Further observations of the ultrastructure of synaptosomes separated from spinal cord and medulla, with especial emphasis on the postsynaptic membrane. Synaptosomes from rat medulla and spinal cord have been examined in an attempt to formulate morphological criteria for distinguishing between those found in two subfractions of P1 (nuclear fraction). The mean diameter of those in the lighter of the subfractions (P1C) is 0.6 mum, with a preponderance in the range 0.4-0.6 mum and a minor peak at 0.7-0.8 mum. Subjunctional bodies are associated with 60.2% of the junctional regions in this subfraction. By contrast, those in the heavy subfraction (P1D) have a larger overall diameter (0.7 mum), a greater percentage of them have visible junctional regions (68.1% opposed to 51.6%), but of the junctional regions a lower percentage have associated subjunctional bodies (36.2%). The subjunctional bodies consist of a central core with five spokes radiating from it. The tips of the spokes are connected by fine strands which connect individual bodies to neighboring ones, as well as to the postsynaptic thickening. The persistence of subjunctional bodies in synaptosomes highlights the strength of the attachment between them and the postsynaptic thickening, and suggests that these bodies may be integral components of the "postsynaptic thickening complex." They may also help in the formulation of criteria by which different populations of these synaptosomes may be separated from each other.


Norepinephrine:adenosinetriphosphate ratios in purified adrenergic vesicles. Norepinephrine (NE):adenosinetriphosphate (ATP) ratios were studied in a highly purified fraction of large dense core vesicles isolated from the bovine splenic nerve. Vesicles prepared from nerves chilled approximately 10 and 30 min post mortem were compared. The NE:ATP molar ratio decreased from 6.3 to 4.8, p less than 0.005; NE decreased from 61 to 42 nmol, while ATP decreased only from 9.6 to 8.8 nmol/mg protein. Animals weighing 180-360 kg were compared with heavier ones weighing 400-700 kg. NE increased from 42 to 68 nmol and ATP increased from 5.9 to 13.2 nmol/mg protein, while the NE:ATP molar ratio decreased from 7.2 to 5.2, p less than 0.005. Changes during vesicle maturation were studied by comparing vesicles identically prepared from equal weights of a proximal nerve segment close to the coeliac ganglion and a distal, intrasplenic segment. NE increased from 45 to 70 nmol while ATP remained unchanged at 10.0 nmol/mg protein and the NE:ATP molar ratio increased from 4.5 to 7.0, p less than 0.005. It was interpreted that vesicle ATP content, like dopamine beta-hydroxylase, was established early in the cell body and remained unchanged during axoplasmic transport. ATP was in a complex which was relatively stable to post mortem hydrolysis at least between 10 and 30 min prior to chilling the nerves. The addition of newly synthesized NE into a readily releasable pool during axoplasmic transport occurs without ATP and can account for the increased ratio above 4:1 in the distal segment vesicles.


Agonistic and antagonistic activity of glutamate analogs on neuromuscular excitation in the walking limbs of lobsters. Forty-six analogs of L-glutamate were tested for activity on muscle fibers in the walking limbs of lobsters. Effects on the membrane potential, input resistance, and amplitude of neurally evoked EPSPs and IPSPs were studied as well as effects on applied L-glutamate. Seventeen of the compounds studied depolarized the muscle fibers in a manner indicative of an agonistic action on receptors in the neuromuscular excitatory membrane. Six analogs selectively reduced the amplitude of evoked EPSPs, and at least three of these (kainic acid, D-glutamate, and D-aspartate) antagonized the excitatory action of applied L-glutamate. Kainic acid was the most potent of the blockers of neuromuscular excitation, but even it was relatively weak since a concentration of 1 mM was required for an apparent effect. Generally those analogs in the L-configuration which possessed activity, had agonistic actions, whereas those in the D-configuration were usually antagonistic. These observations provide pharmacological evidence for the concept that L-glutamate is the transmitter agent which mediates neuromuscular excitation in the walking limbs of lobsters. In addition, our results are consistent with recent studies which indicate that L-aspartate may also function in this neuromuscular excitatory process.


Effects of anisomycin on brain protein synthesis and passive avoidance learning in newborn chicks. The effects of anisomycin (ANM) on newborn chicks have been studied with respect to brain protein synthesis, growth, EEG, toxicity, and several passive avoidance learning tasks. It was found that intracerebral ANM (80 nmol) gave a maximum inhibition of brain protein synthesis of 30%, while a combination of subcutaneous (10 mumol; 53 mg/kg) plus intracerebral (80 nmol; 21 mug) ANM inhibited by 91% in the first 2 hr and by 75% in the subsequent 2 hr period. Cycloheximide (CXM) also in combined injections at the same doses as ANM, inhibited by 97% in the 4 hr that followed injection. However, all the CXM-injected chicks were dead by 18 hr, while the lethality of ANM did not differ from that of saline. ANM also did not affect EEG measured at 1, 3, 5, or 24 hr following the subcutaneous plus intracerebral injections, nor did ANM affect body or brain growth curves or brain protein accretion. In the learning experiments, animals were initially trained to peck at water-coated metal spheres (type A learning) or at water imbibed birdseed (types B and C learning) in less than 1 sec, and were exposed to the same lures treated with the aversant methylanthranilate (MeA) one day later on one occasion (types A and B learning) or exposed twice (type C learning) and tested for learning retention one day later. Learning criterion was set as failure to peck at the lure during the first 20 sec of presentation. If ANM was injected 1 hr prior to MeA exposure, large and highly significant memory deficits were found during the retention test, as compared with saline injected controls. No effect of ANM was seen, however, if it was injected one day after learning, indicating that it did not interfere with retrieval mechanisms. ANM also decreased the external manifestations of fear or displeasure that chicks express during retention testing. Such manifestations have a high correlation with pecking suppression (r = 0.88, P less than 0.001).


Effects of environment on morphology of rat cerebral cortex and hippocampus. Cortical depth differences were found between male rats exposed to enriched or impoverished environmental conditions for successively shorter times, i.e., for 15 days (from 25 to 40 days of age), for seven days (25 to 32 days of age), and for four days (26 to 30 or 60 to 64 days of age). If the experiments began at weaning (at 25 days of age), the cortical depth changes were caused primarily by impoverishment. If the animals were young adults (60 days of age), upon entering their respective conditions, the cortical changes were induced by enrichment. No cortical depth differences were found between enriched and impoverished rats after one day of differential experience, from 60 to 61 days of age. In every age group and for every duration, except for the one day group, the dorsal-medial segment of the occipital cortex responded to the environmental conditions. No significant hippocampal depth differences were noted between enriched and impoverished animals.


Dystrophia myotonica. Peripheral nerve involvement and pathogenetic implications. A comparative electrophysioloical study of patients with dystrophia myotonica and control subjects is presented. The study includes estimation of the number of motor axons innervating the extensor digitorum brevis muscle and measurements of the conduction of M- and F-waves along the deep peroneal nerve. There is unequivocal electrophysiological evidence of nerve involvement in the disease. This was indicated by (a) prolongation of the terminal latencies and slowing of the motor conduction of the deep peroneal nerve (P less than 0.001), (b) delayed conduction of the F-wave along the proximal segments of the nerves (P less than 0.02-0.01), (c) reduced number of motor axons innervating the extensor digitorum brevis muscle (P less than 0.001), (d) high amplitude motor unit potentials and discrete EMG activity on the maximal volitional contraction of minimally affected muscles in one patient. However, if the muscle changes were secondary to the nerve involvement occurring in the disease, one would expect that the electrophysiological findings of neuropathy would become more prominent in patients with severe muscle wasting and weakness. Our results showed that in some patients with marked muscle atrophy and weakness there was no evidence of nerve involvement while in other patients with slight to moderate degree of muscle weakness the electrophysiological studies indicated peripheral neuropathy. Therefore, it appears that both the nerves and the muscles are independently affected by the pleiotropic action of the responsible gene and the evidence does not suggest that the muscle atrophy of patients with dystrophia myotonica is entirely neural.


Radiculomyelitis complicating acute haemorrhagic conjunctivitis. A clinical study. Fourteen patients with radiculomyelitis following acute haemorrhagic conjunctivitis (AHC) were seen in Bangkok during October to December 1974. Most patients developed weakness of extremities 2 weeks after AHC. Prodromal symptoms consisted of fever and malaise for a few days, followed by the acute onset of root pain in the legs and flaccid paralysis. Knee and ankle reflexes were absent or diminished. Cerebrospinal fluid examination revealed lymphocytosis and an increase in protein. Electromyographic findings were consistent with anterior horn cell or  motor root lesions. Ten of the 12 cases in which virological studies were performed showed definite serological evidence of AHC virus infection. Six patients received corticosteroid treatment but apart from relief of pain no significant improvement was seen. Motor weakness in 10 patients was less at the end of 2 months, but in 4 it remained unchanged. The occurrence of disabling neurological sequelae calls for effective public health control of AHC outbreak.


Polymyositis in Kaposi syndrome.

Polymyositis in Kaposi syndrome. Polymyositis in association with Kaposi sarcoma occurred in a 60-year-old black man. Muscle biopsy revealed prominent plasmacytic and eosinophic inflammatory infiltration resembling the myopathy of Sjögren's syndrome. Nonspecific changes were seen by electron microscopy of post mortem muscle. The myopathy could be interpreted as a remote effect of neoplasm.


Measurements of oxygen tension in the cerebral cortex of baboons. A polystyrene-covered platinum electrode (100-150 mum diameter) has been used to measure cortical tissue oxygen tension in baboon brains. The method of preparation, calibration, and the importance of small residual current (less than 40 nA) as an attribute of a reliable electrode, are described. With electrodes of this size, there was a large  (16 +/- 12nA/torr) and linear current output with pO2 changes. The effect of avrious gases in addition to oxygen is described; halothane inhalation increases the apparent pO2 and hydrogen, used for blood flow estimations, reduces the recorded pO2. In 48 separate electrode placements in 13 baboons, the mean cortical qo2 was 23.8 +/- 12 mm Hg, with a range from 1-79 mm Hg; following occlusion of one middle cerebral artery, 37 electrodes recorded a pO2 of less then 5 mm Hg pO2 Oscillations were invariably noted in control conditions, independent of blood pressure; these waves disappeared during MCA occlusion and appeared to be augmented following release of the clip. Blood pressure "spikes" produce immediate and synchronous changes in all electrodes entirely different from the spontaneous waves. Such blood pressure changes may mask the true effect of hypercapnia on tissue pO2 and, if ignored, may lead to erroneous assumptions regarding local neural control of the circulation, the increased pO2 secondary to hypertension being regarded as evidence of regional vasodilation. A SUdden change in inspired pO2-the "air test"-was performed in control conditions and following the ischaemic insult, and the rate of change of cortical pO2 compared. The gradient was significantly greater (P less than 0.05) following ischaemia, suggesting a changed ratio in the tissue's flow to oxygen requirements and/or a persisting vasodilatation.


