Biomedical subjects
Publications and source records attributed to V Susić.
Investigations with dihydroergotoxine (DHE 1.0; 3.0 and 5.0 mg/kg i.p.) indicate that DHE exerts effect on the sleep-wakefulness cycle of the cat. In doses of 3.0 and 5.0 mg/kg i.p. DHE has a suppressant effect on sleep, and in particular on REM sleep, while wakefulness was increased. With a dose of 1.0 mg/kg, wakefulness and REM sleep were decreased, while slow-wave sleep was increased.
A study was made of brain nucleotides and glycolytic intermediates in paradoxical sleep (PS)-deprived and recovery-sleeping rats. It was observed that PS deprivation of 24 h produced a fall in glucose, glucose 6-phosphate and pyruvate in cerebral frontal lobes. After three hours of recovery sleep all values returned toward their predeprivational levels. In cerebellar hemispheres ATP was increased, while glucose 6-phosphate and pyruvate were decreased. After three hours of recovery sleep, glucose 6-phosphate was increased and pyruvate decreased, indicating restoration of glycogen and creatine phosphate respectively.
This study examined the effects of clozapine on sleep-wakefulness profile in cats prepared for chronic recording of sleep. Clozapine in single dose (i.p.) of 5 mg/kg drastically reduced slow-wave sleep (SWS) and paradoxical sleep (PS), while wakefulness and drowsy pattern were increased. These changes lasted approximately 24 h and were followed by sleep recovery. PS had a priority of recovery. Some similarities between clozapine effects on sleep in cat and human were mentioned.
The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.
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INTRODUCTION: Audiogenic seizures (AGS) are induced by high intensity sound stimulation in genetically susceptible rats or in animals subjected to chemical or electrical manipulation. Epileptic seizure may result from an impaired balance between excitation and inhibition in the CNS. The effect of NMDA (N-methyl-D-aspartic acid) on metaphit 1-(1(3-isothiocyanatophenyl-ciclohexyl)-piperidine) induced audiogenic seizures was evaluated in rats. METHODS: Male Wistar albino rats were divided into 4 groups: 1) saline; 2) metaphit (10 mg/kg); 3) metaphit + NMDA; 4) NMDA (70 mg/kg). Animals were injected with metaphit intraperitoneally (i.p.) and exposed to sound stimulation (100 +/- 3 dB, 60 s) at hourly intervals. The incidence and severity (running, clonus and tonus) of seizures were analyzed. NMDA alone was administered i.p. to 6 rats. In group metaphit + NMDA only animals which did not exhibit any seizure during 8 hours were injected with NMDA i.p. after the 8th audiogenic testing. For electroencephalograph (EEG) recordings three gold-plated screws were used. Convulsive behaviour was assessed by incidence of motor seizure and by seizure severity grade, determined by use of a descriptive rating scale with range of 0-3; 0-no response; 1-wild running only; 2-wild running followed by clonic seizures of all four limbs with body rollover; 3-wild running progressing to generalized clonic convulsions and then a tonic extension of the fore and hind limbs and tail. Sound onset, seizure events, and sound offset, along with the animals behaviour (convulsive or other) were recorded as the correlates to the respective EEG responses. RESULTS: In most animals the administration of metaphit (10 mg/kg) resulted in electrographic abnormalities, elicited epileptiform activity in the form of spikes, polyspikes and spikewave complexes (Fig. 1.). Maximum incidence and severity of metaphit convulsions occurred 8 h after the injection (9/12, 75%) (Fig. 2, 3.), then abated gradually and disappeared 30 h later. NMDA (70 mg/kg) alone induced no seizure response but isolated spiking activity, and sporadic slow-wave complexes were recorded (Fig. 4). NMDA induced stereotyped behaviour in the form of asymmetric posture, loss of righting reflex and tonic hindlimb extension, which lasted for 60-90 min. Subconvulsive dose of NMDA potentiated the metaphit-induced audiogenic seizures in rats. Two hours after NMDA administration 3 of 17 metaphit-treated rats convulsed, which in 8 previous testings never displayed seizures. Maximum incidence was 8 of 17 (53%), 5-6 h after NMDA administration and seizures lasted for 9 hours. DISCUSSION: Several authors reported that metaphit dose of 10 mg/kg accompanied by some REM sleep deprivation (REM-D) procedures [4], or subconvulsive doses of NMDA [25] provoked seizures of higher intensity and incidence. Metaphit treatment (10 mg/kg) followed 24 h later by NMDA dose of 50 mg/kg provoked no spontaneous convulsions, while metaphit in combination with a higher NMDA dose of 70 mg/kg resulted in spontaneous and AGS-induced seizures only in one time point [25]. It was found that the incidence and severity of convulsive responses were highest 8-12 h after metaphit injection (10 mg/kg) [23, 24]. Although about 8 h after metaphit administration the power spectra increased and were more intense in the period of sound onset and seizure events. CONCLUSION: The results of the present study strongly suggest that treatment of adult rats with the combination of metaphit and NMDA in the doses employed here followed by AGS provides a suitable animal model for examinations of epileptic seizures.
