Cystic spinal neurilemmoma on magnetic resonance imaging.

We report a complete cystic change of intradural neurilemmoma at the T12-L1 level. T1-weighted MRI images with gadolinium-DTPA clearly enhanced the thin capsule of the cystic tumour.


CT-guided chemical rhizotomy of the C1 root for occipital neuralgia.

Sensation in the parasagittal occipital region is usually provided by fibres from the second cervical root via the greater occipital nerve. In the case presented occipital neuralgia could be relieved only by coagulation of the C1 nerve root with 96% ethyl alcohol. Possible explanations for this observation are discussed and a technique for CT-guided treatment is described.


The value of intraoperative scans during CT-guided stereotactic procedures.

The accuracy stereotactic procedures performed during the pre-computed tomography (CT) era was confirmed by intraoperative X-ray pictures. With the availability of CT it is now possible to confirm the position of the probe-tip on an image of the target. For biopsy of small lesions in critical areas of the brain, permanent placement of radioactive seeds, or thalamotomy, it would be desirable to have confirmation of the site of the probe-tip prior to performing the main step of the procedure. Intraoperative CT was performed in 216 stereotactic procedures carried out on the scanner table including biopsies, aspiration of cysts, brachytherapy, aspiration of abscesses, thalamotomy, and evacuation of intracerebral hematoma. In 6 cases, inaccuracies were detected, which it was possible to correct so as to place the probe where desired.


Successful treatment of neonatal aneurysmal dilatation of the vein of Galen: the role of prenatal diagnosis and trans-arterial embolization.

We report a neonate with aneurysmal dilatation of the vein of Galen diagnosed prenatally by color Doppler sonography and MRI at 37 weeks' gestation. The child was treated by transarterial embolization of micro-coils 2 and 8 days after birth. The aneurysmal dilatation of the vein of Galen markedly decreased after embolization and the patient is developing normally at 2 years 5 months of age. Prenatal diagnosis and early intervention by transarterial embolization produced in a good outcome in this patient.


Arteriovenous fistula of the internal maxillary artery in a child: case report.

Direct arteriovenous fistulae supplied by the external carotid artery are unusual. Rarely, congenital fistulae have been described involving the head and neck. We describe the first case of congenital internal maxillary arteriovenous fistula in a child. Balloon embolization is currently considered the method of choice for treatment of direct arteriovenous fistula.


Benzodiazepines block long-term potentiation in slices of hippocampus and piriform cortex.

The effects of two benzodiazepines, diazepam and triazolam, on long-term potentiation were tested in slices of hippocampus and piriform cortex. The drugs had little influence on baseline synaptic responses but both were very effective in blocking LTP elicited by theta pattern stimulation. The effects were fully reversible upon washout. Diazepam reduced the increase in burst responses that occurs during theta stimulation and thus appears to interfere with the initial triggering events for long-term potentiation. This may reflect the enhancing action of the drug on GABA-mediated inhibitory potentials. Triazolam did not detectably change the burst responses elicited by theta pattern stimulation. Experiments with slices of piriform cortex indicated that triazolam also failed to disrupt the development of long-term potentiation but instead caused the potentiation to decay back to baseline in 15-30 min. Triazolam thus seems to act on the mechanisms that stabilize long-term potentiation. These results provide a possible explanation for the amnestic effects of benzodiazepines in humans and animals and support the hypothesis that long-term potentiation contributes to memory encoding.


G-protein mediation in nociceptive signal transduction: an investigation into the excitatory action of bradykinin in a subpopulation of cultured rat sensory neurons.

Bradykinin is one of several pro-inflammatory, pain-inducing substances produced during inflammation--the body's response to injury. In previous work we have shown that bradykinin and guanosine-5'-O-3-thiotriphosphate increase excitability in a subpopulation of cultured neonatal rat dorsal root ganglion neurons. We now describe experiments in which the mechanism underlying the stimulatory action of these two substances has been examined in more detail. Using the whole-cell voltage-clamp technique, bradykinin-sensitive cells were distinguished by their response to a 1-s depolarizing voltage-pulse which evoked more than one inward current during the step command. The secondary inward currents are likely to represent action potentials generated at the poorly clamped neurites of these cells. Bradykinin- and guanosine-5'-O-3-thiotriphosphate-induced changes in excitability were measured indirectly by a change in the number of inward currents recorded during the 1-s depolarizing voltage-step. The effect of activators and inhibitors of protein kinase C, arachidonic acid metabolism, G-protein activation and release of intracellular Ca2+ were examined on this response. In the presence of extracellular staurosporine (1.0 microM) or nordihydroguaiaretic acid (10 microM), these excitatory effects were reduced but not abolished, whilst indomethacin (20 microM) had no effect. Intracellular application of guanosine-5'-O-2-thiodiphosphate (10 mM) or ryanodine (100 microM) substantially reduced the effect of bradykinin. The excitatory effect of internal guanosine-5'-O-3-thiotriphosphate (500 microM) occurred gradually over time, and this was mimicked by internal application of myo-inositol 1,4,5-trisphosphorothioate (1.0 microM). From the results, it is proposed that G-protein activation is an essential component of the bradykinin response, which may also require a Ca(2+)-activated conductance modulated by protein kinase C and lipoxygenase metabolites of arachidonic acid.


Capsaicin differentially influences somatosensory cortical responses evoked by peripheral electrical or mechanical stimulation.

The effects of capsaicin injected intraperitoneally (200 micrograms/kg) or applied locally to the cortical surface (10(-5) M) were studied on cortical potentials evoked by peripheral electrical or mechanical stimulation. Capsaicin treatment (i.p.) differentially influenced the cortical evoked potentials depending on the type of stimulation. Just after both types of capsaicin application, the responses to both kinds of stimuli decreased in amplitude. Additionally, during this time a short fall in blood pressure was observed. Half an hour later, however, only in the case of interperitoneal application the potentials evoked by electrical stimulation were facilitated, while the potentials evoked by vibrissa deflection had recovered and stayed around the control levels thereafter. In addition, the responsive cortex area activated by electrical stimulation became enlarged after the i.p. injection of capsaicin, while that of the cortex region activated by mechanical stimulation did not change significantly. Capsaicin applied locally to the cortex resulted neither in the facilitation of evoked potentials nor in the enlargement of the responsive cortical area. The present findings are the first to demonstrate that the i.p. (but not local) administration of capsaicin, in low dosage, differentially influences the cortical responses evoked by electrical and mechanical stimulation of somatosensory afferents.


Performance in an escape task induces fos-like immunoreactivity in a specific area of the motor cortex of the rat.

The expression of the c-fos proto-oncogene was studied in two different areas of the motor cortex and in the hippocampus of the rat after performance in an escape task in a Skinner box. Performance in this task caused an increase in the number of cells showing fos-like immunoreactivity in layers V and VI of the forelimb motor-sensory cortex with respect to yoked animals which had received the same amount, frequency and duration of aversive stimulation and manipulation as the trained animals. Therefore, this increase is the specific effect of performing the behavioral task. In the hindlimb motor-sensory cortex there were no differences between the trained and the yoked animals in any of the cortical layers. No differences were observed in the dentate gyrus of the hippocampus between trained and yoked animals, while the control animals showed a much lower fos-like immunoreactivity. In conclusion, infragranular layers in the forelimb representation of the primary motor cortex become activated with respect to the expression of fos-like immunoreactivity after performance in an escape task in a Skinner box. This result is consistent with the idea that even in complex structures such as the cerebral cortex, specific trace systems become activated for the performance of complex behavioral tasks.


The appearance of Fos protein-like immunoreactivity in the hypothalamus of developing rats in response to cold ambient temperatures.

This study examined cellular activity in the hypothalamus of developing rats in response to cold environmental temperatures. The appearance of the nuclear protein, Fos, in response to cold ambient temperatures in rats three to 35 days of age was used as a marker of neuronal activation. Fos-positive nuclei were first seen in response to cold ambient temperatures in the ventromedial nucleus at three days of age, the paraventricular nucleus at eight days of age, the preoptic-anterior hypothalamus at 10 days of age and the anterior hypothalamic nucleus at 21 days of age. The rectal temperature of the 10-day-old pups dropped by less than half that measured in the nine-day-old pups after 1 h in the cold. It is possible that the activation of neurons in the preoptic-anterior hypothalamus in the 10-day-old animal may contribute to the decreased hypothermia observed in the 10-day-old after 1 h in the cold. The high density of Fos-like immunoreactive-labeled nuclei in the preoptic-anterior hypothalamus in the 10-day-old rats that were exposed to the cold environment indicates increased neuronal activity at this site. The results suggest that, at least in the preoptic-anterior hypothalamus, the appearance of the cellular response to cold ambient temperatures is coincidental with a thermogenic response.


Increase in cytoplasmic free Ca2+ elicited by noradrenalin and serotonin in cultured local interneurons of mouse olfactory bulb.

Effects of noradrenalin and serotonin on cytoplasmic free Ca2+ concentrations ([Ca2+]i) were studied by using the fluorescent indicator fura-2 in cultured local interneurons of mouse olfactory bulb. Application of noradrenalin (0.1-100 microM) caused a rapid and concentration-dependent rise in [Ca2+]i, while isoproterenol was ineffective at concentrations up to 100 microM. The noradrenalin (1 microM)-induced increase in [Ca2+]i was completely inhibited by pretreatment with alpha 1-antagonist, prazosin (100 nM), whereas the inhibitory effect of alpha 2-antagonist, yohimbine, was about 100-times less potent. Serotonin (0.1-100 microM) also caused the dose-dependent rise in [Ca2+]i, which was inhibited by serotonin2 antagonist, ketanserin. Even in the absence of the extracellular calcium, the noradrenalin- or serotonin-induced increase in [Ca2+]i was observed. These results indicate that both noradrenalin and serotonin elicit the rise in [Ca2+]i in local interneurons of the olfactory bulb. They also suggest that the rise in [Ca2+]i is mediated by alpha 1-adrenergic and serotonin2 receptors, and that the increased calcium is mainly derived from intracellular calcium storage sites. The above results provide evidence to suggest that in the olfactory bulb, noradrenergic and serotonergic centrifugal fibers exert modulatory influences on synaptic interactions between mitral/tufted cells and local interneurons by increasing cytoplasmic Ca2+ in local interneurons.


