[The canine neuronal ceroid-lipofuscinosis: a review]. / Die neuronale Ceroid-Lipofuszinose beim Hund: Eine Übersicht.

The present article gives a survey over the current scientific knowledge of the canine neuronal ceroid-lipofuscinosis (NCL). NCL is a heterogenous group of lysosomal storage diseases in humans and animals. In consequence of a gene mutation, there is an accumulation of ceroid-lipofuscin in neurons, cells of the retina and the skin and other cells. The stored ceroid-lipofuscin in neurons leads to an impaired cell function and subsequently to cell death. Recently, the underlying genetic defect was discovered in several dog breeds. Genetic testing permits an ante mortem diagnosis of the disease, which up to now was only possible with a positive biopsy result. Another advantage is the identification of carrier animals to eliminate the deleterious alleles.

Le présent travail donne un aperçu ainsi qu'un résumé des connaissances actuelles sur la Céroïde-lipofuscinose neuronale (CLN) chez le chien. La CLN constitue un groupe hétérogène de maladies lysosomales chez l'homme et les animaux. Suite à une mutation génétique, il se produit une accumulation de céroïde-lipofuscine dans les cellules nerveuses, les cellules de la rétine, dans la peau ainsi que dans d'autres cellules du corps. L'accumulation de céroïde-lipofuscine dans les neurones conduit à une détérioration progressive de leurs fonctions et, finalement, à la mort de ces cellules. Le défaut génétique à l'origine de cette affection a été récemment identifié chez le quelques races de chiens. Des tests génétiques permettent de diagnostiquer la maladie sur des animaux vivants, ce qui n'était jusqu'alors possible que par biopsie. Il est en outre possible d'identifier les porteurs hétérozygotes et de les exclure de l'élevage.

Impact of COVID-19 pandemic on radiographers in the Republic of Cyprus. A questionnaire survey.

INTRODUCTION: Imaging is essential for the initial diagnosis and monitoring of the novel coronavirus, which emerged in Wuhan, China. This study aims to assess the insight of radiographers on how the COVID-19 pandemic has affected their work routine and if protective measures are applied. METHOD: A prospective observational study was conducted among radiographers registered in the Cyprus Society of Registered Radiologic Technologists & Radiation Therapy Technologists. A questionnaire composed of 28 multiple choice questions was utilised, and the data analysis was performed using SPSS software with the statistical significance assumed as p-value < 0.05. RESULTS: Out of 350 registered radiographers, 101 responses were received. The results showed that there are statistically significant differences regarding the working hours, the feeling of stress, the work effectiveness, the average examination time, the presence of a protocol used among the different workplaces of the participants; a private radiology centre, a private hospital or a public hospital, with a p-value 0.0022, 0.015, 0.027, 0.001, 0.0001 respectively. Also, statistically significant differences were observed in the decontamination methods used for equipment (p-value 0.007), for air (p-value 0.04) and when decontamination takes place (p-value 0.00032) among the different workplaces of the participants. Nonetheless, the majority of radiographers believe that their workplace is sufficiently provided with PPE, cleaning supplies, equipment, and with cleaning personnel and are optimistic regarding the adequacy of these provisions in the next three months. CONCLUSION: This study showed that in the Republic of Cyprus, there are protocols regarding protective measures against COVID-19, and the radiographers are adequately trained on how to face an infectious disease outbreak. However, work is needed in order to develop protocols that reassure the safety of patients and medical personnel while managing the excess workload effectively. IMPLICATIONS FOR PRACTICE: This study indicates the importance of applying protective measures and protocols in the radiology departments in order to minimise the spread of the virus.

Assessing radiation protection knowledge in diagnostic radiography in the Republic of Cyprus. A questionnaire survey.

