Brain cortex phospholipids liposomes effects on CSF HVA, 5-HIAA and on prolactin and somatotropin secretion in man. Liposomes obtained from bovine brain cortex phospholipids (BC-PL), which display several effects on brain function in mice, have been administered intravenously (200 mg) to healthy subjects at various times before diagnostic lumbar puncture. HVA and 5-HIAA concentrations in CSF have been evaluated with the aim of assessing changes of monoamines metabolism. An increase of HVA occurs after 2 hours from BC-PL administration, reaching its peak after 6--7 hours. The finding is interpreted as an index of an increased turnover of brain DA. 5-HIAA changes are less impressive and a smaller increase of the metabolite is observed. They cannot correctly be related to brain changes of serotonin metabolism, since 5-HIAA originates also from the spinal cord. No effects are observed on the secretion of prolactin, but somatotropin increases sharply between 2 and 7 hours from treatment, suggesting the possibility of an activation of the dopaminergic pathway, stimulating STH secretion.


Peripheral nerve biopsies in the diagnosis of leprosy in Aboriginal patients from the Northern Territory of Australia. In the 12 years from 1964 to 1976, 171 peripheral nerve biopsies were taken from 81 Aboriginal patients in the Northern Territory of Australia, in whom a diagnosis of leprosy was either known or strongly suspected. Sixty-eight biopsy samples were from 19 patients known to have leprosy, and who were under assessment for nerve grafting, results of which have already been published. We describe here the histopathological findings in the remaining 62 patients, in whom a diagnosis of leprosy was suspected on clinical grounds, backed in many cases by abnormalities of nerve conduction. Forty-one patients (66%) had abnormal histopathological findings in the nerve biopsy sample, 19 (31%) showing definite evidence of leprosy. Several patients with enlarged peripheral nerves, in whom the biopsy findings did not confine leprosy, remain under observation; their future investigation will include lymphocyte transformation tests and testing with refined lepromin, together with repeat nerve biopsy, where ethical and feasible. The clinical and epidemiological data suggest that a previous, and perhaps self-healing, form of leprosy may account for the neurological findings.


Incidence, severity, and time-course of motoneurone dysfunction in myotonic dystrophy: their significance for an understanding of anticipation. The numbers of functioning motor units and the amplitudes of the maximum evoked muscle responses have been measured in 198 muscles of 102 patients with myotonic dystrophy. Losses of units could be demonstrated in most of the extensor digitorum brevis and thenar muscles but less commonly in the hypothenar groups. A more proximal limb muscle, the soleus, was also shown to be involved frequently. Investigation of two premature infants withmyotonic dystrophy also revealed reductions of functiong units; in one infant clinical improvement was associated with increased muscle innervation. Repeated examinations of 10 adult patients disclosed an abnormal decline in neuromuscular function below the age of 60 years. The reduction in functioning units amounted to approximately 3% of the mean control value per annum. Analysis of 19 families showed that the severity of neuromuscular involvement was nearly always greater in members of later generations. If the predicted deterioration was also taken into account, the results strongly suggested that anticipation was a true genetic phenomenon rather than an artefact of selection. The combined results are considered to strengthen the concept of motoneurone dysfunction as the major pathogenetic factor in this form of dystrophy.


Correlation between regional cerebral blood flow and brain atrophy in dementia. Combined study with 133Xenon inhalation and computerised tomography. Measurement of the regional cerebral blood flow (rCBF) by the 133Xenon inhalation method and computerised tomography were performed in 25 patients with presenile and senile dementia. Reduction of rCBF and various degrees of ventricular enlargement and cortical sulcal widening were demonstrated in the majority of demented subjects. However, there was no correlation between rCBF values and the severity of ventricular dilatation or cortical atrophy. These findings suggest that loss of brain substance is not an important factor in the reduction of rCBF in dementia.


Effect of tinofedrine (Homburg D8955) on cerebral blood flow in multi-infarct dementia. Tinofedrine, a new derivative of l-norephedrine, was examined for cerebral vasodilator activity in man. Ten patients with reduced cerebral blood flow (CBF) and multi-infarct dementia were given the drug intravenously. Cerebral blood flow increased significantly by 28% from a mean of 43.3 to 55.5 ml/100 g/min.


Electroencephalography and computerised tomography in vascular and non-vascular dementia in old age. Nine normal elderly subjects and 81 patients with dementia have been studied by computerised tomography (CT) and electroencephalography (EEG). There was a broad relationship between slowing of the basic frequency of the EEG and the severity of mental impairment. Localised slow-wave activity was found in 19% of those with non-vascular dementia and 72% of those with dementia of vascular origin. The mean size of the ventricles, as determined from CT scans, was larger in the vascular than in the non-vascular group. Within the vascular group it was larger in those without than in those with visible infarcts. There was no relationship in either group between ventricular size and dominant EEG frequency.


Carbamazepine as a single drug in the treatment of epilepsy. A prospective study of serum levels and seizure control. Serum levels and seizure control were investigated in a prospective study when carbamazepine was given as a single drug to 32 patients with a variety of seizures. The patients included 13 previously untreated patients (group 1), and 19 who were unresponsive to other anticonvulsant drugs used in different combinations or as a single treatment (group 2). Thirteen patients (10 from group 1, and three from group 2) became seizure-free, and a greater than 50% reduction in seizure frequency occurred in 10 patients (nine from group 2, and one from group 1). Less than 50% reduction in seizure frequency occurred in five patients from group 2. As a wide range of serum levels was associated with complete freedom from seizures, or a greater than 50% reduction in seizure frequency, it was not possible to define a therapeutic range for carbamazepine. Side effects occurred at the start of treatment or after a dose increase. A wide range of serum levels was associated with side effects, and some patients could not tolerate levels greater than 42 mumol/l.


Effects of levodopa alone and in combination with dopa-decarboxylase inhibitors on plasma renin activity in patients with Parkinson's disease. Plasma renin activity (PRA) of patients with Parkinson's disease was measured in recumbency, upright position, and after frusemide administration. The results show that the renin responses to both stimuli are significantly reduced as compared with those obtained in a group of normal subjects, while recumbent PRA levels of Parkinsonism patients are not significantly lower than those found in recumbent normal subjects. Levodopa treatment, alone or in combination with two different dopa-decarboxylase inhibitors, benserazide and carbidopa, does not modify the renin response to posture or to frusemide. Although the reduced activity of the renin-angiotensin system can play some role in the genesis of orthostatic hypotensive episodes encountered in patients with Parkinsonism, the greater incidence of orthostatis hypotension in patients treated with levodopa seems to be unrelated to any effect of this drug on the renin release.


Unloading and shortening reactions in Parkinson's disease. The unloading reflex was tested on both sides of a patient with asymmetrical Parkinsonism. The motor activity after the silent period was significantly greater on the more affected side. The findings support the hypothesis that the response to unloading and the shortening reaction share a common mechanism which is exaggerated in Parkinsonism.


Transient decrease in number of motor units after immobilisation in man. On the day after the removal of a long leg cast, when the patient could just bend his knee, the electrical activity in the disused quadriceps muscle showed changes that indicated a reduction in the number of motor units. At 10 to 75% of maximum force the number of turns and the mean amplitude of the needle-recorded EMG were reduced in the disused muscle. Eight days later, when half the initial loss of force had been regained, the electrical activity was normal. The electrical activity produced during a constant force of 5 kg did not differ in the disused and in the contralateral muscle. From the findings in normal subjects it was deduced that the compensatory increase in turns in the EMG pattern to be expected from the decrease in cross-sectional area of the muscle fibres was within the error of the method. The transient decrease in the number of turns and in mean amplitude of the EMG of the disused muscle are an indication of the plasticity of the motor system.


Coital cephalgia and ischaemic muscular work of the lower limbs. A case is reported of a patient who presented with coital cephalgia, and in whom an obstructive lesion of the lower aorta was demonstrated. Bicycle ergometry evoked an abnormal pressor response. The condition was cured by restoration of normal circulation. An abnormal pressor response to treadmill exercise was shown to exist in subjects with intermittent claudication, and in normal subjects with circulation to lower limbs artificially occluded. A pressor response to buttock or leg exercise or both is suggested as the cause of the coital cephalgia.


Recovery in hydrocephalic dementia after shunt operation. Twenty-three patients with hydrocephalic dementia were studied before and after shunt operation, and improvement was found in 12. Before operation, the improved cases showed more symptoms of confabulation, gait disturbance, urinary incontinence, lack of insight, and constructional apraxia. The improvement was also most marked in these symptoms. The significance of general versus specific symptoms, duration, and aetiology is discussed from a differential diagnostic standpoint, and we conclude that the adequate and early diagnosis of hydrocephalic dementia is essential for good outcome after shunt operation, and that psychiatric and psychometric evaluation enable such a diagnosis to be made.


Predictive value of serum lactate dehydrogenase in head injury. Serum total lactate dehydrogenase (LDH) was estimated serially for up to 15 days in 110 patients with head injuries who had no extraneural injury. Increase in LDH activity generally indicated the degree of parenchymal brain damage. The prognostic value of LDH was established by correlating its activity with clinical criteria such as duration of unconsciousness and post-traumatic amnesia, type of brain damage, and quality of survival. A significant rise in LDH activity suggested severe brain damage and poor prognosis.


Prevalence of stuttering.

Prevalence of stuttering. The prevalence of stuttering in a university population was 2.1%; 3.4% were former stutterers. More men than women stuttered. Right handed female stutterers were less likely to have "lost" their stutter than were right handed males. Stutterers, past stutterers, and questionable stutterers all had a family history of stuttering. The significant prevalence of stuttering, the increased prevalence among males, the lack of a decline of this disorder over the past few decades despite the increased number of speech clinicians and data concerning handedness, emphasise the need to investigate organic causes of stuttering.


Lack of evidence of generalised sensory neuropathy in patients with carpal tunnel syndrome. Radial and ulnar sensory nerve action potentials were recorded in patients referred for the electrophysiological confirmation of the carpal tunnel syndrome. Comparisons with values obtained in control neurological patients provided no evidence of a generalised neuropathy in such patients, as had previously been suggested.