Membrane retrieval following exocytosis in isolated neurosecretory nerve endings.

In the neurosecretory nerve endings of the neurohypophysis depolarization-induced exocytosis is followed by endocytosis of vacuole-like structures with diameter similar to that of neurosecretory granules. However, it remains unknown whether the membrane of the endocytotic vacuoles is comprised primarily of retrieved secretory granule membrane, plasma membrane or of a mixture of the granule and plasma membrane. In the present paper membrane retrieval following depolarization-induced exocytosis has been studied in isolated neurosecretory nerve endings from the rat neurohypophysis. The origin of the retrieved membrane was assessed by pre-labeling the plasma membrane with an antibody against neural cell adhesion molecule, a plasma membrane specific protein. Horseradish peroxidase was used as an index of fluid endocytosis and secretion of vasopressin was measured by radioimmunoassay. Following potassium-induced depolarization, endocytotic vacuoles showed labeling with the fluid phase marker horseradish peroxidase but never showed significant neural cell adhesion molecule labeling. The time-course of endocytosis following closely that of exocytosis as endocytotic vacuoles labeled with horseradish peroxidase were only observed when the fluid phase marker was present in the extracellular medium during the period of evoked exocytosis. Our results are consistent with a model in which in neurosecretory nerve endings, after transient exocytotic fusion of the granule membrane with the plasma membrane, the granule membrane is rapidly and selectively retrieved into the nerve endings in the form of vacuoles similar in size to that of the neurosecretory granules.


Virtual trajectories, joint stiffness, and changes in the limb natural frequency during single-joint oscillatory movements.

In the framework of the equilibrium-point hypothesis, virtual trajectories and patterns of joint stiffness were reconstructed during voluntary single-joint oscillatory movements in the elbow joint at a variety of frequencies and against two inertial loads. At low frequencies, virtual trajectories were in-phase with the actual joint trajectories. Joint stiffness changed at a doubled frequency. An increase in movement frequency and/or inertial load led to an increase in the difference between the peaks of the actual and virtual trajectories and in both peak and averaged values of joint stiffness. At a certain, critical frequency, virtual trajectory was nearly flat. Further increase in movement frequency led to a 180 degree phase shift between the actual and virtual trajectories. The assessed values of the natural frequency of the system "limb + manipulandum" were close to the critical frequencies for both low and high inertial loads. Peak levels and integrals of the electromyograms of two flexor and two extensor muscles changed monotonically with movement frequency without any special behavior at the critical frequencies. Nearly flat virtual trajectories at the natural frequency make physical sense as hypothetical control signals, unlike the electromyographic recordings, since a system at its natural frequency requires minimal central interference. Modulation of joint stiffness is assumed to be an important adaptive mechanism attenuating difference between the system's natural frequency and desired movement frequency. Virtual trajectory is considered a behavioral observable. Phase transitions between the virtual and actual trajectories are illustrations of behavioral discontinuities introduced by slow changes in a higher level control parameter, movement frequency. Relative phase shift between these two trajectories may be considered an order parameter.


Conduction properties of spinal cord axons in the myelin-deficient rat mutant.

Spinal cords of myelin-deficient and normal age-matched (control) rats were removed and their conduction and pharmacological properties studied in an in vitro brain slice chamber. The conduction velocity of the myelin-deficient dorsal column axons was reduced to about 25% of control axons; however, the amyelinated myelin-deficient axons displayed refractory periods and the ability to sustain high-frequency action potential discharge similar to that of dorsal column axons in control rats. Pharmacological results suggest that the myelin-deficient dorsal column axons qualitatively express a normal complement of ion channels and receptors. The demonstration of a normal representation of channels and receptors on these axons supports the proposal that the oligodendrocyte, and not the axon, is the site of the primary defect in the myelin-deficient rat mutant. It is concluded that, unlike acutely demyelinated axons which display marked frequency-dependent conduction block, amyelinated axons of the myelin-deficient rat spinal cord develop compensatory mechanisms to stabilize action potential conduction.


Developmental regulation of parasympathetic nerve density by sympathetic innervation in the tarsal smooth muscle of the rat.

The developmental influence of sympathetic innervation on parasympathetic nerve density was investigated in the tarsal smooth muscle of the rat. Specificity of acetylcholinesterase staining as a marker for parasympathetic innervation was first determined by acute selective denervations. Excision of the ipsilateral superior cervical ganglion caused a 39% reduction in the density of acetylcholinesterase-positive nerves seven days later, indicating that sympathetic nerves contribute to cholinesterase-positive tarsal muscle innervation. Excision of the pterygopalatine ganglion concurrent with superior cervical ganglionectomy caused a virtually complete disappearance of acetylcholinesterase-positive innervation within seven days, indicating that non-sympathetic cholinesterase-positive fibers derive from the pterygopalatine ganglion and are presumed to be parasympathetic. Analysis of the control population indicated that parasympathetic nerve density did not vary significantly between males and females, between the superior and inferior muscles, or in rats studied at four and 12 months of age. The influence of sympathetic innervation on parasympathetic nerve density during postnatal development was examined by conducting surgical sympathectomies on postnatal day 5 and quantifying acetylcholinesterase-positive nerve density at four months of age. Neonatal sympathectomy caused a 46% reduction in cholinesterase-positive nerve density beyond that which occurred in acutely sympathectomized adult controls. It is concluded that sympathetic innervation is required for developing parasympathetic nerves to attain their normal density within the rat tarsal muscle. This finding is consistent with the idea that sympathetic nerves can exert positive effects on parasympathetic nerve outgrowth during development.


Behaviour-dependent changes in acetylcholine release in normal and graft-reinnervated hippocampus: evidence for host regulation of grafted cholinergic neurons.

Grafted neurons obtained from the fetal basal forebrain can provide a functional cholinergic reinnervation of the hippocampal formation in rats with a lesion of the intrinsic septal cholinergic afferents. In the present experiments graft-derived acetylcholine release in the hippocampus was studied by microdialysis in awake rats during different types of behaviours which are known to activate the innate septohippocampal cholinergic system and during different activity periods of the day-night cycle. Two types of basal forebrain grafts were studied: cell suspensions implanted into the hippocampus in rats with an aspirative lesion of the fimbria-fornix, and grafts of solid tissue implanted as a tissue bridge into the fimbria-fornix lesion cavity. Increased acetylcholine overflow was seen in both groups with grafts during sensory stimulation (by handling). The strongest response (50% increase in acetylcholine release) was seen in rats with solid basal forebrain grafts (equivalent to two-thirds of that seen in intact rats). Immobilization stress and motor activity (swimming) also resulted in increased, but more variable, acetylcholine release (+ 30%; about one-third of the normal response). None of these effects was seen in the control rats with fimbria-fornix lesion only. The two-fold difference in hippocampal acetylcholine release in normal animals between day and night was absent in both types of grafted rats. An acute knife-cut, transecting the connections between the solid basal forebrain graft and the host hippocampus, caused an immediate 75% reduction in acetylcholine release (similar to the effect of an acute fimbria-fornix transection in the normal rats) and the response to swimming was no longer evident. The results show that grafted cholinergic neurons can be functionally integrated into the host brain, allowing the grafted neurons to be activated in the correct behavioural contexts, although the changes in acetylcholine overflow were overall smaller and more variable than normal. The ability of the host to influence cholinergic graft activity, most probably mediated via activation of afferent host-graft connections, may contribute to the efficacy of basal forebrain grafts in the amelioration of behavioural impairments in animals with lesions of the forebrain cholinergic system.


N-methyl-D-aspartate receptor complex in the hippocampus of elderly, normal individuals and those with Alzheimer's disease.

The various ligand binding sites of the N-methyl-D-aspartate receptor complex in the hippocampal formation and parahippocampal gyrus of Alzheimer's disease patients and age-matched normal individuals were examined using quantitative autoradiography. The hippocampus and parahippocampal gyrus of the normal elderly brain exhibited virtually identical distributions of L-[3H]glutamate, [3H]5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-iminemaleate ([3H]MK-801), [3H][(+/-)2-carboxypiperazine-4-yl]propyl-1-phosphonic acid ([3H]CPP) and strychnine-insensitive [3H]glycine binding sites (r greater than 0.87) suggesting that binding occurred to different domains of the same receptor macromolecule. The binding of [3H]MK-801 to channel-associated phencyclidine sites appeared to be most severely impaired in Alzheimer's disease, especially at the anterior hippocampal level. When the data were averaged and the means for Alzheimer's disease and control group compared, a 34% decrease (P less than 0.01) in [3H]MK-801 binding was identified in the CA1 stratum pyramidale and a smaller decrease was found in the dentate gyrus molecular layer, parahippocampal gyrus and subiculum. The CA1 region exhibited a similar 35% reduction (P less than 0.05) in L-[3H]glutamate binding to N-methyl-D-aspartate-sensitive sites. This decrease most probably reflected a decline in receptor density. Binding of [3H]CPP to antagonist-preferring sites and [3H]glycine to glycine modulatory sites did not change significantly. However, a marked intersubject variability in N-methyl-D-aspartate receptor binding was observed in control and Alzheimer's disease groups. This variability was not related to age, sex or post mortem delay. Some Alzheimer's disease patients showed markedly reduced receptor binding levels, while others showed no changes or even increased binding. The loss of N-methyl-D-aspartate-sensitive sites did not correlate with a loss of neurons in the CA1 region (r = 0.286). Similarly, no correlation between the level of binding to N-methyl-D-aspartate-sensitive sites and the density of neuritic plaques and neurofibrillary tangles was found. Intersubject variability in N-methyl-D-aspartate receptor responses in the Alzheimer's disease group may partially explain conflicting reports in the literature on the N-methyl-D-aspartate receptor changes in Alzheimer's disease, and imply that caution should be exercised before making any generalizations about receptor changes in Alzheimer's disease based on mean values only. The analysis of the individual Alzheimer's disease cases may also be valuable in determining the mechanism(s) underlying the disease.


