. Pregnant gilts and sows were given a single intramuscular injection of from 5-10 mg of prostaglandin F2alpha-tromethamine salt (dependent on liveweight) on day 111, 112 or 113 of pregnancy (first day of estrus = day 0) to induce parturition. When injected on day 111, 44% of the pigs farrowed within 40 hours compared with 93% injected on days 112 or 113. The mean time to the induced parturition was 27.3 +/- 4.7 hours. Signs of discomfort were observed during the first hour posttreatment but there were no apparent effects on lactation or on the mothering ability of the dams after farrowing.


Depression of hyperglycemic response to glucagon by parenteral lead administration in sheep. The insulin and glucose responses to glucagon infusions (27 microgram/hr) were determined in sheep before and after parenteral lead treatment (6 mg/kg intravenously). Glucose production was measured by primed continuous infusion of [6-3H]glucose. Glucagon and insulin concentrations before and during glucagon infusions were not significantly different between lead treatment and control experiments. Lead administration did not affect the concentration or production of glucose in the preinfusion period. However, depressed hyperglycemia during glucagon infusion in lead treated experiments tended to be associated with decreased glucose production. The reduced glucogenic response to glucagon may be the result of reduced function of pyruvate carboxylase, a key hepatic gluconeogenic enzyme in sheep, from lead induced impairment of mitochondrial function.


Acute urea toxicity in sheep.

Acute urea toxicity in sheep. Twenty-seven sheep were assigned to three groups in order to study acute urea toxicity. Groups I, II and III were dosed with 0.5, 0.6 annd 0.75 g/kg of urea, respectively. The mean survival times were 165, 109 and 60 minutes, respectively. The following clinical signs such as pronounced muscle fasciculation, trembling, grinding teeth, ataxia, lateral recumbency, bloating, regurgitation, hyperesthesia, mydriasis and convulsions were observed. Anuria and lack of salivation were also present. The primary cause of death in this study was due to respiratory arrest and not cardiovascular collapse. Plasma examinations showed a marked increase in glucose, ammonia and urea levels but no change in ketone body concentration.


The effects of hemolyzed blood on pulmonary and systemic arterial pressure and heart rate of the dog. The injection of hemolyzed blood into the venous system of the dog produced a rise in the pulmonary arterial pressure and a fall in the systemic arterial pressure. There were variable changes in the heart rate. Comparison with serotonin injections indicated that the above responses were produced by factors other than serotonin.


A bovine herpesvirus isolated from sheep. A viral agent was isolated from the trachea of a lamb that was suffering from a respiratory disorder. The physical and chemical properties of the isolates are characteristic of the herpesvirus group. It contains DNA in its virion, is ether sensitive, acid labile at pH 3.0 and heat labile at 56 degrees C after five minutes. The cytopathology observed provided further evidence of a herpesvirus isolate. The neutralization of the infectivity of the isolate with antiserum to bovine herpesvirus 1 is evidence that it should be considered an isolate of bovine herpesvirus 1. It is concluded that this is a report of a bovine herpesvirus infection in sheep.


Serum cobalamin and folate in the optic neuropathy associated with tobacco smoking. The concentrations of vitamin B12 in the sera from 77 patients diagnosed as suffering from the toxic optic neuropathy associated with tobacco smoking were compared with control levels and with serum folic acid concentrations from the same patients. Of these, 17 patients had associated pernicious anaemia. Serum vitamin B12 levels were significantly lower, whereas the folic acid concentrations showed great variation. Folic acid levels in the serum tended to be high when the vitamin B12 level was low (r = 0.29). The results suggest that the role of folic acid in the genesis of the optic neuropathy is not marked. However persistently low levels of folic acid occurred in one subject and significant clinical improvement resulted only from specific therapy.


Senile disciform macular degeneration and smoking. We studied the smoking habits of 114 patients with senile disciform degeneration of the macula. The mean age at onset of blindness in the first eye was 64 years in those currently smoking; this was significantly less than the mean age in those who had never smoked (71 years). We advise all patients with disciform degeneration to stop smoking.


Orbital extension of retinoblastoma: a clinicopathological study. We have studied all cases of orbital extension of retinoblastomas at the Edward S. Harkness Eye Institute in New York since 1925. Only 9.4% of the patients lived more than 2 years after diagnosis. Orbital retinoblastoma is frequently associated with systemic metastases. We emphasize the significance of massive choroidal involvement and periemissarial extension. Careful handling of the enucleation specimen at the time of surgery and during histologic preparation is important to avoid cell spillage and artifacts. Treatment should be early, multidisciplinary and include adjuvant chemotherapy.


[Papillary hemorrhage associated with posterior vitreous detachment]. Three cases of papillary hemorrhage associated with posterior vitreous detachment are reported. One still has a visual field defect after two years. The resemblance between these hemorrhages and those found in some cases of chronic simple glaucoma is discussed.