INTRODUCTION: Radiation protection knowledge is essential for medical personnel in ensuring that the possible risks do not outweigh the benefits of diagnostic imaging. This study aimed to assess the radiation protection knowledge of radiographers in Cyprus. METHODS: A cross-sectional study was carried out among radiographers in Cyprus through the Cyprus Society of Registered Radiologic Technologists & Radiation Therapy Technologists. The study was a quantitative descriptive analysis, using a questionnaire with 22 multiple-choice questions. Analysis of the data was done using the statistical software Stata, by performing mean knowledge score comparisons by different participants' characteristics, using t-test and analysis of variance test. Statistical significance was assumed as a p-value < 0.05. RESULTS: The answers provided for each question indicate that some areas of radiation protection are less known compared to others, as there is quite a wide range of correct-to-incorrect ratios. The analysis based on participant characteristics in relation to overall radiation effects knowledge, identified important determinants, namely the workplace of the participant (p = 0.006), the type of work licence the participant held at the time of the questionnaire (p = 0.024), and the years of clinical experience of the participant (p = 0.021). CONCLUSION: The study showed that the levels of knowledge in radiation protection are of a very good standard. However, work is needed to clarify the specifics of dose limits and the national radiation protection legislation with regards to informing patients about the possible effects of ionising radiation. IMPLICATIONS FOR PRACTICE: The study results indicate the importance of educating radiographers about the requirements of national radiation protection legislation and how this new knowledge can be linked with practise.

Congenital cervical kyphosis in two young sighthounds.

INTRODUCTION: Cervical vertebral (C) malformation is rarely reported in large breed dogs. Congenital cervical kyphosis (CCK) may result from defects of vertebral segmentation, failure of formation or both. This report describes two cases of C3-C4 CCK in young sighthounds, treated surgically. CASE DESCRIPTION: An 18-month-old female Deerhound and a six-week-old female Borzoi dog were presented because of the complaints of reluctance to exercise and signs of of neck pain. Both dogs were neurologically normal. Diagnostic imaging revealed C3-C4 deformity, moderate kyphosis, and spinal canal stenosis associated with chronic spinal cord pressure atrophy. Both dogs underwent surgical treatment. RESULTS: A staged two-step surgery starting with dorsal decompression was elected in the Deerhound. After the first surgical procedure, the dog developed focal myelomalacia and phrenic nerve paralysis and was euthanatized. A ventral distraction-fusion technique with two locking plates was performed in the Borzoi. This patient recovered uneventfully and long-term follow-up computed tomography revealed complete spondylodesis. CLINICAL SIGNIFICANCE: Until now, CCK has only been described in sighthounds. Congenital cervical kyphosis might be considered a differential diagnosis in these breeds that are presented with signs of cervical pain. Ventral realignment-fusion and bone grafting may be considered for surgical treatment, although the earliest age at which this procedure can and should be performed remains unclear.

Herpes simplex virus encephalitis: new diagnostic and clinical features and results of therapy.

Six patients with herpes simplex virus (HSV) encephalitis underwent diagnostic and clinical evaluation. The HSV or its antigenic material was found in three brain biopsy specimens. In the remaining three cases, the diagnosis was supported by detection of HSV antibodies in the CSF. Cell count and total protein concentration in the CSF reached a maximum level at three weeks and two months, respectively. The IgG index and HSV antibody level in the CSF often remained constant after reaching maximal values. In three patients, a transient low serum sodium level was observed. Characteristic EEG changes were present five to 11 days after the onset of symptoms. Computerized tomographic scanning revealed a temporal low-density lesion. Three patients became deeply comatose and had respiratory failure. The patient without vidarabine therapy and one of the five patients treated with vidarabine died.

Influence of rearing conditions on the acquisition of the two-way active avoidance responses by rats septalectomized at an early age.

When performed in the adult 3-month old rat, septal lesions facilitated the acquisition of a two-way active avoidance (AA) task as compared to animals sham-operated at the same age. When performed in the 7-day-old rat pup, the same lesion also clearly facilitated the 2-way AA acquisition by the rats when adult and, more especially so, when the rats were isolation-reared from weaning. The performances of these early-septal rats reared in isolation did not differ from those of rats septalectomized at adult age, while the performances of the early-septal rats that had been group-reared from weaning proved to be lower than that of adult-operated rats, with regard to both number of shocks avoided and mean response latencies in the initial phase of acquisition. The improvement of the 2-way AA acquisition following septal lesion may result from an increased responsiveness to aversive stimulation and this responsiveness may be enhanced if the early-septal rats are reared in isolation from weaning.

