Spinocerebellar tracts in the brush-tailed possum, Trichosurus vulpecula. The direct projections of the spinal cord onto the cerebellar cortex were traced using Nauta method following the placement of cervical or thoracic spinal cord hemisections in six brush-tailed possums. Degenerating fibres reached the cerebellum via typically placed dorsal and ventral spinocerebellar tracts. Although complete differentiation of the terminations of ventral and dorsal tracts was not possible, it was found that the dorsal tract terminates mainly in the ipsilateral anterior lobe ermis and in the pyramis and paraflocculus of the ipsilateral posterior lobe. The ventral tract ends almost entirely in the anterior lobe with the majority of fibres terminating contralateral to the side of the hemisection. Within the anterior lobe, degenerating fibers were distributed fairly symmetrically about the midline in five sagittal rows. Three such rows were found in the posterior lobe. The relatively small number of rows in the anterior lobe (five) may be a characteristic feature of marsupials when compared with eutherian mammals.


Tail pinch-induced arousal and stimulus-bound behavior in rats with lateral hypothalamic lesions. Further evaluation of hypothalamic control of feeding and drinking. Arousal induced by tail pinching results in stimulus-bound feeding, licking and gnawing in male rats during the aphagic and adipsic phase that follows electrolytic damage to the lateral hypothalamus (LH). Such stimulus-bound behavior is very similar to electrically induced stimulus-bound behavior. Furthermore, brain-damaged animals during tail pinch-induced drinking trials are responsive to the sensory properties of the test liquid. Chocolate milk is consumed but tap water is actively rejected. Tail pinch to sham-operated control rats failed to induce such behavior; instead, it induced rage behavior towards the hand that pinched the tail. The results support the conclusion that rats with LH lesions require an arousing stimulus for feeding but that the same externally applied arousing stimulus enhances active rejection of tap water.


Pattern generator for repetitive avian vocalization: preliminary localization and functional characterization. Electrical stimulation of the midbrain call areas was used to drive medullary neurons. Their activity was recorded with fine (25 mum) wire electrodes that allowed the nearer ones to be resolved as units. Syringeal (hypoglossal) motor neurons were identified by antidromic activation. Various units were turned on, speeded, slowed, stopped, or caused to fire in repetitive bursts. All units that were antidromically activated by hypoglossal stimulation fired in repetitive bursts with a rhythms which closely resembled that of calling. Many other units also fired in this bursting pattern, and the large majority of them were found at the obex or caudal to it despite extensive search rostrally. The nature of likely inputs to the medullary call neurons is discussed.


Persistence of the pattern of feeding in chicks with hyperstriatal lesions. Chicks with dorsal midline hyperstriatal lesions (DMHA) were trained to prefer red to yellow food before being presented with a choice from a plain floor (experiment 1) or a pebble-encrusted floor (experiment 2). On both tests DMHAs showed a relatively stable pattern of choice compared to controls. In experiment 1, controls decreased their intake of non-preferred yellow food on day 1, but this sharply increased on subsequent tests. In experiment 2, controls increased the number of pebbles pecked, and thus, the length of a run of pecks on non-preferred food changed with respect to DMHAs. Chicks with more lateral lesions gave patterns distinct from controls and DMHAs showing an initial disruption of the trained preference. The choice of chicks with more ventral or posterior lesions could not be distinguished from controls. The lack of lability of the trained feeding behavior of DMHA-lesioned chicks is interpreted as consistent with the suggestion that the DMHA may have functions which are similar to the "hippocampus" of mammals.


Comparisons between brains of a large and a small hystricomorph rodent: capybara, Hydrochoerus and guinea pig, Cavia; neocortical projection regions and measurements of brain subdivisions. Somatic sensory, auditory and visual areas of cerebral neocortex were mapped in anesthetized capybaras using surface macroelectrode-evoked potential recording methods. The cortical motor area was mapped using electrical stimulation methods. The results of these experiments in the largest living rodent were similar to those found for the cortical sensory and motor areas of guinea pigs, a small rodent in a closely related family. The representation of the perioral skin in SI cortex was relatively large in capybaras and guinea pigs. In capybara, several cortical sulci reliably demarcate different cortical projection areas from one another. Quantitive neuroanatomical comparisons of volumes and neuron numbers in several major prosencephalic nuclei revealed that all nuclear masses are larger in capybara than in guinea pig, but that different nuclei are enlarged to different degrees. Possible causes of larger brains in larger animals are discussed.


Somatic sensory cortex of llama (Lama glama). The somatic sensory cortex (SI and SII) was mapped in llamas using microelectrode mapping methods developed earlier in a study of SI of the slow loris. Projections to SI from the llama's prehensile browsing lips were differentially enlarged when compared to those reported for sheep. In llama, SII was reversed in its mediolatreal pattern from that reported for SII in most other mammals. Fissural landmarks reliably demarcated different projections within SI, between SI and SII and between SI or SII and other surrounding nonsensory areas. The use of microelectrode mapping methods in different mammals to determine gyral and fissural homologies is discussed.


Some morphological, physiological and behavioral specializations in North American beavers (Castor canadensis). In order to gain insight into the functional properties of the tail in North American beavers (Castor canadensis) we (1) examined morphological features of skeletal, muscular, vascular, cutaneous and neural structures; (2) determined the segmental organization of spinal roots and certain stimulus-response features of receptive fields of single dorsal root fibers; (3) mapped the main somatic sensory area (SI) of the cerebral neocortex, and (4) attempted to relate these findings to observations of tail behavior in living beavers. The behavioral observations revealed the beaver capable of forceful yet discrete movements of the tail in water. A morphological correlate of these motor skills was the distinct segmentally organized pattern of serial muscle tendon arrangements and spinal sensory and motor innervation. Neither the receptors innervating the scales or hairs of the tail, the stimulus-response properties of single dorsal root afferents, nor the representation of the tail in SI suggested unusual cutaneous sensory capabilities associated with the morphological and behavioral specializations exhibited by the beaver's tail.


Mapping the brain. Historical trends in functional localization. This essay presents a brief review and evaluation of some guiding concepts during the past century of inquiry into localization of brain functions. Mapping methods are described and discussed as one useful set of approaches to defining functional localization. Each neurobiological discipline: neuroanatomy, neurophysiology, neurochemistry neuropsychology, neuroethology, clinical neurology, biophysics and bioengineering, all use map-making strategies in their search for valid spatial and temporal definitions of the phenomena in their field of interest. Particular emphasis is given to neurophysiological mapping procedures. How these procedures have evolved to become important tools for testing hypotheses about the neuroelectric, behavioral and psychological functions of specific neuroanatomical structures is discussed. The continued importance is emphasized of neurophysiological mapping as a basic set of descriptive sampling strategies for testing hypotheses about specific neural mechanisms and their adaptive operations.


Microperoxisome distribution in the central nervous system of the rat. The distribution of microperoxisomes was studied in areas of the central nervous system having high concentrations of catecholaminergic neurons and in areas lacking this neuron type, using the alkaline DAB cytochemical method for catalase. Substantial numbers of microperoxisomes are found in neurons in the locus coeruleus and in nucleus A1 of the medulla, as well as in the substantia nigra, whereas few catalase-reactive bodies are seen in neurons of the cerebrum and cerebellum. The number of catalase-reactive microperoxisomes per unit area in the catecholaminergic neurons of the CNS is comparable to the number seen previously in neurons of the peripheral cervical sympathetic ganglia. Some spinal cord neurons also contain reactive microperoxisomes. Catalase-reactive microperoxisomes are numerous in oligodendrocytes of all areas studied, and in ependymal cells bordering the third and fourth ventricles. Astrocytes contain few reactive structures in the cytoplasm near the nucleus, but they are readily found in astrocytic processes and end-feet.


Efferent projections of the insular and temporal neocortex of the cat. Anterograde degeneration resulting from small lesions placed in either the insular or temporal cortex were traced with the Fink-Heimer reduced silver procedure. In neocortical regions ipsilateral to the lesion axonal degeneration was present in auditory subdivisions AI, AII, Ep, I, T, in the second somatosensory area (SII), in the anterior and middle suprasylvian gyrus, in the posteromedial suprasylvian and posterior lateral gyri, in the posterior splenial gyrus, in the anterior two-thirds of the cingulate gyrus and in the orbitofrontal regions. With respect to interhemispheric connections, evidence was obtained for a dual pattern of projection. In addition to significant amounts of axonal and terminal degeneration in the corresponding insular or temporal fields, axonal degeneration was also present in posterior AII. In the thalamus degeneration was found in the medial dorsal, suprageniculate, and lateral posterior-pulvinar nuclei. In the posterior nuclear group (Po) and the principal division of the medial geniculate (GMp) evidence was obtained for a topographic pattern of projection; significantly more degeneration occurred in caudal Po following insular lesions whereas with temporal lesions more degeneration occurred in caudal GMp. Degeneration was also found in the dorsal cortex of the ipsilateral inferior colliculus, bilaterally in the deep layers of the superior colliculus and the periventricular central gray region, ipsilaterally in the ventromedial aspects of the head and body of the caudate nucleus, and in the lateral and central nuclei of the amygdala. These findings are discussed in terms of their significance for a possible role for the insular and temporal neocortex (I-T) in both multimodal sensory discrimination and sensory-visceral integrative functions.


Inputs to trigeminal brain stem neurones from facial, oral, tooth pulp and pharyngolaryngeal tissues: I. Responses to innocuous and noxious stimuli. Responses evoked in anaesthetized or decerebrate cats by stimulation of afferents supplying the face, mouth, pharynx, larynx, tooth pulp and jaw muscles were recorded from single neurones located in the trigeminal (V) main sensory nucleus, V nucleus oralis, and adjacent regions. Many cells (both V-thalamic relay and non-relay with localized V mechanoreceptive cutaneous fields could be activated by stimulation of a number of these afferents. A particularly prominent short-latency (often monosynaptic) input was noted from the canine tooth pulp, stimulation of which is generally considered to elicit only responses of pain in man. Control experiments showed that pulp-evoked responses were not the result of stimulus spread to tissues outside the pulp. The interaction of these various inputs to neurones at this level of the V brain stem complex typically resulted in a prolonged period of inhibition that was sometimes preceded by a short-lasting facilitatory phase. This inhibitory effect was also apparent in neurones located outside the complex, although a late facilitatory phase was frequently also noted. Our findings indicate a significant nociceptive input to V main sensory-oralis neurones, a proportion of which relay directly to the ventrobasal thalamus. The interactions described may be involved in perceptual and reflex aspects of responses to noxious and innocuous V stimuli.