The neurofilament triplet is present in distinct subpopulations of neurons in the central nervous system of the guinea-pig.

It is commonly assumed that most, if not all, neurons contain the intermediate filament protein class known as the neurofilament protein-triplet. The following study investigated the distribution of neurofilament protein-triplet immunoreactivity in selected regions of the guinea-pig central nervous system using monoclonal antibodies directed against phosphorylation-independent epitopes on the three subunits under optimal tissue processing conditions. Neurofilament protein-triplet immunoreactivity was present in distinct subpopulations of neurons in the cerebellar cortex, neocortex, hippocampal formation, retina, striatum and medulla oblongata. In many of these regions, labelled neurons represented only a small proportion of the total. The selective distribution of this intermediate filament protein class was confirmed in double-labelling experiments using antibodies to the neurofilament protein-triplet in combination with antibodies to other neuronal markers. The distribution of neurofilament protein-triplet immunoreactivity also correlated with the distribution of staining observed with a silver impregnation method based on Bielschowsky. The present results in combination with previous observations have demonstrated that the neurofilament protein-triplet is found in specific subclasses of neurons in different regions of the nervous system. Content of this intermediate filament protein class does not appear to be correlated with neuronal size or length of projection. These results also suggest that the selectivity of staining between neuronal classes observed with classical silver impregnation methods may be due to the presence or absence of the neurofilament protein-triplet. The present results may also provide a new perspective on the basis of the selective vulnerability of neurons in degenerative diseases.


Vestibularly induced slow oscillations in climbing fiber responses of Purkinje cells in the cerebellar nodulus of the rabbit.

In this report we describe an interesting form of plasticity in climbing fiber responses evoked in Purkinje cells of the rabbit cerebellum by periodic vestibular stimulation. The cerebellar nodulus receives a vestibular as well as a visual climbing fiber afferent input from the contralateral inferior olive. The vestibular input to the inferior olive originates from the ipsilateral medial and descending vestibular nuclei and terminates within the beta-nucleus. This projection to the beta-nucleus from secondary vestibular neurons is GABAergic. This means that vestibularly evoked activity of neurons in the beta-nucleus is controlled by modulation of an inhibitory input, rather than by modification of an excitatory input. We have recorded the climbing fiber responses of single Purkinje cells in the uvula-nodulus (lobules 9c, 9d and 10) of rabbits and we have characterized the climbing fiber response of each Purkinje cell from which we recorded by testing its sensitivity to otolithic stimulation, semicircular canal stimulation and optokinetic stimulation. Vestibularly evoked climbing fiber responses recorded from the left nodulus were stationary. They were repeatedly evoked, for tens of minutes, by sinusoidally rotating the rabbit about the longitudinal axis onto its left side (Fig. 1B). When the vestibular stimulus was stopped the discharge of these climbing fiber responses returned to non-periodic spontaneous levels. However, the vestibularly evoked climbing fiber discharge of approximately 5% of Purkinje cells was not stationary.(ABSTRACT TRUNCATED AT 250 WORDS)


Descriptive morphology of developing fetal neostriatal allografts in the rhesus monkey: a correlated light and electron microscopic Golgi study.

Primate fetal striatal neurons were transplanted into the ibotenic acid lesioned rhesus monkey striatum. Ten weeks after transplantation the monkeys were transcardially perfused and graft tissue was histologically stained. Golgi impregnated, and processed for electron microscopy. The monkeys received magnetic resonance imaging (MRI) scans before lesioning, after lesioning, and ten weeks after transplantation to noninvasively study the striatal grafts. The study demonstrated that fetal striatal grafts, measuring up to 0.4 x 0.8 cm, can survive for extended periods of time in the non-human primate. Hematoxylin-eosin stained sections of the transplant demonstrated that neuronal, glial, vascular, and lymphocytic cells were present in the graft. The majority of the neurons had somatic diameters between 8 and 20 microns and were characterized by nuclei containing multiple nucleoli. A few neurons within the graft had somatic diameters up to 40 microns. These larger neurons exhibited more mature cytoplasm containing a moderate amount of Nissl substance. Some of the blood vessels within the graft were surrounded by a large number of plasma cells, but there was no evidence of hemorrhage or necrosis. Bielschowsky staining and Golgi impregnation of the transplanted tissue demonstrated that there were neurons at various degrees of differentiation. Some of the neurons had varicose dendrites, growth cones, and filopodia, which are all characteristics of immature neurons, while others had a much more mature appearance, including a moderate number of dendritic spines. Some of these neurons had an appearance typical of differentiating "medium spiny" neurons of the normal striatum. Electron microscopic analysis of the transplanted tissue and individual Golgi-impregnated neurons within the transplant confirmed that there were developing neurons within the graft. These neurons had an increased nuclear-to-cytoplasmic ratio and had nuclei containing multiple nucleoli. The neuropil surrounding these neurons was loosely organized and contained large areas of extracellular space. The neuropil exhibited developing dendrites, numerous growth cones, and mature synapses. In summary, the study demonstrated that fetal striatal allografts can survive for up to three months in the rhesus monkey and undergo normal differentiation as assessed by Golgi impregnation and electron microscopy.


Calretinin distribution in the thalamus of the rat: immunohistochemical and in situ hybridization histochemical analyses.

The distribution of calretinin-containing cells was examined by in situ hybridization histochemistry and compared with the immunohistochemical mapping of calretinin in the thalamus of the rat. Results revealed a close correspondence between the immunohistochemical localization of cell bodies and the messenger RNA label produced by the calretinin oligonucleotide probe. Calretinin cells were most prominent in the midline (paraventricular, reuniens, rhomboid) and intralaminar (central medial, paracentral) nuclei and in a group of cells along the rostral central gray which appeared continuous with the caudal extent of the midline nuclei. A subpopulation of calretinin cell bodies was also identified in the reticular nucleus. The mediorostral lateral posterior nucleus, subparafascicular, lateral geniculate and habenular nuclei also contained calretinin messenger RNA probe label. In contrast, no positive cells were found in the anterior, ventral or posterior thalamic nuclei. The distribution of calretinin cells did not correspond directly with that of other histochemical markers. Thus, the in situ hybridization histochemical and immunohistochemical results revealed calretinin as a unique identifying marker for distinct sets of thalamic neurons.


Microstimulation mapping of the basal forebrain in the anesthetized rat: the "preoptic locomotor region".

Previous studies have indicated that the basal forebrain at the level of the preoptic area contains neurons which participate in the initiation of locomotion. This study attempted to localize those neurons by mapping sites at which 25- and 50-microA stimulation (50 Hz, 0.5 ms cathodal pulses, 10-s trains) initiated hindlimb stepping. Anesthetized rats were held in a stereotaxic apparatus supported by a sling so that stepping movements rotated a wheel. Anesthesia was maintained by periodic injections of Nembutal (7 mg/kg) supplemented by lidocaine injections. Stimulation was applied through 50-70-microns diameter pipettes filled with 2 M NaCl at approximately 1600 sites in the basal forebrain, adjacent thalamus, and striatum. A circumscribed grouping of 25-microA locomotor sites, centered in the lateral preoptic area, defined the preoptic locomotor region. It extended into the ventral bed nucleus of the stria terminalis, the lateral part of the medial preoptic area, the anterior hypothalamic area, the medial and rostral parts of the ventral pallidum, medial substantia innominata, and the horizontal limb of the diagonal band. This general region is known to project to the midbrain locomotor region and the ventral tegmental area; it is proposed to initiate locomotion in service of primary motivational systems. Among the structures generally negative for locomotor sites were the dorsal and ventral striata, septal complex, bed nucleus of stria terminalis, and lateral ventral pallidum and substantia innominata. These findings indicate that low current stimulation applied to a circumscribed area centered in the lateral preoptic area produces locomotor stepping in the anesthetized rat. Whether the activated elements in this preoptic locomotor region are cells or fibers is not yet known. The degree of localization afforded by these findings indicates that the areas that are most likely to contain the mediating elements are quite limited in extent.


Changing pattern of c-FOS expression in spinal cord neurons after electrical stimulation of the chronically injured sciatic nerve in the rat.

Immunocytochemical technique was used to study the distribution of c-FOS protein immunoreactive cells in the spinal cord and gracile nuclei 2 h after electrical stimulation of the sciatic nerve in ketamine/xylazine/acepromazine-anesthetized adult rats. Quantitative examination of the c-fos-labeled cells in the spinal cord laminae was made in unoperated and sham operated controls, after sciatic nerve transection without electrical stimulation, and after electrical stimulation at C-fiber or A alpha/beta-fiber intensity, both in normal animals and at various survival times after chronic sciatic nerve injury (transection and ligation) or crush. Unoperated animals showed very few c-fos-labeled cells, and sham operated controls showed labeled cells located mainly outside the sciatic nerve projection territory. A small increase in number of c-fos protein positive cells was seen after sciatic nerve transection without electrical stimulation. Stimulation of the normal sciatic nerve at C-fiber intensity resulted in c-fos protein-positive cells within the sciatic projection territory in the ipsilateral dorsal horn. Labeled cells were seen in all spinal cord laminae except lamina IX, with the vast majority in lamina I and outer lamina II. No labeled cells were seen in the gracile nucleus. Stimulation at A alpha/beta fiber intensity resulted in no or only a very small number of c-fos-positive neurons. Electrical stimulation of the injured sciatic nerve at C-fiber intensity, using the uninjured contralateral side as control, resulted in significant decreases in c-fos-immunoreactive cells in lamina I plus the outer portion of lamina II at 12 and 39 days survival after injury. A non-significant decrease was seen in these laminae also after 21 days. Significant increases were seen in laminae III and IV at 21 days. Decreases in laminae V, VI and more ventral laminae were significant at 21 and 39 days after injury. At longer survival times, the difference between the normal and injured side seen weeks after injury tended to disappear. Stimulation at A alpha/beta fiber intensity 21 days after injury resulted in increases in the numbers of labeled cells in ipsilateral laminae II, III and IV and in the gracile nucleus. Sciatic nerve stimulation after crush injury resulted in more variable side differences, with tendencies for the same alterations as those noted after chronic transection-ligation.(ABSTRACT TRUNCATED AT 400 WORDS)


Inflammatory mediators and nociception in the joint: excitation and sensitization of slowly conducting afferent fibers of cat's knee by prostaglandin I2.