Flight induced by microinjection of D-tubocurarine or alpha-bungarotoxin into medial hypothalamus or periaqueductal gray matter: cholinergic or GABAergic mediation?

Microinjections of various doses (50-300 ng) of the nicotinic antagonist D-tubocurarine (TUBO) into the rat's medial hypothalamus (MH) or dorsal periaqueductal gray (PAG) produced flight reactions characterized by jumps. Two different types of flight reactions were produced depending on whether the drug was injected into the MH or into the PAG. MH injections provoked an increase in both locomotor activity and rearing together with well-oriented jumps. PAG injections provoked either freezing reactions or running with explosive jumps, but no increase in rearing. In addition, the rat exhibited an asymmetry in responsiveness to tactile stimulation. These reactions also differed depending on whether the drug was injected into the dorsal or ventral PAG. Behavioral reactions similar to those produced by TUBO were also produced by microinjection of the GABA receptor antagonist bicuculline into the same brain sites. Among the 4 putative cholinergic antagonists tested under the same conditions only alpha-bungarotoxin produced effects that were qualitatively similar to those induced by D-tubocurarine or bicuculline. Gallamine and hemicholinium produced tremor when injected into sites located near the ventricular system at either the MH or the PAG level, while vocalizations were only produced by PAG injections. Hexamethonium produced no marked effect. The hypothesis that flight reactions induced by D-tubocurarine or alpha-bungarotoxin do not result from their antinicotinic action but rather from a direct effect on GABAergic transmission is discussed.

Escape and approach induced by brain stimulation: a parametric analysis.

The study reported pursued two general aims: (a) to find out whether a brain-stimulation-induced escape response results from the bringing into play of similar mechanisms irrespective of whether the stimulation is applied to a site located in the mesencephalic central gray (CG), in the medial hypothalamus (MH) or in the lateral hypothalamus (LH); and (b) to verify whether escape and approach that can be induced by stimulating one and the same hypothalamic site result from a combined activation of two distinct neuronal systems, by means of specifying some of their functional characteristics that would possibly allow differentiation between them. Three experiments were carried out using a situation (shuttle-box) that allowed the measurement, for each given brain site, of both the time for which the rat underwent the stimulation before interrupting it (stimulation time, st., corresponding to an escape latency) and the time for which the animal remained non-stimulated before eventually restarting the stimulation himself (non-stimulation time, nst, corresponding to an approach latency). The following stimulation parameters were varied: the pulse duration (D), the stimulation intensity (I) and the interpulse interval (IPI = 1/stimulation frequency), i.e. the time interval that separated the beginning of a stimulating pulse from the beginning of the next one. The results obtained suggest the following. (1) Some of the mechanisms implicated in the elaboration of an escape response are similar irrespective of whether escape is induced by stimulating a site located in the CG, in the MH or in the LH.

Unit activity alterations induced in the mesencephalic periaqueductal gray by local electrical stimulation.

In the framework of a series of investigations concerning the neural substrate of aversion, electrophysiological methods were used in order to specify, within the rat's periaqueductal gray (PAG), functional properties, viz. conduction velocity and refractory period, of PAG neurons already assessed in previous studies by means of behavioral methods, and to gather data on their local synaptic relationships. Unit activities were recorded from the periaqueductal gray with the aim of analyzing those alterations that would be induced by locally applying an electrical stimulation with parameters shown to elicit escape behavior. An implanted row of electrodes allowed the application of a stimulation to several sites aligned along a mediolateral or a rostrocaudal axis through the periaqueductal gray. The results indicate that an electrical stimulation applied to the periaqueductal gray may induce its effects through the activation of a number of dendrites and many slow conducting fibers running in a great variety of directions and branching within the periaqueductal gray. Their refractory period was surprisingly low (0.6 ms) for slow conducting fibers (below 1 m/s). The local circuitry appears to include many inhibitory connections. Their organization is assumed to be partly recurrent. Stimulation-induced inhibition becomes predominant when the stimulation is moved away from the recorded neuron along the mediolateral axis, but not along the rostrocaudal axis.