Angiographically occult arteriovenous malformations of the brain. Six patients with cerebral arteriovenous malformations which did not show any pathological circulation at angiography are described. Computed tomogram appearances of such lesions may be difficult to distinguish from tumours. The need for surgical exploration in localised high attenuation lesions of uncertain nature is stressed, and the literature is reviewed.


Superior sagittal sinus thrombosis: an evaluation of the changes demonstrated on computed tomography. Five female patients, all either on contraceptive medication or in the postpartum period, with angiographically confirmed superior sagittal sinus thrombosis have been scanned. CAT appearances are nonspecific, but when taken in conjuction with the symptoms should suggest the possible diagnosis. The most consistent appearance was of diffuse cerebral swelling with subsequent return to normal. Bilateral low attenuation lesions with haemorrhagic areas were noted in one patient.


The Pulfrich spatial frequency phenomenon: a psychophysical method competitive to visual evoked potentials in the diagnosis of multiple sclerosis. The results of a study in which visual evoked responses (VERs) and a modified Pulfrich method were compared showed that both methods are very effective for the diagnosis of multiple sclerosis. With VERs, 97% of the multiple sclerosis cases were diagnosed correctly, while the corresponding value for the Pulfrich method was 93%. In contrast to VERs, the Pulfrich method allows only measurement of latency differences between the two visual pathways. This method involves measuring the speed required to cause a shift in the apparent depth location of a large, moving, striped pattern observed with a neutral density filter over one eye. A pathological transmission time was inferred when the patients observed a shift in the depth of the moving pattern either without any filter at all or with a filter whose attentuation was no more than 0.2 log units. A further criterion for pathology was a difference of more than 10% between the two eyes in the retinal speed required for a depth displacement using a 1.5 log unit filter. This test requires about 15 minutes, and can be carried out by a technical assistant.


Suppression of congenital nystagmus.

Suppression of congenital nystagmus. Suppression of congenital nystagmus by eyelid closure was studied by electrooculography in four cases under various conditions in order to elucidate whether the suppression is caused by blocking of fixation or not. The nystagmus persisted in the light as well as in the dark provided that the eyes were kept open. Frenzel's glasses did not suppress the nystagmus except for one case in whom jerky nystagmus was attenuated. In the other cases, only voluntary lid closure suppressed the nystagmus. Passive lid closure while the patient attempted to keep eyes open did not suppress the nystagmus except in one case. Reflex eyelid closure by glabellar tap did not suppress the nystagmus in spite of the occurrence of Bell's phenomenon. Passive eyelid opening while the patient attempted to keep eyes closed, on the other hand, did not reproduce the nystagmus. The suppression of congenital nystagmus by lid closure, at least in some cases, seems to be related to the voluntary effort to keep eyes closed but not specifically to blocking of fixation.


Reflex vertical gaze and the medial longitudinal fasciculus. Extraocular movements were investigated in a patient with bilateral vascular lesions of the medial longitudinal fasciculus. The patient showed voluntary and reflex horizontal gaze consistent with his lesion, but had absent reflex vertical gaze. Voluntary vertical gaze was present. Necropsy was performed, and the findings suggest that the medial longitudinal fasciculi in the pons conveys impulses for reflex vertical gaze, but are not required for voluntary vertical gaze.


Electrophysiological aspects of sensory conduction velocity in healthy adults. 1. Conduction velocity from digit to palm, from palm to wrist, and across the elbow, as a function of age. The sensory conduction velocity from digit to palm and from palm to wrist was determined in median (digit 3) and ulnar (digit 5) nerves in 47 healthy subjects with age range from 21 to 77 years. The decrement of the sensory conduction as a function of age was more marked in the palm to wrist than in the digit to palm segment. Sensory conduction velocity of the ulnar nerve across the elbow was also studied. Irregularities in the shape of the sensory evoked potential recorded above the cubital sulcus were found in 12.76% of cases, especially in subjects over 50 years of age. These results suggest that aging causes decrement in sensory conduction and changes in the shape of the evoked potentials, especially at points where the nerves are more frequently compressed.


Electrophysiological aspects of sensory conduction velocity in healthy adults. 2. Ratio between the amplitude of sensory evoked potentials at the wrist on stimulating different fingers in both hands. The normal ratio between the amplitude of the sensory evoked potential (SEP) at the wrist on stimulating digits 1, 2, 3, and 5 was determined in 44 healthy adult subjects. The first digit had the larger amplitude, and the fifth digit the smallest SEP. The amplitude expresses the density of sensory innervation in each finger. The ratio between the amplitude of different fingers varied according to the age of the subject. The amplitude of the SEP from a digit innervated by the median nerve decreased in the elderly more than the SEP amplitude of the digit innervated by the ulnar nerve, probably because of a chronic compression in the carpal tunnel. The changes in the normal amplitude ratio can be applied to the topographic diagnosis of radicular and brachial plexus lesions if a fixed segmental sensory innervation of the hand is accepted. In 44 right handed subjects the amplitude of the sensory evoked potentials at the wrist was significantly larger in the left hand. This asymmetry of sensory innervation between hands could be physiological, and suggests a greater density of sensory innervation in the left hand of right handed subjects.


Numerical grading of clinical neurological status after serious head injury. A scheme to quantitate the clinical neurological status of the seriously head-injured patient has been devised. The neurological parameters used to quantify the degree of injury are based on neurological functions which have previously been accepted as indicators of the severity of the head injury. A numerical value is assigned to each parameter with emphasis on defining the level of consciousness. The accrued point total of each examination represents the neurological status of the patient at that time. Mean values and standard error from the means are determined from repeated examinations during a single 24 hour period, and are plotted against days after injury. From this graph a line which represents the rate of clinical recovery is determined by least squares analysis. General intensive care nurses were trained to score patients independently; their determinations were found to be in statistical agreement with scores derived from examinations by the attending physicians. The data presented highlight the effects of hypoxaemia in impeding the rate of neurological recovery from a serious head injury. This simple clinical analytical scheme for the quantitative assessment of patients with head injury permits evaluation of the efficacy of various modes of therapy in altering the rate of recovery.


Neurological asymmetries immediately after unilateral ECT. Twenty-nine right handed patients were examined neurologically before and immediately after each of 62 unilateral ECTs to the dominant and non-dominant hemispheres. Most convulsions were followed by signs of transitory neurological dysfunction referable to the treated hemisphere. These signs included deep tendon reflex asymmetry, hemiparesis, tactile and visual inattention, and homonymous hemianopia. After treatment to the right hemisphere some patients had left visuospatial neglect, while all patients who had dominant hemisphere ECT were transiently dysphasic. All neurological abnormalities tested resolved within 20 minutes of treatment.


Increase in CSF protein in association with ECT. In this case report we describe a 44 year old man who developed a transient increase of CSF protein in association with a course of electroconvulsive therapy for depression. Neurological evaluation failed to show any other abnormalities. The finding seems to reflect a transient dysfunction of the blood-brain barrier.


Localization of olivo-cerebellar fibers in inferior cerebellar peduncle in man. The localization of the olivo-cerebellar fibers in the inferior cerebellar peduncle was examined in a patient who showed severe degeneration of the left olivary nucleus due to an old hemorrhagic infarct in the contralateral cerebellum. Other precerebellar nuclei which send their cerebellipetal axons to the inferior cerebellar peduncle, such as the external cuneate nucleus, the lateral reticular nucleus and the arcuate nucleus, were normally preserved. The dorsal spino-cerebellar tract and the vestibular nuclei, together with the juxtarestiform body were also intact. Degeneration of the inferior cerebellar peduncle was noted only in its ventromedial portion contralateral to the olivary lesion. As a result, it is concluded that the olivo-cerebellar fibers seem to be located in this portion of the inferior cerebellar peduncle.


Neurogenic and vascular claudication.

Neurogenic and vascular claudication. Intermittent claudication from peripheral vascular disease is sometimes difficult to distinguish from similar claudication due to degenerative disease of the lumbar spine. In the present study 26 patients with vascular disease were compared with 23 patients with lumbar degenerative disease. Assessment was by clinical and radiological examination. In the vascular group characteristic distinguishing features were: abnormal foot pulses, arterial bruits, relief of symptoms by standing, a constant claudicating distance and stocking sensory loss. In the lumbar group typical findings were: discomfort on lifting, bending, coughing or sneezing, pain on standing, history of back injury, variable claudicating distance and segmental sensory loss.


The significance of ragged-red fibres in neuromuscular disease. The pathological significance of ragged-red fibres is uncertain. We have studied ragged-red fibres in the muscle biopsies of 3 adults; one with polymyositis and two with progressive external ophthalmoplegia. All the ragged-red fibres were Type 1 fibres. In two patients the mean diameter of the ragged-red fibres was significantly smaller than the unaffected Type 1 fibres. Some of these fibres showed features of regeneration, and others of degeneration. In the patient with polymyositis the mitochondria were proliferated and contained osmiophilic dense bodies; in the other two patients paracrystalline mitochondrial inclusions were prominent. These findings suggest that ragged-red fibres do not represent a single pathological process.


Multiple specificities of antibrain antibodies in multiple sclerosis and chronic myelopathy. The presence of complement-fixing antibodies against brain antigens was tested in paired serum and cerebrospinal fluid (CSF) samples from 60 multiple sclerosis (MS) patients, 15 patients with chronic myelopathy of undetermined cause (CM) and 60 control patients. Six MS sera, 34 MS CSF, 4 CM sera, 3 CM CSF, 4 control sera and 1 control CSF gave positive reactions either with a lipid extract or a saline extract of normal human brain. The proportion of anticomplementary CSF was significantly higher in the MS group than in the control group (15% vs 0%, P less than 0.01). The reactivity of a large number of individual positive samples was further investigated. Seven antibody specificities were discerned in the MS samples. Most samples reacted with non-lipid antigens, the dominating being a heat-labile, nonlipid component associated with CNS myelin. Antibodies to cerebroside and sulfatide were detected in a few patients. A number of samples reacted with cholesterol in combination with a variety of lipids. Positive samples from the CM patients exhibited a similar heterogeneity. In the control group positive reactions were seen in one patient with systemic lupus erythematosus (SLE), two patients with rheumatoid arthritis (RA), and one with a spinal meningioma. The reaction patterns of these patients were different from those commonly seen in MS patients. The complement-fixing antibrain antibodies in MS CSF are usually of IgG class (Ryberg 1976). This applies also to the positive MS sera in this study. The distribution of the antibodies between serum and CSF indicated, in several cases, an intrathecal synthesis. All of a number of human brains, including one MS brain, contained all 6 antigens (haptens) reactive in saline extracts. Antibodies to tissues outside the CNS were rarely detected in MS patients. The varied humoral autoimmune response in MS might reflect a heterogeneity in the MS patients, the disease itself or its causative agent.


