Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment for the degree Masters of Medicine in Paediatrics (MMed) Johannesburg 2014 / Introduction Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis (EPTB) in children, particularly under 5 years of age. Children are vulnerable to EPTB as they are immunologically immature and unable to contain Mycobacterium tuberculosis (MTB) infection in the lung. Common neurological sequelae of TBM include focal motor deficits, vision loss and hydrocephalus. Early stage diagnosis and timeous anti-tuberculosis treatment decreases the case fatality rate of TBM. Objective To characterise the burden, clinical presentation, laboratory markers and short-term outcome of TBM in HIV-infected and HIV-uninfected children. Methods The electronic databases of admission of children at Chris Hani Baragwanath Academic Hospital (CHBAH), between January 2006 and December 2011 with a diagnosis of TBM were reviewed. Individual patient records were retrospectively reviewed for clinical and laboratory data. In addition, admissions from the neurosurgery wards were also reviewed. In patients whose medical records were unavailable, laboratory data was used. Results The overall incidence of TBM in 2006 was 6.96 per 100 000 (95% Confidence Interval [95%CI]: 4.46-10.36), peaked at 9.87 per 100 000 (95% CI: 6.91-13.67) in 2009 and subsequently declined to 3.18 per 100 000 by 2011 (95% CI: 1.64-5.56). There was a 38.6% (95% CI: 10.0-58.0; p=0.011) reduction in the overall incidence of TBM when comparing the period 2006-2009 with the period 2010-2011. This decline was particularly evident in HIV-infected children (49.6% reduction; 95%CI: 1.05-74.35; p=0.042). There were no differences in the clinical symptoms of TBM or tuberculosis between HIV-infected and -uninfected children. Previous history of TB was significantly higher in HIV-infected children compared to HIV-uninfected children (OR 4.63; 1.40-15.22; p=0.011). Tuberculin skin test positive-reactivity (OR 0.09; 0.02-0.43; p=0.002) and sputum culture positivity (OR 0.29; 0.10-0.86; p=0.025) were less common in HIV-infected compared to -uninfected children. Cerebrospinal fluid cytology and biochemistry results were similar between HIV-infected compared to -uninfected children. Morbidity (22.7% in HIV-infected vs. 33.0% in -uninfected) and mortality (6.4% in HIV-infected vs. 6.9% in -uninfected) were similar between HIV-infected and -uninfected children. Conclusion The incidence of TBM has decreased over the study period 2006 to 2011.This decrease was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.

Elk (Cervus elaphus) were historically present throughout Kentucky, but were extirpated by the mid 19th century. Kentucky Department of Fish and Wildlife Resources initiated elk reintroduction efforts in 1997, resulting in a self-sustaining population. I designed this project to study the effects of a parasitic nematode, meningeal worm (Parelaphostrongylus tenuis), on Kentucky’s elk herd. I examined potential maternal transfer of P. tenuis antibodies to elk calves, and investigated the relationship between elk habitat use and meningeal worm infection. I captured neonatal elk in 2004-06, fitted them with VHF transmitters, and collected blood samples for an enzyme-linked immunosorbent assay (ELISA) to determine P. tenuis infection. I monitored animals to determine habitat use, and attempted to recapture each individual to collect a follow-up blood sample. I found substantial rates of maternal meningeal worm antibody transfer (55%) over the course of the study. Neither sex nor predicted birth weight was associated with increased likelihood of obtaining maternal antibodies. Habitat variables associated with P. tenuis infection included herbaceous, shrub, and bare cover types, herbaceous mean core area, forest edge density, and forest mean core area. Confounding variables complicated habitat data analysis, but high rates of maternal P. tenuis antibody transmission suggested that meningeal worm infection does not threaten the long-term viability of the Kentucky elk herd.

No description available.