Morphine injected into the periaqueductal gray attenuates brain stimulation-induced effects: an intensity discrimination study.

A discrimination situation was used to study the effects of morphine microinjected into the periaqueductal gray (PAG) on the aversive effects induced by PAG or medial hypothalamic (MH) electrical stimulation. Rats were trained in a T-maze to interrupt a high intensity (HI) stimulation inducing a short escape latency by pressing the lever (HI lever) located in one arm of the maze and a low intensity (LI) stimulation inducing a longer escape latency by pressing the lever (LI lever) located in the other arm. Microinjections of 15 nmol (5 micrograms) or 40 nmol (13 micrograms) of morphine both lengthened the escape latencies and shifted towards the LI lever the animal's choice in order to interrupt HI stimulations. This effect of morphine showed a similar time course as regards both escape latency and lever choice; it was more marked on PAG than on MH stimulation-induced aversive effects. The data are discussed in terms of morphine microinjections into PAG lengthening the escape latency by decreasing the aversiveness of PAG or MH stimulation rather than by affecting the animals' ability to respond to such stimulations.

Central gray and medial hypothalamic stimulation: correlation between escape behavior and unit activity.

A chronic experiment and an acute one were carried out in the same rat in order to get information on the neuronal events correlated with the escape latency (EL) induced by an electrical stimulation in the mesencephalic central gray (CG) or in the medial hypothalamus (MH). Escape latencies as well as unitary MH and CG neuronal responses (104 units in 25 rats) were studied as functions of the intensity and the pulse duration of a 50 pulses/sec stimulation train. The CG and/or the MH neuronal firing rate was either synchronized or diffusely altered, either inhibited or activated, by the CG or the MH stimulations. Many neuronal firing rate alterations were highly correlated with the escape speed (ES = 1/EL) induced by the same stimulation. Intensity duration trade-off functions were computed from both the EL and the unit recordings. Chronaxie determinations were performed from these data: the behaviorally determined chronaxies did not differ from the unitary ones (limit values: 0.05-0.42 msec). The discussion bear on the possible role of the observed neuronal alterations induced by CG or MH stimulations in relation to their behavioral effects.

Flight induced by infusion of bicuculline methiodide into periventricular structures.

Microinjections of different doses of bicuculline methiodide (BM) were performed into the mesencephalic central gray (CG), the medial hypothalamus (MH) and lateral hypothalamus (LH). Flight reactions could be induced by microinjections of BM into either the CG or the MH. However, the type of flight behavior was different whether the injection was made in the CG or the MH. Furthermore, microinjections of 35 ng of BM in either structure produced an increase in locomotor activity whose time course differed according to the injected structure, and an increase in rearings was induced at MH but not at CG sites. At lateral hypothalamic sites, BM produced an increase in locomotor activity and rearings but no jump. These effects were antagonized in a dose-dependent manner by a local pretreatment with 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), a GABA agonist. These results suggest that (1) at the level of both the MH and the CG, a GABAergic link is involved in the inhibition of a substrate whose activation produces aversive effects, and (2) the aversive effect induced by CG BM microinjection seems to be different from that induced by MH BM microinjection.

Distribution of GABA in the periaqueductal gray matter. Effects of medial hypothalamic lesions.

Gas chromatography and chemical ionization mass spectrometry were used in order to measure the GABA (gamma-aminobutyric acid) concentration in a series of successive horizontal slices of the mesencephalic periaqueductal gray (CG) as well as in a series of successive frontal CG slices in the rat. Along the dorso-ventral axis, the GABA concentration (3.5-7 microgram/mg protein) was found first to increase and then to decrease, a maximum concentration being found at the level of the aqueduct. In contrast, no concentration gradient was found along the caudo-rostral axis. In an additional experiment, the medial hypothalamus (MH) was lesioned on one side and the effect of such a unilateral MH lesion on the caudo-rostral distribution of GABA was investigated. Fifteen days after performing the lesion, a graded decrease in GABA concentration--with a maximum in the rostral CG--was found to occur mainly on the lesioned side.