Malignant glaucoma - the long and short of it. Malignant glaucoma is a serious complication of surgery for angle-closure glaucoma. We describe three cases which exemplify important aspects of the onset and the management of the condition. It may develop soon after the original operation or only after many years, when it can be difficult to recognize. Simmon's approach to management is highly recommended, and intra-vitreous surgery is only employed if a five-day trial of intensive medical therapy fails.


Intracameral phosphate buffer in alkali burns. We perfused the eyes of albino rabbits with a phosphate buffer to see if the damage to cornea and lens produced by alkali might be reduced. The rabbits were divided into five groups: in the first (control) group undamaged eyes were perfused; in the other four the corneas were burned with sodium hydroxide. The second group was not treated; the remaining three were treated with buffer at once, after fifteen minutes and after thirty minutes. Our results showed that provided this regime is used within thirty minutes of exposure, the effects of the insult are reduced.


Brucellosis in reindeer, Rangifer tarandus L., inoculated experimentally with Brucella suis, type 4. An investigation of brucellosis caused by Brucella suis, type 4, in reindeer, Rangifer tarandus L., and other ungulates inoculated experimentally with virulent isolates was undertaken to observe the course of infection, follow titres of serum agglutins, and determine the extent to which intraspecific and interspecific transmission might occur among confined animals. Titres rose to maximum levels within 1 to 2 months following inoculation, decreased during the next 4 months, and persisted at low levels thereafter. Titres in uninoculated associates of these animals followed the same pattern, but at lower levels. Abortion occurred in reindeer that received large numbers of organisms; females receiving smaller numbers at an earlier stage of gestation produced normal fawns. Possible explanations for the holarctic distribution of B. suis, type 4, in reindeer are considered.


Biosynthesis of chloramphenicol. Studies on the origin of the dichloroacetyl moiety. Chloramphenicol produced by cultures of Streptomyces species 3022a supplemented with sodium [1,2-13C]acetate was labelled with 13C exclusively in the dichloromethine (2.6 +/- 0.1%) and carbonyl (0.59 +/- 0.05% carbon atoms. Satellite signals from 13C-13C coupling between covalently bonded 13C-enriched carbon atoms were too intense to be attributed to random combination of labelled atoms at the average enrichments measured, but their intensity relative to those of the signals for uncoupled 13C atoms indicated that most of the precursor had been incorporated after 13C-13C bond fission. Since [2,3-13c]succinic acid enriched only the carbonyl carbon atom of chloramphenicol, these results suggest that neither acetate nor a Krebs cycle intermediate is a direct precursor of the dichloroacetyl group. Cultures supplemented with [2-3h]-or [2h2]-dichloroacetic acid incorporated negligible amounts of isotope into the antibiotic; on this evidence, the free acid is not an intermediate in chloramphenicol biosynthesis and the acylation step may precede chlorination.


Inducing effect of plant cells on nitrogenase activity by Spirillum and Rhizobium in vitro. Eleven different plant cell tissue cultures of both legume and non-legume origin have been grown in direct association, and in separate but close proximal association with both Spirillum lipoferum and Rhizobium sp. 32H1. Basic similarities were found in the nutritional requirement for the induction of nitrogenase activity (C2H2) in both organisms. In the absence of plant cell cultures both organisms need to be provided with a pentose sugar and a tricarboxylic acid to induce high levels of nitrogen-fixing activity. Plant cell callus tissue appears only capable of supplying the tricarboxylic acid to induce high levels of nitrogen-fixing activity. Plant cell callus tissue appears only capable of supplying the tricarboxylic acids needed but not the sugar component. The plant tissue, however, seems able to activate certain carbohydrates, which in themselves are incapable of substituting for the pentose additive.


The envelope of Micrococcus radiodurans: isolation, purification, and preliminary analysis of the wall layers. Two methods are presented that separate the complex envelope of Micrococcus radiodurans, strain Sark, into its constituent layers. The first involved treating whole cells with 0.025 M Tris buffer (pH 7.5) containing 2 mM of calcium and 3 mM of magnesium, resulting in the degradation of an intermediate ('compartmentalized') layer and consequent sloughing of the outer subunit and interior layers to form vesicles. This treatment also appears to show that the interior layer may be connected with the peptidoglycan-containing 'holey' layer. The second method involves treating whole cells with benzene followed by sonication; the results suggested that this treatment only released the outer layers from the 'compartmentalized' layer and did not degrade layers. Following benzene treatment, digestion of the 'compartmentalized' layer with cold sodium dodecyl sulfate (SDS) released the 'holey' layer. Electrophoretic analysis of some of the isolated layer preparations suggested that the subunit layer consisted of three major proteins of 90 000, 92 000, and 94 000 molecular weight, one minor protein of 100 000, a small amount of carbohydrate associated with the 94 000 protein, and a small amount of a 55 000 lipoprotein. The interior layer contained at least 10 proteins and may be attached to the peptidoglycan-containing 'holey' layer by means of the 55 000 lipoprotein.


Cleavage planes in the envelope of Aquaspirillum bengal. The cell surface of Aquaspirillum bengal was devoid of superficial wall structure. When cells were freeze-cleaved and etched, multiple fracture planes through the cell envelope were exposed, which was unusual for an aquaspirillum. These included both convex and concave surfaces and they are compared with those of other gram-negative bacteria.