Changes in regional cortical tissue oxygen tension and cerebral blood flow during temporary middle cerebral artery occlusion in baboons. Cortical tissue oxygen measured by a platinum cathode, and cerebral blood flow recorded by a hydrogen clearance technique, were measured in 13 baboons before, during and after temporary occlusion of the middle cerebral artery. Mean control pO2 was 23.8 +/- 14 mm Hg and mean flow 51.3 +/- 12 ml/100g/min. During the occlusion, there was a gradation in pO2 from values in the opercular area of 3.6 +/- 5.9 mm Hg, to values in the high parietal area of 11.9 +/- 11.7, these being statistically different (P less than 0.05) from each other. The corresponding flow values were 5.5 +/- 7.5 (opercular) and 22.3 +/- 21.7 ml/100 g/min parietal (P less than 0.01). Following removal of the MCA clip, between 20% and 30% of the electrodes registered an early hyperoxia and hyperaemia, which lasted up to 5 min. A late and prolonged hyperoxia, with less evidence of hyperaemia, was also noted in about 20%. The mean tissue pO2, however, at 5-min intervals up to 40 min following the removal of the clip only reached 60-80% of control values in the most ischaemic areas. Only the parietal region showed a mean pO2 above control levels. The mean flow data were uniformly reduced in all regions to about 80% of control values. During and after a second occlusion in 6 animals, similar changes were noted but with even fewer instances of hyperoxia. The mean oxygen and flow results were lower than with the first occlusion, but the reduction was not significant. There was no overall effect of hypercapnia on cortical tissue pO2 during the control period, but there was a significant (P less than 0.05) reduction during the same procedure after the period of ischaemia. An increase in pO2 during hypercapnia could be observed if there were arousal responses of blood pressure "spikes".


Lightning eye movements.

Lightning eye movements. Physiologic studies were performed on a patient who demonstrated lightning eye movements, palatal myoclonus and myoclonic jerks of the left platysma and sternocleidomastoid muscles. The myoclonus and lightning eye movements were separate phenomena with no defined relationship to each other. Analysis of this ocular dyskinesia identified strictly horizontal saccadic oscillations, 2 to 5 Hz in frequency, with amplitudes varying greatly but often reaching 25 degrees. A brief stationary period between each saccadic oscillation was frequently observed. They were particularly induced by vertical or horizontal ocular pursuit as well as sustained upward or downward ocular deviation. Caloric nystagmus abolished the oscillations but they persisted, irregularly, during optokinetic nystagmus. Thus a faulty visual fixation mechanism is postulated to precipitate lightning eye movements. Constrast studies revealed a mass lesion arising from the right dorsolateral portion of the medulla. These results indicate that lightning eye movements occur with caudal as well as rostral brain-stem lesions. From the clinical findings cerebellar pathway involvement is likely.


[Iatrogenic myoclonic encephalopathies caused by bismuth salts]. Since the beginning of 1974, we have studied 17 cases of iatrogenic encephalopathy due to the ingestion of bismuth taken for the treatment of chronic digestive disorders. More than 100 similar cases have been reported in France within the same period. The clinical picture is remarkably consistent: there is a relatively long prodromal phase with difficulties in gait and writing, followed by a phase characterised by four signs, namely a severe confusional syndrome, myoclonus, astasia-abasia and sisorders of language. In our cases, after withdrawal of bismuth, recovery invariably began within 2 to 3 weeks but fatal cases have been described. All our patients had taken, for periods of between 3 weeks and 20 years, bismuth subnitrate. The levels of bismuth in the blood and urine in these patients were between 10 and 100 times as great as those in patients who had taken the same treatment without ill effect. The exact mechanism by which bismuth causes this complication, described only recently, is totally unknown.


Acute idiopathic polyneuritis. A clinical and electrophsiological follow-up study. Fifty patients with acute idiopathic polyneuritis have been studied clinically and electromyographically, and sural nerve biopsy was performed on 8 patients. Motor and sensory conduction studies were within the normal range in 7 patients (14%), and there was pronounced slowing of motor conduction in 25 patients (50%). There was no apparent correlation between the degree of conduction, and the clinical disability of the patient or the duration of the acute illness. Eighteen patients were re-examined at intervals up to 5 1/2 years after the onset of their illness. Eight patients (44%) were clinically normal at follow-up examination and 4 patients (22%) had a significant disability. There was no relationship between the clinical disability at follow-up examination and the results of initial or final nerve conduction studies. Electromyographic evidence of denervation, however, may indicate that complete clinical recovery will not occur. Segmental demyelination was the primary pathological change found in sural nerve biopsies and there was a significant reduction in the density of myelinated fibres in 2 nerves. It is suggested that a subacute onset of the illness,electromyographic evidence of denervation or gross slowing of conduction, and significant reduction of numbers of myelinated fibres or onion-bulb formation on sural nerve biopsy are factors which may indicate a prolonged course of the illness or incomplete recovery.


Morphometry of myelinated fibers of fasciculus gracilis of man. The number of myelinated fibers per square millimeter of fasciculus gracilis, and of large and small myelinated fibers per square millimeter of fasciculus gracilis, at the C3 and T5 segements of spinal cord from 22 persons of different ages have been estimated, with a 95% confidence limit, assisted by semi-automatic methods of measurement and using programmed calculation and plotting. In addition, the histograms for diameter of myelinated fibers and mean diameter were obtained. At C3, the numbers of myelinated fibers ranged from 19,647/mm2 to 35,773/mm2, with a mean of 25,267/mm2. The number is less with older age. At T5, numbers of myelinated fibers ranged from 17,804/mm2 to 29,486/mm2, with a mean of 23,069/mm2. The number of myelinated fibers was greater at C3 than at T5 in subjects under 45. The mean diameter of myelinated fibers at C3 was smaller than that at T5. The normative data presented here should be useful for comparing with similarly derived data from patients with diseases of peripheral nerves, in evaluating the three-dimensional morphologic alteration of primary afferent neurons.


Endotoxin leucoencephalopathy in the telencephalon of the newborn kitten. Prolonged exposure of the neonatal kitten to a lipopolysaccharide results in a telencephalic leucoencephalopathy characterized by astrogliosis and necrosis. The visceral organs of neonatal kittens and the telencephalon of mature cats are relatively resistent to the adverse effects of this lipopolysaccharide.


Parabiotic reinnervation in normal and myopathic (BIO 14.6) hamsters. Parabiotic reinnervation is a technique whereby the muscles of one animal can be reinnervated by peripheral nerves of another animal. This technique has been used to test the hypothesis that the myopathy in the BIO 14.6 strain of hamster may result from a derangement of the trophic function that a nerve exerts upon the muscle which it innervates. The percentage of internal nuclei in muscle fibres has been used as a criterion to define the myopathic state. The percentage of internal nuclei was high in myopathic hamster muscles but very low in normal or "self-reinnervated" normal muscles. There was no indication that the percentage of internal nuclei in myopathic muscles fell after parabiotic reinnervation with normal nerves. Similarly, there was no evidence that the percentage increased in normal muscles that had been parabiotically reinnervated with dystrophic nerves. On the basis of these results, it was concluded that there was no positive evidence in favour of a neural aetiology for the myopathy in the BIO 14.6 strain of hamsters.


Luft's disease. Further biochemical and ultrastructural studies of skeletal muscle in the second case. In the second known case of non-thyroidal hypermetabolism (Luft's disease), there were large areas of mitochondrial aggregates in all fibers. Many mitochondria were abnormally large and contained packed cristae. In isolated mitochondrial fractions, studies of oxidative phosphorylation showed defective respiratory control and normal phosphorylation capacity ("loose coupling"). Spectra and content of cytochromes were normal. Basal ATPase activity was seven times greater than normal and poorly stimulated by 2,4-dinitrophenol. The rate of energy-dependent calcium uptake by isolated mitochondria was normal, but the amount of calcium accumulated was much decreased. Calcium could not be retained and was spontaneously released into the medium within 30 seconds. "Recycling" of calcium between mitochondria and cytosol may take place in vivo and result in sustained stimulation of respiration and loose coupling.


Spinal cord blood flow after acute experimental cord injury in dogs. Spinal cord blood flow (SCBF) was measured in dogs before and following acute injury with 300 or 500 g-cm force (GCF). In addition, the responses to high and low PaCO2 and low PaO2 levels were studied. The hydrogen clearance technique was used and 0.3 mm platinum electrodes were placed in grey matter, central white matter or peripheral white matter of the L2 segment. The pre-trauma flows were: grey matter 12.5 +/- 2.7; central white matter 14.4 +/- 3.6 and peripheral white matter 15.1 +/- 4.2 ml/100g/min. Following a 300 GCF injury, a marked and progressive reduction in SCBF occurred in the grey and central white matter. This was present for the subsequent 4 hr of the study. The flow was lower than pre-trauma values during the second hour in the grey matter (9.0 +/- 1.4) and the third hour in the central white matter (10.8 +/- 1.8). By the fifth hour after trauma the flow in the grey matter was 5.0 +/- 3.5 and in the central white matter 9.7 +/- 1.5. In the peripheral white matter the SCBF was 10 +/-3.7 during the third hour but subsequently the flow increased to 11.5 +/- 3.9. Paired t-tests showed that this still significantly lower than pre-trauma levels. Two dogs showed a hyperaemic response which was persistent in one case but only temporary in the other dog. The vasodilatatory effect of CO2 was lost after trauma and in some cases a steal phenomenon was present. The sensitivity to an increase in CO2 was 0.48 +/- 0.23 ml/100g/min Hg before injury and this decreased to 0.0075 +/- 0.137 during the second hour after injury. The vasodilatation to hypoxia (30-40 mm Hg) was also absent but the vasoconstrictor effect to low PaCO2 appeared better preserved. These findings also applied to the peripheral white matter where the SCBF was not significantly reduced. The results were similar but more pronounced after 500 GCF injury. The results show that following injury the central areas of the cord become rapidly and progressively ischaemic. The peripheral white matter does retain a reasonably normal flow depending on the magnitude of the impact force. However, the vessels in all these areas lose their ability to respond to normal physiological stimuli.