Diamide acts intracellularly to enhance transmitter release: the differential permeation of diamide, DIP, DIP+1 and DIP+2 across the nerve terminal membrane. The actions of the new potent thiol oxidizing agents, diazene dicarboxylic acid bis (N'-methyl piperazide) (DIP) and the N'-methyl iodide (DIP + 1) and the bis-N'-methyl iodide (DIP + 2) salts of DIP, were tested at the frog neuromuscular junction. At 20 degrees C, DIP was as fast as the thiol oxidizing agent, diamide, in evoking transmitter release but was appreciably less effective at 6 degrees C. DIP + 1 and DIP + 2 did not increase transmitter release. Since the three agents are potent oxidizers of glutathione and since the effectiveness of the compounds appears to depend on their ability to exist, at least in part, in a neutral form at physiological pH, it is concluded that their action as promoters of transmitter release depends on their ability to permeate nerve terminal membranes. Thus, both diamide and DIP act to increase transmitter release by the intracellular oxidation of glutathione. The two charged agents, DIP + 1 and DIP + 2, are potent muscular depolarizing agents. It is probable that the quaternary nitrogen groups of these compounds render them cholinomimetics.


The influence of methylxanthines on precursor incorporation into protein and RNA of mouse brain. Pentoxifyline at 1 mM had no effect on [14C]isoleucine incorporation into mouse brain tissue suspension. At 5-20 mM, this compound inhibited incorporation. The inhibition was prompt, and it was reversible. Aminophyline at 3-12 mM produced inhibition, but theophyline at 2-16 mM had no effect. Pentoxifylline inhibited the incorporation of uridine into brain RNA to the same extent and with a similar time course as its effect on protein synthesis.


Ascending collaterals of cutaneous neurons in the fasciculus gracilis of the cat. Primary sensory neurons with myelinated axons in the sural nerve of the cat were found to be divisible into 3 systems on the basis of the length of their central collaterals in the dorsal columns. The short system consists of neurons that ascend only a segment or two in the fasciculus gracilis above their level of entry into the spinal cord. It is composed of all neurons with peripheral conduction velocities in the Adelta range and thus includes both D hair and nociceptive neurons. Approximately 35% of the Aalpha neurons join the intermediate system and ascend 4-12 segments before leaving the forsal columns. This system is composed of all sural type I neurons, as well as about 40% of the G2 hair, 40% of the intermediate field, and 50% of the F2 field neurons in the nerve. Those nociceptive neurons conducting at Aalpha velocities also contribute to the intermediate system. The remaining G2 hair, intermediate field, and F2 field neurons, together with almost all the sural type II, G1 hair, intermediate hair and F1 field neurons, join the long system and ascend to the nucleus gracilis. Fibers in the intermediate system showed a relatively abrupt decrease in conduction velocity usually of 50% or more (median 71%) a few millimeters rostral to their entry into the spinal cord. Members of the long system also decreased in conduction velocity at this point, but the magnitude of the changes was typically less than 50% of the peripheral velocity (median 36%). In addition, the ascending collaterals of the long system underwent a second reduction in conduction velocity near the cervical enlargement.


Uptake and binding of [3H]hydrocortisone by various pig brain regions. The cytosol fraction of septum, hypothalamus, and hippocampus of intact and adrenalectomized pigs possessed greater concentrations of radioactivity than the cytosol fraction of amygdala, pituitary, and cortex after an intraventricular injection of [1,2-3H]hydrocortisone. Nuclear extracts from the same brain regions possessed higher concentrations of radioactivity than nuclear extracts of the other brain regions of intact pigs. Nuclear extracts of amygdala, pituitary and hypothalamus from adrenalectomized pigs exhibited the greatest increase over intact pigs in labeled hormone concentration. When adrenalectomized pigs were administered dexamethasone prior to [3H]hydrocortisone, uptake of label was most depressed in hippocampal cytosol and cuclear extract. Also sensitive to the competitive effects of dexamethasone were septal and pituitary nuclear extracts. In intact pigs, pituitary, hippocampus and cortex exhibited higher ratios of bound to total hormone in the cytososl fraction than the other brain regions. Hippocampal and amygdala cytosol possessed the greater magnitude of increase in the ratio of bound to total hormone in adrenalectomized versus intact pigs. The pituitary, septum, amygdala, and cortex of intact and adrenalectomized pigs possessed a ratio of bound to total hormone in nuclear extract 5-10 times greater than that in hippocampus and hypothalamus. However, the latter two regions exhibited a greater increase in bound: total hormone after administration of labeled hormone to adrenalectomized pigs than nuclear extracts of the other brain regions.


Ascending collaterals of cutaneous neurons in the fasciculus gracilis of the cat during peripheral nerve regeneration. Dorsal column projection patterns and conduction velocities of regenerating myelinated sensory neurons were studied at intervals between 1 and 12 months after transection of the sural nerve. The neurons had significantly decreased conduction velocities, both in the fasciculus gracilis and in the periphery. Although dorsal root reflexes were temporarily abolished, there was no evidence of gross rearrangement of the neurons' ascending collaterals in the dorsal columns in response to transection of their peripheral processes or as a result of reestablishment of functional peripheral connections. These findings support the hypothesis that when a regenerating cutaneous sensory neuron reforms functional peripheral connections in tissue it originally innervated, its receptor properties are similar to those it had before the nerve was lesioned.


Homology of the giant serotonergic neurons (metacerebral cells) in Aplysia and pulmonate molluscs. The properties of the giant cerebral serotonin-containing neurons of the opisthobranch mollusc Aplysia californica were studied and were compared to the existing data on the giant serotonin-containing neurons (metacerebral cells) of pulmonate mulluscs. Among the properties examined were: axonal distribution, synaptic input and output, pharmacological responses, biophysical characteristics, and plasticity. With only minor exceptions, the properties of the serotonin-containing neurons of Aplysia and of pulmonate molluscs were remarkably similar, and it was concluded that these identified neurons are true homologues. The establishment of the homology of the metacerebral cells of Aplysia to the metacerebral cells of pulmonate molluscs extends the known distribution of these neurons to a second major subclass (Opisthobranchiata) of molluscs. Since pulmonate and opisthobranch molluscs differ substantially in behavioral and anatomical features, the study of the metacerebral cells of these two groups may promote the understanding of the evolutionary adaptation of the nervous system to different environmental pressures.


A quantitative correlation between single unit activity and fluorescence intensity of dopamine neurones in zona compacta of substantia nigra, as demonstrated under the influence of nicotine and physostigmine. In order to investigate the possible relationship between neuronal activity and cellular fluorescence intensity, extracellular recordings of single unit activity and determinations of fluorescence intensity of dopamine (DA) neurones by histochemical microfluorimetry were performed in the same (rostral) part of zona compacta of substantia nigra in male rats. In urethane anaesthesia, zona compacta neurones characteristically showed a slow and fairly regular type of firing. Nicotine (1 mg/kg s.c.) induced a transient decrease in unit activity for 1 min followed by a sustained increase in firing rate. During that stage, 4-5 neurones/rat were recorded at different anteroposterior levels, each during 200 sec. Microfluorimetric examination of the fluorescence intensity developed at the end of the 30-min observation period by the DA neurones of the same area revealed a marked rise in cellular fluorescence intensity. Similar results were obtained with a lower dose of nicotine and/or a shorter observation period. Additional microiontophoretic experiments supported the view that extracellular recordings of the correlative electrophysiological-microfluorimetric investigation belonged to DA neurones. Release of DA from terminals was indicated by an increase in HVA concentration of caudate-putamen in rats subjected to the same nicotine treatment. When tested on one cell during a prolonged period of time, physostigmine (0.25 mg/kg i.p.) caused an initial increase in firing rate of zona compacta neurones (5-10 min) followed by a decrease of unit activity (15-23 min). In agreement with previous observations in mice, fluorescence intensity of nigral DA neurones likewise showed a biphasic change with an initial rise and subsequent decrease (examined at 9.5 and 22-23.5 min, respectively). When mean unit activity and mean fluorescence intensity of individual rats out of various experimental groups were related to each other, a highly significant positive correlation between neuronal fluorescence intensity and firing rate was found. The results obtained with physostigmine demonstrate that mean intensity closely paralleled mean unit activity in time, so that this correlation was maintained. These findings indicate that cellular fluorescence intensity of DA neurone groups can be used as an index of the level of neuronal activity, except for cases where a drug treatment interferes directly with catecholamine synthesis or storage mechanisms.


Morphology of rats AV thalamic nucleus in light and electron microscopy. The structure of the rat's antero-ventral thalamic (AVTh) nucleus has been investigated in order to provide background information for the accompanying study in which an attempt was made to identify the synaptic terminals of the different afferent fiber systems to this nucleus by means of both EM autoradiography and the EM degeneration techniques. Nissl stained sections showed that the rat's AVTh nucleus contains mainly relatively light staining neurons which in Golgi material were found to possess tufted dendrites. In EM material three types of synaptic terminals were found which showed a topical distribution over the neuronal surface. Soma and stem dendrites carry a limited number of terminal with symmetrical synapses and flattened vesiclesmproximal dendrites carry mainly large asymmetrical synaptic terminals while distal dendrites are crowded with small asymmetrical synaptic terminals.


The precise localization of nigral afferents in the rat as determined by a retrograde tracing technique. Afferent innervation of the rat substantia nigra (SN) was studied by the retrograde horseradish peroxidase (HRP) method. High concentrations of HRP were deposited in discrete subregions of the SN by means of a microiontophoretic delivery system. Using this technique it was possible to demonstrate that the caudatonigral projection system is arranged topographically; All portions of the caudate-putamen except for a central medial core were found to contain HRP positive cells, indicative of retrograde transport. In the positive areas a much larger percentage of cells (30-50%) were found to participate in this projection than has previously been reported. Only medium size cells (12-20 mum) were found to contain the HRP reaction product. Other areas found to heavily innervate the SN were the globus pallidus, central nucleus of the amygdala and dorsal raphe nucleus. Areas containing fewer reactive cells but which also appear to innervate the SN included the prefrontal cortex and lateral habenula. These results emphasize the importance of striatonigral projections which recent studies have suggested contain a GABAergic link.