From a historic point of view, epilepsy and its eponyms were in an ontogenetic symbiosis throughout their history. Epilepsy is a disease with a history of eponyms presenting the frame of mind of both streetwise as well as skilled "authors" about its origin and nature. From ancient times the names for epilepsy, archetypal Hippocratic disease, just as rich in number as varied in their implication, reflected the local folkways of thinking. In this article we briefly presented more than 50 eponyms and patrons of epilepsy. As the source of information we used both the apocryphal, canonical and hagiographic as well as heretic literature, legends and iconography from the Middle Ages of domestic and foreign origin. Pre- and post-Hippocratic era, apart from stemming from the oldest written medical sources, point to the position that the disease had organic origin located in the brain. The period of Rome adopted the attitudes set by Galen which remained en vogue throughout the emerging Middle Ages and Renaissance. These eras generated new eponyms which reflected a downfall in the manor, stating that the disease is the consequence of supernatural forces. In the "Age of darkness" eponyms for epilepsy reflected more the relation of men to the Nature than to the disease or a sick man; this is evidenced through the generation of number of patrons for the disease. The most famous patron of patients with epilepsy was St. Valentine (after conversion from pagandom he died in Rome as a martyr, c. 270). He was allotted a patronage either due to the phonic resemblance of his name with the (past participle of the) verb "fallen"-as Martin Luther claimed, or due to a cure of epilepsy of the son of a Roman rhetor who built for him a chapel in which he continued to cure the sick. The emergence of a flamboyant personality of Paracelsus on the historic scene of the XVI century represents a less successful attempt to revoke the way of thinking set by the old Greek doctors; however, it brought about the precipitous decay of attitudes that started with Romans and inaugurated the way of thinking characteristic of Renaissance and the ages thereafter. Serbian literature of the Middle Age was strongly impacted by influences that fanned from Italy (Salerno) and south France (Montpellier), reflecting the attitudes of medical schools and universities prevailing at that time Europe. The name [symbol: see text] from Hilandar Medical Codex No 517 (XV-XVI century) is obviously taken from Byzantine medicine, which was founded on the works of Hippocrates, Galen and Dioscurides. It came down to us through the Serbian folk Byzantine codices named "latrosophia of Hilandar", preserved mostly from the author Michail Pselos (XI century). On the other hand, the name [symbol: see text] or morbus magnus, reflects its Roman origin. The name [symbol: see text] meaning fainting, loss of consciousness or syncope, stems from the same source. The name [symbol: see text] designated epileptic disease in Serbian monks, monasteries probably being the only niche where epileptics could find refuge. Children's epilepsy or convulsions are expressed as [symbol: see text] No mention is found of epileptic status except for the notion [symbol: see text] meaning "to be without consciousness for a longer period of time'; it does not, however, refer directly to epilepsy or convulsions. It is worthy noting that already in the XIV century Serbs had their medical literature translated to their own language, and were the only one of all Slavic peoples that did so. Nevertheless, both apocryphal and canonical, as well as consecrated medicine were based on magic, astrology and occultism. The magic formulas used in Middle Age Serbia for the cure of epileptics as well as sick in general, were basically irrational; still, as a trace of its descension they contained unintelligible words of the eastern origin (Greek, Persian or Jewish). (ABSTRACT TRUNCATED)
The history of eponyms for epilepsy in the lands of the Eastern globe present the portrait of the attitudes of both the laymen and skilled people towards the disease and patient, as well as to the Nature itself. As opposed to the West which during the Middle ages changed its concepts of epilepsy as the organic brain disease for the sublime 'alchemic' position, the people of the East were more prone to consider from the beginning of their civilization till the XIX century that epilepsy is the consequence of the evanescent spiritual and extracorporal forces which by themselves were out of their reach. As compared to the western civilization, the historical resources are, often as a consequence of a linguistic barriers, more scarce-as consequently is the number of eponyms, but are nevertheless picturesque. The medical science from Babylonian period presumed that epileptic manifestations are the consequence of the demonic or ill spiritual actions. There existed an attitude that at the beginning of an epileptic attack the patient was possessed by a