Febrile Infections in Children with Leukemia with Special Reference to Respiratory Viral Infections

Leukemiaa sairastavien lasten kuumeiset infektiot, erityisesti respiratoriset virusinfektiot Tausta: Hengitysteiden virusinfektiot ovat lasten tavallisimpia sairauksia. Infektiota aiheuttava virus voidaan uusilla menetelmillä löytää lähes kaikissa tapauksissa. Leukemiaa sairastavilla lapsilla on perustaudin ja leukemian hoitojen takia tavallista suurempi infektioalttius, ja kuumeilu on tavallista leukemiahoidon aikana. Suurin osa syöpähoidon aikaisten kuumejaksojen syistä jää kuitenkin selvittämättä. Tavoitteet: Prospektiivisen 5 vuotta kestäneen monikeskustutkimuksen tavoitteena oli etsiä uusimmilla mikrobiologisilla menetelmillä leukemiaa sairastavien lasten kuumeen syy. Tätä varten tutkittiin 16 virusta virusviljelyllä, antigeeniosoituksella ja nukleiinihappo-osoituksella. Näytteitä otettiin nenästä, ulosteesta, virtsasta ja verestä. Lisäksi tutkittiin MxA-proteiinin kykyä osoittaa virusinfektio syöpälapsella. Tulokset: Tutkimuksen aikana analysoitiin 138 kuumejaksoa 51 leukemialapsella. Kokonaisseuranta-aika oli 1.5 vuotta/lapsi. Kuumejaksojen ilmaantuvuus oli 2.1 jaksoa potilasta kohden suhteutettuna vuoden riskiaikaan. Hengistysteiden virusinfektio voitiin osoittaa 82 kuumejaksossa (59%). Kaksi tai useampi virus löydettiin 12 %:ssa kuumejaksoista. Tavallisimmat virukset olivat rhinovirus (22 %), respiratory syncytial virus eli RS-virus (11 %), human herpes virus 6 (7 %), human bocavirus (5 %), sytomegalovirus (5 %), parainfluenssavirukset (5 %) ja influenssa A -virus (4 %). Kahdelle potilaalle kehittyi pneumonia, muilla oireet olivat lievät. Veriviljely oli positiivinen 19 kuumejaksossa (14 %), ja puolessa tapauksista löydettiin samanaikaisesti respiratorinen virus. MxA proteini ilmeni veren lymfosyyteissä useimmilla virusinfektioon sairastuneilla syöpälapsilla. Päätelmät: Kuumeiset respiratoriset virusinfektiot ovat tavallisia leukemiaa sairastavilla lapsilla. Infektion oireet ovat tavallisesti vähäiset, mutta pienelle osalle voi kehittyä veriviljelypositiivinen sepsis tai pneumonia. Kuumeen syy jäi selvittämättä vain harvoissa tapauksissa.

Kainic acid-induced seizures: inflammation and excitotoxic neuronal damage in the developing rat hippocampus

Epileptic seizures are harmful to the developing brain. During epileptic seizures, overactivation of glutamate receptors (GluR) leads to neuronal degeneration, defined as excitotoxicity. The hippocampus is especially vulnerable to excitotoxic neuronal death, but its mechanism has remained incompletely known in the developing brain. Recently, signs of activation of inflammatory processes after epileptic seizures have been detected in the hippocampus. The purpose of this thesis was to study the inflammatory reaction and death mechanisms in excitoxic neurodegeneration induced by the glutamate analogue kainic acid (KA) in the developing hippocampus. Organotypic hippocampal slice cultures (OHCs), prepared from 6-7-day-old rats (P6-7) and treated with KA, served as an in vitro model. KA-induced status epilepticus in P9 and P21 rats was used as an in vivo model. The results showed that the pyramidal cell layers of the hippocampus were the most susceptible to irreversible and age-specific neurodegeneration, which occurred in the juvenile (P21), but not in the immature (P9), rat hippocampus. The primary death mechanism was necrosis as there were no significant changes in the expression of selected apoptosis markers and morphological cellular features of necrosis were found. Inflammatory response was similarly age-dependent after KA treatment as a rapid, fulminant and wide response was detected in the juvenile, but not in the immature, rat brain. An anti-inflammatory drug treatment, given before KA, was not neuroprotective in OHCs, possibly because of the timing of the treatment. In summary, the results suggest that KA induces an age-dependent inflammatory response and necrotic neurodegeneration, which may cause disturbances in hippocampal connectivity and promote epileptogenesis.