Radioautographic study of in vivo incorporation of 3H-monoamines in the cat caudate nucleus: identification of serotoninergic fibers. The localization of radioactivity was examined in the caudate nucleus of the cat, treated with an MAO inhibitor, following local superfusion of the ventricular surface of the structure with low concentration of 3H-catecholamines or [3H]5-HT. The caudate nucleus was superfused continuously from 30 to 240 min using a cup technique. Light microscope or high resolution radioautographs revealed: (1) a rather diffuse incorporation of 3H-catecholamines under the subependymal region which could be hardly attributed to a specific population of nerve terminals. A loose binding of 3H-catecholamines into dopaminergic terminals could be involved in this effect. (2) An intense and selective uptake of [3H]5-HT in fine scarce varicose nerve fibers localized in the ventricle as in the subependymal layer and in the neuropil of the nucleus. The labeled fibers contained numerous round or elongated large granular vesicles of 80-120 nm and exhibited only very few synaptic contacts suggesting a possible extrasynaptic liberation of 5-HT.


Cytochemical studies of lectin binding sites in smooth membrane cisternae of rat brain. The cytochemical localization of concanavalin A (con A) binding sites has been studied in Purkinje cell axons and presynaptic terminals of rat cerebellum. Smooth membrane cisternae just beneath the axolemma contain con A binding sites on the side of the membrane facing the cisternal space. At certain regions, such as the node of Ranvier, these cisternae lie in virtual apposition to the axolemma. Such a specialized system of cisternae could serve as a channel through which some of the materials synthesized in the Purkinje somata are moved to the axon terminals. The close association of the cisternae and axolemma at certain regions could be a site at which some of the transported materials contribute to renewal of the axolemma. The con A binding sites on intracellular membranes of the Purkinje cell are removed by prior glycosidic and proteolytic enzyme digestions. The results suggest that at least some of the carbohydrates lining membrane cisternae are glycoprotein in nature.


Effects of early retinal lesions on conduction velocity relationships in the dorsal lateral geniculate nucleus of the cat. Bilateral retinal lesions have been made in and around the area centralis in 5 kittens 23-28 days of age. Twelve to 14 months later, microelectrode recordings were made in the LGN of these animals. Penetrations through the medial, deafferented portion of the nucleus encountered retinally innervated cells at the same rate as penetrations through the intact lateral half of the nucleus or through the LGN of normal adult cats. The correlation between orthodromic anc antidromic latency for LGN relay cells in experimental animals was reduced when compared to normal animals, and the percentage of cells receiving dual fast and slow retinal input was increased in experimental animals. These observations are interpreted as evidence that the medial portion of the LGN was reinnervated following the neonatal retinal lesions, and that the specificities that normally exist between relay cells and their retinal afferents in terms of axonal conduction velocity were not maintained during the course of this reinnervation.


The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain. The importance of extrapyramidal and mesolimbic function for circling behaviour was investigated by placing 6-hydroxydopamine (6-OHDA) and electrolesions in the cell bodies, axons and terminals of each system. Circling behaviour was weak when 6-OHDA was placed at the centre of the substantia nigra (SN), but the characteristic contralateral/ipsilateral turning to apomorphine/amphetamine were recorded. Circling was more marked when 6-OHDA was placed anterior to the SN but was generally absent following injections posterior to the SN. However, 6-OHDA placed in the medial forebrain bundle in the lateral hypothalamus resulted in intense contralateral/ipsilateral turning to apomorphine/amphetamine. Generally, the intensity of circling responses was related to the degree of striatal dopamine (DA) depletion but the more effective lesions also caused reductions in mesolimbic DA content. However, circling was not observed following any 6-OHDA injection into the mesolimbic DA system and it is concluded that mesolimbic DA function is not essential for the initiation of circling. In contrast to the 6-OHDA lesions, rats circled ipsilateral to both apomorphine and amphetamine when the SN was damaged by electrocoagulation to cause marked depletion of striatal dopamine. Lesser depletions of striatal dopamine after electrocoagulation in different regions of the medial forebrain bundle were associated with a lower intensity of ipsilateral circling to both drugs. In general, the differences between 6-OHDA and electrolesions could not be explained by additional damage to ascending noradrenaline or 5-hydroxytryptamine pathways. Lower doses of apomorphine were effective in the 6-OHDA circling rats, and the ipsilateral striatum of such rats was more sensitive to directly applied DA. Higher doses of apomorphine were required to produce circling after chronic electrolesions which rendered the ipsilateral striatum insensitive to DA. The contralateral circling to apomorphine after 6-OHDA lesions was abolished by chronic but not by acute electrolesion of the SN. It is suggested that electrolesions of the SN cause different effects to 6-OHDA because they destroy neuronal pathways in addition to the dopaminergic nigrostriatal tract. These appear to be required for the expression of circling behaviour caused by stimulation of the denervated striatum. Whereas 6-OHDA lesions result in super-sensitivity of the denervated strital DA receptors, electrolesions may cause a hypo-sensitivity of the same receptor sites.


Comparative studies of intra- and extramitochondrial calcium phosphates from the hepatopancreas of the blue crab (Callinectes sapidus). Subcellular fractions of cytoplasmic mineral granules and mineral-loaded mitochondria were isolated from whole homogenates of hepatopancreas of the blue crab (Callinectes sapidus). Chemical, physical, and morphologic studies were carried out on both subcellular fractions, with and without prior removal of organic components by hydrazine extraction. In contrast to cytoplasmic granules, whole mitochondria contained appreciable amounts of mineral ions not associated with a solid mineral phase. Quantitative analyses and infrared spectroscopy showed cytoplasmic and mitochondrial mineral phases to be calcium phosphates of similar but not identical composition. Both cytoplasmic and mitochondrial mineral phases, as in synthetic amorphous calcium phosphate, show noncrystalline patterns when examined by infrared spectroscopy and x-ray diffraction, and a common ultrastructure of clustered spheres of approximately 100 A diameter. The findings suggest that amorphous calcium phosphate in biological systems may exhibit appreciable variation in Ca/P and in the content of foreign ions such as Mg2+, ADP, and ATP. A mitochondriogenic mechanism of calcification could not be confirmed nor refuted by this study.


Intestinal mitochondrial calcium uptake during adaptation to dietary calcium restriction. In order to evaluate the role of mitochondrial calcium uptake in intestinal calcium absorption, the effect of adaptation to dietary calcium deficiency on the in vitro uptake of calcium by isolated duodenal mitochondria was studied. Experiments were performed utilizing 28-day-old cockerels which had received a diet adequate in vitamin D3 and phosphate and containing either 0.08% or 1.20% calcium. Mitochondrial 45Ca uptake from chicks deprived of dietary calcium was not significantly different from controls. These results suggest that increased calcium uptake by intestinal mitochondria is not crucial for adaptation to a low calcium diet.


The secretory stage of amelogenesis in rat mandibular incisor teeth observed by scanning electron microscopy. In the scanning electron microscope (SEM), the structural organization of rat incisor enamel was divided into five regions: the initial prismless layer at the dentin-enamel junction; the decussating rods of inner enamel; intermediate enamel, where the structure changes from inner to outer enamel; outer enamel with parallel rods; and the surface prismless layer. There were alterations in the orientation of the ameloblasts and characteristic changes in the morphology of the Tomes' processes during the secretion of each of these regions. Initially, the developing Tomes' processes were seen within shallow pits which also contained fibrous material from dentin matrix. During the deposition of inner enamel, alternate rows of Tomes' processes were held at right angles to each other by cytoplasmic projections which originated from the proximal regions of the Tomes' processes. The cytoplasmic projections reorganized to perpendicular orientation relative to the enamel surface during the synthesis of outer enamel. Tomes' processes of outer enamel appeared as elongated flaps extending parallel to the long axis of the tooth. In the late secretory stage, the microvillous projections disappeared and the Tomes' processes were withdrawn into button-shaped structures which coalesced to form a smooth surface that rested on the enamel.


Anticholinergic premedication.

Anticholinergic premedication. Two hundred and forty-four surgical patients who received no anticholinergic premedication were compared with 160 patients who had received atropine or scopolamine before the induction of anaesthesia. Infants and patients undergoing heart surgery were excluded. Eleven anaesthetists participated in the study. They were asked to report problems with oropharyngeal and tracheobronchial secretions. Two per cent of unpremedicated patients experienced problems with secretions of a degree sufficient to require treatment. This small percentage appears insufficient to warrant routine preoperative anticholinergic medication.


Cardiac effects of succinyldicholine and succinylmonocholine. The present study evaluated possible contribution of succinylmonocholine in producing serious cardiovascular effects with or without succinyldicholine, using albino rabbits as the experimental animal. Forty-eight experiments were performed, 22 in vivo and 26 in vitro (Langendort heart). Succinyldicholine and succinylmonocholine administered separately or together produced an immediate bradycardia in vivo as well as in vitro. The combination of these drugs had a direct arhythmogenic effect as well as an indirect reflux mediated cardiac effect. When succinyldicholine was given within five minutes following a dose of succinylmonocholine there was significant nodal and ventricular ectopic beats, but no bradycardia. Dysrhythmias in in vivo hearts were abolished by cord trans-section, trimethaphan and reserpine pretreatment. There was no evidence in vivo that succinylmonocholine produced more serious bradycardia, dysrhythmias or hypotension than succinyldicholine,


Experiences with physostigmine in the reversal of adverse post-anaesthetic effects. Physostigmine salicylate has proved to be a very useful agent for use in the recovery room. All but two of our first 110 patients receiving it were returned to full consciousness, whether they had been comatose or agitated. In our hands it has been used to reverse the adverse central effects of tranquilizers, antihistamines and belladonna alkaloids.


[A new way of access into the internal jugular vein]. This paper describes a new technique for the canulation of the internal jugular vein. A transsection of the neck at the level of C4 (upper border of the thyroid cartilage) (Figure 1) shows the relative position of the internal jugular vein, the carotid artery and the sternocleidomastoid muscle. The internal jugular vein at this level is more superficial than is usually imagined. A cutaneous point of entry placed at the level of the thyroid cartilage on the medial border of the sternocleidomastoid muscle would be directly above, at the zenith of the carotid artery. From that point, moving a needle externally hugging the posterior aspect of the muscle will make it possible to reach the vein while actually moving away from the carotid artery.