Regional cerebral blood flow in parkinsonism. Measurement before and after levodopa. Data from recent studies in experimental animals suggest that central dopaminergic mechanisms may be involved in regulation of the regional cerebral blood flow (rCBF) in the mammalian brain. In order to evaluate possible effects of dopaminergic stimulation on human cerebral circulation, rCBF was measured by the 133Xenon inhalation technique in 26 patients with Parkinson's disease before and after the chronic oral administration of levodopa combined with a peripheral Dopa-decarboxylase inhibitor. Treatment with levodopa did not induce significant alterations in the mean brain, mean hemispheric or regional flow values in these patients. These findings suggest that the dopaminergic system does not play an important role in modulation of the rCBF in man.


Globoid cell leukodystrophy (Krabbe's disease). Metabolic studies with cultured fibroblasts. Metabolism of tritium-labelled galactosylceramide and lactosylceramide added to the culture medium was examined in cultured skin fibroblasts from 4 patients with globoid cell leukodystrophy (GLD) and 4 control individuals. The uptake of [3H]galactosylceramide and [3H]lactosylceramide by the fibroblasts continued actively at least up to 3 days. Approximately 30--40% of the galactosylceramide, which had been taken up, was released subsequently from the cells in a 4-day period, whereas only 10% of lactosylceramide was released during the same period. The GLD fibroblasts showed no abnormality in the kinetics of the uptake and in the release of these glycosphingolipids which are natural substrates of the beta-galactosidase genetically deficient in the disorder. This finding differs from that reported for fibroblasts from patients with metachromatic leukodystrophy, which showed abnormal accumulation and retention of sulfatide added to the culture media. However, degradation of added galactosylceramide to [3H]galactose by the GLD fibroblasts was only 25% of the control cells, while lactosylceramide was degraded at 70% of the normal rate. These findings are consistent with the known substrate specificities of the two acidic beta-galactosidases in human tissues; galactosylceramide is hydrolyzed almost exclusively by galactosylceramidase, while lactosylceramide can be hydrolyzed by both galactosylceramidase and GM1-ganglioside beta-galactosidase.


Experimental (-) emetine myopathy. Ultrastructural and morphometric observations. The ultrastructural changes induced by (-) emetine hydrochloride were studied in two skeletal muscles of the rat. (-) Emetine was administered at a dose level of 2 mg/kg for periods ranging from one to four weeks. Changes were noted after the one week stage and were progressive with all muscle components appearing to be affected.  Myofibrillar changes included Z line streaming, rod formation, myofilament loss and contraction clumping. Mitochondrial degeneration was detected, but the most striking feature of the induced myopathy was the extensive membrane proliferation. The membranes were considered to be involved in the isolation of sarcoplasmic constitutents in the production of autophagic vacuoles. Morphometry was carried out in order to quantify some of the changes in the fibre components.


N-ethyl-N-nitrosourea-induced teratogenesis of brain in the rat. A cellular and cytoarchitectural analysis of the neocortex. N-Ethyl-N-nitrosourea (ENU) was administered intravenously to pregnant Wistar-albino rats on days 14--21 of gestation in order to study the teratological effects of the carcinogen on the developing brain. Offspring were killed 60 days postnatally, and the brains examined histologically by cresyl violet staining and Golgi-Cox preparations. Macroscopic examination of the brains revealed a graded pattern of microcephaly. Injection of ENU on day 14 of gestation gave the most severe effects and injection on day 21 the least effects. Microscopic examination of the neocortex revealed a graded reduction in the lateral and sagittal lengths, thickness, and the number of cells in a sample slab of the cortex. In the Golgi-Cox preparations the pyramidal neurons of cortical layers III and V, as well as neurons of other layers, were seen to have fewer secondary and tertiary dendrites, and the length of their dendrites appeared stunted. These characteristics also were graded in relation to the day of injection of ENU. Altered cytology and cytoarchitecture of the neocortex and possible underlying mechanisms are discussed.


Quantitative studies of ciliary and sphenopalatine ganglia in familial dysautonomia. In 3 patients with familial dysautonomia (FD) sphenopalatine ganglia were less than one fifth normal in volume and their total neuronal content was reduced to a mean of 1,510 (control mean 56,500). Parasympathetic denervation accounts for absence of overflow tears in FD. Ciliary ganglia were not reduced in volume and in 4 patients the mean neuron total was only slightly diminished to 2,900 (control 3,670, P less than or equal to 0.05). This does not appear sufficient to account for pupillary supersensitivity to methacholine in FD on the basis of denervation. Temporal differences in the embryogenesis of sphenopalatine and ciliary ganglia may underlie the observed differences in neuronal populations and suggest that the developmental anomaly in FD does not occur early in gestation.


Virus-associated demyelination. A model using avirulent Semliki Forest virus infection of mice. Lesions produced by the infection of Swiss/A2G mice with a single inoculation of an avirulent strain of Semliki forest virus have been studied by light and electron microscopy. Whilst a mild encephalitis was detected in the great majority of mice infected, focal areas of myelin loss were observed in the cerebellar white matter of only 25% of cases. The incidence of myelin loss in other strains of mice ranged from 21% in BSVS mice to 8% in SJL/J mice. The possible mechanisms involved in the pathogenesis of the myelin loss are discussed.


Delay in the maturation of muscle fibers in infants with congenital hypotonia. Muscle biopsies of hypotonic children have shown delayed maturation of a fetal type of muscle fibers: subsarcolemmal halo devoid of activity for mitochondrial dehydrogenases, type II predominance and in some cases abnormal dispersion of fiber diameter. Fiber subtypes within group II were also abnormal. One case has definite embryonic characteristics with presence of myoblasts. Not a single clinical pattern was present in these patients and a variety of associated disorders were recognized. Some patients had a clinical picture corresponding to congenital benign hypotonia as described by Walton.


Fine structure of the rubrospinal terminals in the cervical cord of the cat. Rubrospinal fibers in cat do not terminate on anterior motor horn cells in the spinal cord but on the interneurons, mostly in the lateral portion of Rexed's lamina of V-VII, the so-called Lateral Basal Region. The ultrastructure of rubrospinal terminals at the cervical cord level (C8) was investigated in 8 adult cats with partial or complete stereotaxic lesions of the red nuclei. Animals were sacrificed from 1 to 7 days after the lesions were made and the earliest forms of degeneration found were infrequent dense preterminal axon changes and clumping and coalescing of synaptic vesicles in the terminals. Multiple dense or polymembranous inclusions were seen in some terminals and these contained vesicular profiles; dense terminal shrinking was seen in others after 24 hours. Neurofilamentous proliferation appeared in some degenerating terminals after 48--72 hours. Degenerating terminals were related to different sized dendrites to determine regional axodendritic specificity for rubrospinal endings on LBR neurons.


Paraproteinosis and amyloidosis of the cerebral vessels and senile plaques. A case is reported of progressive dementia and a terminal picture of generalized tetaniform contractures. The relationship of the generalized tetaniform contractures to the stiff-man syndrome is discussed. Morphologically, diffuse amyloid deposition was found in the pial and cortical vessels, accompanied by amyloid deposition in the senile plaques in the cortical and cerebellar cortex. Apart from the typical staining and ultrastructural aspects of amyloid, a deposition of material was observed, corresponding in optical and electron microscopy to a paraprotein. This case demonstrated not only the relationship between the deposition of amyloid and the formation of senile plaques, but also sustains the direct connection between amyloid in senile plaques and the paraprotein substances deriving from the blood. The probable relationship between the unusual deposition of paraproteins in the vessels and nervous system and the treatment with immunoglobulins is discussed.


Quantitative studies of sympathetic ganglia and spinal cord intermedio-lateral gray columns in familial dysautonomia. In adult patients with familial dysautonomia the mean volume of superior cervical sympathetic ganglia is reduced to 34% of the normal of 222 mm3. Packing density of neurons is reduced to 37% of normal. The mean total number of ganglionic neurons is 120,000 as compared to 1,060,000 in controls. The mean totals of preganglionic neurons in the first three thoracic cord segments are 13,600 in patients and 25,150 in controls. Deficits in sympathetic neurons account for many of the clinical, pharmacological and biochemical manifestations of familial dysautonomia.


Development of normal and dystrophic chick muscle in tissue culture. Production and release of creatine kinase and acetylcholinesterase. Creatine kinase (CK) and acetylcholinesterase (AChE) were followed during the course of development of embryonic muscle in tissue culture for periods of up to 8 weeks. Control muscle cultures released CK and AChE into the medium for the first 2-3 weeks, after which time measurable enzyme release ended. In dystrophic muscle cultures release of CK and AChE continued over most of the 8-week culture period. Cumulative measurable activity of CK was significantly greater than that of controls by the 3rd week and thereafter and cumulative AChE release was greater than that of controls by the 5th week and averaged about twice that of controls by the end of the culture period. Total cell CK activity of the dystrophic muscle cultures was greater than control values but results of cellulose acetate electrophoretic analysis of CK isozyme composition indicated that control muscle cultures attained higher percentage levels of MM isozyme type and lower levels of MB isozyme. Breast muscle extracts from adult dystrophic chickens had an approximately 10--13% content of MB isozyme while in similar extracts of control chicken muscle only the MM isozyme was detectable and total activity was greater than in dystrophics. Bound AChE activity of dystrophic muscle was significantly greater than control levels subsequent to the 2nd week in culture. Soluble AChE activity of dystrophic muscle was somewhat greater than comparable control activity in 2 of 3 tissue culture series at approximately the same period. In 7--10 week-old dystrophic chickens, both soluble and bound AChE activities of dystrophic breast muscle extracts were markedly increased over control values.