Selvitys suomalaisten belgianpaimenkoirien kohtausten yleisyydestä ja luonteesta

Sirpa Teikari

Neurofilament proteins in the postnatal rat hippocampus. Developmental expression and changes in experimental epilepsy

Neurofilament proteins (NFs) are the major components of the intermediate filaments of the neuronal cytoskeleton. The three different NF proteins; the low (NF-L), medium (NF-M),and dendrites.NF proteins play an important role in neuronal development, and plasticity,and seem to contribute to the pathophysiology of several diseases. However, the detailed expression patterns of NF proteins in the course of postnatal aturation, and in response to seizures in the rat have remained unknown. In this work, I have studied the developmental expression and cellular distribution of the three NF proteins in the rat hippocampus during the postnatal development. The reactivity of NF proteins in response to kainic acid (KA)-induced status epilepticus (SE)was studied in the hippocampus of 9-day-old rats, and using in vitro organotypic hippocampal slices cultures prepared from P6-7 rats. The results showed that NF-L and NF-M proteins are expressed already at the postnatal day 1, while the expression of NF-H mainly occurred during the second postnatal week. The immunoreactivity of NF proteins varied depending on the cell type and sub-cellular location in the hippocampus. In adult rats, KA-induced SE typically results in severe and permanent NF degradation. However, in our P9 rats KA-induced SE resulted in a transient increase in the expression of NF proteins during the first few hours but not degradation. No neuronal death or mossy fiber sprouting was observed at any time after SE. The in vitro studies with OHCs, which mimick the in vivo developing models where a local injection of KA is applied(e.g. intrahippocampal), indicated that NF proteins were rapidly degraded in response to KA treatment, this effect being effectively inhibited by the treatment with the AMPA receptor antagonist CNQX, and calpain inhibitor MDL-28170. These compounds also significantly ameliorated the KA-induced region-specific neuronal damage. The NMDA receptor antagonist and the L-type Ca2+ channel blocker did not have any significant effect. In conclusion, the results indicate that the developmental expression of NF in the rat hippocampus is differentially regulated and targeted in the different hippocampal cell types during the postnatal development. Furthermore, despite SE, the mechanisms leading to NF degradation and neuronal death are not activated in P9 rats unlike in adults. The reason for this remains unknown. The results in organotypic hippocampal cultures confirm the validity of this in vitro model to study development processes, and to perform pharmacological studies. The results also suggest that calpain proteases as interesting pharmacological targets to reduce neuronal damage after acute excitotoxic insults.

Brand Protection Perspectives

The main focus of this qualitative study is to explore and understand the boundaries of a brand protection program by assessing risks caused directly or indirectly by counterfeiting and finding remedies for treating those risks. 12 of 20 brand protection managers, anti-counterfeiting experts and marketing professors completed anonymously an internet-mediated questionnaire. During this study, a pattern of risk tolerance level within the sample was identified. The empirical results suggest that this pattern influences participants’ risk perception of and attitude towards counterfeiting; these also imply that, in risk treatment, this pattern influences decision- making as well as selection of countermeasures. Further, the results propose that brand equity and reputation are compared to other brand variables more vulnerable to the impact of counterfeiting. In addition, the results obtained in the question whether companies should employ public announcements of counterfeit seizures as an additional brand protection tool were contradictory. Companies were more apprehensive towards this solution than marketing professors. Thus, further investigation on this subject is recommended. This study concludes that as long as the impact of counterfeiting cannot be measured properly, the true damage on a brand or company and their reputation cannot be determined.

Detection of Epilepsy with a Commercial EEG Headband

Epilepsy is a chronic brain disorder, characterized by reoccurring seizures. Automatic sei-zure detector, incorporated into a mobile closed-loop system, can improve the quality of life for the people with epilepsy. Commercial EEG headbands, such as Emotiv Epoc, have a potential to be used as the data acquisition devices for such a system. In order to estimate that potential, epileptic EEG signals from the commercial devices were emulated in this work based on the EEG data from a clinical dataset. The emulated characteristics include the referencing scheme, the set of electrodes used, the sampling rate, the sample resolution and the noise level. Performance of the existing algorithm for detection of epileptic seizures, developed in the context of clinical data, has been evaluated on the emulated commercial data. The results show, that after the transformation of the data towards the characteristics of Emotiv Epoc, the detection capabilities of the algorithm are mostly preserved. The ranges of acceptable changes in the signal parameters are also estimated.