Olfactory epithelium of Necturus maculosus and Ambystoma tigrinum. The morphological study presented here provides a general description of the elements of the olfactory epithelium in the mud puppy and tiger salamander,, and gives evidence about their dynamic activity and interrelationships. There are morphological indications of local bursts of reduplication and a continual line of differentiation of receptor cells from basal cell progenitors through stages of mature development to senescence (indicated by the accumulation of pigment granules) and cell death and disposal (by expulsion of pycnotic cell nuclei and by phagocytosis by macrophages). The supporting cells probably play several roles: a secretory role which supplements the activity of Bowman's glands, a minor insulating role in which some dendrites are shielded from the surrounding milieu, and a skeletal role in which they facilitate the efficient displacement of dendrites. The dendrites are regularly arranged in organized relationships with one another and are for the most part in direct apposition, separated only by a 200 A intercellular gap, thus suggesting the possibility of functional interrelationships. This study emphasizes the fact that efficient planning of experimental investigations must include knowledge and consideration of the thickness of the particular olfactory epithelium under study. It also suggests that because of the large receptor-cell size, the mud puppy and/or tiger salamander would make good model systems for single cell recording. Further, the olfactory epithelia of these species are suggested as favorable targets for studies of the aging process in nerve cells.


Junctional subsurface organs in frog sympathetic ganglion cells. Subsurface cisternae in frog sympathetic ganglion cells were studied and shown to have similar features to those of the C.N.S. A number of special features were, however, revealed by  high resolution microscopy. Highly flattened subsurface cisternae occurred in close proximity to the ganglion cell membrane and formed structures comparable to gap junctions. These subsurface cisternae appeared to be elongated plates (about 0.3 X 2.5 mum) specifically restricted to the area of the ganglion cell membrane adjacent to nerve endings, although often with the intervention of a thin satellite sheath. Thus they have been termed here 'junctional subsurface organs', although the nerve terminals opposing them did not show any synaptic specialization. The junctional subsurface organ was often accompanied by closely arrayed endoplasmic reticulum and/or mitochondria. Where the junctional subsurface organ intervened between plasma membrane and endoplasmic reticulum or mitochondria, faint particles appeared to traverse both sides and bridge the narrow spaces to the opposing plasma membrane and endoplasmic reticulum or mitochondria. The possible functional significance of the junctional subsurface organs is discussed.


Non-innervated sense organs of the lateral line: development in the regenerating tail of the salamander Ambystoma mexicanum. New lateral organs (neuromasts) are formed in regenerating tails of the larvae of a urodele, the axolotl (Ambystoma mexicanum), even in the absence of the lateral line nerve, as confirmed by electron microscopic examination. The non-innervated organs are similar to normal innervated organs. The hair cells are polarized in opposite directions, and despite the lack of nerve endings, contain synaptic bodies, which in normal innervated organs are found in relation to afferent boutons.


Ultrastructure of the terminals of an identified 5-hydroxytryptamine-containing neurone marked by intracellular injection of radioactive 5-hydroxytryptamine. The axons and terminal processes of an identified 5-hydroxytryptamine-containing neurone were located for study with the electron microscope. Tritiated 5-hydroxytryptamine was injected into the neurone's cell body,, and after allowing time for the radioisotope to pass along the processes of the neurone, tissue was examined by electron microscope autoradiography. Terminal processes were observed at approximately 1 cm from the injected cell body, in areas of the nervous system where previous electrophysiological work had shown the presence of postsynaptic neurones. Dense-cored vesicles of mean diameter 100 nm were observed in the axons and terminal processes of the neurone. The terminal processes also contained aggregates of clear vesicles of mean diameter 65 nm. Structures resembling lysosomes, which were frequently labelled, were present in the axons of the neurone. No membrane specializations associated with typical synapses were observed.


The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. I. General description. Lesions were made in the lateral geniculate nucleus of the rat and the consequent degeneration in area 17 of the cerebral cortex was studied by light and electron microscopy. These lesions produced prominent degeneration of axon terminals in layer IV extending into layer III and a much lesser amount in layers I and VI. The darkened degenerating axon terminals forming asymmetric synaptic junctions and were frequently surrounded by hypertrophied astrocytic processes. These terminals appeared to be disposed randomly, forming no discernible patterns. In layer IV 83% of the synapsing, degenerating terminals formed junctions with dendritic spines, 15% with dendritic shafts, and 2% with neuronal perikarya. The dendritic shafts and neuronal perikarya appeared to belong to spine-free stellate cells. The dendrites giving rise to the spines receiving degenerating axon terminals could not be identified, for most of the spines appeared as isolated profiles that could not be traced back to their dendritic shafts. One example of a degenerating axon terminal synapsing with an axon initial segment was encountered. Small, degenerating myelinated axons were prevalent in layers VI, V and IV, but were only infrequent in the supragranular layers. These results are compared with those obtained in other studies of thalamocortical projections.


The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. II. Terminations upon neuronal perikarya and dendritic shafts. The forms of dendrites in layer IV receiving degenerating thalamocortical axon terminals directly on their shafts were examined in serial thin sections. Reconstructions showed these dendrites varied in thickness between 2.5 and 0.5 mum. They had essentially smooth contours and rarely showed evidence of protrusions or spines. They were further characterized by the presence of many synapses along their shafts. Only about one in 12 of these synapses was formed by degenerating thalamocortical axon terminals. These smooth dendrites emerged from neuronal perikarya that also received degenerating axon terminals which formed asymmetric synaptic junctions. Such cell bodies bore both symmetric and asymmetric synaptic junctions, and not all of the latter were caused to degenerated after a thalamic lesion. These postsynaptic neurons appeared to be of two kinds, ones with thin dendrites that often contained closely packed microtubules, and others with thicker dendrites that emerged from the poles of oval perikarya.


Medial reticular and perihypoglossal neurons projecting to cerebellum. Almost 10% of neurons in the medial reticular nucleus or adjacent thereto were invaded antidromically in response to stimulation of the fastigial and interpositus nuclei. The fraction was 77/835 for the bulbar and caudal pontine levels, but 0/167 for rostral pontine levels. The mahority, 49, of the neurons projecting to the cerebellum were superficially located in the region of the perihypoglossal nucleus, but 23 were scattered through the medial reticular nucleus, being 2.5-5.0 mm below the bulbopontine dorsum. Both classes of cerebellopetal neurons had a similar range of antidromic latencies, usually from 0.8 to 2.0 ms, but some were ober 3 ms. Both classes responded to volleys from limb nerves and inputs from cutaneous mechanoreceptors, with ranges of excitatory and inhibitory latencies that were similar to those for other medial reticular neurons. It is conjectured that the axonal projection is primarily to the cerebellar cortex and that the branches to the nuclei are often slender, hence the long antidromic latencies; 31 of 59 neurons tested projected to cerebellar nuclei on both sides, often with a considerable latency differential. Rarely, there were also axonal branches projecting up the central tegmental tract. The experimental findings are in very good accord with the anatomical descriptions of Brodal and associates (4, 5, 8, 19). It is suggested that the paramedian reticular and the perihypoglossal nuclei may provide a background excitatory input to the interpositus nuclei.


Topographic studies on medial reticular nucleus. Several distinct classes of neurons have been identified in the medial reticular nucleus of the medulla and pons and in proximity thereto. Neurons projecting down the spinal cord comprised the principal class with two subclasses according as the neurons did or did not receive monosynaptic inputs from the fastigial nuclei of the cerebellum. Two other classes were recognized accordings as they projected to the cerebellum or rostrally to the mesencephalon. Topographic planar maps giving the location of these neurons have been constructed by exploring the nucleus with series of microelectrode tracks in parasagittal or in transverse planes. The different classes of neurons were not arranged in large discrete nuclei. In part they appeared to be randomly distributed, but many colonies of one or another class of neurons could be recognized with 3-11 neurons in zones with dimensions of a millimeter or so. Because of the limitations of sampling by microelectrode tracks at spacings of 0.5 mm, single colonies might have an actual population of 100 or more. Many of the class of neurons projecting to the cerebellum were in the region of the perihypoglossal nucleus. However, almost as many were located deep in the medial reticular nucleus. None was found at the pontine level. Reticulospinal neurons with fast axonal conduction velocities tended to be located dorsally to those with slow velocities. Correlation with the findings of Ito et al. leads to the conjecture that the neurons with fast axons are excitatory, while those with slow axons are primary inhibitory neurons. There is a brief reference to the problems raised by the admixture of the various neuronal classes, there being discrete colonies immersed in a scattered arrangement of all classes.


Improvement in linearity and regulation of stiffness that results from actions of stretch reflex. We studied stretch reflexes of soleus muscles of intercollicularly decerebrated cats using a new technique for estimating the component of a stretch reflex that results from the purely mechanical properties of the active muscle (mechanical response). The difference between a net stretch reflex and its underlying mechanical response provided a direct measure of reflex action. 1. The relative contributions of reflex action and the mechanical response are different for stretch and release. With stretch, reflex action is generally large and the mechanical response small. The opposite is true with release. The property that remains relatively constant, when stretch and release are compared, is the net stiffness in opposition to length change. We concluded that reflex action compensates for variations in the inherent stiffness of the muscle. 2. Compensation is effective over a range of intermediate values of initial force, but it fails whenever the reflex force approaches zero or the maximal force at that length. 3. Reflex action is capable of modifying muscular force within 22 ms of the onset of length change. This indicates that even during a fast gallop, there is sufficient time for reflex action. 4. The mechanical properties of the active soleus muscle are highly nonlinear; e.g., muscular stiffness becomes negative transiently during stretch. In stable decerebrate preparations we found that reflex action resulted in a considerable improvement in linearity. 5. Our results support two complementary hypotheses: a) stiffness may be the regulated property of the stretch reflex, and b) the main function of autogenetic reflexes may be to conpensate for variations in the properties of skeletal muscle rather than to oppose changes in load.