The effects of prostaglandin I2 on the discharge properties of fine articular afferents (group III and group IV fibers) in the cat were examined by extracellular recordings from single units dissected from the medial articular nerve of the knee joint. Prostaglandin I2 was applied intra-arterially close to the joint in doses of 0.3-30 micrograms per 0.3 ml bolus injection, and its effects on the spontaneous activity as well as on discharges evoked by mechanical and chemical stimulation (bradykinin) were monitored. Prostaglandin E2 was also applied and the effects of prostaglandins I2 and E2 on particular units were compared. An excitatory effect of prostaglandin I2 was observed in 49% of 37 group III and in 37% of 27 group IV units. A sensitization to passive movements of the joint occurred in 71% of 31 group III and 48% of 21 group IV units. Sixty-seven per cent of 32 units (groups III and IV) were both excited and sensitized by prostaglandin I2 to movements of 27% were sensitized but not excited. In 64% of 11 group III and 63% of eight group IV units studied the responses to bradykinin were enhanced by prostaglandin I2. Prostaglandin E2 had qualitatively similar effects as prostaglandin I2 but excited and sensitized a lower proportion of articular afferents. Forty-one per cent of the units were sensitive to both prostaglandins but 26% of the fibers were only sensitive to prostaglandin I2. None of the units was exclusively sensitive to prostaglandin E2. In general, the excitatory and sensitizing effects of prostaglandin E2 had a longer duration than those exerted by prostaglandin I2. We conclude that prostaglandin I2 increases the sensitivity to mechanical stimuli as well as to chemical stimulation by bradykinin in the majority of articular group III and group IV fibers. Moreover, in a large proportion of articular afferents, prostaglandin I2 had an excitatory effect. Thus, prostaglandin I2 may be an inflammatory mediator which is important for inflammation-evoked activity in slowly conducting afferents and it may participate in the development of arthritic hyperalgesia and pain.


B-50/GAP43 localization in polarized hippocampal neurons in vitro: an ultrastructural quantitative study.

Hippocampal pyramidal neurons cultured in vitro gradually develop morphologically and biochemically distinct axons and dendrites, resulting in functional neuronal polarization [Dotti C. G. et al. (1988) J. Neurosci. 8, 1454-1468]. We have studied the distribution of the growth-associated protein B-50 in hippocampal neurons of the rat at stage 3 of development by means of light and electron microscopic immunocytochemistry. Hippocampal neurons grown for two to three days in vitro were aldehyde fixed and immunolabelled using polyclonal rabbit antibodies to B-50 and goat anti-rabbit immunoglobulins tagged with 1 nm gold particles. In order to permit visualization by both light and electron microscopy, the gold probes were silver intensified. Light microscopy demonstrated the absence of B-50 immunostaining in living neurons and the presence after permeabilization by fixation and subsequent treatment of the neurons with sodium borohydride, indicating that B-50 is located intracellularly. Both immunofluorescence and immunogold-silver labelling revealed that B-50 immunoreactivity outlined all neurites of the morphologically polarized neurons. For quantitative electron microscopy, six morphologically polarized neurons (developmental stage 3) were carefully selected from immunolabelled Epon-embedded neurons and processed completely to ultrathin sections. In this way the ultrastructural localization of B-50 has been studied in the cell body, the neurites and their growth cones. For each sectioned neuron, the relative distribution of the gold-silver deposits (representing B-50) over the plasma membrane of various cellular compartments was quantitated. B-50 is located at the plasma membrane of the neuronal cell body and all neurites including their growth cones. The density of B-50 on the plasma membrane of growth cones is not different from that of the neuritic shaft. In addition, B-50 is present on the cytosolic side of the membrane of small electron-lucent vesicles (average diameter 102.7 +/- 2.5 nm) resembling transport vesicles. These vesicles are present in the cell body and the neurites. A two-fold concentration is found in the central region of the growth cones, suggesting a role of these vesicles in axonal transport, membrane insertion and (or) recycling. Since, at the onset of neuronal polarization, B-50 is present at the plasma membrane in all compartments of the hippocampal neuron, we suggest that at this stage of development B-50 does not participate directly in the processes leading to morphological polarization.(ABSTRACT TRUNCATED AT 400 WORDS)


Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve.

Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukemia antigen (CALLA), is a cell surface zinc metalloprotease that has the ability to hydrolyse a variety of physiologically active peptides. Interest in this enzyme is based on the view that it may play a role in the regulation of peptide signals in different tissues, including the nervous and immune systems. We have previously shown that endopeptidase-24.11 is present in Schwann cells in the peripheral nervous system of newborn pigs [Kioussi C. and Matsas R. (1991) J. Neurochem. 57, 431-440]. In the present study we have investigated the developmental expression of the endopeptidase by Schwann cells in the rat sciatic nerve, from embryonic day 16 to maturity. Endopeptidase-24.11 was monitored enzymatically as well as by immunoblotting and immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. We found an age-dependent decline in both the enzyme activity and the levels of immunoreactive protein. Endopeptidase-24.11 was first detected at embryonic day 18 and was present in all neonatal and early postnatal Schwann cells. However, as myelination proceeded the endopeptidase was gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. At this stage, only very few large diameter myelinated fibers expressed weakly endopeptidase-24.11. Schwann cells dissociated from postnatal day 5 nerves and cultured up to one week in the absence of axons expressed endopeptidase-24.11. These results show that the endopeptidase has a distinct developmental profile in the rat sciatic nerve, similar to that of a group of other Schwann cell surface antigens, including the cell adhesion molecules N-CAM and L1 and the nerve growth factor receptor. We suggest that, as is the case with these antigens, endopeptidase-24.11 may play a role in nerve development and/or regeneration. In addition, persistence of endopeptidase-24.11 in a minority of adult myelin-forming Schwann cells suggests a possible role for the enzyme in axon-myelin apposition and maintenance, especially of larger diameter axons.


Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat.

Recent evidence has shown that activation of the N-methyl-D-aspartate receptor mediates the thermal hyperalgesia produced in a model of neuropathic pain. As the acute nociceptive effects of N-methyl-D-aspartate have been reported to be mediated through production of nitric oxide and activation of soluble guanylate cyclase, these experiments were designed to determine whether the thermal hyperalgesia produced in a rat model of neuropathic pain is also mediated through the production of nitric oxide and activation of soluble guanylate cyclase. Loose ligation of the sciatic nerve with chromic gut sutures, but not bilateral sham rats, demonstrated evidence of a marked thermal hyperalgesia on day 3 post-surgery. In bilateral sham rats, intrathecal administration of either an alternate substrate for nitric oxide synthase, NW-nitro-L-arginine methyl ester, or the soluble guanylate cyclase inhibitor, Methylene Blue, did not produce any change in thermal nociceptive withdrawal latencies. These same treatments blocked the thermal hyperalgesia in rats with chromic gut ligatures for a period of 2 and 4 h, respectively. These results suggest that a sustained production of nitric oxide and subsequent activation of soluble guanylate cyclase in the lumbar spinal cord mediate the thermal hyperalgesia produced in a model of neuropathic pain in the rat.


Epidermal growth factor affects both glia and cholinergic neurons in septal cell cultures.

The effects of epidermal growth factor on high density primary cultures of fetal (embryonic day 17) rat septal cells were examined. Under serum-free conditions, the continuous exposure of these cultures to epidermal growth factor for seven days significantly decreased choline acetyltransferase (EC 2.3.1.6) activity in a dose-dependent manner. Maximal decreases were observed from 1 to 10 ng/ml epidermal growth factor. This effect was completely abolished by the addition of anti-epidermal growth factor antibodies. The epidermal growth factor-mediated decrease in choline acetyltransferase activity was culture-time dependent, being first detectable after five days of factor application and may likely represent an inhibition of the spontaneous increase in enzyme activity that occurs with time in culture. Concomitant with changes in enzyme activity, epidermal growth factor produced a significant and proportional decrease in the number of acetylcholinesterase-positive neurons. This decrease in acetylcholinesterase-positive cells did not reflect a decrease in cholinergic cell survival as nerve growth factor could restore the number of acetylcholinesterase-positive neurons in epidermal growth factor-treated cultures to control levels. Furthermore, in these high-density cultures, epidermal growth factor did not affect general neuronal survival, while it did produce an increase in the number and intensity of glial fibrillary acidic protein-immunoreactive astroglia as well as in the number of macrophage-like cells. The proliferative response of these non-neuronal cells to epidermal growth factor, as assessed by [3H]thymidine incorporation, was evident after three days of epidermal growth factor application, persisted thereafter, and could be antagonized by the inclusion of the antimitotic 5-fluorodeoxyuridine. Furthermore, 5-fluorodeoxyuridine completely blocked the epidermal growth factor-mediated decrease in choline acetyltransferase activity. However, when epidermal growth factor was tested in pure glial cultures, it only directly induced proliferation of astrocytes. These results suggest that the proliferative response of either one or both of these glial cell types in the mixed cultures may be indirectly affecting cholinergic cell expression.