Behavioral effects of microinjections of SR 95103, a new GABA-A antagonist, into the medial hypothalamus or the mesencephalic central gray.

The behavioral effects of unilateral microinjections of SR 95103, a new GABA-A receptor antagonist, into periventricular structures were studied. When injected into the medial hypothalamus (MH) or into the dorsal part of the mesencephalic central gray (CG), SR 95103 produced a dose-dependent behavioral activation together with jumps. However, the characteristics of this behavioral activation differed according to whether SR 95103 was injected into the MH or into the CG. The behavioral activation was found to be attenuated by pretreatment with THIP, a GABA receptor agonist. When injected into the CG or into the deep layers of the superior colliculus, SR 95103 proved to affect the rat's reactivity to tactile stimuli as evidenced by ipsilateral 'neglect' combined with contralateral hyperreactivity expressed as withdrawal reactions and jumping. Similar results were obtained following microinjections of bicuculline methiodide at the same sites. These data confirm that in both the MH and the CG, GABA-A receptors are involved in the neural control of the generation and/or expression of aversive effects. The data further suggest that at the level of the CG and the deep layers of the superior colliculus, GABA is also involved in the gating of sensory information towards the substrate underlying the generation of such aversive effects.

High-energy phosphate compounds in slow-twitch and fast-twitch muscle fibres. Changes during exercise in some neuromuscular diseases.

Concentrations of the high-energy phosphates, ATP and creatine phosphate, were investigated in slow-twitch (ST) and fast-twitch (FT) muscle fibres of patients with myotonia congenita (n = 6), dystrophia myotonica (n = 5), myopathia ocularis (n = 2) and hyperornithinemia with gyrate atrophy (HOGA) (n = 3) and compared with those of normal subjects (n = 4). At rest, the patients with HOGA had lower values of ATP in ST muscle fibres than the controls (P less than 0.05). They also had lower values of creatine phosphate in these fibres than the patients with dystrophia myotonica (P less than 0.03) and myotonia congenita (P less than 0.05). After 30 s bicycle ergometer exercises there was an increase in ATP in the ST muscle fibres of the patients with myotonia congenita, but in all other patient groups there was a decrease.

Erythrocyte flexibility, ATPase activities and Ca efflux in patients with Duchenne muscular dystrophy, myotonic muscular dystrophy and congenital myotonia.

Erythrocyte flexibility measured by a polycarbonate membrane filtration method showed increased fragility (265 +/- 163 Hb mg/l vs. controls 86 +/- 72 Hb mg/l; mean +/- SD; P less than 0.0025) and increased rigidity (123 +/- 96 mm Hg vs. 79 +/- 19 mm Hg; P less than 0.05) in patients with congenital myotonia, while both parameters were normal in patients with Duchenne muscular dystrophy or with myotonic dystrophy. Erythrocyte ghosts obtained from patients with MyD displayed highly significant increases in both (Na+ + K+)-ATPase and (Ca2+ + Mg2+)-ATPase activities (P less than 0.005) and to a lesser extent in Mg2+-ATPase activity (P less than 0.05), while no difference was seen between patients with DMD and age-matched controls. The efflux of Ca2+ was increased from erythrocytes of patients with DMD as compared to age-matched controls (82 +/- 2% vs. 70 +/- 4%; P less than 0.005), while no difference was detected between patients with MyD and age-matched controls.

Ambulatory electrocardiographic recording in mild or moderate myotonic dystrophy and myotonia congenita (Thomsen's disease).

Ambulatory electrocardiographic recording (AER) was performed on 27 adult patients with mild or moderate myotonic dystrophy (MD) and in 12 adult patients with mild myotonia congenita (MC) to determine whether characteristic arrhythmias and conduction disturbances occur in the early stages of these myotonic disorders. In MD and MC, AER showed at least one finding regarded as normal in 93% and 0% of cases, respectively. The most common abnormalities in MD were first degree atrioventricular (A-V) block (in 70% of cases) and QTc greater than or equal to 0.46 s (in 33%). Abnormal sinus intervals and frequent second degree A-V block were rare, each occurring in 4% of patients. Ventricular tachycardia did not occur. It is concluded that signs of involvement of cardiac conductive tissue in the MD disease process are very common, even in the early stages. Delayed A-V conduction in the most common single finding. Sinus nodal dysfunction, severe disturbances in A-V conduction, and ventricular arrhythmias are not common in mild disease. Repeated AER is indicated, to evaluate whether conduction disturbances in MD are progressing.