The use of procaine in acquired malignant hyperthermia in a patient with malignant melanoma metastatic to the parathyroid gland: a case report. The use of intravenous procaine in the treatment of hyperpyrexia in a patient with hyperparathyroidism has not been previously reported. A case of metastatic malignant melanoma precipitating the syndrome of hypertonicity of muscle, hyperpyrexia, acidemia, hypercalcemia and elevated serum parathormone levels is presented. Mithramycin was used in an attempt to reduce elevated serum calcium concentrations. The use of intravenous procaine in "caffeine rigor" and malignant hyperthermia due to succinylcholine and halothane formed the basis for its trial in this case. The relationship between cyclic AMP and calcium ions is discussed in postulating mechanism of procaine action.


The adenosine triphosphate (ATP) depletion test: comparison with the caffeine contracture test as a method of diagnosing malignant hyperthermia susceptibility. The adenosine triphosphate (ATP depletion ratio, which is the ratio [ATP] in skeletal muscle equilibrated with carbogen and 4% halothane for 30 minutes divided by [ATP] in skeletal muscle equilibrated with carbogen alone for 30 minutes is less than normal in most but not in all rigid MHS patients. The ratio is normal in non-rigid MHS patients. This diagnostic tool is, therefore, useful in the diagnosis of rigid MH. It is not, however, such a sensitive diagnostic parameter as the caffeine contracture test.


Awareness and dreams during general anaesthesia for Caesarian section a study of incidence. One hundred Nigerian patients presenting for emergency caesarian section were interviewed within the first 24 hours post-operatively. The purpose was to determine the incidence of awareness and dreams. The standard anaesthetic technique consisted of atropine 0.6 mg and thiopentone 250 mg given intravenously at the time of induction, suxamethonium bromide 40 mg intravenously to facilitate tracheal intubation and nitrous oxide/oxygen/pancuronium for maintenance. The incidence of awareness was 4% while the incidence of dreaming was 17%. Most (94%) of the patients said they dreamed only occasionally at home and of these, 15% claimed they dreamed more frequently when pregnant than when not pregnant.


Urinary morphine excretion during and after morphine anaesthesia for open-heart surgery in children. The urine of 20 children undergoing complete correction of atrial septal defect (ASD) or tetralogy of Fallot (TF) were analyzed for morphine and its glucuronide conjugation product before and after induction of morphine anaesthesia, throughout the operation and for two hours post-operatively. Children with ASD had a higher, mean urine flow rate during anesthetic induction and during the entire operation than those with TF (P less than 0.01). ASD children excreted a greater percentage of the administered morphine by the time they reached the recovery room and after two hours in the recovery room than those with TF. Urinary morphine in the glucuronide form increased progressively from anaesthetic induction until the post-operative period in both groups and was more than 93% after two hours in the recovery room. Fifty-five per cent of ASD patients had respiratory dynamics that enabled them to be extubated within six hours of the end of their operation. Those that could be extubated after six hours had excreted a significantly greater percentage of morphine than those that couldn't (P less than 0.025). None of the children with TF could be extubated until the day after operation. These data demonstrate that the ability to maintain adequate spontaneous respiration after morphine anaesthesia is directly related to urinary output during anaesthesia and operation.


Diazepam-ketamine anaesthesia for open heart surgery a "micro-mini" drip administration technique. Two hundred open-heart cases were anaesthetized with a diazepam-ketamine combination. The results were excellent. A "Micro-Mini" drip technique insured low, even, but adequate dose levels of ketamine and less drug was used. Induction and maintenance are simple and smooth. Effects on the cardiovascular system and respiratory system are minimal. The margin of safety is wide and 100% oxygen can be used whenever needed.


Normocapnic ventilation using the circle system. A formula is derived for maintaining normocapnia during controlled ventilation using a circle system without carbon dioxide absorption. In a series of 70 patients, unselected in terms of age, sex, obesity, ASA status, body position during operation, type of anaesthetic administered or type of circle system used, it was found that a total fresh gas flow of 50 ml/kg body weight/min and a minute ventilation of 120 to 150 ml/kg body weight at a rate of 10 to 12/min achieved normocapnia. For moderate hypocapnia a total fresh gas flow of 60 ml/kg body weight/min and a minute ventilation of 120 ml/kg at a rate of 10-12/min is suggested.


The amino acid sequence of wheat beta-purothionin. The complete amino acid sequence of beta-purothionin, a low molecular weight, very basic, protein isolated from wheat endosperm material, has been determined. beta-purothionin is toxic to some bacteria, to yeasts, and to animals when injected. The protein contains 45 amino acid residues and has a molecular weight of 4913. The 8 cysteine and 10 basic residues are distributed throughout the molecule. The primary structure of the protein shows considerable homology to those of the viscotoxins, which are toxic, small, basic proteins found in the leaves and stems of European mistletoe (Viscum album L.).


Relationships between nucleoside triphosphate pyrophosphohydrolase activity and inosine triphosphate accumulation in human erythrocytes. The relationship between nucleoside triphosphate pyrophosphohydrolast (NTPH) (EC 3.6.1.19) activity in erythrocyte lysates and accumulation of radioactive inosine triphosphate (ITP) in human erythrocytes incubated in vitro with [14C]hypoxanthine, was studied in 93 humans. When ITP accumulation, expressed as percentage of total radioactive nucleotides, was plotted against NTPH specific activity, an inverse relationship was found to exist. A continous spectrum of NTPH specific activities and ITP accumulation values exists in the human population and the relationship between these two parameters follows the relationship of substrate concentration to enzyme activity predicted by Michaelis-Menten enzyme kinetics. One interpretation of these data is that the ITP concentration in human red blood cells is controlled by the degradation of ITP to IMP and pyrophosphate catalyzed by NTPH.


Chloroplastic proteins of wheat and rye grown at warm and cold-hardening temperatures. Soluble proteins and membrane polypeptides were separated from chloroplasts isolated intact from a cultivar each of spring wheat, winter wheat, and more freeze-resistant rye, and changes in them associated with cold hardening were detected by means of polyacrylamide gel electrophoresis. No drastic changes in chloroplast membrane polypeptides occurred during growth at low temperatures in the three cultivars. However, subtle changes were evident in the soluble chloroplast protein fraction. In this fraction at least one varietal difference was discernable, yet all cultivars produced a new protein band of lowest mobility during growth at low temperatures. After the preparations were fractionated by Sephadex G-50 all unhardened plant material displayed two peaks in the region of the fraction I protein band, whereas all cold-hardening material displayed one peak. A different band of soluble protein was present only after cold hardening in Kharkov whear and Puma rye, and was not present in extracts from the cold-grown spring wheat.


Structure and function of insulin: preparation and biological activity of guinea pig des B-Asp30,des-A-Asn21-insulin. Bovine des-B-Ala30,des-A-Asn21-insulin and guinea pig des-B-Asp30,des-A-Asn21-insulin were prepared from bovine and guinea pig insulin by digestion with carboxypeptidase A (EC 3.4.12.2). As reported by other investigators, the biological activity of bovine des-Ala30,des-Asn21-insulin was less than 10% that of bovine insulin. Contrary to theoretical consideration, removal of A-Asn21 and B-Asp30 from the carbosyl termini of guinea pig insulin resulted in a loss of more than 90% of the biological activity. Receptor binding studies of these insulin derivatives demonstrated a good correlation between the loss of biological activity and the decrease in binding affinity. It is suggested that the carboxyl terminal A-Asn21 of insulin may interact directly with the insulin receptor.


Amino acid sequence of penicillopepsin. I. Isolation and characterization of the chymotryptic peptides. The amino acid sequences of 48 peptides obtained from a chymotryptic digest of the mould acid protease, penicillopepsin (EC 3.4.23.7), have been determined. These peptides established the sequences of 26 unique fragments of up to 28 residues in length. The 28-residue fragment was identified as the N-terminal region. The C terminal region is represented by a 13-residue fragment. The amino acids contained in these fragments account for some 85% of the residues of the enzyme.


Amino acid sequence of penicillopepsin. III. Isolation and characterization of amino terminal, tryptic, and tryptophanyl peptides. The amino acid sequence of peptides isolated from a tryptic digest of penicillopepsin (EC 3.4.23.7), a subtilisin (EC 3.4.21.14) digest of maleylated penicillopepsin, and a chymotryptic digest of penicillopepsin modified with dinitrophenylsulfenyl (DNPS) chloride have been determined. The first two digests identified four of the five lysyl residues of the enzyme as well as the N-terminal peptide. The third digest provided overlaps at three of the tryptophanyl residues. The DNPS-tryptophan peptides were isolated on an affinity column prepared by coupling dinitrophenyl antibody raised in sheep to cyanogen bromide-activated Sepharose.


Four-and five-step kinetic models of lactate dehydrogenase. A five-step model for the reaction catalyzed by beef heart lactate dehydrogenase (EC 1.1.1.27) reconciles differences observed in the four-step model if pre-steady-state data in the forward direction are compared with similar data in the reverse direction. The relationship between the four-and five-step models indicates what problems can develop when an incomplete model is proposed. Nevertheless, there are advantages to using the less complicated four-step model when comparing the molecular kinetics of enzymes catalyzing the same reaction but obtained from different sources.


Binding constants for tetramethylammonium ion determined with irreversible inhibitors of acetylcholinesterase. The reversible binding constant (Ki) for tetramethylammonium ion (TMA) was determined from the decrease in the bimolecular rate constant (ki) observed with each of 21 organophosphate or carbamate inhibitors of acetylcholinesterase (EC 3.1.1.7). The Ki values obtained were reasonably constant (5.8 X 10(-4) +/- 0.38 M), and this is consistent with reports indicating that TMA binds to a single site on the enzyme.


Genetic effects of feeding irradiated wheat to mice. The effects of feeding irradiated wheat in mice on bone marrow and testis chromosomes, germ cell numbers and dominant lethal mutations were investigated. Feeding of freshly irradiated wheat resulted in significantly increased incidence of polyploid cells in bone marrow, aneuploid cells in testis, reduction in number of spermatogonia of types A, B and resting primary spermatocytes as well as a higher mutagenic index. Such a response was not observed when mice were fed stored irradiated wheat. Also there was no difference between the mice fed un-irradiated wheat and stored irradiated wheat.