Basic fibroblast growth factor-like immunoreactivity in Purkinje cells of the rat cerebellum.

An antiserum against basic fibroblast growth factor was characterized by immunoblot experiments and used to investigate immunohistochemically the projection fields and fine structures of basic fibroblast growth factor-containing cerebellar Purkinje cells. The antiserum demonstrated clearly purified basic fibroblast growth factor and basic fibroblast growth factor-like molecules of the same molecular weight in homogenates of the adult rat cerebellum. Light and electron microscopic immunohistochemistry revealed that a large number of Purkinje cells, if not all, send immunoreactive dendrites to the molecular layer and basic fibroblast growth factor-containing axons to the deep cerebellar and lateral vestibular nuclei, where basic fibroblast growth factor nerve terminals form synapses with the soma and dendrites of neurons labeled weakly with basic fibroblast growth factor. Nerve cells with basic fibroblast growth factor had immunoreaction deposits mainly in free ribosomes, those attached to the endoplasmic reticulum and in the nuclear euchromatin. These findings suggest that basic fibroblast growth factor is present in cerebellar Purkinje cells and undergoes two modes of transport, one to axon terminals and the other to nuclear euchromatin, known as the RNA transcription zone.


Anticipation in myotonic dystrophy. I. Statistical verification based on clinical and haplotype findings.

To determine whether anticipation in myotonic dystrophy (DM) is a true biologic phenomenon or an artifact of ascertainment bias, we studied 201 members of nine DM kindreds, including 67 individuals with the clinical diagnosis of DM. Of 49 parent-child pairs in which both the parents and the children were clinically affected, the onset of DM occurred in an earlier decade of life in the child than the parent in 44 pairs and in the same decade in five pairs (p < 0.001). To eliminate direct ascertainment bias, we excluded nine pairs involving the index patients. Indirect ascertainment bias due to incomplete penetrance was unlikely, since 55% of the children of DM parents had DM. However, by haplotype analysis of restriction fragment length polymorphisms, we diagnosed DM in one of the 42 asymptomatic children of affected parents and excluded DM in twenty-eight. We estimated that patients with early-onset DM would have produced an additional 25 DM children if they had normal fertility and nuptiality. Assuming that the expected age-of-onset distribution occurs without anticipation in these 25, only seven would have had the onset of DM earlier than their parents. With the corrected result, the child would have been affected earlier than the parent in 53 pairs, and the parent would have been affected at the same age as or earlier than the child in 13 pairs (p < 0.001). Thus, the observed anticipation is unlikely to be totally attributable to ascertainment bias, suggesting the potential importance of biologic mechanisms.


Anticipation in myotonic dystrophy. II. Complex relationships between clinical findings and structure of the GCT repeat.

We studied the expansion of the GCT repeats within the myotonic dystrophy protein kinase gene in nine myotonic dystrophy (DM) kindreds. Southern blot and polymerase chain reaction analyses of the repeat region demonstrated the expansion in all 62 patients with the diagnosis of DM. Among 43 DM parent-child pairs, age of onset in the child was earlier than in the parent in 36 pairs, in the same decade as the parent in five, and undetermined in two. The clinical anticipation observed in the 36 pairs accompanied an increase in the fragment size in 32, a decrease in two, and no apparent change in two pairs. In the remaining pairs without documented clinical anticipation, the fragment size increased in four, decreased in two, and was apparently unchanged in one. Overall, the size of expansion showed an inverse correlation with the age of onset (p < 0.001). In all seven pairs in which the fragment did not increase in size, the affected parent was male. Two congenital DM children born to affected mothers had expanded DNA greater than 4.5 kb. The differences between parent and child in age of onset significantly correlated with the differences in the expansion size among father-child pairs (p < 0.001) but not mother-child pairs (p > 0.5). Our data suggest that the expansion of the GCT repeats plays an important role in anticipation although other factors, including the sex of the affected parent, may have significant effects on molecular mechanisms of anticipation.


Post-lumbar puncture headaches: experience in 501 consecutive procedures.

To ascertain the frequency and risk factors for post-lumbar puncture headache, we studied all adults who had an ambulatory lumbar puncture (LP) in a 1-year period. Patients filled out a questionnaire detailing their headache experience on the day of, and the 6 days following, LP. Those who did not return the questionnaire were telephoned. We systematically collected and analyzed many items, including the lumbar puncturist's experience, the degree of difficulty of the LP, CSF findings, final diagnosis, and the patient's demographic characteristics. Patients reporting headache before LP were more likely to report post-LP headaches. In addition to this, younger female patients with a lower body mass index have the highest risk of developing post-LP headaches. CSF opening pressure, cells, and protein, patient's position during LP, the duration of recumbency following LP, and the amount of CSF removed at the time of LP did not influence the occurrence of headache.


The epidemiology of myasthenia gravis in central and western Virginia.

We conducted a study of the epidemiology of myasthenia gravis (MG) in four locations in central and western Virginia from 1970 through 1984. The population surveyed was 555,851 in 1984. A total of 73 new cases of MG occurred during the survey period, producing an overall average annual incidence rate of 9.1 per million. The point prevalence rate in 1980 was 13.4 per 100,000, and in 1984 it was 14.2. Approximately 15% of the population was black, and we found that incidence and prevalence rates for the black population were higher than the corresponding white population. When the population was subdivided into <50 and 50+ age groups, the incidence and prevalence were significantly higher in the older group. The rates we report here are higher than rates reported from any other locality. The reasons for the higher rates include optimal case identification, survey of a population with a higher incidence, and increasing aging of the population.


Parkinson's disease in twins studied with 18F-dopa and positron emission tomography.

We used 18F-dopa PET to examine concordance for dysfunction of the nigrostriatal dopaminergic system in 18 co-twins of patients with Parkinson's disease (PD) and scanned one clinically concordant monozygotic (MZ) twin pair, 17 asymptomatic co-twins (10 MZ, 7 dizygotic [DZ]), and 13 twins with PD (8 MZ, 5 DZ). Mean 18F-dopa uptake of the twins with PD was significantly reduced in putamen to 38% and in caudate to 66% of normal. Mean putamen 18F-dopa uptake for the 17 asymptomatic co-twins was also significantly reduced (86% of normal), as was putamen tracer uptake for the 10 MZ (87% of normal) and seven DZ (83% of normal) asymptomatic co-twin subgroups. Four of 10 MZ and two of seven DZ asymptomatic co-twins had putamen 18F-dopa uptake reduced more than 2 SDs below the normal mean. Three of these four asymptomatic MZ co-twins had tremor on examination at the time of PET and one has now developed PD 2 years later. Our PET findings give concordances for nigral dysfunction of 45% in the MZ pairs and 29% in the DZ pairs at a 2-SD threshold, and 18% in MZ and 0% in DZ pairs at a 3-SD threshold of significance. These data suggest that the concordance for nigral pathology in PD twins may be higher than previously realized and that the presence of an isolated postural or rest tremor may be a phenotypic expression of PD.


Prevalence of Parkinson's disease and other types of parkinsonism: a door-to-door survey in three Sicilian municipalities. The Sicilian Neuro-Epidemiologic Study (SNES) Group.

We investigated the prevalence of Parkinson's disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinson's disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinson's disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinson's disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment.


Multiple sclerosis with very late onset.

Multiple sclerosis (MS) can present clinically after age 59, but only rarely. In a large MS population (N = 2,019), 0.6% of patients had their first symptom at age 60 or older. Of this group, six had clinically definite MS, two had laboratory-supported definite MS, and four had clinically probable MS. The onset at this age was characteristically a slow deterioration of motor function. Most (10 of 12) of these very late-onset patients had a progressive course of disease from onset.


National General Practice Study of Epilepsy (NGPSE): partial seizure patterns in a general population.

The National General Practice Study of Epilepsy (NGPSE) is a prospective community-based study of newly diagnosed epileptic seizures. Of 594 patients with definite epileptic seizures, 160 (26.9%) had seizures with a clinically localizable onset: 36 (22.5%) frontal, 52 (32.5%) central sensorimotor, 43 (27%) temporal, nine (5.6%) frontotemporal, and 10 each (6.3%) parietal and other posterior cortex. There was no difference among these groups in seizure frequency or remission rate; 46.5% were seizure free and 6.9% had severe epilepsy. Etiology was identifiable in 41% and focal CT and EEG abnormalities in 33% and 19%, with results discordant with the clinical seizure localization in 21% and 20%. Temporal lobe epilepsy may be underreported, as it may be more difficult to localize clinically. Extratemporal seizures are extremely common in the general population, especially frontal and central sensorimotor, in relation to cerebrovascular disease. Prognoses are similar for partial epilepsies with different clinical patterns and regions of onset and are much better than suggested in hospital-based studies. The clinical, EEG, and CT localizations may frequently be discordant in this nonrefractory group.


Localization of emotional and volitional facial paresis.

Emotional facial paresis is characterized by impaired activation of face muscles with emotion but normal voluntary activation. We report seven patients with this sign. Their lesions involved the frontal lobe white matter, the striatocapsular territory, the anterolateral thalamus and insula, the posterior thalamus and operculum, and the mesial temporal lobe and insula each in one patient, and the posterior thalamus in two patients. Volitional facial paresis affects facial movements with voluntary effort, sparing activation on emotion. We report four such patients, with lesions involving the motor cortex in one and the pyramidal tract in the cerebral hemisphere in three.


HIV-1 infection and intravenous drug use: longitudinal neuropsychological evaluation of asymptomatic subjects.