Labelled acetone and levulinic acid are formed when [14C]acetate is being converted to mycophenolic acid in Penicillium brevicompactum. Evidence is presented that is compatible with the hypothesis that the farnesyl unit involved in the biosynthesis of mycophenolic acid in Penicillium brevicompactum is degraded by two successive oxidative cleavages at the double bonds distal from the phthalide nucleus. Acetone and levulinic acid are two non-aromatic degradation products.


Transformation of Azotobacter vinelandii strains unable to fix nitrogen with Rhizobium spp. DNA. The phenotypes of Azotobacter vinelandii ATCC 12837 strains defective in nitrogen fixation (Nif-) were characterized by intrageneric transformation with known Nif- strains of A. vinelandii OP. These former mutant strains were used as recipients for intergeneric transformation by deoxyribonucleic acid (DNA) prepared from Rhizobium spp. to determine if the rhizobia would transform the Azotobacter Nif- phenotypes to Nif+. The frequency of Nif+ transformants using Rhizobium DNA was always less than the frequency using Azotobacter wild-type DNA but was greater than the spontaneous reversion frequency. The Azotobacter Nif+ recombinants also were stable. DNA from all of the Rhizobium spp. transformed to Nif+ Azotobacter mutants defective in the nitrogenase component I (molybdoferredoxin); however, some recombinants had a lower nitrogenase activity and a delayed nitrogenase depression time. Mutants defective in the pleiotrophic transcriptional control of both nitrogenase components were transformed to Nif+ by the asymbiotic nitrogen fixing Rhizobium sp. 32H1 and 41A1, but not the symbiotic nitrogen-fixing species. The significance of these results and the possible future applications of this system are discussed.


Biosynthesis of chloramphenicol in Streptomyces sp. 3022a. Properties of an aminotransferase accepting p-aminophenylalanine as a substrate. In the presence of alpha-ketoglutarate, cell-free extracts of Streptomyces species 3022a catalysed transfer of the amino group from p-aminophenylalanine, yielding an unstable product similar to that obtained by the action of D- and L-amino acid oxidases on the amino acid. The enzyme, purified 16-fold from cell homogenates by chromatography on ion-exchange celluloses, hydroxyapatite, and cross-linked dextran gel, has a molecular weight of 90 000 and a broad pH optimum at 8.0. It is active with L-phenylalanine and L-tyrosine as well as p-amino-DL-phenylalanine as amino donors, and its relative activity towards these substrates did not change during purification. Polyacrylamide disc-gel electrophoresis of the partially purified enzyme gave single zones with identical mobility when the gels were assayed for activity with p-aminophenylalanine and tyrosine as amino donors. The results indicate that synthesis of p-aminophenylalanine en route to chloramphenicol uses a multispecific aminotransferase for aromatic amino acids. With L-phenylalanine as substrate, the preferred amino-accepting co-substrate was alpha-ketoglutarate. Some kinetic constants for the enzyme were determined, and its requirement for pyridoxal phosphate was demonstrated.


In situ degradation of oil in a soil of the boreal region of the Northwest Territories. Replicate field plots comprising a control; control plus oil; control plus oil and fertilizer (urea phosphate, 27:27:0); control plus oil and bacteria; and control plus oil, fertilizer, and bacteria were established at Norman Wells, N.W.T., Canada. Plots were monitored over a 3-year period for changes in microbial numbers and the chemical composition of recovered oil. Where fertilizer was applied, there was a rapid increase in bacterial numbers, but no increase in fungal propagules. This was followed by a rapid disappearance of n-alkanes, isoprenoids, and a continuous loss in weight of saturate compounds in recovered oil. Changes in the content of asphaltenes, aromatics, and nitrogen-, sulphur-, and oxygen-containing fractions also are discussed. The seeding of oil-soaked plots with oil-degrading bacteria did not have any effect on the composition of recovered oil. Fertilized plots showed a more rapid rate of vegetation with cotton grass and Labrador tea being the dominant species in revegetation.


ICMSF methods studies. X. An international comparative study of four media for the enumeration of Staphylococcus aureus in foods. An international comparative study, undertaken by six laboratories to assess the performance of four selective media commonly used for the enumeration of Staphylococcus aureus in foods, revealed that Baird-Parker agar performed most satisfactorily. There was no significant difference among milk salt, tellurite polymyxin egg yolk, and kalium rhodanid - actidione - natriumazid - eigelb - pyruvat (KRANEP) agars. The type of food examined appeared to influence the performance of the media, but no specific patterns could be determined. Cultures yielding 3+ and 4+ coagulase reactions are most likely to possess thermostable nuclease activity, and are therefore most likely to be S. aureus.