Effect of auditory neocortex ablation on pitch perception in the cat. Cats which received one- or two-stage bilateral ablations of auditory cortex were compared to unoperated cats on a test involving the discrimination of increases (1.2 kHz) from decreases (0.8 kHZ) in the frequency of ongoing 1.0-kHz tone pulses. Whereas two-stage cats exhibited more evidence of postoperative retention for the original task than did one-stage cats, both groups relearned the discrimination in approximately the same number of trials as normal cats. Individual differences in difficulty of relearning apparently reflected the degree of undercutting of the polysensory association areas of the suprasylvian and lateral gyri. Following retraining, all cats received two discrimination transfer tests. The first test was identical to the original dis crimination problem in all respects except that different frequency values were substituted for the original set (i.e., 1.6-kHz tones alternating with either 2.0- or 1.2-kHz signals). Whereas both unoperated and two-stage cats had difficulty discriminating the new positive from negative trials, the one-stage cats exhibited a significant tendency to continue responding to changes invoving 1.2-kHz tones in the same manner as in the original discrimination task. In the second test the cats were asked to discriminate the original 1.2- and 0.8-kHz tones against a silent background. Both operated and unoperated cats performed significantly above chance on this test. These results suggest that the cats solved the original discrimination on the basis of absolute frequency cues rather than the directionality of frequency changes. The significance of these findings are discussed in relation to current concepts of the functional capacity of auditory decorticate animals.


Depolarizing afterpotentials and burst production in molluscan pacemaker neurons. 1. Spikes in molluscan bursting cells are followed by depolarizing afterpotentials (DAPs) which are not seen in nonbursting cells in the same ganglia. DAPs from successive spikes sum to provide a depolarizing drive capable of sustaining multiple discharge. 2. Subthreshold depolarization activates a DAP-like process in bursters. 3. DAP amplitude increases as the cell is hyperpolarized beyond the potassium equilibrium potential. The amplitude is not changed by intracellular iontophoresis of TEA-Cl. DAP amplitude is reduced by 39% after a 10-min exposure to CA++-free saline, and by 66% after 10 min in 4% Na+ (Tris substituted) saline. The amplitude is unchanged by exposure to K+-free saline. 4. During repetitive stimulation the amplitude of the summed DAP declines. 5. It is concluded that DAP results from a slowly decaying component of Ca++ and Na+ permeability.


Synaptic events and discharge patterns of cochlear nucleus cells. I. Steady-frequency tone bursts. Unitary discharge patterns (peristimulus time histograms or PSTH) and synaptic events were studies with intracellular recording techniques in 164 cat cochlear nucleus cells to steady-frequency tone bursts 250 ms in duration. There were four response types defined on the basis of the shape of the discharge patterns to tones at the characteristic or best frequency. Primarylike units resemble eighth nerve fibres and have a maximum discharge at tone onset, followed by a smooth decline to a steady level of activity. Buildup units have a transient response at tone onset, followed a period of little or not activity before gradually increasing their discharge rate for the remainder of the tone burst. Onset units have an initial burst of spikes at the onset, with little or no activity for the remainder of the tone burst. Pause units have a long latency (10-30 ms) between tone onset and the appearance of low levels of unit activity, which then gradually increase in rate for the remainder of the tone burst. Changes in signal frequency or intensity within the excitatory response area did not modify response patterns of primarylike and onset units, but could evoke primarylike patterns in buildup and pause units. Inhibition manifested by suppression of spontaneous activity and membrane hyperpolarization were of three kinds: 1) in response to signals at the edges of the excitatory response area (i.e., the inhibitory surround) and detected in onset buildup, and pause units but not in primarylike units; 2) occurring at the offset of tones in the excitatory response area and detected in all four types of cochlear nucleus cells; 3) during excitatory tone bursts in onset and buildup units associated with the periods of suppressed unit activity. Membrane hyperpolarization did not accompany the delay in unit activity after tone onset in pause units. Inhibitory events in cochlear nucleus cells provide mechanisms for producing diversity in the temporal pattern of discharges to acoustic signals which may underly the encoding of complex features of sounds.


Synaptic events and discharge patterns of cochlear nucleus cells. II. Frequency-modulated tones. Responses of 99 cochlear nucleus cells and 24 cochlear nerve fibers were studied with FM signals; 14 cochlear nerve fibers and 57 cochlear nucleus cells were studied at four rates of modulation and several signal intensities. Classification of FM response patterns as symmetrical, asymmetrical, or unidirectional was based on the calculation of a symmetry factor (S), which compared the number of discharges evoked by the ascending and by the descending phases of the FM sweep. Certain FM response patterns could not adequately be described by the symmetry factor along and variables of modulation rate and signal intensity had significant influence. A correspondence was found between the four response classes evoked by a steady-frequency tone burst (primarylike, buildup, onset, and pause) and the FM response pattern. Cochlear nerve fibers showed symmetrical response patterns to FM stimulation. Primarylike units were similar to eighth nerve fibers and generally showed symmetrical FM responses. Occasional eighth nerve fibers and primarylike cells developed asymmetry at the fastest rate of modulation (50 sps). Buildup units showed a variety of response patterns to FM signals. Onset units generally showed asymmetrical response patterns with the greater response occurring to the ascending than to the descending phase of the FM sweep. Pause units showed a characteristic inhibition of activity at 5 sps (rate-dependent inhibition). Of the 57 cochlear nuclear cells studied in response to FM signals, 16 were symmetrical, another 16 were symmetrical except at the fastest modulation rate, 12 were asymmetrical, 3 were unidirectional, and 10 showed complex responses to certain signal rates or intensities. It is clear the the cat cochlear with its complex cytoarchitecture is involved in the recoding of acoustic information. Some units in cochlear nucleus demonstrate differential responses to the direction and to the rate of frequency movement. Other cochlear nucleus cells respond as eighth nerve fibers and may serve as simple "relays" in transmitting information from the cochlea to higher auditory centers.


Interaction of pulmonary afferents and pneumotaxic center in control of respiratory pattern in cats. The interaction between the pulmonary afferents (PA) and the pneumotaxic center (PC) in control of respiratory pattern was studied in lightly anesthetized paralyzed cats before and after bivagotomy or lesions of the PC using inflations controlled by the onset or cessation of phrenic nerve discharge, i.e., cycle-triggered inflations. This interaction was also studied using electrical stimulation of the central stumps of cut vagi. Introduction of a delay between inspiratory onset and the commencement of an inflation at constant flow and duration resulted in increases of the durations of inspiration (T1) and expiration (TE) and amplitude of the integrated phrenic nerve discharge (A). The lung volume at inspiratory cutoff, i.e., the volume threshold, increased markedly as T1 increased. There were linear relationships between T1 and TE and between T1 and A. At constant alveolar CO2 and tidal volume, the quantitative effects of delay were dependent on the rate of inflation; i.e., when the flow increased, the volume threshold for a given T1 decreased. Bilateral vagotomy abolished the effects of delay and flow. PC lesions, which  resulted in apneusis when the cycle-triggered inflations were stopped, produced the following changes compared to the delay effects seen in intact cats: a) the volume threshold for zero delay doubled and its rate of decrease with increased T1 was significantly smaller, and b) the change in TE for a given change in T1 was reduced markedly. Introduction of a delay between inspiratory onset and the start of electrical stimulation of the afferent vagi resulted in effects similar to those seen for delays in cycle-triggered inflations. The T1-TE relationship remained linear when the stimulus trains ended with inspiratory cessation. These results suggest that: a) the inspiratory cutoff mechanism is responsive to the rate, as well as the level, of lung inflation; b) all of the lung volume information affecting inspiratory cutoff in paralyzed cats is carried via the vagi; c) an intact PC is necessary for the generation of a normal time dependence of the volume threshold for inspiratory cutoff; d) the PC plays an important role in matching TE to T1 when the latter changes. For inflations and vagal stimulations applied during expiration, with introduction of a delay between inspiratory cessation and the start of cycle-triggered inflation or vagal stimulation, the results indicated that the expiratory cutoff mechanism has an irrevocable phase of 300-450 ms.


Effects of static tilt on cervical spinoreticular tract neurons. The activity of axons located mainly in the ventral part of the lateral funiculi of the cervical segments C2-C3 were recorded in precollicular decerebrate cats and their responses to lateral tilt of the whole animal studied. Units were identified according to their antidromic and/or transynaptic responses to stimulation of the ipsilateral lateral reticular nucleus (NRL) as well as their responses to ipsilateral and/or contralateral forelimb nerve stimulation. In most respects, those units which could be antidromically identified as cervical ascending tract axons showed properties similar to those described for neurons of the spinoreticular pathway, the bVFRT. Among the 106 recorded units, 42 responded to 15 degrees tilts in the median plane. Steady changes in unit discharge frequency were evoked by tilting, which lasted as long as the position of the cat was maintained. The response of the units to tilting consisted of increased in discharge rate during tilt in one direction, while tilt in the opposite direction resulted in a decrease in discharge rate. The magnitude of the responses was clearly related to the degree of tilt. All the units affected by tilt, except one, received inputs from both ipsilateral and contralateral forelimb nerves and some of them also from high-threshold neck muscle afferents. Furthermore, 12 of these units could be orthodromically excited at short latency from the ipsilateral brain stem, suggesting a possible monosynaptic input perhaps transmitted via the lateral vestibulospinal tract. The responses of the cervical ascending spinal tract units to tilt did not appear to depend on peripheral proprioceptive or cutaneous feedback since a number of precautions were taken to eliminate such influences, while control experiments in animals submitted to partial or complete bilateral VIIth nerve section showed the number of neurons responsive to tilt to be profoundly reduced or eliminated. It appeared also that the average spontaneous discharge rate of the ascending units was much lower following bilateral VIIth nerve section than that obtained from the corresponding units recorded in preparations with the VIIth nerves intact. These findings suggested that the responses of the cervical ascending neurons to tilt as well as their spontaneous background activity depended on influences arising from the macular labyrinthine receptors. The observation that the responses of these ascending neurons to peripheral nerve stimulation are modified by tilt further suggested that the macular system may interact with the somatosensory system originating from the forelimb and the neck musculature, thus being able to produce the fine adjustments that cerebellar and brain stem structures exert in the control of posture and movements.