Linkage disequilibrium between functionally related enzyme loci of Drosophila mojavensis. Gametic frequencies at four enzyme loci of the second chromosome of Drosophila mojavensis race B were obtained from six localities. The four loci were selected so that they code for functionally related enzymes; two code for esterases, one for xanthine dehydrogenase and one for acetaldehyde oxidase. In Drosophila the two latter enzymes are under the same regulatory control and their physiological functions might be related as well. Electrophoretic variants at the locicoding for these two enzymes were found not tobe in pair-wise linkage equilibrium. Other pair-wise combinations were in linkage equilibrium. It is argued that selectively maintained nonrandom associations may occur frequently between linked loci, the enzymatic products of which are functionally related, share common subunits or are under the same regulatory control.


The Giemsa banding pattern of the Australian Swamp Buffalo (Bubalus bubalis): chromosome homology with other bovidae. A Giemsa banding method was used to obtain preparations from which a G-band idiogram for the chromosomes of the Australian Swamp Buffalo (Bubalus bubalis) was constructed. Comparison with the G-banding patterns for goat, sheep, and ox chromosomes showed a remarkably close similarity individual paris, banding pattern homologies for the buffalo metacentric autosomes being identifiable among the acrocentric autosomes of the other species. However, the goat and sheep lacked a comparable autosome to the buffalo 10, the buffalo lacked an autosome comparable to the ox 12, the acrocentric X chromosome of the buffalo banded most closely to the goat X and was least like the ox. The buffalo Y chromosome was unlike its counterpart in the other species. The results are in keeping with the previously expressed view of evolution within the Bovidae by a Robertsonian mechanism modified by the apparent absence of one pari of autosomes from the buffalo and of a different pari from sheep and goats.


Quantitative aspects of secretion and hepatic removal of glucagon in sheep. The secretion of immunoreactive glucagon (IRG) into the portal blood and its removal by the liver were determined in conscious-fed sheep by simultaneous measurement of venoarterial plasma concentration differences and portal and hepatic plasma flows. IRG was determined using Manns' antiserum and Unger's 30K antiserum, the latter being highly specific for pancreatic glucagon. In 21 experiments in which Manns' antiserum was used the IRG secretory rate was 7.1 +/- u.4 mug/h. The value using 30K antiserum was lower (5.5 +/- 1.3, n=6), but not significantly different. Although the hepatic extraction ratio (hepatic removal - total IRG presented to the liver) was only 7%, the hepatic removal of 2.4 +/- 0.5 mug/h was equivalent to 31-35% of the portal IRG secretory rate. Since during steady-state conditions, glucagon secretion equals glucagon removal, the liver must account for approximately one-third of the glucagon degraded by the entire body.


The influence of acute diazepam pretreatment on the action and disposition of [14C]pentobarbital in rats. Diazepam (DZP) pretreatment (100mg/kg, ip) of rats 6 h before pentobarbital administration (45 mg/kg, ip) prolonged the barbiturate-induced narcosis. The concentrations of [14C]pentobarbital and total pentobarbital derivatives in blood or brain showed no differences between control and DZP-pretreated animals. The brain and blood concentrations of pentobarbital, when measured at a time corresponding to the respective arousal times from pentobarbital narcosis, were lower in the DZP-pretreated group. These results indicate that acute DZP pretreatment increases the sensitivity of the rat brain to pentobarbital rather than inducing changes in the disposition of the barbiturate.


The perifused isolated left atrium: a preparation for studies on sugar transport in the myocardium. A procedure is described for the in vitro perifusion of the rat left atrium by recirculating medium through the atrial cavity and around the tissue, and for making the left atrium completely quiescent using surgical methods. The main advantage of this preparation is that it provides direct data on metabolic and transport processes in resting myocardium. Its use is illustrated by data on the time course, concentration dependence, insulin sensitivity and chemical specificity of the sugar transport system; in all these respects the resting left atrium resembles resting skeletal muscle.


Effect of adrenaline on sugar transport in the perifused left atrium. The effect of adrenaline on the membrane transport of 3-methylglucose was studied in perifused isolated rat left atria that had been fully arrested. In this preparation a high concentration of adrenaline stimulated and a low one decreased sugar transport. The stimulatory effect was strongly inhibited by the beta-adrenergic blocker propranolol and by the antilipolytic agent nicotinic acid. As the atria were not beating, the effects were not mediated by changes in the rate or strength of muscular contraction. The possible mechanisms of these effects of adrenaline on sugar transport are discussed.


Influence of the degree of hydrolysis of beef tallow on its absorption in the young pig. Beef tallow was hydrolyzed to produce a series of fats with 3, 10, 20, 46, and 100% free fatty acids, which were incorporated at the level of 10% into semipurified diets. These diets along with a low-fat control diet were each fed to five piglets from 10 to 22 days of age. Tridodecyl glycerol ether was used as an indicator of fat absorption. Feces samples were collected between 19 and 22 days of age and the pigs were killed to allow samples of digesta to be collected. Analysis of feces and digesta allowed the progress of fat absorption to be monitored through the digestive tract. The corrected absorbability of the total lipid was between 88 and 93% for the partially hydrolyzed tallows, but was only 75% for the completely hydrolyzed tallow. The oleic acid was well absorbed (95-99%) in all the diets; palmitic and stearic acids were also well absorbed in the intact and partially hydrolyzed tallow (82-84% and 63-77%, respectively, the for palmitic and stearic acids), but their absorption was impaired in the completely hydrolyzed tallow (62% and 38ll intestine is the major site of fat uptake. Comparison of the amounts of fatty acids in the ileal digesta and in thl feces showed that there was no change in the total amount of fat in the digesta as it passed through the large intestine.


The composition of lipids in intestinal digesta of young pigs receiving diets containing tallow and tallow fatty acids. Three semipurified diets containing a low level of fat or 10 percent of either beef tallow or beef tallow free fatty acids were fed to young pigs. Jejunal digesta was sampled 1.5, 2.5, 3.5, and 4.5 h after feeding by aspiration through tubes leading from the jejunal lumen to the exterior. The samples were forced through Millipore filters (1 x 10(-7) m pore size) to separate aqueous phase and oil phase lipid. The total and aqueous phase lipid was separated into triglyceride, monoglyceride, and free fatty acid, and the fatty acid composition of each fraction determined. The concentration of aqueous phase lipid was not influenced by diet, although the concentration of the oil phase lipid was generally higher for the addition of fat to the diets; the increase was greater for the beef tallow free fatty acid diet than for the beef tallow diet. Free fatty acids were the predominant component of the aqueous phase lipid along with some monoglyceride and traces of triglyceride. The major component of the oil phastions of triglyceride and monoglyceride. These must have been derived from endogenously secreted lipid in the case of the tallow fatty acid diet. Thus, the lower digestibility of completely hydrolyzed beef tallow than of conventional beef tallow was not due to an absence of monoglyceride in the intestinal lumen. The proportion of stearic acid in the jejunal digesta was greater than in the dietary lipid, whereas there were lower proportions of palmitic and oleic acids in the jejunal digesta than in the diet; the effect being most pronounced for the tallow free fatty acid diet. The ratio of oleic to palmitic acid in the aqueous phase was less than in the lipid phase suggesting preferential uptake of oleic acid from the micelle by the intestinal mucosa.


Insulin resistance and its reversal by in vivo infusion of ATP in hermorrhagic shock. Hemorrhagic shock in rats was produced by bleeding the animals to a mean arterial pressure of 40 mmHg, which was maintained for 2 h. Muscles from these animals ('shock' muscles) demonstrated basal glucose uptake values unchanged from control values but, unlike the control muscles, the "shock' muscles showed resistance to the stimulation of glucose uptake by insulin. Infusion of ATP-MgCl2, ADP-MgCl2, adenosine-MgCl2, or GTP-MgCl2 to animals following shock had no effect on basal glucose uptake; however, ATP-MgCl2 but not the other nucleotides permitted insulin to exert its stimulatory effect on such muscles. An optimal insulin effect in ATP-MgCl2 treated 'shock' muscles occurred at an insulin concentration of u.001 U/ml, which is also the concentration required to produce optimal insulin effect in control muscles. Following 1-h incubation in Krebs-HCO3 medium, intracellular ATP contents of 'shock' muscles were about 50% lower than in control muscles. Treatment with ATP-MgCl2 following shock, however, resulted in ATP contents in such muscles similar to those in control muscles. Possible mechanisms for this reversal of insulin resistance by in vivo infusion of ATP-MgCl2 in shock are discussed.


Uptake of ATP by liver and kidney in vitro. Rat liver and kidney slices were incubated at 37 degrees C for 1 h in 1.0 ml of Krebs-HCO3 buffer containing 10mM glucose and one of the following: 5 mM [8-14C]ATP, 5 mM [8-14C]ADP, 5 mM [8-14C]AMP, or 5 mM [8-14C]ation medium and tissue extract were subjected to electrophoretic separation and the radioactivity present in ATP, ADP, AMP, IMP, inosine, adenosine, and hypoxanthine was counted. Extensive degradation of the added nucleotide was observed in the presence of both tissues. The concentrations of 14C-labeled ATP and ADP found in the liver and kidney indicated that these compounds were present within the cells. Evidence is presented which suggests that ATP, and to a lesser extent ADP, entered the liver and kidney as such and were not synthesized within the cell from 14C-labeled adenosine.


Phenobarbitone-induced urinary excretions of D-glucaric acid and 6beta-hydroxycortisol in man. The urinary excretion of D-glucaric acid and 6beta-hydroxycortisol were determined in normal subjects before, during, and after 14 days treatment with placebo or phenobarbitone. The excretion of both metabolites was significantly potentiated by phenobarbitone and returned to baseline values 1 month after treatment was withdrawn. It was suggested that the determination of urinary D-glucaric acid reflects the activity of the hepatic microsomal mixed function oxidase system after the administration of an inducing agent such as phenobarbitone.


The effects of AMP on the potential of rat cerebral cortical neurones. Intracellular recordings have shown that AMP, applied extracellularly, consistently produces a hyperpolarization in the absence of any pronounced alterations in membrane conductance and causes a reduction in spontaneously occurring and evoked postsynaptic potentials. Potential mechanisms of action of AMP are discussed, including the possibility that it may depress transmitter release from presynaptic nerve terminals.