An ecological study of bacteriophages of Vibrio natriegens. Effects of temperature and anaerobic conditions on the replication of two bacteriophages, nt-1 and nt-6, of the estuarine bacterium Vibrio natriegens were studied. Reduction in temperature resulted in longer latent periods and reduced burst sizes for both phages. Replication under anaerobic conditions resulted in longer latent periods; however, phage nt-6 had a reduced burst size, whereas phage nt-1 had an increased burst size, resulting in a rate of phage production nearly equal to that observed under aerobic conditions. Therefore the distribution of the phages in marsh areas could be influenced by temperature and anaerobiosis.


Breakdown of psyllium hydrocolloid by strains of Bacterioides ovatus from the human intestinal tract. Strains of Bacteroides ovatus from human feces produced extracellular enzymes which degraded psyllium hydrocolloid. Other species of saccharolytic bacteria which are found in high concentrations in human feces did not degrade psyllium.


Chroma-Memo-Flow technique for rapid sequential analysis of regional cerebral blood flow (rCBF) responses. This is the first report of a method of sequential regional cerebral blood flow (rCBF) analysis, called Croma-Memo-Flow. This technique is a computerized modification of the initial slope method of regional cerebral blood flow (rCBF init.), allowing temporal resolution of the flow pattern by calculation of the slopes of sequential segments of the initial 1-2 minutes of the Xenon-133 washout curve. The same theoretical analysis applies to this method as to the rCBF init. method. Each flow calculation is based on the slope of a discrete 16 second segment of the initial washout; and each second the segment is advanced by one second. A new flow calculation is made each second and is displayed as a color coded map on a TV screen. Each map is labelled, indicating the time in seconds following Xenon injection, and sequential rCBF changes during the clearance period can be immediately visualized. This allows for almost instantaneous analysis and display of rapid or transient rCBF responses to activation and deactivation of the cerebral cortices. The data is stored in a 35 channel memory for deliberate replay, photography, and analysis. Functional tests may be applied during the initial washout period and both the magnitude and chronological relationships of the evoked regional cerebrovascular responses observed. A clinical study is presented to illustrate the possibilities of applying the technique to assess cortical reactivity.


Familial hyperbilirubinemia in Friedreich's ataxia. The combined metabolic stresses of fasting and the intravenous injection of 50 mg nicotinic acid in Friedreich's ataxia resulted in the delineation of two sub-groups of responses. High bilirubin ataxics maintained abnormally elevated levels of bilirubin, while normal bilirubin ataxics behaved like the normal control group. It is postulated that this finding infers the possible linkage of the gene for Friedreich's ataxia and that for Gilbert's disease.


Lipoamide dehydrogenase regulation in rat brain. The Pyruvate dehydrogenase multienzyme complex (PDHC) purified from rat brain is phosphorylated in the presence of low concentrations of ATP and MgCl2. The phosphorylated PDHC is incapable of catalyzing the oxidative decarboxylation of pyruvate. In the presence of high concentrations (10 mM) of MgCl2, the phosphorylated (inactive) PDHC is converted back to the dephospho-form of PDHC which is catalytically active. The dihydrolipoyl dehydrogenase (LAD) component, E3, of PDHC is inactivated by pyridoxal phosphate (PLP) and the PLP-inactivated LAD can be reactivated by an amino acid, taurine. These results indicate the reversible formation of Schiff base between PLP and LAD. They also provide clear evidence for the involvement of LAD (E3) in the previously reported inactivation of PDHC by PLP.


Serum and platelet lipoamide dehydrogenase in Friedreich's ataxia. Pyruvate dehydrogenase (PDH), alpha-keto glutarate dehydrogenase (alpha-KGDH) and lipoamide dehydrogenase (LAD) were measured in platelets of 11 patients with typical Friedreich's ataxia and 10 normal control subjects. Serum LAD was also evaluated in the same patients. No statistically significant changes were found in platelets for the group as a whole, although some patients had low values (more than one standard deviation below control mean). Serum LAD was significantly reduced in the patients with Friedreich's ataxia. This was not due to associated diabetes.


Lipoamide dehydrogenase in Friedreich's ataxia fibroblasts. Lipoamide dehydrogenase was measured in cultivated skin fibroblasts from twelve patients with Friedreich's ataxia and nine normal controls. No difference in specific activity, subcellular distribution and Vmax or Km was observed between patients and controls.


Platelet taurine uptake in spinocerebellar degeneration. The uptake of 14C-taurine was studied in the platelets of 20 ataxic patients and 20 age-matched normal control subjects. No significant differences were found in uptake or kinetics of taurine between the two groups of subjects. If a transport defect in taurine exists in Friedreich's ataxia, it is not present in all tissues. Preliminary indication was obtained in favor of heterogenity of the uptake pattern between ataxic individuals.


Taurine in cerebrospinal fluid in Friedreich's ataxia. In a previous study we reported low values of taurine and aspartic acid in the CSF of patients with Friedreich's ataxia, when the results were compared to the literature. Further studies have revealed that unforetold difficulties with the advertised methodology of sequential multi-sample amino acid analysis were responsible for low values in the determination of these two amino acids in the small volumes necessary for CSF. A corrected method is presented. With the latter method the differences disappear for CSF taurine and aspartic acid, but they remain valid for the previously reported blood and urine values in Friedreich's ataxia. GABA levels are also normal in Friedreich's ataxia CSF.