Migraine is one of the most prevalent contributors to the global burden of mental and neurological disorders. It is a complex episodic condition that presents as intense recurrent unilateral headaches lasting hours to days that can be accompanied by nausea, photophobia, phonophobia and other neurological symptoms. The causes of migraine appear multifactorial and are not fully understood. However, activation of the trigeminovascular system and sphenopalatine parasympathetic neurons and the resulting vasodilation of meningeal arteries have been associated with the development of migraine pain. Recently, the neurotransmitter and neurotrophic peptide pituitary adenylate cyclase activating polypeptide (PACAP) has been implicated in this migraine headache pathway. The effects of PACAP parallel those of other migraine inducing agents and notably PACAP induces vasodilation of the MMA concurrent with the genesis of migraine headache when administered to human subjects. The mechanisms by which PACAP induces dilation are presently unclear. The objective of this present work was to elucidate the signaling pathways linking PACAP to MMA dilation. To achieve this objective, we developed an ex vivo approach to study isolated MMA at physiologically relevant intravascular pressure. Using this preparation we found that PACAP dilates MMA at picomolar concentrations via PAC1 receptors. Further, in MMA, PACAP-induced dilation is mediated exclusively though activation of KATP channels. While investigating the mechanisms of PACAP-induced dilation of MMA we discovered that basal KATP channel activity influences MMA diameter. Inhibition of KATP channels with glibenclamide or PNU37883 at physiological intravascular pressure resulted in a vasoconstriction of ≈ 20 %. Also consistent with basal KATP activity, glibenclamide induced a membrane potential depolarization of ≈ 14 mV. Further, in MMA loaded with the ratiometric Ca2+ indicator, Fura-2-AM, glibenclamide-induced MMA constriction was correlated with a simultaneous increase in the ratio of 340 nm/380 nm excited fura-2 fluorescence, consistent with an increase in intracellular Ca2+. Vascular smooth muscle KATP channels can be phosphorylated and activated by PKA, resulting in membrane potential hyperpolarization. KT5720, a PKA inhibitor, induced a constriction in MMA similar to that of glibenclamide (≈ 25 %). Additional treatment with glibenclamide did not induce further constriction suggesting that PKA activity may underlie tonic KATP channel activation. Together these results suggest that tonic PKA activity underlies basal KATP channel activity and together play a key role in regulation of MMA diameter. In summary, results presented in this dissertation suggest that picomolar PACAP-induced dilation of MMA is via activation of the PAC1-Hop1 receptor splice variant and KATP channel activation. Furthermore, KATP channels are also involved in tonic regulation of MMA diameter due to basal PKA activity. These unique features of the MMA provide additional insight into potential therapeutic targets in the development of treatments for migraine.

by Wang Siu Wai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 78-101). / Acknowledgments --- p.i / Abstract --- p.ii / Abbreviations --- p.v / Table of Content --- p.vi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.4 / Chapter Chapter 3 --- Materials and Methods --- p.38 / Chapter Chapter 4 --- Results --- p.52 / Chapter Chapter 5 --- Discussion --- p.61 / Chapter Chapter 6 --- Conclusion and Further Studies --- p.75 / References --- p.78 / Appendix --- p.102 / Micrographs and Tables

No description available.