A randomized controlled trial of home care: clinical outcome for five surgical procedures. The clinical function of patients receiving home care after five surgical procedures was assessed. Hospital patients who normally would have received minimal nursing care at the end of their hospital stay were randomly assigned to an experimental home-care group or a control group who were discharged from hospital after the normal length of stay. Comprisons of "untoward events" (discomfort, infection, delayed healing, or complications) are reported for the two groups in five surgical categories (varicose vein stripping, herniorrhaphy, cholecystectomy, anal and rectal operations and abdominal hysterectomy) where the home-care program operated efficientyl. No apparent differences in the rates of untoward events were noted between hospital and home-care groups. It is concluded that home care should be considered for reasons other than clinical function, such as socio-economic functioning, the wishes of the patient, or more efficient use of hospital space.


Spontaneous rupture of liver in patient on oral contraceptives. Hemoperitoneum as a result of spontaneous rupture of the liver occurred in a 28-year-old woman who had been takingoral contraceptives for 7 years. The hemorrhage occurred between a benign tumour and the liver and was treated by left hepatic lobectomy. The pathologic aspects of this tumour are discussed and the current literature is reviewed. Conservative excision compatible with hemostasis is the recommended treatment.


Acute cardiac failure: the relation between coronary flow and cardiac function. To study the effects of acute coronary hypotension on the working dog heart in situ, both coronary arteries were cannulated and perfused with oxygenated blood at controlled pressures (40 to 120 mm Hg). At a perfusion pressure of 120 mm Hg, total coronary artery flow appeared to be sufficient (0.95+/-0.08 ml/min-g) to maintain normal cardiac performance for a 2.5-hour observation period. During incremental decreases in coronary perfusion pressure, significant linear correlations were found between coronary flow and cardiac index (r=0.84), left ventricular maximum dP/dt (r=0.83), stroke index (r=0.82), stroke work (r=0.83) and mean arterial pressure (r=0.62). During simulated shock conditions (systolic arterial pressure, less than 75 mm Hg), relative reductions in coronary flow (-60.9+/-4.0%) paralleled changes seen in cardiac function and persisted for 28+/-4 min.


Sagittal hemipatellectomy in the treatment of chondromalacia patellae. A study of the preoperative assessment, surgical technique and follow-up in 17 surgical procedures (16 patients) indicates that sagital hemipatellectomy is an acceptable alternative form of surgical treatment in patients with chronic painful chondromalacia patellae. The study series comprised 16 patient (mean age, 21 years) in whom the duration of symptoms averaged 5 years, 2 months. In all patients the procedure relieved the pain and permitted a return to their accustomed work and exercise routine within 3 to 6 months after operation. The duration of follow-up is still too short to permit evaluation of possible late complications of this procedure.


Prosthetic replacement of the anterior cruciate ligament in dogs. Prosthetic cruciate ligaments are now used clinically. Long-term results are not yet available and for that reason an attempt has been made to reproduce the clnical situation in dogs. Post-traumatic osteoarthritis was inevitably noted following simple excision of the anterior cruciate ligament in a control group of 10 animals. Different prosthetic materials were used and their breaking point was compared with that of normal anterior cruciate ligaments. The longest follow-up period was 6 months. Although some animals had no clinically demonstrable instability, at autopsy all prosthetic ligaments were noted to have failed. The degree of post-traumatic osteoarthritis was directly related to the duration of follow-up. The causes of failure of the prosthetic ligament do not appear to be related to the method of anchorage to bone but rather to the type of prosthetic material used. Although the tensile strength may occasionally have been sufficient, the materials did not have the required elastic characteristics to meet the physiologic demands of a normal cruciate ligament.


The Canadian influenza decision, 1976.

The Canadian influenza decision, 1976. This paper explains the Canadian decision process following the isolation and identification of A/New Jersey/8/76 at Fort Dix, New Jersey in February 1976. The cause for concern was the emergence of a swine-like strain related to that which caused the 1918-19 pandemic, together with proved man-to-man transmission. This concern was reinforced since all new influenza A strains known to have infected the number of persons involved at Fort Dix have become strains of epidemic importance. The Fort Dix outbreak gave sufficient warning to allow implementation of a national vaccination program, to prevent and protect against influenza. In the past such an opportunity had not occurred, and vaccine use had, at best, constituted an intervention in the course of an outbreak. The National Advisory Committee on Immunizing Agents had all available information when it reached its decision to recommend vaccination with bivalent (A/Victoria and A/New Jersey) or with monovalent (A/New Jersey) vaccine for selective, high-risk groups. This was an independent, scientifically based decision.


Alcohol and acetaldehyde metabolism in Caucasians, Chinese and Amerinds. Ethanol (0.4 to 0.8 g/kg in 30 minutes) was given by mouth to 102 healthy young volunteers (37 Caucasian men, 21 Caucasian women, 20 Chinese men and 24 Ojibwa men). Venous blood concentrations of ethanol and acetaldehyde 60, 90, 120 and 150 minutes after the end of drinking were measured by gas chromatography. The calculated rates of ethanol metabolism in the Caucasian men and women did not differ, but the overall group means for subgroups of Caucasians (103.6 mg/kg-h), Chinese (136.6 mg/kg-h) and Ojibwa (182.7 mg/kg-h) with decreasing postabsorption values differed significantly from each other. Mean acetaldehyde values paralleled the rates of ethanol metabolism: Ojibwa, 14.6 mug/ml; Chinese, 10.0 mug/ml; and Caucasians, 9.4 mug/ml. The high rate of ethanol metabolism in Amerind subjects differs from previous findings. Habitual level of alcohol consumption, proportion of body fat and genetic factors appear to account for most of the group differences.


Survey of impaired drivers, fatally injured or surviving, who caused fatal highway accidents in Alberta in 1970-72. In 1970-72, 456 (53.4%) of 854 drivers responsible for a motor vehicle accident in which either they or other persons were killed had been drinking beforehand. Of surviving culpable drivers tested for blood alcohol concentration 81.7% were found to be legally impaired; however, only 24.8% of these drivers were tested. Because surviving culpable drivers pose a possible future hazard to highway safety it is important that data on this group be collected and analysed.


Saskatchewan dial-access drug information service. In September 1974 the colleges of pharmacy and medicine of the University of Saskatchewan began offering a drug information service to the pharmacists and physicians of Saskatchewan without charge. With the help of a radio-page system, calls are taken immediately by experienced pharmacists and pharmacologists. The cost of long-distance phone calls is borne by grants from the Saskatchewan medical and pharmaceutical associations. During the 1st year of operation 415 requests for information were received. Of 93 persons who called up to Feb. 28, 1975, 76% responded to an evaluation questionnaire; virtually all described the service as very valuable. The information received resulted in the alteration of drug therapy in one third of calls requesting information to assist in current treatment of a patient.


Miliary tuberculosis presenting with hyponatremia and thrombocytopenia. A 74-year-old woman with miliary tuberculosis had moderately severe hyponatremia due to inappropriate secretion of antidiuretic hormone (SIADH) and very severe thrombocytopenia without other hematologic abnormalities. She was treated with isoniazid, rifampin, ethambutol, prednisone, vincristine and fluid restriction and recovered completely. The SIADH may have been a response by the posterior pituitary to a decrease in intravascular volume resulting from the extensive pulmonary disease or associated hypoxia, or the tuberculous lung may have released ADH or an ADH-like substance. The thrombocytopenia may have resulted from a direct or indirect toxic effect of infection or, less likely, the tuberculosis may have activated latent idiopathic thrombocytopenic purpura.


Evolution of an active psychogeriatric day hospital. A geriatric day hospital was established as part of the psychogeriatric unit of the Royal Ottawa Hospital. While initially this day hospital was integrated with day hospital programs of other units, it became apparent that a separate facility was desirable. The activities and programs of the psychogeriatric day hospital, run by one registered nurse, were integrated with those of the geriatric inpatient unit. It was found to be advantageous for inpatients and day hospital patients to share the same physical facilities. The majority of day hospital patients came from the inpatient unit; almost all had affective disorders. The emphasis was on reintegration into the community. During the 1st year of operation there were 75 patients in the program; only 3 needed admission to the inpatient unit and 1 was readmitted after discharge.


Variation in response to dexamethasone of a patient with Cushing's syndrome. A patient with Cushing's syndrome due to a nonresectable chromophobe adenoma underwent external irradiation of the hypothalamic-pituitary area. The signs of Cushing's syndrome ameliorated subsequently but recurred eventually, necessitating bilateral adrenalectomy 30 months after initial presentation. Response to dexamethasone suppression testing on four occasions varied greatly. These results may reflect alterations in sensitivity of the tumour or the hypothalamic-pituitary axis to feedback inhibition by glucocorticoids.


Dermatitis herpetiformis and leiomyomas with HLA-B8, a marker of immune diseases. Multiple cutaneous leiomyomas and dermatitis herpetiformis (DH) were found in the same patient. This association has not been previously described, although the association of malignant tumours and DH is well known. HLA-B8 was found in this patient as well as in an older brother with polymyositis; this antigen is known to be associated with other immune diseases.


Woringer-Kolopp disease. An epidermotropic variant of mycosis fungoides. Woringer-Kolopp disease is characterized by the presence of a monomorphic, tumorous infiltrate in the epidermis. A light- and electron microscopic study, and cytophotometry, of one case were performed and the results are discussed. No explanation has been found for the epidermotropic character of this condition, although an intraepidermal origin of the tumor infiltrate seems improbable. The cytomorphologic characteristics of the tumor cells shows a striking analogy to the atypical cells in the Sezary syndrome and mycosis fungoides. These findings support the hypothesis that Woringer-Kolopp disease represents a clinical variant of mycosis fungoides and the Sezary syndrome.


Combination chemotherapy of Hodgkin's disease in children. Forty-five children with advanced Hodgkin's disease (stages III and IV) received combination chemotherapy in three schedules: MOPP (mustargen, Oncovin, procarbazine, prednisolone); COPP (cyclophosphamide was substituted for mustargen); and CVPP (cyclophosphamide, vinblastine, procarbazine, prednisone). The results showed the efficacy of all drug combinations (93% complete and partial remissions). However, the superiority of the MOPP program in prolonging the duration of the complete remission rate was demonstrated. Of 29 patients who showed complete response, 24 continued in complete remission from 8 to 53 months (median duration, 21 months). The other five patients relapsed within 2 to 6 months. Thirty-six of the 45 treated patients are still alive after an average period of follow-up of 19 months. The nine patients who died were followed for an average of seven months. The histologic type, prior chemotherapy, and the age of the patients influenced the results of treatment. The role of maintenance therapy is not discussed in this series


Erythroplasia of Queyrat: treatment with topical 5-fluorouracil. Seven adult men with biopsy-confirmed erythroplasia of Queyrat (EQ) were cured of their disease with topically applied 5-fluorouracil (5-FU) under occlusion. Post-treatment biopsy specimens revealed normal histologic findings and recurrence-free follow-up periods extended up to 70 months. It is suggested that topical 5-FU is the treatment of choice for histologically confirmed EQ because of its superior results compared with thoseof surgery or radiation therapy. Our view is corroborated by several single case reports of EQ similarly treated.