A previous baseline cross-sectional comparison of cognitive performance of a group of AIDS-free, HIV-seropositive intravenous drug users with seronegative control intravenous drug users revealed no significant differences attributable to HIV. We now present longitudinal follow-up results from the same cohort of 160 intravenous drug users. There were no differences in performance by serostatus group at either 6- or 12-month follow-up visits, although differences by age and education were observed. Improvement in performance secondary to practice effects was comparable in both serostatus groups. These findings confirm that chronic intravenous drug use may be associated with a wide range of neuropsychological deficits, but there is no evidence that such preexisting deficits interact with HIV infection to produce additional cognitive impairment in otherwise asymptomatic intravenous drug users. Together with results from other high-risk groups such as homosexual/bisexual men and hemophiliacs, these results confirm that neurocognitive abnormalities during the presymptomatic stages of HIV infection are rare, regardless of the route of acquisition of the virus.


Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients.

We reviewed the clinical findings in 55 patients with cerebellar degeneration associated with the anti-Yo antibody (an anti-Purkinje cell antibody identified in this study by histochemistry and Western blot). The patients were all women, 26 to 85 years old. Fifty-two of them proved to have malignancies, almost exclusively breast or gynecologic cancers and usually confined to the involved organs and local lymph nodes. One woman had adenocarcinoma of the lung, and in three no malignancy has yet been identified. In 34 of 52 patients with cancer, the neurologic syndrome preceded the diagnosis of cancer and in many led to that diagnosis. Patients subacutely developed a pancerebellar disorder that was substantially disabling in most, with 37 of 48 assessable patients being unable to walk or sit unassisted. Laboratory evaluation revealed lymphocytic pleocytosis in 35 patients, with eventual cerebellar atrophy on imaging studies in seventeen. The disabling neurologic syndrome generally did not respond to treatment, but the cancer was often successfully treated. The presence of the anti-Yo antibody in patients with cerebellar symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer, as many are curable at the time neurologic symptoms develop.


Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin's disease.

We reviewed clinical findings and serologic data on 18 men and three women with paraneoplastic cerebellar degeneration (PCD) associated with Hodgkin's disease (HD). The patients were 20 to 77 years old (median, 44). The lymphoma preceded neurologic symptoms by 1 to 54 months in 17/21 patients, but stage or activity did not correlate with severity of neurologic disease; six developed PCD while in HD remission. PCD evolved subacutely (over weeks to months) and was pancerebellar in most. Ten had downbeat nystagmus. Thirteen stabilized in a disabled state (wheelchair- or bed-bound), five stabilized ambulatory, and three, who had progressed to a nonambulatory state, recovered. The clinical findings were usually only cerebellar but one patient had an encephalopathy, three long-tract signs, and two sensory neuropathy. Plasmapheresis (seven patients) and corticosteroids or other immunosuppressant medication (eight patients) did not help; one improved dramatically after treatment with clonazepam. Two patients improved spontaneously. Six patients had serum antibodies that reacted specifically with Purkinje cells. The pattern was distinct from that of PCD with gynecologic cancer (anti-Yo) or small-cell lung cancer (anti-Hu). Western blotting failed to identify a discrete Purkinje cell antigen. Seropositive patients did not differ clinically from their seronegative counterparts. HD-associated PCD is more common in men and in a younger age group than in PCD with other malignancies.


Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.


Magnetic brain stimulation: the silent period after the motor evoked potential.

In 25 normal subjects, we studied the EMG silent period following the magnetic motor evoked potential (MEP) when the target muscle was tonically contracted (post-EMP silent period [PMSP]). In the first dorsal interosseous muscle (FDI), PMSP duration increased in linear proportion to stimulus intensity, but not to the size of the preceding MEP. The PMSP was longer in hand and forearm muscles than in upper arm muscles. In the FDI, PMSP was longer than the peripheral silent period (PSP) even when multiple peripheral stimuli were used to get M responses whose twitch force was equivalent to that of MEPs. Weak magnetic stimuli evoked silent periods preceded by no MEP in several subjects. Spinal alpha-motoneurons (alpha-MNs) were partially inhibited during the first PMSP portion, but later this effect recovered. MEPs due to weak electrical stimuli to motor cortex were only slightly inhibited during the late PMSP. Segmental inhibitory loops evoked by the muscle twitch and inhibitory projections descending to alpha-MNs from the cortex predominantly underlie earlier PMSP portions, but recurrent intracortical inhibition may also contribute. Later portions are predominantly due to other stimulus-related cerebral inhibitory or suppressing phenomena.


Differential effects of congenital versus acquired unilateral brain injury on dichotic listening performance: evidence for sparing and asymmetric crowding.

We assessed dichotic speech and complex-pitch discrimination in nine young patients with unilateral left-hemisphere injury and eight young patients with unilateral right-hemisphere injury incurred in the pre-perinatal (congenital) period. As in adults with acquired unilateral lesions, both congenital lesion groups demonstrated poor performance on stimuli presented to the ear contralateral to the lesion. In overall performance on speech discrimination, however, the left-hemisphere congenital lesion group performed significantly better than the acquired-lesion group did. On complex-pitch discrimination, the right-hemisphere congenital lesion group performed significantly better than did the acquired-lesion group, but both left- and right-hemisphere congenital lesion groups were significantly worse at complex-pitch discrimination than were their age- and gender-matched normal controls. These results indicate that although congenital damage produces a "lesion effect" in dichotic listening similar to that after damage acquired in adulthood, overall function is relatively spared. To the extent that complex-pitch discrimination is affected by congenital damage to either hemisphere but speech discrimination is not, the present results are consistent with an asymmetric form of crowding during reorganization after congenital unilateral brain damage.


Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome?

We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to "strategic-infarct dementia."


Ictal head deviation: lateralizing significance of the pattern of head movement.

To resolve the controversy surrounding the lateralizing value of ictal head deviation, we analyzed head-turning movements in relation to the actions of the two divisions of the sternocleidomastoid muscle. In 12 (75%) of 16 patients with surgically confirmed lateralized seizure foci, the face rotated upward and contraversive to the hemisphere of seizure origin, consistent with activation of the ipsilateral sternomastoid muscle. One patient showed a sustained, downward ipsiversive head tilt consistent with the action of the ipsilateral cleidomastoid muscle, and three patients had a combined ipsiversive head tilt and contraversive face rotation. No patient exhibited ipsiversive upward face rotation or contraversive head tilting, as would be expected if the contralateral sternocleidomastoid were activated. Our findings indicate that hemispheric seizure foci activate one or both divisions of the ipsilateral sternocleidomastoid muscle. Accurate lateralization of the seizure focus is possible only when ictal head deviation is assessed in the context of the different actions of the sternomastoid and cleidomastoid muscle divisions.


Specific neurobehavioral profile of Williams' syndrome is associated with neocerebellar hemispheric preservation.

Previous work demonstrated enlargement of the neocerebellar vermis in Williams' syndrome (WS), despite diminished volumes in the cerebral hemispheres. We present the first in vivo volumetric study of any structure within the cerebellar hemispheres. Using MRI, we identified and reliably measured the neocerebellar tonsils in WS subjects; Down's syndrome (DS) subjects matched for age, IQ, and cerebral volume; and age-matched normal controls. WS tonsils were equal in size to control tonsils and larger than DS tonsils. In proportion to the cerebrum, WS tonsils were larger than controls'. These results coincide with the remarkable neuropsychological preservation of language and affect in WS, despite general cognitive impairment. They contrast with the neocerebellar vermal hypoplasia seen in autism, with its communicative and affective deficits. Additionally, two WS subjects showed Chiari type I malformations, but the average tonsillar position in WS was not found to be different than in controls.


Valproate acute administration, EEG epileptic abnormalities, and ammonemia.

Acute, oral administration of 14.3 to 37.5 mg/kg magnesium valproate (peak serum concentrations, 65 to 139 micrograms/ml) increases spike-wave frequency at 2, 3, 4, and 5 hours postdrug, in the absence of hyperammonemia or significant correlations with ammonemia fluctuations. This observation suggests a direct role of valproate on neural activity.


Amphotericin B-associated leukoencephalopathy.

We report instances of fatal leukoencephalopathy associated with the intravenous administration of the antifungal agent amphotericin B (AmB) to a 16-year-old girl treated for acute lymphoblastic leukemia and a 22-year-old man who underwent bone marrow transplantation for a myelodysplastic syndrome. Both received AmB in association with cranial irradiation and developed a subacutely evolving neurologic disorder characterized by personality change and confusion rapidly progressing to akinetic mutism. Neuroimaging studies disclosed diffuse nonenhancing abnormalities of the cerebral, particularly frontal, white matter that included hypodensity on CT and increased signal on T2-weighted MRI. Postmortem examinations demonstrated a diffuse, noninflammatory leukoencephalopathy with florid astrogliosis, demyelination, and infiltration of the hemispheric white matter by foamy macrophages. In neither case was there evidence of opportunistic infection or neoplastic infiltration of the nervous system. We review the evidence that polyene macrolide antibiotics such as AmB are potential leukotoxins.


Lateralization of human focal epilepsy by 31P magnetic resonance spectroscopic imaging.

We attempted to lateralize the epileptogenic focus (seven temporal lobe hippocampal foci, one frontal lobe focus) in medically refractory unilateral complex partial seizures, using noninvasive 31P magnetic resonance spectroscopic imaging (MRSI) blindly and interictally to compare hippocampal or frontal regions. The seizure foci were more alkaline (intracellular pH = 7.17 +/- 0.03) compared with the contralateral region (7.06 +/- 0.02, p < 0.01) in all eight cases; the inorganic phosphate was relatively increased (240 +/- 50% of contralateral, seven of eight cases, p < 0.01); and phosphomonoesters were relatively reduced (68 +/- 9% of contralateral, seven of eight cases, p < 0.01). Other phosphorus metabolites were symmetric (+/- 10%). 31P MRSI correctly lateralized the seizure focus in all eight cases. By comparison, imaging correctly lateralized four cases and SPECT, two cases. In conclusion, 31P MRSI is a useful tool for the noninvasive clinical assessment of focal epilepsy and can accurately lateralize the epileptogenic focus.