Σκοπός. Η δραστηριότητα της β-γλυκουρονιδάσης στο εγκεφαλονωτιαίο υγρό (ΕΝΥ) είναι αυξημένη στην βακτηριακή μηνιγγίτιδα, αλλά η πορεία της κατά τη διάρκεια της θεραπείας είναι άγνωστη. Σκοπός της μελέτης ήταν η μέτρηση της δραστηριότητας της β-γλυκουρονιδάσης κατά τη διάρκεια της θεραπείας και η σύγκρισή της με άλλες κυτταρικές και βιοχημικές παραμέτρους του ΕΝΥ. Μέθοδος. H δραστηριότητα της β-γλυκουρονιδάσης, ο αριθμός κυττάρων, η συγκέντρωση πρωτεΐνης και ο λόγος γλυκόζης ΕΝΥ/αίματος μετρήθηκαν κατά τη διάρκεια της θεραπείας σε 47 ασθενείς με βακτηριακή μηνιγγίτιδα, από τους οποίους 4 ήταν νεογνά και 97 μάρτυρες. Οι ασθενείς υποβλήθηκαν σε 1 ή 2 επαναληπτικές οσφυονωτιαίες παρακεντήσεις. Επίσης η δραστηριότητα της β-γλυκουρονιδάσης μετρήθηκε σε 8 ασθενείς με πυελονεφρίτιδα και στείρα πλειοκυττάρωση ΕΝΥ. Αποτελέσματα. Πριν τη θεραπεία η διάμεση δραστηριότητα της β-γλυκουρονιδάσης σε ασθενείς βρεφικής μέχρι εφηβικής ηλικίας ήταν 136 moles 4-methylumbelliferone/ml/ώρα (με διακύμανση από 44 έως 826), ενώ στους μάρτυρες ήταν 14 nmoles/ml/ώρα (με διακύμανση 7 έως 23) (p<0,000001). Σε όλους τους ασθενείς με κλινική βελτίωση, η δραστηριότητα της β- γλυκουρονιδάσης ήταν χαμηλότερη σε δείγματα ΕΝΥ, τα οποία ελήφθησαν μετά πάροδο τουλάχιστον 6 ωρών από την έναρξη της θεραπείας. Έξι μέχρι 12 ώρες μετά την έναρξη της θεραπείας η διάμεση δραστηριότητα της β-γλυκουρονιδάσης είχε ήδη μειωθεί κατά 59%. Αντιθέτως, οι υπόλοιποι παράμετροι του ΕΝΥ έδειξαν μεταβλητότητα των τιμών τους, κατά τις πρώτες 24 ώρες της θεραπείας, η οποία ήταν ανεξάρτητη από την πορεία της νόσου. Σε 1 ασθενή με πνευμονιοκοκκική μηνιγγίτιδα, ο οποίος ενεμφάνισε επιδείνωση των συμπτωμάτων του 22 ώρες μετά την έναρξη της θεραπείας, η δραστηριότητα της β-γλυκουρονιδάσης αυξήθηκε κατά 89%. Στη νεογνική μηνιγγίτιδα η δραστηριότητα της β-γλυκουρονιδάσης πριν τη θεραπεία ήταν αυξημένη, αλλά η παρακολούθηση της πορείας της νόσου απαιτεί παρατεταμένη περίοδο ενζυμικών μετρήσεων, για έγκαιρη ρύθμιση της θεραπείας επί υποτροπών και αναμολύνσεων. Συμπεράσματα. Η δραστηριότητα της β-γλυκουρονιδάσης του ΕΝΥ είναι αξιόπιστος δείκτης βακτηριακής μηνιγγίτιδας, που μπορεί να προσδιορίσει, νωρίς στην πορεία της νόσου, την ανταπόκριση στην θεραπεία. / Aim: β-Glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the β-glucuronidase activity in the cell-free CSF of bacterial meningitis, its course during treatment and compare it to other CSF parameters. Methods: The β-glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 47 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had 1 or 2 follow-up lumbar punctures. Results: The β-glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136 moles 4-methylumbelliferone/L/h (range 44-826) and in controls 14 (7-23). In all patients who improved, the activity was lower in the follow-up CSF samples. Six to 12 hours after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 hours of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had 2 follow-up punctures showed that the β-glucuronidase activity was the best prognostic index. Conclusion: β-Glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.