Early detection of chemotherapy-related pancreatic enlargement in children using abdominal sonography: a preliminary report. At least two chemotherapeutic agents, prednisone and L-asparaginase, have been demonstrated to produce pancreatic injury. Early diagnosis of pancreatitis is frequently not possible, as symptoms are vague, physical findings may be minimal, and laboratory studies are frequently inconclusive until the injury is severe. Abdominal echography, as a monitor of pancreatic size, has proven to be helpful in the diagnosis of subclinical and early pancreatic injury of 14 of 19 selected children receiving prednisone and/or L-asparaginase therapy for acute leukemia or non-Hodgkin's lymphoma at the M.D. Anderson Hospital and Tumor Institute. Employment of this new diagnostic method permits prompt withdrawal of the causative agent(s), thus preventing further insult.


Nafoxidine--an antiestrogen for the treatment of breast cancer. Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the Investigational Drug Branch of the National Cancer Institute. It has been used effectively in the treatment of breast cancer patients. A cumulative response rate of 31% is reported for a total of 200 patients treated with this drug. Most patients have been treated with a dose of 60 mg three times a day. Side effects include dryness of skin, photosensitivity reactions and, less commonly, partial hair loss. There is a strong correlation of response to nafoxidine with the presence of estrogen receptor in the tumor and also with the response to previous hormonal treatment. Nafoxidine is a useful addition to the list of hormonal treatments in the therapy of breast cancer.


Indium bone marrow scintigraphy as an aid in selecting marrow biopsy sites for the evaluation of marrow elements in patients with lymphoma. One hundred and two previously treated lymphoma patients were studied with 111Indium bone marrow scans and bone marrow biopsies. The biopsies were considered to represent sampling errors when the cellularity of the biopsy did not reflect the general state of the marrow organ cellularity as demonstrated by the scan. In each instance the accuracy of the scan was confirmed by either another biopsy or the subsequent clinical course of the patient. Sampling errors were infrequent (1/51) in patients with normal peripheral blood counts and whose marrow had never been involved with tumor. Errors were especially likely (17/51) in patients who had had marrow involvement or those who had anemia, leukopenia, or thrombocytopenia. The 111Indium bone marrow scan allows the clinician to avoid selecting a biopsy site with a high risk for sampling error.


Lymphographic evaluation of 250 patients with malignant melanoma. Foot lymphography was performed in a selected group of 250 patients with malignant melanoma, with different sites of origin and of various stages. The overall incidence of metastases was 40%. The case material was evaluated in detail; the tumors of the inferior limb and those on different sites, e.g., vulva and abdomen, were considered separately. In the group of 188 patients with melanoma of the inferior limb, the incidence of metastases was 42%. In 51%, histologic confirmation was obtained. In the group of 62 patients with melanoma of different sites of the body, the incidence of metastases was 34% and histologic confirmation was obtained in 21 patients. The values of accuracy, sensitivity, and specificity based on the histologic confirmation of the lymphographic reports ranged from 88% to 96%. These data justify the use of lymphography in the initial diagnostic work-up and in the follow-up of these patients.


Brain scanning in patients with recurrent breast cancer. Brain scans were performed on 116 patients with recurrent breast cancer. Seventy-eight of 79 (98%) asymptomatic patients with recurrent disease had negative brain scans. Eleven of 37 (30%) patients with central nervous system (CNS) symptoms had scans indicative of intracranial metastases. There was no difference in the distribution of extracranial metastaic disease in patients who had positive brain scans when compared with those who did not. Brain scaning is of value in detecting intracranial metastases in patients with CNS symptoms. Brain scanning seems unnecessary, however, in the staging of patients with recurrent breast cancer who have no CNS symptoms.


Angioimmunoblastic lymphadenopathy: a case study. The case of a 57-year-old man with lymphadenopathy fever, splenomegaly, and polyclonal gammopathy is described. The difficult clinical course, the short lived response to cytotoxic treatment, the frequent infections, the immunologic abnormality, and the histologic findings in lymph node biopsy and postmortem material justified our diagnosis of angioimmunoblastic lymphadenopathy with dysproteinemia, a new entity described recently.


Environmental factors in cancer of the larynx: a second look. During a retrospective case-control study of recent laryngeal cancer patients, several associated factors were studied to determine possible changes in the epidemiology of laryngeal cancer between 1956 and 1974. The large sex difference noted in the early survey (male: female ratio of 14.9:1) diminished considerably in the present sample (4.6:1) because more women are cigarette smokers in the cancer age group today than was the case 20 years ago. Laryngeal cancer patients tended to be less educated than the controls and included a smaller proportion of Jews and more Catholics than the control group. The risk for developing laryngeal cnacer was considerably lower for exsmokers and long-term (10+ years) filter cigarette smokers as compared with non-filter smokers. At each level of alcohol consumption, the risk increased as exposure to tobacco increased. Occupations associated with wood exposure were found to affect the development of laryngeal cancer, independently of smoking status. Future studies should include an extensive study of nutritional deficiencies associated with alcoholism to determine if a correlation exists between such deficiencies, socioeconomic status, and an increased risk of laryngeal cnacer.


Increase of serum complement levels in cancer patients with progressing tumors. Complement levels (CH50, C3, C4 and C1q) were determined in sera of 90 healthy subjects and 200 cancer patients. Complement levels of cancer patients were significantly higher than those of the healthy subjects, but there was a stage-linked increase of complement levels. Patients in remission had nearly normal complement levels, but patients with local tumor had increased complement levels, and a further increase was observed in patients with distant metastases. Treatment of these patients with radiotherapy or cytostatic drugs lowered the complement levels. At the terminal phase of the disease we also noted a drop in complement levels.


Carcinoid tumor occurring in cystic teratoma of the kidney: a case report. Although carcinoid tumors have occurred rarely in benign teratomas of the ovary and the testis, we believe this case is the first reported of carcinoid arising in a benign cystic teratoma of the kidney. The patient was admitted to the Tagawa Hospital with a left abdominal mass and severe epigastric pain. Retrograde and intravenous pyelograms revealed marked dilatation of the left kidney; a renal tumor was diagnosed clinically. At operation, a polycystic tumor weighing 1400g was removed. Histologically, a carcinoid tumor was evident among teratoid tissues, such as columnar epithelium, cartilage, smooth muscle, and mucous secretory glands. The patient did not have a carcinoid syndrome and had an uneventful recovery.


Cervical lymph node metastasis as the first manifestation of localized extramedullary plasmacytoma. Two patients who had cervical lymph node metastases as the first symptom of a localized soft tissue extramedullary plasmacytoma of the epiglottis and nasopharynx, respectively, are described. Classical multiple myeloma was excluded by bone marrow biopsies and x-ray studies of the skeleton. In both patients, the primary tumor was diagnosed 2 years after excision of the cervical lymph node. One patient had a IgD, lambda myeloma protein in the serum and excreted lambda Bence-Jones protein into the urine. No M-component was found in the other patient. Both are living with a long survival of 8 and 4 years respectively. The presence of a cervical lymph node plasmacytoma should suggest an upper respiratory tract or oropharynx plasmacytoma rather than a primary lymph node plasmacytoma.


Parathyroid hyperplasia in primary hyperparathyroidism: a review of 85 cases. Parathyroid hyperplasia of all four glands was found to be the cause of primary hyperparathyroidism in 85 of 557 cases seen at the Massachusetts General Hospital between 1930 and 1973. There were 66 cases of chief cell hyperplasia and 19 cases of clear cell hyperplasia that were grossly, microscopically, and ultrastructurally distinct. Although the clinical findings overlap, there are several differences in the signs and symptoms between these two forms of hyperplasia. Both types are treated by subtotal removal of all the parathyroid tissue. Removal of insufficient tissue has left residual hyperparathyroidism in 45% of those with chief cell hyperplasia and 11% of those with clear cell hyperplasia after what was thought to be definitive surgery. Postoperative hypoparathyroidism was found in 15% of the patients with chief cell hyperplasia and in none with clear cell hyperplasia. These findings further suggest that removal of three and one-half glands in the more than 86% of patients with one gland involvement (adenoma or carcinoma) as the cause of primary hyperparathyroidism is unwarranted.


Water clear cell hyperplasia of parathyroid: autopsy report of a case with supernumerary glands. An unusual case of primary hyperparathyroidism involving six parathyroid glands is reported. Despite markedly elevated parathormone levels, neoplastic features were not found. This patient also had ovarian dysgenesis and hypertrophy and clear cell appearance of the salivary glands.


Human chorionic gonadotrophins (hCG) in non-trophoblastic neoplasms. Assessment of abnormalities of hCG and CEA in bronchogenic and digestive neoplasms. Evaluation of plasma hCG measurement in the diagnosis of nontrophoblastic neoplasms and assessment of the value of concomitant measurement of plasma hCG and CEA in patients with bronchogenic carcinoma and neoplasms of the digestive tract were undertaken. Only one of 70 normal control subjects had positive plasma hCG (3.5 ng/ml), whereas 54 of 320 patients with nontrophoblastic neoplasms had measurable plasma hCG (1.9 to 160 ng/ml). Forty of these patients had less than 5.1 ng/ml. Elevated plasma CEA levels of 3.6 to 140 ng/ml were found in 38 of the 70 patients with bronchogenic carcinoma and 30 of the 72 patients with neoplasms of the digestive tract in this series. Concomitant positive hCG was found in only six of the 68 patients who had elevated CEA levels, and positive hCG was found in eight of 74 patients who had normal plasma CEA. The low frequency and the modest elevation of plasma hCG, despite frequent advanced disease, indicate plasma hCG has limited value as a biologic marker for diagnosis and assessment of non-trophoblastic neoplasms.