An unusual neurological disorder of copper metabolism clinically resembling Wilson's disease but biochemically a distinct entity. A patient with progressive neurological disease resembling Wilson's disease but in whom Kayser-Fleischer rings were absent, was given 67Cu and 64Cu, orally and intravenously, to measure the rate of absorption of copper using a convolution integral. The data show an abnormal distribution of body copper resulting in low copper concentrations in plasma, urine and liver but with an accumulation in the lower bowel probably due to a defect in mucosal transport. The importance of differentiating this condition from Wilson's disease is stressed.


Features of foreign proteins affecting their retrograde transport in axons of the visual system. The retrograde axoplasmic transport of foreign proteins in the rat visual system shows certain specificities. The molecular features of these proteins which may underlie their entry into the retrograde phase have been examined using biochemical and morphologic techniques. Of the isoenzymes of horseradish peroxidase (HRP), the basic isoenzyme C is strongly transported, while the acidic isoenzymes Abeta and Aalpha are transported weakly and not at all, respectively. Decreasing the isoelectric point (pI) of isoenzyme C from 8.2 to 4.4 decreases its transport, but a basic pI is not the sole requisite for transportability since two other basic peroxidases (turnip isoenzyme P7 and lactoperoxidase) are not transported in retrograde. The sugar component as a whole of isoenzyme C does not appear to be required for determining transport. Isoenzyme C and the other proteins which are transported enter multivesicular bodies in axons and axon terminals, as well as synaptic and coated vesicles and fine tubules in axon terminals. The non-transported proteins enter only the vesicular organelles thought to be involved in neurotransmitter recycling in axon terminals and do not enter multivesicular bodies. Thus the two systems of axonal membraneous compartments involved in local synaptic recycling versus the retrograde phase of transport do not show the same specificity of uptake of extracellular tracers and can be dissociated by the experimental use of these peroxidases.


Structure of cell coats during initial stages of synapse formation on isolated cultured sympathetic neurons. The mordant tannic acid was applied after routine aldehyde and osmium fixation in order to study the ultrastructure of membrane coat material during synaptogenesis in combination cultures of superior cervical ganglion neurons and spinal cord explants. All contact between cultured neurons was mediated by coat material; apposition of outer membrane leaflets never occurred. In most areas, the contact found between membrane coat material lacked special arrangement, but in areas of contact between spinal cord growth cones and sympathetic ganglion neurons, distinct patches of bilateral membrane specialization were seen. Here apposed coat material interdigitated across the intracellular gap, outer membrane leaflets were parallel and dense material was evident in the adjacent cytoplasm. These 'differentiated' contacts were seen both prior to and simultaneously with the appearance in the same area of other synaptic organelles; they did not appear to be precursors of synaptic active zones. Findings suggest that a mosaic of specificities in neuronal coat material may determine the site of 'differentiated' contacts and that these contacts may be relevant to the subsequent formation of a synaptic active zone.


The formation of photoreceptor synapses in the retina of larval Xenopus. The first appearance and early development of synapses between photoreceptors, bipolar cells and horizontal cells were studied in the retina of larval Xenopus, between stages 37/8 and 46. Synapse morphology was reconstructed from examination of serial sections. Additional data were obtained from E-PTA stained tissue, Photoreceptors initially contacted horizontal cell dendrites via ribbon synapses at the photoreceptor basal surface (stages 37/8--39). Later, horizontal cell dendrites penetrated the receptor as digitiform processes (stages 39--40) which subsequently expanded extensively within the invagination (stages 40--44). At stages 41--46, a photoreceptor ribbon generally was associated with two horizontal processes in a synaptic dyad complex; each ribbon participated in 1 or 2 such complexes. Bipolar cell dendrites made contact with receptors via superficial or invaginating basal-type junctions. Such junctions were observed first at stage 39, but increased greatly in number beginning at stage 42. Basal junctions were characterized by marked staining of the paramembranous receptor cell cytoplasm and a 9--13 nm wide cleft containing an electron-dense material. No association of bipolar cell dendrites with photoreceptor ribbons was noted. Junctional complexes presumed to be gap junctions first were observed at stage 39 between photoreceptor bases and basal processes emitted by neighbouring photoreceptors.


The neuropathology of DFP at cat soleus neuromuscular junction. The fine structure of the cat soleus neuromuscular junction was studied following a single intra-arterial injection of di-isopropylfluorophosphate (DFP) into the right femoral artery. DFP induced separate subacute and delayed morphologic changes in soleus non-myelinated motor nerve terminals. Three days after DFP administration motor nerve terminals were reduced in number. Subacute DFP damage was also noted in the subneural apparatus and in the immediate subjacent muscle. Both pre- and post-junctional subacute changes were resolved two weeks post-DFP. One week following this initial regeneration, soleus motor nerve terminals underwent a delayed transient degeneration, followed by reinnervation of damaged endplates 6--8 weeks following DFP. Quantitative analysis of methylene blue-stained intramuscular nerves indicated that both subacutely and chronically denervated soleus muscle fibres were reinnervated by regeneration of the original motor axon. Reinnervation by means of collateral sprouting was insignificant. This mechanism of reinnervation and the rapidity with which it occurred suggests that both subacute and delayed soleus motor nerve damage is initiated from local actions of DFP on the non-myelinated terminal. The subacute reaction probably results from a direct cytotoxic action of DFP at pre- and post-junctional sites. The delayed nerve terminal degeneration may also stem from an acute effect not immediately detrimental to nerve function.


Effects of monocular lid closure on development of receptive-field characteristics of neurons in rabbit superior colliculus. 1. The receptive-field characteristics of superior colliculus neurons were studied in rabbit pups that had one eyelid sutured prior to eye opening. Units recorded from the superior colliculus (SC) receiving input from the unsutured eye provided normal developmental data, and those from the colliculus receiving input from the sutured eye were used to study the effect of visual deprivation. 2. A total of 1,054 cells recorded from 89 animals ranging in age from 7 to 35 days were obtained, 514 cells in the normal colliculus and 540 cells in the deprived colliculus. During normal development, three nonoriented cell types (concentric, uniform, motion) showed a progressive increase in relative frequency of occurrence, starting at about 7 days and reaching the adult level at about 15 days. Directionally selective cells developed slightly later, reaching an adult level at 3 wk. Oriented directional cells were the slowest to mature, requiring about 4 wk to reach the final level. 3. Eyelid suturing significantly affected the oriented directional cell development; these cells developed at a normal rate for about 3 wk, then rather abruptly began to decrease in number; a stable relative frequency of about one-fourth the normal value was reached at about 4 wk. A corresponding increase in the relative number of indefinite cells to above the normal level also occurred. In contrast, the development of nonoriented cells and directionally selective cells was not affected by the deprivation. 4. The development of rabbit superior colliculus receptive fields was found to be, in general, similar to development of kitten SC receptive fields. It also correlates well with developmental changes seen in rabbit ganglion cell receptive fields and with anatomical changes in developing rabbit SC. Indirect support is given for the hypothesis that changes seen in SC with deprivation are secondary to changes in the visual cortex.


Development of single-neuron responses in kitten's lateral geniculate nucleus. 1. In the lateral geniculate nucleus (LGN) of 18 kittens whose ages ranged from 6 to 40 days, 445 cells were studied. 2. LGN cells of kittens younger than 21 days are characterized by very low maintained rates, long latencies to full-field flash, response fatigue, large receptive field, absence of surround responses and surround inhibition, poor responses to fast-moving stimuli, and low-amplitude responses to flashing spots. 3. Cells were characterized as sustained or transient, and on, off, or on-off by their responses to flashing spots of light, and as X-like of Y-like by their responses to contrast reversal. Prior to 21 days, cells are hard to classify as X or Y. 4. A large proportion of cells in kitten LGN have both on- and off-responses to small and center-sized spots of light. This proportion decreases with development. 5. A small number of cells develop mature receptive-field properties very early (14--20 days). These are cells with X-type responses (linear summation) to contrast reversal and tend to have sustained responses to flashing spots. 6. Y-like cells, with nonlinear summation, develop mature receptive-field properties later than 34 days of age and later than all X-cells. 7. We conclude that there are different developmental patterns for cells of the kitten LGN. These different patterns may be important in determining the visual responses of cortical cells and their degree of susceptibility to environmental modification.


Development of functional motor innervation in supernumerary hindlimbs of the chick embryo. 1. The development of functional motor innervation in supernumerary chick hindlimbs transplated to host embryos at stages 16--18, was studied throughout the embryonic period from stage 27 when peripheral synapses were first formed. 2. The innervation pattern, defined as the number and sequential order of spinal nerves innervating individual muscles, were determined for supernumerary hindlimbs innervated by thoracic, lumbosacral-thoracic, or wholly lumbosacral spinal cord segments. Spinal nerves were electrically stimulated and muscle contraction was scored visually or by tension measurement and compound action-potential recordings were made from muscle nerves. 3. There was no tendency for spinal nerves to grow to or to synapse with the muscles which they normally innervate. Rather, they formed functional connections with inappropriate muscles, which were maintained throughout the developmental period studied. The localization of the motoneuron cell bodies was confirmed with retrograde transport of horseradish peroxidase (HRP) and shown to be adjacent to the spinal nerves through which their axons exited. Motoneurons innervating specific muscles occupied a similar medial-to-lateral position in the cord in both control and supernumerary limbs. 4. In all supernumerary limbs a definite peripheral innervation pattern was formed, which approximated the normal pattern. Specifically, the relative craniocaudal position of motor columns innervating individual muscles was conserved, even though the actual spinal nerves innervating the transplant were different from animal to animal. In limbs reversed along the anterior-posterior axis, the innervation pattern was also reversed. 5. The results suggest that motoneurons have not been rigidly specified to innervate certain muscles at the time when the limb buds were transplanted. Further, the limb itself can apparently influence the innervation pattern in an important manner, possibly by specifying motoneurons or by subsequently directing axon outgrowth and synapse formation.