Interactions between aversive and rewarding effects of hypothalamic stimulations.

Interactions between aversive and rewarding effects of brain stimulations were studied by assessing the variation of both escape and approach responses induced in a shuttle box by applying electrical stimulations of various intensities simultaneously to a medial hypothalamic (MH) site and to a lateral hypothalamic (LH) site. The results obtained show that: (1) LH stimulation produces two effects whose relative strengths appear to depend on both the location of the stimulation site and the intensity applied: (a) a suppressant effect correlated with the rewarding effect, which reduces MH escape responding; and (b) an enhancing effect correlated with the aversive effect, which increases MH escape responding. (2) MH stimulation similarly produces two effects whose relative strengths vary with both the location of the stimulation site and the intensity applied: (a) an enhancing effect which increases LH approach responding and (b) a suppressant effect which decreases LH approach responding. (3) The above-mentioned effects occur irrespective of whether the two stimulation sites (MH and LH) are ipsi- or contralateral to each other. These results suggest that the effects of LH stimulation on MH induced escape as well as those of MH stimulation on LH induced approach are related to the affective (aversive, rewarding) properties of the stimulation.

Mapping of jumping, rearing, squealing and switch-off behaviors elicited by periaqueductal gray stimulation in the rat.

Rats readily learn to escape from a stimulation applied to most mesencephalic periaqueductal gray (PAG) sites. In the present study, we tried to find out to what extent the differential effects induced by such stimulations actually reflect the existence of intraPAG functional subdivisions. To that end, a row of five electrodes was implanted into the PAG of each of 29 rats. Two kinds of effects were analyzed, the stimulation-elicited overt behaviors and the generalization of switch-off responding from one stimulation site to the others. Further, switch-off latency versus interpulse interval (IPI) relationships were established and both the threshold IPIs and the ceiling switch-off latencies were determined. The most commonly elicited behaviors (jumping, rearing and squealing) as well as the threshold IPIs and the ceiling switch-off latencies were mapped within the PAG. Switch-off behavior was elicited from all the stimulation sites studied. However, in the dorsal PAG the switch-off latency was found to decrease more steeply with decreasing IPI than it did in the ventral PAG. Switch-off generalization was less frequently observed between dorsally located stimulation sites. Jumps were most often elicited from dorsally and rostrally located PAG sites while squeals were more frequently elicited from the caudal part of the PAG and rearings from PAG subareas surrounding the aqueduct.

Effect of medial hypothalamic stimulation inducing both escape and approach on unit activity in rat mesencephalon.

The activity of central gray (CG) neurons was previously shown to be affected by medial hypothalamic (MH) stimulation, and the discharge rate alterations were found to be often closely correlated with the vigor of the stimulation-induced escape responses. Since MH stimulation induces not only escape responses but also approach responses, this allowed a further investigation of the degree of specificity of the correlation between stimulation-induced neuronal activity and escape responses. Out of 129 CG units studied (in 39 rats), 26 clearly responded to the MH stimulation. When the stimulation parameters were varied, the mean discharge rate alterations of 9 units located in the dorsal part of the mesencephalic CG proved to be closely correlated exclusively with the alterations that affected the stimulation-induced escape responses. Furthermore, the variation of the most frequent interspike interval (modal ISI) proved to be closely correlated with the variation of the escape response in 3 instances in which the mean discharge rate showed no such correlation. In a few instances (2 units located much more ventrally, the spike rate alterations were closely correlated only with the alterations that affected the approach responses. It is suggested that neuronal activity in the dorsal part of the CG is rather specifically implicated in the generation of MH stimulation-induced aversive effects and escape responses.