Fecal bile acids and neutral sterols in patients with familial polyposis. Fecal neutral steroids and bile acids were measured in patients with familial polyposis, family controls who are immediate relatives of patients, and controls other than relatives. All subjects were consuming a mixed Western diet at the time of collection of stool specimens. Although the total fecal neutral sterol concentrations were not different between the groups, the patients with familial polyposis excreted a high amount of cholesterol and low levels of coprostanol and coprostanone compared with other groups. Patients with familial polyposis excreted levels of total bile acids in their feces comparable to those excreted by controls; lithocholic acid excretion was decreased in patients with familial polyposis. These findings suggest that analysis of stools for cholesterol and its metabolites be useful in screening the siblings of polyposis families for latent disease.


Mucoepidermoid carcinoma of the conjunctiva: a clinicopathologic study of five cases. Five patients with mucoepidermoid carcinoma of the conjunctiva were studied. The tumors were located close to the limbus in three patients, in the bulbar conjunctiva in one, and in the lower cul-de-sac in the remaining patient. Histopathologically, they exhibited lobules of tumor cells showing an admixture of epidermoid and mucus-secreting cells. Histochemical stains for mucin were most useful in arriving at a correct diagnosis. Follow-up information revealed that all five tumors recurred rapidly, invading the corneal stroma, intraocular structures, and orbit. Biologically, these tumors appear to be locally aggressive and should be differentiated histopathologically from the conventional squamous cell carcinoma of the conjunctiva, which carries a better prognosis. They should be managed by wide local excision, and the margins should be carefully examined for residual tumor. Frequent follow-up is recommended to detect early recurrence.


Verrucous carcinoma of skin: epithelioma cuniculatum plantare. Eight patients had plantar growths that were usually irregularly shaped, sharply outlined, verrucous, and several centimeters in greatest dimension. Clinical diagnoses included viral wart, deep mycosis, pyogenic granuloma, amelanotic melanoma, basal cell carcinoma, and eccrine poroma. The median age of the patients, and duration of the growth, were 52 and 16 years, respectively. Therapeutic modalities other than total excision were ineffective. The tumor, derived from surface epidermis, was composed of masses of pale-staining benign-appearing prickle cells, deeply invaginated by thick, compact, partially parakeratotic horn. Several lesions have recurred; amputation was required in one patient. This distinctive entity, apparently not described in the American literature, has been reported from Europe under such titles as epithelioma cuniculatum and papillomatosis cutis carcinoides. We believe that it is best interpreted as a form of verrucous carcinoma, the first cutaneous tumor--as opposed to lesions of mucous membranes and mucocutaneous junctions--to be so classified.


Bone marrow manifestations of Hodgkin's disease. Bone marrow trephine biopsies were performed on 107 previously untreated patients with Hodgkin's disease (HD). Fifteen patients (14%) exhibited bone marrow involvement. These consisted of two of three patients (67%) with lymphocyte depletion, six of 27 patients (22%) with mixed cellularity, five of 64 patients (8%) with nodular sclerosis, and two who were unclassified. Twelve patients manifested a diffuse pattern of involvement; three, a focal pattern. In eight patients more than 70% of the marrow biopsy was replaced by Hodgkin's tissue, in one patient 50% of the marrow biopsy was replaced, and in six patients less than 30% of the marrow biopsy was replaced. Typical Reed-Sternberg (RS) cells were found in the trephine biopsies in 13 of the 15 patients and mononuclear RS variants in two. Bone marrow involvement was the only evidence of stage IV disease in 10 of the 15 patients. In addition to the 15 patients with initial involvement with HD, 11 patients without marrow involvement exhibited granulomas (six) and benign lymphocytic aggregates (five) in their trephine sections. Hematological parameters were studied in all pretreatment patients. Only in the nodular sclerosis group were these parameters useful in differentiating patients with and without Hodgkin's involvement of the marrow. Seventeen additional patients who had been previously treated at the time HD was demonstrated in their bone marrow were also studied. Large areas of necrosis were frequently seen in previously treated patients and one patient demonstrated cryptococcosis in the bone marrow.


Hypertrophic pulmonary osteoarthropathy in Hodgkin's disease: reversal with chemotherapy. A case of nodular sclerosis Hodgkin's disease, stage IVB, with lung involvement and hypertrophic pulmonary osteoarthropathy (HPOA), was treated with quadruple cytotoxic chemotherapy. The pulmonary lesions, which were thin walled cavities, and the lymphadenopathy resolved completely after two courses of chemotherapy. The clubbing and all evidence of periosteal new bone formation disappeared after six courses of treatment. Complete reversal of the syndrome by chemotherapy has not been previously described. A literature review revealed 13 more cases of Hodgkin's disease associated with HPOA. The syndrome occurred for the first time at the time of diagnosis of Hodgkin's disease in 11 cases, and at recurrence in two. Tha majority of patients had advanced disease (Stage IIIB or IV). Mediastinal involvement was present in all 12 cases for which data were given; lung involvement was present in six cases and pleural involvement in three. Three cases were of the nodular sclerosis type, and one of the lymphocyte-depletion type. The HPOA syndrome in young patients with malignancy is indicative of tumors other than primary bronchial carcinomas.


Hodgkin's disease complicated by the nephrotic syndrome. A 12-year-old boy with nodular sclerosis Hodgkin's disease demonstrated nephrotic syndrome. A renal biopsy studied with light microscopy, electron microscopy, and immunofluorescence showed minimal change glomerulonephritis and some foci of fluorescence with anti-IgM. A literature review revealed that 35 cases of Hodgkin's disease with nephrotic syndrome have been reported. Possible etiologic mechanisms are discussed.


Brenner tumor of the uterus.

Brenner tumor of the uterus. Extraovarian Brenner tumors are extremely rare. Three paratesticular lesions have been observed in men. The only extraovarian Brenner tumor in a woman previously reported was located in the broad ligament. This paper describes a small tumor with histologic features of Brenner tumor within the wall of the uterus. The possible histogenesis is briefly discussed.


Formalin treatment for intractable hemorrhagic cystitis: a review of the literature with 16 additional cases. Acute, exsanguinating hemorrhagic cystitis secondary to cyclophosphamide therapy, radiation therapy, or an infiltrating bladder tumor may be managed successfully with intravesical Formalin therapy. The indications for its use, the technique, success rates, and complications are discussed. This treatment was effective in 14 of 16 patients in the present series and 79 of 90 cases reported in the literature. Dilutions of 4% or less were as effective as a 10% dilution and were associated with far fewer complications. The early use of Formalin in the treatment of intractable hemorrhagic cystitis is recommended.


Primary pleural mesothelioma.

Primary pleural mesothelioma. In this series of nine patients with primary pleural mesothelioma, three patients, all women, had "localized benign" tumors located in the left chest, although one had a recurrence on the right. Five patients all male, had the "diffuse malignant" type, and one woman had "multiple discrete" pleural tumors. Classification on the basis of gross appearance is useful clinically and prognostically, as reflected by the relatively benign behavior of localized pleural mesothelioma in contrast to the relentless lethal nature of the diffuse type. Although seven patients had pleural effusion, cytologic studies were of little help in establishing the diagnosis and all underwent thoracotomy. None of these patients had hypoglycemia or evidence of asbestosis, although three patients had a history of previous asbestos exposure.


Breast cancer--influence of growth rate on prognosis and treatment evaluation: a study based on mastectomy scar recurrences. The growth rate of a mammary cancer can be calculated when a recurrence appears in the mastectomy scar. Growth rate can, at times, be approximated from the patient's history with reasonable accuracy. Approximately half of breast cancers exhibit rapid growth (tumor doubling time (Td), up to 25 days); one-third grow at an intermediate rate (Td 26 to 75 days) and 15% grow slowly (Td 76 days or longer). Anatomic (TNM) staging does not define a homogeneous patient group in breast cancer. Within each stage, there are rapid, intermediate, and slow-growing tumors. The prognosis varies importantly with the growth rate characteristics of the tumor. Survival is the product of the tumor doubling time and the number of tumor doublings through which the patient lives. Slowly growing and intermediate growth rate tumors are associated with a high percentage of 5-year survivors after mastectomy (between 80 and 100%). Rapidly growing tumors have few 5-year survivors. When survival after mastectomy is measured in the number of tumor doublings, the differences in survival of the three groups tended to disappear, indicating that in this select group of patients with scar recurrence there was no therapeutic advantage in any of the three groups, despite the differences in the survival times. The appreciable number of patients with tumors exhibiting slow or intermediate growth rates, in any series, suggests that the use of the 5-year interval is an inadequate measure of therapeutic response in breast cancer and may actually be misleading.


Rebound response after estrogen therapy for metastatic breast cancer. The estrogen rebound response in metastatic breast cancer has been reported in the past as a rare and short-lived phenomenon, not clearly associated with any aspect of the patient's clinical profile. In this series, 25% of patients responding to estrogen therapy had a further response when they no longer received the hormone. The median duration of this palliation was a minimum of 18 months and was similar to that of the initial estrogen response. Patients with a rebound response had significantly longer disease-free intervals before estrogen therapy and estrogen remissions than those who did not have a rebound response. These clinical factors may, therefore, be helpful in predicting the chances of a rebound response in any given patient. It is urged that patients be observed for objective improvement without therapy upon escape from estrogen palliation. Further palliative therapy should not be offered until definite progression of disease has been documented after any rebound response that occurs.


The rare problem of late recurrence in neuroblastoma. Two-year disease-free survival is considered highly predictive of therapeutic success with neuroblastoma and death from neuroblastoma greater than 5 years after diagnosis is a rare event. We report of an unusual case of death from neuroblastoma 20 years after diagnosis; a literature review and discussion of this rare phenomenon of late recurrence is also included. Five additional cases of late recurrence, defined as greater than 5 years after diagnosis, were found in the literature with adequate detail to be reviewed. Advanced disease was present at diagnosis in five of six cases; three of six had disseminated disease. No age or sex differences were noted. A peculiar tencency for recurrence during the teenage years, preceded by a long disease-free interval, was also present in all cases, perhaps a reflection of maturational alterations in the immune system or hormonal changes that previously had suppressed extensive disease. This phenomenon of late recurrence in neuroblastoma, albeit rare, adds another facet to the clinical behavior of an enigmatic and therapeutically unyielding childhood tumor.


Bilateral Sertoli cell tumor of testes with feminizing and masculinizing activity occurring in a child. A case of an unusual, histologically atypical, bilateral Sertoli cell tumor of testis, in association with masculinization and feminization effects, that occurring in a 5-year-old boy, is presented. Although Sertoli cell tumors are not infrequent, this case is morphologically and endocrinologically unique.