Functional and anatomical consequences of neonatal visual cortical damage in superior colliculus of the golden hamster. 1. In normal hamsters the visual cortex sends a retinotopically organized projection to the ipsilateral superior colliculus. 2. Acute or chronic unilateral ablations of visual cortex in adult animals decrease the incidence of directionally selective cells encountered in the superficial laminae of the ipsilateral colliculus, but not in the deeper layers (those ventral to the stratum opticum). 3. Unilateral ablations of visual cortex in infant hamsters induce an aberrant crossed projection to the contralateral superior colliculus, confirming the finding of Mustari and Lund (58) in the rat. Horseradish peroxidase (HRP) experiments demonstrated that the cells whose axons comprise the normal as well as the anomalous projection are pyramidal neurons in layer V of cortex. 4. In adult hamsters that underwent early brain damage, about 13% of the cells in the colliculus could be activated by stimulation of the contralateral visual cortex. Only 1 unit (of the 159 cells tested) could be driven by similar stimulation in normal adult hamsters. This indicates that the anomalous crossed projection forms functional synapses in the contralateral tectum. 5. No cells (of the 113 tested) could be activated from the contralateral cortex in hamsters that sustained chronic ablations of visual cortex in adulthood; thus indicating that there is some limited time period during development when unilateral ablations of visual cortex induce an anomalous corticotectal pathway. 6. The visual response properties of superior collicular neurons in the neonatally brain-damaged animals were compared to those of normal hamsters, as well as to those with acute or chronic ablations of visual cortex sustained in adulthood. 7. There was no indication that the anomalous projection contributes to the organization of normal visual response properties in the superior colliculus of the neonatally brain-damaged animals. In fact, the incidence of directionally selective cells in these hamsters was found to be significantly lower than that of normals in both the superficial and deep laminae of the colliculus. 8. We conclude that while unilateral damage of visual cortex in the hamster induces an anomalous corticotectal projection that makes functional synapses, this aberrant input does not compensate for missing, normal corticotectal pathway in the organization of superior collicular response properties.


Neuronal responses to electrosensory input in mormyrid valvula cerebelli. 1. We have examined a large portion of the valvula cerebelli of the mormyrid fish Gnathonemus petersii for responses related to the three known classes of electroreceptors. Evoked potential and extracellular single-unit records from curarized and non-curarized preparations show that a separate area of the valvula is related to each of the different electrosensory modalities. 2. The area related to ampullary receptors is also strongly affected by mechanical stimulation to the skin. In the mormyromast and Knollenorgan regions, responses to sensory stimuli depend on when they are given in relation to the command to fire the electric organ. In the Knollenorgan region the interaction is quite simple. Responses are completely blocked if the stimulus is given during a brief period when the electric organ discharge occurs. A greater variety of interactions is seen in the mormyromast region. 3. Large areas of the valvula do not appear to be clearly and strongly retated to any of the three electrosensory modalities, suggesting the possibility that much of the structure is not devoted to electrosensory processing.


Lateral cervical nucleus in the cat: functional organization and characteristics. 1. The lateral cervical nucleus (LCN) was investigated with extracellular recordings in the anesthetized cat. A total of 556 LCN units were characterized; the locations of most of these were histologically verified. Half of these had receptive fields on the rostral third of the ipsilateral body surface including the face; 14% had fields on the thorax or abdomen, 33% had fields on the hindlimb or tail, and about 3% had receptive fields larger than one limb. 2. The LCN was observed to be somatotopically organized in experiments using angled microelectrode penetrations. Hindlimb units were dorsolateral, forelimb units ventromedial, and face units most medial within the LCN. In regions where LCN cells were present only in the medial portion of the dorsolateral funiculus, they were all forelimb units. 3. A special subpopulation (17%) of cells were clustered most ventromedially in the LCN. These units had large or disjoint receptive fields, and/or responded to deep, visceral, or noxious stimulation. A third of these did not project in the medial lemniscus (ML); many were synaptically activated by stimulation of the ML. Those that did project in the ML had significantly longer latencies than all other LCN units. It is suggested that this subpopulation contains local LCN interneurons. 4. The specific mechanoreceptor inputs were identified for each of 121 projecting LCN units. Receptor inputs were uniform across each receptive field; that is, each unit that responded to a given receptor type was observed to respond to receptors of that type throughout its receptive field. Input from large-fiber-diameter, velocity-sensitive mechanoreceptors was predominant. The absence of input from slowly adapting type I and II receptors and from joint receptors was confirmed. A significant number of units (17.3%) could be driven by only one receptor type. The LCN sample profile agrees closely with the receptor representation in the hindlimb portion of the spinocervical tract. It is concluded that these data that anatomic specification of convergence occurs in the LCN with respect to receptor connectivity, and that this specification originates in lamina IV of the dorsal horn. 5. Stimulation of the dorsal column nuclei synaptically excited 23% of the LCN units tested. In two cases it was possible to demonstrate, by collision, that this occurred via collaterals of spinocervical tract axons. It is concluded that some spinocervical axons have collaterals terminating in the rostral parts of the dorsal column nuclei.


Functional characteristics of cochlear nucleus in behaving cat examined by acoustic masking of electrical stimuli. 1. Cats were trained, using an operant procedure, to detect and respond to electrical stimulation delivered in the vicinity of the cochlear nucleus. The electrical stimuli were presented both in silence and in synchrony with repeated noise bursts to determine whether detection thresholds for the electrical stimuli were elevated by the acoustic masking noise. 2. For stimulation sites centered within auditory structures (cochlear nucleus or acoustic nerve root), the acoustic maskers caused a consistent elevation of the electrical detection thresholds. For stimulation sites that were in or bordered on nonacoustic neural structures (e.g., vestibular), the acoustic maskers caused little or no elevation of electrical detection thresholds. 3. The magnitude of the acoustic masking effect was monotonically related to the intensity of the acoustic masker across the range of intensities tested. 4. The magnitude of the masking effect was strongly dependent on the relative timing of the stimulus pulse and the masker noise burst. Maximum masking occurred when the pulse just followed the onset of the neural activity in cochlear nucleus evoked by the masker burst. Less masking occurred when the electrical pulse occurred at the middle or end of the masker burst, and still less when the pulse occurred just prior to the onset (backward masking) or just after the offset (forward masking) of the masker burst. 5. The magnitude of the masking effect also depended on the frequency of the acoustic masker. For tone bursts, masking was maximal for each electrode at a particular frequency and declined monotonically for masker frequencies above or below the optimal frequency. 6. It is concluded that the masking of an electrical stimulus by an acoustic stimulus depends on a direct interaction between the neural responses evoked by the two stimuli, and that similar central, neural interactions may contribute to acoustic masking of acoustic stimuli. It is also concluded that the technique of masking an electrical stimulus by an acoustical stimulus is a precise and useful tool for the study of sensory-neural organization in intact behaving animals.


Signs of functional maturation of peripheral auditory system in discharge patterns of neurons in anteroventral cochlear nucleus of kitten. 1. Responses to pure tones were recorded from single neurons in the anteroventral cochlear nucleus (AVCN) in kittens ranging in age from 4 to 45 days. Different response properties mature at different times after birth. 2. The shapes of response areas of AVCN neurons after the 1st postnatal week resemble those recorded in the AVCN and auditory nerve of the adult. During the 1st wk after birth the high-frequency portion of the response area is extended. Phase-locked responses to stimulus frequencies below about 600 Hz occur at this time. Phase vs. frequency measurements and shapes of response areas indicate that by the end of the 1st postnatal week the cochlear partition may be capable of supporting a traveling wave along most of its length. 3. Functional development proceeds through a second phase which lasts until the end of the 2nd or the beginning of the 3rd wk of life. During that time threshold, maximal discharge rate, and average first-spike latency achieve adult values. 4. Phase-locking to low-frequency tones, to the extent displayed by phase-sensitive neurons in the adult AVCN or auditory nerve, is achieved last, after the 3rd or 4th wk postpartum.


Controlled locomotion in the mesencephalic cat: distribution of facilitatory and inhibitory regions within pontine tegmentum. 1. The contribution of postural tonus to controlled locomotion elicited by the stimulation of mesencephalic locomotor region (MLR) was studied in the acute precolicular-postmammillary decerebrate (mesencephalic) cat. 2. A microelectrode was placed in the unilateral MLR and another was placed systematically at 1-mm increments throughout the pons (H--4 to H--1O) at level ranging from P2 to P11 dorsoventrally and mediolaterally from 0 to L or R6. Depending on the general condition of the animal, stimuli through this second electrode were delivered preceding, succeeding, or simultaneous with the MLR stimulation. 3. Stimulation of the ventral part of the caudal tegmental field (P3 to P9, H--6 to H--8) increased extensor tonus of the hindlimbs, as assessed by recording muscle activity. Concomitant stimulation of this region converted MLR-elicited hindlimb stepping to coordinated four-legged locomotion and also elicited locomotion even when stimulation of the MLR alone failed to elicit locomotion. Stimulation of this ventral tegmental region alone at a larger stimulus intensity elicited spastic locomotor movements associated with a substantial increase in extensor tonus. 4. Stimulation of the lateral tegmented field surrounding the pontine locomotor region (PLR) also facilitated MLR effects, but had a relatively weaker facilitatory effect on postural tonus then stimulation of the ventrocaudal tegmental field. PLR stimulation alone was also ineffective when postural tonus was not well maintained. 5 Stimulation of the dorsal part of caudal tegmental field (P3 to P9, H--4 to H--6) in its midline dramatically decreased extensor tonus of the hindlimbs. MLR-elicited controlled locomotion was completely suppressed during concomitant stimulation of this inhibitory region. 6. These results indicated clearly that the degree of existing postural tonus greatly affects MLR-elicited locomotor movements and that an increase in postural tonus and an activation of the spinal stepping generator are not separate phenomenia.