Submitted by Isabela Leite Ferraz Cabral (isabelalferraz@hotmail.com) on 2018-04-19T13:07:04Z No. of bitstreams: 1 Isabela Leite Ferraz (após a defesa).pdf: 2321770 bytes, checksum: 6bfabab6d5e2449baea610ec9c7969ec (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-04-19T17:32:17Z (GMT) No. of bitstreams: 1 cabral_ilf_dr_bot.pdf: 2321770 bytes, checksum: 6bfabab6d5e2449baea610ec9c7969ec (MD5) / Made available in DSpace on 2018-04-19T17:32:17Z (GMT). No. of bitstreams: 1 cabral_ilf_dr_bot.pdf: 2321770 bytes, checksum: 6bfabab6d5e2449baea610ec9c7969ec (MD5) Previous issue date: 2018-02-21 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Justificativa e objetivo: o hábito de tatuar o corpo faz parte da cultura de muitos povos no mundo. A partir do início dos anos 1990, passou a ser utilizada por alguns grupos sociais e em faixa etária determinada como uma forma de arte no corpo. Os pigmentos podem conter componentes orgânicos e inorgânicos, metais e solventes. Há grande variação na composição química destes, o que dá origem às diferentes cores. Pouco se conhece sobre as possíveis implicações da introdução de uma agulha para realização de anestesia regional sobre uma pele tatuada. Alguns autores questionam se o pigmento contido na tatuagem pode desencadear aracnoidite química. Estudo experimental determinou infiltrado inflamatório linfoplasmacitário perivascular nas meninges de coelhos, 6 meses após punção subaracnoidea sobre pele tatuada. O objetivo desta pesquisa foi avaliar se a punção subaracnoidea realizada sobre a pele tatuada de coelhos ocasiona alterações histológicas precoces nas meninges. Material e Métodos: após a aprovação da Comissão de Ética e Pesquisa no Uso de Animais, foram utilizados 28 coelhos adultos jovens, da raça Grupo Genético de Botucatu, com pesos entre 3300 e 5400g e comprimento de medula espinal (espaço medido entre a base do crânio e o espaço lombossacral) entre 38 e 41 cm, fornecidos pelo Biotério da Faculdade de Medicina de Botucatu. Os animais foram divididos em 2 grupos (G): G1- punção subaracnoidea sobre tatuagem e injeção de solução salina a 0,9% e G2 - punção subaracnoidea sobre pele não tatuada e injeção de solução salina a 0,9%. Após anestesia venosa com xilazina e cetamina, os animais de G1 foram tatuados e, após 30 dias, sob a mesma anestesia, foi realizada a abordagem do espaço subaracnoideo, com agulha de Quincke 22G 21/2”, no espaço intervertebral entre a primeira e a segunda vértebra sacral, guiada por ultrassom. Os animais de G1 e G2 receberam as soluções correspondentes em volume de 5 μL por centímetro de medula espinal (aproximadamente 0,2 mL). Os animais foram avaliados clinicamente quanto à sensibilidade e à motricidade por 30 dias, após os quais foram sacrificados e retiradas as porções lombar e sacral da medula espinhal para exame histológico por microscopia óptica. Resultados: onze animais (78,6%) de G1 apresentaram lesões histológicas focais na pia-máter e aracnoide. Nos animais de G2 não foram encontradas alterações histológicas no tecido nervoso, nos vasos sanguíneos ou nas meninges. Conclusão: são precoces as alterações histológicas meníngeas desencadeadas pela introdução do pigmento da tatuagem após punção subaracnoidea. / Background: body tattooing is cultural for many people around the world. Since the early 1990s, it began to be used by some social groups and some age groups as a body art. The pigments may contain organic and inorganic components, metals and solvents. There is a great variation in the chemical composition of these pigments and that is why they produce different colors. We don’t know the possible implications of introducing a needle for performing regional anesthesia on a tattooed skin. Some authors question whether the pigment contained in the tattoo can trigger chemical arachnoiditis. One experimental study showed perivascular lymphoplasmacytic inflammatory infiltrate in rabbit meninges, 6 months after subarachnoid puncture on tattooed skin. The aim of this study was to evaluate if the subarachnoid puncture performed on the tattooed skin of rabbits already causes early histological changes in the meninges. Material and Methods: after Ethics Committee’s approval, it was used 28 young adult rabbits from Botucatu’s genetic group. The rabbits weights were between 3000 and 4500g and the length of spine (space measured from the base of the skull to lumbosacral space) were between 38 and 41 cm provided by the Medical Center of Botucatu