Amyloidoma of the CNS. I. Clinical and pathologic study.

We report a 32-year-old man with a 4-year history of headaches, seizures, and dementia secondary to multifocal amyloidomas in the white matter. Immunohistochemical and electron microscopic analyses suggest that the amyloidomas resulted from processing of plasma-cell-derived amyloidogenic protein by microglial cells.


Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type.

We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age-matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of the DNA duplication 17p11.2 in Charcot-Marie-Tooth neuropathy type 1 pedigrees: additional evidence for a third autosomal CMT1 locus.

We have restudied two clinically typical Charcot-Marie-Tooth neuropathy type 1 (CMT1; also known as hereditary motor and sensory neuropathy 1) pedigrees that were previously reported to be unlinked to the regions of proximal chromosome 1q and chromosome 17p by multipoint linkage analyses. In these two pedigrees, there is no evidence for linkage to additional DNA markers that flank and span the CMT1A locus on chromosome 17p11.2, and a duplication associated with CMT1A is not present in these pedigrees. These findings confirm that the CMT1 locus in these two pedigrees does not map to chromosome 17p11.2 or 1q, and provide further evidence for the existence of a third autosomal locus for CMT1.


The effect of exercise on levodopa absorption.

We studied the effect of exercise using cycle ergometry on levodopa absorption in ten patients with Parkinson's disease. Oral levodopa was administered during exercise and at rest on separate days. Exercise delayed levodopa absorption in five patients, increased it in three, and did not influence it in two. We conclude that exercise can either increase or decrease levodopa absorption.


Homozygosity for the transthyretin-Met30 gene in three Japanese siblings with type I familial amyloidotic polyneuropathy.

We report the cases of three siblings homozygous for a mutated transthyretin (TTR) gene that causes type I familial amyloidotic polyneuropathy (FAP), in whom we made the diagnosis by identifying both the mutated TTR gene and a variant TTR in their sera. Their serum levels for the variant TTR are twice those of patients heterozygous for the gene, but two have late-onset FAP and the third is an elderly asymptomatic carrier. TTR abnormality is a necessary condition for the development of FAP, but there may be other factors that retard or prevent its clinical development.


Hemodynamic and electrophysiological evaluation following extracranial/intracranial bypass surgery.

We examined 50 patients with an extracranial/intracranial bypass using transcranial Doppler blood flow mapping, somatosensory evoked potentials, and computer-assisted EEG analysis. The investigation was supplemented by temporary compression of the extracranial supplying vessel. Transcranial Doppler sonography revealed in addition to 4 patients with nonpatent anastomoses, a bypass-mediated retrograde flow in the ipsilateral middle cerebral artery beyond a depth of 40 mm in the majority of patients. In 9 patients, retrograde flow could be demonstrated in the whole proximal (M1) MCA segment. The precommunicating segment of the anterior cerebral artery (A1) could be reliably insonated in all but 5 patients. Bypass-compression dependent alterations in the SSEP and in EEG analysis were only observed in a small number of patients. Transcranial Doppler sonography, with the aid of the flow mapping system, appears therefore, to be a reliable and repeatedly performable noninvasive technique for the assessment of intracranial hemodynamics following bypass surgery.


Dermoid and epidermoid cysts of the midline in the posterior cranial fossa.

Clinical features and surgical outcome of 16 patients with dermoid or epidermoid cysts on the midline of the posterior cranial fossa are compared. Salient points in the comparison are the younger age, presence of associated malformations and better prognosis of dermoid cyst.


Spontaneous intracerebral hemorrhage.

We report on 146 patients with spontaneous intracerebral hemorrhage treated in the period between 1984 and 1988. The aim of this retrospective study was to point out factors for operative respectively conservative treatment. Looking for etiology, age, unconsciousness, localization and extension of hematoma as well as bleeding into the ventricles our results showed that patients over 70 years of age and/or in coma III and IV (Brussels Coma Scale) have a bad prognosis as well as patients with intraventricular bleeding. Patients seem to benefit from operation if hematoma is located in the hemisphere or cerebellar and the extension ranges from 3 to 5 cm.


Malignant tumors of the anterior cranial skull base.

Malignant tumors of the anterior cranial skull base are still a challenge for radical surgical treatment. Several different techniques and approaches have been developed over the years and the results, with mortality rates over 50%, are still not encouraging. Here we present our results of an interdisciplinary, one-stage, neurohino transfronto-transbasal surgical approach in twelve patients with such tumors. The long-term survival rate in our patients is now 83% with a mean postoperative follow-up of 19.3 months. Two patients died due to early recurrencies and metastasis after 10 and 13 months after initial treatment and postoperative irradiation. Another five patients with a follow-up of 34.2 months have had tumor recurrencies diagnosed at 19.5 months postoperatively. These patients have survived their recurrent tumor for 14.7 months. Five patients, 41% of the whole group, have been living without evidence of tumor recurrence for between 2 and 35 months.


The use of Nd:YAG laser in pituitary surgery and evaluation of visual function by visual evoked potential (VEP).

Surgery of pituitary tumors has been improved by microneurosurgical methods. However, despite improvements in surgical results, pituitary tumors still continue to represent a problem and, therefore, prompt a search for new surgical techniques. Since Nd:YAG laser energy penetrates the target tissue more deeply than other instruments, its use in the para- and suprasellar region should be considered. It is well known that Visual Evoked Potential (VEP) is a sensitive and objective method for the valuation of compressive or destructive lesions in or around the optic nerve. Visual function correlates with the latency and amplitude of P100 wave in VEP. We used the Nd:YAG laser in 50 transsphenoidal operations of pituitary adenomas. Postoperative effects of the laser on visual function was evaluated by conventional neurophthalmological tests as well as VEP and was compared with preoperative values. Following surgery using Nd:YAG laser, both conventional neurophthalmological tests and VEP values improved due to decompression of optic nerves by tumor removal. In this study, we also examined anterior lobe functions and found that Nd:YAG laser does not affect these functions. Our study shows that Nd:YAG laser has no harmful effects and seems to be very helpful especially for surgery for invading hormone-active adenomas.


Traumatic brain edema induced by ventricular puncture. A study by magnetic resonance imaging.

Magnetic resonance imaging demonstrates after ventricular catheterization a focal brain hypersignal corresponding to a parenchymal edema along the drain track. In the course of our daily clinical activity, this hypersignal extension seemed more pronounced when catheterizing the frontal area than the junctional parieto-temporo-occipital parenchyma (or trigonal area). In order to confirm this impression, we prospectively studied ten consecutive patients with normal pressure hydrocephalus in whom both of these brain regions were successively catheterized first by a frontal puncture for intracranial pressure monitoring and then by a trigonal one for a ventricular shunt. Each patient was evaluated by serial magnetic resonance imaging. The extension of the hypersignal induced by both catheterizations was estimated on a scale of five grades (0 to 4) of hypersignal extension. A statistically significant more important hypersignal extension was demonstrated at the level of frontal area when compared to the trigonal one. We discuss the likely underlying mechanisms of this phenomenon.


Neoplastic and reactive human astrocytes express interleukin-8 gene.

Expression of lymphokine genes in the human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and fresh brain specimens by PCR. mRNA transcripts for IL-8 were detected in all neuroglial cells. In addition to the cultured cells, we examined IL-8 gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The result shows that tumor and cells of the surrounding reactive lesion express IL-8 genes, but it is not expressed in normal brains. Next, the concentration of IL-8 in supernatants of cultured cells was measured quantitatively by a solid phase ELISA assay. IL-8 activity was produced constitutively in all astrocytomas and increased markedly upon stimulation with IL-1 beta or TNF alpha, in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived IL-8 may take part in neutrophil-mediated inflammation which accompanies infection, degeneration and malignancy in the brain.


The frontoorbital advancement--on the use of 3D-CT and the miniplate osteosynthesis.

Between 1987 and 1991 we performed a unilateral or bilateral frontoorbital advancement to correct trigono- or plagiocephaly in 10 children: Three-dimensional CT provides an exact basis for operation planning. Titanium miniplates allow an already primarily rather stable osteosynthesis. The best time for this intervention is the end of the third month of life.


Pneumosinus dilatans after prolonged cerebrospinal fluid shunting in young adults with cerebral hemiatrophy. A report of two cases and review of the literature.

Pneumosinus dilatans is a generalized or partial enlargement of the paranasal sinuses containing only air. Pneumosinus dilatans occurs as an idiopathic disorder as well as in association with other disorders, including cerebral hemiatrophy. We report two cases of patients with congenital cerebral hemiatrophy who developed juvenile pneumosinus dilatans of the frontal, ethmoidal, and sphenoidal sinus. The hydrocephalus of both patients was treated by prolonged cerebrospinal fluid shunting. The development of hyperpneumatization of the paranasal sinuses was proved by plain radiographs and CT. Previous reports of pneumosinus dilatans are reviewed, and the effect of prolonged cerebrospinal fluid shunting in our cases is discussed. Cerebrospinal fluid shunting during the period of physiological pneumatization of paranasal sinuses might have increased hyperpneumatization.


Primary Ewing's sarcoma of the skull: follow-up with bone scanning.

The authors report and discuss an extremely rare case of primary Ewing's sarcoma originating in the flat bones of the skull. The case was followed up by serial bone scanning during the postoperative period. A subclinical recurrence was detected as a focus at the original site 2.5 years after the first operation. Following a second operation and adjuvant chemotherapy the patient is still asymptomatic.


Metastasis of a renal carcinoma to a cerebellar haemangioblastoma in a case of von Hippel-Lindau disease.

A patient with Von Hippel-Lindau disease had a long-standing cerebellar cyst which recurred for the fifth time. At operation there was evidence of a renal carcinoma metastasis in the wall of the cyst which was probably a haemangioblastoma.