Nociceptive responses of neurons in medial thalamus and their relationship to spinothalamic pathways. 1. An extracellular study of the cat medial thalamus has revealed four types of somatosensory neurons. These were located primarily in the n. parafascicularis, n. subparafascicularis, and n. centralis lateralis; none were found in the n. centrum medianum. There was no functional segregation of neurons within each nucleus or between nuclei. Each type of neuron had large and often bilateral receptive areas. No somatotopic organization of neurons was found within the medial thalamus. 2. Noxious (N) and noxious-tap (NT) neurons comprising 72% of the sample (78 of 109 total) were considered to be nociceptive. N cells responded exclusively to noxious mechanical stimulation of skin, muscle fascia, tendons, and joints, and to direct stimulation of A-delta- and C-fiber groups in cutaneous, articular, and muscle nerves. NT cells responded to noxious and tap stimulation in a differential manner and to stimulation of the entire spectrum of A- and C-fibers. N and NT cells accurately signaled the duration of noxious mechanical stimulation. Their nociceptive responses were also graded as a function of both noxious stimulus intensity and the number of activated A-delta- and C-fibers. Stimulation of A- and C-fibers evoked, respectively, an inital burst and a late burst of discharges. A brief period of inhibition intervened between the initial and late bursts of NT cells. Prolonged afterdischarge was often observed following noxious natural stimulation or stimulation of A-delta- and C-fibers. The phenomenon of discharge "windup" was observed during iterative stimulation of C-fibers. 3. Tap (T) neurons (10%) responded only to brisk but innocuous taps applied to skin or underlying tissue. These cells were driven only by activation of A-alpha- and A-beta-fibers. The response to such stimulation was seen as an initial burst of discharges followed by an inhibitory period. 4. Inhibited (I) neurons (18%) had resting discharges that were inhibited by noxious stimuli and stimulation of A-beta- and C-fiber groups. 5. The results obtained from monitoring the peripherally evoked responses of nociceptive N and NT neurons before and after selective lesions of the spinal cord strongly suggested that the spinothalamic tracts were the only spinal projections mediating A- and C-fiber input to these cells. Each spinothalamic tract apparently carried information originating from both sides of the body.


Excitatory termination of abducens internuclear neurons on medial rectus motoneurons: relationship to syndrome of internuclear ophthalmoplegia. 1. Field potentials and intracellular records were obtained from the medial rectus subdivision of the IIIrd nucleus in anesthetized cats following electrical stimulation of the abducens nuclei, vestibular nerves, pontomedullary brain stem, and the medial longitudinal fasciculi (MLF). 2. Stimulation of the contralateral abducens nucleus produced unique field potentials in the medial rectus subdivision. They consisted of an early sharp transient volley followed by a slower postsynaptic negativity. 3. Monosynaptic EPSPs were evoked in medial rectus motoneurons following contralateral abducens nucleus stimulation. The EPSP amplitudes were graded when the stimulus intensity was increased from threshold to supramaximal. EPSPs produced by contralateral abducens nucleus stimulation were larger in amplitude than those produced by ipsilateral vestibular nerve stimulation. The current-voltage relationship and reversal potentials for Vi- and abducens-evoked EPSPs were similar and indicated an overlapping location of excitatory synaptic terminals on medial rectus motoneurons. 4. Secondary vestibular axons activated monosynaptically by ipsilateral vestibular nerve stimulation were not recruited by abducens nucleus stimulation. 5. Ipsilateral MLF stimulation produced EPSPs with similar profiles as those observed following abducens nucleus stimulation; however, stimulation of the contralateral MLF at comparable stimulus intensities did not produce any changes in transmembrane potential. 6. When higher intensity stimuli were applied to the contralateral MLF, the synaptic potentials recorded in the medial rectus were occluded by those produced by weaker stimulation applied to the ipsilateral MLF. This suggests that the potentials resulting from stronger contralateral stimulation were due to current spread to the ipsilateral MLF. 7. While recording in the medial rectus subdivision, various sites in the ponto-medullary brain stem were explored with a stimulating electrode. Analysis of evoked field potentials suggested that the ascending internuclear axons were contained only in the MLF ipsilateral to the medial rectus. Acute brain stem lesions confirmed this suggestion. 8. Chronic lesions were placed in the brain stem to isolate the abducens nucleus from either extrinsic fibers of passage or axon collaterals. Acute electrophysiological experiments in these chronic animals corroborated the suggestion that the medial rectus pathway originated from within the abducens nucleus. 9. We conclude that axons from the internuclear neurons of the abducens nucleus exit from the nucleus medially, cross the midline, ascend in the opposite MLF, and terminate monosynaptically on medial rectus motoneurons. 10. we believe that the syndrome of internuclear ophthalmoplegia associated clinically with lesions of the medial longitudinal fasciculus could be due to the absence of ascending physiological activity from internuclear neurons of the abducens nucleus.


Response properties and electrical constants of caudate nucleus neurons in the cat. 1. Response properties and passive electrical constants were assessed for caudate nucleus neurons in pentobarbital-anesthetized cats. The neurons studied were those which could be monosynaptically excited by substantia nigra and thalamic (centromedian-parafascicular) stimulation. 2. Input resistance and membrane time constant were estimated from the plateau value and time course, respectively, of the neuronal membrane response to intracellularly applied current pulses. The average values obtained were 16.5 Momega and 11.3 ms. Specific resistance and capacitance values were calculated. 3. Single or repetitive spikes were readily evoked by nigral or thalamic stimuli or by the application of direct depolarizing currents. Spike thresholds were higher for direct than for synaptic activation (7.2 vs. 5.6 mV). 4. Direct depolarizing stimuli with durations up to 600 ms elicited repetitive discharge with little adaptation of firing rate. The maximum discharge rates induced by direct stimuli were near 200 spikes per second. 5. The intracellular application of tetraethylammonium chloride (TEA) produced spike-prolongation effects in caudate neurons that were similar to the effects reported for other nerve membrane. 6. The probable identity of the recorded neurons as medium spiny neurons was discussed and, in addition, it was proposed that the characteristic silence of these cells is not likely due to intrinsic membrane specialization.


The rhetoric of specialization. The 1978 Harvey Cushing oration. The 1978 Cushing Orator shows the role of rhetoric in the process by which various specialties change in response to sociological and legislative demands. He discusses the effect of applying concepts of restraint of trade to medicine, and welcomes a closer liaison through the American College of Surgeons between general surgeons and other surgical specialties.


Management of 136 consecutive supratentorial berry aneurysms. A series of 103 consecutive cases admitted to the University of Chicago Hospitals with a recently ruptured supratentorial aneurysm were medically managed by antifibrinolytic medication, and, when applicable, by hypotension, intracranial pressure control, and respiratory support. Nine patients deteriorated and died, and six rebled and died before they were judged fit for surgical treatment. Four were treated by carotid occlusion. Nine, because of refusal or medical judgment, did not have surgical treatment. Sixty-nine of these patients and a further 33, electively admitted, underwent craniotomy. In these 102 patients, there was no mortality. Seven developed postoperative hemiparesis or hemiplegia. Six recovered. One has a residual monoparesis.


An investigation with serial angiography into the evolution of cerebral arterial spasm following aneurysm surgery. Serial postoperative angiograms were performed in 28 patients with intracranial aneurysms, 26 of whom had presented with a subarachnoid hemorrhage. The clinical state and intracranial pressure (ICP) were also measured. Angiograms were performed in the ward using a cannula, which was passed into the proximal external carotid artery via the superficial temporal artery. Measurements of the vessel diameters were made, with the preoperative angiogram as a baseline. Patients could be placed into one of five groups depending on the presence or absence of significant arterial spasm, the clinical state of the patient, and the normality or otherwise of the ICP. No patient's condition deteriorated without an elevated ICP and/or significant arterial spasm. The study shows that this spasm is usually associated with a poor clinical state if it reaches a maximum 8 to 12 hours after the operation, although the clinical deterioration is not apparent for a further 6 to 12 hours. Knowledge of the natural history of postoperative arterial spasm may allow earlier treatment of the spasm, which may be more successful than delaying treatment until clinical deterioration has occurred. The worth of the varied drugs proposed for the treatment of spasm may be assessed using this type of protocol.


Foramen magnum tumors. Analysis of 57 cases of benign extramedullary tumors. This study involved 57 patients with benign extramedullary tumors of the foramen magnum (19 neurinomas, 37 meningiomas, and one teratoma), who were operated on between 1957 and 1976. The 37 meningiomas represented 3.2% of 1139 meningiomas of the neuraxis. The initial neurological examinations of about half of these patients were unremarkable. The clinical presentation of tumors of the foramen magnum frequently mimics multiple sclerosis, cervical spondylosis, intramedullary tumor, syrinx, carpal tunnel syndrome, and even normal-pressure hydrocephalus. All operations were performed through a posterior approach, and two surgical deaths (3.5%) were recorded. No surgery for recurring of tumor was recorded. The follow-up review of 56 patients (98.2%) showed good functional results if the tumor was detected before severe neurological deficits occurred. The possible mechanism of the sensory symptoms and muscle atrophy of the hands is discussed, and the electromyographic findings are reviewed.


The neurosurgical management of spinal metastases causing cord and cauda equina compression. The authors report a series of 100 consecutive patients with spinal metastases causing cord or cauda equine compression, who were treated with surgical decompression. Of these, 30% (all women) had breast cancer. The most common primary neoplasm in man was prostatic carcinoma. Pain was the earliest and most prominant symptom, followed by weakness. Bladder dysfunction was recorded in 40 patients. The thoracic region was the most common site of cord compression (76 patients). Surgical treatment involved urgent and extensive laminectomy decompression. Concomitant spinal stabilization was required in 10 cases, involving posterior rib graft fusion in seven and Harrington rod instrumentation in three. At last follow-up review, 29 of these patients were living with an average postoperative survival of 2.3 years; 71 patients had died with an average survival of 8.8 months. Surgical decompression produced effective pain relief in 70% of the patients. Postoperatively, 58 patients could walk; of these, 40 were walking and continent of urine 6 months following surgery (including five patients who were totally paraplegic on admission). Positive approach and aggressive management in this problem can achieve results superior to those generally reflected in the literature.


Regional spinal cord blood flow in rats after severe cord trauma. Spinal cord blood flow (SCBF) was measured in 12 albino rats following acute cord injury produced by the extradural clip compression technique. Severe injury was produced with the clip compressing the cord with a force of 180 gm for 5 minutes, an injury previously shown to produce a severe functional deficit. Regional SCBF was measured 15 minutes, 2 hours, and 24 hours after injury by the 14C-antipyrine autoradiographic technique and a scanning microscope photometer. At 15 minutes and 2 hours, white and gray matter blood flow was severely diminished, and, at 24 hours, there was only minimal improvement. Focal decreases in blood flow were seen in white and gray matter for a considerable distance proximal and distal to the site of cord trauma. Thus, it has been confirmed in this model that severe cord compression injury produces severe posttraumatic ischemia in the cord which lasts for at least 24 hours.