demon (the Akkadic, i.e., Babylonian verb "sibtu" denoting epilepsy, had the meaning "to seize" or "to be obsessed"); at the end of the clonic phase the demon departed from the body. Different demons were responsible for different forms of epilepsy such as nocturnal and children epilepsy, absence epilepsy and pure convulsions, simple and complex automatisms, and gelastic epilepsy. Thus, the doctors from the period of Babylon aside from making primordial classification of epilepsies, knew about their clinical picture (prodromal symptoms and aura, Jackson's epilepsy. Todd's paralysis), postictal phenomena and intericatl emotional instability; provocative factors were also known (sleep deprivation, emotions, as well as alcohol, albeit in a negative sense-as a cure for epilepsy). There is no doubt than in the period of Babylon the clinical picture of serial fits and its progress to status epilepticus were clearly recognized and considered as life threatening events. Persian history of epilepsy, except from the 6th century Zoroastrian "Avesta" document, lacks the written or spoken medical heritage untill the 7th century A.D. and the Arabic conquest of the entire Moslem world. On the other hand, Islamic medicine should be freed from the simple prejudice that the Moslem authors were only the translators of Greek medicine; contrary to such a view, their work contains a high degree of individuality. Although Mohammed introduced a lot of novelty into medicine, Khoran and the Sayings do not explicitly refer to epilepsy. Of importance is to notice that Moslem medicine did not have demons in the "repertoire" of direct causes of epilepsy. The causes and the cures of epilepsy were more magic-mystical and occult in nature, which is reminiscent of the European, as well as Serbian Middle age attitudes. Avicenna recognized difference between children and adult epilepsy. He considered insomnia and afternoon siesta as well as intensive sounds and light to be a provocative factors, whereby we see that at least empirically he knew of sleep (deprivation), startle and reflex epilepsy. The XIII century invasion of Mongols brought about the recession in Moslem Medicine; it recovered only in the XVIII century under the strong influence of European medicine handed over to us through Jewish doctors of various nationalities. The story of the China history of epilepsy has its debut approximately in the 8th century B. C. Medical texts from this period name epilepsy "Dian" and "Xian" which meant "the falling sickness" and "convulsions", respectively. Chinese medical terminology often interchangeably used the words "mania", "madness" and "psychosis" for "epilepsy" which, aside from a prominent language barrier, brings additional confusion. Although Chinese documents gave the first description of the grand mal epileptic attack already in the 8th century B. C. (ABSTRACT TRUNCATED)
With this brief review we honor the memory of the great French doctor Jean Baptiste Edouard Gélineau. Dr. Gélineau was born on December 23, 1828 at Blaye, Gironde, close to the Bordeaux region. His name is connected with the first clinical description of the disease for which he, both by the right of the primacy as well as ad valorem of his first two names, coined the name "narcolepsy". He was the first to notice the intrinsically evanescent symptoms of narcolepsy, such as excessive daytime somnolence, imperative sleep habits and cataplexy or "astasia" as he called it, and incorporate them into a single clinical syndrome. In 1881 Gélineau discussed Kaffe's case of "maladie du sommeil" as a proof of the existence of the new disease described a year before. As a good clinical observer Gélineau noticed the close relation of emotional engagement and astasia. His attitude was that narcolepsy was a nosologic entity, a disease sui generis, but admitted that it could appear purely as a symptom only. This was in discordance with the views in England where (in 1928) Dr. Samuel Alexander Kinnier Wilson repudiated such convictions; in 1930 Lhermitte still shared the same opinion. Gélineau differentiated narcolepsy from epilepsy with the elegance of clinical reasoning. Overall, Gélineau described three elements of the narcoleptic pentade. Sleep paralyses were first described by Mitchell in 1876, and were first attributed to narcolepsy by Wilson in 1928; in 1930 Lhermitte first described hypnapompic, and Daniels, in 1934, hypnagogic sleep paralysis. Hypnagogic hallucinations were described by Maury in 1848 and subsequently by de Saint Denis in 1867. In twenties they were thoroughly studiesed during the epidemic encephalitis and after the Big War in 1922 by Levy. The life story of Dr. Gélineau covers multivarious activities. As a young student of the Rochefort Navy Medical School he took part in the fight against colera which deluged the city of La Rochelle. In 1849 he became the "Intern" of the Navy Hospital and next year a "Surgeon of the Third Class". As a Navy surgeon he visited French