Quantitative study of cortical orientation selectivity in visually inexperienced kitten. 1. Extracellular recordings were made from single units in the visual cortices of six kittens deprived of experience with pattern vision by binocular lid suture. 2. Selectivity for stimulus orientation was quantitatively assessed in 98 units; 90 responded selectively to the orientation of a moving bar stimulus, the remainder responding nonselectively or too poorly to classify. Cells in these visually inexperienced kittens were similar in their degree of selectivity for orientation to cells tested in adult cats. However, responses tended to be weaker and somewhat more erratic. 3. About half the cells in this simple responded to both directions of stimulus motion at the optimal orientation. Most of those responding to only one direction of motion were considered orientation rather than direction selective because they responded more strongly or more selectively to a moving bar than to a moving spot. 4. Cells appeared to be organized within the cortex in a pattern similar to that found in adult cats, with cells in one column selective for the same orientation, and adjacent column having similar preferred orientations. 5. It is concluded that selectivity for stimulus orientation in the cat's visual cortex is innately determined.


Interaction between foreign and original nerves innervating gill muscles in fish. Foreign somatic motor nerves were made to innervate denervated gill muscles of the perch. The foreign innervation remained functional after reinnervation by the original nerve. Intracellular recordings showed that individual muscle fibers could be activated by both foreign and original neurons. Extensive foreign innervation appeared to inhibit the ability of the original nerve to reinnervate its own muscle. These studies provide evidence for a functional coexistence of appropriate and inappropriate innervation and show that foreign synapses need not be repressed by the "correct" nerve.


Topography of visual and somatosensory projections to mouse superior colliculus. In adult mice of the C57BL/6J strain the projection of the visual field was systematically mapped under direct vision. As in other vertebrate species the nasal (anterior) field projected anterolaterally, and the inferior field posterolaterally. Values of magnification-1 (m-1, or degrees of visual field per millimeter tectal surface) were calculated over most of the tectum, for measurements in the coronal and sagittal planes. Whereas m-1 was fairly constant for measurement pairs in sagittal planes, for coronal planes there was a rather large, elongated, horizontally oriented area in the upper field of vision within which m-1 was smaller than elsewhere. In this area m-1 was anisotropic, with a ratio of almost 2:1 between sagittal and coronal planes. In a previously study we had observed that many cells recorded in deeper tectal layers responded to somatosensory stimulation, with whiskers especially conspicuous. In a given penetration perpendicular to the tectal surface, somatosensory receptive fields recorded in the deeper tectum were always concerned with that group of whiskers or with those parts of the body that crossed the regions of visual field represented in the superficial layers directly above. Given this information on the visual coordinates associated with certain somatosensory fields, the detailed mapping of the visual field onto the tectum made it possible to prepare a map of the somatosensory projection on the tectum. The resulting representation differed markedly from maps described for the classic somatosensory pathway. In the tectum the somatosensory map was dictated by the visual-field projection rather than by the peripheral tactile innervation density. Whiskers were thus featured much more prominently in the tectum, and structures close to the eye, such as the pinna and cheek, receive more representation than the tail or hindpaws.


Aneurysm of a superior cerebral vein.

Aneurysm of a superior cerebral vein. Among 880 specimens of cerebral dura mater with enclosed sinuses, one had a sharply delineated bulbous conformation of the distal segment of a superior cerebral vein. There was no evidence of an arteriovenous malformation. Early plaque formation was present in the inner aspect of the thick wall of the dilated segment of vein.


Functional representation on the medial aspect of the frontal lobes in man. Sensorimotor responses to stimulation of the medical frontal and cingulate area were studied in seven unrestrained, unsedated patients who suffered from intractable seizures. Complex postural synergies involving the trunk and proximal extremities appeared contralaterally or occasionally bilaterally. Contraversive turning of head and eyes was not observed. Sensory responses from the supplementary motor area were referred contralaterally and focally; those from the cingulate gyrus were widely referred. Speech impairment from stimulation of the supplementary motor area showed striking similarities with that obtained from stimulation in the frontostriatal region or lateral aspect of the frontal lobe. The observations support the hypothesis that interference with striatal function may be the basis of speech inhibition produced by stimulation of the frontal lobe.


Selection of patients for extra-intracranial arterial bypass surgery based on rCBF measurements. Extracranial intracranial arterial anastomosis is gaining acceptance as a form of treatment in selected cases with ischemic cerebrovascular disease. To establish indications for this operation and to provide an objective assessment of postoperative results, regional cerebral blood flow (rCBF) studies were performed in 110 patients with cerebrovascular insufficiency considered for extra-intracranial bypass surgery. The 133Xe intracarotid injection method with 16 externally placed detectors was used for measuring rCBF. Postoperatively, rCBF was measured in 40 patients. From these results our present criteria for surgery have evolved. The probability of a good postoperative result is best in patients who showed focal cerebral ischemia or a moderate general reduction of CBF with an additional ischemic focus. The operation is contraindicated in patients with either normal or severely reduced CBF values (less than 60% of normal).


Clinical experience with extra-intracranial arterial anastomosis in 65 cases. Clinical results of an extra-intracranial arterial bypass (EIAB) procedure for cerebral ischemia are assessed in 65 patients. The 5-year-study suggests that the EIAB procedure has a protective effect against further clinically significant cerebrovascular accidents in properly selected patients. Correlation with angiography and regional cerebral blood flow (rCBF) studies are discussed. It is felt that rCBF measurements offer the best diagnostic test to determine which patients are suitable for surgery by revealing if an ischemic or relative ischemic focus is present. The surgical procedure is contraindicated in acute cerebral ischemia and when the rCBF study reveals general reduction of cerebral blood flow as opposed to a localized ischemic focus.


Experimental bypass for sagittal sinus repair. Preliminary report. Bypasses of the sagittal sinus, 2.5 mm in diameter, were carried out in 25 dogs with venous (13 cases) and arterial (12 cases) autogenous grafts, by classical microtechniques. Animals were sacrificed 10 to 75 days after the operation, average 40 days. The patency rate was 54% in the venous autograft group; in all cases, thrombosis occurred early and was due to technical factors. The immediate postoperative patency rate was 100% in the arterial graft group, but this type of graft showed a tendency to progressive occlusion because of extensive fibrosis of the arterial wall; thus the patency rate was 75% at the time of autopsy. This preliminary work demonstrates the technical feasibility of bypass procedure which could be used for sagittal sinus repair.


Intradural lipomas of the spinal cord. A clinicopathological correlation. Nine original cases of intradural spinal cord lipomas have been examined from a clinical and pathological standpoint. These tumors occur more commonly in men in the second to fourth decade and are found most frequently in the thoracic spinal cord. Paraparesis, sensory changes, urinary incontinence, and pain are frequent presenting complaints. Myelography is the diagnostic study of choice. All lipomas in this series were located primarily within the cord; four of these also presented an extramedullary extension. Admixed nerve bundles were present in five cases with associated hypertrophic onion-bulb formation in three. Decompression with biopsy or subtotal resection is the operative procedure of choice.


Endothelial growth factor present in tissue culture of CNS tumors. Human endothelial cells obtained from postpartum umbilical veins and placed in primary tissue cultures were treated with media from cultures of human and experimental central nervous system tumors. Endothelial proliferation was determined by the uptake of 3H thymidine with autoradiography and represented as the thymidine labeling index (TI), which is the proportion of 3H thymidine-labeled endothelial cells to total number of cells counted. There was a marked increase in the TI when tumor-conditioned medium was added to endothelial cultures (range 28.7% to 98.3%) when compared to controls (2.1%) and endothelium with conditioned media from fibroblasts (4.5%). This study demonstrates the presence of a chemical substance produced by tumor cells which results in endothelial proliferation. The system described provides a useful assay technique for the further characterization of this endothelial growth factor.


Surgical anatomy of the proximal anterior cerebral artery. The authors present this study of proximal anterior cerebral arteries in the normal human to provide a clearer basis for strategy in aneurysm surgery. They describe patterns of origin of branches, their subarachnoid course, and parenchymal distribution. Branches that originate from the anterior cerebral artery at the internal carotid bifurcation perfuse the genu and contiguous posterior limb of the internal capsule and the rostral thalamus. Proximal 4-mm branches supply the anterior limb of the internal capsule, the neighboring hypothalamus, anteroventral putamen, and pallidum. The remaining anterior cerebral artery proximal to the communicating artery sends branches to the optic chiasm, the adjacent hypothalamus, and the anterior commissure. Heubner's artery arises directly opposite the anterior communicating artery to supply much of the striatum and internal capsule rostral to the anterior commissure. The anterior communicating artery branches supply the fornix, corpus callosum, septal region, and anterior cingulum. The parenchymal distribution of these end arteries may be surmised from the site of origin named vessels. With this anatomical information one can avoid interruption of blood supply to vital structures when dealing with the anterior cerebral artery and its branches.


Jefferson fracture of the atlas. Report of six cases. Six cases of Jefferson fracture of the atlas are summarized. None had recognizable neurological signs that resulted from the injury when seen in the hospital. With conservative treatment, pain subsided and the fracture stabilized in a short period in all six patients. None of the patients underwent fusion of the cervical spine.


Treatment of Jefferson fracture with a halo apparatus. Report of two cases. Two patients with bursting fractures of the atlas vertebra are presented. The use of a halo apparatus as an effective alternative to bedrest and cervical traction in these patients is discussed. Polytomography was helpful in establishing an accurate diagnosis.


Cerebrovascular accident after percutaneous rf thermocoagulation of the trigeminal ganglion. Case report. A case of cerebrovascular accident associated with percutaneous radiofrequency thermocoagulation of the trigeminal ganglion is presented in the hope of alerting other surgeons to this possible complication.