Lymphocytic infiltrates in primary glioblastomas and recidivous gliomas. Incidence, fate, and relevance to prognosis in 228 operated cases. The correlation existing in several human malignancies between lymphocytic infiltration and prolonged survival prompted this study. Two hundred selected patients who were operated on for glioblastoma were reviewed to investigate the incidence of the lymphocytic infiltration in the histological slides and its possible relevance to a better clinical course. The group that exhibited a definite lymphocytic infiltration (Group A, 11.5%) had a significantly longer preoperative history and postoperative survival (p less than 0.01) than the other two groups that presented slight or no infiltration (Group B, 23%, and Group C, 65%, respectively). In addition, biopsies of 28 recidivous gliomas were reviewed to study the fate of this lymphocytic infiltration in relation to time and therapy, such as irradiation and steroids which are known to depress the immune response. The authors found that severe lymphocytic infiltration is a rare immunobiological reaction which significantly improves the prognosis of a malignant brain tumor and seems not to be influenced by time, local x-ray therapy, or steroids.


Catecholamine response to intracranial hypertension. Pulmonary congestion, hemorrhage, and edema, produced in the experimental animal by various methods of disturbing the central nervous system, have led to the concept that such neurogenically-initiated changes are mediated through the autonomic nervous system. Blocking the sympathetic nervous mechanisms prevents these changes. Little is found concerning the expected role of catecholamines. In this study, using a standard model of increasing intracranial pressure (ICP), intense cardiovascular changes, with blood pressure rising above 320 mm Hg and heart rate of 180 beats per minute, were noted. Within seconds, plasma catecholamine levels rose as much as 1200 times the highest normal values for epinephrine, 145 times for norepinephrine, and 35 times for dopamine. These changes occurred only when raised ICP was sustained and spatial compensation of the brain was exceeded. It is not unlikely that these events are related not only to increased ICP, but also to the effects of physical distortion of the brain stem with structural, functional, and vascular alterations within it.


Prophylaxis of postmyelogram headaches.

Prophylaxis of postmyelogram headaches. One hundred patients undergoing myelography received prophylactic autologous epidural blood patches to prevent postmyelogram headache. The results indicate a significant reduction in the incidence and severity of this problem compared to a control group, without any significant side effects.


Exploration of selected brachial plexus lesions by the posterior subscapular approach. The application of an old surgical technique, previously employed for treatment of thoracic outlet syndromes, to lesions of the brachial plexus is discussed. Positioning of the patient, the surgical procedure, and selected indications for a posterior subscapular approach with resection of the first rib are discussed. The indications for the use of this approach are: proximal plexus lesions involving roots and/or trunks believed to be repairable, complicated thoracic outlet syndromes, prior anterior exploration for vascular or nervous structure disease, and progressive plexus palsy associated with damage to the soft tissue of the anterior chest wall and supraclavicular regions secondary to irradiation. The authors' experience to date with 12 such cases is presented in chart form, while five cases are presented in some detail.


Supratentorial intracerebral hemorrhage following posterior fossa surgery. Five cases of supratentorial intracerebral hemorrhage following posterior fossa surgery are reported. Possible etiologies are discussed, but in only one case can a definite etiology (hypertension) be found. The differential diagnosis of declining level of consciousness after posterior fossa surgery must include supratentorial intracerebral hemorrhage, and computerized tomography seems to be the diagnostic method of choice.


Fibrosarcoma of the scalp. Case report.

Fibrosarcoma of the scalp. Case report. A parieto-occipital scalp tumor, noted in a Nigerian boy during the first month of his life, gradually increased in size, and after two attempts at partial removal there was a rapid increase in its size. When he was 17 years old, it measured 21 X 17 X 16 cm. There was no underlying skull defect. Complete excision of the tumor was achieved, and on histological examination it was found to be a fibrosarcoma. The patient was given a course of radiotherapy following wound healing. He remained well for 5 1/2 months but then had manifestations of small local recurrence and distant metastases that responded only minimally to another course of radiotherapy combined with cancer chemotherapy.


Subarachnoid hemorrhage secondary to ruptured aneurysms in infants. Report of two cases. Two infants with subarachnoid bleeding from middle cerebral artery aneurysms are presented, with detailed case histories.


Giant serpentine intracranial aneurysm after carotid ligation. Case report. A case is reported of a giant aneursym of the intracavernous portion of the left internal carotid artery that was treated initially with a left common carotid artery ligation. Six months later the aneurysm was partially removed. During this time the development and evolution of thrombus formation, a serpentine channel, and a hypervascular capsule was easily followed with recreated computerized tomography and angiography of the aneurysm.


Hemangiopericytoma of the spinal canal. Report of three cases. Hemangiopericytoma is a vascular neoplasm consisting of capillaries outlined by an intact basement membrane that separates the endothelial cells of the capillaries from the spindle-shaped tumor cells in the extravascular area. These neoplasms are found in soft tissues but have rarely been shown to involve the spinal canal. This is a report of three such cases. Surgical removal of the tumor from the spinal canal was technically difficult. A high risk of recurrence has been reported but in these three cases adjunctive radiotherapy appeared to be of benefit in controlling the progression of the disease. These cases, added to the six cases in the literature, confirm the existence of hemangiopericytoma involving the vertebral column with extension into the spinal canal. This entity should be included in the differential diagnosis of lesions of the spinal canal. The risk of intraoperative hemorrhage should be anticipated.


Extradural lumbar cryptococcosis. Case report. An 85-year-old woman presented with back and leg pain. Plain films showed destruction of the posterior elements of L-5 and myelography demonstrated a large extradural mass at that level. Exploration revealed a huge gelatinous extradural mass with invasion of the paraspinal muscles. Fungal stains showed that the mass consisted of innumerable Cryptococci. There was no evidence of cryptococcal involvement elsewhere.


Extensive cerebral nocardiosis cured with antibiotic therapy alone. Case report. A 34-year-old renal transplant recipient developed multiple soft tissue and extensive cerebral nocardiosis. The number and locations of the cerebral abscesses and probable areas of cerebritis precluded surgical drainage procedures. Gradual resolution of all the cerebral lesions occurred over a period of 6 months with antibiotic therapy alone. A review of the literature revealed only one previous case of a patient with pulmonary nocardiosis who had a probable secondary brain abscess and who survived without surgical drainage. Thus, if surgical drainage is not possible, antibiotic therapy alone may offer a hope of survival in what otherwise has been considered a uniformly fatal disease.


Modification of intracranial aneurysm clip. Technical note. A modification of the Mayfield aneurysm clip is described which is thought to decrease the chance of slippage of the clip, mainly in the case of large-necked and atherosclerotic aneurysms.


Studies of skeletal tracer kinetics. I. Digital-computer solution of a five-compartment model of [18F] fluoride kinetics in humans. We have developed a new model of short-term fluoride kinetics in humans and have solved the model on a digital computer using the SAAM-25 program. The solution accords well with available data. About 60% of intravenously administered [18F] fluoride is taken up by bone. Evaluation of the rate constants of tracer egress from blood indicates that about 17% of the cardiac output is distributed to the skeleton. When the model was perturbed to simulate changes in systemic or skeletal blood flow, we found that the system behaves in a nonlinear manner; even a five-fold increase in systemic or skeletal blood flow did not appreciably increase the amount of fluoride taken up by bone 1--2 hr later, the time when scans are usually made. A simulated increase in bone extraction rate, however, had a marked effect on bone-fluoride uptake. These findings suggest an important homeostatic role for bone in the regulation of blood calcium concentration and have considerable bearing on the interpretation of bone scans.


Experimental fracture healing: evaluation using radionuclide bone imaging: concise communication. Radionuclide bone imaging was performed in a rabbit model to observe the course of fracture healing and to establish criteria for distinguishing nonunion and delayed healing from normal healing. Sequential gamma-camera images (with pinhole collimator) were collected and subjected to computer analysis. Five groups were established: a) control--immobilization; b) control--immobilization plus periosteal stripping; c) simple fracture--osteotomy; d) delayed union--osteotomy plus periosteal stripping; and e) nonunion--osteotomy, periosteal stripping and polymethyl methacrylate interposed between fracture fragments. Histographic representation of absolute count rates along rabbit tibias followed a predictable pattern in the simple-fracture and delayed-union groups. They differed only in the time of appearance of phases. The nonunion group demonstrated no recognizable sequential pattern. In this experimental model, serial bone scanning with quantitative data analysis has shown potential for indicating the course of healing in fractures and for serving as a guide to treatment.


Sequential [125I]-o-iodohippurate renograms from rabbit kidneys after temporary renal ischemia. Serial renography with [125I]-o-iodohippurate was performed in 42 rabbits after temporary clamping of the renal artery for 1--3 hr and contralateral nephrectomy. Renograms were done before and after warm ischemia and followed 2, 4, 6, and 14 days after restoration of circulation. Correlation was found between duration of ischemia and severity of postischemic renographic changes. Most sensitive was the third phase, which showed distortion after 1 hr of ischemia; the second phase decreased after 2 1/2 hours of ischemia. The profound changes seen on the second day were shown to be due to further damage of the tubular cell system after restored flow. In vitro [125I]-o-iodohippurate uptake in cortex slices showed a significant decrease after warm ischemia damage and 48 hours restored flow. The second phase recovered more rapidly than the excretory function.


V/Q mismatches unassociated with pulmonary embolism: case report and review of the literature. A case is reported in which an intrathoracic stomach produced a ventilation/perfusion (V/Q) mismatch on lung scan. Causes of V/Q mismatch other than pulmonary embolism are reviewed.


Radionuclide assessment of Gaucher's disease. Gaucher's disease involves multiple organs and may present with variable severity. The scintigraphic appearance of the reticuloendothelial system and bone are described in three patient's with Gaucher's disease. Scintigraphic abnormalities reflected the severity of organ involvement and correlated well with the patients' clinical status. Scintigraphy appears useful for the evaluation and followup of patients with Gaucher's disease.