Medical School. The animals were divided into 2 groups (G): in G1 group there was a subarachnoid puncture on tattooing and injection of 0.9% saline solution while in G2 group there was a subarachnoid puncture on non-tattooed skin and injection of 0.9% saline solution. After venous anesthesia with xylazine and ketamine, the G1 animals were tattooed. After 30 days, under the same anesthesia, the subarachnoid space were accessed, with Quincke's Needle 22G 21/2” , in the intervertebral space between the first and second sacral vertebra. All the procedure was ultrasound guided. The rabbits of G1 and G2 groups received the corresponding volume solutions of 5 μl per centimeter of spinal cord (approximately 0.2 mL). The animals were clinically assessed for sensitivity and motor function for 30 days. After that, they were sacrificed and the lumbar and sacral portions of the spinal cord were removed for histological examination by light microscopy. Results: eleven animals (78.6%) of G1 group had focal histological lesions in the pia mater and arachnoid. No histological changes were found in nervous tissue, blood vessels or meninges on G2 group. Conclusions: early meningeal histological changes are triggered by introduction of tattoo pigment into central nervous system after subarachnoid puncture. / FAPESP - Proc 2014/24053-9

Orientador: Eliana Marisa Ganem / Resumo: Justificativa e objetivo: o hábito de tatuar o corpo faz parte da cultura de muitos povos no mundo. A partir do início dos anos 1990, passou a ser utilizada por alguns grupos sociais e em faixa etária determinada como uma forma de arte no corpo. Os pigmentos podem conter componentes orgânicos e inorgânicos, metais e solventes. Há grande variação na composição química destes, o que dá origem às diferentes cores. Pouco se conhece sobre as possíveis implicações da introdução de uma agulha para realização de anestesia regional sobre uma pele tatuada. Alguns autores questionam se o pigmento contido na tatuagem pode desencadear aracnoidite química. Estudo experimental determinou infiltrado inflamatório linfoplasmacitário perivascular nas meninges de coelhos, 6 meses após punção subaracnoidea sobre pele tatuada. O objetivo desta pesquisa foi avaliar se a punção subaracnoidea realizada sobre a pele tatuada de coelhos ocasiona alterações histológicas precoces nas meninges. Material e Métodos: após a aprovação da Comissão de Ética e Pesquisa no Uso de Animais, foram utilizados 28 coelhos adultos jovens, da raça Grupo Genético de Botucatu, com pesos entre 3300 e 5400g e comprimento de medula espinal (espaço medido entre a base do crânio e o espaço lombossacral) entre 38 e 41 cm, fornecidos pelo Biotério da Faculdade de Medicina de Botucatu. Os animais foram divididos em 2 grupos (G): G1- punção subaracnoidea sobre tatuagem e injeção de solução salina a 0,9% e G2 - punção subaracnoidea s... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: body tattooing is cultural for many people around the world. Since the early 1990s, it began to be used by some social groups and some age groups as a body art. The pigments may contain organic and inorganic components, metals and solvents. There is a great variation in the chemical composition of these pigments and that is why they produce different colors. We don’t know the possible implications of introducing a needle for performing regional anesthesia on a tattooed skin. Some authors question whether the pigment contained in the tattoo can trigger chemical arachnoiditis. One experimental study showed perivascular lymphoplasmacytic inflammatory infiltrate in rabbit meninges, 6 months after subarachnoid puncture on tattooed skin. The aim of this study was to evaluate if the subarachnoid puncture performed on the tattooed skin of rabbits already causes early histological changes in the meninges. Material and Methods: after Ethics Committee’s approval, it was used 28 young adult rabbits from Botucatu’s genetic group. The rabbits weights were between 3000 and 4500g and the length of spine (space measured from the base of the skull to lumbosacral space) were between 38 and 41 cm provided by the Medical Center of Botucatu Medical School. The animals were divided into 2 groups (G): in G1 group there was a subarachnoid puncture on tattooing and injection of 0.9% saline solution while in G2 group there was a subarachnoid puncture on non-tattooed skin and injection of 0.... (Complete abstract click electronic access below) / Doutor