Carotid-anterior cerebral artery anastomosis. Case report. The angiographic and anatomical features of an anomalous communication between the intradural internal carotid artery and the anterior cerebral artery are described. Essential features of the anastomosis include an origin at, or close to, the origin of the ophthalmic artery, a course ventral to the ipsilateral optic nerve and anterior to the optic chiasm, and a termination near the anterior communicating artery. Although rare, the condition should be considered as an entity. The incidence of associated berry aneurysm and other congenital vascular anomalies is high.


Tension pneumocephalus after insertion of ventriculoperitoneal shunt for aqueductal stenosis. A case of tension pneumocephalus after the insertion of a ventriculoperitoneal shunt for aqueductal stenosis is reported. The possible mechanisms producing this complication are discussed.


Myxochondrosarcoma of the fourth ventricle. Case report. The authors report a case of myxochondrosarcoma of the fourth ventricle. The tumor was heavily calcified and proved impossible to remove at surgery. Histological examination revealed areas of loose fibroblastic tissue, hyaline cartilage, osteoid, and bone. It is postulated that the tumor arose from the stroma of the choroid plexus.


Sagittal synostectomy. Technical note.

Sagittal synostectomy. Technical note. A procedure for correction of scaphocephaly is described. It differs from strip craniectomy in that it provides early correction of the deformity by removing the protuberances at the bregma and at the occiput. The morbidity and mortality of this procedure is no greater than with the more standard linear craniectomy.


Measures of clinical efficacy. III. The value of the lung scan in the evaluation of young patients with pleuritic chest pain. The usefulness of various modalities in evaluating pleuritic pain in young patients and in isolating cases of pulmonary embolism was assessed using likelihood ratios and the receiver operating characteristic (ROC) curve. History and physical, laboratory, and radiographic finding were used disjunctively to establish an ROC curve. The percentage of patients found to have pulmonary embolism increased monotonically with certain critical pieces of diagnostic data. For example, a history and physical examination alone detected 80% of patients with pulmonary embolism; a chest radiograph raised the percentage to 95%; and the addition of a lung scan increased the percentage to 100%. Thus, with proper interpretation of clinical and radiographic data, the lung scan has only a marginal impact upon the sensitivity with which pulmonary embolism is detected. Its major value is an increased specificity in the diagnosis of pulmonary embolism.


Use of 99mTc-labeled albumin microspheres in cerebral vascular disease. The intracarotid injection of radioalbumin microspheres (15 and 30 mum) is followed by scanning procedures that permit the description of the cerebral bloodflow distribution. The method is reproducible. Injection can be made into the internal and common carotid arteries, as well as into the aortic arch or the left ventricle. This last procedure makes it easy to examine patients with severe extracranial vascular stenosis or thrombosis and permits comparison of the two hemispheres. Most patients (88%) injected on the affected side showed one or more local vascular deficits. The method therefore is more efficient than pertechnetate scanning or arteriography.


Serial bone-scan changes in recurrent bone infarction. Recurrent bone infarcts in a black man produced a changing pattern of bone-scan abnormalities. Areas initially cold at the infarction site returned to normal over a period of months. Hyperconcentration was frequently noted during the healing phase. In the acute phase scanning was specific and more sensitive than radiography.


Osteoblastomas of the axial skeleton shown by skeletal scanning: case report. Two patients with osteoblastoma of the axial skeleton showed intense uptake of 99mTc-polyphosphate and 99mTc-diphosphonate on skeletal scans. Although this lesion is uncommon, it should be included in the differential diagnosis for young patients who show abnormal accumulation of 99mTc-phosphates in the axial skeleton.


Abnormal radionuclide angiogram in proven intracranial fibromuscular dysplasia: case report. Left internal carotid occlusion with collateral perfusion was shown by radionuclide and contrast angiography in a 22-year-old women. Fibromuscular dysplasia, intimal fibroplasia type, was found at autopsy in the intracranial carotid vertebral, and basilar arteries.


Displacement of the spleen in infected pancreatic pseudocyst: case report. In two patients with infected pancreatic pseudocyst 99mTc-sulfur colloid scans showed similar medial and inferior displacement of the spleen.


Rat model for acute myocardial infarction: application to technetium-labeled glucoheptonate, tetracycline, and polyphosphate. Cauterization of rat myocardium serves as a quick (2 min) inexpensive technique to create an animal model of acute myocardial infarction useful in evaluating radiopharmaceuticals as potential clinical imaging agents. Preliminary evidence indicates that is correlates well with behavior in man. Application of the model led to the discovery, confirmed by later investigators, that chelating agents such as glucoheptonate and polyphosphate show significant uptake in recent myocardial lesions.


Selenium-75-19-selenocholesterol-a new adrenal scanning agent with high concentration in the adrenal medulla. A tissue distribution study with 75Se-19-selenocholesterol in rats, rabbits, and dogs showed high adrenal concentrations and good adrenal images. In the dog, higher concentrations were obtained in the adrenal medulla than in the cortex at Days 1 and 7 after dosing. Extraction and thin-layer chromatography of the adrenal lipid in dogs given this compound showed that 75Se in the adrenal is still attached to the steroid moiety. A reduction in production costs is expected from its longer shelf life. Selenium-75-19-selenocholesterol is being evaluated in humans not only for routine use as a adrenal  cortex scanning agent, but also for the detection of pheochromocytomas and other sympathetic tissue tumors, especially neuroblastomas.


Radiorespirometric study of carbohydrate metabolism in childhood liver disease. The need for a suitable parameter to evaluate patients with chronic liver disease has been felt for some time, especially in order to judge the response to surgical shunts and the influence of certain drugs and diets on the liver. Since the liver is a major organ for carbohydrate metabolism, it was decided to analyze the in vivo oxidation of such substrates as glucose and galactose labeled with 14C. Moderately advanced "Indian childhood cirrhosis" and idiopathic fatty hepatic infiltration were selected to represent diffuse chronic liver disease. Oral administration of 14C-U-glucose or 14C-1-galactose was followed by analyses of 14CO2 in breath by liquid scintillation counting. Conversion of 14C-glucose to 14CO2 was accelerated by both diseases. On the other hand, oxidation of 14C-galactose was slowed in fatty infiltration and was markedly subnormal in Indian childhood cirrhosis.


The assay of iodine-123.

The assay of iodine-123. Compounds labeled with 123I are becoming more common in scintillation imaging due to the convenient combination of the 13.3-hr half-life and the 159-keV gamma radiation. Here attention is drawn to the particularly large summing effects observed when 123I is counted in a well counter. These could lead to errors in the assay of doses if the analyzer windows used are too narrow.


Efficiency of phenylpyruvic and phenyllactic acids as substitutes for phenylalanine in the diet of the growing rat. Male weanling albino rats fed a diet containing all nutrients for optimal growth, including 45.4 mumoles of phenylalanine/g, gained weight at an average of 6.5 g/day. Removal of phenylalanine caused an average weight loss of 1.1 g/day. Addition of graduated increments of phenylalanine led to progressive increases in growth rate; the increases being proportional to the dietary content of this amino acid. When phenylpyruvic or L-phenyllactic acids were added isonitrogenously to the phenyl-alanine-free diet, growth rate also increased. Percent efficiency of these amino acid analogues as dietary substitutes for phenylalanine, calculated as (see article) varied from 50% to 70% for phenylpyruvic acid and 65% to 95% for L-phenyllactic acid. Efficiency increased as dose of analogue increased. Non-isonitrogenous substitution did not change growth rates. Supplementation with a megadose of pyridoxine did not increase the efficiency of phenylpyruvic acid. D-phenyllactic acid and cinnamic acid were completely ineffective as substitutes for phenylalanine. When tyrosine was withdrawn from the diet, efficiency of phenylpyruvic acid was 70% at several doses. The efficiency of L-phenyllactic acid was 65 to 40%, decreasing with increasing dose.


The effect of vitamin B-6 deficiency on the fatty acid composition of the major phospholipids in the rat. We have studied the effect of vitamin B-6 deficiency in the rat on the fatty acid spectrum of phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and phosphatidylethanolamine (PE) in liver, plasma and kidneys. In general, vitamin B-6 deficiency decreased the proportion of arachidonic acid in the phospholipid fraction studies and increased that of linoleic acid. These changes seem to be greatest in the liver, whose changes were reflected quite faithfully in the plasma and were least in the kidneys, especially in the case of PE. These differences of order of magnitude may be due to differences in the site of synthesis, in the function or in the turnover of these phospholipids in the different tissues. We have attempted to explain these changes on the basis of a decrease in the synthesis of PC by the pathway of methylation of PE, a pathway which leads mainly to the information of arachidonoyl-PC. The relative importance of the de novo pathway, via CDP-choline, which produces mainly linoleoyl PC would thus increase. This mechanism, associated or not with a decrease in the synthesis of arachidonic acid from linoleic acid, could produce the effects observed on the fatty acid spectrum of the various phospholipids.


Studies on the changes in reduced glutathione of chick tissues during onset and regression of nutritional muscular dystrophy. Nutritional muscular dystrophy (NMD) in the chick results from a simultaneous deficiency of vitamin E and cystine. Muscle and liver of dystrophic and nondystrophic chicks were assayed for nonprotein sulfhydryl (NP-SH), reduced glutathione (GSH) and glutathione reductase. Red blood cells were assayed for NP-SH and GSH content. Glutathione peroxidase was determined in muscle, plasma and liver. Dystrophic muscle GSH was increased and at times was approximately double that of normal muscle, while liver GSH was lower in dystrophic than in normal chicks. During recovery from NMD, brought about by addition of either vitamin E or cystine to the dystrophogenic diet, muscle GSH declined and liver GSH increased to normal levels. Glutathione peroxidase was equivalent in both dystrophic and nondystrophic plasma and liver, but was significantly increased in dystrophic muscle. The mode of action of dietary cystine in preventing NMD in chicks remains unknown; it is not mediated through the role of amino acid as a component of the GSH needed for the action of glutathione peroxidase.