Analysis of personnel doses from nuclear medicine procedures. With the rapid growth of the use of radiopharmaceuticals for medical diagnostic and therapeutic procedures, radiation protection of personnel has become important. In this paper, the radiation doses of 337 persons in 16 nuclear medicine centers in India are analyzed. In 1976 the average annual dose per person was 0.028 rem. The highest average dose per person per working week was 2.62 mrem. Analysis of the dose records of three major institutions for recent years reveals an increase in the average dose per worker.


Effect of d,l-alpha-tocopheryl esters on vitamin E-deficient rats. The data in our previous paper demonstrated that some alpha-tocopheryl esters administered orally were absorbed in their unchanged form through the lymph, while some other esters were absorbed after being hydrolyzed individually to different degrees. The hydrolysis during absorption seems to be related to the structure of the ester group of alpha-tocopherol at the 6-position. The purpose of this work is to study the metabolism and biological effect of tocopherol esters in vitamin E-deficient rats. Three esters were used on the basis of their behavior during absorption through the lymph, as follows; alpha-tocopheryl acetate (an easily hydrolyzable ester), the nicotinate (a moderately hydrolyzable one) and the pivalate (a scarcely hydrolyzable one). The easily hydrolyzable esters will suffer the same metabolic fate through absorption as alpha-tocopherol. The moderately and scarcely hydrolyzable ones have a tendency to show different physiological effects from alpha-tocopherol due to absorption of the unchanged ester. The effect of these esters on the microsomal enzymes in the liver such as cytochrome P-450, cytochrome b5, aniline and hexobarbital difference spectra and NADPH-dependent cytochrome c reductase was determined. It was shown that the pivalate inhibited the release of NADPH-dependent cytochrome c reductase activity to supernatant in spite of low distribution in the 105,000 X g sediment. The result suggests that the pivalate as a model compound may be interesting to examine for its membrane stabilizing effect of alpha-tocopherol.


Modes of proteolysis of cystathionase and ornithine aminotransferase by serine protease from the rat small intestine. The mechanisms of proteolysis of two apo-forms of pyridoxal enzymes, cystathionase [EC 4.2.1.15] and ornithine aminotransferase [EC 2.6.1.13] by serine protease from the rat small intestine were compared. The apo-forms of these two pyridoxal enzymes are susceptible to the serine protease, whereas the holo-forms of the enzymes are not. Pyridoxal phosphate, the coenzyme of these two enzymes, prevented their inactivation by the serine protease. The difference in susceptibility of the apo- and holo-forms to the serine protease was due to the difference in their conformations. The time course of inactivation of cystathionase by the protease was apparently biphasic. During the first phase of inactivation, disappearance of the band corresponding to the native protomer, with a molecular weight of 47,000, was accompanied by accumulation of new material with a molecular weight of 39,000. In the late stage of proteolysis, extensive degradation of the large molecular weight intermediate was observed. This large intermediate product was isolated and found to compete with intact cystathionase as a substrate for the protease. Proteolysis of cystathionase was accompanied by both dissociation of the enzyme molecule and loss of its antigenicity. Limited proteolysis of ornithine aminotransferase apoenzyme by the serine protease resulted in formation of a large molecular weight product similar to the native apoenzyme, but with nicks in the molecule. Dodecylsulfate-polyacrylamide gel electrophoresis showed that the apoenzyme is degraded to intermediate forms (molecular weight 41,500 and 15,000) and later, to stable forms (molecular weight 25,500 and 13,500).


Metabolism of injected flavins studied by using double-labeled [14C]flavin adenine dinucleotide and [14C, 32P]flavin mononucleotide. The metabolism of flavins in mouse was studied with [F-(2)-14C, A-(2,8)-14C]FAD and [F-(2)-14C, 32P]FMN. Ninety minutes after injection, radioactive isoalloxazine nucleus of double-labeled FAD was markedly incorporated into FAD, FMN and riboflavin in the liver, whereas a small amount of radioactive adenine nucleus of double-labeled FAD was found in FAD in the liver. In the case of FMN, radioactive isoalloxazine nucleus of double-labeled FMN was markedly incorporated into FAD, FMN and riboflavin in the liver, whereas only a minute amount of radioactive phosphorus was incorporated into FMN and FAD in the same organ. These results indicate that FMN and FAD injected are rapidly hydrolyzed and resynthesized in animal body.


Identification and determination of 25-hydroxyvitamin D3 in the blood and liver of vitamin D-deficient rats irradiated with ultraviolet light. The intestinal calcium transport activity and serum calcium and phosphorous concentrations of vitamin D-deficient rats were increased by irradiation with an ultraviolet (UV) lamp. The existence of 25-hydroxyvitamin D3(25-OH-D3) in their bloods and livers was physicochemically confirmed by high-performance liquid chromatography (HPLC), gas-liquid chromatography (GLC) and mass fragmentography, whereas the compound could not be detected in the tissues of non-irradiated rats. The results strongly suggested that vitamin D3 in vivo generated in irradiated rat skin might be normally metabolized and utilized to prevent rickets. The level of 25-OH-D3 in the tissues was determined by a HPLC method.


Effects of dietary fats on the activity of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol synthesis in the liver of fasted-refed rats. The time course of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity and lipogenesis and cholesterogenesis from 1-14C-acetate and 2-14C-mevalonate was examined in the liver of rats refed diets containing different fats at the 10% level after 48 hr fasting. Fasting caused a profound depression of the reductase activity and sterol and fatty acid synthesis. In rats refed for 30 hr, the activity of HMG-CoA reductase was restored to about one-half of the level observed in prefasting rats, irrespective of the type of dietary fats. When safflower oil and trilaurin were dietary fats, the activity remained this level until 78 hr, then declined, whereas with tristearin, activity progressively increased until 78 hr. On refeeding for 174 to 222hr, the reductase activity was significantly higher in the tristearin than in the trilaurin group. Similar patterns were demonstrated in cholesterogenesis either from acetate or mevalonate, though extents of activation after refeeding were markedly different in these precursors. Dietary fat dependent changes in the content of hepatic cholesterol and in the concentration of plasma cholesterol were also observed.


Comparative absence experience among employees covered by a prepaid or a Blue Cross/Blue Shield health insurance program. Health maintenance organizations report lower hospitalization and surgical experience than fee-for-service practice. If this is true, then sickness absence should be less. This pilot study compared morbidity experience of 247 pairs of Mountain Bell Telephone Company employees--HMO-enrolled employees matched with employees covered only by Blue Cross/Blue Shield. The study period extended before and after enrollment of the HMO subjects. Rates for the HMO group for hospitalization and surgery decreased after enrollment, whereas rates for the Blue Cross/Blue Shield group increased. The absence disability rate for the HMO group remained constant but increased for the BC/BS group. Differences in absenteeism may exist due to the type of medical insurance. The potential impact of such a difference upon absence costs is considerable.


The "healthy worker effect"--fact or artifact? Workers in five chemical plants with diverse characteristics were studied by attempting to locate all white male employees who worked at least 12 months over a 25 to 30 year period. Former employees were contacted directly, rather than using questionnaires or Social Security Administration files. The data were analyzed by comparing observed mortality to expected mortality based on age-sex-race specific death rates in the U.S. population. The results indicate that the mortality experience of the chemical workers studied is essentially that of the general population. It is suggested that the "healthy worker effect" may be due to methods frequently employed in searching for death claims which understate the true experience of the employee group studied, or if present, does not affect mortality rates for neoplastic or cardiovascular disease.


Health effects of long-term exposure to sodium sulfate dust. Information on adverse health effects of occupational exposures to sodium sulfate dust is lacking. A study was conducted on 119 workers from five sodium sulfate surface solution mines in Saskatchewan. The investigation involved the older workers and the workers at highest dust exposure levels and included general medical screening with emphasis on the existence of hypertension, edema, calcium tetany, anemia, common skin problems, nasal septum perforation, persistent diarrhea; lung function tests; serum analyses for sulfate, calcium, sodium, and chloride content; and urinary inorganic sulfate output. All measured properties, including lung function, serum sulfate, calcium and electrolytes, were found to be within normal ranges. Forty-two workers with more than 10 years exposure experience show no significant differences in these properties compared to 77 workers with less than 10 years exposure experience. No abnormality could be discovered that might be related to such exposure.


Partial splenectomy in staging laparotomy for Hodgkin's disease: an alternative approach. Partial splenectomy, with resection of the lower one-fourth to one-third spleen, was performed in 10 children with Hodgkin's disease as part of an otherwise standard staging laparotomy. The technique proved to be safe and practical, with no postoperative complications. No evidence to date indicates that splenic involvement was missed, and all the children have thus far continued to do well, with no deaths from either underlying disease or postsplenectomy sepsis. The procedure is undergoing a prospective clinical trial in an effort to determine whether or not it is comparable from a diagnostic point of view to total splenectomy. Available data indicate that the risk of missing intraabdominal disease in a staging laparotomy with a partial splenectomy is quite low. Such a procedure should eliminate the substantial risk of postsplenectomy sepsis in such children.


Protective effect of residual splenic tissue after subtotal splenectomy. Studies in animals and clinical experience in man have demonstrated that splenectomy leads to increased susceptibility to infection with encapsulated bacteria. Splenic tissue has an excellent ability to regenerate, even when implanted into subcutaneous tissue or the abdominal cavity. These implants, however, do not protect against bacterial challenge despite the fact that a number of other functions can be restored. We therefore studied the ability of residual splenic tissue to protect against challenge following subtotal splenectomy in Sprague-Dawley rats. Subtotal splenectomy was performed on 48 animals in which approximately 75% of the spleen was removed and left with a branch of its normal blood supply; 48 animals underwent total splenectomy and 48 had sham operations. Six months after surgery the groups were challenged intravenously with type 25 pneumococci to determine the LD50 for each group. Animals that had undergone subtotal splenectomy were more resistant to pneumococcal challenge than were asplenic animals, but they were not as resistant as normal animals. In addition, there was marked delay in death in the animals with subtotal splenectomy as compared with asplenic animals. Thus residual splenic tissue after subtotal splenectomy appears to confer some degree of protection against pneumococcal challenge.