Cerebellar ataxia produced by 3-acetyl pyridine in rat. A single intraperitoneal injection of 3-acetyl pyridine produces, within 24 hours of administration, signs of cerebellar ataxia and damage to the medulla oblongata and to the climbing fibers of the cerebellum. These changes are accompanied by changes in the concentration of certain amino acids in the appropriate areas. Glutamic acid is decreased in cerebellum, medulla, cortex, striatum, hippocampus, retina and olfactory bulbs, while taurine is specifically decreased in the cerebellum and medulla oblongata and aspartic acid in the retina. The concentrations of GABA and glycine are not modified in any of the areas studied. Glutamine is generally increased in concentration in areas of cell damage.


Effect of alloxan diabetes on cerebellar amino acids. Rats rendered diabetic by alloxan monohydrate were studied to investigate the effect of increased blood glucose upon the concentration of various putative neurotransmitter amino acids in the cerebellum. No modification was found in the concentrations of glutamate, gamma aminobutyric acid (GABA), glutamine, glycine or taurine, but there was a significant decrease in the cerebellar concentration of aspartate in the diabetic animals. This raises the question of the specificity of the aspartic acid defect found in some form of ataxia.


Antagonism by taurine of morphine induced growth hormone secretion. The intraperitoneal (IP) or intraventricular (IVT) administration of small amounts of taurine did not modify pentobarbital-induced sleep or pituitary hormone release. However, the drastic increment in plasma GH values induced by morphine administration was completely blocked by the IVT injection of the amino acid. Whether taurine plays a physiological role in the control of GH secretion is highly speculative.


Purine metabolism in Friedreich's ataxia. In a detailed investigation of nucleotide synthesis, interconversion and degradation, no difference was found between subjects with Friedreich's Ataxia and normal controls. It appears improbable that this disorder is related to a primary defect in purine metabolism.


Friedreich's Ataxia 1978--an overview.

Friedreich's Ataxia 1978--an overview. In the present overview an attempt is made to summarize the investigations carried out during the first part of Phase Two of the Quebec Cooperative Study of Friedreich's Ataxia. These investigations delineated the relative importance of various biochemical leads uncovered during the preliminary survey. It is possible to indicate some findings that may be primary and which should be pursued in subsequent investigations. Among these, the observation of an abnormal composition of high density lipoproteins in Friedreich's Ataxia appears to be the most important.


Microvascular anastomosis for cerebral ischemia in 19 patients: a preliminary report. The general principles of bypass surgery as they affect the cerebral circulation are reviewed. The preliminary results of an extracranial intracranial bypass operation performed on a group of 19 patients suffering from cerebral ischemia are presented. The results of the surgery compare favorably with those published in the literature.


Cytochemical localization of adenylate cyclase in broken cell preparations of the cerebral cortex. Broken cell preparations derived from rat cerebral cortical grey matter were studied cytochemically to localize adenylate cyclase (AC) activity in subcellular organelle membranes. AC activity was localized by visualizing reaction product in brain particulate fractions by electron microscopy. Activity was found in the endoplasmic reticulum, on the inside of the inner mitochondrial membrane and on both leaflets of the nuclear membrane. Reaction product was found in the postsynaptic density area of most synapses. The reaction product tended to be more prominent in the presence of fluoride. A synaptosome-rich fraction was shown to have NE stimulated AC activity which was blocked in vitro by both a alpha- and an beta-blocker and in vivo by propranolol.


Anesthesia in multiple sclerosis.

Anesthesia in multiple sclerosis. The effect of general anesthesia on 42 multiple sclerosis (MS) patients who underwent 88 episodes of general anesthesia was analyzed. One patient experienced a relapse after a procedure under general anesthesia, which is compatible with the natural history of the disease. A literature review revealed little information on this subject or on the use of particular anesthetic agents in MS. Our experience with spinal and local anesthesia is reported. In the evaluation of the former our limited data suggested that spinal anesthesia is less preferable than other alternatives in MS. Local anesthetics had a benign effect on the course of MS.


Microangiography and vascular permeability of the subependymal matrix in the premature infant. The microvascular architecture of the subependymal matrix in premature infants was studied with microangiography and benzidine stains. This revealed that the subependymal matrix is the end zone or the border zone between cerebral arteries and the collection zone of the deep cerebral veins. Focal hypoxic changes of this subependymal matrix may occur in hypoxemia and ischemia because of the characteristic architecture. The vascular permeability of these vessels was studied in rabbits using three different molecular weights of FITC-dextran. Vascular permeability was increased in the subependymal matrix by hypoxia and especially by hypoxia associated with an increased venous pressure. These findings may be related to the pathogenesis of subependymal hemorrhage in prematurity.