Maintenance requirement and energetic efficiency of lean and obese Zucker rats. The body balance technique was used to determine the maintenance requirement and the energetic efficiency of 6-week-old male lean and obese Zucker rats. Fifteen lean and 15 obese rats were assigned to three groups of five each and fed three levels of food intake: ad libitum, 75% of ad libitum, and 50% of ad libitum, for a 4-week period. The obese rats consumed more food and gained significantly more weight than the lean rats. Obese rats utilized dietary energy more efficiently than lean rats but the opposite was true for dietary protein. The efficiency with which obese rats utilized metabolizable energy for gain was 36% compared with efficiency of utilization of metabolizable energy above maintenance for obese and lean were 51.4% and 21.4%, respectively. The maintenance requirement on the basis of metabolic body size for the obese and lean was calculated to be 122 and 130.5 kcal ME per day per kg.75 for the 4-week period. These results indicate that the energetic efficiency is higher in obese than in lean Zucker rats and suggest that the higher energetic efficiency is not the result of a significantly lower maintenance requirement.


Interactions of trace metals in mouse and rat tissues; zinc, chromium, copper, and manganese with 13 other elements. Tissues  of rats and mice fed a nonessential metal in drinking water for life were analyzed for the essential metals chromium, copper, manganese and zinc. The study involved 505 rats and 843 mice. Livers, lungs, hearts, kidneys and spleens were pooled in groups according to age at death, averaging 5 for rats and 8 for mice, in order to provide adequate sample weight. Copper was significantly higher in livers of rats fed tin, germanium, niobium and zirconium than in controls. Similarly, niobium was associated with deposition of manganese in heart and zinc deposition in liver. Chromium levels were depressed in heart, kidney and spleen by germanium. In mice the greatest effects occurred when indium and rhodium were fed, all four essential trace metals exhibiting raised levels principally in kidney but also in heart and spleen. Chromium levels were raised in all organs but heart when hexavalent chromium was fed. From these data it is apparent that the ingestion of a nonessential metal can enhance the retention of an essential trace metal, perhaps thus avoiding toxicity from the nonessential one.


Lenticular opacities in young rats as a consequence of maternal diets low in tryptopham and/or vitamin E. The relative effect upon lens transparency of a diet low in both tryptophan and vitamin E was compared to diets low in either nutrient alone during development. Thirty-three percent of 126 progeny from 19 litters at weaning were found to have either unilateral or bilateral lenticular opacities when the maternal diet during gestation and lactation provided only 75 mg L-tryptophan and 0.1 mg dl-alpha-tocopheryl acetate per 100 g diet. No opacities were seen in 179 progency from 20 litters when tryptophan alone was restricted, and only 6% incidence was detected when vitamin E was the sole limiting nutrient. The data reveal a previously unrecognized association between tryptophan and vitamin E relative to fetal lens development.


Regulatory role of dietary leucine on plasma branched-chain amino acid levels in young men. Four healthy young men were studied to explore the effects of dietary leucine intake on plasma levels of leucine,isoleucine and valine. Leucine-, valine-, leucine-valine-, and leucine-isoleucine-valine-free amino acid mixtures were studied during four-day experimental diet periods. The effects of giving amino acid mixtures with high-carbohydrate, low-fat or low-carbohydrate, high-fat diets were also studied. Deficient leucine intake increased plasma levels of valine and isoleucine, but a valine-free diet did not affect plasma levels of the other branched-chain amino acids. Leucine influence was evident during the postprandial and fasted phases. Valine and isoleucine levels were less markedly reduced when diets devoid of these amino acids were also leucine-free, as compared with a diet providing adequate leucine. Changes in the major dietary energy source failed to influence the qualitative effects of dietary leucine adequacy on the branched-chain amino acid levels in plasma. The results suggest that leucine facilitates both tissue uptake of branched-chain amino acids and their intracellular metabolism.


Biological availability of iron supplements for rats, chicks and humans. Fourteen experiments were concluded on the effect of protein and carbohydrate sources in the assay diets on the relative biological values (RBV) of food grade sodium iron pyrophosphate (NaFePP) and ferric orthophosphate (FePO4) vs. ferrous sulfate (FeSO4) for rats and chicks, using the response in blood hemoglobin to graded levels of supplemental iron as the assay criterion. Two trials were made with volunteers to estimate the RBV of NaFePP and FePO4 for humans, based on the increase in plasma iron 2 hours after ingestion of 100 mg of iron of a test dose following an overnight fast. The RBV of iron from NaFePP and FePO4 for rats were consistently lower when the basal diet contained nonfat dried milk (9 to 16 and 28, respectively, vs. FeSO4=100) than when casein was used (25 to 28 and 49, respectively). The addition of 22% beta-lactose, replacing sucrose in a diet containing casein fed to rats, significantly reduced the RBV of iron from NaFePP from 25 to 15; the addition of 22% alpha-lactose or 40% glucose in place of sucrose had no effect on the RBV of this iron source. The RBV of iron from NaFePP and FePO4 for chicks were 4 to 6 and 4, respectively, with the source of dietary protein having no effect. Very low RBV of iron from NaFePP and FePO4 (4.3 and 5.9, respectively, vs. FeSO4=100) were also obtained with human subjects.


Studies with chicks on the growth depressing factor(s) in faba beans (Vicia faba L. var. minor). The growth response of broiler chicks was improved when they were fed diet containing high levels (greater than 85%) of heat treated as compared to raw faba beans. Pelleting and microwave treatment of faba beans containing 10% moisture resulted in maximal improvements in chick growth rates and feed efficiency of only 6% and 8%, respectively. Steam autoclaving (121 degrees for 20 minutes), extrusion (130 degrees or 152 degrees), or microwave treatment of faba beans containing 18% added water resulted in maximal improvements of 16% in growth rates and 19% in feed: gain ratios. the above study, a time course study of the relationship between faba beans autoclaving time anc chick growth response, and studies with individual faba bean fractions (starch isolate and protein isolate) suggests that processing improves the utilization of faba bean mainly through its effects on components associated with the protein and possibly the hull portions of faba beans. The utilization of faba bean starch is not improved with processing. Although the nature of the growth depressing factor(s) has not been established, the results from this study indicated that the major component does not appear to be a tryspin inhibitor, hemagglutinin, some other heat labile protein, or vicine.


Prevention of bony fluorosis in aluminum smelter workers. Excretion of fluorides during a seven-day workweek -- Pt. 2. 1. The excretion of fluoride is examined among aluminum smelter workers over the course of a seven-day workweek. The data for the first three days of work is best described by the first cycle of a parabolic curve. Each curve is characteristic of the level of exposure associated with specific jobs and individual smelter hygienic conditions. 2. The variability associated with the post-shift values after apparent equilibrium is attained is extreme. Such variability is probably due in large part to differences in exposure occurring during the last few hours of that work-day. This is further augmented as essentially all the absorbed fluoride is excreted as the near-equilibrium state is attained. 3. Because of this variability, the use of the post-shift urinary fluoride concentration as an indicator of exposure conditions should be limited to groups of workers, rather than individuals, at possible risk. 4. It appears that a urinary fluoride sample taken any day after the third day of the shift is an adequate post-shift fluoride exposure indicator among these groups of workers.


Prevention of bony fluorosis in aluminum smelter workers. A five-year study of fluoride absorption and excretion -- Pt. 3. 1. A study of over 52,000 urinary fluoride determinations collected over a 5-year period among aluminum smelter workers is described. The pre-shift urinary fluoride concentration (representative of bony burden) appears to increase less rapidly than the post-shift concentration. This slow rate of bony buildup of pre-shift urinary fluoride concentrations reflects the relatively slow uptake of fluoride by osseous tissues at these levels of exposure. 2. The utility of post-shift urinary fluoride analysis is reflected by its close correlation with improvement or deterioration in work practices which determines the degree of potential fluoride exposure. 3. Over 16,000 urinary tests for protein were performed in aluminum smelter workers. The absence of correlation between urinary fluoride concentrations and the presence of albuminuria indicates the absence of renal alteration among these workers.


Prevention of bony fluorosis in aluminum smelter workers. A 15-year retrospective study of fluoride excretion and bony radiopacity among aluminum smelter workers -- Pt. 4. 1. Fifty six aluminum smelter workers with 10 to 43 years' occupational exposure, and who had been previously studied medically, were re-x-rayed. Average urinary fluoride concentrations since 1960 were estimated to range from 2.78 mg/liter preshift and 7.71 mg/liter postshift. 2. Roentgenographic studies in 1960-66 and 1974 failed to reveal any evidence of fluoride associated bony change. 3. Although these workers represent a self-selected group, their magnitude and duration of exposure far outweighs any other group working at present or in the past at this plant. The implication that they have uniformly self-selected as fluoride resistant individuals is improbable. 4. These data indicate that group post-shift ur a long period is not associated with enhanced risk of bony fluorosis. If preshift urinary fluoride concentrations are less than 4 mg/l, the same results appears to apply.


The effect of myocardial infarction on the cardiac sensitization potential of certain halocarbons. We have previously shown that many halocarbons and hydrocarbons are capable of producing cardiac sensitization. Briefly, the test method involved exposure of healthy, unanesthetized, beagle dogs to various inspired levels of sensitizing agent, followed by an intravenous dose (8 mug/kg) of epinephrine. Along, this epinephrine dose produces only mild ECG alterations, but, at threshold levels of a sensitizing agent, may induce a serious cardiac arrhythmia and sometimes death. Using the same test protocol, dogs with experimentally-induced myocardial infarctions were used to determine whether this type of heart condition might significantly lower the threshold for cardiac sensitization. Test results on three halocarbons showed no greater potential for cardiac sensitization among dogs having recovered from myocardial infarction as compared to normal, healthy animals.


The health of long service tetraethyl lead workers. Detailed comparison of extensive medical information (results of periodic medical examinations, of medical records of absence from work due to non-occupational illness, and of cumulative medical diagnoses) for workers with 20 years or more TEL service to a matched (for age, sex, race and length of service) group of workers with no occupational lead (TEL or other) exposure shows no significant health differences between the two populations. The conclusion is drawn that, under the conditions have existed at this facility, workers having long occupational exposure to levels of lead (chiefly TEL) sharply in excess of that of the general public, but within a range termed "safe" by current industrial medical standards, have not suffered detectable impairment of health.