[Noninvasive evaluation of cardiac index and ejection fraction in ischemic heart disease. Comparison of thoracic bioimpedance, thermodilution and cineventriculography].

Aim of the study was to verify the reliability of thoracic bioimpedance cardiography (TEB) in detection, non-invasively, cardiac index (IC) and ejection fraction (FE), compared to simultaneous evaluation by invasive thermodilution (TD) in 39 patients with acute myocardial infarction in Killip class I-II (group I), and by cineventriculography (CVG) in 26 patients with chronic coronary artery disease in NYHA class I-II (group II). In order to define the reproducibility of TEB values, in the latter patients, the above mentioned parameters were evaluated 6 times more, running the first evaluation. The statistical analysis was performed by the linear regression test and the Student's "t" test and by the test of variance for the reproducibility evaluation. Results (mean +/- SD) were as follows: group I: TEB-IC 2.89 +/- 0.63; TD-IC 2.83 +/- 0.56 (1/min/m2); r = 0.68; p < 0.01. Group II: TEB-IC 2.88 +/- 0.71; CVG-IC 3.48 +/- 0.66; r = 0.77; p < 0.001; TEB-FE 57.7 +/- 6.8%; CVG-FE 58.1 +/- 13.7%; r = 0.40; p = ns. Results of the reproducibility referred to the 6 measurements (mean +/- SD) were the follows: TEB-IC (1/min/m2) (1) 2.83 +/- 0.76; (2) 2.85 +/- 0.73; (3) 2.8 +/- 0.79; (4) 2.83 +/- 0.71; (5) 2.87 +/- 0.81; (6) 2.88 +/- 0.8, p = ns, the variability was assesses within +/- 9.3%. TEB-FE (%): (1) 56.7 +/- 6.2; (2) 55.8 +/- 5; (3) 57.1 +/- 5.5; (4) 56.1 +/- 6.1; (5) 55.4 +/- 5.8; (6) 57.3 +/- 6.3, p = ns; the variability was assessed within +/- 9.1%. The analysis of the results showed a good correlation in the IC detection among TEB and the compared techniques, conversely TEB evaluation of FE appear of poor values in this kind of patients. Relatively to the results of the reproducibility this unquestionable characteristic of TEB was demonstrated.


[Hemostatic parameters in patients with type IIA and IV hyperlipoproteinemia].

In order to assess the interrelationships between the lipemic and the haemostatic balance the Authors studied the behaviour of some thrombotic markers in hyperlipemic subjects. The series consists of 35 subjects (15 m, 20 f, mean age 56 +/- 9 years) suffering from primary polygenic hyperlipoproteinemia of type IIA (23 cases) and type IV (12 cases) (cholesterol and triglyceride values exceeding respectively 250 and 180 mg%); 38 control subjects matched for sex, age and body weight were also examined; all the subjects were without hepato-renal and endocrine-metabolic disorders as well as without clinical signs of arteriosclerotic vasculopathy. For each subject the Authors performed the assay of the fasting plasma levels of total cholesterol (TC), triglycerides (TG) (enzymatic methods), fibrinogen (F) (coagulometric method), factor VII (coagulometric method) (F VII), antithrombin III (AT III) (chromogenic method), tissue activator of plasminogen (tPA), beta-thromboglobulin (BTG) and D-dimer (D-D) (ELISA method). The type IIA hypercholesterolemic subjects showed a not significant trend in a thrombophilic sense of the markers (increase of F, F VII, BTG and D-D, decrease of AT III); the type IV hypertriglyceridemic subjects exhibited a significant (0.05) increase of factor VII, BTG and D-D compared to the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


[Echocardiographic changes in patients with polycystic nephropathy].

We have studied with the echocardiography M-Mode, 2-D, Doppler three groups of 15 subjects for testing the presence of cardiac abnormalities probably related to primary collagen defect in patients with autosomal dominant polycystic kidney disease (ADPKD) The first group was made up of patients with ADPKD and normal renal function, the second of patients with ADPKD in hemodialysis (HD), the last one of patients in HD for other renal disease. In the first group we found no cardiovascular abnormalities while we found an increased incidence of valvular disease (p = 0.016) in patients with ADPKD in HD and an increased incidence in valvular disease (p = 0.016) and left atrial dilatation (p = 0.006) in patients in HD for different renal disease. When we estimated the cases on the ground of dialytic age uncorrelated with the initial renal disease, only the incidence of valvular calcifications was increased in patients on HD more than 3 years (p = 0.034). In our group of patients the echocardiographic abnormalities seem to be related more to uremic cardiomyopathy even if we cannot deny the existence of primary cardiac disease in patients with ADPKD.


[Antibiotic pretreatment of heart valve prostheses].

Bacterial endocarditis on cardiac valvular prosthesis is still a frequent and dangerous complication: septicemia, embolism, valvular dysfunction and mortality. To prevent these complications, intraoperative treatment of prosthesis, by immersion in antibiotic solution, was performed in 1262 patients. The postoperative results have been compared with results of a nontreated group. The incidence of endocarditis in the treated group was 1.3%, in non-treated cases 5.45%. The cases of early endocarditis, was 0.08% of total cases of complications in the treated patients group; and 4.54% in the nontreated patient group. This study's results, confirm the utility of valvular prosthesis antibiotic treatment in cardiac surgery.


[Abnormalities of the sensing function. Further contributions to the current classification].

With systemic unipolar pacemaker control by chest wall stimulation and interference we have obtained further data of the sensing function in more the 5000 clinical controls. A better classification of abnormal sensing function is important for a full electrocardiographic interpretation. We have established that the oversensing is always a primary evident or concealed phenomenon. Undersensing is a primary or secondary phenomenon provoked by a concealed oversensing in refractory period.


[Inter-electrode distance and atrial sensing. Our experience with atrial-guided pacing (VDD) in the biennium 1990-1991].

We implanted 47 Phymos VDD pacemakers (53.7% for complete atrioventricular block-42.57% for symptomatic lower heart block) in the 1990-91 period. In this series of cases with EDE 830-830S leads by means Holter technique we evaluated the atrial trigger. A high percentage of atrial sensing (97.8%) was found with 11 cm leads. The right atrial motion study is realized to explain the atrial sensing with floating leads.


[Iatrogenic torsade de pointes induced by thioridazine].

Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis. Traditionally, torsade de pointes has been described in association with a congenital or acquired (including drug and metabolic) causes of QT prolongation. Clinical outcomes range from asymptomatic, self-terminating arrhythmias to ventricular fibrillation resulting in cardiac arrest. For the treatment of torsade de pointes, the conventional antiarrhythmic drugs cannot be relied on, cardiac pacing should be instituted as soon as possible; however, as this technique may not always be immediately available, isoproterenol infusion may be the first-choice treatment. Potassium and magnesium repletion appear to be essential in abolishing drug-induced torsade de pointes. This report describes a case of thioridazine-induced torsade de pointes treated efficaciously with magnesium sulphate and overdrive right ventricular pacing.


[Gallbladder calculi: what therapy of choice?].

The Authors have analyzed all different methods for the treatment of gallbladder stones which are performed today: the non invasive treatment of the gallstones (oral dissolution therapy and the extracorporeal shockwave lithotripsy), the minimally invasive procedures (contact dissolution therapy and the cholecystolithotomy) and at the end the new surgical techniques (the "minicholecystectomy" and the laparoscopic cholecystectomy). From this study and their experience, based upon 1346 standard cholecystectomy, the Authors have reached the following conclusions: 1) the cholecystectomy remains the only definitive therapy for the gallbladder stones and it is the gold standard to which must be compared the other alternative therapies; 2) the laparoscopic cholecystectomy, even though introduced recently, would become the only method used for cholecystectomy.


[Diagnostic "gold standard" in cerebrovascular insufficiency. Comparison of angiographic and ultrasonic imaging].

The Authors consider the complex diagnostic problems of cerebrovascular disorders, with particular concern to angiography and echography. After a complete analysis of different aspects of angiographic and echographic lesions, considering their experience, they identify chances and limits of the two methods, they draw the conclusion that each of the two techniques has a proper role, and only a correct correlation between them can depict correctly the pathologic lesions.


[Tumor markers in colorectal cancer].

Over the past ten years numerous studies have been carried out to identify tumour markers able to diagnose cancer of the digestive tract. The paper reports the combined use of some markers (CEA, TPA, GICA, CA 125) in patients with carcinoma of the colon-rectum. The Authors conclude that although these markers are of little use, especially in association, in the early diagnosis of disease, it is very important to utilise these markers to monitor patients following surgical, chemotherapeutic or radiotherapeutic treatment.


[Role of endoscopy in the diagnosis and follow-up of bleeding lesions of the colon].

Considering the results of the centre of colonoscopy we can draw some considerations about the irreplaceable role of endoscopy in the diagnosis of bleeding colonic lesions and about its greater security in comparison with the traditional radiologic exam, about its possibilities to be sometimes resolutive even for the therapy and about its great importance in the follow-up of patients treated for lesions of this kind.


[Acute enterorrhagia. A diagnostic-therapeutic approach].

The Authors report their experience in cases of severe lower intestinal bleeding. On the basis of personal data and previously reported results, endoscopy is shown to be the primary and sometimes essential method, especially in the case of colo-rectal bleeding, both in terms of its diagnostic precision and possible therapeutic uses. This technique was used to treat all emergency cases, obtaining a diagnostic resolution in 85.6% and hemostasis and/or the concomitant removal of the lesion in 52.3% of cases.


[Squamous papillomas of the esophagus].

The paper reports 14 cases of squamous papilloma of the esophagus which were removed using an endoscopic method: this is a comparatively rare benign pathology of which an increasing number of cases have been recently observed. Endoscopic controls were carried out in all cases and the results of the follow-up are reported.