Autosomal recessive spastic ataxia of Charlevoix-Saguenay. A new syndrome of autosomal recessive spastic ataxia has been isolated in the Charlevoix-Saguenay region of Quebec. This syndrome is remarkably homogeneous and includes: spasticity, dysarthria, distal muscle wasting, foot deformities, truncal ataxia, absence of sensory evoked potentials in the lower limbs, retinal striation reminiscent of early Leber's atrophy and the frequent presence (57%) of a prolapse of the mitral valve. Biochemically, many cases show impaired pyruvate oxidation, others have hyperbilirubinaemia and some have low serum beta-lipoproteins and HDL apoproteins. These features are similar to those found in typical Friedreich's ataxia.


Clinical and electronystagmographic findings in Friedreich's ataxia. A thorough investigation of vestibular function has been carried out in 16 patients with typical Friedreich's ataxia. Electronystagmography and caloric tests revealed a number of inconstant abnormalities. Most abnormal findings were related to ocular dysmetria, disorganized pursuit and square waves.


HLA and complement typing in olivo-ponto-cerebellar atrophy. HLA antigen typing was carried out in a family with an autosomal dominant form of spinocerebellar degeneration [possibly olivoponto cerebellar atrophy (O.P.C.A.)--Type 1]. Eleven ataxic patients, three possibly ataxic subjects, two unrelated spouses and 13 clinically normal at risk siblings were typed for ABO and Rh blood groups, HLA-A and HLA-B antigens, C4 component of the complement and a number of other serum proteins (Clq, beta-1A, beta-1C, C5, beta-lipoproteins). No solid evidence for linkage between the ataxia gene and the HLA or C4 loci could be demonstrated in this family. Certain serum proteins, and particularly beta-lipoproteins were found to be significantly reduced in some sub-groups of subjects.


Spontaneous dissection of cervico-cerebral arteries. Sixteen cases of spontaneous dissection of the cervical internal carotid artery (6 verified) are described. The mean age was 45 years. The clinical picture varied from simply headache and a bruit to hemiplegia and aphasia. Eleven patients had transient ischemic attacks. Headache, facial pain, a subjective bruit, oculo-sympathetic palsy and transient monocular blindness were present in various combinations in two-thirds of cases and their presence suggested the correct diagnosis. Examples of suspected dissection of the intracranial internal carotid, middle cerebral, posterior cerebral and extracranial vertebral arteries are also presented. Spontaneous dissection is more common than the literature indicates.


Oxygen transport in patients with Friedreich's ataxia. The hypothesis is that an abnormal oxygen-hemoglobin dissociation curve is a primary or a secondary defect in patients with Friedreich's ataxia was investigated in 12 subjects with this disease. Hemoglobin and P50 were measured and compared with age and sex matched controls. The mean hemoglobin concentration was 14.2 g% and the P50 was 26.25 torr for the patients and 13.8 g% and 26.27 torr in the controls. These results indicate that the oxygen transport system is normal in this disease and likely exclude an abnormal oxygen dissociation curve as a primary or a secondary factor in the pathophysiology of the cardiomyopathy and the neuromyopathy found in this disease.


Clinical value of gastrointestinal fiberoptic endoscopy. This review describes the contribution of fiberoptic endoscopy and its associated ancillary procedures to the improved diagnosis of some common gastrointestinal disorders. The diagnostic approach to esophagitis and carcinoma of the esophagus and stomach is outlined. Swallowed foreign bodies that do not pass out of the stomach can be removed with relative ease by endoscopic ancillary procedures. The role of endoscopy in duodenal ulcer disease and the effects on morbidity and mortality of the vigorous diagnostic approach in upper gastrointestinal hemorrhage are discussed. Endoscopy is invaluable for assessing the condition of the stomach postoperatively. Colonoscopic polypectomy has lent support to the "poly-cancer" hypothesis. The role of colonoscopy in the evaluation of inflammatory bowel disease must still be delineated. Endoscopic retrograde cholangiopancreatography is of value in the investigation of obstructive jaundice and pancreatic disease. In the former, noninvasive techniques of ultrasonography and computerized tomography scanning complemented by fine-needle transhepatic cholangiography will probably be the preferred methods of investigation. The impact of the contribution of fiberoptic endoscopy on health care will be maintained only if the physician has been properly trained in its use and has an understanding of the different diseases.


Symposium on colorectal cancer. 1. Pathology of colorectal cancer. Most colorectal cancers arise from pre-existing adenomas (the adenoma-carcinoma sequence). The histology, cytology and malignant potential of the adenoma group of tumours are described. From a study of the life history of the adenoma-carcinoma sequence in cases of both familial polyposis and isolated adenoma it would appear that most colorectal cancers evolve over a long period. The adenoma is important as a marker for increased risk of colorectal cancer, in clinical practice and in epidemiologic studies. Local excision for carefully selected early colorectal cancers is justified on the basis of the results of a long-term prospective study.


Epidemiology and colorectal cancer.

Epidemiology and colorectal cancer. Data from international sources and from Canada are reviewed concerning the incidence and mortality for colorectal cancer. Nutritional factors are almost certainly relevant in etiology although, with differing sex ratios for different sites of the colon and rectum, it cannot be assumed that they will operate to the same extent throughout the large bowels. The results of studies currently available are conflicting and further study is obviously required.