Prevention of bony fluorosis in aluminum smelter workers. Absorption and excretion of fluoride immediately after exposure -- Pt. 1. 1. A program for the prevention of excessive fluoride absorption among aluminum smelter workers is described. This surveillance is based upon knowledge of the portals of entry, distribution, bone deposition and excretory patterns of this element. 2. The control program is based on the thesis that the concentration of fluoride in the urine two to three days after cessation of work-related exposure reflects the bony burden of this element among this occupational group. Further, this program assumes that the concentration of urinary fluoride after three to five days of shift work reflects the extent of work exposure, adequacy of hygienic and engineering controls and work practices. The limitations of such program as it applies to individual samplings of workers is emphasized. 3. A balance between inhaled fluoride and urinary excretion over a 24-hour period (beginning with work exposure) is attempted. An approximate model for aluminum smelter workers in a near equilibrium F balance is constructed. The role of particle size distribution as a determinant of body loading is emphasized. Because of considerable variation in uptake possible with differing particle size distributions, the actual body F loading potential is inadequately determined on the basis of F concentrations in air. These data also suggest that gaseous fluoride is probably adsorbed upon particulates and absorbed at the alveolar level in the same fashion as respirable particulate fluoride. 4. The regression of ambient fluoride on urinary excretion suggests that the present threshold limit value for fluoride might be more appropriately set at 2 mg/M33 for an eight-hour day.


The supervisor's role with the problem drinker employee. In a large company, a group of problem drinker employees selected from the Alcoholic Rehabilitation Program at Illinois Bell, and a group of supervisors of such employees were participants in the study. Questionnaires as well as interviews were utilized. Comparative tables were discussed. A definite, yet flexible role of the supervisor was seen operative throughout the different processes of recognition, confrontation, referral, and treatment. Certain conclusions were drawn from the perspective of the patients, the supervisors, and the company.


Tuberculosis in a New York plant: analysis and observations. A case of active open pulmonary tuberculosis was accidently and randomly encountered in the midst of a population of middle-aged service employees. A tuberculin survey and x-ray study did not reveal transmission of disease to coworkers. This fortuitous outcome was unexpected. Hypothetical explanations are advanced to account for the extraordinarily high rate of tuberculin reactors in the plant (21.4% to 47.4%) and for the apparent low level or limited infectivity of the index case. The investigation was pursued methodically with selective use of the attack rate to develop successive hypotheses from a spate of complex findings. It is suggested that (because of inherent similarities) occupational physicians will find this type of approach to be effective in the investigation of outbreaks of occupational disease.


The multiplicity of roles of the occupational physician. The contemporary occupational physician serves many roles as he practices occupational medicine in the complexities of our industrial society. He is a physician, administrator, supervisor, interpreter, teacher, counselor, social worker, rehabilitationist, motivator, or advocate, as employee needs require. When performing well in these roles, he will serve best the employer, the worker, and himself, and, in the words of Rutherford T. Johnstone, will sense the poetry and romance of occupational medicine.


Prothrombin complex concentrate (Konyne) in the treatment of hemophilic patients with factor VIII inhibitors. Two prothrombin complex concentrates, Auto-Factor IX and Proplex, have been reported to be effective in controlling bleeding in hemophilic patients with factor VIII inhibitors. A third PCC, Konyne, was used to treat 64 bleeding episodes (130 infusions) in five hemophilic patients with factor VIII inhibitors. Prompt control of bleeding was observed in each instance with doses of 15 to 100 units of factor IX/kg; no complications were encountered. Konyne resulted in in vivo and in vitro shortening of the partial thromboplastin time of patients with factor VIII inhibitors, but the mechanism of action is unknown. If further studies confirm the efficacy and safety of PCC in the treatment of such patients, its use for this purpose could lead to significant saving of factor VIII concentrates.


Gonadal function, testicular histology, and meiosis following cyclophosphamide therapy in patients with nephrotic syndrome. Gonadal function, histology, and meiosis were studied in patients after puberty who had received cyclophosphamide in the treatment of nephrotic syndrome. Four males with minimal lesion nephrotic syndrome received cyclophosphamide, 2 to 4 mg/kg/24 hr, during periods ranging from 49 to 60 days and had normal semen at 15 3/12 to 22 3/12 years of age. Four males who received cyclophosphamide, 2 to 5 mg/kg/24 hr, during 89 to 489 days were azoospermic at 15 6/12 to 21 11/12 years of age. Plasma testosterone levels were normal in both groups. LH and FSH levels were elevated in the azoospermicgroup. Light and electron microscopy and meiotic analysis of testicular tissue were normal in two normospermic patients tested. Germinal cells were absent but Leydig and Sertoli cells were present in three azoospermic patients tested. No neoplasia was observed. Two preadolescent and two postadolescent males received 64 to 129 mg/kg of cyclophosphamide during 14 to 45 days and have since fathered normal children. One preadolescent female received 182 mg/kg of cyclophosphamide during 49 days and later bore a normal child. Two preadolescent females who died of complications of their nephrotic syndrome during childhood after courses of cyclophosphamide had normal preadolescent ovaries.


Small bowel mucosal dysfunction in patients with cystic fibrosis. Jejunal biopsies were obtained from 37 children with cystic fibrosis, 16 with gluten-induced enteropathy, and 18 control subjects for the following studies: (1) disaccharidase activity, (2) L-ALA-L-Phe hydrolase activity, and (3) intestinal uptake of three 14C-labeled amino acids. Values were significantly reduced in the three determinations in patients with gluten-induced enteropathy as compared to control subjects. Lactase and L-ALA-L-Phe hydrolase activities were significantly reduced (p less than 0.01) in CF patients as compared to control subjects. Definite hypolactasia was also observed in 23% of the children with CF. Uptake of lysine was normal in CF patients whereas that of phenylalanine and cycloleucine was reduced as compared to control subjects. This study suggests an intestinal component to the malabsorption of patients with CF.


Iron deficiency in an Eskimo village. The value of serum ferritin in assessing iron nutrition before and after a three-month period of iron supplementation. The serum ferritin concentration, a new means of assessing iron nutrition, was utilized in conjunction with the hematocrit value, serum iron concentration, and total iron binding capacity to determine the effect of a three-month period of iron supplementation in a group of 146 Eskimo children in Chevak, Alaska. Before treatment, 41% of the children had concentrations of serum ferritin below normal, 18% had a subnormal serum transferrin saturation, and 26% were anemic. After supplementation, only 6% had a subnormal serum ferritin concentration. Despite this evidence of improved iron stores in the group as a whole, the prevalence of low serum transferrin saturation and of anemia remained high, 15% and 17%, respectively. These results could be explained by a high incidence of infection, which, like iron deficiency, is associated with anemia and a low serum transferrin saturation. We conclude that the serum ferritin determination reflected an improvement in iron nutrition that was not as readily apparent by other measurements, and that factors other than iron deficiency also played an important role in the mild anemia that was prevalent in Chevak.


Beta-methylcrotonic aciduria associated with lactic acidosis. A patient is described in whom lactic acidosis of very severe degree was found to coincide with the presence of beta-methylcrotonic acid and rho-hydroxyphenyllactic acid in urine in large amounts, while beta-hydroxyisovaleric acid was found to be a relatively minor excretion product. Beta-methylcrotonic acid is demonstrated, for the first time, to be present in blood and CSF. These findings are discussed in relation to the patients previously reported to have beta-methylcrotonylglycinuria and raise the possibility that our patient's organic aciduria may be secondary to acquired disease rather than to an inborn error of metabolism.


Familial hepatic venoocclusive disease with probable immune deficiency. Five infants from three families died between the ages of 2 and 7 months with venocclusive disease of the liver. No dietary, toxic, or other extrinsic cause was uncovered. In one family the first infant was breast-fed; the second one received no breast milk. In two of the families the parents were cousins. All infants had some evidence of immune deficiency, including hypogammaglobulinemia in at least three, multiple infections especially Pnumocystis carnii and enteroviruses, and lymphoid tissues devoid of germinal centers and mature plasma cells. Other findings in some of the infants, not previously recorded in venoocclusive disease, were microcephaly, multiple small cerebral softening, and left atrial endocardial fibrosis. A congenital cause for venoocclusive disease is suggested in these cases.


The Hajdu-Cheney syndrome. Report of two cases and review of the literature. The Hajdu-Cheney syndrome includes short stature, characteristic facies, and a slowly progressive skeletal dysplasia which affects skull, spine, and long bones. Two patients with this syndrome are presented. In the first patient the most distinctive skeletal feature, acro-osteolysis, was shown to be absent at age 6 years but was present at age 11 years. Diagnosis was made in the second case in the absence of acroosteolysis because of otherwise typical findings. Abnormalities affecting vision, hearing, and dentition occur and these, along with the other characteristic physical and radiographic features of the syndrome, should enable diagnosis prior to the onset of acro-osteolysis.


Rocking waterbeds and auditory stimuli to enhance growth of preterm infants. Preliminary report. In this study certain features of intrauterine environment were stimulated. Preterm infants were placed on waterbeds, gently rocked, and exposed to auditory stimuli. The stimulated group exhibited significantly better growth for weight, head circumference, and biparietal diameter of the head than did the control infants. Healthy preterm infants placed on rocking waterbeds and exposed to auditory stimuli had growth characteristics comparable to fetuses during the thirty-second to the thirty-sixth week of gestation.


A danger of haloperidol therapy in children. Attention is directed to the potential danger of therapy with haloperidol in children. Its value in reducing the excessive movements of Sydenham chorea must be weighed against the usual tendency of this disorder to remit spontaneously and the occasional tendency of the drug to cause castastropic adverse reaction


"Pulse" methylprednisolone therapy in the treatment of severe glomerulonephritis. Eight patients with severe glomerulonephritis and an average inulin clearance of 21.7 ml/min/1.73 m2 body surface were treated with high-dosage intravenous methylprednisolone, 30 mg/kg given over a one-hour period on each of six alternate days. The mean inulin clearance rate doubled after this "pulse" therapy. In the six patients treated early in the course of their disease, GFR increased to a mean of 100.2 ml/min/1.73 m2 during the follow-up period extending for up to three years and was accompanied by clinical improvement. These observations suggest that "pulse" methylprednisolone may be beneficial in treating some patients with potentially life-threatening severe glomerulonephritis.