colonies in the Indian ocean: first the Reunion island and then Mayotte island of the Commores Archipelago. Of this period he wrote "Voyage a i'lle de la Réunion", memoirs published much later, in 1905, in which he described colonial life and abolition of slavery. The story of Elise, a beauteous Creole woman, a concubine of a young naval Commander, who delivered a child that soon died, inexorably points to the autobiographic character of his work. He defended a doctoral thesis "Aperçu Medical de I'lle de Mayotte" at Montpellier University School of Medicine in 1858, using the data collected during his year-and-a-half stay on a Mayotte island; at that time he was a "Navy Surgeon of the Second Class". For his dedication in fighting against epidemics that broke out during the French-German war in 1870 he was nominated for the Legion of Honor, but received it only later. In 1871 Gélineau introduced "Doctor Gélineau's tablets" for the treatment of epilepsy (contained bromide and arsenic). He was a member of the Société de Médicine, Société d' Hypnologie, La-Société Française d' Hygiène, and a few others. After retirement at the age of 72, Gélineau switched to wine production, continuing the family tradition; for the quality of his Bordeaux wines he was awarded gold medals at the Anvers and Paris Exhibitions. Dr. Gélineau died on March 2, 1906, at Argeles Gazost in Pyrnees honored by the titles of Chevalier de la Légion d' Honneur, Officier d'Academie and Commander of Nichan of the Ottoman Empire.
The great English neurologist, Dr. John Hughlings Jackson was born in Providence Green, Yorkshire, north England, in 1835. He spent his apprenticeship in the city of York, continued his medical education at St. Bartholomew's hospital in London, and qualified in medicine in 1856. After working in the city of York, he studied in London and in 1860 graduated at St. Andrews university in Scotland. He died in London in 1911, famous and celebrated by his colleagues as the "father of British neurology". Jackson was a prolific writer, witty and ingenious person, but also solitary and absent minded, with a lat of "tiny peculiarities of a genius". At first he was committed to become a philosopher but was persuaded by Jonathan Hutchinson, one of his rare friends, to enter medicine. His "Selected Writings" were first published in 1931 and reprinted recently, in 1996, by Arts & Boeve. Jackson, unlike William Richard Gowers, wrote his articles in a style which was not palatable to his contemporary colleagues. This could be the reason that his medical work was not widely known and would have remained in shadow had it not been rediscovered mostly by German neurologists, who preceded their English colleagues and collected the fame. Jackson gave the first classification of epileptic seizures acceptable, to a degree, even today. It was twofold: the first, taxonomic, which corresponds to contemporary classification of seizures, he compared to the attitude of a gardener who classifies flowers according to their beauty, height or color, and was aware of its purely phenotypic, descriptive and utilitarian character; the second was scientific, physiologic and it would correspond nowadays to the current concept of syndromic classification. Jackson was aware that this 'scientific classification' was to await for the future time, when the knowledge of the real nature of epilepsy became fundamentally broadened. On the other hand, he thought that all the epilepsies were partial becoming generalized only secondarily. Partial epilepsies were the starting point in his work. He realized that epileptic attacks are not different types of epilepsies with different pathophysiological mechanisms, but that they differ in respect to the focus of origin; he stressed their gray matter (cortical) arigin with the cause located as the rule "on the side of the brain, opposite to the body convulsed". Jackson's ideas on epileptogenesis and the localization of epileptogenic processes represent his fundamental contribution to the understanding of their pathophysiology. His most philosophical contribution to neurology was the concept of the evolution and dissolution of the nervous system, which was the consequence of his ideas on its organization. Symptoms observed after the lesion of a certain part of the brain are not the consequence of its function; they are the result of the function of the remaining non-lesioned regions which are in a certain way freed from the adjacent or a higher control. This concept of interpretation af the symptoms of the nervous diseases remains applicable even today. Jackson was the first to stress the importance of ophthalmoscopy in neurology in all cases of neurologic disease, especially in cases of optic neuritis (papilloedema) which may be present even if the patient did not notice the minimized visual acuity. The way of thinking that Jackson introduced in medicine and neurology may be his most precious legacy to the generations that followed.