Immunology and immunotherapy of colorectal cancer. Adenocarcinoma of the human colon produce carcinoembryonic antigen (CEA), one of a family of glycoprotein molecules that may be produced by various human cancers and, occasionally, by other abnormal tissues. The physicochemical nature and tissue distribution of CEA have been well established and a variety of radioimmunoassays have been developed for the detection of this material in the circulation of patients with CEA-producing tumours. Although the assay should not be used as a screening test for cancer of the bowel, it may serve as a helpful adjunct in the diagnosis of digestive system tumours in conjunction with other routine investigations. More important is the utilization of the radioimmunoassay for CEA under the following circumstances: 1. Preoperatively as an indicator of tumour dissemination based upon the quantitative concentrations of CEA in the circulation. 2. As an indicator of potentially curative resection manifested by a decrease in circulating concentrations of CEA to below detectable limits. 3. As an early warning of recurrent tumour growth, by detecting the reappearance of CEA in the circulation of a patient rendered CEA-negative after tumour resection, 3 months to 2 years or more before any other presently available technology can detect clinical evidence of recurrence. This last observation is now under investigation for its potential value as an indicator for second-look surgery in patients who have undergone potentially curative surgery for colorectal cancers.


Surgery of colorectal cancer.

Surgery of colorectal cancer. Studies on lymphatic spread of rectal cancer have established the rationale for sphincter preservation in the treatment of midrectal cancer. This entity comprises lesions located 5.5 to 10 cm above the anal verge in women and 7 to 11 cm in men. Abdominosacral resection is a logical means for restoring intestinal continuity after radial resection for midrectal cancer. Direct posterior exposure of the distal limit of resection above the pelvic floor allows accurate construction of the anastomosis without disturbing the anorectal structures or their innervation and maintains essentially normal anal continence. The procedure is preferable to the various pull-through operations. Survival rates for patients undergoing anterior resection, abdominosacral resection and abdominoperineal resection are comparable.


Radiotherapy of colorectal cancer.

Radiotherapy of colorectal cancer. Radiotherapy has an increasingly important place in the management of patients with colorectal cancer. At present the exact indications have not been made based on preliminary experience at the Princess Margaret Hospital, Toronto: 1. Radical irradiation could be a valuable alternative to the classical Miles' abdominoperineal excision of extraperitoneal rectal cancer. 2. Preoperative irradiation may be used for all patients undergoing surgical excision and restoration of bowel continuity. 3. Postoperative radiotherapy can be administrated (a) when the tumour has penetrated the bowel wall to the serosa or beyond, (b) when the lymph nodes are involved secondarily and (c) when the distal line of resection is less than 4.0 cm from the tumour (as measured in the fixed pathological specimen). 4. Radiotherapy is useful for palliation of postsurgical recurrences and symptomatic distant metastases.


Chemotherapy of colorectal cancer.

Chemotherapy of colorectal cancer. Although considerable research effort has been expanded to improve the drug treatment of colorectal cancer, progress has been slow. 5-fluorouracil (5-FU) is still the agent of choice and no other drug or combination of drugs has been found superior. When combined with radiation therapy 5-FU is superior to irradiation alone in the treatment of localized carcinoma of the rectum. When used as an adjuvant in the management of patients with a poor prognosis after definitive surgical resection, 5-FU has not improved survival or delayed the time to recurrence. Further controlled trials are modalities of therapy to improve these results.


Importance of mixed venous oxygen saturation in the care of critically ill patients. The relation between mixed venous oxygen saturation and cardiac index was determined in 11 children who underwent surgical treatment for congenital heart disease. The correlation between these two variables was found to be reliable (r = 0.78, P = 0.001). The simple determination of mixed venous oxygen saturation performance, particularly when sophisticated equipment for measuring cardiac output is not available.


Wilder Penfield Lecture: nature and management of penetrating head injuries during the Civil War in Lebanon. During the recent war in Lebanon- at one hospital one fifth of all casualty admissions were patients with skull injuries associated with penetrating brain damage. Wounds inflicted by high velocity missiles carried the greatest mortality. The patient's state of consciousness afforded the best guide to prognosis. Craniotomy, when feasible, was found preferable to the accepted technique of crainectomy in the management of these cases. Thorough débridement and complete hemostasis are essential, and when these have been accomplished, deeply placed bony fragments may be left in situ with impunity. Traumatic aneurysms develop by no means rarely and therefore postoperative arteriography is advisable.


Annular pancreas: a new classification and clinical observations. Seven cases of annular pancreas are described. In all the diagnosis was confirmed at autopsy or at operation. This study provides a new, original classification for annular pancreas. Two distinct subtypes are described: type 1, extramural and type 2, intramural. In type 1 the presenting symptoms are those of high gastrointestinal obstruction. In type 2 the symptoms are those of duodenal ulceration. For extramural obstructing annuli surgical intervention, if indicated, should be a bypass procedure; for intramural types with duodenal ulcer, subtotal gastrectomy with or without vagotomy is the procedure of choice.


Nonoperative removal of retained common-bile-duct stones. The discovery of retained common-bile-duct stones after operations on the gallbladder continues to be a frustrating experience for the general surgeon. Until recently this problem was solved in most patients by surgical re-exploration of the common bile duct. However, several alternatives to surgery are gradually gaining acceptance because of their lower morbidity and mortality. These methods are discussed with special emphasis on the use of a catheter with a steering mechanism and the Dormia basket (Burhenne's technique). This is the best alternative to surgery as it has no reported mortality, few complications and causes the least discomfort to the patient. It is highly successful and requires no hospitalization.


Survival after late disc dislodgement of a mitral Wada-Cutter prosthesis. A 33-year-old woman, 6 years after placement of a Wada-Cutter prosthesis, suffered from free mitral regurgitation secondary to the dislodgement of the disc occulder into the left atrium. She was operated on approximately 14 hours after the onset of symptoms and survived; this patient is the third reported survivor following dislodgement of a Wada disc.


Long-term follow-up of triple arthrodesis. Thirty-seven children in whom 46 triple arthrodeses had been performed were followed up for 19 to 33 years (average, 24 years). Better results were evident in patients who had been operated on because of poliomyelitis, pes cavus or pes planus than in patients operated on for club foot, cerebral palsy or spina bifida. The use of staples appeared to improve the result. A neutral position of the heel is desirable. Varus positions required revision in three patients. A heel-toe gait was noticeable in 74% of patients. Osteoarthritis occurred 24% and pseudarthrosis in 4% of our patients. In 91% of patients the functional result could be described as good or excellent.


Trichobezoar: an uncommon pediatric problem. Trichobezoar, the "hair-ball" occasionally found in the stomach of emotionally disturbed adults, particularly women, is an uncommon finding in the pediatric age group. The diagnosis often rests on the suspicion of the alert physician since most patients will not volunteer information about swallowing hair. The presence of a palpable upper abdominal mass associated with progressive intolerance to food, with weight loss and with weakness, and the roentgenographic appearance of a mass after a barium meal confirms suspicion. Treatment consists of laparotomy and gastrotomy to permit removal of the foreign material. Psychiatric assistance should be sought.


Survival in colorectal cancer.

Survival in colorectal cancer. The authors studied the hospital records of 258 patients with colorectal cancer diagnosed between 1965 and 1974 at l'Hôpital du Saint-Sacrement, Quebec and computed expected and relative survival rates to adjust for deaths from other causes. Life-table methods based on full intervals only were used to analyse survival. The patients (138 men and 120 women) ranged in age from 24 to 96 years (mean, 64.9 +/- 12.7 years). The 5-year relative survival rate expressed as a percentage was 48.6 +/- 4.7 for the total group and 64.1 +/- 5.6 for patients in stages A, B and C of Dukes' classification. The overall operative mortality rate of 2.7% compared favourably with that reported elsewhere. Among patients with cancer of the sigmoid colon or rectum (the most readily detectable), the diagnosis was made at stage A in one out of nine and at stage D in approximately one out of four. Despite the introduction of universal medical insurance in Quebec in 1970, there has been no significant trend towards earlier diagnosis.


The gastroplasty tube as a method of reflux control. Follow-up of 135 patients who underwent Belsey gastroplasty because of intractable reflux demonstrated that 44% had continued reflux and 25% had symptoms of reflux that were serious, despite a very low rate of anatomic recurrence. Most of the patients with symptomatic reflux had major preexisting esophageal pathologic conditions related to previous surgery, esophageal ulceration, stricture, or scleroderma. In this group Belsey gastroplasty was not an effective method of reflux control. Total fundoplication gastroplasty (TFG) in 100 consecutive patients has so far had the same low rate of anatomic recurrence, most likely related to the gastroplasty tube; however, longer follow-up is necessary to confirm this fact. TFG is effective in controlling reflux; none of the 100 patients so treated had clinical or radiologic evidence of reflux on follow-up examination.


Lipid alterations in acute pancreatitis. The authors studied the lipid profile in acute pancreatitis in humans and also in dogs in which this disease had been induced experimentally. Blood samples were analysed by mass spectroscopy and gas chromatography. During the acute phase of the pancreatitis there was a significant reversal of the ratio of unsaturated fatty acids. There was a marked increase in the concentration of fatty acids in the blood with monounsaturation in both carbon-16 and carbon-18 chains and diunsaturation in the later carbon chains. These changes have not been reported in any disease state.


[Atherosclerotic aneurysm of the subclavian artery]. An aneurysm of the right subclavian artery, a rare pathologic entity, is described. The presence of a pulsatile mass in the cervical region should always suggest the diagnosis, which is best confirmed by arteriography. Approaching the lesion by partial sternotomy extending to the third intercostal space gives excellent exposure. The aneurysm should be resected and vascular continuity re-established by the use of a synthetic prosthesis.